Further research concerning the detection of oxidation products of THC-COOH following urinary adulteration

University of Technology Sydney. Faculty of Science.In Australia and throughout the world, cannabis is one of the most widely used recreational substances. Whilst the recreational use of cannabis remains widely controversial, and the detection of its use in a range of biological matrices is of vital importance for drug testing laboratories and law enforcement agencies. The detection of drugs of abuse is critical in various areas, including pre-employment and post-incident drug screening, and sports drug testing. The use of cannabis by an individual may be ascertained by identifying the main metabolites of the major psychoactive constituent of cannabis, Δ⁹-tetrahydrocannabinol (THC), in biological matrices such as urine. The principal metabolite of THC is 11-nor-Δ⁹-tetrahydrocannabinol-9-carboxylic acid (THC-COOH), and may be detected in urine in both its free and glucuronide-bound form, with detection of either regarded as compelling evidence for the use of cannabis by an individual. Detection of THC-COOH by a range of instrumental techniques in drug testing laboratories is well established. However, this metabolite is known to be susceptible to reaction with certain adulterants. Adulteration of urine samples with oxidising adulterants has been shown to effectively mask cannabis use through reaction with THC-COOH. As such, the primary goals of this research are to assess the efficacy of a range of adulterants on the detection of THC-COOH in vitro, ascertain whether novel reaction products specific to the reaction of THC-COOH with selected adulterants form, and to assess the potential of these compounds to act as markers of both cannabis use and urine adulteration. Successful detection of a range of reaction products of THC-COOH was achieved, and three adulterants selected for further research: pyridinium chlorochromate, Betadine and bleach. Structural elucidation of these reaction products was attempted, and validated methods were developed for the quantitative detection of THC-COOH and qualitative detection of the targed reaction products following urine adulteration. Kinetics, pH and stability studies demonstrated that these reaction products formed under a range of pH and sample storage conditions, and critically, remained detectable for at least twenty days following adulteration. Detection of these potential markers of urine adulteration was also successfully achieved through the adulteration of authentic cannabis-positive urine specimens. This detection in authentic urine specimens is considered significant, as it highlights the potential for these novel compounds to be incorporated into current drug testing regimes employed by drug testing laboratories, and a potential means by which both cannabis use and urine adulteration may be conclusively identified

How do urban forms enable political projects? The affordance of nationalism and nationhood during the modernisation of European cities.

How do ideologies and cities shape each other? This work offers a theoretical strategy for explaining how urban forms and political projects have afforded each other's development historically, while avoiding a deterministic account of how political aims are realised in particular urban forms. To do this it focuses on the emergence of nationalism in the context of the modernisation of European cities in the nineteenth century and early twentieth century. As background, the development of the concept of citizenship in the context of the medieval city is explored and an understanding of the exceptional political space of the city in political philosophy is outlined. The political philosophy of nationalism is seen to engender an urban-rural tension and the works of Rousseau and Herder are read to understand further the relationship between nationalist thought and the modern city. Then in order to structure an investigation of how urban form and ideology interact, an analytical framework is developed using JJ Gibson’s theory of affordances. The framework is applied to European urban forms which developed during the rise of nationalism, specifically in three historical city cases: Budapest, Vienna and Venice. The cases share in common an experience of Habsburg administration and the rise of nationalism in the nineteenth century but have quite different formal contexts. Urban forms and affordances are discussed more generally using the phenomenon and concept of Haussmannisation and the usefulness of that concept is discussed. More general conclusions are drawn in which political ideas, ideologies and urban forms are understood to afford each other ranges of such possibilities without determining them

Electrochemical Quantification of D-Glucose during the Production of Bioethanol from Thermo-Mechanically Pre-treated Wheat Straw

Mechanical pre-treatment (disc refining) of wheat straw, at both atmospheric and elevated pressure, is shown to be an efficient process to access fermentable monosaccharides, with the potential to integrate within the infrastructure of existing first-generation bioethanol plants. The mild, enzymatic degradation of this sustainable lignocellulosic biomass affords ca. 0.10-0.13 g/g (dry weight) of D-glucose quantifiable voltammetrically in real time, over a two hundred-fold range in experimental laboratory scales (25 mL to 5.0 L), with pressure disc refining of the wheat straw enabling almost twice the amount of D-glucose to be generated during the hydrolysis stage than experiments using atmospheric refining (0.06 – 0.09 g/g dry weight). Fermentation of the resulting hydrolysate affords 0.08 – 0.10 g/g (dry weight) of ethanol over similar scales, with ethanol productivity at ca. 37 mg/(L h). These results demonstrate that minimal cellulose decomposition occurs during pressure refining of wheat straw, in contrast to hemicellulose, and suggest that the development of green, mechanochemical processes for the scalable and cost-effective manufacture of second-generation bioethanol requires improved cellulose decomposition

JNK1-dependent PUMA expression contributes to hepatocyte lipoapoptosis.

