Hitting the Jackpot – development of gas chromatography–mass spectrometry (GC–MS) and other rapid screening methods for the analysis of 18 fentanyl-derived synthetic opioids

© 2020 John Wiley & Sons, Ltd. In recent years, the occurrence of synthetic opioid fentanyl and its derivatives has grown significantly in forensic casework. This study presents the synthesis and analysis of 18 fentalogs, selected based on information received from local law enforcement. This study provides colorimetric tests, thin-layer chromatography (TLC) which can potentially be utilized for presumptive screening of the target compounds, as bulk powders or as trace-level adulterants. The fully validated confirmatory GC–MS method (employing SIM mode) allows the identification of the 18 derivatives, five commonly encountered controlled substances and four adulterants, within 20 minutes. The cross-validated method described herein provides a sensitive screening and quantitation method for the illicit (and potentially harmful) components at trace levels (LOD = 0.007–0.822 μg/mL and LOQ = 0.023–2.742 μg/mL respectively). Spectral data [1H-NMR, 13C-NMR, 19F-NMR, FT-IR, and HRMS] and assignments for the synthesized reference materials are also provided in the Supplementary Information for laboratories engaged in the routine analysis of fentanyl and its derivatives

Accounting for Equity Considerations in Cost-Effectiveness Analysis : A Systematic Review of Rotavirus Vaccine in Low- and Middle-Income Countries

Additional file 3: Appendix C. Full data table of results

The rate of cellular hydrogen peroxide removal shows dependency on GSH: Mathematical insight into in vivo H2O2 and GPx concentrations

Although its concentration is generally not known, glutathione peroxidase-1 (GPx-1) is a key enzyme in the removal of hydrogen peroxide (H2O2) in biological systems. Extrapolating from kinetic results obtained in vitro using dilute, homogenous buffered solutions, it is generally accepted that the rate of elimination of H2O2 in vivo by GPx is independent of glutathione concentration (GSH). To examine this doctrine, a mathematical analysis of a kinetic model for the removal of H2O2 by GPx was undertaken to determine how the reaction species (H2O2, GSH, and GPx-1) influence the rate of removal of H2O2. Using both the traditional kinetic rate law approximation (classical model) and the generalized kinetic expression, the results show that the rate of removal of H2O2 increases with initial GPxr, as expected, but is a function of both GPxr and GSH when the initial GPxr is less than H2O2. This simulation is supported by the biological observations of Li et al.. Using genetically altered human glioma cells in in vitro cell culture and in an in vivo tumour model, they inferred that the rate of removal of H2O2 was a direct function of GPx activity × GSH (effective GPx activity). The predicted cellular average GPxr and H2O2 for their study are approximately GPxr ≤ 1 μm and H2O2 ≈ 5 μm based on available rate constants and an estimation of GSH. It was also found that results from the accepted kinetic rate law approximation significantly deviated from those obtained from the more generalized model in many cases that may be of physiological importance

Tectonic evolution of the southern margin of the Amazonian craton in the late Mesoproterozoic based on field relationships and zircon U-Pb geochronology

New U-Pb zircon geochronological data integrated with field relationships and an airborne geophysical survey suggest that the Nova Brasilândia and Aguapeí belts are part of the same monocyclic, metaigneous and metasedimentary belt formed in the late Mesoproterozoic (1150 Ma-1110 Ma). This geological history is very similar to the within-plate origin of the Sunsás belt, in eastern Bolivia. Thus, we propose that the Nova Brasilândia, Aguapeí and Sunsás belts represent a unique geotectonic unit (here termed the Western Amazon belt) that became amalgamated at the end of the Mesoproterozoic and originated through the reactivation of a paleo-suture (Guaporé suture zone) in an intracontinental rift environment. Therefore, its geological history involves a short, complete Wilson cycle of ca. 40 Ma. Globally, this tectonic evolution may be related with the final breakup of the supercontinent Columbia. Mafic rocks and trondhjemites in the northernmost portion of the belt yielded U-Pb zircon ages ca. 1110 Ma, which dates the high-grade metamorphism and the closure of the rift. This indicates that the breakup of supercontinent Columbia was followed in short sequence by the assembly of supercontinent Rodinia at ca. 1.1-1.0 Ga and that the Western Amazon belt was formed during the accretion of the Arequipa-Antofalla basement to the Amazonian craton

