Dissertations / Theses on the topic 'Hepatitis C – Psychological aspects'

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Introdução: Adesão ao tratamento refere-se a um comportamento ativo do paciente em relação à doença e ao tratamento compartilhando as decisões com o profissional de saúde. Considera-se a adesão um fenômeno resultante da interação de fatores de diferentes naturezas que afetam diretamente o comportamento do paciente: fatores relacionados ao indivíduo; fatores sociais, econômicos; fatores relacionados ao serviço de saúde e aos profissionais de saúde e ainda os fatores relacionados à doença e ao tratamento. Objetivo: Este estudo propõe-se a realizar uma revisão integrativa da literatura nacional e internacional sobre fatores associados à adesão ao tratamento da Hepatite C, com especial ênfase aos fatores psicológicos e sociais. Método: Foram estabelecidas as várias fases deste estudo, segundo o procedimento proposto: elaboração da pergunta de pesquisa, estabelecimento dos critérios para seleção da amostra, apresentação das características das pesquisas selecionadas, análise dos dados, interpretação dos resultados e a síntese da revisão. Realizou-se busca dos artigos nas bases de dados: Medline, Web of Science, Cinahl, Lilacs, Psycinfo, Scopus e Scielo. Foram incluídos artigos nos idiomas português, inglês e espanhol, publicados entre os anos 2000 a 2016 e excluídos os artigos que não foram considerados pertinentes ao objeto de estudo. Resultados: Obteve-se um corpus com 14 artigos, totalmente estrangeiro, publicado em inglês, nos anos de 2001 a 2015, majoritariamente indexados no Medline, o método quantitativo predominou entre as pesquisas selecionadas (onze artigos) em relação aos qualitativos (três artigos). As variáveis psicológicas pesquisadas em relação à possível associação com a adesão/não adesão ao tratamento de Hepatite C, nos estudos quantitativos, foram: presença de sintomas psicológicos, como ansiedade e depressão, raiva, hostilidade, transtornos psiquiátricos, autoeficácia, ainda foram investigados funcionamento social, problemas interpessoais e comportamentos relacionados à saúde. Esses estudos avaliaram também a possível influência na adesão ao tratamento de características sociodemográficas: idade, ocupação, escolaridade, sexo, etnia, apoio social e ainda o uso de álcool e outras drogas (abstinência e tratamento). Entre estes fatores foi verificada associação significativa entre não adesão e presença de transtornos psiquiátricos, sintomas de depressão, ansiedade fóbica, comportamento hostil, intrusividade, uso regular de substâncias, idade (ser mais jovem), desemprego, não estar em relacionamento estável. Já as variáveis associadas estatisticamente com adesão ao tratamento foram iniciar medicação psiquiátrica durante o tratamento, comportamentos relacionados à saúde (dieta e comportamento alimentar), menor distância do centro de tratamento, genótipo 3, coinfectado HIV e virgens de tratamento. Também foram avaliados três estudos qualitativos em que foram apontadas e discutidas como barreiras e como facilitadores da adesão ao tratamento: percepção e experiências com o tratamento, presença de estigma, apoio social, estratégias de enfrentamento, sistemas de crenças, medo e ansiedade. Conclusões: Conhecer os fatores que podem interferir na adesão ao tratamento da Hepatite C é extremamente importante, seja pela gravidade da doença, pelo aumento de sua incidência, pela complexidade e custo do tratamento que exige adesão completa para se obter RVS, além do impacto pessoal e social dessa doença e de seu tratamento, que faz da Hepatite C um problema de saúde pública. Considera-se que a relevância desta revisão está ainda em apontar a necessidade de se ampliarem as pesquisas sobre o papel das variáveis psicológicas e sociais sobre as características da comunicação com os profissionais de saúde que possam favorecer melhor adesão. Pesquisas com esse intuito, ainda tão ausentes na literatura, poderão contribuir para o desenvolvimento de programas psicoeducativos para que se amplie a adesão aos tratamentos hoje disponíveis.
Introduction: Adherence to treatment refers to an active patient behavior regarding the disease and treatment by sharing decisions with the health professional. Adherence is considered a phenomenon resulting from the interaction of factors of different nature that directly affect patient behavior: factors related to the individual; social and economic factors; factors related to health care and health care professionals and also factors related to the disease and treatment. Objective: This study aims to carry out an integrative review of national and international literature of factors associated with adherence to treatment of hepatitis C, with special emphasis to psychological and social factors. Method: We establish the various stages of this study according to the proposed procedure: the development of the research question, establishment of criteria for sample selection, presentation of the characteristics of the selected research, data analysis, interpretation of results and a summary of the review. A search of articles was conducted in the following databases: Medline, Web of Science, CINAHL, Lilacs, Psycinfo, Scopus and Scielo. Complete articles were included, in Portuguese, English and Spanish, published between 2000 and 2016, and articles considered not relevant to the object of study were excluded. Results: Obtained a corpus with 14 totally foreign articles published in English between 2001-2015, mainly indexed in Medline, the quantitative method predominated among the selected studies (eleven articles) against three articles using the qualitative method. The psychological variables studied in relation to the possible association with adherence/non-adherence to treatment of hepatitis C, in the quantitative study were: presence of psychological symptoms such as anxiety and depression, anger, hostility, psychiatric disorders, and self-efficacy, but social functioning, interpersonal problems, behaviors related to health and quality of life were also investigated. These studies also assessed the possible impact on treatment adherence of sociodemographic characteristics: age, occupation, education, gender, ethnicity, social support and even the use of alcohol and other drugs (abstinence and treatment). Among these factors there was significant association between non-adherence and presence of psychiatric disorders, symptoms of depression, phobic anxiety, hostile behavior, intrusiveness, regular substance use, age (being younger), unemployment, not being in a stable relationship. The variables statistically associated with adherence to treatment were: starting psychiatric medication during treatment, health-related behaviors (diet and eating behavior), shorter distance from the center of treatment, genotype 3, HIV co-infected and treatment first timers. The three qualitative studies were also evaluated and the barriers and facilitators of adherence to treatment were identified and discussed: perception and experiences with treatment, presence of stigma, social support, coping strategies, belief systems, fear and anxiety. Conclusions: Knowing the factors that can interfere with adherence to hepatitis C treatment is extremely important because the severity of the disease, the increase in incidence, the complexity and cost of treatment that requires full adherence to achieve SVR in addition to the personal and social impact of the disease and its treatment, which makes it a public health problem. It is considered that the relevance of this review is still to point out the need to expand research on the role of psychological and social variables on the characteristics of communication with health professionals who can promote better adherence. Research to this end, yet so absent from the literature, may contribute to the development of psychoeducational programs to broaden adherence to currently available treatments.