Free fatty acids (FFA) induce hepatocyte lipoapoptosis by a c-Jun N-terminal kinase (JNK)-dependent mechanism. However, the cellular processes by which JNK engages the core apoptotic machinery during lipotoxicity, especially activation of BH3-only proteins, remain incompletely understood. Thus, our aim was to determine whether JNK mediates induction of BH3-only proteins during hepatocyte lipoapoptosis. The saturated FFA palmitate, but not the monounsaturated FFA oleate, induces an increase in PUMA mRNA and protein levels. Palmitate induction of PUMA was JNK1-dependent in primary murine hepatocytes. Palmitate-mediated PUMA expression was inhibited by a dominant negative c-Jun, and direct binding of a phosphorylated c-Jun containing the activator protein 1 complex to the PUMA promoter was identified by electrophoretic mobility shift assay and a chromatin immunoprecipitation assay. Short hairpin RNA-targeted knockdown of PUMA attenuated Bax activation, caspase 3/7 activity, and cell death. Similarly, the genetic deficiency of Puma rendered murine hepatocytes resistant to lipoapoptosis. PUMA expression was also increased in liver biopsy specimens from patients with non-alcoholic steatohepatitis as compared with patients with simple steatosis or controls. Collectively, the data implicate JNK1-dependent PUMA expression as a mechanism contributing to hepatocyte lipoapoptosis

The message on the bottle:Rethinking plastic labelling to better encourage sustainable use

This is the author accepted manuscript. The final version is available from Elsevier via the DOI in this recordPlastic pollution continues to worsen globally in volume and complexity. The complexity in plastic production, use and disposal is significant, highlighting the importance of clear communication to consumers. Yet despite this, poor plastic labelling is clear, evident from poor waste management metrics even in the most equipped countries. Plastic labelling must change to contribute to a holistic intervention on global plastic mismanagement. Discussion on this topic leads to three key recommendations: 1. An accurate and clear “sustainability scale” to empower consumers to make decisions informed by environmental and human health implications; 2. Directions for appropriate disposal action in the region of purchase; 3. A comprehensive list of plastic composition, including additives.Natural Environment Research Council (NERC)QUEX InstituteQueensland Health, AustraliaMinderoo Foundation, Australi

Antivenom Treatment Is Associated with Fewer Patients using Opioids after Copperhead Envenomation

Introduction Copperhead envenomation causes local tissue destruction, leading people to seek treatment for the pain and swelling. First-line treatment for the pain is opioid medications. There is rising concern that an initial opioid prescription from the emergency department (ED) can lead to long-term addiction. This analysis sought to determine whether use of Fab antivenom (FabAV) for copperhead envenomation affected opioid use. Methods We performed a secondary analysis using data from a randomized clinical trial designed to determine the effect of FabAV on limb injury recovery following mild to moderate copperhead envenomation. Opioid use was a defined secondary outcome in the parent trial. Patients were contacted after discharge, and data were obtained regarding medications used for pain and the patients’ functional status. This analysis describes the proportion of patients in each treatment group reporting opioid use at each time point. It also assesses the interaction between functional status and use of opioids. Results We enrolled 74 patients in the parent trial (45 received FabAV, 29 placebo), of whom 72 were included in this secondary analysis. Thirty-five reported use of any opioids after hospital discharge. A smaller proportion of patients treated with FabAV reported opioid use: 40.9% vs 60.7% of those in the placebo group. The proportion of patients using opioids remained smaller in the FabAV group at each follow-up time point. Controlling for confounders and interactions between variables, the model estimated that the odds ratio of using opioids after hospital discharge among those who received placebo was 5.67 times that of those who received FabAV. Patients who reported higher baseline pain, those with moderate as opposed to mild envenomation, and females were more likely to report opioid use at follow-up. Patients with ongoing limitations to functional status had an increased probability of opioid use, with a stronger association over time. Opioid use corresponded with the trial’s predefined criteria for full recovery, with only two patients reporting opioid use in the 24 hours prior to achieving full limb recovery and no patients in either group reporting opioid use after full limb recovery. Conclusion In this study population, the proportion of patients using opioids for pain related to envenomation was smaller in the FabAV treatment group at all follow-up time points

The Efficacy of Crotalidae Polyvalent Immune Fab (Ovine) Antivenom Versus Placebo Plus Optional Rescue Therapy on Recovery From Copperhead Snake Envenomation: A Randomized, Double-Blind, Placebo-Controlled, Clinical Trial

Study objective: Copperhead snake (Agkistrodon contortrix) envenomation causes limb injury resulting in pain and disability. It is not known whether antivenom administration improves limb function. We determine whether administration of antivenom improves recovery from limb injury in patients envenomated by copperhead snakes. Methods: From August 2013 through November 2015, we performed a multicenter, randomized, double-blind, placebo- controlled, clinical trial to evaluate the effect of ovine Crotalidae polyvalent immune Fab (ovine) (CroFab; FabAV) antivenom therapy on recovery of limb function in patients with copperhead snake envenomation at 14 days postenvenomation. The study setting was 18 emergency departments in regions of the United States where copperhead snakes are endemic. Consecutive patients aged 12 years or older with mild- to moderate-severity envenomation received either FabAV or placebo. The primary outcome was limb function 14 days after envenomation, measured by the Patient-Specific Functional Scale. Additional outcomes included the Patient-Specific Functional Scale at other points; the Disorders of the Arm, Shoulder, and Hand, Lower Extremity Functional Scale, and Patient’s Global Impression of Change instruments; grip strength; walking speed; quality of life (Patient-Reported Outcomes Measurement Information System Physical Fucntion-10); pain; and analgesic use. Results: Seventy-four patients received study drug (45 FabAV, 29 placebo). Mean age was 43 years (range 12 to 86 years). Fifty-three percent were men, 62% had lower extremity envenomation, and 88% had mild initial severity. The primary outcome, the least square mean Patient-Specific Functional Scale score at 14 days postenvenomation, was 8.6 for FabAV-treated subjects and 7.4 for placebo recipients (difference 1.2; 95% confidence interval 0.1 to 2.3; P1�4.04). Additional outcome assessments generally favored FabAV. More FabAV-treated subjects experienced treatment- emergent adverse events (56% versus 28%), but few were serious (1 in each group). Conclusion: Treatment with FabAV reduces limb disability measured by the Patient-Specific Functional Scale 14 days after copperhead envenomation. [Ann Emerg Med. 2017;70:233-244.