Dissertations / Theses on the topic 'Tobacco Use Disorder'

Regional pulmonary blood flow and volume was measured in ten rabbits anesthetized with pentobarbital (30 mg/kg). Tracheostomy was performed and catheters were placed into the jugular vein and carotid artery. The cardiac ⁹⁹mtc output was measured using the indicator-dilution technique using Tc labelled RBC followed by an injection of radiolabelled macroaggregates (MAA) to mark regional blood flow. Measurements were made both before and after either exposure to cigarette smoke (3 cigarettes for ten minutes at 4 puffs/minute) or sham exposure to air. The animals were sacrificed and the lungs were removed with the vessels tied. The lungs were then inflated and rapidly frozen over liquid nitrogen. The lungs were sampled into slices by vertical height, each slice was further sampled and then gamma counted for the injected isotopes. Regional pulmonary blood flow was calculated by setting the total lung MAA counts for each MAA equal to the cardiac output so that the sample flow was calculated as the fraction of sample counts to total counts times the cardiac output. The blood volume was marked by the labelled RBC and RBC transit was calculated as blood volume (ml) divided by blood flow (ml/sec). In a second series of experiments (N=10) , ⁵¹Cr PMN were injected as a bolus along with ⁹⁹mtc RBC in an indicator-dilution run. Following the injection of the cells, the blood flow was marked with MAAs and then the same sham or smoke treatments were given as in the previous experiments. At the end of ten minutes, the animals were sacrificed and the lungs were processed the same as before. Regional PMN retention was calculated as the [formula omitted]. The data show that smoke exposure increased pulmonary blood volume (p<.01), pulmonary transit time (pMedicine, Faculty of
Pathology and Laboratory Medicine, Department of
Graduate

Political science and tobacco policy--Theories of policy change--The global policy context--European countries and the EU--The UK: a case study--The United States--Other advanced industrial countries--Tobacco control policymaking in developing regions--The WHO Framework Convention on Tobacco Control (FCTC)
https://dc.etsu.edu/etsu_books/1104/thumbnail.jpg

Orientador: Daniela Leal Zandim Barcelos
Resumo: O propósito deste estudo foi determinar a influência do tabagismo nos níveis de beta-defensina 3 (hBD 3) no fluido crevicular gengival (FCG) de indivíduos com periodontite crônica e avaliar sua relação com saúde e doença periodontal. Além disso, foi investigada a correlação deste peptídeo antimicrobiano com metaloproteinase da matriz (MMP-8) e citocinas pró (IL-10) e anti-inflamatórias (IL-1β, IFN-γ e TNF-α). Um total de 40 indivíduos com periodontite crônica, sendo 20 fumantes (PF) e 20 não fumantes (PNF), e 20 indivíduos sem doença periodontal (S) foram incluídos no estudo. Amostras de FCG de sítios sadios e doentes dos indivíduos com periodontite, e apenas de sítios sadios dos indivíduos periodontalmente saudáveis, foram coletadas com tiras de papel absorvente. A quantificação da hBD 3 foi feita pela técnica ELISA sanduíche e dos marcadores biológicos por ensaio Multiplex. Níveis significativamente menores de hBD 3 foram identificados nos sítios doentes de PF em comparação aos sítios doentes de PNF (p=0,02). Por outro lado, os níveis de hBD 3 nos sítios sadios de PF foram significativamente maiores que nos sítios sadios de PNF e S (p=0,006). Na comparação dos sítios dentro do grupo PF, foi verificado que os sítios doentes apresentavam níveis reduzidos de hBD 3 em comparação com sítios sadios (p=0,04). Já no grupo PNF, os níveis de hBD 3 foram mais elevados nos sítios doentes que nos sítios sadios (p=0,02). Uma correlação negativa foi observada entre os níveis de hBD 3 e MM... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: The purpose of this study was to determine the influence of smoking on gingival crevicular fluid (GCF) levels of beta-defensin 3 (hBD 3) in individuals with chronic periodontitis and to evaluate its relationship with health and periodontal disease. In addition, the correlation of this antimicrobial peptide with matrix metalloproteinase (MMP-8) and pro (IL-10) and anti-inflammatory cytokines (IL-1β, IFN-γ and TNF-α) was investigated. A total of 40 individuals with chronic periodontitis, including 20 smokers (PS) and 20 non-smokers (PNS), and 20 subjects without periodontal disease (H) were included in the study. GCF samples from healthy and diseased sites of individuals with periodontitis, and only from healthy sites of periodontally healthy individuals, were collected with absorbent paper strips. Quantification of hBD 3 was performed by a sandwich ELISA assay and the biological markers levels were analyzed by a multiplex assay. Significantly lower levels of hBD 3 were identified in diseased sites of PS compared to diseased sites of PNS (p = 0.02). On the other hand, the levels of hBD 3 in healthy sites of PS were significantly higher than in healthy sites of PNS and H (p = 0.006). The comparison between the sites within the groups with periodontitis showed reduced levels of hBD 3 in diseased sites of PS compared to healthy sites (p = 0.04), while higher levels of this peptide was detected in diseased sites of PNS compared to healthy sites (p = 0.02). A negative correlation wa... (Complete abstract click electronic access below)
Mestre

BACKGROUND: Of the 22 known measures of nicotine dependence (ND), none capture the overall disease severity of physical dependence alone. Instead, they capture constructs related to dependence, such as perceived risk, psychological addiction, smoker motivations, or smoking related behaviors, but none of the measures include only physical withdrawal symptoms to capture physical dependence on nicotine. AIM: To develop a range of nicotine dependence measures that capture physical dependence on nicotine. METHODS: The final measures were developed in a cross-sectional study conducted in three phases: 1) candidate item development through literature review and cognitive interviews, 2) developing and pre-testing the survey, and 3) survey administration and psychometric evaluation to validate three distinct measures. The final survey was conducted at four health clinics and three high schools. Psychometric tests used to select the final measure items included inter-item correlations, sensitivity analyses done by subgroup, item-total correlations, convergent validity tests, and confirmatory factor analysis. The final measures were evaluated using confirmatory factor analysis (CFA), internal reliability, total score distributions, and convergent validity correlations. Relative validity analyses were also conducted using a ratio of F-Statistics to compare the ability of each new measure to differentiate dependent smokers as compared previous measures. RESULTS: The final sample included 275 smokers ranging from 14 to 76 years old (mean=30.9, SD=16.2), who smoked an average of 11.5 cigarettes per day (range=0-50, SD=9.4). The sample was 86.5% white and 57.5% male. The three new measures developed included: 1) the 4-item Withdrawal-Induced Craving Scale (WICS) used to capture severity of craving, the most common physical withdrawal symptom; 2) the 12- item Nicotine Withdrawal Symptom Checklist (NWSC), which measures both overall disease severity and the severity of a comprehensive list of individual physical withdrawal symptoms including withdrawal-induced craving, anger, anxiety, depression, headache, insomnia, loss of focus, restlessness, and stress; and 3) the 6-item brief NWSC (NWSC-b), a short measure which only captures overall disease severity. All of the new measures exhibited a unidimensional factor structure loading highly on a single factor (thought to be physical dependence). They also correlated highly (over 0.6) and significantly (p<0.001) to a battery of convergent validity indices including four widely used nicotine dependence measures: Hooked on Nicotine Checklist (HONC), the Autonomy Over Tobacco Scale (AUTOS), the Fagerström Test for Nicotine Dependence (FTND), and self-rated addiction. CONCLUSION: The WICS, NWSC, and NWSC-b provide three distinct validated tools that can be used by researchers, clinicians, and educators to track the progression of physical dependence on nicotine across a range of smoking behaviors and histories.

