Nicotine absorption from e-cigarettes over 12 months

Background Research indicates that, over time, exclusive e-cigarette users (vapers) gradually reduce the nicotine concentration in their e-liquid and transition to more sophisticated devices. Alongside this, consumption of e-liquid increases and constant cotinine levels are maintained. Aims We aimed to confirm these observations in 27 experienced vapers tested at baseline and 12 months later, by measuring nicotine absorption (via salivary levels of the nicotine metabolite cotinine; ng/mL), nicotine concentrations in e-liquid (mg/mL), volume of e-liquid consumed (mL per day), device types and flavours used, both at baseline and 12 months. Results Vapers reduced both their nicotine concentrations in e-liquid over 12 months (from 13.83 mg/mL at baseline to 9.91 at follow up) but significantly increased their e-liquid consumption (from 4.44 to 6.84 mL). No significant changes in salivary cotinine concentrations (370.88 ng/mL at baseline and 415.78 ng/mL at follow up) were observed. There was an increase in sub-ohming (using an atomiser coil with resistance of <1 Ω with increased power) at 12 months, and in the use of fruit flavoured e-liquids. Conclusions Our sample of experienced vapers reduced the concentration of nicotine in their e-liquid over time, but maintained their nicotine intake possibly through self-titration via more intensive puffing. Findings suggest there may be little benefit in reducing nicotine e-liquid concentration since this appears to result in higher e-liquid consumption which may incur both a financial and health cost. Gaining an understanding of underlying reasons for lowering e-liquid concentration would be a useful line of empirical enquiry

Assessment of allergenic potential of genetically modified foods: an agenda for future research.

Speakers and participants in the workshop "Assessment of the Allergenic Potential of Genetically Modified Foods" met in breakout groups to discuss a number of issues including needs for future research. These groups agreed that research should progress quickly in the area of hazard identification and that a need exists for more basic research to understand the mechanisms underlying food allergy. A list of research needs was developed

Induced antiferromagnetism and large magnetoresistances in RuSr2(Nd,Y,Ce)2Cu2O10-d ruthenocuprates

RuSr2(Nd,Y,Ce)2Cu2O10-d ruthenocuprates have been studied by neutron diffraction, magnetotransport and magnetisation measurements and the electronic phase diagram is reported. Separate Ru and Cu spin ordering transitions are observed, with spontaneous Cu antiferromagnetic order for low hole doping levels p, and a distinct, induced-antiferromagnetic Cu spin phase in the 0.02 < p < 0.06 pseudogap region. This ordering gives rise to large negative magnetoresistances which vary systematically with p in the RuSr2Nd1.8-xY0.2CexCu2O10-d series. A collapse of the magnetoresistance (MR) and magnetisation in the pre-superconducting region may signify the onset of superconducting fluctuations.Comment: 22 pages, 11 figure

Involvement of a putative intercellular signal-recognizing G protein-coupled receptor in the engulfment of Salmonella by the protozoan Tetrahymena

In an effort to investigate the molecular basis of protozoa engulfment-mediated hypervirulence of Salmonella in cattle, we evaluated protozoan G protein-coupled receptors (GPCRs) as transducers of Salmonella engulfment by the model protozoanTetrahymena. Our laboratory previously demonstrated that non-pathogenic protozoa (including Tetrahymena) engulf Salmonella and then exacerbate its virulence in cattle, but the mechanistic details of the phenomenon are not fully understood. GPCRs were investigated since these receptors facilitate phagocytosis of particulates byTetrahymena, and a GPCR apparently modulates bacterial engulfment for the pathogenic protozoan Entamoeba histolytica. A database search identified three putative Tetrahymena GPCRs, based on sequence homologies and predicted transmembrane domains, that were the focus of this study. Salmonella engulfment by Tetrahymenawas assessed in the presence of suramin, a non-specific GPCR inhibitor. Salmonella engulfment was also assessed in Tetrahymena in which expression of putative GPCRs was knocked-down using RNAi. A candidate GPCR was then expressed in a heterologous yeast expression system for further characterization. Our results revealed that Tetrahymena were less efficient at engulfing Salmonella in the presence of suramin. Engulfment was reduced concordantly with a reduction in the density of protozoa. RNAi-based studies revealed that knock-down of one the Tetrahymena GPCRs caused diminished engulfment of Salmonella. Tetrahymena lysates activated this receptor in the heterologous expression system. These data demonstrate that the Tetrahymena receptor is a putative GPCR that facilitates bacterial engulfment by Tetrahymena. Activation of the putative GPCR seemed to be related to protozoan cell density, suggesting that its cognate ligand is an intercellular signaling molecule