Hepatitis C virus (HCV) is the main cause of viral hepatitis in the UK and leads to chronic liver disease in many infected individuals. There is a substantial burden on diagnostic laboratories to provide rapid, cost-effective tests for monitoring HCV infection. Commercial assays are expensive and so the development of validated in-house methods is beneficial. This thesis describes the development and implementation of rapid and inexpensive real-time PCR assays for HCV quantitation and genotyping to support clinical practice. Additionally, the development of methods for defining HCV isolates at the subtype level, important in epidemiological and transmission studies, is described. These assays were utilised in a study on spontaneous HCV clearance, the results of which suggest that HCV type 1 infection and younger age at infection are factors which are associated with spontaneous viral clearance. Chronic HCV infection is linked to oxidative stress with numerous deleterious cellular effects. Mitochondrial DNA (mtDNA) is more susceptible to oxidative damage than nuclear DNA making it an ideal marker to assess the overall level of cellular DNA damage - including deletions and mutations. This thesis illustrates the development of real-time PCR assays to detect and quantify two major mtDNA deletions. The D-Ioop region of mtDNA is particularly prone to damage - with two well recognised 'hotspots of mutation'. The creation of an RSCA (heteroduplexbased) method using capillary electrophoresis, to detect and quantify damage in this region, is described. To evaluate the clinical utility of these assays, a study of mtDNA damage in patients with liver disease was undertaken. The aim of this study was to identify whether chronic HCV infection results in increased levels of mtDNA damage compared to other liver pathologies. Low levels of mtDNA deletions were detected in the majority of liver biopsy specimens and there was no correlation between liver aetiology and quantity of deletions. The RSCA method identified numerous D-Ioop mtDNA species within the liver tissue of several individuals. There was no correlation between liver aetiology and the presence of multiple D-Ioop species.

[Truncated abstract] The hepatitis C virus (HCV) is a significant human pathogen for which there are limited post-infection therapies and no effective vaccine. Research into HCV is notoriously difficult due to the absence of suitable in vitro and in vivo model systems with which to study the virus. Furthermore, our understanding of HCV host interaction is limited and the mechanisms by which it subverts the host immune system remains largely unknown. Due to the difficult nature associated with studying HCV, the work presented in this thesis was designed to addresses a broad range of issues relating to both clinical and molecular aspects of HCV. Chronic HCV infection is often associated with the development of cirrhosis, end stage liver disease and hepatocellular carcinoma. To date, histological examination of liver biopsies provides the only approved method with which to assess the level of liver damage. While clinically informative, liver biopsies are highly invasive and may be contraindicative for patients such as haemophiliacs. Cytokine specific ELISPOT assays were used to determine whether cytokine secretion from PBMCs isolated from chronically infected HCV patients could be used as a non-invasive method to assess liver damage. Chronically infected patients with sever liver fibrosis demonstrated a significantly reduced ability to produce IFN-γ in response to HCV Core, but not other unrelated antigens, indicating that decreased IFN-γ secretion by PBMCs in response to HCV antigen could be used as a non-invasive marker for the development of liver fibrosis ... A series of HCV expression vectors covering the full length of the HCV ORF were constructed and their expression extensively tested before being used to assess the ability of HCV proteins to interact with Jak/STAT mediated Type I IFN signalling. Additionally, an alternative set of HCV IRES-EGFP reporter vectors were developed and used to access HCV IRES functionality between different eukaryotic cell lines. HCV Core protein expressed alone or in concert with E1-P7 and non-structural protein NS5B were shown to significantly reduce Jak/STAT mediated IFN expression. While the influence of HCV Core on Type I IFN signalling is consistent with previous reports in the literature, these results identify a new role for NS5B as a possible candidate protein involved in inhibition of Type I IFN signalling.

This work concerns itself with understanding the organisation of cellular immune responses to three major human pathogens - HIV, CMV and Hepatitis C (HCV). Each was studied to form three projects, each undertaken with a different approach - arrived at independently - and largely owing their origins to opportunity and circumstance as much as design. Each project led to exploration of a particular aspect of T-cell phenotype (that is the expression of particular molecular markers on T-cells) and its’ broader biological significance. I found that T-cell phenotype was strongly linked to the magnitude of T-cell responses (CMV) and the ability of T-cells to control infection (HIV). Finally I explored the significance of expression of a molecule known as CD161 on the surface of HCV specific CD8+ T-cells, indicating a phenotype of T-cell that may not follow the ‘normal rules’ applicable to T-cells in general.

Hepatitis C Virus (HCV) infection is a hepatotropic, enveloped virus with a positive sense RNA genome. The prevalence rate of the virus has been shown to be 2.9% of the world population, equating to around 170 million infected individuals. Due to the high level of chronic infection and progressive nature of the liver disease, HCV is a major health concern. Four host proteins have so far been indicated as viral receptors; scavenger receptor BI, CD81, Claudin1 and Occludin. The interaction of CD81 and Claudin1 has been previously demonstrated which lead us to determine whether specific interactions are essential for HCV entry. Using a combination of imaging and biochemical methods we were able to demonstrate that only receptor active Claudins specifically interacted with CD81. We also evaluated the ability of previously published Claudin1 mutants to interact with CD81 and demonstrated that receptor inactive mutants no longer form an association with CD81. A bioinformatic model predicted the association of the T149, E152 and T153 residues of CD81 EC2 with the 62-66 region of Claudin1. Mutation of these residues lead to an ablation of Claudin1 association and a reduction in on HCV entry, further indicating the requirement of the Claudin1-CD81 complex in the entry process.

Hepatitis C Virus (HCV) poses a global health problem, leading to progressive disease often culminating in conditions such as hepatocellular carcinoma. HCV has a propensity to persist, with 70-80% of infected individuals failing to clear the virus. Recent evidence suggests that HCV entry is dependent on at least three cellular entry factors: CD81, Scavenger Receptor B-I (SR-BI) and Claudin-1. SR-BI is a receptor for high density lipoprotein (HDL), it is predominantly expressed in the liver and steroidogenic tissue. HCV is believed to interact with SR-BI via the viral envelope protein E2, interestingly the SR-BI ligand HDL enhances HCV infection. In this study we have investigated the interaction of HCV soluble glycoprotein with cell expressed SR-BI. We have shown that over expression of SR-BI in human hepatoma cells enhances HCV infection, indicating that SR-BI surface expression levels limit infection. Furthermore, anti-SR-BI serum inhibits HCV. We demonstrate that a cell culture adapted HCV mutant has a reduced dependency on SR-BI. This altered receptor dependency is accompanied by an increased sensitivity to neutralisation by soluble CD81 and enhanced binding of E2 to cell surface expressed CD81. The adapted variant also exhibits an altered relationship with lipoproteins and a heightened sensitivity to neutralising antibodies.

