Metabolomics is the systematic analysis of low-molecular weight compounds (metabolites) within biological systems that represent molecular endpoints of gene expression and environmental exposures. A major goal of metabolomics is achieving better understanding of the pathophysiology of complex disease processes while elucidating mechanisms of action of nutrients, toxins, and/or drugs. Multisegment injection-capillary electrophoresis-mass spectrometry (MSI-CE-MS) is a high-throughput microseparation platform that is ideal for the analysis of polar/ionic metabolites from volume-restricted biological samples. This thesis includes two major metabolomics projects using MSI-CE-MS that are aimed at contributing new advances in public health and chronic disease prevention. Chapter II presents an analysis of the metabolome from patients with phenylketonuria (PKU) — a genetic disease affecting phenylalanine (Phe) metabolism that requires lifelong dietary restriction to prevent irreversible intellectual disabilities. A targeted and nontargeted metabolomics approach using matching urine and plasma samples was conducted to confirm known markers of PKU and identify new markers associated with dietary adherence and disease progression. Along with increased excretion of Phe catabolites in urine, high plasma Phe was associated with decreased excretion of acylcarnitines and greater excretion of histidine catabolites, suggesting impaired fatty acid oxidation and micronutrient deficiencies, respectively. Overall, this may provide a strategy to objectively monitor dietary adherence beyond standard dietary records or patient recall. Chapter III investigates the impact of electronic cigarette smoke exposure on the placental metabolome as a model cell line of fetal development. Evidence of altered amino acid metabolism, in addition to changes in acylcarnitines and metabolites associated with cellular proliferation, were observed in more susceptible first trimester placental cells and were attributed to flavouring agents irrespective of nicotine dosage. This work supports the hypothesis that flavoured e-cigarette formulations pose a significant health risk in comparison to unflavoured formulations and supports the need for further risk assessment and careful regulation of these products to prevent deleterious birth outcomes in pregnant mothers. / Thesis / Master of Science (MSc)

No description available.

