Thesis (M.S.)--Boston University / PLEASE NOTE: Boston University Libraries did not receive an Authorization To Manage form for this thesis or dissertation. It is therefore not openly accessible, though it may be available by request. If you are the author or principal advisor of this work and would like to request open access for it, please contact us at open-help@bu.edu. Thank you. / 2031-01-01

A research report submitted to the faculty of health sciences, University of the Witwatersrand, Johannesburg, in partial fulfillment of the requirements for the degree of master of medicine in family medicine October 2017 / MT2018

Faculty of Science School of Animal,Plant,Enviromental Sciences 0311595p NicrosM@social.mpu.gov.za / The antifolate combination of sulfadoxine and pyrimethamine (SP) is one of few remaining affordable drug combinations available for wide-scale treatment of uncomplicated Plasmodium falciparum malaria in Africa. In vivo studies of SP efficacy conducted during 1998, 2000 and 2002 at the Naas sentinel site in Mpumalanga province, South Africa, demonstrated a gradual non-significant increase in late treatment failure (LTF) and early treatment failure (ETF) resistance to SP, while gametocyte carriage increased significantly between 1998 and 2002 (p < 0.0001). This study aimed to determined and compare the frequency of dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) resistant haplotypes in P. falciparum parasites from patients treated with SP in three consecutive standardized in vivo therapeutic efficacy studies in Mpumalanga province, since implementation of SP as first line treatment in 1998, and to investigate associations between the presence of mutations and treatment outcomes after SP treatment. Four hundred-and-three samples were studied and 358 yielded polymerase chain reaction products. A novel high throughput sequence-specific oligonucleotide probe-based approach was used to examine the resistance status of the three in vivo P. falciparum populations. Screening for the presence of all known point mutations in dhfr and dhps genes revealed that only five dhfr and three dhps allelic haplotypes were present. In all the samples investigated, point mutations were identified only at codons 108, 51 and 59 of the dhfr gene and at codons 347 and 540 of the dhps gene. The prevalence of dhfr resistant haplotypes was 35.4% in 1998, 38.7% in 2000, and 41.0% in 2002, while the prevalence of dhps resistant haplotypes was 9.7% in 1998, 7.2% in 2000 and 41.6% in 2002, the latter representing a significant increase (p < 0.002). The prevalence in both dhfr and dhps gene resistant haplotypes were selected gradually during the three in vivo studies in Mpumalanga province. Infection with parasites having triple dhfr mutations and double dhps mutations, "the quintuple mutant", was associated with SP treatment failure (p < 0.001). Mutations at both dhfr and dhps loci may be important predictors of SP resistance in Mpumalanga province.

