Retinal degenerative diseases are diseases that may severely affect vision of people at different ages. These include retinitis pigmentosa (RP) and age-related macular degeneration (AMD). The current treatments for these diseases are limited. Since dysfunction and atrophy of the RPE are the key factors in the development of retinal degenerative diseases, transplantation of healthy retinal pigment epithelial (RPE) cells might be a promising therapeutic strategy. However, homologous RPE cells may lead to host immune rejection and harvesting autologous RPE cells may cause severe complications. Autologous iris pigment epithelial (IPE) cells, which are relatively easy to obtain, possess the same embryonic origin and share similar characteristics as RPE cells. Therefore, they may be used as a substitute of RPE cells for transplantation. Increasing interests have been demonstrated with the use of substrate to support cell attachment, proliferation and differentiation, so that transplanted cells could maintain the differentiated phenotype and perform their normal functions. However, degradation of biodegradable substrates may cause the breakdown of functional cell monolayer and produce toxic byproducts. Therefore, the aim of current study is to investigate the in vitro characteristics of rat IPE cells cultured on surface modified non-degradable expanded-polytetrafluorethylene (ePTFE) substrates and host response to the substrates without cells. Primary pure IPE cells were successfully isolated from rat eyes, which provided abundant cells for subsequent experiments. IPE cells harvested from both Long Evans rats and Dark Agouti rats proliferated and reached confluence on fibronectin coated n-heptylamine modified (F-HA) ePTFE substrates. These cells exhibited cuboidal or polygonal morphology with heavy pigmentation. In addition to the typical epithelial cell morphology, rat IPE cells grown on F-HA ePTFE substrates were able to form a cell monolayer with functional formation of tight junctional complex between neighboring cells. The IPE cell monolayers also demonstrated increased phagocytosis of photoreceptor outer segments (POS) with time and expression of cellular retinylaldehyde-binding protein (CRALBP) that served an important role in the conversion of all-trans-retinal to 11-cis-retinal in visual cycle. In the in vivo study, F-HA ePTFE substrate was successfully transplanted into the subretinal space of Royal College of Surgeons (RCS) rat, which is a well-recognized animal model of retinal degeneration. The F-HA ePTFE substrate remained flat up to 4 weeks after transplantation and did not induce significant up-regulation of pro-inflammatory cytokines TNFα and IL1β as well as activation of Müller cells and astrocytes which occurred in response to retinal inflammation. In conclusion, rat IPE cells that were grown on F-HA ePTFE substrate were able to establish a monolayer with functional tight junctions and RPE-specific functions. The F-HA ePTFE substrate demonstrated good biocompatibility in the subretinal space of RCS rats. These findings provide a potential therapeutic strategy for retinal degeneration. / published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Protecting and promoting patients’ and families’ sense of dignity at end-of-life is an indispensable goal, one that palliative care professionals have pursued unceasingly in the modern era. While researchers have made several attempts to uncover the intricate meaning and constitution of dignity and dignified end-of-life care in recent years, their works are solely based upon a Western individualistic paradigm that may not be applicable in Eastern collective societies. This limitation underscores that the existing body of knowledge is missing an important articulation on the Chinese experience. Thus, to fill this important knowledge gap, this study has applied ‘micro’, ‘meso’ and ‘macro’ levels of inquiries to attain a holistic understanding of dignity and dignified end-of-life care in the Hong Kong Chinese context. Through meaning-oriented interviews with 18 Chinese palliative terminal cancer patients and 18 of their family caregivers, as well as four interpretive-systemic focus groups with 30 key informants involved in a novel end-of-life care pathway programme (N=66), a total of 31 themes that elucidate dignity and dignified end-of-life care have been generated. These 31 themes are carefully organized into 9 categories that reflect the Individual, Familial and Institutional dimensions of dignity at end-of-life. First, the Individual dimension includes: 1) “Personal Autonomy”, which consists of Regain Control, Self-Sufficiency, Informed Care Decisions and Future Planning; 2) “Family Connectedness”, which consists of Express Appreciation, Achieve Reconciliation, Fulfill Family Obligations and Strengthen Family Bond; and 3) “Spiritual Plasticity”, which consists of Enduring pain, Spiritual Surrender, Moral Transcendence and Transgenerational Unity. Second, the Familial dimension involves: 1) “Social Agency”, which comprises of Caregiving