Dissertations / Theses on the topic 'Musculoskeletal system Diseases Diagnosis'
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Chan, Cho-cheong, and 陳楚莊. "Magnetic resonance elastography: neuronal andmuscular studies, and a novel acoustic shear wave generator." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B38643868.
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Mendonça, José Alexandre 1969. "O ultrassom articular = uma ferramenta importante de avaliação no diagnóstico na artrite reumatóide inicial." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/310630.
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Orientador: Manoel Barros BértoloTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Objetivo: Avaliar sinovite pelo ultrassom (US) articular em pacientes com artrite reumatóide (AR) inicial e correlacionar com os dados clínicos, radiográficos e laboratoriais. Pacientes e Métodos: Este estudo avaliou 832 articulações de 32 pacientes (24 mulheres e 8 homens) com AR inicial selecionados no período de 2008 a 2010 do ambulatório de artrite da Universidade Estadual de Campinas, caracterizado por 20 (62.5%) caucasóides e 12 (37.5%) não caucasóides; um tempo médio de doença de 13 meses, com média de idade de 42 anos. Nesta amostra foram detectadas, pelas escalas semiquantitativas cinza (SG) e pelo power Doppler (PD), 173 articulações com sinovite de grau 0 a 3. Foi usado um ultrassom GE LOGIQ XP-linear de alta frequência (8-10 MHz). Todas as mãos foram radiografadas e analisadas pelo score de Larsen com variação de grau entre 0 a V. Resultados: Este estudo evidenciou correlações significativas e positivas entre os dados ultrassonográficos, clínicos e laboratoriais: SGUS e PDUS do punho D e PCR (r=0.41 a 0.42), SGUS do 3ªMTF D, 4ªMTF D com o HAQ - DI (r=0.37 a 0.38), SGUS do 4ªMTF E e o PCR (r=0.42), SGUS do 2ªMTF D e o FR (r=0.40), SGUS-Score 7mod com o DAS28 (PCR) (r=0.38) e o PDUS-Score 7mod com o PCR (r=0.39). Houve correlações significativas negativas com o SGUS 2ªMTCF D com a dose e o tempo de uso MTX (r=-0.36 a -0.37). O PCR nesta amostra pode ser considerado um indicador de atividade inflamatória quando existe sinovite detectada pelo US. Conclusão: A utilização do US mostrou ser uma importante ferramenta na avaliação de AR inicial e dá um suporte mais seguro no diagnóstico para iniciativas terapêuticas mais precisas e seletivas
Abstract: This study evaluated 832 joints of 32 patients (24 women and 8 men) with early RA enrolled for the period 2008 to 2010 of the arthritis clinic of the Universidade Estadual de Campinas (UNICAMP), characterized by 20 (62.5%) Caucasians, 12 (37.5%) non-Caucasians, an average disease was 13 months, with a mean age of 42 years. This sample was detected by semi-quantitative gray scale (GS) and power Doppler (PD) 173 joints with synovitis of degree 0 to 3. It was used a GE LOGIQ XP-linear ultrasound and high frequency (8-10 MHz) transducer. All hands were X-rayed and analyzed by the Larsen score, with grades ranging from 0 to V. This study showed positive and significant correlation between sonographic, clinical and laboratory data: GSUS/PDUS of right wrist and CRP (r = 0.41 to 0.42), GSUS of the right 3ºMTP, GSUS of the right 4ºMTP and HAQ - DI (r = 0.37 to 0.38), GSUS of the left 4ºMTP and CRP (r = 0.42), GSUS of the right 2ºMTP and FR (r = 0.40), GSUS 7mod-score with the DAS28 (CRP) (r = 0.38) and PDUS 7mod-Score to CRP (r = 0.39). There was a significant negative correlation with the right 2ºMCP with dose and duration of MTX use (r = -0.36 to -0.37). The CRP in this sample can be considered an indicator of inflammatory activity, when analyzed separately or with all the joints committed. Using the US was an important tool in the evaluation of RA and gives a more secure support for initiatives in the diagnosis and treatment more precise and selective
Doutorado
Clinica Medica
Doutor em Clínica Médica
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Johansson, Jan Å. "Psychosocial factors at work and their relation to musculoskeletal symptoms." Lund : Dept. of Psychology, Göteborg University, 1994. http://catalog.hathitrust.org/api/volumes/oclc/39775906.html.
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Stover, Bert D. "Validation and evaluation of a disability measure for upper extremity musculoskeletal disorder screening in the workplace and prognostic factors of long-term disability /." Thesis, Connect to this title online; UW restricted, 2004. http://hdl.handle.net/1773/5407.
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Spielholz, Peregrin. "A comparison of upper extremity physical risk factor measurement methods /." Thesis, Connect to this title online; UW restricted, 1999. http://hdl.handle.net/1773/8468.
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Renz, Miriam Christina. "Laboratory investigation of a simulated industrial task pre- and post-ergonomics intervention." Thesis, Rhodes University, 2004. http://hdl.handle.net/10962/d1015806.