Hepatitis C is a serious disease that affects about 200 million people worldwide. No anti-HCV vaccine or specific anti-viral drugs are available today. Non-structural protein 3 (NS3) of HCV is a bifunctional serine protease/helicase, and the protease has become a prime target in the search for anti-HCV drugs. In this work, the complete HCV NS3 gene has been cloned and expressed, and the protein has been purified using affinity chromatography. An assay for measuring the protease activity of full-length NS3 protease has been developed and used for inhibition studies. A series of peptide-based inhibitors of NS3 protease varying in length, the composition of the side-chain and the N- and C-terminal groups have been studied. Potent tetra-, penta- and hexapeptide inhibitors of the NS3 protease were discovered. Hexapeptides with an acyl sulfonamide C-terminal residue were the most potent inhibitors of the NS3 protease, having nanomolar Ki-values. The selectivity of the inhibitors was assessed using other serine and cysteine proteases. NS3 protease inhibitors with electrophilic C-terminal groups were non-selective while those comprising a C-terminal carboxylate or acyl sulfonamide group were selective. All inhibitors with a small hydrophobic P1 side-chain residue were non-selective for the NS3 protease, being good inhibitors of human leukocyte elastase. This result highlights the importance of the P1 residue for inhibitor selectivity, which stems from the major role of this residue in determining substrate specificity of serine proteases. Electrophilic inhibitors often cause slow-binding inhibition of serine and cysteine proteases. This was observed with other proteases used in our work but not with NS3 protease, which indicates that mechanism of inhibition of NS3 protease by electrophilic inhibitors may not involve formation of a covalent bond. The structure-activity relationships obtained in this work can be used for improvement of peptide-based inhibitors of HCV NS3 protease towards higher inhibitory potency and selectivity.

Bakgrund: Hepatit C är en leverinflammation som orsakas av ett virus. HCV räknas som blodburen smitta. Den största riskgruppen för att få smittan är sprutnarkomaner, vårdpersonal och patienter som fick smittan i vårdsammanhang, innan blod som användes inom sjukvården testades på viruset.

Syftet: Att beskriva hur människor med kronisk hepatit C upplever att leva med sin sjukdom och hur bemötandet från sjukvården och omgivningen upplevs.

Metod: Litteraturöversikt med kvalitativ ansats. Sju vetenskapliga, kvalitativa artiklar användes och en manifest innehållsanalys genomfördes.

Resultat: Informanterna upplevde en förlorad tro på den egna kroppsförmågan och en sämre livssituation på grund av de fysiska sjukdomssymtomen. Att leva med hepatit C gjorde att framtiden kändes osäker och oförutsägbar. Familjen var ett viktigt stöd. De upplevde ofta negativa attityder och bemötande från omgivningen och sjukvården. Informanterna valde oftast att inte avslöja sin sjukdom på grund av rädsla för social utstötning. Sjukvårdens bemötande upplevdes ofta som fördomsfull och dömande av informanterna.

Slutsats: Sjukdomens fysiska symtom var tidvis så dominanta att hela personens liv påverkades. Omgivningens attityder kunde leda till utsatthet och utanförskap. Det fördomsfulla bemötandet medförde att många drabbade distanserade sig från sjukvården och fattade egna beslut kring sin vård. Bristen på kunskap om sjukdomen hos allmänheten och i sjukvården är viktig att uppmärksamma för att minska lidande.

 

 

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Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
O presente estudo teve por objetivo descrever características sóciodemográficas, psicossociais, clínicas, índices de qualidade de vida, ocorrência de transtorno mental comum, de sintomas depressivos de pacientes portadores de Hepatite C crônica, em tratamento no Ambulatório de Hepatites Virais da Disciplina de Gastroenterologia Clínica do HC da FMB-UNESP, em três momentos de seu tratamento com Interferon Peguilado e Ribavirina: antes do início, nas 12ª e 24ª semanas de tratamento. Foram também estudadas as associações das variáveis sócio-demográficas e clínicas, de transtorno mental comum (TMC), sintomas depressivos, da forma de tratamento com índices de qualidade de vida (QV) nos três momentos estudados e com os resultados de exames indicativos da resposta virológica ao tratamento (detecção do RNA do vírus da Hepatite C pelo método de PCR). Método: Realizou-se estudo transversal e de seguimento. Uma amostra de conveniência foi estabelecida, tendo-se estudado 82 pacientes no estudo transversal e feito o seguimento de 46 no terceiro e sexto mês após o início do tratamento. Utilizou-se formulário estruturado para investigar aspectos sócio-demográficos e clínicos. Sintomas depressivos foram avaliados pelo Beck Depression Inventory (BDI). Utilizou-se o Self Reporting Questionnaire (SRQ) para avaliar Transtorno Mental Comum e o uso nocivo de álcool foi avaliado por meio do Alcohol Use Disorders Identification Test (AUDIT). A qualidade de vida foi estudada por meio do The Medical Outcomes Study 36 item Short-Form Health Survey (SF-36). O estudo das associações entre variáveis categoriais foi feito pelo teste do Qui–quadrado (ou Fisher, se adequado). Os Testes de Mann–Whitney e de Kruskal Wallis foram utilizados para comparar as distribuições dos vários domínios do SF-36. Para comparação entre os dados nos momentos subseqüentes foram...
This study aimed at describing socio-demographic, psychosocial and clinical characteristics as well as quality of life indexes, occurrence of common mental disorder and depressive symptoms of patients with chronic hepatitis C undergoing treatment at the Viral Hepatitis Outpatient Unit of the Botucatu Medical School – UNESP, at three different moments of their treatment with Peguilated Interferon and Ribavirin: immediately before treatment, 12 and 24 weeks after its introduction. The association of socio-demographic and clinical variables as well as those for common mental disorder (CMD), depression symptoms and form of treatment with quality-of-life (QL) indexes was evaluated at the three studied moments. The association of such variables with test results indicating virological response to treatment (detection of the hepatitis C virus RNA by the PCR method) was also investigated. Method: A convenience sample was established, and 82 patients were studied in a cross-sectional and follow-up investigation. Forty-six patients were followed 3 and 6 months after the beginning of treatment. A structured questionnaire was used to investigate socio-demographic and clinical aspects. Depression symptoms were evaluated by the Beck Depression Inventory (BDI). The Self Reporting Questionnaire (SRQ) was utilized to evaluate common mental disorder, and harmful use of alcohol was evaluated by the Alcohol Use Disorders Identification Test (AUDIT). Quality of life was assessed by the Medical Outcomes Study 36-item Short-Form Health Survey (SF-36). The study of the associations between categorial variables was performed by the chi-square test (or Fisher, if adequate). The Mann-Whitney and Kruskal Wallis tests were used to compare the distribution of various domains of SF-36. McNemar’s Exact Test was used for category variables to compare the data at the subsequent moments, and Friedman’s Test was... (Complete abstract click electronic access below)