Nicotine dependence is hypothesized to be due to neuroadaptations that ultimately drive compulsive nicotine use. The studies in this thesis aim to understand how the “upregulation” of nicotinic acetylcholine receptors (nAChRs) caused by chronic exposure to nicotine contributes to nicotine reward and nicotine withdrawal. Previous studies have shown that chronic nicotine induces upregulation of nAChRs containing the α4 subunit (α4* nAChR) within the Ventral Tegmental Area (VTA), a brain region critical for the rewarding properties of all illicit drugs. Curiously, α4* nAChR upregulation occurs specifically in the inhibitory GABAergic neuronal subpopulation of the VTA. To determine if increased expression and activation of α4* nAChRs in VTA GABAergic neurons contributes to nicotine dependence behaviors, I devised a viral-mediated, Creregulated gene expression system that selectively expressed α4 nAChR subunits containing a “gain-of-function” point mutation (a leucine mutated to a serine residue at the TM2 9´ position: Leu9´Ser) in VTA GABAergic neurons of adult mice. Sub-reward doses of nicotine were sufficient to activate VTA GABAergic neurons in mice expressing Leu9´Ser α4 nAChR subunits in VTA GABAergic neurons (Gad2VTA: Leu9´Ser mice) and exhibited acute hypolocomotion upon initial injection of low doses of nicotine that developed tolerance with subsequent nicotine exposures compared to control animals. In the conditioned place preference procedure, nicotine was sufficient to condition a significant place preference in Gad2VTA: Leu9´Ser mice at low nicotine doses that failed to condition control animals. I conclude from these data that upregulating α4* nAChRs on VTA GABAergic neurons increases sensitivity to nicotine reward. In a separate study testing the hypothesis that overexpression of Leu9´Ser α4* nAChRs in VTA GABAergic neurons disrupts baseline behavior and promotes anxiety-like behaviors, I found that overexpressing Leu9´Ser α4* nAChRs in VTA GABAergic neurons had a minimal effect on unconditioned anxiety-like behaviors. Drug naïve Gad2VTA: Leu9´Ser and control mice failed to exhibit any behavioral differences in the open-field, marble burying test and elevated plus maze compared to control. Together, these data indicate that overexpression of the “gain-of-function” α4* nAChRs in VTA GABAergic neurons contributes to reward sensitivity without increasing susceptibility to nicotine withdrawal symptoms. My data indicates that nAChRs expressed in VTA GABAergic neurons may be a suitable target for the development of better smoking cessation aids.

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Tobacco is one of the leading causes of premature death in the world and its dependence is maintained by nicotine and determined by biological, behavioral, psychological and sociocultural processes. Intensified consumption makes abstinence symptoms more probable to appear. The social factors that contributed to the experimentation become less motivating and the dependence happens to be controlled by the avoidance of the symptoms of the abstinence. The continued use of the cigarette causes changes in brain physiology that makes its cessation process something continuous and complex. Some triggers identified as abstinence-hindering refer to deficits in social skills. The term HS is used to designate learned behavioral capacities that involves social interactions. The present study was conducted from February to March 2017 and evaluated and correlated degree of nicotine dependence and social skills in sixty smokers patients hospitalized by vascular surgery team at a general hospital in the interior of the State of São Paulo, with the purpose of suggesting a therapeutic group where the deficits in social skills found in this study will be able to be work on. A descriptive type of search was performed. Participants were approached and invited to participate in the research whose data were analyzed quantitatively. Of the 60 participants, 23 were women and 37 were men, mean age was 62.85 years, with 52.51 years using cigarette. Only 18.33% tried to stop smoking and the beginning of use for them were at 10.33 years. Only 21.66% of the dependents did not have a smoker's family member, and 5% reported that their support group were non-smoker. According to the Fagerström test for nicotine, the majority of the evaluated patients have low and medium degree of dependence (adding up the two values). For social skills, the total scores for both genders correlate with the Fagerström test, which shows that the more dependent the more socially skilled, which may mean that the tobacco user feels socially skillful without being, if it is so, largely from a social skills training as part of the smoking cessation treatment.
O tabaco é uma das principais causas de morte prematura no mundo e sua dependência é mantida pela nicotina e determinada por processos biológicos, comportamentais, psicológicos e socioculturais. O consumo intensificado torna possível o surgimento dos sintomas de abstinência. Os fatores sociais que contribuíram para a experimentação passam a ser menos motivadores e a dependência passa a ser controlada pela evitação dos sintomas da abstinência. O uso contínuo do cigarro causa alterações na fisiologia cerebral que farão o processo de cessação do mesmo ser contínuo e complexo. Alguns gatilhos identificados como dificultadores da abstinência referem-se a déficits em habilidades sociais. O termo HS é utilizado para designar capacidades comportamentais aprendidas que envolvem interações sociais. O presente trabalho foi realizado de fevereiro à março de 2017 e avaliou e correlacionou grau de dependência de nicotina e habilidades sociais em sessenta pacientes tabagistas internados pela equipe de cirurgia vascular em um hospital geral do interior do Estado de São Paulo com o intuito de sugerir um grupo terapêutico para que os déficits em habilidades sociais encontrados sejam trabalhados posteriormente. Foi realizada uma pesquisa do tipo descritiva. Os participantes foram abordados e convidados a participar da pesquisa cujos dados obtidos foram analisados quantitativamente. Dos 60 participantes, 23 eram mulheres e 37 eram homens, de idade média de 62,85 anos, com 52,51 anos de uso de cigarro. Apenas 18,33% tentaram parar de fumar e o início do uso foi aos 10,33 anos. Apenas 21,66% dos dependentes não possuíam nenhum familiar também tabagista e 5% referiu que o grupo de apoio não era fumante. Segundo o teste Fagerström para Nicotina a maioria dos avaliados encontra-se com grau de dependência baixa e média (somando-se os dois valores). Quanto as habilidades sociais os escores totais para ambos os gêneros correlacionam -se com o teste de Fagerström, o que mostra que quanto mais dependente mais habilidoso socialmente, o que pode significar que o usuário do tabaco se sinta habilidoso socialmente sem o ser, beneficiando-se assim, largamente de um treino de habilidades sociais como parte do tratamento de cessação do tabagismo.