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The focus of the present study was on the investigation of the effects of an intervention strategy on an industrial task in situ and a simulation of the same task within a laboratory setting. The task of offloading crates from a truck at a local business was simulated in a laboratory setting for rigorous analysis. The effect of an ergonomically sound intervention on selected physical, physiological and perceptual variables was evaluated in a test - retest experimental set-up using 28 young, healthy male students. Each of the two experimental conditions lasted for 16 minutes. In the pre-intervention task subjects were required to transfer the crates from one point to another by sliding them along the floor. During the execution of the post-intervention task responses to reductions in the stacking height and modifications of the working method were evaluated. Results obtained for spinal kinematics during the simulated industrial task indicated a high biomechanical risk, due to large ranges of motion, high velocities and accelerations in the sagittal and transverse planes. The heavy workload of the task was also evident in elevated physiological responses (HR, RF, VT, VE, VO2, RQ, EE) and perceptual ratings (RPE, Body Discomfort). Assessment of the intervention strategy revealed that the high risk industrial task was reduced to moderate acceptable, with measurements of spinal kinematics, physiological and perceptual variables being significantly reduced. An in situ re-assessment of the workers responses to the intervention also elicited reductions in heart rates and perceptual ratings compared to the original task.
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Li, Sin Wan. "Development of immunoassays for prognosis and diagnosis of cardiovascular diseases /." View abstract or full-text, 2007. http://library.ust.hk/cgi/db/thesis.pl?CHEM%202007%20LI.
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Blosser, Peter, Remil Simon, and Courtney Ridner. "Differential Diagnosis of Pan-Uveitis: Behçet’s Disease." Digital Commons @ East Tennessee State University, 2018. https://dc.etsu.edu/asrf/2018/schedule/2.
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This report describes the case of a 56-year-old man who presented with blurry vision, increased intraocular pressure, and conjunctival injection after posterior chamber intraocular lens implantation. Initially post-operative endophalmitis and foreign body inflammation were considered as differential diagnoses, but after further examination pan-uveitis was diagnosed. Uveitis is an ocular finding that may indicate several diseases, one of which is Behçet’s Disease. During the interview, the patient mentioned a history of apthous ulcers and genital ulcers which then lead to the clinical diagnosis of Behçet’s Disease. This report emphasizes that Behçet’s Disease is rare in Caucasians. Therefore, is frequently misdiagnosed in North America due to variable presentations and by not exploring the option when analyzing differential diagnoses. Early diagnosis and intervention will prevent the development of blindness and fatality due to complications of the disease.
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Dillard, E. Margo (Edna Margo). "An Epidemiological Survey of Musculoskeletal Pain Among a Self-Selected Population of Organists." Thesis, University of North Texas, 1998. https://digital.library.unt.edu/ark:/67531/metadc935779/.
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The purpose of this study was to investigate problem areas of organists' performance as indicated by common experiences of pain. The research problems were to determine the specific areas of the body that were affected by pain, to determine the perceived level of that pain on a scale indicative of its severity, and to explore the relationship between demographic and performance-related factors within the population and specific area of reported pain. An examination of the demographic, performance-related, and pain data, as well as subject comments, indicated possible relationships of the pain experience to other factors. Organists attributed their pain to instrument characteristics, such as keyboard action, music rack height, bench design, and pedalboard shape. Pain was also associated with the time spent playing the organ, playing literature which required large reaches and rapid passage work, such as french toccatas, or playing with incorrect posture. To explore these relationships to spinal and upper extremity pain, further research is indicated.
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Harben, Alan M. "An Electromyographic kinetic model for passive stretch of hypertonic elbow flexors." Diss., Georgia Institute of Technology, 2000. http://hdl.handle.net/1853/20301.
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Horwood, Alan C. "Computer diagnosis of tomographic pulmonary images." Thesis, University of Bristol, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.324376.
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Alzubaidi, Rania S. M. "Fully automated computer system for diagnosis of corneal diseases. Development of image processing technologies for the diagnosis of Acanthamoeba and Fusarium diseases in confocal microscopy images." Thesis, University of Bradford, 2017. http://hdl.handle.net/10454/17142.
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Confocal microscopy demonstrated its value in the diagnosis of Acanthamoeba and fungal keratitis which considered sight-threatening corneal diseases. However, it can be difficult to find and train confocal microscopy graders to accurately detect Acanthamoeba cysts and fungal filaments in the images. Use of an automated system could overcome this problem and help to start the correct treatment more quickly. Also, response to treatment can be difficult to assess in infectious keratitis using clinical examination alone, but there is evidence that the morphology of filaments and cysts may change over time with the use of correct treatment. An automated system to analyse confocal microscopy images for such changes would also assist clinicians in determining whether the ulcer is improving, or whether a change of treatment is needed.
This research proposes a fully automated novel system with GUI to detect cysts and hyphae (filaments) and measure useful quantitative parameters for them through many stages; Image enhancement, image segmentation, quantitative analysis for detected cysts and hyphae, and registration and tracking of ordered sequence of images.
The performance of the proposed segmentation procedure is evaluated by comparing between the manual and the automated traced images of the dataset that was provided by the Manchester Royal Eye Hospital. The positive predictive values rate of cysts for Acanthamoeba images was 76%. For detected hyphae in Fusarium images, many standard measurements were computed. The accuracy of their values was quantified by calculating the percent error rate for each measurement and which ranged from 23% to 49%.
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Al-Kabir, Zul Waker Mohammad, and N/A. "A Knowledge Based System for Diagnosis of Lung Diseases from Chest X-Ray Images." University of Canberra. Information Sciences & Engineering, 2007. http://erl.canberra.edu.au./public/adt-AUC20070823.160921.
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The thesis develops a model (that includes a conceptual framework and an
implementation) for analysing and classifying traditional X-ray images (MACXI)
according to the severity of diseases as a Computer-Aided-Diagnosis tool with three
initial objectives.
� The first objective was to interpret X-ray images by transferring expert knowledge
into a knowledge base (CXKB): to help medical staff to concentrate only on the
interest areas of the images.
