published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

published_or_final_version / Nursing Studies / Master / Master of Nursing in Advanced Practice

published_or_final_version / Community Medicine / Master / Master of Public Health

published_or_final_version / Nursing Studies / Master / Master of Nursing

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

Obesity is closely related to many medical complications such as type 2 diabetes, hypertension and heart failure. Obesity and other factors, including elevated blood glucose levels, hypertension, and dyslipidemia, constitute a constellation of symptoms known as the metabolic syndrome, which are the risk factors for coronary artery disease. Lipocalin-2 is a pro-inflammatory adipokine causally involved in the development of obesity-associated metabolic and cardiovascular diseases. Recent clinical and experimental evidences demonstrate an association between augmented circulating lipocalin-2 and cardiac dysfunction. However, little is known about the detailed roles of lipocalin-2 in regulating pathophysiological functions of the heart. The present study was designed to compare the heart functions of mice with normal (WT) or deficient lipocalin-2 (Lcn2-KO) expression and to examine the molecular mechanisms underlying lipocalin-2-mediated deteriorated effects in hearts. Echocardiographic analysis revealed that the myocardial contractile function was significantly improved in hearts of Lcn2-KO mice, under both standard chow and high fat diet conditions. The heart function before and after I/R injury (20-min of global ischemia followed by 60-min of reperfusion) was assessed using the Langendorff perfusion system. Compared with WT littermates, hearts from Lcn2-KO mice showed improved functional recovery and reduced infarct size following I/R. These phenomena can be observed in mice under both standard chow and high fat feeding conditions. Under baseline condition, the mitochondrial function of hearts from Lcn2-KO mice was significantly enhanced, as demonstrated by biochemical analysis of respiratory chain activity, markers of biogenesis and oxidative stress, as well as electron microscopic investigation of the mitochondrial ultrastructure. Acute or chronic administration of lipocalin-2 impaired cardiac functional recovery to I/R and dampened the mitochondrial function in hearts of Lcn2-KO mice. These effects were associated with an extensive modification of the fatty acyl chain compositions of intracellular phospholipids. In particular, lipocalin-2 facilitated the redistribution of linoleic acid (C18:2) among different types of phospholipid, including cardiolipin, which is exclusively located in the mitochondria inner membrane. The direct effects of lipocalin-2 on both H9c2 and NCM cells were also examined. TUNEL assay and flow cytometry analysis demonstrated that lipocalin-2 treatment promoted apoptosis in cardiomyocytes. Lipocalin-2 induced an early phase of phosphatidylserine exposure, followed by Bax-translocation and caspase-3 cleavage. The results collectively suggested that lipocalin-2 initiated the intrinsic mitochondria-mediated apoptotic pathway. In the hearts of Lcn2-KO mice, significantly reduced number of apoptotic cells was observed after I/R injury. In conclusion, lacking of lipocalin-2 improved heart function recovery during I/R injury via mitochondrial function restoration, phospholipids remodeling, and inhibition of cardiomyocytes apoptosis. / published_or_final_version / Pharmacology and Pharmacy / Doctoral / Doctor of Philosophy

Background: Liver transplantation is a curative method for end-stage liver diseases, small unresectable hepatocellular carcinoma and acute liver failure. The discovery of immunosuppressive drugs increases the survival rate of liver transplanted recipients by reducing the incidence of graft rejection. Several complications such as renal dysfunction and increase risk of malignancy result from life-long treatment of transplanted recipients with immunosuppressant. If recipients are over-immunosuppressed, the risk of infection might be increased. On the other hands, if recipients are under-immunosuppressed, the risk of rejection would be increased. It should be useful if a test or a bio-marker that could predict and differentiate infection and rejection in transplanted recipients. Therefore, patients could be treated before adverse conditions. Although therapeutic drug monitoring has been performed as a routine test, it is mainly targeted for minimizing drug toxicity but little help in predicting infection and rejection. A new assay named Cylex? Immuknow? assay is designed to measure global cell mediated immunity of immunosuppressed population, by quantifying the amount of ATP synthesis by CD4+ T cells in response to PHA stimulation. It is undergoing evaluation in assessing the immune status of patients in order to predict the risk of infection and rejection, and also other conditions. (1, 2) Objectives: In this pilot study, we would like to evaluate ImmuKnow for predicting the risk of infection and rejection in liver transplanted recipients in Hong Kong. Methods: Blood samples were collected from liver transplanted recipients at different time intervals. The immune cell response of these patients was measured by Immuknow assay. Patients with low immune response might have a high risk of infection, patients with high immune response might have a high risk of rejection, and patients with moderate immune response should be clinically stable. Results and conclusion: Twenty-six blood samples were collected from eight transplanted recipients. The average Immuknow assay value for the post-transplant samples was 304.6 ng/mL ATP which represented moderate immune cell response according to the interpretation table. (Table 3) This was reasonable as the subjects were all clinically stable by well-controlled immunosuppression. The result was consistent with other studies. (1, 3) However, the association between low immune cell response and infection, and the association between high immune cell response and graft rejection could not be investigated as both of these conditions were not found in this pilot study. A larger study including episodes of infection and rejection should be conducted in order to evaluate the value of Immuknow assay more completely. / published_or_final_version / Pathology / Master / Master of Medical Sciences