Functional Characterization of a Novel Family of Acetylcholine-Gated Chloride Channels in Schistosoma mansoni

Acetylcholine is the canonical excitatory neurotransmitter of the mammalian neuromuscular system. However, in the trematode parasite Schistosoma mansoni, cholinergic stimulation leads to muscle relaxation and a flaccid paralysis, suggesting an inhibitory mode of action. Information about the pharmacological mechanism of this inhibition is lacking. Here, we used a combination of techniques to assess the role of cholinergic receptors in schistosome motor function. The neuromuscular effects of acetylcholine are typically mediated by gated cation channels of the nicotinic receptor (nAChR) family. Bioinformatics analyses identified numerous nAChR subunits in the S. mansoni genome but, interestingly, nearly half of these subunits carried a motif normally associated with chloride-selectivity. These putative schistosome acetylcholine-gated chloride channels (SmACCs) are evolutionarily divergent from those of nematodes and form a unique clade within the larger family of nAChRs. Pharmacological and RNA interference (RNAi) behavioral screens were used to assess the role of the SmACCs in larval motor function. Treatment with antagonists produced the same effect as RNAi suppression of SmACCs; both led to a hypermotile phenotype consistent with abrogation of an inhibitory neuromuscular mediator. Antibodies were then generated against two of the SmACCs for use in immunolocalization studies. SmACC-1 and SmACC-2 localize to regions of the peripheral nervous system that innervate the body wall muscles, yet neither appears to be expressed directly on the musculature. One gene, SmACC-1, was expressed in HEK-293 cells and characterized using an iodide flux assay. The results indicate that SmACC-1 formed a functional homomeric chloride channel and was activated selectively by a panel of cholinergic agonists. The results described in this study identify a novel clade of nicotinic chloride channels that act as inhibitory modulators of schistosome neuromuscular function. Additionally, the iodide flux assay used to characterize SmACC-1 represents a new high-throughput tool for drug screening against these unique parasite ion channels

Differential regulation of TNF-α and IL-1β production from endotoxin stimulated human monocytes by phosphodiesterase inhibitors

The effect of selective PDE-I (vinpocetine), PDE-III (milrinone, CI-930), PDE-IV (rolipram, nitroquazone), and PDE-V (zaprinast) isozyme inhibitors on TNF-α and IL-1β production from LPS stimulated human monocytes was investigated. The PDE-IV inhibitors caused a concentration dependent inhibition of TNF-α production, but only partially inhibited IL-1β at high concentrations. High concentrations of the PDE-III inhibitors weakly inhibited TNF-α, but had no effect on IL-1β production. PDE-V inhibition was associated with an augmentation of cytokine secretion. Studies with combinations of PDE isozyme inhibitors indicated that PDE-III and PDE-V inhibitors modulate rolipram's suppression of TNF production in an additive manner. These data confirm that TNF-α and IL-1β production from LPS stimulated human monocytes are differentially regulated, and suggest that PDE-IV inhibitors have the potential to suppress TNF levels in man

Nonlinear Aerodynamic Damping of Sharp-Edged Beams at Low Keulegan-Carpenter Numbers