� The second objective was to analyse and classify X-ray images according to the
severity of diseases through the knowledge base equipped with an image
processor (CXIP).
� The third objective was to demonstrate the effectiveness and limitations of several
image-processing techniques for analysing traditional chest X-ray images.
A database was formed based on collection of expert diagnosis details for lung images.
Five important features from lung images, as well as diagnosis rules were identified and
simplified. The expert knowledge was transformed into a Knowledge base (KB) for
analysing and classifying traditional X-ray images according to the severity of diseases
(CXKB). Finally, an image processor named CXIP was developed to extract the features
of lung images features and image classification.
CXKB contains 63 distinct lung diseases with detailed descriptions. Some 80-chest X-ray
images with diagnosis details were collected for the database from different sources,
including online medical resources. A total of 61 images were used to determine the
important features; 19 chest X-ray images were not used because of low visibility or the
difficulty of diagnosis. Finally, only 12 images were selected after examining the
diagnosis details, image clarity, image completeness, and image orientation. The most
important features of lung diseases are a pattern of lesions with different levels of
intensity or brightness. The other major anatomical structures of the chest are the hilum
area, the rib area, the trachea area, and the heart area.
Seven different severity levels of diseases were determined. Development and
simplification of rules based on the image library were analysed, developed, and tested
against the 12 images. A level of severity was labelled for each image based on a
personal understanding of all the image and diagnosis details. Then, MACXI processed
the selected 12 images to determine the level of severity. These 12 images were fed into
the CXIP for recognition of the features and classification of the images to an accurate
level of severity. Currently, the processor has the ability to identify diseased lung areas
with approximately 80% success rate.
A step by step demonstration of several image processing techniques that were used to
build the processor is given to highlight the effectiveness and limitations of the
techniques for analysing traditional chest X-ray images is also presented.
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Al-Kabir, Zul Waker Mohammad. "A knowledge based system for diagnosis of lung diseases from chest x-ray images /." Canberra : University of Canberra, 2007. http://erl.canberra.edu.au/public/adt-AUC20070823.160921/index.html.
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Thesis (PhD) -- University of Canberra, 2006.Thesis submitted in fulfilment of the requirements for the degree of Master of Information Science in the School of Information Sciences and Engineering under the Division of Business, Law and Sciences at the University of Canberra, May 2006. Bibliography: leaves 120-132.
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Panta, Utsab, Adam chan, and Debalina Das. "Osteonecrosis of Jaw: Common etiologies, uncommon treatments." Digital Commons @ East Tennessee State University, 2019. https://dc.etsu.edu/asrf/2019/schedule/201.
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Introduction
First described in 2002, osteonecrosis of the jaw (ONJ, or avascular necrosis of the jaw) is an uncommon but potentially serious side effect of treatment with bisphosphonates. Although typically identified in patients with multiple myeloma and other malignancies, a few cases have been reported in patients taking bisphosphonates - a potent drug class used in the treatment of osteoclast-mediated bone resorption issues, including postmenopausal osteoporosis, Paget's disease, multiple myeloma, and malignant hypercalcemia. The clinical diagnosis of ONJ can be obscured by jaw pain, abscess, swelling, and fistulas, but exposed bone is a distinctive sign. This reports a case of ONJ secondary to bisphosphonate use in a 65-year-old woman and clinical management complications.
Case Presentation
A 65-year-old lady with history of age-related osteoporosis and compression fractures on alendronate for 4 years, squamous cell carcinoma of neck status post excision and radiotherapy 11-years prior, Sjogren's syndrome and discoid lupus on hydroxychloroquine, diabetes, hypertension, stroke and multiple dental abscesses presents with persistent neck pain. Initial CT neck with contrast showed diffuse fat stranding. Subsequently, alendronate was discontinued due to jaw necrosis suspicion. Eight months later, repeat CT scan showed new non-mass-like soft tissue thickening in the subcutaneous fat abutting the right anterior mandible with mandibular teeth cavities and periapical lucencies, likely to be periodontal cellulitis versus radiation osteonecrosis. Later, patient complained of a piece of bone penetrating the skin of her chin and presented with continuous drainage from sinus tract in her mandible, which was diagnosed as osteonecrosis attributed to bisphosphonates, previous radiation therapy, and dental abscesses. Patient was started on abaloparatide, an osteo-anabolic medication for osteoporosis and enrolled in hyperbaric oxygen therapy which immensely helped in controlling sinus drainage. Patient is currently awaiting mandibular reconstruction surgery.
Discussion
ONJ, often associated with pain, swelling, exposed bone, local infection, and pathologic fracture of the jaw, is a rare complication of bisphosphonate therapy. Currently, no prospective data exists to advise the benefits of therapy discontinuation however most clinical practices tend to discontinue at least temporarily. The incidence increases with longer treatment duration, particularly when therapy exceeds four years. Risk factors for developing ONJ while taking bisphosphonates include IV administration, anticancer therapy, dose and duration of exposure, dental extractions/implants, glucocorticoids, smoking, diabetes, and preexisting dental disease.
Case reports and series suggest benefit from hyperbaric oxygen therapy in wound healing, pain, and quality of life at three months, however no significant differences exist with outcomes beyond three months. Patients being considered for therapy with a bisphosphonate should be thoroughly evaluated for dental issues, prior to initiating therapy. Conservative management with limited debridement, antibiotic therapy as needed, and topical mouth rinses rather than aggressive surgical resection are recommended. Conservative therapy may result in healing in a significant proportion of patients. Surgical resection of necrotic bone should be reserved for refractory or advanced cases. Providers should remain cautious while prescribing high doses of bisphosphonates in patients with increased risk factors to prevent, timely diagnose and treat this condition.