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Os carcinógenos do tabaco estão relacionados a diversos tipos de câncer incluindo o carcinoma de células escamosas (CCE) bucal. Aliado ao álcool, o tabaco contribui para o desfecho desfavorável destes casos. A susceptibilidade individual ao câncer pode estar relacionada a expressão das enzimas que metabolizam tais carcinógenos. O objetivo deste trabalho é avaliar a expressão dos genes CYP1A1, CYP1B1, CYP2A6 e CYP2E1 no CCE bucal por meio de qPCR. Foram coletadas amostras de 32 indivíduos com CCE e de 15 controles submetidos a cirurgias bucais por lesões benignas. Foram constituídos quatro grupos: Grupo CCE fumante (n=26), Grupo CCE não fumante (n=6), Grupo controle fumante (n=9) e Grupo controle não fumante (n=6). O Teste de Fagerström para Dependência a Cigarros (TFDC) foi usado para avaliar a dependência nicotínica (DN) e AUDIT para avaliação do consumo de etílicos. Houve diminuição da expressão do gene CYP1B1 nos casos de CCE comparados aos controles. Foram encontradas diferenças estaticamente significativas de expressão gênica de CYP1B1 entre os Grupos CCE fumante e controle fumante (p=0,0018), Grupo CCE não fumante e controle não fumante (p=0,0079) e CCE fumante com CCE não fumante (p=0,0385) e entre os quatro grupos (p<0,0001). Houve diminuição da expressão do CYP2A6 no Grupo CCE fumante em relação ao Grupo controle, mas apenas um paciente do Grupo controle expressou este gene. Houve aumento da expressão de CYP2E1 entre os Grupos CCE fumante e controle fumante (p=0,0424). Concluindo, foi encontrada grande variabilidade interindividual no estudo da expressão dos genes estudados. Houve maior expressão de CYP1A1 e CYP2E1 em amostras de indivíduos fumantes com CCE. Os genes CYP1B1 e CYP2A6 estavam menos expressos no Grupo CCE fumante em relação ao Grupo controle. Para os genes CYP1B1 e CYP2E1 foram encontrados valores significativos na correlação entre a expressão gênica e parâmetros demográficos e de perfil tabágico no Grupo controle fumante, e do AUDIT no Grupo CCE não fumante. O gene CYP2E1, além de estar relacionado ao metabolismo do álcool, também deve ser considerado importante marcador do metabolismo dos carcinógenos derivados do tabaco.
Tobacco carcinogens are related to various types of cancer, including oral squamous cell carcinoma (OSCC). Allied to alcohol, tobacco contributes to the unfavorable outcome of the cases. Individual cancer susceptibility may be related to an expression of the enzymes that metabolize such carcinogens. The aim of this work is to evaluate the expression of the genes CYP1A1, CYP1B1, CYP2A6 and CYP2E1 on OSCC by qPCR. Samples were collected from 32 individuals with OSCC and 15 controls submitted to oral surgeries due to benign lesions. There were four groups: Smoker SCC group (n = 26), nonsmoker SCC group (n = 6), Smoker control group (n = 9) and nonsmoker control group (n = 6). The Fagerström Test for Cigarette Dependence (TFCD) was used to evaluate nicotinic dependence (ND) and AUDIT for the evaluation of alcohol consumption. There was a decrease in CYP1B1 gene expression in cases of SCC compared to controls. (P = 0.0018); smoker CCE and non-smoker control (p = 0.0079); smoker SCC with nonsmoker SCC (p = 0.0385) and between the four groups (p <0.0001). There was a decreased expression in CYP2A6 in the smoker SCC Group compared to the control group, but only one control group patient expressed this gene. There was an increased expression of CYP2E1 between the smoking and nonsmoking SCC groups (p = 0.0424). In conclusion, large interindividual variability was found in the study of the expression of the genes studied. There was greater expression of CYP1A1 and CYP2E1 in samples from smokers with SCC. The CYP1B1 and CYP2A6 genes were less expressed in the smoker SCC Group. Significant values were found for the CYP1B1 and CYP2E1 genes in the correlation between a gene expression and a parameter and a non-smoker control group, non-smoker control group and AUDIT. The CYP2E1 gene, besides being related to alcohol metabolism, should also be considered an important marker of the metabolism of the carcinogens derived from tobacco.
2016/08633-0

Lung cancer is the leading cause of cancer-related mortality worldwide. The main risk factor associated with lung cancer is cigarette smoking. Research through the years suggests that nicotine in cigarettes promotes lung cancer by activating signaling pathways that lead to cell proliferation, cell survival, angiogenesis, and metastasis. Nicotine’s cellular actions are mediated by its cognate receptors, nicotinic acetylcholine receptors (nAChRs). Here, I describe the expression levels of all known human nAChR subunit genes in both normal and lung cancer cells. Of note, the genes encoding the α5, α3, and β4 subunits (CHRNA5/A3/B4) are over-expressed in small cell lung carcinoma (SCLC), the most aggressive form of lung cancer. This over-expression is regulated by ASCL1, a transcription factor important in normal lung development and lung carcinogenesis. The CHRNA5/A3/B4 locus has recently been the focus of a series of genetic studies showing that polymorphisms in this region confer risk for both nicotine dependence and lung cancer. I show that CHRNA5/A3/B4 depletion results in decreased SCLC cell viability. Furthermore, while nicotine promotes SCLC cell viability and tumor growth, blockade of α3β4 nAChRs inhibits SCLC cell viability. These results suggest that increased expression and function of nAChRs, specifically the α3β4α5 subtype, potentiate the effects of nicotine in SCLC. This dual hit from the carcinogens in tobacco and the cancer-promoting effects of nicotine, may provide a possible mechanism for the increased aggressiveness of SCLC. In addition, nAChRs can be activated by the endogenous ligand, acetylcholine, which acts as an autocrine/paracrine growth factor in SCLC. Increased function of α3β4α5 nAChRs in SCLC could also potentiate acetylcholine’s mitogenic effects. This mechanism, combined with other known autocrine/paracrine growth loops in SCLC, may help explain the ineffectiveness of available therapies against SCLC. In an effort to add to the current arsenal against SCLC, I screened a 1280-compund library using a bioluminescence-based viability assay I developed for high-throughput applications. Primary screening, followed by secondary and tertiary verification, indicate that pharmacologically active compounds targeting neuroendocrine markers inhibit SCLC cell viability.

INTRODUÇÃO: O aneurisma da aorta abdominal (AAA) tem grande importância clínica em função de sua incidência e das complicações que pode acarretar, entretanto sua etiopatogenia não está completamente esclarecida. A associação entre tabagismo e desenvolvimento de AAA tem sido repetidamente confirmada. Apesar de o AAA ter sido inicialmente atribuído à aterosclerose, observou-se associação negativa entre diabetes (um dos principais fatores de risco para aterosclerose) e doença vascular aneurismática. O estudo biomecânico e histológico da parede aórtica pode contribuir para a elucidação da etiopatogenia dos aneurismas. OBJETIVOS: Avaliar as propriedades biomecânicas e histológicas da aorta abdominal de ratos em três situações: exposição à fumaça do cigarro, induzidos ao desenvolvimento do diabetes mellitus e com a associação desses dois fatores. MÉTODOS: Setenta e cinco ratos Wistar foram distribuídos em quatro grupos: controle (GC), tabagista (GT), diabético (GD), diabético e tabagista (GDT). Os ratos dos GT e GDT foram expostos à fumaça de cigarro por 30 minutos ao dia, 5 dias por semana. O diabetes foi induzido por injeção endovenosa de estreptozotocina. Após 16 semanas, os animais foram sacrificados para a coleta da aorta abdominal. Testes de tração uniaxiais destrutivos foram realizados para a obtenção das seguintes propriedades biomecânicas: força, tensão, estresse, deformação e energia de deformação. A análise histológica desses fragmentos consistiu na avaliação das fibras colágenas e elásticas e verificação da deposição de elementos da matriz extracelular na túnica média e avaliação da sua composição. Através da zimografia foi quantificada a atividade da metaloproteinase-2 nos espécimes aórticos obtidos. RESULTADOS: Foram analisados os testes biomecânicos válidos de 52 espécimes, sendo que 11 pertenciam ao GC, 10 ao GD, 16 ao GT e 15 ao GTD. A análise biomecânica dos fragmentos não revelou diferença entre os grupos controle, GD, GT e GDT. A deposição de colágeno também não apresentou diferença estatística significativa entre os grupos estudados. A contagem total de lâminas elásticas foi maior nos ratos diabéticos (GD e GDT) quando comparados aos do GT. Foi observada resposta inflamatória mais intensa, com significância estatística, em todos os grupos estudados quando comparados ao GC. A atividade da MMP-2 apresentou diminuição no GD em relação ao GDT, com significância estatística. CONCLUSÕES: As propriedades biomecânicas da parede da aorta de ratos relacionadas à resistência e elasticidade não apresenta diferença entre o GC e os GD, GT e GDT. As alterações histológicas relacionadas à contagem total e fragmentação das lâminas elásticas, deposição de matriz pericelular e perda/substituição celular na túnica média são significativas na parede da aorta do GD, GT e GDT em relação ao GC. A atividade da MMP-2 na aorta do GD é menor que na aorta do GDT
INTRODUCTION: Abdominal aortic aneurysm (AAA) is of great clinical importance due to its incidence and complications, but its etiopathogenesis is not fully understood. The association between smoking and AAA development has been repeatedly confirmed. Although AAA was initially attributed to atherosclerosis, there was a negative association between diabetes (a major risk factor for atherosclerosis) and aneurysmal vascular disease. The biomechanical and histological study of the aortic wall may contribute to the elucidation of the etiopathogeny of the aneurysms. OBJECTIVES: To evaluate the biomechanical and histological properties of the abdominal aorta of rats in three situations: exposed to cigarette smoke, induced to the development of diabetes mellitus, and the association of these two factors. METHODS: Seventy-Five Wistar rats were divided into four groups: control (CG), smoker (GT), diabetic (GD), diabetic and smoker (GDT. The GT and GDT rats were exposed to cigarette smoke for 30 minutes a day, 5 days a week. Diabetes was induced by intravenous injection of streptozotocin. After sixteen weeks, the animals were sacrificed for collection of the abdominal aorta. Uniaxial destructive tensile tests were performed to obtain the following biomechanical properties: maximal force, failure stress, failure tension, failure strain and failure strain energy. The histological analysis of these fragments consisted in the evaluation of the collagen and elastin and verification of the deposition of elements of the extracellular matrix in the tunica media and evaluation of its composition. The activity of metalloproteinase-2 in the aortic specimens obtained was quantified by zymography. RESULTS: A total of 52 strips were studied (11 from GC, 10 from GD, 16 from GT and 15 from GDT. The biomechanical analysis of the fragments was not different between the control group and the GD, GT and GDT groups. Collagen deposition also did not present a statistically significant difference between the studied groups. The total of elastic fibers was higher in diabetic rats (GD and GDT) when compared to GT. A higher inflammatory response was observed, with statistical significance, in all groups studied when compared to CG. The activity of MMP-2 showed a decrease in GD in relation to GDT, with statistical significance. CONCLUSIONS: The biomechanical properties of the aortic wall of rats related to resistance and elasticity do not present a difference between GC and GD, GT and GDT. Histological changes related to total count and fragmentation of the elastic lamina, pericellular matrix deposition, and cell loss / substitution in the tunica media are significant in the aorta wall of GD, GT and GDT in relation to GC. The activity of MMP-2 in the GD aorta is smaller than in the GDT aorta

