Photochemical Fingerprinting Is a Sensitive Probe for the Detection of Synthetic Cannabinoid Receptor Agonists; Toward Robust Point-of-Care Detection

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid "photochemical fingerprinting"approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device.</p

Photochemical fingerprinting is a sensitive probe for the detection of synthetic cannabinoid receptor agonists; towards robust point-of-care detection

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid “photochemical fingerprinting” approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device

Determinants of DNA yield and purity collected with buccal cell samples

Buccal cells are an important source of DNA in epidemiological studies, but little is known about factors that influence amount and purity of DNA. We assessed these factors in a self-administered buccal cell collection procedure, obtained with three cotton swabs. In 2,451 patients DNA yield and in 1,033 patients DNA purity was assessed. Total DNA yield ranged from 0.08 to 1078.0 μg (median 54.3 μg; mean 82.2 μg ± SD 92.6). The median UV 260:280 ratio, was 1.95. Samples from men yielded significantly more DNA (median 58.7 μg) than those from women (median 44.2 μg). Diuretic drug users had significantly lower purity (median 1.92) compared to other antihypertensive drug users (1.95). One technician obtained significantly lower DNA yields. Older age was associated with lower DNA purity. In conclusion, DNA yield from buccal swabs was higher in men and DNA purity was associated with age and the use of diuretics

Instant detection of synthetic cannabinoids on physical matrices, implemented on a low-cost, ultraportable device

Synthetic cannabinoids (SCs) make up a class of novel psychoactive substances (NPS), used predominantly in prisons and homeless communities in the U.K. SCs can have severe side effects, including psychosis, stroke, and seizures, with numerous reported deaths associated with their use. The chemical diversity of SCs presents the major challenge to their detection since approaches relying on specific molecular recognition become outdated almost immediately. Ideally one would have a generic approach to detecting SCs in portable settings. The problem of SC detection is more challenging still because the majority of SCs enter the prison estate adsorbed onto physical matrices such as paper, fabric, or herb materials. That is, regardless of the detection modality used, the necessary extraction step reduces the effectiveness and ability to rapidly screen materials on-site. Herein, we demonstrate a truly instant generic test for SCs, tested against real-world drug seizures. The test is based on two advances. First, we identify a spectrally silent region in the emission spectrum of most physical matrices. Second, the finding that background signals (including from autofluorescence) can be accurately predicted is based on tracking the fraction of absorbed light from the irradiation source. Finally, we demonstrate that the intrinsic fluorescence of a large range of physical substrates can be leveraged to track the presence of other drugs of interest, including the most recent iterations of benzodiazepines and opioids. We demonstrate the implementation of our presumptive test in a portable, pocket-sized device that will find immediate utility in prisons and law enforcement agencies around the world

Photochemical fingerprinting Is a sensitive probe for the detection of synthetic cannabinoid receptor agonists; toward robust point-of-care detection

With synthetic cannabinoid receptor agonist (SCRA) use still prevalent across Europe and structurally advanced generations emerging, it is imperative that drug detection methods advance in parallel. SCRAs are a chemically diverse and evolving group, which makes rapid detection challenging. We have previously shown that fluorescence spectral fingerprinting (FSF) has the potential to provide rapid assessment of SCRA presence directly from street material with minimal processing and in saliva. Enhancing the sensitivity and discriminatory ability of this approach has high potential to accelerate the delivery of a point-of-care technology that can be used confidently by a range of stakeholders, from medical to prison staff. We demonstrate that a range of structurally distinct SCRAs are photochemically active and give rise to distinct FSFs after irradiation. To explore this in detail, we have synthesized a model series of compounds which mimic specific structural features of AM-694. Our data show that FSFs are sensitive to chemically conservative changes, with evidence that this relates to shifts in the electronic structure and cross-conjugation. Crucially, we find that the photochemical degradation rate is sensitive to individual structures and gives rise to a specific major product, the mechanism and identification of which we elucidate through density-functional theory (DFT) and time-dependent DFT. We test the potential of our hybrid “photochemical fingerprinting” approach to discriminate SCRAs by demonstrating SCRA detection from a simulated smoking apparatus in saliva. Our study shows the potential of tracking photochemical reactivity via FSFs for enhanced discrimination of SCRAs, with successful integration into a portable device

The SNX-PX-BAR Family in Macropinocytosis: The Regulation of Macropinosome Formation by SNX-PX-BAR Proteins

Background: Macropinocytosis is an actin-driven endocytic process, whereby membrane ruffles fold back onto the plasma membrane to form large (> 0.2 mu m in diameter) endocytic organelles called macropinosomes. Relative to other endocytic pathways, little is known about the molecular mechanisms involved in macropinocytosis. Recently, members of the Sorting Nexin (SNX) family have been localized to the cell surface and early macropinosomes, and implicated in macropinosome formation. SNX-PX-BAR proteins form a subset of the SNX family and their lipid-binding (PX) and membrane-curvature sensing (BAR) domain architecture further implicates their functional involvement in macropinosome formation

Area-level socioeconomic characteristics and incidence of metabolic syndrome: a prospective cohort study

BACKGROUND The evidence linking socioeconomic environments and metabolic syndrome (MetS) has primarily been based on cross-sectional studies. This study prospectively examined the relationships between area-level socioeconomic position (SEP) and the incidence of MetS. METHODS A prospective cohort study design was employed involving 1,877 men and women aged 18+ living in metropolitan Adelaide, Australia, all free of MetS at baseline. Area-level SEP measures, derived from Census data, included proportion of residents completing a university education, and median household weekly income. MetS, defined according to International Diabetes Federation, was ascertained after an average of 3.6 years follow up. Associations between each area-level SEP measure and incident MetS were examined by Poisson regression Generalised Estimating Equations models. Interaction between area- and individual-level SEP variables was also tested. RESULTS A total of 156 men (18.7%) and 153 women (13.1%) developed MetS. Each percentage increase in the proportion of residents with a university education corresponded to a 2% lower risk of developing MetS (age and sex-adjusted incidence risk ratio (RR) = 0.98; 95% confidence interval (CI) =0.97-0.99). This association persisted after adjustment for individual-level income, education, and health behaviours. There was no significant association between area-level income and incident MetS overall. For the high income participants, however, a one standard deviation increase in median household weekly income was associated with a 29% higher risk of developing MetS (Adjusted RR = 1.29; 95%CI = 1.04-1.60). CONCLUSIONS While area-level education was independently and inversely associated with the risk of developing MetS, the association between area-level income and the MetS incidence was modified by individual-level income.Anh D Ngo, Catherine Paquet, Natasha J Howard, Neil T Coffee, Robert Adams, Anne Taylor and Mark Danie