La maladie alcoolique du foie (MAF) et l’hépatite C chronique (HCC) sont les causes les plus fréquentes de cirrhose, carcinome hépatocellulaire (CHC) et transplantation hépatique dans les pays industrialisés. La fibrose hépatique est le stigmate lésionnel de la progression de la maladie vers la cirrhose comme dans toutes les hépatopathies chroniques. Certains facteurs de risque cliniques environnementaux ont été identifiés. Toutefois, ils n’expliquent pas l’extrême variabilité individuelle de la progression de la fibrose. L’influence ethnique à développer une maladie plus sévère ainsi que les études de concordance des jumeaux mono- et di-zygotiques sur la prévalence de la cirrhose alcoolique ont suggéré l’existence de facteurs génétiques associés. Les nombreuses études de gènes candidats réalisées n’ont identifié que très peu de variants associés de manière reproductible. Pour l’HCC par exemple, le score de risque de cirrhose ou « CRS » a montré sa capacité à prédire une fibrose avancée dans diverses cohortes caucasiennes. Récemment, une étude d’association pangénomique (GWAS) dans la stéatohépatopathie non-alcoolique (NAFLD) a mis en évidence un singleton (single nucleotide polymorphism [SNP]) particulier (rs738409 C>G) dans le gène PNPLA3. Ce dernier s’est révélé être, dans diverses études, le SNP ayant l’impact le plus robuste et le plus reproductible dans cette maladie. Par ailleurs, ce même variant a également été significativement associé à la cirrhose alcoolique chez les hispaniques.

Les travaux réalisés dans le cadre de cette thèse ont permis de montrer que :

1) Le CRS avait la capacité de prédire la progression de la fibrose chez des patients caucasiens ayant une HCC dans 2 cohortes européennes indépendantes.

2) Par ailleurs, dans la MAF, nous avons répliqué chez des patients caucasiens l’association entre le SNP rs738409 dans le gène PNPLA3 et la cirrhose. Nous avons également montré pour la première fois, que l’expression de PNPLA3 était significativement diminuée chez les patients avec une fibrose plus avancée. De plus, nous avons observé dans 2 cohortes européennes que rs738409 était également associé à la prévalence du CHC.

3) Enfin, nous avons également mis en évidence l’impact de ce même SNP sur la stéatose hépatique et la fibrose dans l’HCC sans toutefois qu’il influence la réponse à la thérapie antivirale dans 3 cohortes caucasiennes indépendantes.

Ainsi de manière remarquable, un même SNP (rs738409) apparait associé à des lésions hépatiques sévères dans les trois pathologies hépatiques chroniques les plus fréquentes (la MAF, l’HCC et la NAFLD). Ceci suggère des voies pathogéniques communes de la fibrogénèse hépatique. Par ailleurs, ces travaux soulignent indirectement que les GWAS ont la capacité d’ouvrir de nouvelles voies physiopathologiques et d’identifier de nouveaux variants, gènes ou région génétiques capables de constituer de nouveaux biomarqueurs et cibles thérapeutiques dans l’HCC et la MAF.
Doctorat en Sciences médicales
info:eu-repo/semantics/nonPublished

The central aim of this study was to explore the meaning of death as both a literal and an imaginative reality, and to elucidate the fundamental tensions between these meanings of death in modern existence. Recognition was given to the need for a poetic rather than a scientific approach to thanatology, and an epistemological foundation for a poetics of death was sought in the tradition of gnosis. Theoretically, the study was grounded in the analytical psychology of C.G. Jung. It was argued that despite Jung's erratic allegiance to a Cartesian ontology and epistemology, his approach to death was nevertheless fundamentally poetic. The poetic parameters of death and dying were explored in the context of Jung's understanding of the dialectical tension between the ego and the self, and it was concluded that while death represents an opening to the imaginative possibilities of existence, these potentialities can come to the fore only when there is a corresponding willingness to die. In these terms, it was concluded that the tension between life and death forms a pivotal dynamic of human existence. These considerations led to the Question of whether the poetic parameters of death and dying are applicable to the encounter with death as a concrete actuality. It was hypothesised that the approach of death would be met at two levels of reality, that of the ego and that of the self. The expectation was that while death would be seen as a literal ending from the perspective of the former, it may represent the fulfilment of Being from the viewpoint of the self. It was also assumed that the tension between these images of death would be mediated by way of archetypal symbols, which represent the bearers of gnosis in modern culture. To address these issues at an empirical level, a hermeneutically grounded thematic analysis of 108 dreams reported by dying persons was undertaken. Twenty initial themes emerged from the data. Each of these themes was in turn elucidated by way of Jung's method of amplification. This exercise yielded five concise themes, these being (a) death, (b) transformation, (c) the self (d) the Feminine, and (e) the Masculine. It was concluded that dreams manifesting during the dying process reveal a fundamental tension between literal and metaphoric possibilities of death. Dream symbols were also found to mediate between this tension, and to orchestrate the individuation process. It was concluded that in the context of dying, dreams may reflect and facilitate the emergence of a meaningful gnosis of death. The clinical implications of these findings were onsidered, and indications for further research were provided.