M.Sc.(Med.), Faculty of Health Sciences, University of the Witwatersrand, 2008 / Introduction It is widely recognised that stroke is a multi-factorial disorder in which platelets play a crucial role in thrombus formation resulting in ischaemic stroke. Platelet adhesion and aggregation are initiated by the interaction of various platelet glycoproteins (GP’s) such as GPIbα, which binds to von Willebrand Factor and GPIIb/IIIa a fibrinogen receptor. Recent studies have shown that the GP’s are polymorphic and the polymorphisms described within GPIbα such as Kozak- 5T/C, the variable number of tandem repeats (VNTR) and the Human Platelet antigen 2 (HPA2), have been implicated in the development of stroke, while the PIA polymorphism of GPIIb/IIIa was found to contribute to “aspirin resistance”. Therefore, these polymorphisms may be potentially important for early detection and early intervention and thus setting the need to provide for a high volume genotype testing at health care centres. One of the most used techniques to determine platelet function is platelet aggregometry. However, the major disadvantages of platelet aggregation is that it is influenced by a number of environmental factors and its access is limited to tertiary health centres. Platelet aggregation measures the functional expression of platelets, which is known to deteriorate over time. It is for this reason that new methods at molecular level such as polymerase chain reaction (PCR) are needed to explore the role of genotypic expressions, which are not influenced by environmental factors. Currently, conventional PCR is used to detect platelet polymorphisms in the research settings and has limitations as a routine diagnostic test. Furthermore, it is time consuming and is prone to contamination. With the recent advances in real-time PCR it is possible to genotype large sample batches rapidly without compromising on the quality, accuracy and precision of results. This study aims to adapt conventional PCR methodology onto a real-time platform for detecting platelet polymorphisms that have been implicated in both stroke and aspirin resistance. Materials and methods A total of 60 caucasian patients classified as having ischaemic stroke by virtue of MRI and Doppler analysis from the Stroke Clinic at the Johannesburg Hospital were enrolled for this study. Healthy caucasian individuals (38), age and gender matched were enrolled as controls. DNA samples were extracted from all the subjects and the prevalence of the Kozak –5T/C, HPA-2, VNTR and GPIIIa PIA polymorphisms were determined first by using conventional PCR and then the real-time LightCycler TM PCR method. Results The frequency of the unfavourable alleles ( the PIA2 allele for the GPIIIa PIA polymorphism, the T allele for the Kozak –5T/C polymorphism, the B allele for the HPA-2 polymorphism and the C allele for the VNTR polymorphism) of the different GP’s were higher in the stroke patients when compared to the control subjects but did not reach statistical significance. There was complete statistical agreement between the results obtained for the conventional PCR as compared to the results obtained for real-time PCR except for the VNTR polymorphism, due to the difficulty in designing and the unavailability of probes for the real-time PCR assay. However, it is important to note that adapting the real-time PCR as a new methodology would greatly benefit both the patients and the clinicians by providing early detection and the possibility of early therapeutic intervention. Conclusion Therefore in conclusion, it is possible to perform not only conventional PCR for platelet polymorphism but also real-time PCR on a large scale without compromising on the quality, accuracy and precision on platelet polymorphisms that play a significant role in stroke and aspirin resistance. However, a larger population based study needs to be performed to confirm the findings.

Thesis (M.S.)--Boston University / The innovation of a day hospital for the long term mentally ill patient brings to light new areas of possible exploration. This study sought to look at what perceptions six patients and a member of the patients' families had concerning day hospitalization and its effects. The patients, all long term mentally ill females, had been actively participating in a specific day hospital program of a large Boston area state hospital. The patients between the ages of thirty and forty-six years of age had been in the hospital for approximately five and one-half months. Previously, they had been hospitalized from nine months to twenty-seven years with a mean of eighteen years and one month [TRUNCATED]

