Explaining Test Results to Parents

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Triangulating Abuse Liability Assessment for Flavoured Cigar Products Using Physiological, Behavioural Economic and Subjective Assessments: A Within-subjects Clinical Laboratory Protocol

Introduction In the USA, Food and Drug Administration regulations prohibit the sale of flavoured cigarettes, with menthol being the exception. However, the manufacture, advertisement and sale of flavoured cigar products are permitted. Such flavourings influence positive perceptions of tobacco products and are linked to increased use. Flavourings may mask the taste of tobacco and enhance smoke inhalation, influencing toxicant exposure and abuse liability among novice tobacco users. Using clinical laboratory methods, this study investigates how flavour availability affects measures of abuse liability in young adult cigarette smokers. The specific aims are to evaluate the effect of cigar flavours on nicotine exposure, and behavioural and subjective measures of abuse liability. Methods and analyses Participants (projected n=25) are healthy smokers of five or more cigarettes per day over the past 3 months, 18–25 years old, naive to cigar use (lifetime use of 50 or fewer cigar products and no more than 10 cigars smoked in the past 30 days) and without a desire to quit cigarette smoking in the next 30 days. Participants complete five laboratory sessions in a Latin square design with either their own brand cigarette or a session-specific Black & Mild cigar differing in flavour (apple, cream, original and wine). Participants are single-blinded to cigar flavours. Each session consists of two 10-puff smoking bouts (30 s interpuff interval) separated by 1 hour. Primary outcomes include saliva nicotine concentration, behavioural economic task performance and response to various questionnaire items assessing subjective effects predictive of abuse liability. Differences in outcomes across own brand cigarette and flavoured cigar conditions will be tested using linear mixed models

Prior Daily Menthol Smokers More Likely to Quit 2 Years After a Menthol Ban Than Non-menthol Smokers: A Population Cohort Study

BACKGROUND AND AIMS: The province of Ontario, Canada, banned the use of menthol-flavored tobacco products as of January 1, 2017. This study aims to assess the longer-term impact of a menthol ban on smoking behavior at 2 years, which is unknown. METHODS: Population cohort study with baseline survey (n = 1821) conducted September–December 2016 and follow-up survey January–August 2019 among current smokers in Ontario (16+) prior to the menthol ban. Poisson regression was used to assess the probability of quitting smoking by pre-ban menthol status, controlling for differences in smoking and demographic characteristics, with multiple imputations used to address missing data. FINDINGS: Menthol smokers were more likely to report having quit smoking (12% [daily menthol] and 10% [occasional menthol] vs. 3% [non-menthol]; p < .001) than non-menthol smokers in the 2 years after a menthol ban. After adjustment for smoking and demographic characteristics, daily menthol smokers had higher likelihood of quitting smoking (adjusted relative risk [ARR] 2.08; 95% confidence interval [CI] 1.20–3.61) and reported more quit attempts (ARR 1.45; 95% CI 1.15–1.82). Among those who attempted to quit, menthol smoking was not associated with relapse (daily ARR = 0.96; 95% CI: 0.86, 1.07; occasional ARR = 0.99; 95% CI: 0.90, 1.08). However, there was a statistically significant interaction among menthol users who reported using other flavored tobacco products 1 year after the ban (ARR = 0.26 [95% CI: 0.08, 0.90]) CONCLUSIONS: The study found increased probability of quitting among daily menthol smokers and more quit attempts among daily and occasional menthol smokers compared with non-menthol smokers in Ontario 2 years after the implementation of a menthol ban. IMPLICATIONS: This study examines quitting behavior 2 years after a menthol ban in Ontario, Canada. Those who were daily menthol smokers prior to the ban were more likely to quit smoking and make more quit attempts in the 2 years after the ban. While there was no difference in the likelihood of relapse between menthol and non-menthol smokers among those who attempt to quit, there were indications that pre-ban daily menthol smokers who used other tobacco products after the ban were likely to quit

RPA and PCNA suppress formation of large deletion errors by yeast DNA polymerase δ

