Gestational trophoblastic disease (GTD) is arised from the neoplastic trophoblasts in placenta. Trophoblasts have the characteristic of proliferation and invasion. GTD is classified as partial hydatidiform mole (PHM), complete hydatidiform form mole (CHM), invasive hydatidiform mole (IHM), choriocarcinoma (CCA), placental site trophoblastic tumour (PSTT), epithelioid trophoblastic tumour (ETT), exaggerated placental site trophoblastic reaction (EPSR) and placental site nodule (PSN). HM has the potential to develop into malignant trophoblastic disease, and metastasis to other parts of body. FoxD3 gene belongs to Forkhead family. Its protein acts as embryonic stem cell transcription factor and plays an important role in neural crest and placenta development. Previous studies from our team have reported that other embryonic stem cell transcription factors, such as Nanog, Sox2 Oct4 and Stat3, are related with pathogenesis of GTD. This study aim is to investigate the protein expression profile of FoxD3 in different types of GTD using immunohistochemistry method. In this study, 70 formalin fixed paraffin embedded tissue blocks from 16 normal first trimester placenta, 38 CHM, 9 CCA, 5 PSTT and 2 ETT were retrieved. Paraffin sections were prepared and stained with FoxD3 antibody by using immunohistochemistry method. Compared with normal placentas, there was significantly increased expression of FoxD3 in trophoblasts of CM and PSTT (p<0.05). In CCA, there was high expression of FoxD3 in syncytiotrophoblasts and intermediate trophoblasts (p<0.05). In ETT, the immunoreactivity of FoxD3 is not significantly increased when compared with intermediate trophoblasts (p=0.07). To conclude, FoxD3 was found to be over-expressed in GTD. FoxD3 may contribute to pathogenesis of GTD. Further investigations are needed to discover the relationship with other embryonic transcription factors and genes to improve the diagnosis, prognosis and treatment of GTD. / published_or_final_version / Pathology / Master / Master of Medical Sciences

OBJECTIVE To determine whether grading for AMD during a diabetic retinopathy (DR) screening program would be cost-effective in Hong Kong. METHODS A cost-effectiveness analysis based on a Markov model with six mutually exclusive health states was undertaken. It included grading for AMD and treatment with vitamin therapy for those with intermediate AMD. The outcome of the model was cost per quality-adjusted life year (QALY) gained. A public provider perspective was used. The measures of effectiveness were mostly taken from a local DR screening project except the transition probabilities and the utility values which were taken from overseas data. Costs were mainly taken from the Hospital Authority and salary scale 2009. The main assumptions and estimates were tested in sensitivity analyses. In this model, only subjects with non-sight threatening diabetic retinopathy were included and the possibility of disease regression and treatment benefit for those with advanced AMD were not considered. Both costs and benefits were discounted at 3%. RESULTS The cost per QALY gained through grading for AMD at the time of DR screening and treatment with vitamins of appropriate cases was HK$47,397 after discounting. This would be considered highly cost-effective based on the World Health Organization’s threshold of willingness-to-pay (WTP) for a QALY, e.g. less than the annual per capita GDP HK$300,000. One way sensitivity analyses revealed that the cost per QALY was most sensitive to utility value, discount rate, progression rate from intermediate to advanced AMD, and compliance rate for the treatment. The cost-effectiveness acceptability curve showed that at a WTP for a QALY of $100,000 or more, this AMD screening programme has over 90% of probability of being cost-effective compared with no screening. CONCLUSION Our cost-effectiveness analysis demonstrated that grading for AMD at the time of DR screening among diabetic patients would probably be cost-effective in a Hong Kong public hospital setting. / published_or_final_version / Public Health / Master / Master of Public Health

Background: The epidemic of childhood obesity is of increasing public health concern, with major implications for long-term health. Prevention strategies are urgently needed. Most of the evidence concerning risk factors for childhood obesity comes from observational studies, mainly from Western populations. In the West, socio-economic position (SEP) is often associated with potential risk factors and with childhood obesity, making these observational studies open to residual confounding. Evidence from a setting with a different confounding structure can be valuable in disentangling whether associations observed in Western settings reflect potentially reversible causal effects of risk factor or are confounded by SEP. Objectives: This thesis took advantage of a large (n=8327), population-representative Chinese birth cohort from a developed non-Western setting, Hong Kong, where the confounding structure between potential risk factors and childhood obesity is different, to examine the association of four modifiable risk factors (mode of delivery, the timing of solid food introduction, type of child care and dairy product consumption) with adiposity from infancy to early puberty. Methods: Adiposity from infancy to early puberty was proxied by age- and sex-specific body mass index (BMI) standardized scores (z-scores) from 3 months to 13 years, relative to the 2006 World Health Organization (WHO) child growth standards for 0-5 years and the 2007 WHO growth reference for 5-19 years. Overweight (including obesity) was defined according to International Obesity Task Force cut-off. I compared three marginal models (maximum likelihood estimation, generalized estimating equations and quantile regression) to ascertain the optimal way of modeling the population-averaged association of early life risk factors with BMI z-score because of the complex data structure with inevitably some missing data. All three methods were used to examine the adjusted associations of mode of delivery and the timing of solid food introduction with BMI z-score from infancy to early puberty and with overweight (including obesity) from early childhood to early puberty. Multivariable linear and logistic regression were used to examine the adjusted associations of the type of child care at 6 months, 3 years, 5 years and 11 years with BMI z-score and overweight (including obesity) at 13 years, and the association of dairy product consumption at 11 years with BMI z-score at 13 years. Results: My analyses were robust to the choice of marginal model. Mode of delivery, the timing of solid food introduction and dairy product consumption were not associated BMI z-score or overweight (including obesity), but informal child care was associated with higher BMI z-score and overweight at early puberty. Conclusions: In this population-representative birth cohort from an understudied non- Western developed setting with little patterning of childhood adiposity by SEP, informal child care (by family members and/or in-home employed help) may be a target for intervention. Conversely, cesarean section, early introduction of solid food and lack of dairy product consumption do not appear to be contributing to the current obesity epidemic. Non-replication in a different context suggests some observed associations in the West may be indicators of residual confounding rather than of causality. / published_or_final_version / Public Health / Doctoral / Doctor of Philosophy