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Intervenções para tabagismo mediadas por internet disponíveis em língua portuguesa não cobrem todos os conteúdos das diretrizes de tratamento do tabagismo. Não existem intervenções de código-aberto na internet, isto é, que divulgam todo o código-fonte para sua adaptação e replicação para outros contextos e populações. O objetivo do estudo foi descrever uma metologia de desenvolvimento e avaliar a intervenção para tabagismo mediada por internet de código-aberto - “Viva sem Tabaco”. O desenvolvimento aconteceu nas seguintes etapas:(1) desenvolvimento do protótipo, (2) realização de um grupo focal fumantes e correção do protótipo e (3) avaliação da cobertura, precisão e interatividade do conteúdo com base nos 12 componentes das diretrizes de tratamento para tabagismo, e (4) revisão do conteúdo. Com os resultados do grupo focal e na revisão teórica das diretrizes, o protótipo foi desenvolvido e corrigido. Após as correções, o protótipo foi avaliado pelos especialistas e corrigido. O conteúdo da intervenção foi avaliado por dois pesquisadores de forma independente, 9 dos 12 tópicos apresentaram cobertura considerada adequada e 3 com cobertura mínima. Quanto à precisão, 8 tópicos foram avaliados como corretos e 4 como maior parte correto. Dois dos 12 tópicos apresentaram interatividade. Após a avaliação, a intervenção foi corrigida. A versão final da intervenção desenvolvida apresentou convergência com as diretrizes de tratamento. Estudos devem ser conduzidos para avaliar a eficácia da intervenção.
Web-assisted tobacco interventions (WATI) in Portuguese do not cover the standard guidelines for smoking treament and lack content quality. Current web-assisted tobacco interventions are not open-source, which reduce the development speed in developing countries. The objective of this study was to describe a development methodology of a open-source WATI and evaluate its quality. The development comprised the following stages: (1) prototype development, (2) assessment of the prototype using focus groups, and (3) content coverage, accuracy and interactivity evaluation using as reference the guideline “Treating tobacco use and depedence - 2008 update”, and (4) final review. Based on the data from focus groups and content review, the initial prototype was redesigned. The content evaluation, performed independently by two specialists, showed that 9 of 12 components were well covered and 3 minimally covered. Eight of 12 components were classified as correct and 4 as mostly correct. Just two topics were considered interactive. Based on the evaluation, a final review was conducted in the intervention content. The developed intervention was compliant with tobacco treatment guidelines, providing an evidence based guide for smokers who seek help over the internet. Future studies should address the clinical efficacy of the developed intervention.

Research into the comorbidity (or co-occurrence) of mental disorders is a relatively recent phenomenon. Much of this research has been conducted in clinical samples, which are prone to a range of biases that mean that the patterns observed are not representative of the general population. Although population-level research has previously been carried out, this thesis provides the first examination of comorbidity in the Australian population. This thesis examined the comorbidity of substance use and mental disorders among Australian adults. The major empirical work involved an examination of the patterns of homotypic comorbidity (other substance use disorders) and heterotypic comorbidity (mood disorders, anxiety disorders, and psychosis) of alcohol, tobacco and cannabis in the 1997 Australian National Survey of Mental Health and Well-Being (NSMHWB). These drugs were chosen as they are the most commonly used psychoactive substances in the Australian population. The NSMHWB involved a structured diagnostic interview of mental disorders with a representative sample of Australian adults. Three questions were addressed using this data: (1) What patterns of comorbidity exist between tobacco, alcohol and cannabis use, and other substance use and mental disorders?; (2) Are these patterns of comorbidity explained by common factors?; and (3) Does comorbidity affect the likelihood that mental health treatment has been sought? Similar patterns of homotypic comorbidity were observed for all three substances, and they were not explained by the other factors examined (gender, age, education, relationship status, employment and neuroticism). Cannabis dependence was the most strongly associated with other substance use disorders. Heterotypic comorbidity differed between alcohol, tobacco and cannabis use. Tobacco use predicted increased rates of all three groups of mental disorders (mood, anxiety and psychotic disorders). In the case of alcohol, only alcohol dependence was related to increased rates of all groups of mental disorders; alcohol use and abuse were not associated with heterotypic comorbidity. Any level of cannabis involvement was related to a similarly increased risk of mood and anxiety disorders. Cannabis use was linearly related to the risk of screening positively for psychosis. Common factors did not change the patterns of heterotypic comorbidity of tobacco and alcohol use. However, alcohol, tobacco and other drug use appeared to explain the higher rates of mood and anxiety disorders among cannabis users. Treatment seeking was much more likely among alcohol, tobacco and cannabis users when they had comorbid mental disorders. It was moderately increased when they had comorbid substance use disorders. The second piece of empirical work provided a more detailed examination of comorbid substance use problems among persons with psychosis. This topic was selected due to the limited epidemiological research on this issue, and the relatively large burden of disability that psychosis places upon the individual and the community. NSMHWB data were used to examine the prevalence of comorbid substance use disorders among persons who were likely to have met criteria for psychosis (as assessed by a screener used in the NSMHWB). Multiple regression analyses were used to test possible explanations for the higher rates of substance use disorders observed among persons reporting higher numbers of psychotic symptoms. The odds of alcohol dependence and regular tobacco use increased 1.5 times, and the odds of cannabis dependence increased twice, with each additional psychotic symptom reported, after adjusting for other substance use disorders, other mental disorders and demographic characteristics. Given the debate about the reasons for the association between cannabis use and psychosis, the final study used mathematical modelling to test four hypotheses about relationships between cannabis use and psychosis. Specifically, it examined trends in psychosis that would be predicted given the marked increases in the prevalence of cannabis use that have occurred in Australia over the past thirty years. The results suggested that a causal relationship - in which cannabis use caused psychosis among persons who would not otherwise have developed the disorder - is unlikely to explain the association. There was a better fit to the data provided by the other hypotheses examined, namely, that (a) cannabis use precipitates psychosis among vulnerable individuals; (b) cannabis use increases the risk of relapse among persons with psychosis; and (c) persons with psychosis are more likely to become regular cannabis users (without any effect upon the disorder). This thesis has demonstrated that in Australian adults there is significant comorbidity between alcohol, tobacco and cannabis use and other substance use and mental disorders. These patterns differ across the three substances. Some types of heterotypic comorbidity (e.g. between cannabis use and mood/anxiety disorders) are explained by common factors. The limited range of common factors tested here did not explain homotypic comorbidity. This thesis also suggested that mathematical modelling is a useful approach to consider when examining the plausibility of different relationships between risk factors and mental disorders. A number of hypotheses regarding comorbidity could not be tested using NSMHWB data, such as common genetic and other environmental factors. These can best be tested in research with samples of twins, and using longitudinal designs that assess a wide range of social and environmental factors. The findings of this thesis also have implications for treatment, because persons with comorbid disorders are more likely to seek treatment. There is an absence of validated treatments for persons with comorbid substance use and mental disorders, and more research is needed on this issue.

