Enantioselective auto- and cross catalytic reactions

Begrijpen hoe het leven is begonnen blijft een enorme uitdaging en is daarom een sterk motiverende factor in experimentele onderzoeken naar het nabootsen van biologische systemen. Zelfreplicatie en homochiraliteit zijn essentiële karaktereigenschappen van levende organismen. L-aminozuren zijn één van de belangrijkste primaire dragers van homochiraliteit in levende organismen.Er zijn veel hypothesen die proberen uit te leggen hoe de chemische weg naar een asymmetrische samenstelling van chirale biomoleculen, zoals bijvoorbeeld aminozuren, tot stand is gekomen. In één van deze theorieën wordt aangenomen dat in de vroege fasen van het leven, waarin kleine prebiotische moleculen katalytisch actief zouden zijn geweest, kleine chirale onevenwichtigheden versterkt zouden kunnen worden door middel van auto-katalytische processen.Het primaire doel van dit onderzoek was het ontwerpen van een systeem voor de asymmetrische autokatalytische synthese van zowel quaternaire als tertiaire amonizuren. Parallel aan dit onderzoek is de katalytische enantioselectieve synthese van tetrahydroisochinoline derivaten ontwikkeld, welke zéér veel voorkomende motieven zijn in biologisch actieve moleculen en moderne geneesmiddelen. Tevens is intensief onderzoek verricht naar de geobserveerde asymmetrische amplificatie in de 1,2-additie van Grignard reagentia aan α,β-onverzadigde ketonen.An understanding of how life began remains a formidable challenge thus driving considerable experimental research efforts in mimicking biological systems. Self-replication and homochirality are vital characteristics of living organisms. L-amino acids are one of the main carriers of homochirality in the living organisms. Many hypotheses were proposed to explain chemical pathway towards the asymmetric formation of chiral biomolecules such as amino acids. It has been proposed that in the earliest stages of life if small prebiotic molecules were catalytically active then small chiral imbalances would be amplified via auto-catalytic processes. In this research the main goal was to design a system for asymmetric autocatalytic synthesis of both quaternary and ternary amino acids. Next to that catalytic enantioselective synthesis of tetrahydroisoquinoline derivatives which are abundant motives in the structures of bioactive molecules and modern drugs was developed. Furthermore, extensive studies on the asymmetric amplification observed in the reaction of 1,2-addition of Grignard reagents to α,β-unsaturated ketones were undertaken

The Economic Evaluation of Projects as a Structuring Discipline of Learning Processes to Support Decision-Making in Sustainable Urban Transformations

This paper is based on the following research questions: i) In which way could the discipline Economic Evaluation of Projects contribute to conveying the sustainability concept in urban settings among master’s degree students? What are the methods/techniques that can support decision processes of sustainable urban transformation? In response to the two research questions, the paper proposes a multi-methodological framework as a design tool for students (future professionals) aimed at representing the decision problem from a sustainable planning perspective. Through a Problem-Based Learning approach based on a case study, the proposed framework considers: SWOT Analysis, Stakeholder Analysis (SA), Multicriteria Analysis (MCDA), Cash Flow Analysis (CFA), and the application of the Neighborhood Sustainability Assessment Tools (NSATools). The multi-methodological framework has been applied to an experimental teaching case study as part of the Economic Evaluation of Projects module demonstrating its effectiveness in terms of sustainable spatial planning and structuring of the decision process from a multi-actor perspective. Future directions of the research are aimed at tackling two major limitations of the multi-methodological framework as the need to closely reflect a real decision process through an iterative framework and the sometimes hard interpretation of some elements of urban sustainability

Regeneration of Rogoredo railway: a combined approach using multi-criteria and financial analysis