O ofício do psicólogo numa instituição hospitalar é como uma arte que se modula dia-apósdia de trabalho e revela realidades desafiadoras no que se refere à sua inserção e à sua prática. A proposta deste estudo foi discutir o processo de construção do lugar do psicólogo no hospital geral com inspiração no referencial da psicologia analítica. Adotei a cartografia como metodologia de trabalho, utilizando narrativas obtidas a partir de diários de bordo que descreveram inquietações, questionamentos e reflexões sobre situações vivenciadas ao longo do percurso de minha prática enquanto psicóloga num hospital geral do município de São Paulo. O termo lugar, que transcende o espaço físico, foi entendido como disponibilidade emocional mediante situações diversas que se dão em termos de tempo e espaço no hospital. Refere-se a um jeito próprio de ocupar uma morada e que se configura por uma atitude clínica, no seu sentido etimológico. Apropriar-se de seu lugar é um processo de construção, fundamentação e manutenção, permeado por variáveis tais como: formação, supervisão, análise pessoal, conhecimento sobre a realidade e contexto da instituição e apropriação de uma persona criativa para transitar nesse contexto que corresponde a um self institucional. Essa construção se mostra em sincronia com o processo de individuação do psicólogo, em seus aspectos de desenvolvimento profissional. Considerando-se, inclusive, que, no seu trabalho dentro do hospital, sua individuação se cruza com a dos outros personagens que também transitam neste contexto. Através de sua postura de prontidão, o psicólogo ausculta as demandas que lhe são confiadas, clarificando sentidos e cuidando para que o encontro aconteça como possível o for e num processo percorrido junto e de modo que ao outro seja devolvido seu potencial de responsabilidade e cuidado. Importante atentar, inclusive, para sua atitude dentro da equipe e em relação ao modo pelo qual recebe e dá atenção às solicitações de intervenções. Também se faz necessária uma conciliação e flexibilização entre o tempo kairótico e o cronológico: entre a necessidade emocional do paciente, a disponibilidade pessoal do psicólogo e as emergências e urgências práticas do contexto hospitalar. O mito de Héstia pode inspirar-lhe uma atitude acalentadora ao sofrimento e incômodo humanos. Tal como a disponibilidade emocional do psicólogo, a lareira de Héstia é o lugar da passagem e deve sempre ser mantida acesa; ela proporciona o estar para que se restabeleça um cuidar de ser e de resgatar novos modos de continuar sendo. Já a presença inspiradora de Hermes abre caminhos para a transição rumo ao porvir, encaminhando sentidos aos impasses do cotidiano hospitalar. Um questionamento que também se mostrou relevante, pois embasa o lugar da Psicologia em qualquer contexto, refere-se ao que interpela o lugar que cabe à Psicologia enquanto ciência e a qual convocação esta se dirige, atualmente. O lugar do psicólogo no hospital, assim como em qualquer outro local, existe por sua legitimidade. Precisamos apenas reconhecê-lo e habitá-lo. Para isso, não podemos esperar que nos seja indicado; nós devemos clarificá-lo por uma atitude própria
The profession of a psychologist in a hospital institution is like an art that adjusts with every day of work and reveals challenging realities in relation to its insertion and its practice. The aim of this study was to discuss the process of the construction of the psychologists place in a general hospital inspired by references to analytical psychology. I adopted cartography as the work methodology, using narratives obtained from logbooks which described restlessness, questioning and reflections about situations experienced over the course of my work while I was a psychologist at a general hospital in the municipality of Sao Paulo. The term place, which transcends the physical environment, was understood as emotional availability by means of various situations that occur in terms of time and space in the hospital. It refers to a particular way of occupying a residence and which is shaped by a clinical attitude, in its etymological sense. The appropriation of ones place is a process of construction, foundation, and maintenance, permeated by variables such as: formation, supervision, personal analysis, knowledge in relation to the institutions reality and context and the appropriation of a creative persona to make ones way through this context which corresponds to an institutional self. This construction shows itself to be in synchrony with the psychologists process of individuation, in its aspects of professional development. Also taking into account that in such work for the hospital, ones individuation crosses with that of the other characters that are also making their way through this context. Through a posture of readiness, demands are entrusted to the psychologist who listen to them, clarifying meanings so that the meeting happens as possible it can be and in a process travelled together and in such a way that the other person is given back their potential for responsibility and care. It is also important to pay attention to ones attitude within the team and in relation to the way in which you receive and deal with the requests for interventions. It is also necessary a reconciliation and flexibility between kairotic time and chronological time, between the patients emotional needs, the psychologists personal availability and the practical emergencies and pressures of the hospital context. The myth of Hestia may inspire a soothing attitude to human suffering and discomfort. In the same way as the psychologists emotional availability, Hestias hearth is a place of passage and should always be kept lit; it provides the being in order to reestablish a care to be and to rescue new ways to continue being. Meanwhile Hermes inspiring presence paves the way for the transition towards what is still to come, forwarding meanings to the impasses of daily hospital life. A question that also showed to be relevant, as it lays the foundations for Psychologys place in any whatsoever context, refers to that which challenges Psychologys place as a science and to what calling it is currently directed. The psychologists place in the hospital, as in any other place, exists due to its legitimacy. We need merely recognize it and inhabit it. For this reason, we cannot expect that it is shown to us; we have to clarify it by our own attitude

People with hepatitis C (HCV) face stigma and discrimination because of the association of this disease with injecting drug use (IDU). Research has found that many instances of HCV-related discrimination occur in the health care sector. Health care workers' beliefs about their HCV positive clients are likely to influence how they relate to clients and their treatment delivery. This research assessed the implicit and explicit attitudes of both health care workers and their HCV positive injecting drug using (HCV+) clients toward each other and then established whether these affect the treatment experiences of health care workers and clients. The sample consisted of 60 health care workers (doctors and nurses), 120 HCV+ and 120 HCV- clients, recruited from the same treatment facility. Participants were given a series of attitude and treatment experiences measures to complete. Data illustrate that while health care workers' and HCV+ clients' explicit attitudes towards each other were positive, clients with HCV still rated their health care workers less highly and reported less satisfaction with their treatment than HCV- clients. Analyses also indicated that more conservative health care workers displayed greater prejudice toward their HCV+ clients because they believe that injecting drug use is controllable. This prejudice toward IDUs on the part of health care workers was associated with worry about the behaviour of IDU clients and this worry in turn predicted differences in treatment experiences reported by HCV+ and HCV- clients. These data support the contention that health care worker concerns, particularly those related to injecting drug use, underlie discriminatory treatment of people with HCV. Finally the research also addressed the impact of health care worker contact with HCV+ clients on their attitudes towards this group. Analysis revealed that while health care workers who have had more contact with people with HCV show more positive explicit attitudes, they also show less favourable implicit attitudes toward IDUs. This may reflect the difficulties and stresses associated in caring for IDUs and may provide insight into the hidden costs involved for health care workers working with a population that may be challenging and at times difficult to manage.