Resources, Caregiver Assertiveness and Communicative Action; 2) “Family Integrity”, which comprises of Mutual Support, Kinship Involvement and Family Adaptability; and 3) “Filial Compassion”, which comprises of Compassionate Duty, Reciprocal Relationship and Emotional Connection. Third, the Institutional dimension entails: 1) “Regulatory Empowerment”, which encompasses Interdisciplinary Teamwork, Resource Allocation, Culture Building and Collaborative Policymaking; 2) “Family-Centered Care”, which encompasses Continuity of Care, Family Conference and Care Partnership; and 3) “Collective Compassion”, which encompasses Devotion in Care, Empathic Understanding, and Compassionate Action. These 9 categories and their respected 31 themes are clearly interrelated and embedded within the political, cultural, and spiritual contexts of society, highlighting the intricate interplay of systemic structure and social discourse for promoting dignity at end-of-life. These findings have further led to the development of the ‘Patient-Family Model of Dignified Care’ and the ‘Interpretive-Systemic Framework of Dignity at End-of-Life’. The former provides a new clinical protocol for identifying and evaluating the strengths and weaknesses within the personal, interpersonal and transpersonal functioning of the patient-family dyads in Chinese end-of-life care. The latter offers a public health roadmap for social change that accentuates the necessity for a collective consciousness of compassion in pushing forth the ultimate ideal of living and dying with dignity in Hong Kong. Based on this body of work, recommendations for patient-family care at end-of-life, expansion of community-based palliative care, and development of palliative long-term-care for ensuring quality and equality in the care of dying patients and their families are discussed. / published_or_final_version / Social Work and Social Administration / Doctoral / Doctor of Philosophy

WHO and UNICEF recommend the use of “ready-to-use therapeutic food” (RUTF) in the treatment of severely acute malnourished (SAM) children with no complicated medical background. This research paper aims to review the evidence on the use of RUTF in the treatment of SAM children, explore the potential issues with the use of RUTF, and provide suggestions for future research. A total of 7 studies were included for the review on the effectiveness of RUTF treatment. Evidences showed a general improvement in the health outcomes of SAM children, yet failed to yield high-quality evidences to prove its benefits. Potential problems with the reliance on RUTF were identified, further research on the use of RUTF are required. / published_or_final_version / Public Health / Master / Master of Public Health

Anaerobic digestion (AD), as one of the oldest human biotechnology, has attracted revived research focus on the underpinning biological principle in recent years due to its potential in renewable green energy. With the assistance of the latest 454 deep sequencing technology, two independent studies were conducted with a shared goal to understand the operational influences on the AD microbiology from the unprecedented depth and breadth of genetic information. The first study aimed to decipher the contribution of a newly-devised waste sludge pretreatment method, which promised significant improvement in downstream biogas production. The first application of whole genome metagenomic approach on this topic revealed extensive shifts in both microbial and functional consortia towards higher biodegradation after pretreatment; meanwhile dominant acetoclastic and hydrogenotrophic methanogenesis pathways were identified concurrently with an alternative enzymology in Methanosaeta. The second study focused on the temporal dynamics of bacteria residing in production-scale biogas bioreactor coupled with multiple-sampling strategy for a realistic description of the actual microbial structure. Both bacterial fingerprint marked by feedstock and evolutionary drive towards biodegradation were revealed by 16S rDNA amplicon multiplex pyrosequencing, where clustering analyses further delineated the taxonomic plasticity and functional resilience of the bacterial communities over time. Phylogeny coverage of the highly diverse population was also improved by the adopted strategy, providing insights for sampling and sequencing standards. Altogether, the combined results garnered knowledge enrichment to the relationship between AD microbiology and operational parameters, which will assist the design of more efficient bioenergy platform in future. / published_or_final_version / Biological Sciences / Master / Master of Philosophy