Les maladies mentales représentent un ensemble catégoriel très hétérogène, même au sein d’une entité nosographique. L’approche multifactorielle rend compte de l’hétérogénéité clinique des troubles mentaux et du continuum entre certaines dimensions cliniques, voire entre le normal et le pathologique. Parmi ces dimensions, le phénotype psychotique constitue une dimension essentielle du trouble schizophrénique. L’approche dimensionnelle permet d’envisager la recherche d’expériences psychotiques dans la plupart des troubles mentaux ainsi qu’en population générale. Nous faisons l’hypothèse générale que certains troubles psychiatriques avec symptômes psychotiques pourraient être la résultante de l’interaction entre certains facteurs environnementaux précoces (traumatismes obstétricaux par exemple) et tardifs (consommation de toxiques, traumatismes) et le neurodéveloppement de l’individu. Un travail initial a été de rappeler les concepts de vulnérabilité en psychiatrie, et de prendre l’exemple du trouble schizophrénique pour réaliser une revue de la littérature sur les facteurs de risque en fonction de leur interaction précoce ou tardive avec le neurodéveloppement. Ensuite, dans le premier axe de recherche de la thèse, nous évaluons certains marqueurs neurodéveloppementaux précoces (signes neurologiques mineurs, latéralité, cognition). Notre premier travail, concerne la caractérisation clinique, neurologique et cognitive de 64 patients souffrant de trouble schizophrénique, en fonction de leur consommation de cannabis ou pas avant le début des troubles. Il apporte des éléments en faveur d’une charge neurodéveloppementale moins lourde chez les patients ayant consommé du cannabis, et de l’impact potentiel de cette substance chez des sujets vulnérables. Notre second travail, préliminaire, concerne l’impact clinique et cognitif de la latéralité chez les patients souffrant de schizophrénie (n=667) et de trouble bipolaire (n=2445). Nous apportons des arguments pour un poids neurodéveloppemental (mesuré avec cet indice) plus important dans la schizophrénie. Notre deuxième axe de recherche se concentre sur le tabagisme comme facteur environnemental tardif dans le trouble schizophrénique et le phénotype psychotique. Nous montrons dans deux travaux sur la cohorte FACE-SZ (n=361 ; n=474), que ces patients consomment presque deux fois plus qu’en population générale et qu’ils pourraient représenter un sous-groupe présentant des caractéristiques spécifiques d’un point de vue socio-démographique, clinique et thérapeutique. Dans un troisième travail préliminaire, nous comparons les fonctions cognitives de ces patients (n=785) et montrons que l’hypothèse d’automédication ne peut pas rendre compte à elle seule, de la forte prévalence du tabagisme chez ces patients. Dans un quatrième travail, nous étudions l’impact du tabagisme sur le phénotype psychotique dans une approche dimensionnelle, et montrons une association entre le tabagisme et certaines expériences de type psychotique dans un échantillon représentatif de la population générale américaine (NESARC, n=34653). Enfin dans un dernier axe de recherche nous nous intéressons au phénotype psychotique dans une population d’adolescents et jeunes adultes hospitalisés pour un premier épisode psychiatrique (n=50). Dans une étude préliminaire, nous montrons une forte prévalence des expériences de type psychotique chez ces jeunes adultes, quel que soit le diagnostic posé six mois à postériori, soulignant le caractère trans-nosographique du phénotype psychotique lors de l’émergence des troubles. L’ensemble de ce travail reflète l’hétérogénéité clinique des maladies mentales et l’importance de l’approche dimensionnelle et trajectorielle pour identifier des facteurs de risque (ou de protection). Les enjeux sont une meilleure compréhension étiopathogénique, des perspectives de prévention, et une prise en charge personnalisée des patients
Mental diseases represent a very heterogeneous categorical group, even within a given nosographic entity. Multifactorial approaches allow accounting for the clinical heterogeneity of mental disorders, the continuum between certain clinical dimensions, and even between the normal and the pathological. Among such dimensions, the psychotic phenotype constitutes an essential dimension of schizophrenic disorder. The dimensional approach allows for the search of psychotic experiences in most mental disorders as well as in the general population. We make the general hypothesis that certain psychiatric disorders with psychotic symptoms could be the result of the interaction between early- (obstetric traumas for example) and late- environmental factors (toxics, traumatisms) and the neurodevelopment of the individual. The initial step in this thesis work was to better define the concepts of vulnerability in psychiatry, and, based on the example of schizophrenia, to conduct a review of the literature on risk factors according to their early or late interaction with neurodevelopment. Subsequently, the first axis of research of the present thesis was to evaluate early neurodevelopmental markers (neurological soft signs, laterality, cognition). Our first work concerned the clinical, neurological and cognitive characterization of 64 patients suffering from schizophrenia, according to their cannabis use (or not) prior to psychosis. It provided evidence for a lower burden of neurodevelopment in cannabis users, and the potential impact of this substance on vulnerable individuals. Our second work concerns the clinical and cognitive impact of lateralization in patients with schizophrenia (n = 667) and bipolar disorder (n = 2445). We bring arguments for a neurodevelopmental weight (measured with this lateralization index) that is more important in schizophrenia. Our second axis of research focused on tobacco smoking as a late environmental factor in schizophrenia and psychotic phenotype. We showed in two studies on the FACE-SZ cohort (n = 361, n = 474) that SZ patients consumed almost twice as much as the general population and that they could represent a SZ subgroup with specific socio-demographic and clinical characteristics. In a third study, we compare the cognitive functions of these patients (n = 785) and show that the self-medication hypothesis alone cannot account for the high prevalence of their smoking. In a fourth work, we studied the impact of smoking on the psychotic phenotype with a dimensional approach, and showed an association between smoking and certain psychotic-type experiences in a representative sample of the US general population (NESARC, n = 34653). Finally, in a last line of research, we evaluated the psychotic phenotype in a population of adolescents and young adults hospitalized for a first psychiatric episode (n = 50). In a preliminary study, we show a high prevalence of psychotic-like experiences in these young adults, regardless of the diagnosis made six months afterwards, highlighting the trans-nosographic character of the psychotic phenotype during the emergence of different mental disorders. Overall, the present thesis underscores the clinical heterogeneity of mental illnesses and the importance of dimensional and trajectory approaches in identifying risk (or protective) factors, towards a better etiopathogenic understanding, better prevention opportunities, and a personalized patient care

Fifteen nonsmoking and fifteen smoking females 19 to 36 years of age were evaluated on measures of signal-to-noise ratio (SNR), jitter, shimmer, and speaking fundamental frequency (F0). The results indicated that: 1) there is a significant difference between female smokers and nonsmokers on measures of SNR, mean, and maximum F0 and, 2) there is no significant difference between female smokers and nonsmokers on measures of jitter, shimmer and minimum F0 . The SNR was found to be a powerful tool which is capable of distinguishing subtle vocal characteristics between the subject groups. It would appear that cigarette smoking may have an impact on the voice before distinct laryngeal pathologies are present.

