Refining Rates of Active Crustal Deformation in the Upper Plate of Subduction Zones, Implied by Geological and Geodetic Data: The E-Dipping West Crati Fault, Southern Italy

We investigate crustal deformation within the upper plate of the Ionian Subduction Zone (ISZ) at different time scales by (i) refining geodetic rates of crustal extension from continuous Global Navigation Satellite System (GNSS) measurements and (ii) mapping sequence of Late Quaternary raised marine terraces tectonically deformed by the West Crati normal fault, in northern Calabria. This region experienced damaging earthquakes in 1184 (M 6.75) and 1854 (M 6.3), possibly on the E-dipping West Crati fault (WCF) which, however, is not unanimously considered to be a seismogenic source. We report geodetic measurements of extension and strain rates across the strike of the E dipping WCF and throughout the northern Calabria obtained by using velocities from 18 permanent GNSS stations with a series length longer than 4.5 years. These results suggest that crustal extension may be seismically accommodated in this region by a few normal faults. Furthermore, by applying a synchronous correlation approach, we refine the chronology of understudied tectonically deformed palaeoshorelines mapped on the footwall and along the strike of the WCF, facilitating calculation of the associated fault-controlled uplift rates. Raised Late Quaternary palaeoshorelines are preserved on the footwall of the WCF indicating that “regional” uplift, likely related to the deformation associated either with the subduction or mantle upwelling processes, is affected by local footwall uplift. We show that GIS-based elevations of Late Quaternary palaeoshorelines, as well as temporally constant uplift rates, vary along the strike of the WCF, implying normal faulting activity through time. This suggests that (i) the fault slip rate governing seismic hazard has also been constant over the Late Quaternary, over multiple earthquake cycles, and (ii) our geodetically derived fault throw rate for the WCF is likely a more than reasonable value to be used over longer time scales for an improved seismic hazard assessment. Overall, we emphasize the importance of mapping crustal deformation within the upper plate above subduction zones to avoid unreliable interpretations relating to the mechanism controlling regional uplift

Worsening of the Toxic Effects of (±) Cis -4,4′-DMAR Following Its Co-Administration with (±) Trans -4,4′-DMAR: Neuro-Behavioural, Physiological, Immunohistochemical and Metabolic Studies in Mice

© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/4.0/).4,4’-Dimethylaminorex (4,4’-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1–60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4′-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers’ co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.Peer reviewedFinal Published versio

Coupled surface to deep Earth processes: Perspectives from TOPO-EUROPE with an emphasis on climate- and energy-related societal challenges

Understanding the interactions between surface and deep Earth processes is important for research in many diverse scientific areas including climate, environment, energy, georesources and biosphere. The TOPO-EUROPE initiative of the International Lithosphere Program serves as a pan-European platform for integrated surface and deep Earth sciences, synergizing observational studies of the Earth structure and fluxes on all spatial and temporal scales with modelling of Earth processes. This review provides a survey of scientific developments in our quantitative understanding of coupled surface-deep Earth processes achieved through TOPO-EUROPE. The most notable innovations include (1) a process-based understanding of the connection of upper mantle dynamics and absolute plate motion frames; (2) integrated models for sediment source-to-sink dynamics, demonstrating the importance of mass transfer from mountains to basins and from basin to basin; (3) demonstration of the key role of polyphase evolution of sedimentary basins, the impact of pre-rift and pre-orogenic structures, and the evolution of subsequent lithosphere and landscape dynamics; (4) improved conceptual understanding of the temporal evolution from back-arc extension to tectonic inversion and onset of subduction; (5) models to explain the integrated strength of Europe's lithosphere; (6) concepts governing the interplay between thermal upper mantle processes and stress-induced intraplate deformation; (7) constraints on the record of vertical motions from high-resolution data sets obtained from geo-thermochronology for Europe's topographic evolution; (8) recognition and quantifications of the forcing by erosional and/or glacial-interglacial surface mass transfer on the regional magmatism, with major implications for our understanding of the carbon cycle on geological timescales and the emerging field of biogeodynamics; and (9) the transfer of insights obtained on the coupling of deep Earth and surface processes to the domain of geothermal energy exploration. Concerning the future research agenda of TOPO-EUROPE, we also discuss the rich potential for further advances, multidisciplinary research and community building across many scientific frontiers, including research on the biosphere, climate and energy. These will focus on obtaining a better insight into the initiation and evolution of subduction systems, the role of mantle plumes in continental rifting and (super)continent break-up, and the deformation and tectonic reactivation of cratons; the interaction between geodynamic, surface and climate processes, such as interactions between glaciation, sea level change and deep Earth processes; the sensitivity, tipping points, and spatio-temporal evolution of the interactions between climate and tectonics as well as the role of rock melting and outgassing in affecting such interactions; the emerging field of biogeodynamics, that is the impact of coupled deep Earth – surface processes on the evolution of life on Earth; and tightening the connection between societal challenges regarding renewable georesources, climate change, natural geohazards, and novel process-understanding of the Earth system