Thesis (M.S.)--Boston University

Fu Zhenming. / Thesis submitted in: December 2003. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 138-162). / Abstracts in English and Chinese. / List of abbreviations --- p.i / Abstract (in English) --- p.ii / 摘要（中文） --- p.iii / Acknowledgement --- p.iv / Chapter Chapter 1. --- Introduction and Objectives of Study --- p.1 / Chapter 1.1 --- Hepatocellular carcinoma in general --- p.2 / Chapter 1.1.1 --- "Epidemiology, risk factors" --- p.2 / Chapter 1.1.2 --- Pathology and staging --- p.4 / Chapter 1.1.3 --- Treatment --- p.6 / Chapter 1.1.4 --- Improvement of early detection and treatment of HCC --- p.7 / Chapter 1.2 --- General aspects of mitochondria and mitochondrial DNA (mtDNA) --- p.10 / Chapter 1.2.1 --- Structure and dynamics of mitochondria --- p.10 / Chapter 1.2.1.1 --- General introduction of mitochondria --- p.10 / Chapter 1.2.1.2 --- Respiration chain of mitochondria --- p.11 / Chapter 1.2.2 --- The mitochondrial genome --- p.14 / Chapter 1.2.2.1 --- Strucure --- p.14 / Chapter 1.2.2.2 --- Genes for structure proteins --- p.16 / Chapter 1.2.2.3 --- Genes for translation --- p.17 / Chapter 1.2.2.4 --- Imported proteins and RNAs --- p.17 / Chapter 1.2.3 --- Mitochondrial DNA maintenance --- p.19 / Chapter 1.2.4 --- Mitochondrial DNA replication --- p.25 / Chapter 1.2.5 --- Mitochondrial DNA transcription --- p.30 / Chapter 1.2.6 --- Mitochondrial DNA translation --- p.32 / Chapter 1.3 --- MtDNA diseases --- p.35 / Chapter 1.4 --- MtDNA mutation and HCC --- p.35 / Chapter 1.5 --- Aims of the study --- p.39 / Chapter Chapter 2. --- Materials and Methods --- p.41 / Chapter 2.1 --- Materials --- p.42 / Chapter 2.1.1 --- Chemicals --- p.42 / Chapter 2.1.2 --- Primers --- p.42 / Chapter 2.1.3 --- Enzymes --- p.45 / Chapter 2.1.4 --- Cell line --- p.45 / Chapter 2.1.5 --- Collection of specimens --- p.46 / Chapter 2.2 --- Methodology --- p.47 / Chapter 2.2.1 --- "DNA extraction from hcc tissues, cell line Hep3B and PBMCs" --- p.47 / Chapter 2.2.1.1 --- DNA extraction from HCC tissues --- p.47 / Chapter 2.2.1.2 --- DNA extraction from cell line Hep3B --- p.49 / Chapter 2.2.1.3 --- DNA extraction from and PBMCs --- p.50 / Chapter 2.2.1.3.1 --- Preparation of PBMCs --- p.50 / Chapter 2.2.1.3.2 --- DNA extraction from and PBMCs --- p.51 / Chapter 2.2.2 --- Detection of mt whole genome mutation by direct sequencing --- p.51 / Chapter 2.2.2.1 --- Design of mtDNA primers --- p.51 / Chapter 2.2.2.2 --- PCR amplification of the whole mt genome --- p.51 / Chapter 2.2.2.3 --- Direct sequencing of the whole mt genome --- p.52 / Chapter 2.2.2.3.1 --- Primer used in sequencing --- p.52 / Chapter 2.2.2.3.2 --- Purification of the PCR products of the whole mt genome --- p.53 / Chapter 2.2.2.3.3 --- Dye terminator cycle sequencing reaction --- p.53 / Chapter 2.2.2.3.4 --- Purification of extension products --- p.54 / Chapter 2.2.3 --- Detection of mtDNA control region mutation --- p.55 / Chapter 2.2.3.1 --- PCR amplification of D310 in the mtDNA control region --- p.55 / Chapter 2.2.3.2 --- Screening of D310 mutation by PFLDA --- p.55 / Chapter 2.2.3.2.1 --- Making 8% denatured gel mixture --- p.55 / Chapter 2.2.3.2.2 --- Setting up and Pouring the denatured gel --- p.56 / Chapter 2.2.3.2.4 --- Preparing and Loading the PCR products --- p.57 / Chapter 2.2.3.2.5 --- Electrophoresis --- p.57 / Chapter 2.2.3.2.6 --- "Gel fixing, silver staining and color development " --- p.58 / Chapter 2.2.3.3 --- Direct sequencing of D310 in the mtDNA control region --- p.59 / Chapter 2.2.4 --- Detection of mt DNA coding region mutation --- p.60 / Chapter 2.2.4.1 --- PCR amplification of the 5 respiratory chain subunit genes --- p.60 / Chapter 2.2.4.2 --- Restriction enzyme digestion of 5 genes in mtDNA coding region --- p.60 / Chapter 2.2.4.3 --- Screening of mtDNA coding region mutation by SSCP --- p.61 / Chapter 2.2.4.3.1 --- Making 6% 49:1 acrylamide/Bis SSCP gel mixture --- p.61 / Chapter 2.2.4.3.2 --- "Setting up the SSCP gel, loading sample, fixing, staining and developing of the gel " --- p.62 / Chapter 2.2.4.4 --- Sequencing conformation of the mtDNA coding region mutation --- p.62 / Chapter 2.2.5 --- Statistics --- p.63 / Chapter 2.2.5.1 --- The chi-square test --- p.63 / Chapter 2.2.5.2 --- The Friedman test --- p.63 / Chapter 2.2.5.3 --- Wilcoxon signed ranks test --- p.63 / Chapter Chapter 3. --- Results --- p.64 / Chapter 3.1 --- Detection mt DNA whole genome mutation --- p.65 / Chapter 3.1.1 --- Identification of mtDNA whole genome by direct sequencing --- p.65 / Chapter 3.2 --- Detection mt DNA D-loop mutation --- p.76 / Chapter 3.2.1 --- Screening of C-tract alteration in HCC tissus by PCR fragments length detection assay (PFLDA) --- p.76 / Chapter 3.2.2 --- Screening of coding region alteration in HCC tissues by SSCP --- p.77 / Chapter 3.2.2.1 --- Identification of C-tract alterations in HCC and non-tumorous tissues by direct sequencing --- p.77 / Chapter 3.2.3 --- Identification of C-tract alterations by direct sequencing --- p.82 / Chapter 3.2.3.1 --- Identification of C-tract alterations in HCC tissues by direct sequencing --- p.82 / Chapter 3.2.3.2 --- Identification of C-tract alteration in PBMC of normal subjects by direct sequencing --- p.82 / Chapter 3.2.3.3 --- Identification of C-tract alteration in PBMC of HCC patients by direct sequencing --- p.82 / Chapter 3.2.4 --- Statistics of the analysis of C-tract alterations --- p.82 / Chapter 3.3 --- Detection mt DNA mutation in the coding region --- p.87 / Chapter Chapter 4. --- Discussion --- p.98 / Chapter 4.1 --- Detection mtDNA whole genome mutation --- p.99 / Chapter 4.2 --- Detection mtDNA D-loop mutation --- p.107 / Chapter 4.3 --- Detection mtDNA mutation in the coding region --- p.119 / Chapter 4.4 --- Possible mechanisms of mtDNA mutation in HCC carcinogenesis --- p.125 / Chapter 4.5 --- Proposals for prospective studies --- p.126 / Chapter 4.5.1 --- Function of C7 in D310 --- p.128 / Chapter 4.5.2 --- Function changes of mtDNA coding region mutation --- p.130 / Chapter 4.5.3 --- Detection of D310 C-tract mutation in patients' plasma --- p.131 / Chapter 4.5.4 --- Relationship between nMSl and mtMSI --- p.132 / Chapter 4.6 --- Summary --- p.134 / References --- p.137