Silicone oil (SO) is widely used as the long-term intraocular tamponade in treating various eye diseases such as complicated retinal detachment, proliferative vitreoretinopathy, proliferative diabetic retinopathy, giant retinal tear and ocular trauma. However, its propensity to emulsify is an inherent problem of its long-term use in-vivo. Dispersal of SO into many tiny oil droplets causes numerous complications such as inflammation, glaucoma and reproliferation. It may also be responsible for possible toxicity to both retina and optic nerve. Emulsification is one of the problems associated to the use of SO as a long-term intraocular tamponade. This study focused on the understanding on the physical nature and formation of in-vivo SO emulsion and the development of methods to reduce the complications associated with emulsification of SO by engineering approaches. A stepper motor driven mechanical platform was built to study the fluid flow of SO within an eye model chamber during eye-like movements and a quantitative method was established to study SO emulsification, both in-vivo and in-vitro. This method was used to compare the relative resistance of different SO against emulsification. In the last part of the thesis a novel rinse was proposed which aimed at removing the emulsified SO droplets in-vivo in an effective way. In the dynamic eye model experiment, both the increase in shear viscosity of SO and the extent of SO fill had an effect in reducing the shear. These effects were small compared to the effect of indents at reducing shear rate during eye-like movements. When SO emulsions from patients were analyzed it was found that over 90% of the emulsified droplets were outside the observable range under slit-lamp biomicroscopy. When the emulsification resistance of SO was tested using the quantitative method the result confirmed that SO with high-molecular-weight component (HMWC) was more emulsification resistant than SO with the same shear viscosity. The addition of HMWC increases the elasticity and thus increasing its resistance against emulsification. A novel rinse was also proposed to remove the emulsified droplets using physical phenomenon of double emulsification. To conclude, this study improved the understanding of the formation of SO emulsification. The clinical observable emulsified droplets are probably in all cases that was just the tip of the iceberg. Three practical suggestions were made: Firstly, the use of SO and encircling scleral buckling procedure in combination might reduce the shear rate. Secondly, the use of HMWC can reduce emulsification. Lastly, there may be a role in rinsing out the emulsified droplets using the proposed novel solution. The novel solution is going to fully developed and commercialized in the near future. / published_or_final_version / Ophthalmology / Doctoral / Doctor of Philosophy

Background Findings for the association of prenatal maternal infections and schizophrenia are inconsistent. Whether specific maternal infections may contribute to central nervous system dysfunction, like schizophrenia remains unknown. Thus, a systematic review is conducted to clarify the role of infections on the pathogenesis of schizophrenia. Methods A manual and electronic search of the literature for prenatal maternal infection at the individual level and the diagnosis of schizophrenia in offspring was conducted. All the included studies are searched from PubMed and EMBASE databases and generally based on population level datasets with cohort or nested case-control studies designs. We only focus on three kinds of maternal infections in the review (i.e. influenza pandemic, rubella and Toxoplasmosis), other infections such as herpes simples, varicella‐zoster virus and polio were excluded. Positive family history of psychotic illness was excluded as genetic disposition is established as a strong risk factor of developing schizophrenia in offspring. Results Fifteen studies were included in this systemic review. Nine (60%) of these studies reported a positive association between maternal infections and the development of schizophrenia in the later lives of their offspring, while six (40%) of these studies indicated that there is no significant difference among cases of schizophrenia in maternal infections exposure and the control subjects or no association between schizophrenia in offspring and the infections during pregnancy as the exposure. Among all the studies, thirteen cohort studies and two nested‐case studies were examined. Eight (61.5%) showed a positive association, meanwhile five (38.5%) showed a null association. Two nested‐case control studies both suggested that maternal infection exposure is a risk factor for schizophrenia. Conclusion Findings for the association of prenatal maternal infections and schizophrenia are not equal to the evidence for causation. Due to the absence of external validity due to small and non‐representative samples, selection bias was suspected even with a significant result. Additionally, multiple exposures were hard to testify during pregnancy. Even we adjusted for the measured confounders, residual confounding such as genetic disposition and socioeconomic status, as well as unmeasured confounding are concerns. Quasi-experimental methods may help improve causal inference such as the use of instrumental variable analysis in future studies. Preventive strategies such as immunizations need to be deliberated carefully to weight the benefit and the potential impact. / published_or_final_version / Public Health / Master / Master of Public Health

published_or_final_version / Surgery / Master / Master of Surgery