Ketamine chiral analysis in alternative and innovative biological samples

Ketamine ((R,S-2-(2-chlorophenyl)-2-methylamino)cyclohexanone) is a phencyclidine derivative used in human and veterinary clinical practice since 1970. It is a dissociative anaesthetic agent that induces also analgesia by non-opioid mechanisms. Ketamine causes a state of "dissociative anaesthesia", for this reason is used as a recreational drug and has been included in the controlled substance schedules of most countries. As an anaesthetic drug, Ketamine is commercially available as a racemic mixture however, (R)-Ketamine and (S)-Ketamine have significantly different pharmacodynamic activities: the therapeutic potency of (S)-Ket is 2-4 times greater than the that of the (R)-enantiomer, as regards anaesthetic and analgesic effects. Moreover, the post-hypnotic stimulatory properties and agitated behaviour are associated with (R)-Ket. On the other hand, even if Ketamine hallucinogenic potency is still largely unclear, some authors claim that the (R)-enantiomer is the most potent one. It has also been reported that (R)- and (S)-Ket have significantly different pharmacokinetic profiles. Thus, it is evident the need to provide analytical methods able to discriminate and simultaneously quantify both Ketamine enantiomers in biological matrices for pharmacokinetic, toxicological and forensic purposes. The aim of this study is the development of an analytical method for Ketamine chiral analysis in alternative and innovative biological fluids and tissues, such as Dried Blood Spots (DBSs), saliva and hair. Different chromatographic setups were tested to obtain a good enantioseparation by liquid chromatography with fluorimetric detection (HPLC-F). The assays are currently under validation and seem to be promising for a successfull Ketamine enantiomeric resolution and determination, in order to be applied to real biological samples

Dried blood spot testing: an innovative approach to overcome cannabinoid instability in blood

Cannabis is the most widely used illicit drug around the world and among the drugs of abuse (DoA) most frequently involved in street accidents. Therefore, it is important to strictly monitor Cannabis abuse. Until now, the most reliable biological matrix for this purpose is represented by blood (whole blood/plasma), which can provide useful information about drug consumption. However, its sampling and storage require complicated and time consuming precautions, such as centrifugation and refrigeration or freezing, in order to preserve analyte stability. To overcome these disadvantages the use of Dried Blood Spots (DBSs) represents a valid alternative to the \u201cclassical\u201d blood sampling. This innovative biological matrix reproduces the composition of whole blood but its pre-treatment procedure is faster and more feasible. DBSs can be stored for months at room temperature without any appreciable sample degradation, since most enzymatic and non-enzymatic reactions are stopped by the loss of water. The aim of this work is the specific evaluation of cannabinoid stability in DBSs, namely of \u3949 tetrahydrocannabinol (THC), the most important psychoactive cannabinoid, and of its two main metabolites 11-hydroxy-\u3949-tetrahydrocannabinol (THC-OH) and 11-nor-9-carboxy-\u3949-tetrahydrocannabinol (THC-COOH). For this study, blank spiked DBSs were stored at room temperature for up to 3 months after sampling and then analysed by ESI-LC-MS/MS. The sample pre-treatment, based on solvent extraction, provides good extraction yields and selectivity. Preliminary results are very satisfactory, since only minimal differences were observed between the samples analysed immediately after spotting and those analysed after storage. Further assays are in progress to confirm these results and to assess cannabinoid stability in DBSs over longer periods of time

Dried Blood Spot and mass spectrometry: an analytical tool to certify Cannabis actual state of intoxication