Background and aims: This interdisciplinary thesis was designed to deepen understanding of the co-morbidity of anxiety and depression with chronic diseases of the digestive tract, and inflammatory bowel disease (IBD) in particular. The first part of the thesis aimed to explore the prevalence of psychological problems in IBD compared to irritable bowel syndrome (IBS) and chronic hepatitis C (HCV) groups. It also explored the relationship between the number of co-morbid functional gastrointestinal disorders and the severity of psychological problems in IBD and IBS. It also aimed to determine whether there is a relationship between psychological problems and the response to standard medical treatment/physical outcomes in patients with IBD, IBS and HCV. Furthermore, it aimed to explore whether disclosure of the psychological status of depressed and/or anxious IBD patients to their gastroenterologists influences doctors’ behaviour and affects patients’ responses to treatment/physical outcomes. The second part of the thesis aimed to investigate the potential role of antidepressants in IBD and to determine the feasibility of future randomised controlled trials on the role of antidepressants in IBD. Methods: Overall, a cohort of 139 outpatients (64 IBD, 41 HCV, and 34 IBS) and 18 gastroenterologists participated in the six studies comprising this thesis. A mixed methods design was applied. Two cross-sectional studies, an observational cohort prospective management study, a randomised controlled trial, a systematic review and an exploratory interview study were conducted. Differences between the groups for continuous variables were assesed with one way analysis of variance (ANOVA) and independent samples ttests. Differences in categorical variables were assessed with contingency tables with the Chi-Square test and the Fisher’s Exact Test. Propsective analyses were conducted with repeated measures ANOVA, logistic regression and Poisson regression. Qualitative data were analysed using content analysis. Results: Overall, 42% of participants were anxious and 19% were depressed. Participants with HCV had higher levels of psychological impairment compared with the IBS, the IBD group and the general population (p<0.05). Those IBD participants with fewer co-morbid functional disorders had better physical quality of life than participants with a greater number of these disorders (p=0.025). Moreover, depression/anxiety at baseline did not explain medical outcomes after 12 months in this cohort of patients with chronic diseases of the digestive tract. Doctors’ knowledge of patients’ psychological status was found to have no impact on IBD patients’ outcomes after 12 months. However, interestingly, the level of anxiety in IBD participants significantly dropped between the baseline and nine months indicating a possible benefit from participating in the study. In the literature review, insufficient evidence was found to conclude that antidepressants are efficacious for treatment of psychological co-morbidities or somatic complaints in IBD. However, the qualitative interview study indicated a potential positive impact of treatment with antidepressants on coping with disease symptoms and general wellbeing in patients with IBD. Conclusion: The thesis confirms that there is a significant burden of psychological co-morbidity in patients with chronic gastroenterological diseases. Interdisciplinary approaches to the management of these diseases are therefore warranted in Australian gastroenterology clinics. Anxiety targeted interventions and research in this setting are urgently needed, especially with respect to patients with HCV. Larger studies exploring the gastroenterologists’ role in treatment of co-morbid psychological problems in their patients are recommended. Longer prospective studies on homogenous samples of patients are also needed to clarify the nature of the relationship between psychological problems and relapse of somatic symptoms. Finally, randomised controlled trials exploring the efficacy of antidepressants in IBD are warranted.
http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1321006
Thesis (Ph.D.) -- University of Adelaide, School of Population Health and Clinical Practice, 2008

碩士
中國醫藥大學
營養學系碩士班
102
In this study, we recruited 89 heroin users from methadone clinics, prisons or drug abuser treatment center. People who were had medical problems, neurological diseases, HIV, mental handicap, and other barriers were excluded from the study. The purpose of this study was the effect of methadone maintenance treatment (MMT) for drug abusers also suffering hepatitis C on fatty acid metabolism, the degree of depression and gene polymorphism. The 89 drug abusers were divided into two groups, drug abusers with or without hepatitis C. The patient characteristics, biochemical values (SGOT, SGPT, r-GT), types of drug abuse, prevalence of blood-borne diseases, and scales were analyzed. We analyzed the erythrocyte membrane phospholipid of before and after methadone maintenance treatment. Furthermore, we investigated polymorphisms in genes of fatty acid metabolism in heroin users. The results showed that before MMT, drug abusers also suffering hepatitis C had sleep disturbances and lower quality of life scores than after. The difference of erythrocyte membrane phospholipid between MMT before and after, no matter drug abusers also suffering hepatitis C or not, the SFA was significantly increased, PUFA and AA/EPA ratio were decreased significantly. Further, after MMT, AA/EPA ratio of drug abusers also suffering hepatitis C was higher than drug abusers without hepatitis C significantly. It might result in drug abusers also suffering hepatitis C had high prevalence of psychiatric disorders. On the other hand, there is no difference in the allele frequencies of PLA2 and PPAR gamma polymorphisms. There is difference in the allele frequencies of FADS1, FADS2 and FADS3 polymorphisms, but there is no significant difference with n6/n3 PUFAs.

HIV is known to affect the epidemiology, transmission, pathogenesis and natural history of HCV infection whilst studies on the effects of HCV on HIV have shown conflicting results and are confounded by the influence of intravenous drug use and anti-retroviral therapy. This study was conducted in KwaZulu-Natal Province in South Africa where HIV is predominantly a sexually transmitted infection. Intravenous drug use is rare in this region and the study population was naive to anti-retroviral therapy. For this study, specimens from selected sentinel sites submitted to a central laboratory for routine HIV testing were screened for anti-HCV IgG antibodies. HIV positive HCV-positive patients were compared to HIV-positive HCV-negative patients in a subgroup of patients within this cohort in order to determine if HCV sero-prevalence was associated with clinical outcomes in a linked anonymous retrospective chart survey. The prevalence of HCV was 6.4% and that of HIV, 40.2%. There was a significantly higher prevalence of HCV among HIV infected patients as compared to HIV negative patients (13.4% vs. 1.73% respectively). HCV-HIV co-infected patients had significantly increased mortality (8.3 vs. 21%). A significant association was found between HCV serostatus and abnormal urea and creatinine levels. Hepatitis B surface antigen seropo-sitivity was not found to be a confounding factor. This study has found that hepatitis C co-infection is more common in HIV positive individuals and is associated with an increased mortality and renal morbidity.
Thesis (M.Med.)-University of KwaZulu-Natal, Durban, 2008.