References
Edwards BJ, Gounder M, McKoy JM, et al. Pharmacovigilance and reporting oversight in US FDA fast-track process: bisphosphonates and osteonecrosis of the jaw. Lancet Oncol 2008; 9:1166.
Khosla S, Burr D, Cauley J, et al. Bisphosphonate-associated osteonecrosis of the jaw: report of a task force of the American Society for Bone and Mineral Research. J Bone Miner Res 2007; 22:1479.
Hoff AO, Toth BB, Altundag K, et al. Frequency and risk factors associated with osteonecrosis of the jaw in cancer patients treated with intravenous bisphosphonates. J Bone Miner Res 2008; 23:826.
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Cho, Jinsoo. "Velocity-based cardiac segmentation and motion-tracking." Diss., Available online, Georgia Institute of Technology, 2004:, 2003. http://etd.gatech.edu/theses/available/etd-04082004-180106/unrestricted/cho%5Fjinsoo%5F200312%5Fphd.pdf.
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Todd, Bryan S. "A formal approach to the design of medical diagnostic programs." Thesis, University of Oxford, 1988. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.670360.
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Camargo, Anyela. "An automatic system for the detection, diagnosis and control of plant diseases and other agents." Thesis, University of Liverpool, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.426137.
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Tan, Zhen. "Low noise heart sound acquisition in wearable system for individual-centered CVD diagnosis." Thesis, University of Macau, 2017. http://umaclib3.umac.mo/record=b3691773.
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Weissenfels, Robert. "CCL11 as a Biomarker for the In Vivo Diagnosis of Chronic Traumatic Encephalopathy." Scholarship @ Claremont, 2018. http://scholarship.claremont.edu/cmc_theses/1823.
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Chronic traumatic encephalopathy is the neurodegenerative disease that is ascribed to the long term development of cognitive, behavioral, emotional, and motor deficits as a result of the exposure to high amounts of sub concussive traumatic brain injuries. The disease has gained recent popularity in the media for its prevalence in American football as a response to recent research that has suggested the prominence of the disease in nearly every NFL player that is examined post mortem. This has produced a growing concern for the consequences of head impact and participation in contact sports. Despite media attention, little is currently known about the specific causes of the disease and an in life diagnosis is still nonexistent. The present study proposes that the chemokine, CCL11, could prove to be a viable biomarker for recognizing the onset and progression of chronic traumatic encephalopathy. The results of our study suggest that football players who are clinically suspicious of CTE show significantly higher levels of CCL11 in their cerebrospinal fluid than do sedentary controls and noncontact athletes. Our results demonstrate that this increase in CCL11 is correlated with the number of years that a football player had participated in. We also suggest that this increase in CCL11 is associated with a unique immune response through results showing that the CCL11 expression increase is correlated with an increase in the expression of the cytokine IL-4 and substantial decrease in IFN-gamma. The analysis of CCL11 expression levels in the cerebrospinal fluid may prove to be a viable method of diagnosing and providing treatment for patients who may be at risk of chronic traumatic encephalopathy.
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Roberts, Tim S. "The development of an expert system for the diagnosis of diseases in fibre and dairy goats." Thesis, Edith Cowan University, Research Online, Perth, Western Australia, 1990. https://ro.ecu.edu.au/theses/1113.
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This thesis details the development of an expert system for the diagnosis of diseases in fibre and dairy goats. Divided into five sections, five appendices, and a bibliography, this thesis centres on the methods used to build the expert system: the decisions taken at the outset of, and during the course of, development; some of the problems encountered, and the solutions to those problems. A detailed appraisal is made of the development process and suggestions are made for future developments over similar domains (for example, the diagnosis of diseases in animals other than goats). Much emphasis is placed on three topics in particular: the selection of the expert system tool(s) to be used (and the rejection of numerous others); the methodology employed for this selection process; and the methodology used for the process of development. Other topics which are routinely found in texts on expert systems (for example, knowledge elicitation techniques, explanatory facilities, expert system evaluation etc) are dealt with only briefly. However, for the reader interested in further information on these topics, references are made in the text to appropriate sources.
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Brink, Yolandi. "Sitting posture : a predictive factor for upper quadrant musculoskeletal pain in computing high school students." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71876.