Introdução: A identificação de variantes genéticas que predispõem a maior susceptibilidade à dependência à nicotina pode ser importante para a prevenção e o tratamento do tabagismo. No contexto de medicina personalizada, os principais objetivos do presente estudo foram avaliar se polimorfismos nos genes CHRNA2, CHRNA3, CHRNA5 e CHRNB3 estão associados com o nível de dependência em indivíduos fumantes e com o resultado do tratamento antitabágico. Métodos: Estudo de coorte com 1049 pacientes fumantes que receberam tratamento farmacológico (vareniclina, vareniclina e bupropiona, bupropiona e/ou terapia de reposição nicotínica). O sucesso na cessação tabágica foi considerado para os pacientes que completaram 6 meses de abstinência contínua. O teste de Fagerström para a dependência à nicotina (FTND) e o escore de consumo situacional Issa foram utilizados para avaliar a dependência à nicotina. A escala de conforto PAF foi utilizada para avaliar o conforto do paciente durante o tratamento. Os polimorfismos CHRNA2 rs2472553, CHRNA3 rs1051730, CHRNA5 rs16969968, CHRNA5 rs2036527 e CHRNB3 rs6474413 foram genotipados pela análise da curva de melting. Resultados: As mulheres portadoras dos genótipos GA e AA para os polimorfismos CHRNA5 rs16969968 e rs2036527 obtiveram maior taxa de sucesso no tratamento antitabagismo: 44,0% e 56,3% (rs16969968), 41,5% e 56,5% (rs2036527), respectivamente; em comparação com as mulheres portadoras do genótipo GG: 35,7% (rs16969968) e 34,8% (rs2036527), (P=0,03; n=389; P=0,01; n=391). Os genótipos GA ou AA para os rs16969968 e rs2036527 foram associados com maior OR para o sucesso em mulheres (OR=1,63; IC 95%=1,04-2,54; P=0,03 e OR=1,59; IC 95%=1,02-2,48; P=0,04; respectivamente), em um modelo multivariado. Não foi encontrada associação dos polimorfismos no gene CHRNA5 com o escore de FTND. Para os polimorfismos CHRNA2 rs2472553, CHRNA3 rs1051730 e CHRNB3 rs6474413 não foram encontradas associações significativas com os fenótipos estudados. Conclusão: Os polimorfismos rs16969968 e rs2036527 no gene CHRNA5 foram associados com maior taxa de sucesso no tratamento antitabagismo em mulheres. Estes resultados podem contribuir com avanços na terapêutica baseada em medicina personalizada
Background: The identification of genetic variants that predispose increased susceptibility to nicotine dependence becomes increasingly important for the prevention and smoking treatment. In the context of personalized medicine, the main aims of this study were to evaluate whether the CHRNA2, CHRNA3, CHRNA5 and CHRNB3 polymorphisms are associated with the level of dependence in smokers and the result of smoking treatment. Methods: This cohort study enrolled 1049 smoking patients who received pharmacological treatment (varenicline, varenicline plus bupropion, bupropion plus/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores were analyzed for nicotine dependence. PAF comfort scale was used to evaluate the comfort of the patient during treatment. The CHRNA2 rs2472553, CHRNA3 rs1051730, CHRNA5 rs16969968 and rs2036527 and CHRNB3 rs6474413 polymorphisms were genotyped by high resolution melting analysis. Results: Females with GA and AA genotypes for CHRNA5 rs16969968 and rs2036527polymorphisms had higher success rate in smoking cessation treatment: 44.0% and 56.3% (rs16969968), 41.5% and 56.5% (rs2036527), respectively; compared with carriers of the GG genotypes: 35.7% (rs16969968), 34.8% (rs2036527), (P=0.03, n=389; P=0.01, n=391). The GA or AA genotypes to the rs16969968 and rs2036527 were associated with higher odds ratio for success in women (OR=1.63; 95%CI=1.04 to 2.54; P=0.03 and OR=1.59, 95%CI=1.02 to 2.48; P=0.04; respectively), in a multivariate model. We found no association of these polymorphisms with FTND score for nicotine dependence. For the CHRNA2 rs2472553, CHRNA3 rs1051730 and CHRNB3 rs6474413 polymorphisms no significant associations were found with phenotypes studied. Conclusion: The CHRNA5 rs16969968 and rs2036527 were associated with higher success rate in the smoking cessation treatment in women. These results can contribute to major advances in personalized medicine based therapy

