published_or_final_version / Medicine / Master / Master of Medical Sciences

published_or_final_version / Public Health / Master / Master of Public Health

Introduction: Intervertebral disc (IVD) degeneration is suggested to begin from the nucleus pulposus (NP). Evidence from various studies highlights mesenchymal stem cells (MSC), in most cases using bone marrow derived MSC, as a potential stem cell source for NP regeneration. However MSC can be isolated from many sources with various characteristics. There are indications that fetal or close to fetal tissue sources contain MSC with relatively undifferentiated phenotype with respect to MSC from adult sources. Moreover, umbilical cord (C)-MSC may have better chondrogenic differentiation potential than bone marrow (B)-MSC. We hypothesize CMSC are different from BMSC, and more efficient than BMSC in stimulating NP regeneration. Methods: MSC were isolated from human bone marrow and umbilical cord with corresponding ethical approval. BMSC and CMSC were characterized for cell surface marker expression profile and differentiation potential.. RT-PCR of interest genes in NP cells isolated from scoliosis and degenerate discs was performed to search for NP degeneration indicators. Conditioned media (CM) was collected from confluent MSC monolayer, and used for stimulation of four batches of degenerated NP cells isolated from human degenerative intervertebral discs. Cell proliferation and cytotoxicity were assessed by MTT assay. Proteoglycan content were measured by DMMB assay. Gene expression of a series of degeneration related molecules including ACAN, SOX9, CDH2, CD55, KRT19, KRT18, FBLN1 and MGP, and fibrosis related molecules, including MMP12, HSP47, COL1A1, COL3A1 and FN1, of NP cells in MSC-CM were determined by real- time RT-PCR. All results were normalized to the control cells in basal medium. The expression of discogenic, chondrogenic and osteogenic markers on BMSC and CMSC were compared by RT-PCR. Results and Conclusion: CMSC were similar to BMSC and fulfilled the minimum criteria of MSC, however the expression of CD146, CD106 and Stro-1 was different, and BMSC had a spontaneous osteogenesis tendency while CMSC expressed chondrogenic marker even without TGF-beta stimulation. BMSC demonstrated a paracrine effect on modulating human degenerated NP cells towards a non-degenerative phenotype in stimulating cell proliferation, slightly enhancing proteoglycan production, upregulating KRT19 while downregulating MMP12. Compared with BMSC, a higher paracrine effect of CMSC was disclosed in modulating the phenotype of NP cells in all aspects tested, and an intrinsic higher expression on CMSC of ‘potential NP markers’, including KRT19, KRT18 and CD55, but lower expression of osteogenic markers, including RUNX2 and ALPL, was revealed, which indicate a higher potential of CMSC for future clinical application to treat IVD degeneration diseases. KRT19 and MMP12 were also confirmed to be the highest differentially expressed candidate genes between cultured scoliosis and degenerated human NP cells, indicating a high indicator potential of NP degeneration. Furthermore, a subpopulation was detected in the degenerated NP cells that possessed macrophage-like phenotype and activities, which may play a role in the pathogenesis of IVD degeneration. In conclusion, studies in this thesis highlighted CMSC as a superior source than BMSC for IVD repair. Further investigations into the active agents in the conditioned media and the signalling pathway may help to elucidate the mechanism of the effect. / published_or_final_version / Orthopaedics and Traumatology / Doctoral / Doctor of Philosophy

Acute glaucoma is an ocular emergency and sight -threatening disease which is caused by a sudden increase in intraocular ocular pressure (IOP) due to blockage of aqueous humor outflow. Acute glaucoma can result in permanent loss of visual acuity and visual field (VF). Prophylactic or therapeutic medicine is rare for acute glaucoma. In animal studies, a well-established model to investigate this acute IOP spike is by fluid infusion and adjustment of the fluid level to induce high IOP within a few seconds. However, there is no blockage of aqueous outflow and the increase in intraocular pressure is unrealistically rapid. To mimic the IOP profile in human acute glaucoma attack, we propose the use of an ophthalmic viscosurgical device (OVD), Healon 5 (AMO, Santa Ana, CA, USA) which is injected intracamerally to block aqueous outflow. The IOP is allowed to increase naturally inside the globe. We found that Healon 5 can induce an acute elevation in IOP with very similar characteristics to those observed in humans. For example, the IOP profile during the attack, changes in the anterior segment and retinal nerve fibre layer (RNFL) thinning are all consistent with