Vaporized Nicotine Inhalation Increases Arterial Pressure in both Supine and 70o Head-up Positions

ABSTRACT Electronic cigarettes (e-cigs) are popular with smokers looking for a healthier alternative to tobacco cigarettes. E-cigs utilize a battery, activated on inhalation, to heat propylene glycol-suspended nicotine which is inhaled as vapor, and which does not include harmful poisons found in conventional cigarettes. Although the health claims of e-cigs continue to be debated, the effects of nicotine delivered as vapor on the cardiovascular system have not been studied. Because nicotine is a sympathomemetic agent, we tested the hypothesis that e-cigs would increase arterial pressure and protect against challenges associated with upright posture. Ten non-smoking subjects (5 male) participated in two experimental trials, separated by one week (randomized). Seated blood pressures were taken after a 10 min quiet rest period, and then subjects either inhaled (once every 30 s for 10 min) on an e-cig with a placebo cartridge (0 mg nicotine) or an active cartridge (18 mg nicotine). After an additional 10 min quiet seated rest, we measured blood pressure again, and then subjects provided a urine sample for analysis of cotinine (a nicotine biomarker). We recorded ECG and finger photoplethysmographic arterial pressure. Subjects breathed to a metronome set at 15 breaths/min for 5 min supine, 5 min head-up (70o), and 5 min supine (recovery). Cotinine readings failed to register the presence of nicotine in urine, but a majority of subjects experienced dizziness and nausea after the active, but not the placebo cartridge. Seated arterial pressures were similar after the placebo cartridge (p ≥ .05), but increased from 112 ± 3/62 ± 2 mmHg to 115 ± 3/67 ± 3 after the nicotine cartridge (p ≤. 05). Systolic and diastolic pressures were higher (all p ≤ .05) after the nicotine trial compared to placebo for supine (115 ± 3/69 ± 2 vs. 106 ± 4/62 ± 2 mmHg), tilt (105 ± 4/66 ± 3 vs. 93 ± 4/60 ± 3 mmHg), and recovery (117 ± 5/72 ± 2 vs. 106 ± 4/64 ± 3 mmHg). No subject experienced presyncope during tilt for either trial. We show, for the first time, that inhalation of vaporized nicotine increases arterial pressure in the seated, supine and head-up tilt positions - suggesting sympathomemetic properties. Although mild, acute increases in arterial pressure may seem harmless, it is possible that daily, continuous use of e-cigs could result in consistently elevated arterial pressure, resulting in higher afterload and chronic cardiac strain

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Decolonising imperial heroes:Britain and France

The heroes of the British and French empires stood at the vanguard of the vibrant cultures of imperialism that emerged in Europe in the second half of the nineteenth century. Yet imperial heroes did not disappear after 1945 as British and French flags were lowered around the world. On the contrary, their reputations underwent a variety of metamorphoses in both the former metropoles and the former colonies. The introduction to this special issue of the Journal of Imperial and Commonwealth History presents an overview of the changing history and historiography of imperial heroes half a century after the end of empire

Optimization of adsorptive removal of α-toluic acid by CaO2 nanoparticles using response surface methodology

The present work addresses the optimization of process parameters for adsorptive removal of α-toluic acid by calcium peroxide (CaO2) nanoparticles using response surface methodology (RSM). CaO2 nanoparticles were synthesized by chemical precipitation method and confirmed by Transmission electron microscopy (TEM) and high-resolution TEM (HRTEM) analysis which shows the CaO2 nanoparticles size range of 5–15 nm. A series of batch adsorption experiments were performed using CaO2 nanoparticles to remove α-toluic acid from the aqueous solution. Further, an experimental based central composite design (CCD) was developed to study the interactive effect of CaO2 adsorbent dosage, initial concentration of α-toluic acid, and contact time on α-toluic acid removal efficiency (response) and optimization of the process. Analysis of variance (ANOVA) was performed to determine the significance of the individual and the interactive effects of variables on the response. The model predicted response showed a good agreement with the experimental response, and the coefficient of determination, (R2) was 0.92. Among the variables, the interactive effect of adsorbent dosage and the initial α-toluic acid concentration was found to have more influence on the response than the contact time. Numerical optimization of process by RSM showed the optimal adsorbent dosage, initial concentration of α-toluic acid, and contact time as 0.03 g, 7.06 g/L, and 34 min respectively. The predicted removal efficiency was 99.50%. The experiments performed under these conditions showed α-toluic acid removal efficiency up to 98.05%, which confirmed the adequacy of the model prediction