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Thesis (PhD)--Stellenbosch University, 2012.Includes bibliography
ENGLISH ABSTRACT: Introduction: The increased prevalence of adolescent upper quadrant musculoskeletal pain (UQMP) is becoming a great concern to health professionals. The risk factors associated with adolescent UQMP are complex and multifactorial, including, among others sitting as a physical risk factor. However, no evidence exists to support sitting postural angles as a potential predictive factor for adolescent UQMP in computing high school students. Thus, the current project aimed to describe the three-dimensional (3D) sitting postural angles of computing South African high school students in a real-life setting, using a well-tested and documented posture measurement instrument. Methodology: This research project is comprised of seven related studies. Part I of the dissertation presents a systematic review describing the reliability and validity testing of posture measurement instruments. This is followed by three primary correlation and repeated measures observational studies aimed at ascertaining the reliability and validity of a newly developed 3D Posture Analysis Tool (3D-PAT) in the measurement of nine sitting postural angles of computing high school students. Part II of the dissertation presents a systematic review, that evaluates the latest published research evidence of whether sitting is related to UQMP, and, if so, to identify the elements of sitting that significantly contribute to UQMP. This review is followed by a description of a cohort study, with a prospective period of one year. The 3D-PAT was implemented in a clinical research setting in order to measure the 3D sitting posture of a cohort of asymptomatic computing high school students and in order to assess the outcome, seated-related UQMP, prospectively. The prospective study design enabled the research project to contribute to an understanding of any causative relationship between the exposure (sitting postural angles) and the outcome (seated-related UQMP) in a subgroup of adolescents (computer users). Results: After the first phase of psychometric testing of the 3D-PAT using high school students, the findings indicated that the instrument required modifications prior to further psychometric testing. The second phase of testing revealed that the 3D-PAT compared very well with the reference standard for measurement of the X-, Y- and Z-coordinates of the reflective markers on a mannequin. The findings from the phase three study, again using high school students, indicated that the 3D-PAT compared very well with the reference standard and justified its use for the measurement of six sitting postural angles of the upper quadrant in computing high school students. For the cohort study, a 60% response rate for participation was achieved at baseline, with 98% of the students participating at six-month and 80% at one-year follow up. Of the students, 33.5% complained of seated-related UQMP during the follow-up period. Exposure to increased head flexion (>80°) (ρ=0.0001) and the combination of increased head flexion and decreased cranio-cervical angles (ρ=0.007) were significant predictors of seated-related UQMP for those computing high school students complaining of pain greater than the 90th percentile for such. Conclusion: The project described in the current dissertation is the first research project to assess sitting postural angles in asymptomatic high school students, while they worked on desktop computers in a school computer classroom and to assess UQMP prospectively. The research project reports a causal relationship between increased head flexion and seated-related UQMP as increased head flexion was found to be a predictor of seated-related UQMP developing within six to 12 months for computing high school students with a pain score equal or greater than the 90th percentile for pain. The research project emphasises that further research is warranted to investigate the causal pathway between sitting posture and adolescents’ UQMP.
AFRIKAANSE OPSOMMING: Inleiding: Die stygende voorkoms van boonste-kwadrant muskuloskeletale-pyn (BKMP) onder adolessente is besig om ’n groot bron van kommer vir professionele gesondheidswerkers te word. Die risiko-faktore waarmee adolessente BKMP gepaard gaan, is kompleks en multifaktories. Dit sluit onder andere sit as ’n fisiese risiko-faktor in. Daar is egter nog geen bewyse om sittende posturale hoeke as potensiële voorspeller van adolessente BKMP te ondersteun nie. Dus beoog hierdie projek om die drie-dimensionele (3D) sittende posturale hoeke van Suid-Afrikaanse hoërskoolleerders wat ook rekenaargebruikers is, in ’n werklike omgewing te beskryf, deur gebruik te maak van ’n instrument wat postuur meet en wat goed getoets en gedokumenteerd is. Metodiek: Hierdie navorsingsprojek is saamgestel uit sewe studies. Gedeelte I van die proefskrif bied ’n sistematiese oorsig van betroubaarheids- en geldigheidstoetsing van instrumente wat postuur meet. Dit word gevolg deur drie primêre korrelasie studies en studies vir die waarneming van herhaalde meting wat die betroubaarheid en geldigheid van n nuut-ontwikkelde 3D instrument vir posturale analise (3D-PAT) bepaal, wanneer nege sittende posturale hoeke van hoërskoolleerders wat rekenaars gebruik, gemeet word. Gedeelte II van die proefskrif bied ’n sistematiese oorsig van die jongste gepubliseerde navorsing om te evalueer of daar bewyse is dat sit verband hou met BKMP, en, indien wel, om die elemente van sit wat betekenisvol bydra tot BKMP, te identifiseer. Die sistematiese oorsig word deur ’n beskrywing van ‘n jaarlange kohortstudie gevolg. Die 3D-PAT is gebruik in ’n kliniese-navorsingsraamwerk om die 3D-sitpostuur van ’n kohort simptoomvrye hoërskoolleerders wat rekenaargebruikers is, te meet en sitverwante BKMP as uitkoms in die vooruitsig te stel. Die studie ontwerp het dit vir die navorsingsprojek moontlik gemaak om ’n insiggewende bydrae te lewer tot begrip vir enige oorsaaklikheidsverwantskap tussen die blootstelling (sittende posturale hoeke) en die uitkoms (sitverwante BKMP) in ’n subgroup van adolessente (rekenaargebruikers). Resultate: Na afloop van die eerste psigometriese toesting van die 3D-PAT, waarin hoërskoolleerders gebruik is, het bevindings daarop gedui dat die instrument verander moet word voordat toetsing kan voortgaan. Die tweede fase van toetsing het getoon dat die 3D-PAT baie goed vergelyk met die verwysingstandaard vir die meet van die X-, Y- en Z-koördinate van die reflektiewe merkers op ’n mannekyn. Die bevindings van die derde fase van die studie, waartydens hoërskoolleerders weer gebruik is, het aangedui dat die 3D-PAT baie goed vergelyk met die verwysingstandaard. Dit het die gebruik van die instrument om ses sittende posturale hoeke van die boonste kwadrant van hoërskoolleerders wat rekenaars gebruik te meet, bevestig. Die kohortstudie het ’n 60%-reaksiesyfer vir deelname behaal tydens die basislynmetings, waarvan 98% leerders deelgeneem het aan die sesmaande-opvolgmetings en 80% aan die eenjaaropvolgmetings. ’n Totaal van 33.5% van die leerders het gekla van sitverwante BKMP gedurende die eenjaar opvolgperiode. Blootstelling aan ’n vergrootte kopfleksie-hoek (>80°) (ρ = 0.0001) en die kombinasie van ’n vergrootte kopfleksie- en verminderde kranio-servikale hoek (ρ = 0.007) was betekenisvolle voorspellers van sitverwante BKMP vir die hoërskoolleerders wat rekenaars gebruik en kla van groter pyn as die 90ste persentiel daarvan. Gevolgtrekking: Hierdie projek is die eerste navorsing wat sittende posturale hoeke van simptoomvrye hoërskoolleerders wat op tafelrekenaars in die skool se rekenaarklaskamer werk, meet en BKMP voorspel. Die navorsingsprojek rapporteer ‘n oorsaaklikheidsverwantskap tussen ‘n vergrootte kopfleksie-hoek en sitverwante BKMP omdat vergrootte kopfleksie ‘n voorspeller is van sitverwante BKMP wat binne ses tot 12 maande by hoërskoolleerders wat rekenaars gebruik, met ‘n pyntelling gelyk of groter as die 90ste persentiel van pyn, ontwikkel. Die navorsingsprojek beklemtoon dat verdere navorsing om die oorsaaklikheidsroete tussen sitpostuur en adolessente BKMP te ondersoek, geregverdig is.