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A pesquisa objetivou analisar o consumo de bebida alcoólica e tabaco entre trabalhadores de enfermagem de uma Universidade Pública, suas consequências para saúde, perfil socioeconômico e demográfico desses trabalhadores; identificou o consumo e sintomas de dependência do álcool e da nicotina. Para tal realizou-se uma pesquisa exploratória transversal, compondo a população do estudo 129 trabalhadores, auxiliares (24%) e técnicos de enfermagem (51,2%) e enfermeiros (24,8%), da instituição compreendendo o hospital de ensino e o campus universitário. A análise dos dados foi realizada através de estatística descritiva e inferenciais das variáveis socioeconômicos e demográficos, níveis de dependência à nicotina padrão de consumo de álcool. Para análise do AUDIT (Alcohol Use Disorders Identification Test), teste utilizado para categorizar os padrões de consumo de álcool, apresentamos o nível de consumo de álcool em relação aos trabalhadores e em seus níveis profissionais (auxiliar de enfermagem, técnico de enfermagem e enfermeiro) para evidenciar possíveis diferenças. Procedendo da mesma com os resultados do teste de Fagerstrom, utilizado para classificar o nível de depêdencia à nicotina. A população do estudo foi composta em sua maioria por mulheres (74,4%), com idade média de 48 anos (sendo a mínima 24 e a máxima 64), casadas ou em união estável (69,8%) possui filhos (73,4%). O rendimento familiar entre 4 a 10 salários mínimos (73,2%) e pós graduada (58,3%). Relata apenas um vínculo empregatício (72,1%), trabalha em regime diarista ou plantonista (51,2%), com carga horária inferior a 40 horas (71,3%), trabalha em turno diurno (53,1%) faz plantões extras (75,2%). O consumo de álcool foi relatado por 58,6% dos trabalhadores de enfermagem, segundo o teste AUDIT o padrão de consumo de baixo risco prevaleceu (86,2%). O uso do tabaco foi apontado por 8,8% dos trabalhadores e a aplicação do Teste de Fagerstrom revelou nível de dependência a nicotina baixo (50% dos tabagistas). A associação entre o padrão de consumo de álcool e o tabagismo apresentou significância estatística (p=0,042) evidenciando que aqueles que revelaram padrão de consumo mais prejudicial também faziam ou fizeram uso de tabaco. Também foi verificado significância estatística entre padrão de consumo de álcool e sexo (p=0,004) apontando que os homens possuem um consumo de maior risco quando comparado ao das mulheres. As contribuições do estudo para enfermagem no âmbito da saúde do trabalhador foi permitir conhecer o perfil socioeconômico e demográfico dos trabalhadores de enfermagem dessa instituição. Bem como verificar os padrões de consumo de bebida alcoólica e tabaco. Colaborar para fomentar à literatura em relação aos trabalhadores de enfermagem. Possibilitar que esses trabalhadores possam conhecer a situação de saúde e com isso ganhar autonomia de buscar padrões mais saudáveis de vida e também instrumentalizar a equipe de ação de saúde do trabalhador no sentido de oferecer subsídios para uma abordagem mais efetiva e direcionada à sua população.
The research aimed to analyze the consumption of alcohol and tobacco among nursing workers of a public university, consequences for their health, socioeconomic and demographic profile of these workers; has identified consumption and symptoms of alcohol dependency and nicotine dependence. For this realized a transversal exploratory survey, the studied population 129 workers, nurses (24%) and practical nurse (51.2%) and nurses (24.8%) the institution involves the teaching hospital and the university campus. We consider eligible: the effective university research scenario, in exercise of the function. Ineligible: absent workers by reason of sick leave or qualification / training and shift to another institution. Data analysis was carried out by descriptive statistics and inferential of socioeconomic and demographic variables, dependency levels to nicotine standard of alcohol use. AUDIT analysis of the level of alcohol consumption compared to nursing professionals. ranked the classes of nursing: nurses, nursing technician and nursing assistant in order to view the possible levels of formations that make up the nursing differences. Proceeding in the same with the results of the Fagerstrom Test. The study population consisted mostly of women (74.4%) with mean age of 48 years (with a minimum 24 and maximum 64), married or in a stable relationship (69.8%) have children (73,4%). Household income 4 to 10 minimum wages (73.2%) and postgraduate (58.3%). Reports only employment (72.1%), working in diarist or duty physician regimen (51.2%), workload less than 40 hours per week (71.3%), working on day shift (53.1%) causes shifts extras (75.2%). Alcohol use was reported by 58.6% of nursing staff, the AUDIT (Alcohol Use Disorders Identification Test) test used to categorize patterns of alcohol use, has identified the standard of low-risk drinking prevailed (86.2%). Tobacco use was reported by 8.8% of workers and the implementation of the Fagerstrom test revealed the low nicotine dependence level (50% of smokers). The association between standard alcohol consumption and smoking was statistically significant (p = 0.042) evidencing that who have revealed most harmful consumption patterns also did or made use of tobacco. It also found statistical significance between pattern of drinking and sex (p = 0.004) indicating that men have a higher risk of consumption when compared to women. The contributions of the study for nursing within the workers' health was possible to know the socioeconomic and demographic profile of nursing workers of the institution. And to identify the patterns of consumption of alcoholic beverages and tobacco. Collaborate to promote the literature regarding the nursing workers. Enable these workers to know the health status and with that become autonomous to seek healthier living standards and also equip the worker's health action team in order to offer subsidies for a more effective and targeted approach to its population.

Chaque année en France plus de 140000 patients sont victimes d’un accident vasculaire cérébral(AVC). Parmi eux plus d’un tiers développent des troubles émotionnels de type dépression ou anxiété post-AVC (respectivement D-PAVC et A-PAVC). Ces complications contribuent à une altération du pronostic fonctionnel et de la qualité de vie. L’identification et la prise en charge précoce des déterminants des troubles émotionnels est donc un enjeu clinique majeur. En dehors de facteurs non modifiables, tels que les antécédents psychiatriques ou la sévérité de l’AVC,l’influence des modifications d’hygiène de vie recommandées en post-AVC est indéterminée.Dans ce contexte l’influence de la dépendance, telle que conceptualisée en addictologie, à des substances usuelles - dont le tabac et l’alcool - ou émergentes comme l’alimentation hyperpalatable et ultra-transformée n’a pas été explorée.Les objectifs de ce travail étaient d’une part de déterminer les caractéristiques de l’usage problématique de substances dans la population victime d’AVC en termes de prévalence et d’impact sur le statut émotionnel post AVC, et d’autre part d’explorer les mécanismes physiopathologiques sous-tendant l’efficacité des stratégies d’interruption de ces comportements addictifs.Pour répondre au premier objectif, trois cohortes prospectives (respectivement N=2300,66,8±15,1ans, 63% d’hommes, NIHSS à 3mois=1,26±2,60 ; N=74, 60,3±12 ans, 68,9%d’hommes, NIHSS à l’admission= 2,73±3,13 et N=101, 62,8±13,7 ans, 60,4% d’hommes,NIHSS à l’admission= 2,31±3,13) de patients pris en charge dans l’Unité Neuro-Vasculaire du CHU de Bordeaux et ayant bénéficié d’évaluation cliniques et neuropsychologiques ont été analysées. Dans le cadre du second objectif, nous avons mené une analyse systématique de la littérature sur les biomarqueurs anatomo-fonctionnels cérébraux identifiés par Imagerie par Résonance Magnétique comme prédicteurs de la réponse à un traitement d’arrêt du tabac(N=24 études ; Anatomie N=7, Activité cérébrale de repos N=9, Activité cérébrale post-tâche d’activation N= 14). Les résultats de nos travaux suggèrent qu’il y a 1) une proportion importante (30,3%) de patients victimes d’AVC présentant une consommation problématique de substances ; 2) un lien entre la sévérité du profil addictif au tabac et à l’alimentation et la symptomatologie anxieuse et/ou dépressive 3 mois après l’AVC et 3) le rôle clé de l’insula dans les réseaux neuronaux anatomofonctionnels impliqués dans la réponse à un traitement de sevrage au tabac.Ces différents travaux apportent un éclairage nouveau sur l’importance du dépistage et la prise en charge des comportements addictifs dans la prévention secondaire des AVC. L’identificationRésumé6précoce de troubles liés aux consommations de substances tels que définis dans les classifications des maladies mentales, mais aussi de l’addiction à l’alimentation, pourrait permettre d’améliorer le devenir émotionnel des patients et réduire le fardeau humain et sociétal des complications post-AVC. Par ailleurs l’identification de biomarqueurs d’imagerie pourrait constituer la première étape vers une médecine de précision permettant d’adapter les stratégies thérapeutiques à l’échelle individuelle
Every year in France 140000 patients had a stroke. Amongst them, a third develop emotionalimpairments such as post-stroke depression or anxiety (respectively PSD and PSA). These complications contribute to an alteration in the functional prognostic and quality of life of thesepatients. The early identification and management of these emotional impairments is thereforea major clinical issue. Outside of non-modifiable risk factors such as a history of psychiatricdisorders or the clinical stroke severity, the influence of the changes in health lifestyle that are recommended post-stroke is not known. In this context, the impact of problematic substanceuse, as conceptualized in addictology, of usual substances, such as tobacco and alcohol, or ofthe new and emerging hyper-palatable and highly processed (HP) foods, has yet not beenexplored.The objectives of this present work were to determine amongst the stroke population thecharacteristics of such problematic substance use in terms of prevalence and impact on poststrokeemotional impairments, on the one hand, and to explore the pathophysiological mechanisms supporting the response to substance use cessation treatment strategies.In order to answer the first objective, three prospective cohorts comprising of patients admittedto the Neuro-vascular Unit at the University Hospital of Bordeaux and who benefited fromclinical and neuropsychiatric evaluations were analyzed (1: N=2300, 66.8±15.1 years old, 63%males, NIHSS at 3 months=1.26±2.60; 2) N=74, 60.3±12 years old, 68.9% males, NIHSS at admission=2.73±3.13; 3) N=101, 62.8±13.7 years old, 60.4% males, NIHSS at admission= 2.31±3.13). In thecontext of our second objective, we conducted a systematic review of the current literature onthe cerebral biomarkers identified by Magnetic Resonance Imaging as predictors of smokingcessation treatment outcome (N=24 studies: N=7 anatomical, N=9 resting state, N=14activation).The results of our work suggest that 1) there is an important proportion (30,3%) of strokevictims presenting a problematic substance use; 2) a link exists between the addiction profileseverity to tobacco and HP foods and the anxious and/or depressive symptomatology at 3months post-stroke; and 3) highlight the key role of the insula in the neuronal anatomicalfunctionalcircuits implicated in smoking cessation treatment outcome.These different studies offer a new insight into the importance of the screening and managementof addictive behaviours in the secondary prevention of stroke. The early identification of disorders linked to substance abuse, as defined in the classification of mental illnesses but alsoto food addiction, could help to enhance the patients’ emotional well-being and therefore reduceAbstract9the socio-economical burden of post-stroke complications. Moreover, characterizing specificimaging biomarkers of the response to cessation treatment could constitute the first step towardsprecision medicine by prescribing specific therapeutic strategies tailored at an individual scale

