Seven Day E-cigarette Vapor Exposure Does Not Modify Ventilation Patterns in Long-Evans Rats

Electronic nicotine delivery systems or e-cigarettes are devices used to deliver aerosolized liquids often containing nicotine and other chemicals. These devices were originally created as a way to assist with smoking cessation in adults; however, use of these devices is increasing in adolescent and young adult populations. The long and short term effects of vaping are still under active investigation. PURPOSE: The purpose of this study was to investigate the effects of 7 days of e-cigarette vapor exposure in adult rats on lung function and lung tissue inflammatory cytokine expression, specifically IL-1. METHODS: Using random assignment, 10 adult male long-evans rats were assigned to vape (experimental) or air (control) groups. The animals were exposed to either air (n = 4) or 5% nicotine vapor (n=6) using a whole-body exposure chamber, twice a day for ten minutes for seven consecutive days. Ventilation recordings were completed on day 0 (before exposure) and day 8 (after exposure) using unrestrained whole-body plethysmography. Minute ventilation, tidal volume, and breathing frequency were assessed. Blood was collected on day 8 to look for the presence of cotinine (a nicotine metabolite). Whole lung tissue was also collected on day 8 for inflammatory cytokine assay, IL-1 ELISA. RESULTS: Cotinine was found to be present in the serum samples of the vape groups (86.6 ng/ml +/- 1.0 ng/mL) but not the air groups (0.0 ng/mL) confirming drug exposure. Baseline ventilation data collected on day 0 and post-exposure ventilation data collected on day 8 were compared between air and vape groups across three different parameters: minute ventilation, frequency, and tidal volume. These parameters were compared resulting in three distinct two-way ANOVAs comparing the variables time and treatment. No significant difference was found among any of the comparisons (p \u3e 0.05 for all). Similarly, no difference in lung inflammatory cytokine IL-1 was observed in the lung tissue of the air (85.6 pg/mL +/- 10.2 pg/mL) or vape (82.7 pg/mL +/- 14.9 pg/mL) exposure groups (p \u3e 0.05, t-test). CONCLUSIONS: In this study, 7 days of e-cigarette vapor exposure did not affect ventilation parameters or increase the presence of inflammatory cytokine, IL-1, in whole lung tissue. Limitations to this study include a small sample size (n = 10) and unreliable negative-pressure which were used to produce the vapor for the e-cigarette exposure. Future studies will modify the vape exposure system and include a larger sample size

Effects of 14 Day E-Cigarette Exposure on Ventilation and Circulating Pro-Inflammatory Cytokines in Adolescent Rats

Electronic nicotine delivery systems or e-cigarettes are devices used to deliver vaporized liquids often containing nicotine and other chemicals. These devices were originally created as a way to assist with smoking cessation in adults; however, use of these devices is increasing in adolescent and young adult populations. Recent research suggests that exposure to the chemicals in e-cigarette vapor may cause harm to adolescent lung tissue and promote a proinflammatory immune response in the lungs. These molecular changes may lead to functional changes in terms of lung volumes or gas exchange at the respiratory membrane. PURPOSE: The purpose of this study was to investigate the effects of 14 days of e-cigarette vapor exposure in adolescent rats on lung function and lung tissue proinflammatory cytokine expression, specifically IL-1β. METHODS: Using random assignment, 20 adolescent male Long Evans rats were assigned to vape (experimental) or air (control) groups. The animals were exposed to either air (n = 10) or 5% nicotine vapor (n=10) using a whole-body exposure chamber, once a day for ten minutes for fourteen consecutive days. Ventilation recordings were completed on day 0 (before exposure) and day 15 (after exposure) using unrestrained whole-body plethysmography. Minute ventilation/100g, tidal volume/100g, and breathing frequency were assessed. Blood was collected on day 15 and processed to serum. Serum samples were analyzed for circulating levels of the nicotine metabolite, cotinine, and the proinflammatory cytokine, IL-1β, using enzyme linked immunosorbent assays (ELISA). RESULTS: Cotinine was found to be present in the serum samples of the vape groups (20.71 ng/ml +/- 6.875 ng/mL) but not the air groups (0.007 +/- 0.019 ng/mL) confirming nicotine and vapor exposure. Baseline ventilation data collected on day 0 and post-exposure ventilation data collected on day 15 were compared between air and vape groups across three different parameters: minute ventilation/100g , frequency, and tidal volume/100 g. These parameters were compared resulting in three distinct 2x2 (time x treatment) Mixed Model ANOVAs. Between baseline and post-treatment measurements, for both groups, there was a significant decrease in values in minute ventilation (F(1,15) = 5.647, p = 0.0312) and tidal volume (F(1,15) = 12.38, p = 0.0031). Between treatment groups there was also a significant difference in minute ventilation (F(1,15) = 7.979, p = 0.0128) and frequency (F(1,15) = 11.35, p = 0.0042). There was also significantly lower levels observed in the inflammatory cytokine IL-1β (p \u3c 0.0136) for the vape group (22.13 +/- 19.96 pg/mL) in comparison to the air group (3.28 +/- 3.52 pg/mL). CONCLUSIONS: Following 14 days of e-cigarette vapor exposure, ventilation patterns were altered in the vapor exposed animals, specifically decreasing tidal volume and minute ventilation. Additionally, in these same vapor exposed animals, circulating levels of the pro-inflammatory cytokine, IL-1ꞵ, was decreased suggesting dysregulation of immune pathways. Taken together these results suggest that the use of e-cigarettes may lead to both functional and molecular changes in adolescent lungs, interfering with pulmonary function and affecting one’s quality of life

