Is old stuff back? A fatal case of ethyl chloride sniffing

Background: Ethyl chloride (EC) or chloroethane is a colourless halogenated hydrocarbon gas regularly employed as a topical anaesthetic spray for pain-related injuries and muscle spasm in athletes. However, EC became also popular as a street drug in the 1980s. Brief inhalations of EC vapour can result in dizziness, euphoria, confusion, incoordination, hallucinosis, impairment of short-term memory and narcosis. Inhalation of higher doses, usually employed to \u201cget high\u201d, may be related to severe depression of the central nervous system. Indeed, toxicity and deaths have been reported so far. Case presentation: A 40-year-old man was found unresponsive after EC inhalation. EC determination was performed by dynamic headspace gas chromatography coupled to mass spectrometry. EC was detected in the peripheral blood (0.156 g/L), central blood concentration (0.203 g/L) and the lung and brain (19 and 25 mg/kg). EC in the vitreous humour showed a sensitively lower respect to blood (0.018 vs 0.203 g/L). Conclusions: Considering the results of toxicological analyses of investigations on the death scene besides the absence of any signs of trauma, death was attributed to inhalation of ethyl chloride

Valproic acid determination by liquid chromatography coupled to mass spectrometry (LC–MS/MS) in whole blood for forensic purposes

Valproic acid (VPA) is a well-known drug prescribed as anti-epileptic. It has a narrow therapeutic range and shows great individual differences in pharmacodynamics and pharmacokinetics. Consequently, the therapeutical drug monitoring (TDM) in patient's plasma is of crucial importance. Liquid chromatography coupled to mass spectrometry (LC–MS/MS) has gained importance in TDM applications for its features of sensitivity, selectivity and rapidity. However, in case of VPA, the LC–MS/MS selectivity could be hampered by the lack of a sufficient number of multiple reaction monitoring (MRM) transitions describing the molecule. In fact, the product ion scan of deprotonated molecules of VPA does not produce any ion and thus most LC–MS/MS methods are based on the detection of the unique MRM transition m/z 143➔143. In this way, the advantages of selectivity in LC–MS cannot be effectively exploited. In the present method, stable analyte adducts were exploited for the determination of VPA in blood. An Acquity HSS C18 column and mobile phases consisting of 5-mM ammonium formate and acetonitrile both added 0.1% formic acid were used. Source worked in negative acquisition mode and parameters were optimized to increase the adduct (m/z 189) and dimer (m/z 287) stability, and their fragmentation were used to increase the selectivity of MRM detection. The method has been validated according to the toxicological forensic guidelines and successfully applied to 10 real blood samples. Finally, the present method showed suitable for the rapid LC–MS/MS detection of VPA in whole blood, demonstrating the possibility to increase specificity by exploiting stable in-source adducts. This should be considered of utmost importance in the case of forensic applications

Unravelling the hidden ancestry of American admixed populations

The movement of people into the Americas has brought different populations into contact, and contemporary American genomes are the product of a range of complex admixture events. Here we apply a haplotype-based ancestry identification approach to a large set of genome-wide SNP data from a variety of American, European and African populations to determine the contributions of different ancestral populations to the Americas. Our results provide a fine-scale characterization of the source populations, identify a series of novel, previously unreported contributions from Africa and Europe and highlight geohistorical structure in the ancestry of American admixed populations

Developing Central Nervous System and Vulnerability to Platinum Compounds

Comparative studies on the effects of the platinum complexes in use or in clinical trials are carried out in order to discover differences in the neurotoxic potential and the reversibility of neurotoxicity. In this paper, we summarized the current literature on neurotoxicity and chemoresistance of cisplatin (cisPt) and discussed our recent efforts on the interference of cisPt and a new platinum compound [Pt(O,O′-acac)(γ-acac)(DMS)] (PtAcacDMS), with high specific reactivity with sulphur ligands instead of nucleobases as cisPt, on some crucial events of rat postnatal cerebellum development. The acute effects of drug treatments on cell proliferation and death in the external granular layer and granule cell migration and the late effects on the dendrite growth of Purkinje cells were evaluated. Together with the demonstrated antineoplastic effectiveness in vitro, compared with cisPt, data suggest a lower neurotoxicity of PtAcacDMS, in spite of its presence in the brain that involves considerations on the blood brain barrier permeability