Li, Sai Kam.
Thesis (M.Phil.)--Chinese University of Hong Kong, 2007.
Includes bibliographical references (leaves 162-179).
Abstracts in English and Chinese.
Abstract --- p.i
Abstract in Chinese (摘要） --- p.ii
Acknowledgements --- p.iii
Table of Content --- p.iv
Abbreviations --- p.xi
List of Figures --- p.xiv
List of Tables --- p.xvii
Chapter CHAPTER 1 --- INTRODUCTION
Chapter 1.1 --- Hepatitis B Virus
Chapter 1.1.1 --- General information --- p.1
Chapter 1.1.2 --- Classification --- p.2
Chapter 1.1.3 --- Virus life cycle and genome --- p.3
Chapter 1.1.4 --- Hepatitis B virus X protein (HBx) --- p.7
Chapter 1.2 --- Enigmatic functions of HB --- p.x
Chapter 1.2.1 --- HBx as a transactivator --- p.10
Chapter 1.2.2 --- HBx as a cell cycle regulator --- p.12
Chapter 1.2.3 --- HBx as an apoptosis modulator --- p.13
Chapter 1.3 --- Etiology of HBV-mediated hepatocarcinogenesis --- p.14
Chapter 1.4 --- Clinical mutants of HBV --- p.16
Chapter 1.5 --- Hypothesis and aims of the research --- p.16
Chapter 1.6 --- Basis of Tet-On system --- p.18
Chapter CHPATER 2 --- EXPERIMENT MATERIALS
Chapter 2.1 --- Cell culture
Chapter 2.1.1 --- Cell-lines --- p.21
Chapter 2.1.2 --- Culture medium --- p.22
Chapter 2.1.3 --- Culture medium supplements --- p.23
Chapter 2.2 --- Reagents for subcloning
Chapter 2.2.1 --- Reagents for polymerase chain reaction (PCR) --- p.24
Chapter 2.2.2 --- Reagents for restriction enzyme digestion --- p.24
Chapter 2.2.3 --- Reagents for ligation --- p.25
Chapter 2.2.4 --- Reagents for electrophoresis --- p.25
Chapter 2.2.5 --- Reagents for E. coli DH5a preparation --- p.25
Chapter 2.2.6 --- Materials for bacterial culture work --- p.27
Chapter 2.3 --- Reagents for subcellular localization study
Chapter 2.3.1 --- Reagents for cell staining --- p.28
Chapter 2.3.2 --- Reagents for mounting slides --- p.29
Chapter 2.3.3 --- Materials for site-directed mutagenesis --- p.29
Chapter 2.4 --- Reagents for cell cycle analysis and cellular proliferation
Chapter 2.4.1 --- Reagents for cell cycle analysis --- p.29
Chapter 2.4.2 --- Reagents for cellular proliferation study --- p.30
Chapter 2.5 --- Reagents for protein expression study
Chapter 2.5.1 --- Cell lysis buffer --- p.30
Chapter 2.5.2 --- Reagents for SDS-PAGE --- p.30
Chapter 2.5.3 --- Reagents for Western blot --- p.33
Chapter 2.5.4 --- Antibodies --- p.34
Chapter 2.6 --- Reagents for gene expression study
Chapter 2.6.1 --- Reagents for RNA extraction --- p.36
Chapter 2.6.2 --- Reagents for first strand cDNA synthesis --- p.37
Chapter 2.6.3 --- Reagents for real-time PCR --- p.37
Chapter 2.7 --- Reagents for establishment of Tet-On inducible stable cell-lines
Chapter 2.7.1 --- Reagents for MTT assay --- p.38
Chapter 2.7.2 --- Reagents for selection of stable clones --- p.38
Chapter 2.8 --- Vectors used in the project
Chapter 2.8.1 --- Vectors for subcellular localization study --- p.39
Chapter 2.8.2 --- Vectors for establishment of Tet-on inducible cell-lines --- p.39
Chapter 2.9 --- Primers used in the project
Chapter 2.9.1 --- Primers used for subcloning --- p.42
Chapter 2.9.2 --- Primers used for site-directed mutagenesis --- p.43
Chapter 2.9.3 --- Primers used in real-time chain polymerase reaction --- p.43
Chapter CHAPTER 3 --- RESEARCH METHODS
Chapter 3.1 --- Subcloning of HBx and mutant genes into a green fluorescence protein (GFP) expression vector
Chapter 3.1.1 --- Amplification of HBxWt，HBxΔC44 and HBxAN60 genes --- p.45
Chapter 3.1.2 --- Purification of PCR products --- p.46
Chapter 3.1.3 --- Restriction enzyme digestion --- p.47
Chapter 3.1.4 --- Ligation of gene products with pEGFP-C 1 vector --- p.47
Chapter 3.1.5 --- Preparation of chemically competent bacterial cells E. coli strain DH5α --- p.47
Chapter 3.1.6 --- Transformation of the ligation product into competent cells --- p.48
Chapter 3.1.7 --- PCR confirmation of successful ligation --- p.48
Chapter 3.1.8 --- Small scale preparation of bacterial plasmid DNA --- p.49
Chapter 3.1.9 --- DNA sequencing of the cloned plasmid DNA --- p.50
Chapter 3.1.10 --- Large scale preparation of target recombinant plasmid DNA --- p.50
Chapter 3.2 --- Subcellular localization pattern study
Chapter 3.2.1 --- Cell transfection --- p.51
Chapter 3.2.2 --- Mitochondria and nucleus staining --- p.52
Chapter 3.2.3 --- Epi-fluorescence microscopy --- p.53
Chapter 3.2.4 --- Analysis of fluorescence images --- p.53
Chapter 3.2.5 --- In vitro site-directed mutagenesis --- p.53
Chapter 3.3 --- Cell cycle phase analysis with flow cytometry
Chapter 3.3.1 --- Cell transfection --- p.55
Chapter 3.3.2 --- Cell staining --- p.55
Chapter 3.3.3 --- Flow cytometry --- p.55
Chapter 3.4 --- Cellular proliferation quantification by BrdU proliferation assay
Chapter 3.4.1 --- Cell transfection --- p.57
Chapter 3.4.2 --- BrdU ELISA measurement --- p.57
Chapter 3.5 --- Protein expression
Chapter 3.5.1 --- Cell lysate collection --- p.58
Chapter 3.5.2 --- Quantification of protein samples --- p.59
Chapter 3.5.3 --- SDS-PAGE --- p.59
Chapter 3.5.4 --- Western blot --- p.60
Chapter 3.5.5 --- Western blot luminal detection --- p.60
Chapter 3.6 --- Gene expression
Chapter 3.6.1 --- Primer design --- p.61
Chapter 3.6.2 --- Cell transfection --- p.61
Chapter 3.6.3 --- RNA extraction --- p.61
Chapter 3.6.4 --- Reverse transcription for first strand complementary DNA (cDNA) --- p.63
Chapter 3.6.5 --- Quantitative real-time PCR --- p.63
Chapter 3.7 --- Establishment of Tet-On inducible stable cell-lines
Chapter 3.7.1 --- Subcloning of HBx gene into pTRE2 vector --- p.64
Chapter 3.7.2 --- Construction of WRL68/Tet-On stable cell-lines --- p.64