Medical Research Council of South Africa
National Research Fund
Division of Research Development and Support of Stellenbosch University
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Mitchell, Kierra. "Racial Disparities in the Diagnosis and Treatment of Type 1 Diabetes in Black American Youth." Scholarship @ Claremont, 2019. https://scholarship.claremont.edu/scripps_theses/1239.
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Introduction: Rates of childhood-onset type 1 diabetes (T1D) are steadily increasing among American youth, yet Black Americans are more likely to suffer from serious T1D-related complications caused by poor glycemic control. The aim of this thesis is to determine the external factors that are causing discrepancies in the development, diagnosis, treatment, and long-term management of T1D in Black youth.
Methods: Epidemiological studies were compiled from the American Diabetes Association, Center for Disease Control (CDC), International Diabetes Foundation (IDF), Kaiser Family Foundation (KFF), and the Claremont Colleges Library network to identify the sociocultural aspects that negatively affect long-term glycemic control in Black youth.
Results: Studies indicate that Black youth with T1D are more likely to face disadvantages in treatment regimen which are attributed to insurance coverage, socioeconomic status, education level, and implicit bias. Most studies demonstrate that these factors result in poor glycemic control, which subsequently leads to severe dysglycemia-related complications later in life.
Conclusion and Discussion: Many Black youth who suffer from T1D receive insufficient healthcare, which is often exacerbated by a lack of social and economic resources. As a result, they may not have the means to maintain consistent, healthy glycemic levels. System-level changes are necessary to change the morbidity and mortality of T1D in Black youth. Future research should include the analysis of other racial minority groups in order to uncover additional institutional disparities.
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Guo, Ran. "Intelligent method for collecting vital signals in versatile distributed e-home healthcare." Thesis, University of Macau, 2017. http://umaclib3.umac.mo/record=b3691807.
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Ngcamu, Nokubonga Slindele (Sma). "Awkward working postures and precision performance as an example of the relationship between ergonomics and production quality." Thesis, Rhodes University, 2009. http://eprints.ru.ac.za/1561/.
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Nie, Yali. "Automatic Melanoma Diagnosis in Dermoscopic Imaging Base on Deep Learning System." Licentiate thesis, Mittuniversitetet, Institutionen för elektronikkonstruktion, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:miun:diva-41751.
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Melanoma is one of the deadliest forms of cancer. Unfortunately, its incidence rates have been increasing all over the world. One of the techniques used by dermatologists to diagnose melanomas is an imaging modality called dermoscopy. The skin lesion is inspected using a magnification device and a light source. This technique makes it possible for the dermatologist to observe subcutaneous structures that would be invisible otherwise. However, the use of dermoscopy is not straightforward, requiring years of practice. Moreover, the diagnosis is many times subjective and challenging to reproduce. Therefore, it is necessary to develop automatic methods that will help dermatologists provide more reliable diagnoses. Since this cancer is visible on the skin, it is potentially detectable at a very early stage when it is curable. Recent developments have converged to make fully automatic early melanoma detection a real possibility. First, the advent of dermoscopy has enabled a dramatic boost in the clinical diagnostic ability to the point that it can detect melanoma in the clinic at the earliest stages. This technology’s global adoption has allowed the accumulation of extensive collections of dermoscopy images. The development of advanced technologies in image processing and machine learning has given us the ability to distinguish malignant melanoma from the many benign mimics that require no biopsy. These new technologies should allow earlier detection of melanoma and reduce a large number of unnecessary and costly biopsy procedures. Although some of the new systems reported for these technologies have shown promise in preliminary trials, a widespread implementation must await further technical progress in accuracy and reproducibility. This thesis provides an overview of our deep learning (DL) based methods used in the diagnosis of melanoma in dermoscopy images. First, we introduce the background. Then, this paper gives a brief overview of the state-of-art article on melanoma interpret. After that, a review is provided on the deep learning models for melanoma image analysis and the main popular techniques to improve the diagnose performance. We also made a summary of our research results. Finally, we discuss the challenges and opportunities for automating melanocytic skin lesions’ diagnostic procedures. We end with an overview of a conclusion and directions for the following research plan.