Aims: A case-control study is done aiming(i)to explore the prevalence of OCSs and OCD among patients with Schizophrenia treated with Clozapine(Target group)in comparison with those treated with Haloperidol(Control group), (ii) to identify the associative factors in relationship with OCSs and OCD in Schizophrenia patients treated with Clozapine in comparison with Haloperidol , (iii)to find out predictors for the increase of OCSs and OCD among patients treated with Clozapine in comparison with Haloperidol. All these information may contribute to the understanding of the underlying etiology of OCSs and OCD. Method: Sample is comprised with patients aged 18-65 who meet the diagnostic criteria of Schizophrenia-spectrum disorder based on ICD 10 and retrieval of medical records. A total of 120 patients, comprising 30 males and 30 females patients currently prescribed with Clozapine(Target group)whereas30 male and 30 female patients are currently prescribed with Haloperidol (Control group)were identified from the Schizophrenia outpatient clinic in the same hospital. Both groups will be matched with gender. Obsessive compulsive symptoms were measured with the Chinese version of Yale-Brown Obsessive-Compulsive Scale to rate the severity of the symptoms. The severity of Schizophrenia symptoms was rated by the Positive and Negative Syndrome Scale, and the Clinical Global Impression was used to measure severity symptoms in general. The social functioning of patient was rated by The Social and Occupational Functioning Assessment Scale(SOFAS). A clinical interview questionnaire was developed to determine the social and demographic characteristics, as well as other clinical features of the disorder. It included patient’s age, frequency of hospitalisation, age of onset and duration of Schizophrenia, age of onset and duration of OCSs and OCD and age of first hospitalisation, Duration of Untreated Psychosis (DUP) and current antipsychotic medication dosage( Chlorpromazine equivalent dose). Results: From the 120 patients identified and approached, 96 (80%) patients (48 male and 48 female patients) were consented for the study. The current study found that among those prescribed with Clozapine (Target group), there were 26.5% comorbid with OCSs and OCD, whereas none patients reported OCSs and OCD among the Haloperidol Control group. Patients with OCSs and OCD were significantly correlated with PANSS Positive Syndrome Score and PANSS Total Syndrome Score factors analysis by the N Par test of Mann-Whitney U, Wilcoxon W and Z score for Asymp. Using correlations test analysis, the most significantly factors to OCSs and OCD are Clozapine (Target group), PANSS Positive Syndrome Score and PANSS Total Syndrome Score. Result showed that those three factors cannot be the prediction of OCSs and OCD from the Binary logistic regression analysis. / published_or_final_version / Psychological Medicine / Master / Master of Psychological Medicine

Background Breast cancer prevalence is increasing in most countries. Not only the threat of death and impact of breast cancer treatment, but also the participation roles during treatment decision making can be substantial, leading to psychological distress and poor quality of life. Previous studies have explored patients’ participation preference, the extent of participation congruence and related factors, revealing that women suffering from breast cancer may benefit from participation in treatment decision making whilst participation incongruity could be potentially detrimental for women with breast cancer. Objectives This study aimed to systematically review the literature and summarize the extent of breast cancer patients’ participation preference, participation congruence, and related factors. Methods Multiple searches for key words were conducted through electronic sources, including PubMed, PsycINFO, and Medline via Ovid databases for all relevant English language literature. Studies were selected basing on specific inclusion/exclusion criteria. The STROBE checklist was applied for reporting quality assessment. Results A total of 778 studies were identified. Twelve eligible studies were included in this review. Twelve factors relating to breast cancer women’s participation congruence in treatment decision making were identified as follows: age, nature of preferred role of treatment decision making, educational level, time related issues, language/ethnicity, marital status, information and recommendations of treatment, offering treatment options, physician characteristics, type of therapy or cancer program, stage of breast cancer, and surgeon volume. Conclusions Three themes (i.e. patient oriented, physician-patient interaction, and medical provision) of intervention points towards patient participation congruence were synthesized and discussed, and they were useful for improving the quality of existing breast cancer treatment decision making by addressing patient’s perceived participation congruence. / published_or_final_version / Public Health / Master / Master of Public Health