Genome-Wide snp analysis of southern african populations provides new insights into the dispersal of bantu-Speaking groups

The expansion of Bantu-speaking agropastoralist populations had a great impact on the genetic, linguistic, and cultural variation of sub-Saharan Africa. It isgenerally accepted that Bantulanguages originated inanarea around thepresent borderbetweenCameroon and Nigeria approximately 5,000 years ago, from where they spread South and East becoming the largest African linguistic branch. The demic consequences of this event are reflected in the relatively high genetic homogeneity observed acrossmost of sub-Saharan Africapopulations. Inthiswork, weexploredgenome-wide singlenucleotidepolymorphismdata from28populations to characterize the genetic components present in sub-Saharan African populations. Combining novel data from four SouthernAfrican populations withpreviouslypublishedresults,we reject the hypothesis that the" non-Bantu" geneticcomponent reported inSouth-Eastern Africa (Mozambique) reflects extensive gene flow between incoming agriculturalist and resident hunter-gatherer communities.We alternatively suggest that this novel component is the result of demographic dynamics associated with the Bantu dispersal

Screening strategies for the diagnosis of asymptomatic Leishmania infection in dialysis patients as a model for kidney transplant candidates

Despite being considered a tropical disease, visceral leishmaniasis (VL) caused by L. infantum is also endemic in the Mediterranean Europe and represents an increasing cause of morbidity and mortality in solid organ transplant (SOT) recipients. VL occurring in kidney transplant recipients is a severe event, often worsening the renal damage and leading to poor outcome. It is believed that most of VL cases in transplant recipients are caused by reactivation of a pre-existent, dormant leishmanial infection induced by the immunosuppressive drugs. Nevertheless, the prevalence of asymptomatic Leishmania infection in candidates to kidney transplant residing in or visiting endemic areas is unknown. As L. infantum is highly circulating in northeastern Italy, we aimed to examine the occurrence of this parasitic infection in 119 dialysis patients living in the mentioned area, 71 of whom were potential candidates to kidney transplant. By employing a combination of sensitive serological and molecular methods, we observed a prevalence of 15.9% asymptomatic Leishmania infection in the study cohort. This finding emphasizes the need of further evaluating potential screening strategies for Leishmania infection in solid organ transplant candidates residing in or visiting endemic areas

Complex ancient genetic structure and cultural transitions in Southern African populations

The characterization of the structure of southern African populations has been the subject of numerous genetic, medical, linguistic, archaeological, and anthropological investigations. Current diversity in the subcontinent is the result of complex events of genetic admixture and cultural contact between early inhabitants and migrants that arrived in the region over the last 2000 years. Here, we analyze 1856 individuals from 91 populations, comprising novel and published genotype data, to characterize the genetic ancestry profiles of 631 individuals from 51 southern African populations. Combining both local ancestry and allele frequency based analyses, we identify a tripartite, ancient, Khoesan-related genetic structure. This structure correlates neither with linguistic affiliation nor subsistence strategy, but with geography, revealing the importance of isolation-by-distance dynamics in the area. Fine-mapping of these components in southern African populations reveals admixture and cultural reversion involving several Khoesan groups, and highlights that Bantu speakers and Coloured individuals have different mixtures of these ancient ancestries

Dynamical Systems Gradient method for solving nonlinear equations with monotone operators

A version of the Dynamical Systems Gradient Method for solving ill-posed nonlinear monotone operator equations is studied in this paper. A discrepancy principle is proposed and justified. A numerical experiment was carried out with the new stopping rule. Numerical experiments show that the proposed stopping rule is efficient. Equations with monotone operators are of interest in many applications.Comment: 2 figure

A Fluorine-18 Radiolabeling Method Enabled by Rhenium(I) Complexation Circumvents the Requirement of Anhydrous Conditions

Azeotropic distillation is typically required to achieve fluorine-18 radiolabeling during the production of positron emission tomography (PET) imaging agents. However, this time-consuming process also limits fluorine-18 incorporation, due to radioactive decay of the isotope and its adsorption to the drying vessel. In addressing these limitations, the fluorine-18 radiolabeling of one model rhenium(I) complex is reported here, which is significantly improved under conditions that do not require azeotropic drying. This work could open a route towards the investigation of a simplified metal-mediated late-stage radiofluorination method, which would expand upon the accessibility of new PET and PET-optical probes