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Larsman, Pernilla. "On the relation between psychosocial work environment and musculoskeletal symptoms : a structural equation modeling approach /." Stockholm : Arbetslivsinstitutet, förlagstjänst, 2006. http://ebib.arbetslivsinstitutet.se/ah/2006/ah2006_02.pdf.
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Hashmi, Sumaiya F. "A Machine Learning Approach to Diagnosis of Parkinson’s Disease." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/cmc_theses/798.
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I will investigate applications of machine learning algorithms to medical data, adaptations of differences in data collection, and the use of ensemble techniques.
Focusing on the binary classification problem of Parkinson’s Disease (PD) diagnosis, I will apply machine learning algorithms to a primary dataset consisting of voice recordings from healthy and PD subjects. Specifically, I will use Artificial Neural Networks, Support Vector Machines, and an Ensemble Learning algorithm to reproduce results from [MS12] and [GM09].
Next, I will adapt a secondary regression dataset of PD recordings and combine it with the primary binary classification dataset, testing various techniques to consolidate the data including treating the regression data as unlabeled data in a semi-supervised learning approach. I will determine the performance of the above algorithms on this consolidated dataset.
Performance of algorithms will be evaluated using 10-fold cross validation and results will be analyzed in a confusion matrix. Accuracy, precision, recall, and F-score will be calculated.
The expands on past related work, which has used either a regression dataset alone to predict a Unified Parkinson’s Disease Rating Scale score for PD patients, or a classification dataset to determine healthy or PD diagnosis. In past work, the datasets have not been combined, and the regression set has not been used to contribute to evaluation of healthy subjects.
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Bell, Alison. "An ergonomic analysis of vacuum cleaning tasks using observational risk assessment tools." School of Health Sciences - Faculty of Health & Behavioural Sciences, 2008. http://ro.uow.edu.au/theses/126.
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This research thesis examined the risk of upper limb musculoskeletal disorders for cleaning workers while performing vacuum cleaning tasks in the normal course of their employment. The cleaning workers in this study were from three sectors of the workforce – government schools, hospitality and commercial office space. The vacuum cleaning tasks were divided into those performed with a back pack style vacuum cleaning machine and those using a canister/barrel machine. Three observational risk assessment tools were selected to measure the risk of these tasks to cleaning workers. The selected tools were the Manual Tasks Risk Assessment Tool (ManTRA) version 2.0; the Quick Exposure Check (QEC) (Li & Buckle, 1998); and the Rapid Upper Limb Assessment tool (RULA) (McAtamney & Corlett, 1993). Results of this thesis study demonstrated that vacuum cleaning is a risk to the musculoskeletal health of cleaning workers, with some variation between the tool ratings, reflecting the specificity and/or sensitivity of each tool. Differences were found between the three cleaning sectors in terms of overall risk posed by vacuum cleaning tasks. The sector with the greatest risk was found to be the government school cleaners, followed by the hospitality and then commercial office space cleaning sectors. The ‘risk experience’ difference between the sectors cannot be attributed only to vacuum cleaner characteristics, but also, the environment and length of shift worked by the cleaning staff. Further research is required to determine the difference in risk exposure between the two types of vacuum cleaner (back pack and canister).
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Castaneda-Avila, Maira A. "The Role of a Monoclonal Gammopathy of Undetermined Significance Diagnosis in Healthcare Utilization." eScholarship@UMMS, 2021. https://escholarship.umassmed.edu/gsbs_diss/1135.
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Background
Monoclonal Gammopathy of Undetermined Significance (MGUS) is an understudied precursor of multiple myeloma (MM), the second most prevalent hematologic malignancy in the United States. This dissertation was designed to: (1) Describe the trajectories of serum biomarkers over time in patients with an MGUS diagnosis, (2) Determine if an MGUS diagnosis is associated with changes in healthcare service utilization, and (3) explore the patient- and provider-level drivers of healthcare utilization in patients with MGUS.
Methods
Data sources include health claims and electronic health records from a community-based population of patients seeking care in central Massachusetts and primary qualitative data collected from providers and patients’ interviews. The analyses included descriptive statistics, group-based trajectory modeling, conditional Poisson regression, and qualitative data analyses.
Results
(1) Three distinct multi-trajectory groups of creatinine and hemoglobin were identified. (2) The rates of emergency room, hospital, and outpatient visits were higher for patients with MGUS than patients without MGUS. (3) Patients have a basic understanding of MGUS; however, some patients feel anxiety, which may affect other aspects of their lives. Patients primarily see hematologists for follow-up care; other providers have less knowledge about MGUS.
Conclusions
Biomarker trajectories characterize specific subpopulations of patients with MGUS over time. We found that an MGUS diagnosis is associated with higher healthcare utilization, especially during the months surrounding the diagnosis date. Finally, our study suggests that some patients with MGUS may need psychosocial support services and identifies a gap in knowledge around caring for MGUS patients among primary care providers.
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Sitt, Wing-hung Edward, and 薛穎雄. "Is the validity of non-invasive computerized tomography coronary angiography equivalent to invasive coronary angiography for theevaluation of coronary artery disease." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2007. http://hub.hku.hk/bib/B39724578.
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Genes, Nicholas G. "Chondrocyte Adhesion to RGD-bonded Alginate: Effect on Mechanotransduction and Matrix Metabolism: a Dissertation." eScholarship@UMMS, 2003. https://escholarship.umassmed.edu/gsbs_diss/89.
