Passive Sampling of Chemical Warfare Agents in the Marine Environment

Dumping sites of chemical warfare agents related compounds have been created after the two last major wars. The assessment of the risks connected to these sites is a priority as they could threaten the human health directly, through incidents when the dangerous materials come directly into contact with a subject and indirectly, as the poisonous substances can affect the environment and enter the food chain. Many techniques have been involved in the monitoring, for example sediment analysis and mussels bio-monitoring. To overcome the deficiencies of these techniques and to obtain a more complete overview of the situations, new ways of analysis are studied. In this thesis the passive sampler technique was studied as new method to monitor the chemical warfare agents dumping sites. This technique has been often used in the environmental monitoring of air and water samples. In the specific this work focused its attention in the use of silicone sheets as passive samplers, investigating their effectiveness with the substances of interest: sulfur mustard derivatives, arsine related chemical warfare agents derivatives and α-chloroacetophenone. Furthermore, the extraction power of different solvents was tested and a theoretical study of the opposing phenomena that compete in the extraction process was carried out. Finally, the theoretical uptake model was tested on the different substances verifying its validity and showing how the efficacy of the passive sampling technique depends on various factors like the sampler-water partition coefficient, the relative recovery from the sampler and the stability of the compound of interest. The recovery studies have shown how acetone is the best solvent with a wide variety of compounds, but its extraction power can be improved towards less polar compounds using a solution of acetone/ethyl acetate 9:1. The effectiveness of silicone sheets as passive samplers was demonstrated by the kinetic studies. Stable compounds with a high octanol-water partition coefficient (≥ 3) present the best results showing good agreement with the theoretical model. The next step will be testing the silicone sheets near known dumpsites using performance reference compounds as in situ calibration

Web Component per un Design System: un caso di studio aziendale

I contenuti e i servizi offerti dal Web hanno subito negli anni una costante e continua evoluzione, dovuti alla maggiore disponibilità di dispositivi in grado di navigarlo. Oggi i requisiti e le aspettative che gli utenti hanno nei confronti delle applicazioni Web sono sempre maggiori, desiderano un accesso ai contenuti sempre più rapido, interfacce semplici e facili da usare, oltre che reattive, e che tali contenuti siano accessibili da una vasta gamma di dispositivi che presentino sempre più funzionalità. Le aziende devono essere pronte a rispondere a queste esigenze e a fornire agli utenti finali la miglior esperienza possibile, rimanendo aggiornati sulle tecnologie per la creazione di applicazioni Web. Questo è ancora più importante per un'azienda possiede più prodotti, sviluppati da team diversi che usano tecnologie diverse. Per alcune aziende è importante che i propri prodotti, sebbene trattino tematiche differenti, si presentino con interfacce che rimandino al proprio marchio, non solo grazie al nome o al logo, quanto più nei componenti utilizzati per creare le interfacce. Succede così che i vari team devono progettare e sviluppare i componenti nella propria tecnologia, in modo che abbiano le stesse funzionalità, stesso stile e stesso comportamento in ogni situazione. Il più delle volte questo è difficile da realizzare e anche costoso da mantenere. Riuscire a centralizzare lo sviluppo di questi elementi in un unico punto aiuta l'azienda a mantenere bassi i costi di manutenzione e a rendere omogenea l'esperienza degli utenti tra i vari prodotti. Obiettivo del lavoro svolto è illustrare le potenzialità e l'utilità fornite dall'introduzione di una suite di componenti personalizzati, seguendo lo standard dei Web Component, all'interno dei prodotti forniti da una grande impresa. L'analisi si concentra sulll'esperienza di chi utilizza tali componenti all'interno dei propri progetti per creare l'interfaccia utente da presentare poi agli utenti finali

Comparison of Adaptive Neuroprotective Mechanisms of Sulforaphane and its Interconversion Product Erucin in in Vitro and in Vivo Models of Parkinson's Disease

