Welfare policy in Verona: from Sant’Antonio hospital to New hospital complex

The history of the Veronese hospitals constitutes one of the most important and interesting chapters of the urban events. St. Zeno in his sermon on the avarice, already praised the Veronese inhabitants for their great availability toward suffering and sick people, to the point that almost every monastery and parishes became a reception centre for pilgrims, distressed and sick people. Population growth implied to improve the health initiatives. The events happened in Verona at the beginning of the twentieth century are a precious proof of the contribution which doctors and wise administrators offered to the Veronese health care system. It is a history intimately related to the munificent charity thanks to which the local protagonists sustained the birth and the development of the hospital complex (bequest of Alessandri, Cressotti Zorzi, Failoni, Roveda, only for quoting some of them). The hospital administration, together with doctors and inhabitants faced with burning and active debates, the transfer of the civil hospital from its seat, situated in the thin urban fabric of the city centre, to a suburb area: Borgo Trento. Borgo Trento is the hospital which the Veronese feel like their own hospital, characterized by a system of pavilions, long tree-lined avenue and luxuriant gardens. A new hospital complex, Borgo Roma Policlinico, was born in the 1970s in the south suburb of the city, offering great town planning and charitable opportunities. The integration of the two hospitals and the constitution of the Azienda Ospedaliera Integrata Verona are most recent history (2010), but seems follow the steps of the union between the Alessandri Children’s Hospital and the Sant’Antonio Civil Hospital, as a prosecution of the troubled hospital history of fusions, transfers and divisions.Peer Reviewe

Effects of a Multicomponent Exercise Program on Prevalence and Severity of the Frailty Syndrome in a Sample of Italian Community-Dwelling Older Adults

Background: Frailty is a well-known condition that leads to a lack of resilience, with a reduced homeostatic capacity and a consequent higher risk of suffering adverse health outcomes. This study investigated the effectiveness of an exercise program to improve and reverse physical frailty amongst Italian older adults. Methods: One hundred and twenty-three community dwelling older adults (mean age 74 years, SD = 6; 64% women) were involved in an experimental (EG; n = 62) and a control (CG; n = 61) group. Frailty was assessed at baseline and after the intervention using an adapted version of the frailty phenotype. The EG took part in a 16-week exercise program, consisting of endurance, strength, balance and flexibility exercises, while the CG maintained the same routine. Results: After the exercise program, the EG was more robust than the CG (F = 43.51, p < 0.001). Within the EG, 46% of pre-frail and 50% of frail people reached the robust and pre-frail levels, respectively. Effects of training were higher in frail and pre-frail people (reduction of frailty of 0.67 and 0.76 points, respectively) compared to robust ones (who frailty levels increased by 0.23 points; F = 11.32, p < 0.001). Conclusions: A multicomponent exercise program may be effective at improving and reverting frailty, specifically for frail and pre-frail people