Slender sharp-edged flexible beams such as flapping wings of micro air vehicles (MAVs), piezoelectric fans and insect wings typically oscillate at moderate-to-high values of non-dimensional frequency parameter β with amplitudes as large as their widths resulting in Keulegan–Carpenter (KC) numbers of order one. Their oscillations give rise to aerodynamic damping forces which vary nonlinearly with the oscillation amplitude and frequency; in contrast, at infinitesimal KC numbers the fluid damping coefficient is independent of the oscillation amplitude. In this article, we present experimental results to demonstrate the phenomenon of nonlinear aerodynamic damping in slender sharp-edged beams oscillating in surrounding fluid with amplitudes comparable to their widths. Furthermore, we develop a general theory to predict the amplitude and frequency dependence of aerodynamic damping of these beams by coupling the structural motions to an inviscid incompressible fluid. The fluid–structure interaction model developed here accounts for separation of flow and vortex shedding at sharp edges of the beam, and studies vortex-shedding-induced aerodynamic damping in slender sharp-edged beams for different values of the KC number and the frequency parameter β. The predictions of the theoretical model agree well with the experimental results obtained after performing experiments with piezoelectric fans under vacuum and ambient conditions

First versus second generation electronic cigarettes: predictors of choice and effects on urge to smoke and withdrawal symptoms

Aims: To 1) estimate predictors of first vs. second generation electronic cigarette (e-cigarette) choice; 2) determine whether a second generation device was i) superior for reducing urge to smoke and withdrawal symptoms (WS) and ii) associated with enhanced positive subjective effects. Design: Mixed effects experimental design. Phase 1: reason for e-cigarette choice was assessed via questionnaire. Phase 2: participants were randomly allocated to first or second generation e-cigarette condition. Urge to smoke and WS were measured before, and 10mins after, taking 10 e-cigarette puffs. Setting: University of East London, UK. Participants: 97 smokers (mean age 26; SD 8.7; 54% female) Measurements: Single item urge to smoke scale to assess craving; Mood and Physical Symptoms Scale (MPSS) to assess WS. Subjective effects included: satisfaction, hit, ‘felt like smoking’ and ‘would use to stop smoking’ (Yes vs. No response). Findings: Equal numbers chose each device but none of the predictor variables (gender, age, tobacco dependence, previous e-cigarette use) accounted for choice. Only baseline urge to smoke/WS predicted urge to smoke/WS 10 minutes after use (B=0.38; P<0.001 and B=0.53; P<0.001). E-cigarette device was not a significant predictor. Those using the second generation device were more likely to report satisfaction and use in a quit attempt (χ2=12.10, P=0.001 and χ2=5.53, P=0.02). Conclusions: First and second generation e-cigarettes appear to be similarly effective in reducing urge to smoke and WS during abstinence but second generation devices appear to be more satisfying to users

Daily exposure to formaldehyde and acetaldehyde and potential health risk associated with use of high and low nicotine e-liquid concentrations

Recent evidence suggests that e-cigarette users tend to change their puffing behaviors when using e-liquids with reduced nicotine concentrations by taking longer and more frequent puffs. Using puffing regimens modelled on puffing topography data from 19 experienced e-cigarette users who switched between 18 and 6 mg/mL e-liquids with and without power adjustments, differences in daily exposure to carbonyl compounds and estimated changes in cancer risk were assessed by production of aerosols generated using a smoking machine and analyzed using gas and liquid chromatography. Significant differences across conditions were found for formaldehyde and acetaldehyde (p<0.01). Switching from a higher to a lower nicotine concentration was associated with greater exposure regardless of whether power settings were fixed or adjustable which is likely due to increased liquid consumption under lower nicotine concentration settings. Daily exposure for formaldehyde and acetaldehyde was higher for 17/19 participants when using low (6mg/mL) compared with high (18mg/mL) nicotine e-liquid concentration when power was fixed. When power adjustments were permitted, formaldehyde and acetaldehyde levels were higher respectively for 16/19 and 14/19 participants with the use of 6 compared with 18 mg/mL nicotine e-liquid

Photoredox approach to N-Acyl-N'-aryl-N,N'-aminals using enamides and their conversion to γ-lactams

A photoredox catalytic approach to synthetically valuable N-acyl-N'-aryl-N,N'-aminals is described. This method uses the addition of a radical precursor to enamides, with subsequent interception of the cationic iminium intermediate with an arylamine. The reaction has been shown to be compatible with electron-rich and electron-deficient arylamines, and moderate to good levels of diastereoselectivity can be attained using a chiral enamide. Furthermore, the N-acyl-N'-aryl-N,N'-aminal reaction products can be readily cyclized, providing a novel synthetic route to valuable γ-lactams