Plusieurs alternatives ont été mises au point pour réduire les effets de la cigarette sur la santé buccale et générale. La plus récente de ces initiatives est la cigarette électronique. Plusieurs études montrent que la cigarette électronique contient moins de produits toxiques comparativement à la cigarette standard. Ces études concluent que la cigarette électronique est moins nocive pour la santé. Cependant, d’autres études émettent des doutes sur l’innocuité de la cigarette électronique étant donné la présence de multiples produits chimiques. Ces derniers peuvent interagir négativement avec plusieurs parties du corps, dont la cavité buccale. Les objectifs de cette étude sont (i) d’évaluer les effets d’expositions répétées (1, 2 ou 3 fois) au condensé de cigarette électronique sur la morphologie, la croissance, la migration et l’apoptose des fibroblastes gingivaux humains (ii) d’évaluer les effets de la vapeur de la cigarette électronique sur la croissance, la production de chitine et l’expression de certains gènes codant pour des protéines de la famille des "secreted aspartyl proteinases (SAP par C. albicans avec des temps d’exposition de 15 min, deux fois par jour, pendant 2 et 3 jours. (iii) d’évaluer l’interaction des cellules épithéliales gingivales avec C. albicans préalablement exposé à la cigarette électronique. Nous avons utilisé différentes techniques de biologie cellulaire, de biologie moléculaire et de microbiologie. Nos travaux montrent que les fibroblastes exposés au condensé de cigarette électronique ont une morphologie anormale (cellules plus grosses, vacuolées,.) et un taux de prolifération plus faible comparativement aux cellules non exposées. Ces observations sont consolidées par un taux plus élevé de cellules apoptotiques comparativement aux cellules non exposées. L’analyse de la migration cellulaire montre que le condensé de cigarette électronique réduit de façon significative la capacité de migration des fibroblastes. Il est à noter que les effets sont plus importants avec la cigarette, suivi de la cigarette électronique contenant la nicotine, puis celle sans nicotine. Les effets de la cigarette électronique sont moins importants que ceux du condensé de cigarette, mais plus sérieux comparativement aux cellules non exposées. Nos études montrent que l’exposition de C. albicans à la cigarette électronique entraîne une augmentation de sa croissance. Cette observation est supportée par un taux plus élevé de chitine produite par C. albicans exposé à la cigarette électronique. L’analyse de la transformation montre des formes hyphes plus longues après l’exposition à cigarette électronique. Nous avons aussi observé que la cigarette électronique augmente l’expression des gènes SAP2, SAP3 et SAP9 par C. albicans comparativement au contrôle (non exposé). L’exposition de C. albicans à la cigarette électronique favorise l'adhésion de la levure aux cellules épithéliales, augmente le taux de tyransformation de la levure. L’exposition de C. albicans à la cigarette électronique, puis son contact avec les cellules épithéliales cause une libération importante de la lactate deshydrogénase (LDH), et la différenciation des cellules épithéliales, mais réduit le taux de croissance de ces cellules gingivales. Les résultats globaux indiquent que les cigarettes électroniques peuvent interagir avec le microbiome buccal de l’utilisateur. Parce que les cigarettes électroniques réduisent la croissance des cellules gingivales et augmentent l'apoptose cellulaire, cela peut diminuer l'immunité innée dans la cavité buccale, ce qui pourrait augmenter le risque d'infections buccales, telles que la candidose / Electronic cigarettes (e-cigarettes) were designed to replace regular cigarette smoking and to contribute to smoking cessation. E-cigarettes require the use of vaping liquid that contains propylene glycol (PG) and vegetable glycerin (VG) as well as nicotine in various concentrations and flavours. Several studies comparing ecigarettes to conventional cigarettes show that e-cigarettes contain lower levels of toxic compounds and for this reason are deemed safer. However, a growing body of evidence shows that e-cigarettes contain many chemicals including formaldehyde, acetaldehyde, acrolein, and toluene, which may have adverse effects on different body parts, including the oral cavity. The first objective of this study was to investigate the impact of repeated exposures (1, 2, or 3 times) to e-cigarette condensates with or without nicotine on normal human gingival fibroblast morphology, proliferation, migration, and apoptosis. The second objective was to evaluate the effect of e-cigarettes vapors on the growth changes of C. albicans from blastospore to hyphal form and the expression of secreted aspartic proteinases (SAPs) SAP2, SAP3, and SAP9 genes by C. albicans, with exposure times of 15 min twice a day for 2 and 3 days. The third objective was to shed light on the interaction between e-cigarette-exposed C. albicans and gingival epithelial cells. Various cell biology, molecular biology, and microbiology protocols were deployed. Results show that exposure of gingival fibroblasts to nicotine-rich e-cigarette condensate altered both cell morphology and proliferation rate. Exposure to the ecigarette condensate also increased the levels of apoptotic fibroblasts. Fibroblast migration was delayed after culture scratches were exposed to e-cigarette condensate. Although e-cigarettes are considered to be less harmful than are conventional cigarettes, e-cigarettes significantly harmed the fibroblasts compared to non-exposed cells. E-cigarette exposure also increased C. albicans growth and hyphal length. The exposed C. albicans produced high levels of chitin and expressed high mRNA levels of SAP2, SAP3, and SAP9 genes. When in contact with gingival epithelial cells, e-cigarette-exposed C. albicans adhered better compared to the controls. Indirect communication between e-cigarette-exposed C. albicans and gingival epithelial cells led to epithelial cell differentiation, reduced cell growth, and increased lactate dehydrogenase (LDH) activity. Overall results indicate that e-cigarettes may interact with the user’s oral microbiome. Because e-cigarettes reduce gingival cell growth and increase cell apoptosis, this may decrease the innate immunity in the oral cavity, which could increase the risk of oral infections, such as candidiasis.