findings in human acute angle closure glaucoma (AACG). We believed that our new model can more accurately reflect acute glaucoma than other animal models. Based on these findings we further tested the neuroprotective effect of Lycium barbarum polysaccharides (LBP) on retinal neurons against an acute rise in IOP (attack) with the new model. L. barbarum is an herb that has been used in Chinese medicine for thousands of years. The fruit of this plant is believed to be good for the health of the eyes. In our study we found that oral administration of LBP preceding an acute glaucoma attack can preserve the visual function of the animals despite the loss of neurons in the retinal ganglion cell layer (RGCL). L. barbarum intake seems to inhibit secondary cell death and progression of the disease. In conclusion, we had successfully established a new acute glaucoma attack animal model by intracameral injection of Healon 5. This model more closely resembles the condition observed in human acute glaucoma. We also found that LBP has a prophylactic neuroprotective effect against an acute glaucoma attack in animals. It can protect the visual function and possibly inhibit secondary cell death. Oral consumption of LBP as a health supplement may provide extra benefit to people who are at high risk of developing acute glaucoma, in addition to the protective effects of LBP against other diseases. / published_or_final_version / Anatomy / Master / Master of Philosophy

Hong Kong’s compacted urban form brings about potential problems including mental illness. Meanwhile stressful life mainly originates from working pressure brought a lot of physical and mental problems for the people themselves and generating serious family and social problems. As more and more people start to aware mental health issue, the current mental health services system is no longer sustainable due to increasing number of patients. This thesis aims to excavate the potential for landscape to become element in healthcare delivery in the context of community as following: refine the definition of therapeutic landscape, define the scope of work, and identify components essential for therapeutic environment. Last but not least, dig out possible interpretation/physical form through set an example of a particular design introduce for a typical site. Therapeutic landscape which introduce to community recreation system will become a new approach to backup mental health service system as well provide people more convenient and broad healthcare service to cultivate healthy personality. Thus promote community organic development to become a thoughtful and institutional environment. / published_or_final_version / Architecture / Master / Master of Landscape Architecture

The overall objective of this thesis was to test the hypothesis that through developmental programming maternal overnutrition-induced metabolic derangements in the offspring could be offset by supplementing the maternal diet with green tea epigallocatechin gallate (GTEG). The obesogenic diet was a high-fat (HF, 30%) diet. Female Sprague-Dawley rats were fed the HF, low-fat (LF, 7%) or HF diet containing 0.75% or 1.0% GTEG (GT1, GT2) from before conception and throughout gestation and lactation. Both doses of GTEG significantly improved metabolic control of the HF-fed lactating dams. The weaned male pups received the HF, GT1 or GT2 diet forming 6 dam/pup groups: LF/HF, HF/HF, HF/GT1, HF/GT2, GT1/HF and GT2/HF. At wk 13 they had similar weight but insulin resistance index (IRI), serum non-esterified fatty acid (NEFA) and liver triglyceride of rats born to GTEG dams was 57, 23 and 26% lower and accompanied by improved gene/protein expressions related to lipid and glucose metabolism compared to HF/HF rats (P < 0.05). Although the HF/GT1 and HF/GT2 rats had lower serum NEFA, their serum insulin and IRI remained comparable with the HF/HF rats. To determine if there is a critical time period for the actions of GTEG, in the second experiment female rats were fed the LF, HF, or GT1 diet prior to conception and throughout gestation. During lactation, half of the dams had their diet switched from HF to GT1 and vice versa. Pups were weaned to the HF or LF diet, forming the LF/LF/LF, LF/LF/HF, HF/HF/LF, HF/HF/HF, HF/GT1/LF, HF/GT1/HF, GT1/GT1/LF, GT1/GT1/HF, GT1/HF/LF and GT1/HF/HF groups. Metabolic controls of dams given GT1 during gestation or lactation were improved compared with the HF/HF dams (P < 0.05). Three-way ANOVA revealed that 22 wk old offspring born to dams fed the HF diet during gestation had higher serum and muscle triglyceride (TG) concentration and lower ferric reducing ability of plasma (FRAP) (P < 0.05), all of which were reversed by supplementing GT1 to the gestational diet. Oral glucose tolerance at wk 15 was improved in those offspring born to dams