Search

Background: Quitting cigarette smoking can substantially reduce or eliminate the risk of developing numerous chronic diseases. Use of flavored tobacco or nicotine products is commonly cited by adults who smoke cigarettes to be important in helping them reduce or quit smoking. The purpose of this analysis was to understand the association between the levels of use of flavored oral nicotine products and smoking reduction and quitting and how reduction or quitting may differ between predominant users of fruit/other versus mint flavored oral nicotine products after six months of use. Methods: Participants were provided with their choice of a variety of forms and flavors of Rogue® nicotine products (Study Products) over a 6-month actual use period and completed online surveys assessing tobacco, nicotine and Study Product use at Baseline and Months 1, 2, 4, and 6 thereafter. Results: Among the 1393 participants at Month 6, 41.4% and 52.5% used predominantly fruit/other or mint Study Product flavors, respectively. Compared to predominant mint users, predominant fruit/other users had greater cigarette reduction (mean reduction: 50.0% vs. 48.4%) and a higher proportion had quit smoking (proportion quit: 15.4% vs. 11.6%) at Month 6. Additionally, 38.8% of predominant fruit/other users and 39.3% of predominant mint users reduced their cigarette consumption by ≥ 50% from Baseline. Increased use of fruit/other flavors was independently associated with smoking reduction (8.6% greater reduction per 10 pieces/day; p < 0.001) and odds of quitting smoking (OR = 1.29 [95% CI: 1.04–1.59] per 10 pieces/day; p = 0.017). Increased use of mint flavors was independently associated with smoking reduction (7.5% greater reduction per 10 mint pieces/day; p < 0.001) but not with odds of quitting smoking. Conclusions: Increased use of either fruit/other or mint flavored Study Products at Month 6 was associated with significantly increased smoking reduction, whereas only increased use of fruit/other flavors was associated with greater odds of quitting smoking among participants in the study. Trial Registration: This study was observational. Participants were not prospectively assigned to one or more health-related interventions and could choose to use or not use the commercially available study products provided during the study. Thus, the study was not registered in a trial database by the Sponsor. [ABSTRACT FROM AUTHOR]

Abstract Background Short-term laboratory evolution of bacteria followed by genomic sequencing provides insight into the mechanism of adaptive evolution, such as the number of mutations needed for adaptation, genotype-phenotype relationships, and the reproducibility of adaptive outcomes. Results In the present study, we describe the genome sequencing of 11 endpoints of Escherichia coli that underwent 60-day laboratory adaptive evolution under growth rate selection pressure in lactate minimal media. Two to eight mutations were identified per endpoint. Generally, each endpoint acquired mutations to different genes. The most notable exception was an 82 base-pair deletion in the rph-pyrE operon that appeared in 7 of the 11 adapted strains. This mutation conferred an approximately 15% increase to the growth rate when experimentally introduced to the wild-type background and resulted in an approximately 30% increase to growth rate when introduced to a background already harboring two adaptive mutations. Additionally, most endpoints had a mutation in a regulatory gene (crp or relA, for example) or the RNA polymerase. Conclusions The 82 base-pair deletion found in the rph-pyrE operon of many endpoints may function to relieve a pyrimidine biosynthesis defect present in MG1655. In contrast, a variety of regulators acquire mutations in the different endpoints, suggesting flexibility in overcoming regulatory challenges in the adaptation.

Genome-wide gene essentiality data sets are becoming available for Escherichia coli, but these data sets have yet to be analyzed in the context of a genome scale model. Here, we present an integrative model-driven analysis of the Keio E. coli mutant collection screened in this study on glycerol-supplemented minimal medium. Out of 3,888 single-deletion mutants tested, 119 mutants were unable to grow on glycerol minimal medium. These conditionally essential genes were then evaluated using a genome scale metabolic and transcriptional-regulatory model of E. coli, and it was found that the model made the correct prediction in ~91% of the cases. The discrepancies between model predictions and experimental results were analyzed in detail to indicate where model improvements could be made or where the current literature lacks an explanation for the observed phenotypes. The identified set of essential genes and their model-based analysis indicates that our current understanding of the roles these essential genes play is relatively clear and complete. Furthermore, by analyzing the data set in terms of metabolic subsystems across multiple genomes, we can project which metabolic pathways are likely to play equally important roles in other organisms. Overall, this work establishes a paradigm that will drive model enhancement while simultaneously generating hypotheses that will ultimately lead to a better understanding of the organism.

Abstract Background High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers. Results We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation. Conclusions Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level.