CONTEXTE : Le marché de la cigarette électronique a connu une importante hausse dans les dernières années, principalement chez les fumeurs visant l’arrêt tabagique. Toutefois, les effets pulmonaires de l’inhalation de propylène glycol (PG) et de glycérol (Gly), principaux constituants du e-liquide utilisé dans les cigarettes électroniques, demeurent encore inconnus. OBJECTIF : Investiguer les effets pulmonaires des vapeurs de cigarette électronique. MÉTHODES : Un système d’exposition de type « whole-body » a été mis au point. Jusqu’à 40 souris sont exposées 2 h/jour, 5 jours/semaine pour une période de 2 à 8 semaines. Le e-liquide est fabriqué au laboratoire, est composé de 30% de Gly et de 70% de PG, et ne contient ni nicotine ni saveurs. L’inflammation pulmonaire a été déterminée par cytologie des lavages broncho-alvéolaires. Les effets de la cigarette électronique sur le transcriptome pulmonaire ont été évalués à l’aide de puces d’expression génique. RÉSULTATS : L’exposition à la cigarette électronique n’entraine pas d’inflammation pulmonaire significative. Les analyses sur puces d’ADN montrent que la cigarette électronique a un impact sur les gènes impliqués dans la régulation du cycle circadien pulmonaire. Des analyses périodiques sur 24h montrent que la rythmicité de plusieurs gènes impliqués dans la régulation du cycle circadien est dérégulée par l’exposition à la cigarette électronique. On retrouve également ces perturbations dans le foie, le rein et le muscle squelettique, et dans une moindre mesure, dans le cerveau. L’exposition au Gly seul ou au PG seul indique que les deux composés sont responsables des changements observés au niveau systémique. CONCLUSION : La cigarette électronique n’induit pas de réponse inflammatoire, mais semble plutôt causer une perturbation du cycle circadien, tant au niveau pulmonaire que systémique. De plus amples recherches sont nécessaires afin de cerner les effets potentiels d’une perturbation circadienne induite par la cigarette électronique. / RATIONALE. The market for electronic cigarettes has boomed in the past few years, especially among smokers who desire to quit smoking. However, the pulmonary effects on propylene glycol (PG) and glycerol (Gly) inhalation have not been thoroughly investigated. OBJECTIVE. To investigate the effects of vapour on the mouse lungs. METHODS. A whole-body exposure automated system has been designed. Up-to 40 mice are exposed to electronic cigarette vapour, 2 hours/day, 5 days/week, from 2 and up to 8 weeks. E-liquid was fabricated in the laboratory, composed of 30% Gly and 70% PG, and without nicotine or flavor. Parameters of lung inflammation were assessed by cytology and ELISA in the bronchoalveolar lavage (BAL). Effects of electronic cigarette exposure on the pulmonary transcriptome were assessed using gene expression arrays RESULTS. Exposure to electronic cigarette alone does not cause pulmonary inflammation. Transcriptome analysis performed on lung tissue showed that electronic cigarette had a significant impact on genes responsible for regulating the pulmonary circadian cycle. Periodical sacrifices showed that the rhythmicity of key circadian genes was altered by electronic cigarette exposure. Expression of circadian genes in the liver is also altered, but the brain is less affected. Exposure to glycerol or propylene glycol alone indicated that glycerol was largely responsible for dysregulating the pulmonary circadian rhythm. It also showed that both compound had an impact on the liver and brain circadian rhythms. CONCLUSION. Electronic cigarette exposure does not appear to trigger lung inflammatory but rather seems to affect the lung circadian rhythmicity. Further research is required to investigate the possible effects of pulmonary circadian disruption by electronic cigarette.

This master’s thesis is focusing on the research of chosen smoking types and their comparison in regard to emitted particles. Aerosol created during smoking represents a serious threat for human health. For purposes of this work an experimental set-up was constructed in the Laboratory of Aerosol Research at BUT FME and experiments simulating smoking process were carried out. The results of these experiments are presenting objective information about the constitution of produced aerosol which enters smoker’s lungs. There are many myths about the harmful effects of different types of smoking. The goal of this work is to verify and resolve these myths and set the foundation for possible upcoming research in this area.