Spinal Astrocytic Activation Is Involved in a Virally-Induced Rat Model of Neuropathic Pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and “NO-Astrocyte-Cytokine-NMDAR-Neuron” pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN

Revisiting the Twentieth Century Through the Lens of Generation X and Digital Games: A Scoping Review

Video games have been around since the 1960s and have impacted upon society in a myriad of different ways. The purpose of this scoping review is to identify existing literature within the domain of video games which recruited participants from the Generation X (1965–1980) cohort. Six databases were searched (ACM, CINHAL Google Scholar, PubMed, Scopus, and Web of Science) focusing on published journal papers between 1970 and 2000. Search results identified 3186 articles guided by the PRISMA Extension for Scoping Reviews (PRISMA-ScR); 4 papers were irretrievable, 138 duplicated papers were removed, leaving 3048 were assessed for eligibility and 3026 were excluded. Articles (n = 22) were included into this review, with four papers primarily published in 1997 and in 1999. Thematic analysis identified five primary themes: purpose and objectives, respective authors’ reporting, technology, ethics and environment) and seven secondary themes: populations, type of participants (e.g. children, students), ethical approval, study design, reimbursement, language, type of assessments. This scoping review is distinctive because it primarily focuses on Generation X, who have experienced and grown-up with videogames, and contributes to several disciplines including: game studies, gerontology and health, and has wider implications from a societal, design and development perspective of video games

Protocol for a prospective, longitudinal, cohort study of recovery pathways, acute biomarkers and cost for children with persistent postconcussion symptoms: the Take CARe Biomarkers study

INTRODUCTION: The majority of children who sustain a concussion will recover quickly, but a significant minority will experience ongoing postconcussive symptoms, known as postconcussion syndrome (PCS). These symptoms include emotional, behavioural, cognitive and physical symptoms and can lead to considerable disability. The neurobiological underpinnings of PCS are poorly understood, limiting potential clinical interventions. As such, patients and families frequently re-present to clinical services, who are often ill equipped to address the multifactorial nature of PCS. This contributes to the high cost of concussion management and the disability of children experiencing PCS. The aims of the present study are: (1) to plot and contrast recovery pathways for children with concussion from time of injury to 3 months postinjury, (ii) evaluate the contribution of acute biomarkers (ie, blood, MRI) to delayed recovery postconcussion and (3) estimate financial costs of child concussion to patients attending the emergency department (ED) of a tertiary children's hospital and factors predicting high cost. METHODS AND ANALYSIS: Take C.A.Re is a prospective, longitudinal study at a tertiary children's hospital, recruiting and assessing 525 patients aged 5-<18 years (400 concussion, 125 orthopaedic injury) who present to the ED with a concussion and following them at 1-4 days, 2 weeks, 1 month and 3 months postinjury. Multiple domains are assessed: preinjury and postinjury, clinical, MRI, blood samples, neuropsychological, psychological and economic. PCS is defined as the presence of ≥2 symptoms on the Post Concussive Symptoms Inventory rated as worse compared with baseline 1 month postinjury. Main analyses comprise longitudinal Generalised Estimating Equation models and regression analyses of predictors of recovery and factors predicting high economic costs. ETHICS AND DISSEMINATION: Ethical approval has been obtained through the Royal Children's Hospital Melbourne Human Research Ethics Committee (33122). We aim to disseminate the findings through international conferences, international peer-reviewed journals and social media. TRIAL REGISTRATION NUMBER: ACTRN12615000316505; Results