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No description available.

Adherence to antipsychotic medication in schizophrenia has been shown to predict symptom exacerbations; however, adherence remains poor in this population. The concept of taking medication on a maintenance regime is an example of prospective memory (PM). The current investigation is comprised of three studies in which 59 outpatients diagnosed with schizophrenia completed a comprehensive assessment including measures of PM, executive functioning, comprehension of medication instructions, insight into the need for medication, and environmental variables supporting adherence. An objective measure of medication adherence was also collected during a one-month baseline period. In study 1, medication adherence was conceptualized as a PM task and variables for predicting adherence based on PM literature were examined. Of the hypothesized variables, the interactive effect of PM ability and comprehension of medication instructions was the only predictor of adherence to antipsychotic medication. Comprehension of medication instructions alone was the only predictor of adherence to total psychotropic medication regime. Study 2 investigated the role of executive functions in the awareness of PM deficits and use of compensatory strategies. Results indicated that patients with poorer executive skills were less reliable in their report of PM ability compared to performance on PM measures. However, both fair and poor executive functioning groups reported similar use of compensatory strategies. Lastly, the third study manipulated the specificity of retrieval context for a 5-day habitual PM task intended to mimic medication-taking. The aim of this investigation was to examine the effect of retrieval context specificity and executive functioning on task performance. Results demonstrated that patients categorized as fair executive functioning completed significantly more days of the habitual task than patients categorized as poor executive functioning. There was no difference in performance between patients receiving greater retrieval context specificity versus patients receiving a general context. However, there was a trend for individuals with fair executive functioning to benefit from greater retrieval context specificity, implying that a minimum level of executive skill may be necessary for individuals to recognize the risk of a restricted retrieval interval and/or mobilize additional resources for encoding. Clinical implications are discussed. / text

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Public Health / Master / Master of Public Health

Hepatocellular carcinoma (HCC) is the fifth most common malignancy and the third leading cause of cancer related death worldwide. Chemo-therapy has been commonly used to treat unresectable HCC but with limited efficacy. Therefore, there is an urgent demand for the development of better therapeutic approaches. Granulin-epithelin precursor (GEP) is a novel growth factor with over-expression in more than 70% of HCCs and has been demonstrated as potential therapeutic target. The aims of this study are to examine the role of GEP in chemo-resistance and the therapeutic potential of GEP antibody therapy in combination with chemo-therapy in HCC. The role of GEP in HCC chemo-resistance has been examined by HCC in vitro models in the first part of the study and by in vivo human HCC xenograft models in immunocompromised mice in the second part of the study. It was shown that the chemo-therapeutic agents selected HCC cells in vitro and in vivo resulted in increased cellular expression of GEP, ABCB5, hepatic cancer stem cell (CSC) marker CD133/EpCAM positive populations and demonstrated enhanced CSCs properties including colony formation ability and chemo-resistance. Over-expression and knockdown of GEP expressions respectively demonstrated that GEP levels were important in conferring resistance to the chemo-therapeutic agents and the drug-induced apoptosis. GEP antibody therapy not only sensitized the parental HCC populations but also the chemo-resistant subpopulations to chemo-therapy induced apoptosis. Importantly, combination of GEP antibody therapy with chemo-therapy inhibited the chemo-therapy induced GEP, ABCB5 and heaptic CSCs marker over-expression through neutralization of the secretary GEP levels in the culture supernatant, and the serum GEP levels in the HCC orthotopic mice model. In human HCC xenograft models, GEP antibody treatment alone is consistently able to inhibit the tumor growth, but is unable to eliminate the established intrahepatic tumor. Cisplatin treatment, low and high dose respectively, was only able to eradicate a fraction of the intrahepatic tumor and the residual tumors grew aggressively after chemo-drug withdrawal. Combination of GEP antibody with low dose of cisplatin resulted in significant proliferation inhibition and apoptosis induction respectively. Importantly, combination of GEP antibody with high dose of cisplatin resulted in eradication of all established intrahepatic tumor. In addition, chemo-therapy induced the Akt/PKB and MEK/ERK prosurvival pathways, disturbed the balanced between the ratio of pro-apoptotic (Bax) to anti-apoptotic (Bcl-2) member through the induction of Bcl-2. Nonetheless, combination GEP antibody therapy suppressed the chemo-therapy induced phosphorylation of PDK1, Akt, MEK, ERK, and Bcl-2 levels. It was shown that Wortmannin, the PI3K/Akt inhibitor, suppressed the expression of ABCB5 and Bcl-2 induced by chemo-therapy but showed no effect on GEP expression levels. In summary, the study demonstrated the chemo-therapy treatment alone induced the expression of growth factor GEP, drug transporter ABCB5, hepatic cancer stem cell markers expressions, and the residual cancer cells showed enhanced CSCs properties. Combination treatment with GEP antibody reversed the signaling and cancer stem cell properties induced by chemo-therapy alone. Therefore, further investigations of this combination treatment approach may lead to the development of novel therapeutic approach for the clinical treatment of chemo-resistant HCC. / published_or_final_version / Surgery / Doctoral / Doctor of Philosophy

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published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / abstract / toc / Zoology / Master / Master of Philosophy

published_or_final_version / Biochemistry / Master / Master of Philosophy