Ng Sau Kwan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 107-127). / Abstracts in English and Chinese. / ABSTRACT --- p.ii / ACKNOWLEDGEMENTS --- p.vi / TABLE OF CONTENTS --- p.vii / LIST OF TABLES --- p.ix / LIST OF APPENDICES --- p.x / Chapter Chapter 1: --- INTRODUCTION / Background of the study --- p.1 / Significance of the study --- p.3 / Chapter Chapter 2: --- LITERATURE REVIEW / Introduction --- p.6 / Search Strategy --- p.6 / Overview of the Concepts of Pain --- p.7 / Types of Pain --- p.8 / Nature of Postoperative Pain --- p.9 / Effects of Pain --- p.9 / Factors Influencing Pain Management Outcomes / Undermanaged Postoperative Pain --- p.11 / Assessing Pain in Postoperative Patients --- p.14 / Pain Relief and Patient Satisfaction --- p.16 / Health Locus of Control --- p.20 / Health Care Professionals' Attitudes --- p.22 / Barriers to Postoperative Pain Relief --- p.24 / Psychosocial Factors Influencing Patient Satisfaction --- p.26 / Nursing and Quality Assurance of Pain Management --- p.29 / Pain Management Strategies / Organization of an Acute Pain Service --- p.32 / Pharmacological Pain Management --- p.35 / Nonpharmacological Pain Management --- p.37 / Summary of Literature Review --- p.38 / Chapter Chapter 3: --- METHOD / Introduction --- p.41 / Aim and objectives of the study --- p.41 / Research Questions --- p.42 / Research Hypotheses --- p.43 / Operational Definitions --- p.43 / Research Design --- p.44 / Settings --- p.45 / Sample --- p.46 / Instruments --- p.47 / The Modified American Pain Society Patient Outcome Questionnaire (APS-POQ-Modified) --- p.48 / The State Scale of State-Trait Anxiety Inventory (STAI) --- p.50 / The Multidimensional Health Locus of Control Form C Scale (MHLC) --- p.53 / The Modified Patient Satisfaction Questionnaire (PSQ-Modified) --- p.54 / Demographic Data Form --- p.55 / Translation and Content Validity of the Instruments --- p.55 / Pilot Study --- p.57 / Data Collection Procedures --- p.60 / Data Analysis / Effect Size and Power of the Study --- p.62 / Ethical Considerations --- p.64 / Conclusion --- p.65 / Chapter Chapter 4: --- RESULTS / Introduction --- p.66 / Reliability of the Instruments --- p.67 / Demographic Characteristics / Medical Characteristics --- p.70 / Physical and Psychosocial Characteristics of Pain / Pain intensity and pain interference --- p.72 / Beliefs about pain --- p.73 / State anxiety --- p.73 / Health locus of control --- p.73 / Patient satisfaction --- p.75 / Responses to Modified Patient Outcome Questionnaire --- p.75 / Comparisons of Patient Satisfaction Ratings with Demographic / Characteristics --- p.77 / Correlates of Patient Satisfaction --- p.78 / Predictors of Patient Satisfaction --- p.80 / Conclusion --- p.82 / Chapter Chapter 5: --- DISCUSSION / Introduction --- p.84 / Demographic Characteristics --- p.84 / Effect Size and Power of the Study --- p.85 / Patient Satisfaction with Pain Management and Pain Intensity --- p.86 / Multidimensional Health Locus of Control --- p.90 / Beliefs or Misconceptions about pain --- p.94 / Education on Pain Management --- p.98 / Conclusion --- p.101 / Chapter Chapter 6: --- "LIMITATIONS, IMPLICATIONS, RECOMMENDATIONS AND CONCLUSION" / Introduction --- p.102 / LIMITATIONS OF THE STUDY --- p.102 / IMPLICATIONS FOR NURSING PRACTICE --- p.106 / RECOMMENDATIONS FOR FUTURE PRACTICE / AND RESEARCH --- p.110 / CONCLUSION --- p.113 / REFERENCES --- p.115