Several studies suggest that an increase of glutathione (GSH) through activation of the transcriptional nuclear factor (erythroid-derived 2)-like 2 (Nrf2) in the dopaminergic neurons may be a promising neuroprotective strategy in Parkinson's disease (PD). Among Nrf2 activators, isothiocyanate sulforaphane (SFN), derived from precursor glucosinolate present in Brassica vegetables, has gained attention as a potential neuroprotective compound. Bioavailability studies also suggest the contribution of SFN metabolites, including erucin (ERN), to the neuroprotective effects of SFN. Therefore, we compared the in vitro neuroprotective effects of SFN and ERN at the same dose level (5 \u3bcM) and oxidative treatment with 6-hydroxydopamine (6-OHDA) in SH-SY5Y cells. The pretreatment of SH-SY5Y cells with SFN recorded a higher (p < 0.05) active nuclear Nrf2 protein (12.0 \ub1 0.4 vs 8.0 \ub1 0.2 fold increase), mRNA Nrf2 (2.0 \ub1 0.3 vs 1.4 \ub1 0.1 fold increase), total GSH (384.0 \ub1 9.0 vs 256.0 \ub1 8.0 \u3bcM) levels, and resistance to neuronal apoptosis elicited by 6-OHDA compared to ERN. By contrast, the simultaneous treatment of SH-SY5Y cells with either SFN or ERN and 6-OHDA recorded similar neuroprotective effects with both the isothiocyanates (Nrf2 protein 2.2 \ub1 0.2 vs 2.1 \ub1 0.1 and mRNA Nrf2 2.1 \ub1 0.3 vs 1.9 \ub1 0.2 fold increase; total GSH 384.0 \ub1 4.8 vs 352.0 \ub1 6.4 \u3bcM). Finally, in vitro finding was confirmed in a 6-OHDA-PD mouse model. The metabolic oxidation of ERN to SFN could account for their similar neuroprotective effects in vivo, raising the possibility of using vegetables containing a precursor of ERN for systemic antioxidant benefits in a similar manner to SFN

First diagnosis of multisystem inflammatory syndrome in children (MIS-C): an analysis of PoCUS findings in the ED

Children with multisystem inflammatory syndrome (MIS-C) tend to develop a clinical condition of fluid overload due both to contractile cardiac pump deficit and to endotheliitis with subsequent capillary leak syndrome. In this context, the ability of point-of-care ultrasound (PoCUS) to simultaneously explore multiple systems and detect polyserositis could promote adequate therapeutic management of fluid balance. We describe the PoCUS findings in a case-series of MIS-C patients admitted to the Emergency Department. At admission 10/11 patients showed satisfactory clinical condition without signs and symptoms suggestive for cardiovascular impairment/shock, but PoCUS showed pathological findings in 11/11 (100%). In particular, according to Rapid Ultrasound in SHock (RUSH) protocol, cardiac hypokinesis was detected in 5/11 (45%) and inferior vena cava dilatation in 3/11 (27%). Peritoneal fluid was reported in 6/11 cases (54%). Lung ultrasound (LUS) evaluation revealed an interstitial syndrome in 11/11 (100%), mainly localized in posterior basal lung segments. We suggest PoCUS as a useful tool in the first evaluation of children with suspected MIS-C for the initial therapeutic management and the following monitoring of possible cardiovascular deterioration

Design, Synthesis and Biological Evaluation of Novel Triazole N-acylhydrazone Hybrids for Alzheimer's Disease

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that involves different pathogenic mechanisms. In this regard, the goal of this study was the design and synthesis of new compounds with multifunctional pharmacological activity by molecular hybridization of structural fragments of curcumin and resveratrol connected by an N-acyl-hydrazone function linked to a 1,4-disubstituted triazole system. Among these hybrid compounds, derivative 3e showed the ability to inhibit acetylcholinesterase activity, the intracellular formation of reactive oxygen species as well as the neurotoxicity elicited by Aβ42 oligomers in neuronal SH-SY5Y cells. In parallel, compound 3e showed a good profile of safety and ADME parameters. Taken together, these results suggest that 3e could be considered a lead compound for the further development of AD therapeutics

COVID-19 in Infants Less than 3 Months: Severe or Not Severe Disease?