Driving under the influence of Cannabis (DUI) has become a growing concern. Studies investigating the impact of DUI on traffic safety have shown evidence that, during the acute period of Cannabis intoxication, Cannabis diminishes driving faculties greatly increasing the risk of car accidents. However, the actual state of Cannabis intoxication is not easily assessed, particularly in specific contexts such as roadside testing. Until now, the most reliable biological matrix for this purpose in represented by blood but its sampling is invasive and requires a sanitary environment and subsequent treatments or storage precautions, such as centrifugation, refrigeration or freezing. The time lapse between the individuation of a possible intoxication and the blood sampling is very important, since a long delay can mean that, in the meantime, the drug blood levels physiologically decrease under the cut-off value. To overcome this disadvantage, Dried Blood Spots (DBSs) can be a valid alternative to the normal blood sampling by venipuncture. In fact this innovative biological matrix can be obtained after a fast and easy sampling, does not need any particular storage nor transportation precaution and is stable over time. To strictly monitor Cannabis consumption, an original LC-MS/MS method has been developed for the analysis of Cannabinoids in DBSs. Attention has been paid to the determination of \u3949- tetrahydrocannabinol (or THC, Figure 1a), the main psychoactive compound whose presence in blood can be taken as a marker of recent exposure, and its two main metabolites 11-hydroxy-\u3949-tetrahydrocannabinol (THC-OH, Figure 1b) and 11-nor-9-carboxy-\u3949-tetrahydrocannabinol. \ufffc\ufffc\ufffc\ufffc\ufffc\ufffcIn particular the intermediate hydroxylated metabolite (THC-OH) is pharmacologically active and, at the same time, it is a marker of recent Cannabis intake, since it appears in blood about 13 minutes after consumption and has a relatively short half-life. The carboxylated metabolite (THC-COOH) is not psychoactive and has a very long half-life up to one month for chronic users. For this reason the presence of this latter compound alone in blood cannot be taken as a marker of recent exposure. Is evident, therefore, that the simultaneous monitoring of all the three analytes is necessary to outline pharmacokinetic and toxicokinetic state of abusers and contribute to the assessment of psychophysical state, distinguishing between acute or former consumption. The analytical method developed has been fully validated and applied to real DBS samples from Cannabis abusers with satisfactory results, thus confirming the methodology suitability for roadside testings

Permanenza di alterazioni cerebrali dopo assunzione di droghe anche dopo un periodo di cessazione dell’uso: il contributo del neuroimaging

Revisione della letteratura scientifica che ha l’obiettivo principale di definire un più corretto paradigma relativo alla guida sotto l’effetto di sostanze stupefacenti

Population surveys compared with wastewater analysis for monitoring illicit drug consumption in Italy in 2010–2014

Background: Monitoring consumption by population surveys (PS) is an important way to challenge the spread of illicit drugs (ID). To improve the information, we explored a complementary method, particularly wastewater analysis (WWA). Methods: We estimated the prevalence of use by PS, and the consumption by WWA, of cocaine, opioids, cannabis, methamphetamine and MDMA (ecstasy) from 2010 to 2014 in Italy and compared the results. Results: According to PS, cannabis and cocaine were the ID most used in Italy (last month prevalence 3.0% and 0.43% respectively in 2010) followed by opioids (0.17%) and amphetamines (0.14%). WWA gave similar findings, with cannabis consumption (4.35 g THC/day/1000 inhabitants) exceeding cocaine (0.78 g), heroin (0.092 g), methamphetamine and MDMA (0.103 g). The time trend investigated by PS showed significant decreases for all ID from 2010 to 2012. WWA also indicated a reduction of consumption for methamphetamine (p < 0.0001) and heroin (p < 0.01). Both methods showed an increase for cannabis in 2014 (p < 0.001) with the other ID unchanged. Spatial investigations by WWA showed that cannabis and cocaine were consumed significantly more in central Italy than in the north and south. PS indicated the same but only for cannabis. WWA was helpful to study weekly patterns of consumption, showing increases in cocaine and MDMA at weekends. Conclusions: PS and WWA were confirmed as complementary methods and when used together improved the information on ID use in Italy. We suggest that the combined use of the two approaches can give better information on ID use in the population