In fulfilling its biosynthetic roles in nuclear replication and in several types of repair, DNA polymerase δ (pol δ) is assisted by replication protein A (RPA), the single-stranded DNA-binding protein complex, and by the processivity clamp proliferating cell nuclear antigen (PCNA). Here we report the effects of these accessory proteins on the fidelity of DNA synthesis in vitro by yeast pol δ. We show that when RPA and PCNA are included in reactions containing pol δ, rates for single base errors are similar to those generated by pol δ alone, indicating that pol δ itself is by far the prime determinant of fidelity for single base errors. However, the rate of deleting multiple nucleotides between directly repeated sequences is reduced by ∼10-fold in the presence of either RPA or PCNA, and by ≥90-fold when both proteins are present. We suggest that PCNA and RPA suppress large deletion errors by preventing the primer terminus at a repeat from fraying and/or from relocating and annealing to a downstream repeat. Strong suppression of deletions by PCNA and RPA suggests that they may contribute to the high replication fidelity needed to stably maintain eukaryotic genomes that contain abundant repetitive sequences

Comparison of patterns of use, beliefs, and attitudes related to waterpipe between beginning and established smokers

BACKGROUND: To compare patterns of use, beliefs, and attitudes related to waterpipe smoking between university students (beginning smokers) and café customers (established smokers) in Aleppo Syria, in order to explore the evolution of this smoking method. METHODS: Two cross-sectional surveys were conducted among representative samples of university students (total 587, 48.4% men, mean age 22 years), and waterpipe users among cafe' customers (total 268, 60% men, mean age 30 years) in Aleppo, Syria. We used interviewer-administered questionnaire inquiring about pattern of waterpipe smoking (initiation, frequency), situational characteristics of use (partner, place, sharing), beliefs related to waterpipe smoking (harmful/addictive properties of waterpipe), attitudes related to waterpipe smoking (confidence in quitting, will to quit, motivation for quitting, past year quit attempt), and cigarette smoking. RESULTS: Daily and regular patterns of smoking become more prevalent with increased duration of smoking, but intermittent smoking remains the predominant pattern of waterpipe use. Women seem to be drawn later to the habit, which seem to escape the usual taboo against women's cigarette smoking. Patterns and context of waterpipe use tend to change with progress of the practice affecting frequency, setting, and sharing of waterpipe. Unlike beginners, established waterpipe smokers seem more smoking-method oriented, more hooked on the habit, less willing to quit, and less likely to foresee challenges to quitting. CONCLUSION: Use patterns and attitudes related to waterpipe smoking evolve to accommodate the change in dependence and life circumstances of the smoker. Most of use features, beliefs, attitudes, as well as time-course seem unique to this smoking method requiring novel approach to intervention

Histoplasma capsulatum proteome response to decreased iron availability

<p>Abstract</p> <p>Background</p> <p>A fundamental pathogenic feature of the fungus <it>Histoplasma capsulatum </it>is its ability to evade innate and adaptive immune defenses. Once ingested by macrophages the organism is faced with several hostile environmental conditions including iron limitation. <it>H. capsulatum </it>can establish a persistent state within the macrophage. A gap in knowledge exists because the identities and number of proteins regulated by the organism under host conditions has yet to be defined. Lack of such knowledge is an important problem because until these proteins are identified it is unlikely that they can be targeted as new and innovative treatment for histoplasmosis.</p> <p>Results</p> <p>To investigate the proteomic response by <it>H. capsulatum </it>to decreasing iron availability we have created <it>H. capsulatum </it>protein/genomic databases compatible with current mass spectrometric (MS) search engines. Databases were assembled from the <it>H. capsulatum </it>G217B strain genome using gene prediction programs and expressed sequence tag (EST) libraries. Searching these databases with MS data generated from two dimensional (2D) in-gel digestions of proteins resulted in over 50% more proteins identified compared to searching the publicly available fungal databases alone. Using 2D gel electrophoresis combined with statistical analysis we discovered 42 <it>H. capsulatum </it>proteins whose abundance was significantly modulated when iron concentrations were lowered. Altered proteins were identified by mass spectrometry and database searching to be involved in glycolysis, the tricarboxylic acid cycle, lysine metabolism, protein synthesis, and one protein sequence whose function was unknown.</p> <p>Conclusion</p> <p>We have created a bioinformatics platform for <it>H. capsulatum </it>and demonstrated the utility of a proteomic approach by identifying a shift in metabolism the organism utilizes to cope with the hostile conditions provided by the host. We have shown that enzyme transcripts regulated by other fungal pathogens in response to lowering iron availability are also regulated in <it>H. capsulatum </it>at the protein level. We also identified <it>H. capsulatum </it>proteins sensitive to iron level reductions which have yet to be connected to iron availability in other pathogens. These data also indicate the complexity of the response by <it>H. capsulatum </it>to nutritional deprivation. Finally, we demonstrate the importance of a strain specific gene/protein database for <it>H. capsulatum </it>proteomic analysis.</p