13C tracer experiments and 13C-constrained flux analysis were used for examining the metabolic network of Escherichia coli adaptively evolved on lactate. Results suggest an overall increase in fluxes for already-active central pathways.

Background: High-throughput DNA methylation arrays are likely to accelerate the pace of methylation biomarker discovery for a wide variety of diseases. A potential problem with a standard set of probes measuring the methylation status of CpG sites across the whole genome is that many sites may not show inter-individual methylation variation among the biosamples for the disease outcome being studied. Inclusion of these so-called "non-variable sites" will increase the risk of false discoveries and reduce statistical power to detect biologically relevant methylation markers. Results: We propose a method to estimate the proportion of non-variable CpG sites and eliminate those sites from further analyses. Our method is illustrated using data obtained by hybridizing DNA extracted from the peripheral blood mononuclear cells of 311 samples to an array assaying 1505 CpG sites. Results showed that a large proportion of the CpG sites did not show inter-individual variation in methylation. Conclusions: Our method resulted in a substantial improvement in association signals between methylation sites and outcome variables while controlling the false discovery rate at the same level. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the articles "Zero is an important number," by L. Smith, "The comparative safety of buprenorphine versus methadone in pregnancy--what about confounding?," by S. Brogly et al. and "Buprenorphine compared with methadone to treat pregnant women with opioid use disorder: a systematic review and meta-analysis of safety in the mother, fetus and child," by B.K. Zedler.

Objectives: The intranasal route of administration for naloxone delivery is one treatment for opioid overdose, but treatment failures with this modality have been documented. This study determines the incidence of obstructive nasal pathology in patients who experienced serious opioid-induced respiratory depression (OIRD)., Design: Retrospective analysis of the IMS LifeLink: Health Plan Claims Database to detect patients with at least one opioid pharmacy claim from 2009 to 2013 and who experienced serious OIRD. Four controls were randomly assigned to each case., Main Outcome Measures: A multivariable analysis determined the adjusted odds ratio of OIRD for patients with obstructive nasal pathology., Results: A total of 7,234 patients experienced a serious OIRD event; 840 (11.6 percent) had obstructive nasal pathology: 20 (2.4 percent) had deviated nasal septum (International Classification of Disease, 9th revision [ICD-9] 470), 246 (29.3 percent) had polyp of the nasal cavity (ICD-9 470.1), 130 (15.5 percent) had hypertrophy of nasal turbinates (ICD-9 478.0), and 659 (78.5 percent) had other disease of the nasal cavity (ICD-9 478.19). The adjusted odds ratio for patients who experienced serious OIRD having concurrent obstructive nasal pathology was 1.28 (95% confidence interval 1.13-1.46)., Conclusions: Obstructive nasal pathology is relatively common in patients who experience serious OIRD, and in itself is associated with a higher risk of having OIRD.

Background: Untreated opioid dependence in pregnant women is associated with adverse birth outcomes. Buprenorphine and methadone are options for opioid agonist medication-assisted treatment during pregnancy., Objective: The aim of this study was to describe adverse birth outcomes observed with buprenorphine or methadone treatment compared to the general population in Sweden., Methods: Pregnant women and their corresponding births during 2005-2011 were identified in the Swedish Medical Birth Register. Data on stillbirth, neonatal/infant death, mode of delivery, gestational age at birth, Apgar score, growth outcomes, neonatal abstinence syndrome, and congenital malformations were examined. Frequencies were compared using two-sided Fisher's exact tests. Unadjusted estimates of birth outcomes for women treated with buprenorphine or methadone were compared to the registered general population., Results: A total of 746,257 pregnancies among 538,178 unique women resulted in 746,485 live births. Among the 194 women treated with buprenorphine (N = 176) or methadone (N = 52), no stillbirths or neonatal/infant deaths occurred. Neonatal abstinence syndrome developed in 23.3% and 38.5% of infants born to mothers treated with buprenorphine and methadone, respectively. The frequency of the selected adverse birth outcomes assessed in women treated with buprenorphine as compared to the general population was not significantly different. However, a significantly higher frequency of preterm birth and congenital malformations was observed in women treated with methadone as compared to the general population. Compared with the general population, methadone-treated women were significantly older than buprenorphine-treated women, and both treatment groups began prenatal care later, were more likely to smoke cigarettes, and did not cohabitate with the baby's father., Conclusions: An increased frequency of the selected adverse birth outcomes was not observed with buprenorphine treatment during pregnancy. Twofold increased frequency of preterm birth [2.21 (1.11, 4,41)] and congenital malformations [2.05 (1.08, 3.87)] was observed in the methadone group, which may be partly explained by older average maternal age and differences in other measured and unmeasured confounders.