Objective. To examine alternative tobacco product (ATP) use and associated factors among middle school students in Appalachian Tennessee. Method. Data (2015– 2016; N=573) from school-based tobacco surveys in 11 middle schools in Appalachian Tennessee were analyzed. Multiple logistic regression model described factors associated with ATP use. Results. More than one-tenth (13.2%) of participants have ever used ATPs. Approximately 9%, 7%, 6%, and 2% of participants have ever used e-cigarettes, cigarettes, smokeless tobacco, and little cigars or cigarillos, respectively. The following were significantly associated with ever use of ATPs: believing tobacco users have more friends, owning tobacco-branded item(s), living with a tobacco user, having ever smoked cigarettes, and living in homes where smoking is allowed. Conclusion. More than one in 10 of participants have ever used at least one ATP, and association with desirable objects and situations may promote ATP use. Interventions should seek to reduce these positive images and make all tobacco products unappealing.

No description available.

Sin taxes have increased significantly during the past three years. There have been different opinions regarding the levying of sin taxes: in relation to whether it helps the government to raise revenue or reduces the consumption thereof. This study therefore investigates the actual purpose for these taxes by means of a literature and empirical review. An increase in sin taxes affects the poor more than the rich because such taxes are classified as a regressive type of tax. The primary research problem addressed by this literature study was to determine the percentage that the lower income earning group of South African citizens, who are funded by social grants, spend on sin taxed items. This study focused on two areas: the social grant system in conjunction with the Consumer Price Index (“CPI”) and the levying of sin taxes in South Africa. Over the years, South Africa has experienced an increase in its levels of poverty. There are eight types of social grants in South Africa, to which the lower income earning South African citizens, who live below the poverty line, are entitled, depending on their circumstances. This study discusses only seven of the eight social grants, by considering the purpose of the social grant, criteria, means testing requirements and the monthly amount available. These grants include the child support grant, old age grant, disability grant, foster care grant, care dependency grant, grant-in-aid and war veteran grant. The CPI of South Africa is briefly addressed in this study, followed by the increases over the past three years. The escalations of the social grants and that of the CPI of South Africa have been compared in order to determine whether the government remains concerned for their lower income earning citizens most of whom live below the poverty line. For purposes of this study, sin taxes have been narrowed down to include only alcoholic beverages and cigarettes. This study determined the increases of sin taxes on these substances over the past three years as well as the consumption thereof. Their consumption was determined by the sales volume. A comparison of the increases and consumption was made, the purpose of which was to determine government’s motivation for these increases. The empirical review of this study investigated the social grant recipients’ spending habits on these items. This was done by means of a self- developed questionnaire. The purpose of the questionnaire was to determine the percentage of their grant money that the social grant recipients spend on alcoholic beverages and cigarettes. The results and findings led to a conclusion which addressed the problem of this study. This study makes recommendations for further investigation of the sin tax implications for the lower income earning South African citizens, who are funded by social grants. / MCom (Accountancy)--North-West University, Vaal Triangle Campus, 2015