Objectives: Forkhead box protein P1 (FOXP1) is a transcription factor, and a member of the P-subfamily of forkhead box transcription factor and regulate transcription of a subset of genes that involved in various cellular events. It plays a critical role in regulating cell growth and proliferation, differentiation, embryogenesis, adult tissue homeostasis, and possibly tumorigenesis. Predominant nuclear localisation of FOXP1 protein is commonly expressed at low level in normal tissues and upregulated in proliferative cells. Studies have demonstrated that the loss of FOXP1 expression and cytoplasmic mis-localisation is significantly associated with various malignant cancers, including breast cancer. FOXP1 can act either as a tumor suppressor or as an oncogenic protein in cell-type specific functions. It has been shown to be a co-regulator of estrogen receptor alpha and can modify a specific subset of forkhead box transcription factor class O (FOXO)-target genes. We hypothesise that there is association between FOXP1 expression and patient survival, and explore the potential role of FOXP1 expression as a prognostic marker in breast cancer. Methods: One hundred and twenty breast cancer samples in tissue microarray blocks were examined for FOXP1 expression by immuno-histochemistry. Nuclear and cytoplasmic FOXP1 expression patterns were analysed with clinico-pathological parameters. Statistical analysis was performed using SPSS software to determine the correlation between FOXP1 expression and clinico-pathological parameters. The correlation between subcellular FOXP1 expression and survival was evaluated by COX regression analysis. Results: Nuclear or cytoplasmic FOXP1 expression showed no association with clinico-pathological parameters. However, our results showed that there was significant association with estrogen receptor and progesterone receptor when nuclear and cytoplasmic scores were combined as total FOXP1 score (p=0.022 and p=0.028 respectively). In univariate analysis, high nuclear and cytoplasmic FOXP1 expression had no significant correlation with poor survival, while high total FOXP1 expression was associated with poor overall and disease-specific survival (p=0.045). Tumor stage and lymph-node involvement were significantly related to poorer overall and disease-specific survival, while other clinico-pathological parameters did not. In breast cancer with advanced tumor grade and lymph-node involvement, overall and disease-specific survival are significantly associated with high FOXP1 expression (p=0.041 and p=0.015 respectively). Conclusion: Unlike previous reports, our findings show that increased nuclear and cytoplasmic FOXP1 expression were both observed and high total FOXP1 expression was associated with poorer survival, particularly in cases of advance tumor grade and with lymph node metastases. These finding are supported by a recent report that showed that FOXP1 can up-regulate its own expression by binding to the promoter of FOXP1 and promote cell survival of breast cancer cells by suppressing FOXO-induced apoptosis. It may be possible that FOXP1 expression is up-regulated in a positive feedback loop in breast cancer cells such that there is both increased nuclear transcriptional activity and cytoplasm localisation of FOXP1. Further investigation is necessary to understand the role of FOXP1 in the progression of breast cancer and determine its potential use as a prognostic marker. / published_or_final_version / Pathology / Master / Master of Medical Sciences