Nanoscience and nanotechnology have advanced rapidly in recent years and have made a profound impact in the medical field. Nanoparticles have attracted great attention for their potential as diagnostic and/or therapeutic tools in oncology owing to their unique properties. Theranostics are nanodevices with diagnostic, therapeutic and possibly treatment-monitoring functions for treating cancers. Different noble metal nanoparticles can provide the basic unit for theranostics. Suitably designed and developed noble metal nanoparticle-based theranostics will have multiple functions. In this project, the design, fabrication and performance of novel multifunctional nanodevices for cancer detection and treatment were investigated. The foundation of this project was laid by investigating different types of hybrid nanoparticles for novel theranostics. Different approaches were developed for fabricating core-shell structured hybrid nanoparticles. Highly branched gold and gold-silver bimetallic nanoparticles were firstly made. pH-sensitive folic acid-chitosan (CS-FA) conjugate was then introduced on these nanoparticles to form hybrid nanoparticles with a metal core (Au@CS-FA and Au-Ag@CS-FA). Poly(lactide-co-glycolide) (PLGA) and chitosan (CS) micro- or nanoparticles were also produced to serve as the polymer core for forming hybrid particles with a gold or gold-silver nanoshell (PLGA@Au, CS@Au and PLGA@Ag-Au). Furthermore, Fe3O4@Au nanoparticles having both magnetic and plasmonic properties were investigated. Thermo-sensitive poly(N-isopropylacrylamide) (pNIPAm) polymer or pH-sensitive CS-FA was then coated on Fe3O4@Au nanoparticles, forming new hybrid nanoparticles. The formation mechanisms of nanoparticles and hybrid nanoparticles were studied. Raman reporters (Rhodamine B or 4-mercaptobenzoic acid) and anti-cancer drugs (paclitaxel or 5-fluorouracil) were loaded into the polymer core or shell of hybrid nanoparticles to form multifunctional nanodevices. While the noble metal unit in the nanodevices provided high light-scattering enhancement for achieving photothermal effect, the polymer component encapsulated Raman reporter molecules and put them close to the metal nanoparticles for generating high surface enhanced Raman scattering (SERS) signals. These nanodevices could also serve as excellent drug carriers, and the stimulus-triggered release of incorporated drug was studied. It was shown in this project that the conjugation of targeting ligand (e.g. folic acid) or antibody (e.g. anti-HER2 monoclonal antibody) on hybrid nanoparticles had formed novel theranostics which allowed selective detection, continuous imaging of intracellular behavior and killing of targeted cancer cells. These theranostics could be taken up by specific cancer cells through receptor-mediated endocytosis and internalized into cytoplasma of the cell. These theranostics as stable SERS-active tags and imaging agents for HeLa cells, SK-BR-3 cancer cells or MCF-7 cancer cells were demonstrated. The targeting ability and intracellular uptake of these theranostics were studied. The photothermal effect of the theranostics was investigated using different laser irradiation powers. The anti-cancer treatment could be significantly improved by the synergistic effects of chemo- and photothermal therapy when these theranostics were also tasked as the carrier of anti-cancer drugs. Therefore, combining plasmonic metal nanoparticles with targeting ligand or antibody, magnetic nanoparticles, polymer shell or core, and anti-cancer drug has created advanced theranostics for the early detection and effective treatment of cancers. These novel theranostics have greatly improved capability for cancer detection and can provide multifunctions for cancer cell targeting, sensing/imaging and combined therapy. / published_or_final_version / Mechanical Engineering / Doctoral / Doctor of Philosophy

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the second leading cause of cancer-related deaths in the world. It is a disease with poor prognosis with unsatisfactory long-term survival of patients, and thus new strategies to control this disease are warranted. T helper (Th) 17 cells and IL-17 have recently been detected with increased frequency in a number of tumors including HCC. Its role in tumor remains controversial but its presence in HCC has been linked to disease progression, possibly involving angiogenesis. Th17 cells could be homed to inflammatory sites such as tumor microenvironment via CCR6/CCL20 axis and expand locally, and studies from other inflammatory diseases such as autoimmune disease has shown that the gut is the potential source of Th17, where its induction is affected by signals from gut microbiota. Yet this link is not yet shown in extra-intestinal tumors. Probiotics are living microorganisms, which when administered in adequate amounts confer a health benefit on the host. They have been reported to relieve chronic inflammatory diseases in animal and in human intervention studies. It is believed that probiotics regulate signals to gut antigen-presenting cells, which act as the pivot in modulating the systemic immune responses and inactivated bacteria also exhibited immunomodulatory effects in this regard. Accordingly, it was hypothesized that oral feeding of probiotics to HCCbearing animals may affect Th17 polarization and distribution and thereby modulate tumor microenvironment, which may have beneficial effect in tumor development, possibly