A JOURNEY IN THE ORGANOCATALYSED AND MULTICOMPONENT SYNTHESIS OF 3,3-DISUBSTITUTED AND SPIRO-OXINDOLES

2-Oxindoles, especially those 3,3-disubstituted or spiro-fused to other cyclic frameworks, continue to be recognized as valuable compounds for drug discovery. They are present in a large number of natural and unnatural compounds with important biological activities and serve as key intermediates for the synthesis of many kinds of drug candidates.1 In particular, spirooxindoles, having cyclic structures fused at the C3 carbon, move away from the flat heterocycles encountered in many drug discovery programs. For this reason, they are of special interest, being able to potentially provide improved physicochemical properties in their interaction with biological systems.2 As more examples of the enantiospecific biological activity are identified, efficient and reliable asymmetric synthesis of such compounds becomes more and more valuable. In this context, the identification of asymmetric methods that achieve high stereoselectivity in the synthesis of heterocyclic compounds, in particular bearing tetrasubstituted or spiro-stereocenters, remains challenging. In this context, my research was aimed to the synthesis of oxindole-based libraries, exploiting protocols at the cutting edge of synthetic chemistry, such as MCRs and organocatalysis. Considering the great attention around optically active \u3b4-amino-\u3b1,\u3b2-unsaturated carbonyl compounds as important building blocks in the synthesis of biologically active compounds,3 for my first project I focused my attention on the synthesis of 3-amino-3-(5-oxo-2,5-dihydrofuran-2-yl)indolin-2-ones derivatives via a BINOL-based phosphoric acids organocatalyzed vinylogous Mannich-type reaction.4 The desired products were obtained in general good yields and high enantiomeric excesses considering the challenge in the formation of a quaternary stereocenter consecutive with a bulky tertiary one. The stereochemistry of the final products was assigned by chemical correlation with respect to a reported compound5 and the stereochemical outcome was also rationalized by computational study. Moreover, I studied the Biginelli reaction, a three component cyclocondensation between alkyl acetoacetates, urea and a carbonyl compound, as a practical method for the synthesis of biologically important 3,4-dihydropyrimidine-2(1H)-ones.6 In particular, BINOL-phosphoric acids have been used in the development of the first enantioselective organocatalyzed multicomponent Biginelli-like reaction applied to a ketone, allowing to obtain a small library of spiro[indoline-pyrimidine]-dione derivatives in good yields and enantioselectivity.7 During the second year, I focused my attention on the synthesis of 2-oxindoles spiro-fused with four- and five-membered rings. Considering the recent medicinal chemists' interest in oxindole-based thiazolidine compounds as antitumor agents for the inhibition of the p53-MDM2 PPI,8 a novel synthetic approach towards spirooxindole-fused thiazolidines has been developed, based on two sequential multicomponent reactions (MCRs), namely the Asinger and two different Ugi-type reactions, Joulli\ue9-Ugi 3-CR and azido-Ugi 3-CR.9,10 The traditional Asinger 4-MCR11 allows to synthesize the thiazoline scaffold by treating a ketone with sulfur and ammonia with high atom economy. However, considerable more flexible is the \u201cresynthesis protocol\u201d in which an \u3b1-sulfanyl-carbonyl compound is directly used.12 The first part of the project involved the development of an Asinger-type reaction using isatin as the oxo component. After a screening of reaction conditions, the best parameters were selected to perform the substrate scope synthesizing different spirooxindole-fused 3-thiazolines in good yields.13 Spirooxindole-fused 3-thiazolines bearing an hydrogen as substituent on the double bond proved to be useful for the application of sequential MCRs. By application of Joulli\ue8-Ugi and azido-Ugi reactions respectively, two small families of spiro-[indoline-3,2\u2019-thiazolidine] derivatives were obtained in good yields and high diasteroselectivity.14 Another project developed during the second year was focused on the azetidine moiety. This strained four-membered ring system occurs as a structural motif in several natural products and pharmaceutical agents.15 Despite the interest in azetidin-2-ones, azetidines have received much less attention compared to their lower and higher homologues.16 Considering my interest in the synthesis of spirooxindoles derivatives, combined with the growing interest in hybrid drugs as therapeutic agents, I planned to connect the two pharmacologically relevant moieties, oxindole and azetidine, in a spiro arrangement. To do this, the formal [2+2] annulation reaction17 of isatins with allenoates has been considered as a practical and direct strategy to obtain highly functionalized chiral spirooxindole-based 4-methyleneazetidines with a high level of atom-economy.18 After a screening of reaction conditions, the best parameters were selected to extend the substrate scope obtaining different spirooxindole-fused 4-methyleneazetidines in good yield and excellent diasteroselectivity. Considering the increasing interest for the development of catalytic asymmetric synthesis, I spent the third year in the development of a more efficient asymmetric cinchona-based organocatalyzed approach for the synthesis of enantiomerically enriched spirooxindole-fused 4-methyleneazetidines. After a deep screening of catalysts and reaction conditions, best parameters were applied to the reaction scope obtaining spirooxindole-fused 4-methyleneazetidines in good yields and enatiomeric ratios.19 In conclusion, during my PhD, I synthesized six different 3,3-disubstituted and spirooxindole-based scaffolds using innovative approaches. In some cases, novel asymmetric organocatalyzed methodologies have been developed leading to enantiomerically enriched products. In other cases, more relevance was given to the multicomponent synthetic strategy for the rapid construction of highly functionalized scaffolds for drug discovery programs. Indeed, some of these compounds are under biological evaluation in collaborations with Merck (Pharma). References: 1. Singh G. et al. Chem. Rev. 2012, 112, 6104. 2. Yang C. et al. Org. Biomol. Chem. 2015, 13, 4869. 3. Ruan S.T. et al. Org. Lett. 2011, 13, 4938. 4. Rainoldi G. et al. Org. Biomol. Chem. 2016, 14, 7768. 5. Rao V. U. B. et al. Org. Lett., 2014, 16, 648. 6. Goss J. et al. J. Org. Chem. 2008, 73, 7651. 7. Stucchi M. et al. J. Org. Chem. 2016, 81, 1877. 8. Bertamino A. et al. J. Med. Chem. 2013, 56, 5407. 9. Katsuyama A. et al. Org. Lett. 2016, 18, 2552; 10. Nenajdenko G. et al. Eur. J. Org. Chem. 2013, 6379. 11. Asinger F. Angew. Chem. 1956, 68, 377. 12. Keim, W. and Offermanns, H. Angew. Chem. Int. Ed. 2007, 46, 6010. 13. Rainoldi G. et al. Synlett 2016, 27, 2831. 14. Rainoldi G. et al. ACS Comb. Sci. 2017, Just Accepted. 15. Brandi A. et al. Chem. Rev. 2008, 108, 3988. 16. Orr S. T. M. et al. ACS Med. Chem. Lett. 2015, 6, 156. 17. Shi M. et al. J. Org. Chem. 2005. 8. Rainoldi G. et al. Chem. Commun. 2016, 52, 11575. 19. Rainoldi G. et al. Molecules 2017, 22, 2016