Compared to adults, severe or fatal COVID-19 disease is much less common in children. However, a higher risk for progression has been reported in infants. Different pediatric COVID-19 severity scores are reported in the literature

Epidemiology, Clinical Features and Prognostic Factors of Pediatric SARS-CoV-2 Infection: Results From an Italian Multicenter Study

Background: Many aspects of SARS-CoV-2 infection in children and adolescents remain unclear and optimal treatment is debated. The objective of our study was to investigate epidemiological, clinical and therapeutic characteristics of pediatric SARS-CoV-2 infection, focusing on risk factors for complicated and critical disease. Methods: The present multicenter Italian study was promoted by the Italian Society of Pediatric Infectious Diseases, involving both pediatric hospitals and general pediatricians/family doctors. All subjects under 18 years of age with documented SARS-CoV-2 infection and referred to the coordinating center were enrolled from March 2020. Results: As of 15 September 2020, 759 children were enrolled (median age 7.2 years, IQR 1.4; 12.4). Among the 688 symptomatic children, fever was the most common symptom (81.9%). Barely 47% of children were hospitalized for COVID-19. Age was inversely related to hospital admission (p &lt; 0.01) and linearly to length of stay (p = 0.014). One hundred forty-nine children (19.6%) developed complications. Comorbidities were risk factors for complications (p &lt; 0.001). Viral coinfections, underlying clinical conditions, age 5\u20139 years and lymphopenia were statistically related to ICU admission (p &lt; 0.05). Garazzino et al. SARS-CoV-2 in Children and Adolescents Conclusions: Complications of COVID-19 in children are related to comorbidities and increase with age. Viral co-infections are additional risk factors for disease progression and multisystem inflammatory syndrome temporarily related to COVID-19 (MIS-C) for ICU admission

Design, synthesis, and biological evaluation of new thalidomide–donepezil hybrids as neuroprotective agents targeting cholinesterases and neuroinflammation

A new series of eight multifunctional thalidomide–donepezil hybrids were synthesized based on the multi target-directed ligand strategy and evaluated as potential neuroprotective, cholinesterase inhibitors and anti neuroinflammatory agents against neurodegenerative diseases. A molecular hybridization approach was used for structural design by combining the N-benzylpiperidine pharmacophore of donepezil and the isoindoline 1,3-dione fragment from the thalidomide structure. The most promising compound, PQM-189 (3g), showed good AChE inhibitory activity with an IC50 value of 3.15 μM, which was predicted by docking studies as interacting with the enzyme in the same orientation observed in the AChE–donepezil complex and a similar profile of interaction. Additionally, compound 3g significantly decreased iNOS and IL-1β levels by 43% and 39%, respectively, after 24 h of incubation with lipopolysaccharide. In vivo data confirmed the ability of 3g to prevent locomotor impairment and changes in feeding behavior elicited by lipopolysaccharide. Moreover, the PAMPA assay evidenced adequate blood–brain barrier and gastrointestinal tract permeabilities with an Fa value of 69.8%. Altogether, these biological data suggest that compound 3g can treat the inflammatory process and oxidative stress resulting from the overexpression of iNOS and therefore the increase in reactive nitrogen species, and regulate the release of pro-inflammatory cytokines such as IL-1β. In this regard, compound PQM-189 (3g) was revealed to be a promising neuroprotective and anti-neuroinflammatory agent with an innovative thalidomide–donepezil-based hybrid molecular architectur

Multicentre Italian study of SARS-CoV-2 infection in children and adolescents, preliminary data as at 10 April 2020

Data on features of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in children and adolescents are scarce. We report preliminary results of an Italian multicentre study comprising 168 laboratory-confirmed paediatric cases (median: 2.3 years, range: 1 day-17.7 years, 55.9% males), of which 67.9% were hospitalised and 19.6% had comorbidities. Fever was the most common symptom, gastrointestinal manifestations were frequent; two children required intensive care, five had seizures, 49 received experimental treatments and all recovered