Chapter 3.7.3 --- Construction of WRL68/Tet-On HBx and mutants expression cell-lines --- p.68
Chapter 3.7.4 --- Characterization of Tet-On gene expression monoclones --- p.69
Chapter 3.8 --- Statistical analyses --- p.70
Chapter CHPATER 4 --- STUDY ON MITOCHONDRIA TARGETING
Chapter 4.1 --- Establishment of pEGFP-Cl-HBx and mutants constructs --- p.71
Chapter 4.2 --- Transactivation C-terminus domain is essential for granular localization --- p.73
Chapter 4.3 --- Wild-type HBx localizes in mitochondria --- p.76
Chapter 4.4 --- C-terminal transactivation domain is sufficient for mitochondria targeting --- p.79
Chapter 4.5 --- Mapping of the HBx region crucial for mitochondria targeting --- p.81
Chapter 4.6 --- The 111-117 amino acids in HBx do not work as a signal peptide --- p.83
Chapter 4.7 --- Site-directed mutagenesis identifies the key amino acid at 115 in HBx for mitochondrial targeting --- p.85
Chapter CHAPTER 5 --- CELL PROLIFERATION AND REGULATION
Chapter 5.1 --- Alteration of S-phase distribution in cell cycle --- p.88
Chapter 5.2 --- Analysis of DNA synthesis using BrdU proliferation ELISA --- p.92
Chapter 5.3 --- Differential molecular regulation of cell cycle --- p.94
Chapter 5.4 --- Regulation of the mRNA expression levels of cyclin-dependent kinases inhibitors p2raf/cipl and p27kipl --- p.98
Chapter CHAPTER 6 --- TRANSACTIVATION AND RAS/RAF/MAPK PHOSPHORYLATION
Chapter 6.1 --- Determination of p53-dependency of p21、vaf/cipl expression --- p.101
Chapter 6.2 --- Ras/Raf/MAPK pathway activation by HBx variants
Chapter 6.2.1 --- ERK1/2 phophorylation by HBx variants --- p.104
Chapter 6.2.2 --- ERK inhibition blocks the regulation effect on p53Wt and p21waf/cipl --- p.107
Chapter 6.3 --- Transactivation activity on oncogenes/ proto-oncogenes
Chapter 6.3.1 --- Effect on c-myc (NM´ؤ002467) mRNA expression --- p.109
Chapter 6.3.2 --- Effect on RhoC (NM_017744) and Rabl4 (NM´ؤ016322) mRNA expression --- p.112
Chapter CHAPTER 7 --- CONSTRUCTION OF TET-ON INDUCIBLE CELL-LINES
Chapter 7.1 --- Establishment of WRL/Tet-On monoclonal cell-lines Page
Chapter 7.1.1 --- Determination of geneticin selection dosage --- p.116
Chapter 7.1.2 --- Selection of the best WRL/TOn clone using luciferase assay --- p.118
Chapter 7.2 --- Establishment of inducible WRL/TOn/Gene monoclonal cell-lines
Chapter 7.2.1 --- Determination of hygromycin selection dosage --- p.120
Chapter 7.2.2 --- Selection of positive WRL/TOn/Gene clones with viral genes --- p.122
Chapter 7.3 --- Characterization of TOXDC1 cell-line
Chapter 7.3.1 --- Cell morphology --- p.125
Chapter 7.3.2 --- Growth pattern of TOXDC1 --- p.126
Chapter 7.3.3 --- HBxAC44 induced p21waf/cipl mRNA expression --- p.127
Chapter 7.3.4 --- Doxycycline concentration dependent HBxAC44 expression in TOXDC1 --- p.129
Chapter CHAPTER 8 --- DISCUSSION
Chapter 8.1 --- Selection of cell model
Chapter 8.1.1 --- Selection of cell models --- p.130
Chapter 8.1.2 --- Selection of truncation mutant --- p.131
Chapter 8.2 --- Differential sub-cellular localization of HBx and its variants
Chapter 8.2.1 --- Mechanisms of mitochondria targeting --- p.132
Chapter 8.2.2 --- Mitochondria as site of HBx-induced apoptosis --- p.134
Chapter 8.2.3 --- Stimulation of calcium release from mitochondria by wild-type HBx --- p.135
Chapter 8.3 --- Cell cycle distribution profiling and its regulations
Chapter 8.3.1 --- Cell cycle pattern and cell proliferation --- p.136
Chapter 8.3.2 --- Differential cell cycle molecular pathway activation --- p.138
Chapter 8.4 --- Ras/Raf/MAPK mediated transactivation by HBxWt and its mutants
Chapter 8.4.1 --- p53-mediated p21waf/cipl expression --- p.142
Chapter 8.4.2 --- ERK-mediated p21waf/cipl and wild-type p53 mRNA expression --- p.143
Chapter 8.4.3 --- Regulation of oncogenes/ proto-oncogenes expression --- p.147
Chapter 8.5 --- General discussions on differential effects of HBxWt and HBxAC44 --- p.149
Chapter 8.6 --- Establishment of Tet-On/HBxAC44 cell-line TOXDC1 --- p.153
Chapter 8.7 --- Conclusions --- p.154
Chapter 8.8 --- Future Prospects
Chapter 8.8.1 --- From mitochondria targeting to calcium signaling --- p.157
Chapter 8.8.2 --- Construction of a complete cell cycle regulation pathway --- p.158
Chapter 8.8.3 --- Elucidation of the transcriptional transactivation regulation --- p.159
Chapter 8.8.4 --- To make the best use of the Tet-on stable cell-line TOXDC1 --- p.159
Chapter 8.8.5 --- Study with other carboxy-terminal truncation mutants --- p.160
Chapter 8.8.6 --- In vivo study --- p.160
REFERENCES --- p.162

Indiana University-Purdue University Indianapolis (IUPUI)
This thesis project aims to address the following question: How do women who were planning a vaginal birth with limited medical intervention experience an unplanned c-section? Specifically, this research project involved: completing in-depth interviews with 15 women who planned a vaginal birth with limited medical intervention but instead experienced an unplanned c-section between six months and two years ago; discovering and describing the nature of the birth the mothers originally envisioned for their child; exploring the women’s experiences with, and feelings about, the birth itself and how it might differ from what they envisioned; developing a better understanding of how these experiences and feelings affected the women during the first two years following the birth; describing any challenges they faced and how, if at all, they managed such challenges; and identifying strategies that could be used to improve the experience of women recovering from an unplanned c-section who envisioned a vaginal birth with limited medical intervention.