given GT1 supplementation during lactation (P < 0.05). The increased serum NEFA concentration and IRI in offspring of dams fed the HF diet during gestation or lactation were reversible upon GT1 supplementation during either time period (P < 0.05). These rats (HF/GT1/HF, GT1/GT1/HF and GT1/HF/HF) had similar level of hepatic insulin receptor gene expression as well as protein abundance for muscle glucose transporter 4 and hepatic sterol regulatory element binding protein-1c but lower protein mass for hepatic glucose-6-phosphatase (P < 0.05) compared with the LF/LF/HF rats. Hence, maternal overnutrition-induced metabolic derangements in male offspring are reversible through supplementing GTEG to the maternal diet during gestation or lactation and this approach is more effective than giving GTEG to offspring born to overnourished mothers. Offspring metabolism could be programmed via manipulations of the maternal diet. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

The relationship between fructose consumption and metabolic diseases has drawn substantial attention in recent years. Dietary fructose consumption has climbed dramatically in the past 40 years, and this trend coincides with the prevalence of obesity and diabetes worldwide. In rodents, maternal obesogenic diets are associated with higher risks of metabolic derangement later in life whereas bitter melon (BM) supplementation has been shown to improve blood glucose and lipid profiles. The overall objective of this thesis was to test the hypothesis that through developmental programming metabolic derangement in offspring born to rat dams fed a high-fructose (F) diet could be offset by the addition of BM to the maternal diet. Virgin female rats received a control (C), F (60%) or BM-supplemented F (FBM,1%) diet 8 weeks before conception and throughout gestation and lactation. Weaned male offspring consumed C diet (C/C,F/C,FBM/C) for 11 weeks. The concentrations of serum insulin, triglyceride, free fatty acid (FFA), and hepatic lipids in FBM/C offspring matched that in C/C offspring and were significantly lower than F/C offspring. These phenotypic changes were accompanied with suppressed hepatic lipogenic gene expression but enhanced expression of lipid oxidation-related genes. In the second experiment, we extended the earlier findings by examining whether adding BM to F-fed dams would still benefit offspring if they continued to consume the F diet postweaning. This simulates the scenario in affluent societies where fructose overconsumption may occur in two consecutive generations. The dose-response effect of BM at doses of 0.85% (FBM1) and 1% (FBM2) was also examined. Male offspring born to dams fed the C, F, FBM1 or FBM2 diet were weaned to C or F diet (C/C,C/F,F/F,FBM1/F,FBM2/F) for 20 weeks. BM normalized the serum FFA elevation observed in F/F offspring, although hyperinsulinemia remained in FBM1/F and FBM2/F offspring. The altered liver lipid profile and its molecular changes observed in F/F offspring were ameliorated by maternal BM supplementation. Lower adipose expression of mesoderm-specific transcript, hormone sensitive lipase, sterol regulatory element-binding transcription factor 1, and peroxisome proliferator-activated receptor-gamma (PPARγ) and PPARγ-target genes in FBM1/F and FBM2/F offspring indicated that BM could reduce adipocyte size as well as lower lipolysis and lipogenesis. Since FFA stimulates reactive oxygen species generation that enhances cellular stress, oxidative stress and inflammation in offspring of two-generation F exposure with or without maternal BM supplementation were examined. FBM1/F and FBM2/F offspring showed reduced lipid peroxidation but enhanced antioxidant capacity in the liver. BM suppressed the expression of proinflammatory genes and phosphorylation of c-Jun amino terminal kinase1, as well as promoted insulin receptor substrate 1 protein expression. These BM-mediated antioxidant and anti-inflammatory effects may be associated with a reduction of circulating FFA. Taken together, the data support the concept of developmental programming as maternal fructose clearly induced dyslipidemia, adipocyte dysfunction, oxidative stress and inflammation in offspring. That these abnormalities were largely reversed by adding BM to the maternal diet suggests that perinatal BFC supplementation could alter the course of maternal malnutrition-induced metabolic defects later in life. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

