Drug Use Changes at the Individual Level: Results from a Longitudinal, Multisite Survey in Young Europeans Frequenting the Nightlife Scene

Background: Monitoring emerging trends in the increasingly dynamic European drug market is vital; however, information on change at the individual level is scarce. In the current study, we investigated changes in drug use over 12 months in European nightlife attendees. / Method: In this longitudinal online survey, changes in substances used, use frequency in continued users, and relative initiation of use at follow-up were assessed for 20 different substances. To take part, participants had to be aged 18–34 years; be from Belgium, Italy, the Netherlands, Sweden, or the UK; and have attended at least 6 electronic music events in the past 12 months at baseline. Of 8,045 volunteers at baseline, 2,897 completed the survey at both time points (36% follow-up rate), in 2017 and 2018. / Results: The number of people using ketamine increased by 21% (p < 0.001), and logarithmized frequency of use in those continuing use increased by 15% (p < 0.001; 95% CI: 0.07–0.23). 4-Fluoroamphetamine use decreased by 27% (p < 0.001), and logarithmized frequency of use in continuing users decreased by 15% (p < 0.001, 95% CI: −0.48 to −0.23). The drugs with the greatest proportion of relative initiation at follow-up were synthetic cannabinoids (73%, N = 30), mephedrone (44%, N = 18), alkyl nitrites (42%, N = 147), synthetic dissociatives (41%, N = 15), and prescription opioids (40%, N = 48). / Conclusions: In this European nightlife sample, ketamine was found to have the biggest increase in the past 12 months, which occurred alongside an increase in frequency of use in continuing users. The patterns of uptake and discontinuation of alkyl nitrates, novel psychoactive substances, and prescription opioids provide new information that has not been captured by existing cross-sectional surveys. These findings demonstrate the importance of longitudinal assessments of drug use and highlight the dynamic nature of the European drug landscape

Loss of cholinergic innervation differentially affects eNOS-mediated blood flow, drainage of Aβ and cerebral amyloid angiopathy in the cortex and hippocampus of adult mice

Vascular dysregulation and cholinergic basal forebrain degeneration are both early pathological events in the development of Alzheimer’s disease (AD). Acetylcholine contributes to localised arterial dilatation and increased cerebral blood flow (CBF) during neurovascular coupling via activation of endothelial nitric oxide synthase (eNOS). Decreased vascular reactivity is suggested to contribute to impaired clearance of β-amyloid (Aβ) along intramural periarterial drainage (IPAD) pathways of the brain, leading to the development of cerebral amyloid angiopathy (CAA). However, the possible relationship between loss of cholinergic innervation, impaired vasoreactivity and reduced clearance of Aβ from the brain has not been previously investigated. In the present study, intracerebroventricular administration of mu-saporin resulted in significant death of cholinergic neurons and fibres in the medial septum, cortex and hippocampus of C57BL/6 mice. Arterial spin labelling MRI revealed a loss of CBF response to stimulation of eNOS by the Rho-kinase inhibitor fasudil hydrochloride in the cortex of denervated mice. By contrast, the hippocampus remained responsive to drug treatment, in association with altered eNOS expression. Fasudil hydrochloride significantly increased IPAD in the hippocampus of both control and saporin-treated mice, while increased clearance from the cortex was only observed in control animals. Administration of mu-saporin in the TetOAPPSweInd mouse model of AD was associated with a significant and selective increase in Aβ40-positive CAA. These findings support the importance of the interrelationship between cholinergic innervation and vascular function in the aetiology and/or progression of CAA and suggest that combined eNOS/cholinergic therapies may improve the efficiency of Aβ removal from the brain and reduce its deposition as CAA

COMET: A Contextualized Molecule-Based Matching Technique

Context-specific description of entities expressed in RDF poses challenges during data-driven tasks, e.g., data integration, and context-aware entity matching represents a building-block for these tasks. However, existing approaches only consider inter-schema mapping of data sources, and are not able to manage several contexts during entity matching. We devise COMET, an entity matching technique that relies on both the knowledge stated in RDF vocabularies and context-based similarity metrics to match contextually equivalent entities. COMET executes a novel 1-1 perfect matching algorithm for matching contextually equivalent entities based on the combined scores of semantic similarity and context similarity. COMET employs the Formal Concept Analysis algorithm in order to compute the context similarity of RDF entities. We empirically evaluate the performance of COMET on a testbed from DBpedia. The experimental results suggest that COMET is able to accurately match equivalent RDF graphs in a context-dependent manner

NSC114085

The ability of all 11 variable opacity (Opa) proteins encoded by Neisseria gonorrhoeae MS11 to interact directly with the five CD66 antigens was determined. Transfected HeLa cell lines expressing individual CD66 antigens were infected with recombinant N. gonorrhoeae and Escherichia coli strains expressing defined Opas. Based upon the ability of these bacteria to bind and invade and to isolate specifically CD66 antigens from detergent-soluble extracts of the corresponding cell lines, distinct specificity groups of Opa interaction with CD66 were seen. Defining these specificity groups allowed us to assign a specific function for CD66a in the Opa-mediated interaction of gonococci with two different target cell types, which are both known to co-express multiple CD66 antigens. The competence of individual Opas to interact with CD66a was strictly correlated with their ability to induce an oxidative response by polymorphonuclear neutrophils. The same Opa specificity was observed for the level of gonococcal binding to primary endothelial cells after stimulation with TNFalpha, which was shown to increase the expression of CD66a rather than CD66e. As CD66e alone is expressed on other target tissues of gonococcal pathogenicity, Opa variation probably contributes to the cell tropism displayed by gonococci