Magister Scientiae Dentium - MSc(Dent) / The aim of this research project was to assess the accuracy of four different types of VTO [Steyn (1979), Jacobson and Sadowsky (1980), Ricketts (1982) and Holdaway (1984)], in predicting the final result of the incisor and soft tissue response to orthodontic treatment in bimaxillary protrusive patients. / South Africa

Thesis (M.Dev.) --University of Limpopo (Turfloop Campus), 2005 / The aim of this study was to investigate the socio-economic impact of interrupting TB treatment to the families of the TB sufferers and the reasons for patients interrupting treatment. The study was conducted at Mashishimale Village, Ba- Phalaborwa Municipality, Mopani District, Limpopo Province in South Africa. A sample of 35 tuberculosis patients and their family members was drawn from the Mashishimale population. The sample comprised of 17 (49%) males and 18 (51%) females. Self-administered questionnaires were distributed to the participants to complete. The questionnaire elicited demographic information; knowledge about TB, its causes, signs and symptoms, transmission, the reasons for interrupting treatment, and the patients’ coping and support structures. The findings of the study reported that 50% of TB patients are conversant with the signs, symptoms and mode of the spread of TB. However, 43% of the TB patients reported that there was a perception that TB patients are also HIV positive. A further 29% mentioned that there is stigma attached to TB disease. The lack of a Directly Observed Treatment Supporter, poverty and poor nutrition, side-effects of drugs, loss of disability grants, long clinic queues, and traditional healing were some of the reasons cited for the interruption of TB treatment. The interruption of TB treatment had an impact on the socio-economic situation of the family as they often relied on assistance from social grants, other family members and churches.