Asociación mineralógica de la zona de alteración argilica avanzada en un yacimiento de Caolín de la Patagonia Argentina

En la provincia de Río Negro (norte de la Patagonia Argentina) los yacimientos de caolín se encuentran emplazados en rocas volcanoclásticas de edad Triásico Superior – Jurásico Medio. Esta secuencia comienza con andesitas y tobas andesíticas y culmina con riolitas y sus tobas cosanguíneas. La roca de caja del yacimiento estudiado, mina Loma Blanca, es andesítica. Está ubicado a 70 km al NO de la localidad de Los Menucos. En trabajos previos se estudió la geoquímica y zonación de alteración desde la zona propilítica hasta la argílica avanzada, con el propósito de establecer la génesis. Para ello se realizaron análisis químicos de elementos mayoritarios, minoritarios, traza e isótopos de O y D y se concluyó que el yacimiento se formó por la circulación de fluidos hidrotermales de elevada temperatura y presión. Este trabajo consiste en el estudio de los minerales de alteración desarrollados en la zona de alteración argílica avanzada con el propósito de establecer su secuencia de formación a fin de determinar la posible existencia de diferentes pulsos de mineralización relacionados con los sulfuros de Cu, Fe, Pb y Zn mencionados en la bibliografía. Se identificó dickita, caolinita, natroalunita, pirofilita, diasporo y cuarzo secundario. Se utilizó microscopía de polarización sobre secciones delgadas para evaluar las relaciones genéticas, microscopía electrónica de barrido, EDS y difractometría de rayos X para identificar los minerales presentes y el contenido de Na y K de la alunita. Se determinó la siguiente secuencia paragenética: 1. diasporo, 2. pirofilita, 3. natroalunita, 4. dickita, 5. caolinita