Low back pain (LBP) is a common complaint and health problem in Hong Kong, particularly among middle-aged individuals. LBP is the main cause of chronic disability which significantly affects the daily life activities of patients. Pain might result in repeated hospital admissions and subsequently increase the burden on health care providers in Hong Kong. LBP has an enormous effect on quality of life and therefore deserves research attention. Growing evidence shows that yoga may help reduce the level of chronic LBP in adult patients. However, no systematic review has been conducted to support the translation of this theory into practice. Therefore, this thesis aims to evaluate the current evidence on the efficacy of yoga in reducing chronic LBP among adult patients to achieve the following objectives: formulate an evidence-based protocol on yoga practice, assess the implementation potential of the formulated protocol, and develop implementation strategies and evaluation plan for the use of this protocol in a local public hospital in Hong Kong. Five databases were used for the systemic review of relevant studies. These databases were those of Cochrane Library, CINAHL Plus, PudMed, British Nursing Index and Medline (Ovid). A total of eight papers (randomized controlled trials) fulfilled the inclusion criteria of this study. The Scottish Intercollegiate Guidelines Network (SIGN) was used to extract the data and evaluate the paper quality. The findings of the selected papers indicated that yoga practice has a significant effect on reducing pain among adult patients with chronic LBP. The innovation is proposed to be conducted in an adult orthopedic and traumatoloy (O&T) ward. Evidence-based yoga guideline is developed to guide nurses in the effective implementation of the protocol. The SIGN grading system is chosen to grade the recommendations in the guideline. Adult patients with persistent LBP longer than three months are the target population. All study participants practice specific yoga postures under the supervision of yoga instructors and trained nurses in the outpatient clinic. These patients continue home practice for 30 minutes daily or at least twice a week. Based on the findings of the reviewed literatures and the adaptation of these findings into the proposed innovation, the feasibility of implementing evidence-based yoga guideline in the local clinical setting in Hong Kong is demonstrated. An effective communication plan is developed to gain support from stakeholders and efficiently implement the innovation. A two-month pilot study is designed to test the feasibility of the guideline. Pain level, which is the primary outcome of the study, is measured by using Pain Numerical Pain Scale (NRS). Evaluation will be completed after the pilot test and at the end of the whole programme and refinement of the protocol will be accomplished according if necessary. Protocol effectiveness will be determined by a decrease in back pain level after practicing yoga. Other outcomes include the knowledge and satisfactory level of the staff with regards to the protocol, as well as and the costs and benefits of program implementation. / published_or_final_version / Nursing Studies / Master / Master of Nursing

Liver is one of the most important organs in the body that maintains the homeostasis of metabolism, immunity, detoxification and hematopoiesis. A large number of acute and chronic intoxications and diseases can influence the normal functions of the liver, leading to irreversible liver damage and even cancer. Currently, applying herbs or herbal derivatives in the prevention and therapy of acute and chronic liver injury receive numerous attentions since they hold great potentials as food supplements in the treatment strategy of liver injuries. There were two major hypotheses of this current work namely: a)In CCl4-inducedacute liver injury animal model, whether pre-treatment with garlic derived S-allylmercaptocysteine (SAMC)or Wolfberry derived Lycium barbarum polysaccharides (LBP)could reduce liver injury, oxidative stress and inflammation partly through a NF-κB-dependent pathway. SAMC or LBP could also promote liver regeneration after acute damage. b)In non-alcoholic steatohepatitis (NASH)-induced chronic liver injury animal model, whether administration of SAMC or LBP along with high-fat diet induction could attenuate liver injury, lipid metabolism dysfunction, fibrosis, oxidative stress, inflammation, apoptosis and transcription factors activities in the liver. In this study, SAMC and LBP were applied in a carbon tetrachloride (CCl4) induced mice acute liver injury model and a high-fat diet induced non-alcoholic steatohepatitis model. In the acute model, an eight-hour CCl4treatment induced severe acute liver injury. Pre-treatment with SAMC or LBP (1) attenuated hepatic histological injury; (2) reduced serum ALT level; (3) ameliorated oxidative stress; (4) reduced expression of inflammatory mediators and chemokines; (5) promoted liver regeneration; and (6) decreased NF-κB activity. Vehicle-treated SAMC or LBP did not exhibit obvious adverse effects on healthy mice. In the chronic NASH model, when compared with control