The mouse pelage hair consists of three types of hair coined primary (guard), secondary (awls and auchenes) and tertiary (zigzag) hair. They display distinct morphologies and are induced consecutively during hair morphogenesis. Previously two identified regulatory mouse mutants, Yellow submarine (Ysb) and Light coat and circling (Lcc) which the chromosomal rearrangements have disrupted the cis-acting regulatory elements of Sox2; resulting in the loss of Sox2 expression in the inner ear. The mutants displayed lighter hair coat color due to a reduction in the proportion of secondary hair and increased proportion of tertiary hair. Sox18 null mutants display darker coat colour and reduced proportion of zigzag hair. To dissect the underlying mechanisms of the phenotypes in hair type specification in 〖Sox2〗^Ysb and 〖Sox2 〗^Lcc mutants and the role of Sox2 and Sox18 in regulating the process; the expression of Sox2 in the hair follicle and the change in the density of hair types in mutants were analyzed. I have identified the expression pattern of Sox2 in the dermal papilla (DP) of the hair follicle and verified its down-regulation in 〖Sox2〗^Ysband 〖Sox2 〗^Lcc mutants. The DP at the base of hair follicle is the signaling center for the regulation of hair development. Sox2 is specifically expressed in the DP of primary and secondary but not in tertiary hair while Sox18 is expressed in the DP of all hair types. Analysis of Sox2 mutants showed that the number of secondary hair was normal at induction but was reduced and accompanied by an increase in tertiary hair in adult mice. The number of tertiary hair was reduced in Sox18 null mutants. To gain insight into the molecular basis of hair type specification and potential targets of Sox2 in the regulation, gene expression profile in DP cells of 〖Sox2 〗^(EGFP/+)and 〖Sox2 〗^(EGFP/Ysb) mice was examined; the data suggests that genes in the Wnt and BMP signalling pathway were down-regulated in Sox2 mutants; while Runx3 and Corin may act downstream of Sox2 in regulating hair type specification and pigmentation. Hair follicles enter cycles of growth and regression throughout life during the hair cycle. Sox2 was only expressed in the growth phase while Sox18 was persistently expressed throughout the hair cycle. I further asked if Sox2 and Sox18 regulate post-natal hair development by analysing the expression pattern of Sox2 and Sox18 in wildtype mice and mutants throughout the hair cycle and the progression of hair growth in the mutants. The growth phase of the first hair cycle was extended in Sox2 mutants while the hair cycle in Sox18 null mutants was normal. Cell proliferation was compromised during hair regeneration leading to a delay in hair regeneration in Sox2 mutants. Sox2 and Sox18 showed overlapping expression in the DP and both regulate hair type specification. To test if Sox2 and Sox18 synergistically regulate hair development, the 〖Sox2〗^(Ysb/Ysb);〖Sox18〗^(-/-) mutants have been generated. Hair morphogenesis and differentiation were impaired; while the number of tertiary hair was increased with reduced number of secondary hair, which phenocopied that of Sox2 mutants. In conclusion, the results suggest that Sox2 and Sox18 functions synergistically on the regulation of hair growth and differentiation. / published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

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This study evaluated the perceived impact of cigarette advertisement on smoking habit among students in selected Nigerian universities. It also investigated the influences of age and significant others on the students’ smoking habit as well as the relationship between cigarette advertisement and rate of smoking. Data were collected using structured questionnaires. The sample consisted of 566 smokers (503 males and 63 females) selected from among students of six universities in southwest Nigeria. Data obtained were subjected to both descriptive and inferential analyses using the Statistical Package for the Social Sciences (SPSS). Simple regression analysis, analysis of variance (ANOVA) and t- test were used to examine five hypotheses formulated for the study. The study showed a significant impact relationship between cigarette advertisement and motives for smoking ( =0.279; t =. 6.179; p< 0.001) and also between smokers’ perception of the health hazards associated with cigarette smoking and rate of smoking (t (514) = 4.469, p< 0.001). Smokers’ age and influence of significant others had substantial impact on their motive for smoking ( = 0.348; t = 5.99; p< 0.001; F(4,463) = 2.642; p<0.05). There was however, no significant relationship between cigarette advertisement and rate of smoking ( = 0.026; t= 0.581; p>0.562). The study concluded that cigarette advertisement had significant impact on cigarette smoking habit among students in Nigerian universities. The findings are discussed in the light of its implications for designing smoking intervention programmes targeted at youths.

This study evaluated the perceptions of Nigerian university students concerning the influence of cigarette advertisement on their smoking habit. It also assessed the influences of smokers’ age and significant others on their smoking habits. Data were collected using structured questionnaires and focus group discussion (FGD) technique from 566 smokers (503 males and 63 females) selected from among students of six universities in south- western Nigeria. Information obtained from the FGD was analysed qualitatively and presented in this study. Specifically, responses from the FGD was analysed based on the following: History of student’s smoking habit, perceived smoking benefits, health hazards of smoking, advertisement and smoking, roles of families, friends and peers in preventing or promoting smoking habit and attitudes of smokers towards anti-smoking regulations in the country. The study concluded that cigarette advertisement had substantial influence on smoking habit among students in the Nigerian universities. Implications of the findings for designing smoking intervention programmes targeted at the youth are discussed.

ABSTRACT This study evaluated the perceptions of Nigerian university students concerning the influence of cigarette advertisement on their smoking habit. It also assessed the influences of smokers’ age and significant others on their smoking habits. Data were collected using structured questionnaires and focus group discussion (FGD) technique from 566 smokers (503 males and 63 females) selected from among students of six universities in south- western Nigeria. Information obtained from the FGD was analysed qualitatively and presented in this study. Specifically, responses from the FGD was analysed based on the following: History of student’s smoking habit, perceived smoking benefits, health hazards of smoking, advertisement and smoking, roles of families, friends and peers in preventing or promoting smoking habit and attitudes of smokers towards anti-smoking regulations in the country. The study concluded that cigarette advertisement had substantial influence on smoking habit among students in the Nigerian universities. Implications of the findings for designing smoking intervention programmes targeted at the youth are discussed.

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