via affecting angiogenesis. To address this hypothesis, wild-type C57BL/6 mice were fed with different heat-inactivated or viable probiotics– Lactobacillus rhamnosus GG (LGG), Escherichia coli Nissle 1917 (EcN), VSL#3 or mixture of probiotics − Prohep (heat-inactivated LGG, heatinactivated VSL#3 and viable EcN) either one week in advance or at the time of subcutaneous tumor inoculation. Probiotic feeding had improved survival in tumor-bearing mice, slowed down tumor growth and reduced tumor burden when monitored for 38 days. Probiotics showed better efficacy when feeding was given in advance. The anti-tumor effect was related to reduced angiogenesis and reduced IL-17 serum and gene expression within tumor. The mechanistic link between IL-17 modulation and tumor development was further studied in animals by IL-17 neutralization. The anti-tumor efficacy of probiotics, in relation to tumor growth and angiogenesis, was lost after IL-17 neutralization, which was linked to recruitment of myeloid suppressor cells. Since cells from both adaptive and innate immune systems could secrete IL-17, the source of IL-17 production was then identified, and found that Th17 was the major IL-17 secretor being modulated by probiotic feeding. Reduced homing of Th17 to tumor via circulation, with a tendency being recruited from gut was observed. Probiotics-mediated Th17 cell modulation in the gut by inducing the skewing of IL-10 secreting type1 regulatory T cells via dendritic cells may link to limited IL-17 mediated angiogenesis in the tumor microenvironment. With better understanding of the immunomodulation properties of probiotics, prophylactic or therapeutic efficacy in management of other inflammation-associated cancer can be availed. / published_or_final_version / Biological Sciences / Doctoral / Doctor of Philosophy

This study used a qualitative methodology to examine treatment outcome and mechanisms of change from the perspective of the participants in a group cognitivebehavioral therapy intervention for depressed girls (i.e., the ACTION program). Data were collected from seventeen participants using semi-structured interviews. Seventeen initial and seven follow-up interviews were conducted. Interviews were transcribed and analyzed using the grounded theory approach. A theoretical model emerged from the data that explained mechanisms of change in relation to treatment outcome and evaluation. Prior to treatment, all participants were diagnosed with a depressive disorder. At post-treatment, approximately 88% of the sample no longer met criteria for depression. Thus, the ACTION program demonstrated a high rate of efficacy. Additionally, all of the participants described treatment as helpful. Level of helpfulness varied from high to low, with most participants rating treatment as very helpful, and depended on the ways in which the intervention produced positive change in the following areas: stressors, stressor management strategies, emotions, cognitions, and social support. Participants evidenced high levels of pre-treatment stressors, particularly in the interpersonal domain, and low levels of social support. Passive, emotion-focused strategies were used to manage these difficulties; however, they were largely ineffective. Not being able to resolve stressors successfully led participants to experience unpleasant emotions and negative ways of thinking. Together, these variables resulted in high levels depression prior to treatment. At post-treatment, most participants experienced several positive changes, including decreased stressors, increased effectiveness of stressor management strategies, elevated mood, and a more positive outlook. These changes were attributed to the acquisition and application of the core treatment components by the majority of participants. Some participants also experienced an increase in social support, which was associated with characteristics of the treatment structure. Thus, the two most important variables in relation to treatment outcome and evaluation were specific mechanisms of change (i.e., treatment components) and non-specific therapeutic factors (i.e., treatment structure). In addition, treatment outcome was also influenced by participant characteristics. Participants that held unrealistic expectations, were not ready for change, or engaged in limited problem-sharing experienced fewer positive changes over the course of treatment.

Thesis (MTech degree in Nursing)--Tshwane University of Technology, 2011. / Quality of life has been well researched, especially with respect to cancer sufferers, but not necessarily from the perspective of the patient and also not in third-world, resource-poor countries. In this study quality of life was researched from the perspective of the palliative patient living in Soshanguve, a township 45 kilometres from Pretoria in South Africa. The patients were managed at the palliative care nursing community of practice in Soshanguve and suffered from cancer, HIV and AIDS, pulmonary tuberculosis, cerebrovascular incidents and chronic pain due to arthritis.