Study of the urinary biomarkers of synthetic cannabinoid receptor agonists (SCRAs) for the forensic unequivocal proof of consumption: medico-legal implications for drug abuse prevention

Introduction. Synthetic cannabinoid receptor agonists (SCRAs) represent the widest group of New Psychoactive Substances (NPS) and, around 2021-2022, new compounds emerged on the market. The aims of the present research were to identify suitable urinary markers of Cumyl-CB-MEGACLONE, Cumyl-NB-MEGACLONE, Cumyl-NB-MINACA, 5F-EDMB-PICA, EDMB-PINACA and ADB-HEXINACA, to present data on their prevalence and to adapt the methodology from the University of Freiburg to the University of Bologna. Materials and methods. Human phase-I metabolites detected in 46 authentic urine samples were confirmed in vitro with pooled human liver microsomes (pHLM) assays, analyzed by liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qToF-MS). Prevalence data were obtained from urines collected for abstinence control programs. The method to study SCRAs metabolism in use at the University of Freiburg was adapted to the local facilities, tested in vitro with 5F-EDMB-PICA and applied to the study of ADB-HEXINACA metabolism. Results. Metabolites built by mono, di- and tri-hydroxylation were recommended as specific urinary biomarkers to monitor the consumption of SCRAs bearing a cumyl moiety. Monohydroxylated and defluorinated metabolites were suitable proof of 5F-EDMB-PICA consumption. Products of monohydroxylation and amide or ester hydrolysis, coupled to monohydroxylation or ketone formation, were recognized as specific markers for EDMB-PINACA and ADB-HEXINACA. The LC-qToF-MS method was successfully adapted to the University of Bologna, as tested with 5F-EDMB-PICA in vitro metabolites. Prevalence data showed that 5F-EDMB-PINACA and EDMB-PINACA were more prevalent than ADB-HEXINACA, but for a limited period. Conclusion. Due to undetectability of parent compounds in urines and to shared metabolites among structurally related compounds, the identification of specific urinary biomarkers as unequivocal proofs of SCRAs consumption remains challenging for forensic laboratories. Urinary biomarkers are necessary to monitor SCRAs abuse and prevalence data could help in establishing tailored strategies to prevent their spreading, highlighting the role for legal medicine as a service to public health.

Soil quality in an experimental vineyard treated with biochar and compost

In order to increase fertility of agricultural soils, in the framework of circular economy, the use of soil amendments such as biochar, compost, and mixtures of the two, has been implemented in recent years. Although it has been demonstrated that their use can improve the physico-chemical characteristics of soil and plant yield, few studies investigated the effect of these amendments on the soil fauna, and consequently the biological quality of soils. This study aimed to provide information on soil fauna, in particular microarthropods , in plots of an experimental vineyard treated with different soil amendments (biochar, compost, and CB mix, i.e. a mixture of biochar and compost) compared to untreated plots. What emerged from this study is that taxa abundances are significantly increased in compost-treated soil samples compared to untreated and CB mix ones. The value of the QBS-ar index obtained in soil samples treated with CB mix is lower than in samples treated with compost, biochar, and untreated, although the difference was not statistically significant. The physico-chemical soil characteristics are, in general, significantly more favorable in samples treated with CB mix than in the control, although the soil fauna seems to be partially negatively influenced by the treatment with CB mix. In fact, the number of taxa, in particular the number of taxa most adapted to edaphic life, are significantly negatively affected by the application of the CB mix. Concluding, improved physico-chemical characteristics induced by soil amendments do not always correspond to a positive response of the soil fauna, at least with respect to the QBS-ar approach.

“Study of Electro-thermal Effects on PLA Materials Fed with AC Currents”

Given the rise in the emergence of new composite materials, their multifunctional properties, and possible applications in simple and complex structural components, there has been a need to unravel the characterization of these materials. The possibility of printing these conductive composite materials has opened a new area in the design of structural components which can conduct, transmit, and modulate electric signals with no limitation from complex geometry. Although several works have researched the behaviour of polymeric composites due to the immediate growth, however, the electrothermal behaviour of the material when subjected to varying AC applied voltage (Joule’s effect) has not been thoroughly researched. This study presents the characterization of the electrothermal behaviour of conductive composites of a polylactic acid matrix reinforced with conductive carbon black particles (CB-PLA). An understanding of this behaviour would contribute to the improved work in additive manufacturing of functional electro-mechanical conductive materials with potential application in energy systems, bioelectronics, etc. In this study, the electrothermal interplay is monitored under applied AC voltage, varying lengths, and filament printing orientations (longitudinal, oblique, and transverse). Each sample was printed using the fused deposition modeling technique such that each specimen has three different lengths (1L, 2L, 2.75L). To this end, deductions were made on properties that affect composite’s efficiency and life expectancy. The result of this study shows a great influence of printing orientation on material properties of 3D printed conductive composites of CB-PLA. The result also identifies the contribution of AC applied voltage to composites' stabilization time. This knowledge is important to provide experimental background for components' electrothermal interplay, estimate possible degradation and operating limits of composite structures when used in applications.

Qualifica e mappatura di apparecchiature e sistemi rilevanti per l’industria farmaceutica

Il settore farmaceutico è regolato da numerose norme e linee guida al fine di tutelare la salute del consumatore. Infatti, il principio generale che governa lo sviluppo e l’operabilità di un impianto farmaceutico prevede che l’utilizzatore debba fornire l’evidenza documentale che il sistema sia “qualificato” e che il processo produttivo che in esso risiede sia “convalidato” e mantenuto in tale stato. Sulla base di quanto detto risulta essenziale, prima dell'accettazione alla produzione di un nuovo farmaco, che venga confermata una valutazione esatta e affidabile per la sua realizzazione e per la sicurezza degli utilizzatori, garantendone la qualità. Tale elaborato è volto ad analizzare suddetta gestione delle richieste normative in ambito di qualifica dei sistemi farmaceutici, come frutto di un’esperienza formativa svolta presso lo stabilimento di Termoli (CB) della F.I.S. – Fabbrica Italiana Sintetici S.p.A. Il processo di qualifica è stato messo in atto per l’installazione di una nuova centrifuga e per la mappatura termo-igrometrica del nuovo magazzino automatizzato dello stabilimento. Nello specifico, i due casi studio esaminati sono stati individuati grazia ad una prima presentazione del sistema inquadrato nella produzione di principi attivi farmaceutici, seguita dall’analisi dei protocolli (standard e non) di qualifica da compilare nella fase esecutiva. Nell’elaborato sono stata presentate e comparate le normative e le linee guide vigenti del settore, quali EU GMP Guidelines, ISPE Baseline Guide e UNI EN ISO 9001:2015 per la gestione della qualità, e le procedure aziendali, nell’ottica delle norme di buona documentazione e del rispetto del data integrity. L’esecuzione dei due progetti ha permesso l’avvio e la messa in esercizio di sistemi critici per la produzione di principi attivi farmaceutici, garantendo il miglioramento delle prestazioni complessive dell’impianto.