I vuoti urbani, quali ex aree industriali ed ex scali ferroviari, rappresentano oggi un’importante occasione di riconversione delle città, nell’ottica di uno sviluppo in chiave sostenibile, resiliente e circolare. Tuttavia, gli interventi di trasformazione e rigenerazione urbana sono caratterizzati da un elevato grado di complessità e dinamicità, così come da un’elevata interazione tra le diverse componenti urbane, quali gli aspetti economici, ambientali, sociali e tra i diversi attori coinvolti nel processo. In questo contesto, l’approccio metodologico proposto nel presente contributo combina le Analisi-Multicriteri (AMC) con l’analisi Analisi Finanziaria (AF). Questo modello permette di analizzare e supportare il processo decisionale nella sua complessità, considerando sia gli aspetti qualitativi (sociali e ambientali) sia quelli quantitativi (economico- finanziari). Il caso degli scali ferroviari dell’area di Rogoredo a Milano (Italia) rap- presenta un caso emblematico. La stessa città di Milano, già all’interno del Piano di Governo del Territorio (PGT), propone interventi volti alla riconnessione di questo nodo infrastrutturale per renderlo un polo attrattivo e inclusivo. L’obiettivo di questo contributo è quello di applicare le AMC con l’AF per la valutazione di scenari alternativi, volti alla riqualificazione dell’ex scalo ferroviario di Rogoredo. La valutazione diventa, quindi, parte integrante dell’intero processo decisionale, supportandone tutte le fasi, da quella iniziale fino alla definizione dello scenario più idoneo agli obiettivi prefissati e agli interessi degli stakeholder coinvolti. Il valore aggiunto fornito dalla presente applicazione è rappresentato proprio dalla possibilità di considerare sia il punto di vista degli investitori, attraverso l’AF, sia la più ampia prospettiva pubblica, attraverso il supporto delle AMC. In questo modo è stato possibile costruire e valutare scenari di trasformazione in grado di attrarre possibili investitori e al tempo stesso capaci di promuovere modelli di mobilita sostenibile, forme di inclusione sociale, sviluppo eco-sostenibile, miglioramento della qualità ambientale, attraverso la progettazione di nuove aree pubbliche, spazi verdi e servizi per i cittadini. In questo pro- cesso, la valutazione assume un ruolo essenziale in quanto consente di mettere in luce i diversi obiettivi perseguiti dall’intervento di rigenerazione e le loro eventuali conflittualità. Inoltre, la loro identificazione può supportare la definizione di scenari alternativi di sviluppo, rendendo partecipati sia il processo progettuale sia quello decisionale.Abandoned areas such as neglected railways and urban voids represent a suitable opportunity for the regeneration and requalification of cities, according to the paradigms of sustainability and resilience. Urban transformation and urban regeneration processes are characterized by a high level of complexity, a dynamic behavior over time and interactions between the various actors involved in the process. Within this context, the present paper proposes the application of a combined evaluation framework, based on the integration of Multi-Criteria Decision Analysis (MCDA) with a Financial Analysis (FA) to assess different strategic scenarios for the regeneration of the Rogoredo railways area (Milan, Italy). The purpose of this framework is to take into account the complexity of the decision-making process, considering both the qualitative (social and environmental) and quantitative (economic-financial) aspects. In detail, the railway yards in the Rogoredo area in Milan (Italy) represent an emblematic case. The city of Milan, within the Territory Governance Plan (PGT), has already proposed interventions in this site aimed at reconnecting the infrastructural node and making it an attractive and inclusive pole. The present paper demonstrates the usefulness of evaluation procedures in supporting the entire decision-making process and defining the most suitable scenario considering the initial objective and the stakeholders’ interests. The innovative value provided by this application is represented precisely by the possibility of considering both the developer point of view through FA and the broader public perspective through the support of MCDA. This approach allowed to build and evaluate transformation scenarios capable of both attracting potential investors and promoting sustainable mobility models, social inclusion, eco-sustainable development, improvement of environmental quality through the design of new public areas, green spaces, and services for citizens

Dose-Dependent Impairment of the Immune Response to the Moderna-1273 mRNA Vaccine by Mycophenolate Mofetil in Patients with Rheumatic and Autoimmune Liver Diseases

The purpose of this study was to evaluate the efficacy and safety of the Moderna-1273 mRNA vaccine for SARS-CoV-2 in patients with immune-mediated diseases under different treatments. Anti-trimeric spike protein antibodies were tested in 287 patients with rheumatic or autoimmune diseases (10% receiving mycophenolate mofetil, 15% low-dose glucocorticoids, 21% methotrexate, and 58% biologic/targeted synthetic drugs) at baseline and in 219 (76%) 4 weeks after the second Moderna-1273 mRNA vaccine dose. Family members or caretakers were enrolled as the controls. The neutralizing serum activity against SARS-CoV-2-G614, alpha, and beta variants in vitro and the cytotoxic T cell response to SARS-CoV-2 peptides were determined in a subgroup of patients and controls. Anti-SARS-CoV-2 antibody development, i.e., seroconversion, was observed in 69% of the mycophenolate-treated patients compared to 100% of both the patients taking other treatments and the controls (p < 0.0001). A dose-dependent impairment of the humoral response was observed in the mycophenolate-treated patients. A daily dose of >1 g at vaccination was a significant risk factor for non-seroconversion (ROC AUC 0.89, 95% CI 0.80-98, p < 0.0001). Moreover, in the seroconverted patients, a daily dose of >1 g of mycophenolate was associated with significantly lower anti-SARS-CoV-2 antibody titers, showing slightly reduced neutralizing serum activity but a comparable cytotoxic response compared to other immunosuppressants. In non-seroconverted patients treated with mycophenolate at a daily dose of >1 g, the cytotoxic activity elicited by viral peptides was also impaired. Mycophenolate treatment affects the Moderna-1273 mRNA vaccine immunogenicity in a dose-dependent manner, independent of rheumatological disease

Stima della portata della fistola artero-venosa mediante termodiluizione nei pazienti in emodialisi cronica: esperienza monocentrica.

Purpose: Vascular access surveillance in hemodialysis is today an important challenge for nephrologist. Low blood flow is a risk factor for development of thrombosis of native fistula or graft. The aim of the study is to evaluate the correspondence between flow measurement by thermodilution and Color Doppler, and to identify flow rate values using the Blood temperature monitor (BTM) method in the case of stenosis. Methods: We evaluated 29 patients on chronic hemodialysis. The evaluation of blood flow with BTM were performed during the first hour of the hemodialysis session. All patients underwent a color doppler of vascular access within 10 days from the BTM measurements. Results: The mean vascular access flow calculated with BTM resulted 1142 ± 700 ml/min and there was a correlation with color doppler data 1199 ± 644 ml/min (p=0,0001 r=0,829). The flow of patients with hemodynamically significant stenosis was 332 ± 92 ml/min with a minimum value of 270 ml/min and a maximum value of 440 ml/min. Conclusion: the correspondence between thermodilution and color doppler support the implementation of intradialitic evaluation of the vascular access blood flow with the BTM method. Thermodilution allows to identify earlier patients with high risk of vascular access failure and the need for further diagnostic and therapeutic investigations

Microglia control glutamatergic synapses in the adult mouse hippocampus

Microglia cells are active players in regulating synaptic development and plasticity in the brain. However, how they influence the normal functioning of synapses is largely unknown. In this study, we characterized the effects of pharmacological microglia depletion, achieved by administration of PLX5622, on hippocampal CA3-CA1 synapses of adult wild type mice. Following microglial depletion, we observed a reduction of spontaneous and evoked glutamatergic activity associated with a decrease of dendritic spine density. We also observed the appearance of immature synaptic features and higher levels of plasticity. Microglia depleted mice showed a deficit in the acquisition of the Novel Object Recognition task. These events were accompanied by hippocampal astrogliosis, although in the absence ofneuroinflammatory condition. PLX-induced synaptic changes were absent in Cx3cr1−/− mice, highlighting the role of CX3CL1/CX3CR1 axis in microglia control of synaptic functioning. Remarkably, microglia repopulation after PLX5622 withdrawal was associated with the recovery of hippocampal synapses and learning functions. Altogether, these data demonstrate that microglia contribute to normal synaptic functioning in the adult brain and that their removal induces reversible changes in organization and activity of glutamatergic synapses

Morphology of the toe flexor muscles in older people with toe deformities

Objective: Despite suggestions that atrophied, or weak toe flexor muscles are associated with the formation of toe deformities, there has been little evidence to support this theory. This study aimed to determine whether the size of the toe flexor muscles differed in older people with and without toe deformities. Methods: Forty-four older adults (>60 years) were recruited for the study. Each participant had their feet assessed for the presence of hallux valgus or lesser toe deformities. Intrinsic and extrinsic toe flexor muscles were imaged with an ultrasound system using a standardised protocol. Assessor blinded muscle thickness and cross-sectional area was measured using Image J software. Results: Participants with lesser toe deformities (n=20) were found to have significantly smaller quadratus plantae (p=0.003), flexor digitorum brevis (p=0.013), abductor halluces (p=0.004) and flexor halluces brevis (p=0.005) muscles than the participants without any toe deformities (n=19). Female participants with hallux valgus (n=10) were found to have significantly smaller abductor hallucis (p=0.048) and flexor halluces brevis (p=0.013) muscles than the female participants without any toe deformities (n=10; p<0.05). Conclusion: This is the first study to use ultrasound to investigate the size of the toe flexor muscles in older people with hallux valgus and lesser toe deformities compared to otherwise healthy older adults. The size of the abductor hallucis and flexor hallucis brevis muscles were decreased in participants with hallux valgus whereas the quadratus plantae, flexor digitorum brevis, abductor hallucis and flexor halluces brevis muscles were smaller in those participants with lesser toe deformities

COVID-19 in rheumatic diseases in Italy: first results from the Italian registry of the Italian Society for Rheumatology (CONTROL-19)

OBJECTIVES: Italy was one of the first countries significantly affected by the coronavirus disease 2019 (COVID-19) epidemic. The Italian Society for Rheumatology promptly launched a retrospective and anonymised data collection to monitor COVID-19 in patients with rheumatic and musculoskeletal diseases (RMDs), the CONTROL-19 surveillance database, which is part of the COVID-19 Global Rheumatology Alliance. METHODS: CONTROL-19 includes patients with RMDs and proven severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) updated until May 3rd 2020. In this analysis, only molecular diagnoses were included. The data collection covered demographic data, medical history (general and RMD-related), treatments and COVID-19 related features, treatments, and outcome. In this paper, we report the first descriptive data from the CONTROL-19 registry. RESULTS: The population of the first 232 patients (36% males) consisted mainly of elderly patients (mean age 62.2 years), who used corticosteroids (51.7%), and suffered from multi-morbidity (median comorbidities 2). Rheumatoid arthritis was the most frequent disease (34.1%), followed by spondyloarthritis (26.3%), connective tissue disease (21.1%) and vasculitis (11.2%). Most cases had an active disease (69.4%). Clinical presentation of COVID-19 was typical, with systemic symptoms (fever and asthenia) and respiratory symptoms. The overall outcome was severe, with high frequencies of hospitalisation (69.8%), respiratory support oxygen (55.7%), non-invasive ventilation (20.9%) or mechanical ventilation (7.5%), and 19% of deaths. Male patients typically manifested a worse prognosis. Immunomodulatory treatments were not significantly associated with an increased risk of intensive care unit admission/mechanical ventilation/death. CONCLUSIONS: Although the report mainly includes the most severe cases, its temporal and spatial trend supports the validity of the national surveillance system. More complete data are being acquired in order to both test the hypothesis that RMD patients may have a different outcome from that of the general population and determine the safety of immunomodulatory treatments