Sin taxes have increased significantly during the past three years. There have been different opinions regarding the levying of sin taxes: in relation to whether it helps the government to raise revenue or reduces the consumption thereof. This study therefore investigates the actual purpose for these taxes by means of a literature and empirical review. An increase in sin taxes affects the poor more than the rich because such taxes are classified as a regressive type of tax. The primary research problem addressed by this literature study was to determine the percentage that the lower income earning group of South African citizens, who are funded by social grants, spend on sin taxed items. This study focused on two areas: the social grant system in conjunction with the Consumer Price Index (“CPI”) and the levying of sin taxes in South Africa. Over the years, South Africa has experienced an increase in its levels of poverty. There are eight types of social grants in South Africa, to which the lower income earning South African citizens, who live below the poverty line, are entitled, depending on their circumstances. This study discusses only seven of the eight social grants, by considering the purpose of the social grant, criteria, means testing requirements and the monthly amount available. These grants include the child support grant, old age grant, disability grant, foster care grant, care dependency grant, grant-in-aid and war veteran grant. The CPI of South Africa is briefly addressed in this study, followed by the increases over the past three years. The escalations of the social grants and that of the CPI of South Africa have been compared in order to determine whether the government remains concerned for their lower income earning citizens most of whom live below the poverty line. For purposes of this study, sin taxes have been narrowed down to include only alcoholic beverages and cigarettes. This study determined the increases of sin taxes on these substances over the past three years as well as the consumption thereof. Their consumption was determined by the sales volume. A comparison of the increases and consumption was made, the purpose of which was to determine government’s motivation for these increases. The empirical review of this study investigated the social grant recipients’ spending habits on these items. This was done by means of a self- developed questionnaire. The purpose of the questionnaire was to determine the percentage of their grant money that the social grant recipients spend on alcoholic beverages and cigarettes. The results and findings led to a conclusion which addressed the problem of this study. This study makes recommendations for further investigation of the sin tax implications for the lower income earning South African citizens, who are funded by social grants. / MCom (Accountancy)--North-West University, Vaal Triangle Campus, 2015

Introduction: E-cigarettes have been marketed as smoking cessation aids and harm reduction strategies. Prior regional surveys found that physicians are recommending them to patients despite the lack of evidence supporting these industry claims. Yet, little is known about physicians’ beliefs regarding e-cigarettes and whether these beliefs are associated with them recommending e-cigarette use in clinical practice. Methods: This three-manuscript dissertation used a mixed-methods approach including both qualitative and quantitative research methods. The aims were to: (1) Uncover the factors associated with primary care physicians’ (PCPs) decisions to recommend e-cigarettes to their patients for tobacco use cessation; (2) Estimate the prevalence of PCPs who recommend e-cigarettes to their patients as a tobacco use cessation aid; (3) Estimate the influence of factors identified in Aim 1 on PCPs’ decisions to recommend e-cigarettes to their patients for tobacco use cessation; (4) Evaluate the conceptual model which demonstrates the factors contributing to PCPs’ decisions to recommend e-cigarettes to their patients for tobacco use cessation. Results: Study 1 found that PCPs expressed a lack of information about e-cigarette safety and efficacy along with skepticism about the role of e-cigarettes in tobacco control in general and in smoking cessation in particular. However, once a patient initiates a discussion with them, PCPs seem to be endorsing patients’ interests in using e-cigarettes, as well as recommending e-cigarettes to particular types of patients who smoke for both smoking cessation and as a harm reduction strategy. Study 2 found that over three-quarters (82.7%, n=220) of PCPs reported previously discussing e-cigarettes with their patients. Overall, 57.8% (n=155) reported previously recommending e-cigarettes to an adult patient who smoked. Among those recommending e-cigarettes, the majority reported recommending them for smoking cessation and harm reduction (71.6%, n=111), 18.8% for smoking cessation only, and 9.6% for harm reduction only. The likelihood of recommending e-cigarettes to patients was associated with considering their patients’ interest in using e-cigarettes, PCP’s belief that e-cigarettes can help in quitting smoking, and PCP’s belief that e-cigarettes limit secondhand smoke exposure for others. Study 3 found that PCPs intend to recommend e-cigarettes for smokers with prior unsuccessful quit attempts (mean=3.63, ±2.1), followed by heavy smokers wanting to quit (3.57, ±2.2), and heavy smokers refusing to quit (mean=3.50, ±2.2). The mean for PCPs’ recommendation intentions was 3.04 (±2.0) for light smokers wanting to quit, and 3.01 (±1.9) for light smokers refusing to quit. Nevertheless, these recommendation intentions were driven by PCPs’ beliefs and perceptions of e-cigarette benefit and harm; however, these intentions varied by patients’ tobacco use profile. Discussion: Findings across the three studies highlight the significance of PCPs’ beliefs in driving their recommendations of e-cigarettes versus evidence based knowledge, as well as, the importance of patients’ factors and interest in using e-cigarettes for PCPs’ recommendations for e-cigarette use.