rats, NASH rats showed typical clinical features of human NASH patients, including increased liver injury, lipid content, oxidative stress, inflammation, and apoptosis. In comparison, SAMC or LBP co-treated NASH rats showed (1) reduced fat accumulation, cellular necrosis, collagen formation, as well as reduced serum ALT and free fatty acids levels; (2) restored insulin resistance related kinase phosphorylation status which had been altered during NASH; (3) reduced pro-fibrogenic factors; (4) restored antioxidant enzymes, as well as attenuated end-products of lipid peroxidation and NO production through a cytochrome P450 2E1-dependent pathway; (5) reduced hepatic pro-inflammatory mediators and chemokines production; (6) diminished activities of nuclear transcription factors (NF-κB and AP-1); and (7) ameliorated hepatic cellular apoptosis through a p53-dependentpathwaywhich was under the regulation of LKB1/AMPK axis and PI3K/Akt axis. In conclusion, our data demonstrated that SAMC or LBP consumption protects the liver from acute injury caused by CCl4and chronic damages caused by a high-fat diet. These effects were mainly mediated by the amelioration of hepatic oxidative stress, inflammation, and cell death. In the NASH model, SAMC or LBP also improved hepatic lipid metabolism, fibrosis, and apoptosis. Therefore, the present study proposed that both garlic and Wolfberry, which are novel hepatoprotective herbal products, can be taken as part of the daily dietary supplements in the prevention of acute and chronic liver injury. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Introduction: Early childhood caries (ECC) is common among Hong Kong preschool children. It is a disease caused by dental plaque bacteria and may be controlled by good toothbrushing habits. However, preschool children are often too young to perform effective tothbrushing, and therefore parental toothbrushing is recommended for them. The oral hygiene status of Hong Kong preschool children is usually not good and parental toothbrushing is not common. Fluoride varnish is effective in preventing dental caries in school children and adolescents but its effectiveness in preventing dental caries in preschool children is still inconclusive. Objective: To investigate the effectiveness of hands-on training in parental toothbrushing, with or without semi-annual applications of a 5% sodium fluoride varnish in preventing ECC. Methods: Children aged 8-23 months were recruited and randomly allocated to one of three groups: Group 1 - positive control, a brief oral health education to parents; Group 2 - oral health education to parents, hands-on training in parental toothbrushing, and home visits every six months to reinforce parental toothbrushing; Group 3 - application of a 5% sodium fluoride varnish onto the child’s teeth during home visits in addition to the intervention provided to Group 2. Clinical examination of the children and a questionnaire survey of the parents were conducted at baseline. Interventions for the children and parents were delivered according to their group assignment. Evaluation of the main outcome, development of new dental caries, was conducted after 24 months through clinical examination. Information on children’s oral health-related behaviors and parents’ knowledge of and attitude towards their child’s oral health was collected using a questionnaire at the 24-month follow-up. Results: Out of the 450 children recruited at baseline, 415 (92%) children were examined after 24 months and all examined children’s parents completed the questionnaire. Including both noncavitated and cavitated carious lesions, the incidences of ECC in Gp1 to Gp3 were 11.9%, 11.8%, and 17.5%, respectively (p > 0.05) and; the mean dmfs scores in Gp1 to Gp3 were 0.3, 0.2, and 0.4, respectively (p > 0.05). Proportions of parents who practiced parental toothbrushing twice a day were 62.7%, 60.4%, and 65.7% in Gp1, Gp2, and Gp3, respectively (p > 0.05). Results from a logistic regression analysis showed that children who were older, who had poorer oral hygiene, who had high frequency of sugary snack intake, who had visited a dentist during the study, and whose parents had lower education level would have a higher chance to develop new dental caries during the 24-month study period. Conclusion: Hands-on training in parental toothbrushing, reinforced by face-to-face interview every 6 months, with or without a semi-annual application of 5% sodium fluoride varnish, may not have any additional effect on preventing development of dental caries in young children compared to the standard oral health education provided to parents in Hong Kong. The child’s socio-demographic background, oral hygiene status, and frequency of sugary snack intake are related to ECC. / published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy