Concerted versus stepwise proton transfer reactions in the [2, 2'-bipyridyl]-3-3'-diol molecule: A static and dynamic ab-initio investigation.

The double proton transfer (PT) reaction has been investigated in the [2,2'-bipyridyl]-3-3'-diol, a complex molecule where the proton movements is coupled to significant rearrangement of the electronic structure. Moreover, the reaction could be concerted, that is the two protons are exchanged simultaneously, or stepwise, where the two protons are transferred sequentially. To this end, a static exploration of the potential energy surface (PES) was carried together with the analysis of the free-energy surface (FES), both surfaces being evaluated at density functional theory level and different exchange-correlation functionals. While the concerted mechanism has been clearly discharged, the characteristics of the stepwise PT significantly depends on the chosen functionals, some suggesting a clear stepwise mechanism characterized by a stable reaction intermediates and two transitions states, whereas other approaches propend for a asynchronous PT, with a single TS. These features appear on both PES and FES, albeit some differences appears due to their different nature.

"Cyclopropylidene Effect" in the 1,3-Dipolar Cycloaddition of Nitrones to Alkylidene Cyclopropanes: A Computational Rationalization.

The regioselectivity in the 1,3-dipolar cycloaddition (1,3-DC) between five-membered cyclic nitrone and methylenecyclopropane (MCP) has been studied through density functional theory (DFT) calculations. The computational study of 1,3-DC with different 1-alkyl- (or 1,1-dialkyl)-substituted alkenes and the comparison with MCP have evidenced that the electrostatic interaction has a central role in the regioselectivity of the reactions. It has been observed that the electronic effect of the substituent (donor or attractor groups) determines the polarization of the alkene double bond and the reaction mechanism, consequently determining the interaction with nitrones and favoring an orientation between this moiety and the dipolarophile.

Computational Investigation of the Selective Cleavage of Diastereotopic Cyclopropane Bonds in 5-Spirocyclopropane Isoxazolidines Rearrangement.

The complete path of the Brandi-Guarna rearrangement of 5-spirocyclopropane isoxazolidines has been investigated by means of density functional theory calculations to rationalize the competing formation of tetrahydropyridones and enaminones by the determination of the minimum energy reaction paths. Our calculations confirm that the rearrangement is triggered by the homolysis of the isoxazolidine N-O bond followed by cleavage of one of the two C-CH2 cyclopropane bonds as previously proposed by the Fabian group [ Eur. J. Org. Chem. 2001, 2001, 4223]. In addition, the results of this work suggest that in the presence of a stereogenic center at isoxazolidine C-4', the formation of a piperidinone or an enaminone as the final product depends on which of the two diastereotopic C-CH2 bonds of cyclopropane is cleaved in the second step of the process. The result can be of great interest for the understanding of other processes involving the opening of a cyclopropane ring.

Synthesis and biological evaluation of 3-hydroxymethyl-5-(1H-1,2,3-triazol) isoxazolidines.

A synthetic approach towards a series of 3-hydroxymethyl-5-(1H-1,2,3-triazol)isoxazolidines has been reported, according to a procedure based on the cycloaddition reaction, under microwave irradiation, of a nitrone with 1-vinyl triazoles, prepared by a click reaction of azides with alkynes. Biological tests show that the synthesized compounds are able to inhibit proliferation of follicular and anaplastic human thyroid cancer cell lines, with IC50 values ranging from 3.87 to 8.76 lM. The obtained compounds induce caspase-3 activation and DNA fragmentation prevalently in follicular human thyroid cancer cell lines.

Personal eating, lifestyle, and family-related behaviors correlate with fruit and vegetable consumption in adolescents living in sicily, southern Italy.

Lifestyle habits and parental modeling have been reported to influence adolescents’ food choices, such as for fruit and vegetable consumption. The aim of this study was to investigate the association be-tween personal eating (i. e. breakfast and snacking behavior), lifestyle (sedentary and physical activity), and family-related (i. e. consuming meals with parents, family rules, and television use) habits and fruit and vegetable consumption among adolescents living in Sicily, southern Italy. A cross-sectional survey was conducted across 14 schools in urban and rural areas, including 1,135 adolescents (12 - 14 years old). Validated instruments were used to assess possible relationships between the study variables and daily fruit and vegetable consumption. Higher parental education, occupation, and rural environment were positively associated with adolescents’ daily consumption of fruits and vegetables. Both types of food consumption were negatively associated with an increased frequency of between-meal and out-of-home eating, and positively with having meals with parents and higher parental influence in adolescents’ food choices. Television viewing habits were not related with adolescents’ vegetable consumption, whereas having a television in their room and commercial advertisings were negatively associated with daily intake of fruits. Although socioeconomic and cultural status may influence fruit and vegetable consumption, personal eating and family-related behaviors may be targeted for implementing recommendations.

The Impact of Rotavirus Vaccination on Discharges for Pediatric Gastroenteritis in Italy: An Eleven Year (2009-2019) Nationwide Analysis.

In Italy, despite the documented positive effects of rotavirus (RV) vaccination on reducing the burden of RV disease, an updated national assessment of its impact on clinical outcomes is still lacking. This study aims to analyze the implementation of RV vaccination in Italy, evaluating its impact on discharges for acute pediatric gastroenteritis (AGE). A retrospective analysis, including hospital discharge records and data on vaccination coverage for children aged 0-71 months from 2009 to 2019, was conducted. We examined trends in hospital discharge standardized incidence before and after vaccine introduction using a negative binomial mixture model with fixed effects to evaluate the impact of universal vaccination. The percentage of vaccination coverage increased over the years, from <5% between 2009 and 2013 to 26% in 2017, reaching 70% in 2019. The standardized incidence of discharges decreased over the period from 16.6/100,000 inhabitants in 2009-2013 to 9.9/100,000 inhabitants in 2018-2019. In this phase, about 15% of the estimated hospital discharges were avoided compared with those estimated in the first phase. The implementation of RV vaccination reduced AGE incidence discharges in children aged 0-71 months. Further efforts are needed to continue monitoring the vaccination effect over time and to increase vaccination coverage.

Early Warning Systems for Emerging Profiles of Antimicrobial Resistance in Italy: A National Survey.

Antimicrobial resistance (AMR) national surveillance systems in Italy lack alert systems for timely detection of emerging profiles of AMR with potential relevance to public health. Furthermore, the existence of early warning systems (EWS) at subnational level is unclear. This study aims at mapping and characterizing EWS for microbiological threats available at regional level in Italy, focusing on emerging AMR, and at outlining potential barriers and facilitators to their development/implementation. To this end, a three-section, web-based survey was developed and administered to all Italian regional AMR representatives from June to August 2022. Twenty out of twenty-one regions and autonomous provinces (95.2%) responded to the survey. Among these, nine (45%) reported the implementation of EWS for microbiological threats at regional level, three (15%) reported that EWS are in the process of being developed, and eight (40%) reported that EWS are not currently available. EWS characteristics varied widely among the identified systems concerning both AMR profiles reported and data flow: the microorganisms most frequently included were extensively drug-resistant (XDR) Enterobacterales, with the lack of a dedicated regional IT platform reported in most cases. The results of this study depict a highly heterogeneous scenario and suggest that more efforts aimed at strengthening national AMR surveillance systems are needed.

Exploring the effect of Mg2+ substitution on amorphous calcium phosphate nanoparticles.

HYPOTHESIS: The study of Amorphous Calcium Phosphate (ACP) has become a hot topic due to its relevance in living organisms and as a material for biomedical applications. The preparation and characterization of Mg-substituted ACP nanoparticles (AMCP) with tunable Ca/Mg ratio is reported in the present study to address the effect of Mg2+ on their structure and stability. EXPERIMENTS: AMCPs particles were synthesized by precipitation of the precursors from aqueous solutions. The particles were analyzed in terms of morphology, crystallinity, and thermal stability, to get a complete overview of their physico-chemical characteristics. Computational methods were also employed to simulate the structure of ACP clusters at different levels of Mg2+ substitution. FINDINGS: Our results demonstrate that AMCP particles with tunable composition and crystallinity can be obtained. The analysis of the heat-induced crystallization of AMCP shows that particles' stability depends on the degree of Mg2+ substitution in the cluster, as confirmed by computational analyses. The presented results shed light on the effect of Mg2+ on ACP features at different structural levels and may be useful guidelines for the preparation and design of AMCP particles with a specific Ca/Mg ratio.