UBVRI Light Curves of 44 Type Ia Supernovae

We present UBVRI photometry of 44 type-Ia supernovae (SN Ia) observed from 1997 to 2001 as part of a continuing monitoring campaign at the Fred Lawrence Whipple Observatory of the Harvard-Smithsonian Center for Astrophysics. The data set comprises 2190 observations and is the largest homogeneously observed and reduced sample of SN Ia to date, nearly doubling the number of well-observed, nearby SN Ia with published multicolor CCD light curves. The large sample of U-band photometry is a unique addition, with important connections to SN Ia observed at high redshift. The decline rate of SN Ia U-band light curves correlates well with the decline rate in other bands, as does the U-B color at maximum light. However, the U-band peak magnitudes show an increased dispersion relative to other bands even after accounting for extinction and decline rate, amounting to an additional ~40% intrinsic scatter compared to B-band.Comment: 84 authors, 71 pages, 51 tables, 10 figures. Accepted for publication in the Astronomical Journal. Version with high-res figures and electronic data at http://astron.berkeley.edu/~saurabh/cfa2snIa

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease

Peer reviewedPublisher PD

Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization.

The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD

Testosterone and Cortisol Release among Spanish Soccer Fans Watching the 2010 World Cup Final

This field study investigated the release of testosterone and cortisol of a vicarious winning experience in Spanish fans watching the finals between Spain and the Netherlands in the 2010 FIFA World Cup Soccer. Spanish fans (n = 50) watched the match with friends or family in a public place or at home and also participated in a control condition. Consistent with hypotheses, results revealed that testosterone and cortisol levels were higher when watching the match than on a control day. However, neither testosterone nor cortisol levels increased after the victory of the Spanish team. Moreover, the increase in testosterone secretion was not related to participants' sex, age or soccer fandom, but the increase in total cortisol secretion during the match was higher among men than among women and among fans that were younger. Also, increases in cortisol secretion were greater to the degree that people were a stronger fan of soccer. Level of fandom further appeared to account for the sex effect, but not for the age effect. Generally, the testosterone data from this study are in line with the challenge hypothesis, as testosterone levels of watchers increased to prepare their organism to defend or enhance their social status. The cortisol data from this study are in line with social self-preservation theory, as higher cortisol secretion among young and greater soccer fans suggests that especially they perceived that a negative outcome of the match would threaten their own social esteem

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

The Neural Basis of Decision-Making and Reward Processing in Adults with Euthymic Bipolar Disorder or Attention-Deficit/Hyperactivity Disorder (ADHD)

Attention-deficit/hyperactivity disorder (ADHD) and bipolar disorder (BD) share DSM-IV criteria in adults and cause problems in decision-making. Nevertheless, no previous report has assessed a decision-making task that includes the examination of the neural correlates of reward and gambling in adults with ADHD and those with BD

Genome-wide association studies identify 137 genetic loci for DNA methylation biomarkers of aging

Background Biological aging estimators derived from DNA methylation data are heritable and correlate with morbidity and mortality. Consequently, identification of genetic and environmental contributors to the variation in these measures in populations has become a major goal in the field. Results Leveraging DNA methylation and SNP data from more than 40,000 individuals, we identify 137 genome-wide significant loci, of which 113 are novel, from genome-wide association study (GWAS) meta-analyses of four epigenetic clocks and epigenetic surrogate markers for granulocyte proportions and plasminogen activator inhibitor 1 levels, respectively. We find evidence for shared genetic loci associated with the Horvath clock and expression of transcripts encoding genes linked to lipid metabolism and immune function. Notably, these loci are independent of those reported to regulate DNA methylation levels at constituent clock CpGs. A polygenic score for GrimAge acceleration showed strong associations with adiposity-related traits, educational attainment, parental longevity, and C-reactive protein levels. Conclusion This study illuminates the genetic architecture underlying epigenetic aging and its shared genetic contributions with lifestyle factors and longevity.Peer reviewe