Research Doctorate - Doctor of Philosophy (PhD)
Co-occurring substance use and mental disorders are a major health problem. Substance use disorders are very common among people with mental disorders, cost health care systems large amounts of money and have been consistently linked to a number of adverse consequences among this population. It is clear therefore that effective intervention and preventative strategies are needed to address these co-occurring disorders and it is suggested that a clear understanding of people’s attitudes and perceptions regarding substances is needed to develop such strategies. Very little research investigating the substance related attitudes and perceptions among people with mental disorders exists. The broad aim of this thesis was to generate a greater understanding of attitudes and perceptions regarding tobacco, alcohol and cannabis among people with mental disorders. To address this aim the thesis presents five papers. Paper 1 describes a systematic review of current literature investigating attitudes and perceptions towards tobacco, alcohol and cannabis among people with mental disorders. The review aimed to identify the strengths, weaknesses and gaps in this literature. Paper 2 and Paper 3 describe a study of attitudes and perceptions regarding tobacco, alcohol and cannabis among people with psychotic disorders. This study elicited both quantitative and qualitative data and aimed to identify any similarities and differences between participants’ reasons for tobacco, alcohol and cannabis use. It also aimed to generate some initial insights regarding the perceived effectiveness of anti-tobacco public health campaigns among people with mental disorders. Paper 4 describes a study which investigated reasons for tobacco, alcohol and cannabis use among people with depression or a psychotic disorder. It aimed to identify similarities and differences in reasons for substance use between people with different mental disorders. Paper 5 describes a qualitative study of attitudes and perceptions regarding tobacco, alcohol and cannabis among people with a psychotic disorder, current symptoms of depression or without a mental disorder. The study aimed to generate insights regarding a range of substance related attitudes and perceptions by employing a flexible interview schedule that allowed issues important to the participants to be raised. The concluding chapter of this thesis reviews and synthesizes the main findings of these five papers and discusses their implications for future research and the development of effective intervention and prevention strategies. The findings of this thesis suggest that attitudes and perceptions regarding tobacco, alcohol and cannabis differ considerably. While all three substances were found to be used to cope with stress and to relax, this reason was particularly important for tobacco use among people with and without mental disorders. Social factors were found to play an important role in the alcohol use of people with and without mental disorders, while cannabis was often used as a source of pleasure by people with and without mental disorders. The type of harm these substances were perceived to cause was also found to differ considerably. Very few differences between the attitudes and perceptions of people with and without mental disorders, regarding tobacco, alcohol and cannabis, were found. However, among people with mental disorders specifically, mental health and substance use were perceived to interact. Anti-substance use campaigns were perceived to be ineffective by people both with and without mental disorders. Attitudes and perceptions towards tobacco, alcohol and cannabis were also found to differ between people with a psychotic disorder and people experiencing depression. The findings of this research add considerably to our understanding of the attitudes and perceptions regarding tobacco, alcohol and cannabis use held among people with mental disorders. The findings also suggest that it may be important to tailor intervention and prevention strategies regarding tobacco, alcohol and cannabis by substance type and perhaps type of mental disorder.

No
Observational studies have shown that attentional bias for smoking-related cues is associated with increased craving and relapse. Laboratory experiments have shown that manipulating attentional bias may change craving. Interventions to reduce attentional bias could reduce relapse in smokers seeking to quit. We report a clinical trial of attentional retraining in treatment-seeking smokers. This was a double-blind randomised controlled trial that took place in UK smoking cessation clinics. Smokers interested in quitting were randomised to five weekly sessions of attentional retraining (N=60) or placebo training (N = 58) using a modified visual probe task from one week prior to quit day. Both groups received 21 mg nicotine patches (from quit day onwards) and behavioural support. Primary outcomes included change in attentional bias reaction times four weeks after quit day on the visual probe task and craving measured weekly using the Mood and Physical Symptoms Scale. Secondary outcomes were changes in withdrawal symptoms, time to first lapse and prolonged abstinence. No attentional bias towards smoking cues was found in the sample at baseline (mean difference = 3 ms, 95% CI = -2, 9). Post-training bias was not significantly lower in the retraining group compared with the placebo group (mean difference = -9 ms, 95% CI = -20, 2). There was no difference between groups in change in craving (p = 0.89) and prolonged abstinence at four weeks (risk ratio = 1.00, 95% CI = 0.70, 1.43). Taken with one other trial, there appears to be no effect from clinic-based attentional retraining using the visual probe task. Attentional retraining conducted out of clinic may prove more effective. CLINICAL TRIAL REGISTRATION: UK Clinical Trials ISRCTN 54375405.

Indiana University-Purdue University Indianapolis (IUPUI)
Drug addiction is a behavioral disorder characterized by impulsive behavior and continued intake of drug in the face of adverse consequences. Millions of people suffer the financial and social consequences of addiction, and yet many of the current therapies for addiction treatment have limited efficacy. Therefore, there is a critical need to characterize the neurobiological substrates of addiction in order to formulate better treatment options. In the first chapter, the striatal dopamine system is interrogated with [11C]raclopride PET to assess differences between chronic cannabis users and healthy controls. The results of this chapter indicate that chronic cannabis use is not associated with a reduction in striatal D2/D3 receptor availability, unlike many other drugs of abuse. Additionally, recent cannabis consumption in chronic users was negatively correlated with D2/D3 receptor availability. Chapter 2 describes a retrospective analysis in which striatal D2/D3 receptor availability is compared between three groups of alcohol-drinking and tobacco-smoking subjects: nontreatment-seeking alcoholic smokers, social-drinking smokers, and social-drinking non-smokers. Results showed that smokers had reduced D2/D3 receptor availability throughout the striatum, independent of drinking status. The results of the first two chapters suggest that some combustion product of marijuana and tobacco smoke may have an effect on striatal dopamine concentration. Furthermore, they serve to highlight the effectiveness of using baseline PET imaging to characterize dopamine dysfunction in addictions. The final chapter explores the use of [18F]fallypride PET in a proof-of-concept study to determine whether changes in cortical dopamine can be detected during a response inhibition task. We were able to detect several cortical regions of significant dopamine changes in response to the task, and the amount of change in three regions was significantly associated with task performance. Overall, the results of Chapter 3 validate the use of [18F]fallypride PET to detect cortical dopamine changes during a impulse control task. In summary, the results reported in the current document demonstrate the effectiveness of PET imaging as a tool for probing resting and activated dopamine systems in addiction. Future studies will expand on these results, and incorporate additional methods to further elucidate the neurobiology of addiction.