Nicotine and Cardiovascular Health: When Poison is Addictive – a WHF Policy Brief

Nicotine is universally recognized as the primary addictive substance fuelling the continued use of tobacco products, which are responsible for over 8 million deaths annually. In recent years, the popularity of newer recreational nicotine products has surged drastically in many countries, raising health and safety concerns. For decades, the tobacco industry has promoted the myth that nicotine is as harmless as caffeine. Nonetheless, evidence shows that nicotine is far from innocuous, even on its own. In fact, numerous studies have demonstrated that nicotine can harm multiple organs, including the respiratory and cardiovascular systems. Tobacco and recreational nicotine products are commercialized in various types and forms, delivering varying levels of nicotine along with other toxic compounds. These products deliver nicotine in profiles that can initiate and perpetuate addiction, especially in young populations. Notably, some electronic nicotine delivery systems (ENDS) and heated tobacco products (HTP) can deliver concentrations of nicotine that are comparable to those of traditional cigarettes. Despite being regularly advertised as such, ENDS and HTP have demonstrated limited effectiveness as tobacco cessation aids in real-world settings. Furthermore, ENDS have also been associated with an increased risk of cardiovascular disease. In contrast, nicotine replacement therapies (NRT) are proven to be safe and effective medications for tobacco cessation. NRTs are designed to release nicotine in a slow and controlled manner, thereby minimizing the potential for abuse. Moreover, the long-term safety of NRTs has been extensively studied and documented. The vast majority of tobacco and nicotine products available in the market currently contain nicotine derived from tobacco leaves. However, advancements in the chemical synthesis of nicotine have introduced an economically viable alternative source. The tobacco industry has been exploiting synthetic nicotine to circumvent existing tobacco control laws and regulations. The emergence of newer tobacco and recreational nicotine products, along with synthetic nicotine, pose a tangible threat to established tobacco control policies. Nicotine regulations need to be responsive to address these evolving challenges. As such, governments should regulate all tobacco and non-medical nicotine products through a global, comprehensive, and consistent approach in order to safeguard tobacco control progress in past decades

Proteomic Interrogation of Human Chromatin

Chromatin proteins provide a scaffold for DNA packaging and a basis for epigenetic regulation and genomic maintenance. Despite understanding its functional roles, mapping the chromatin proteome (i.e. the “Chromatome”) is still a continuing process. Here, we assess the biological specificity and proteomic extent of three distinct chromatin preparations by identifying proteins in selected chromatin-enriched fractions using mass spectrometry-based proteomics. These experiments allowed us to produce a chromatin catalog, including several proteins ranging from highly abundant histone proteins to less abundant members of different chromatin machinery complexes. Using a Normalized Spectral Abundance Factor approach, we quantified relative abundances of the proteins across the chromatin enriched fractions giving a glimpse into their chromosomal abundance. The large-scale data sets also allowed for the discovery of a variety of novel post-translational modifications on the identified chromatin proteins. With these comparisons, we find one of the probed methods to be qualitatively superior in specificity for chromatin proteins, but inferior in proteomic extent, evidencing a compromise that must be made between biological specificity and broadness of characterization. Additionally, we attempt to identify proteins in eu- and heterochromatin, verifying the enrichments by characterizing the post-translational modifications detected on histone proteins from these chromatin regions. In summary, our results provide insights into the value of different methods to extract chromatin-associated proteins and provide starting points to study the factors that may be involved in directing gene expression and other chromatin-related processes