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The mechanism of mechanotransduction in chondrocyte matrix metabolism is not well understood, in part because of the density of cartilage and in part because of limitations in in vitroculture systems. Using alginate covalently modified to include the integrin adhesion ligand R-G-D (arginine-glycine-aspartate) represents a unique approach to studying mechanotransduction in that it allows for exploration of the role of integrin adhesion in mediating changes to chondrocyte behavior.
The hypothesis of this research was that chondrocytes will form a cytoskeletal adhesion to RGD-alginate mediated integrins, that this attachment will enable chondrocyte sensation of mechanical signals, and this signaling will alter chondrocyte matrix metabolism. The first aim of this research was to characterize chondrocyte attachment to RGD-alginate, and assess the role of substrate mechanics on chondrocyte attachment kinetics and morphology. Secondly, the effect of chondrocyte attachment to RGD-alginate in 3D culture on matrix biosynthesis was assessed, as were changes in substrate mechanics. Finally, this research aimed to determine the metabolic response of chondrocytes to changes in intrinsic and extrinsic mechanics.
It was found that the RGD ligand functionalized the alginate scaffold, enabling chondrocytes to sense the mechanical environment. Attachment kinetics, morphology, and proteoglycan metabolism were found to adapt to hydrogel matrix stiffness when an integrin adhesion was present. Externally applied compression was transmitted through this integrin attachment, causing changes in proteoglycan synthesis. Components of media serum were found to modulate the effects of integrin mechanotransduction.
These results were obtained by analyzing a novel approach with established techniques, such as the DMB dye assay for sulfated GAG content. The conclusions conform to diverse data from cartilage explant loading and monolayer culture studies, yet were accomplished using one versatile system in a straightforward manner. The potential of this system extends further, into identification of intracellular signaling pathways and extracellular modulation of matrix components. Seeded RGD-alginate is well suited for studying consequences of integrin attachment.
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Matzelle, Melissa M. "Inflammation Inhibits Osteoblast-Mediated Bone Formation in Rheumatoid Arthritis and Regulates the Wnt and BMP Signaling Pathways: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/596.
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Osteoclast-mediated focal articular bone erosion is a hallmark of rheumatoid arthritis, a disease of inflammation-induced bone loss. Inflammation in the bone microenvironment enhances osteoclast differentiation leading to bone erosion. Simultaneously, inflammation also inhibits osteoblast-mediated bone formation, further contributing to the net loss of bone. Previous studies have shown a paucity of mature osteoblasts at eroded bone surfaces correlating with suppression of bone formation and upregulation of antagonists of the Wnt pathway, a signaling cascade essential for osteoblast lineage commitment. Despite these observations, the exact pathogenesis of impaired bone formation in the setting of inflammation is not clearly understood.
This dissertation aims to delineate the mechanisms by which inflammation suppresses osteoblast differentiation and activity in inflammatory arthritis. Specifically, this research elucidates how inflammation-induced alterations in the Wnt and bone morphogenetic protein (BMP) osteogenic signaling pathways contribute to bone loss and formation at distinct inflammatory microenvironments within the bone. Secondly, the means by which cellular mediators, including lymphocytes and macrophages, facilitate bone erosion and formation was addressed.
Taken together, the research in this dissertation underscores the relationship between inflammation-induced bone loss and alterations in osteogenic signaling. Using an innovative murine inflammatory arthritis model, this study definitively demonstrates that resolving inflammation promotes osteoblast-mediated bone formation. Repair of erosions correlates with upregulation of synovial expression of Wnt10b, a Wnt agonist, and downregulation of sFRP1 and sFRP2, Wnt antagonists. This work also directly evaluates the contribution of sFRP1 to inflammation-induced bone destruction. Furthermore, this research demonstrates that expression of BMP3, a negative regulator of BMP signaling, is upregulated in osteoblasts by IL-17, a pro-inflammatory cytokine. BMP3-expressing osteoblasts are also observed at erosion sites in murine arthritis. Lastly, evaluation of the mediators of inflammation-induced periosteal bone formation implicates BMP2 as a means by which inflammation may positively regulate osteoblast function.
This dissertation further elucidates the role of T cells and macrophages in the erosion and formation processes, respectively. In the absence of lymphocytes, bone erosion occurred normally, demonstrating that RANKL-expressing lymphocytes are not absolutely required for the bone erosion. Preliminary studies also suggest that M2 macrophages are potential mediators of bone formation via the expression of BMP2.
In conclusion, this dissertation explores the ability of inflammation to act as a rheostat, which controls the fate of bone by modulating not only osteoclast differentiation, but also osteogenic signaling pathways and cellular mediators in the bone microenvironment. The soluble mediators and cell types identified in this research highlight novel mechanisms by which inflammation may regulate osteoblast activity within the bone microenvironment. Collectively, these data imply that strict control of inflammation may be necessary in order to create an anabolic environment that preserves bone architecture in diseases of inflammation-induced bone loss.
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Al, Talalwah Waseem. "The vascular variability of the iliac system and clinical diagnosis in radiology and neurology." Thesis, University of Dundee, 2013. https://discovery.dundee.ac.uk/en/studentTheses/1aa955a0-1289-4670-b226-0eea5425ae0b.
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The sciatic nerve is the largest nerve in the human body giving both motor and sensory innervations to the lower limb. It can be affected in chronic diseases, such as diabetes, or compressed anatomically by structures such as piriformis and aneurysms leading to sciatica or paralysis of the lower limb. The current study therefore focuses on the arterial supply of the sciatic nerve as well as its course. Embryologically, the sciatic nerve is supplied via the axial artery during the first trimester. As the axial artery regresses, the iliac system develops. A failure of sciatic artery regression leads to several variations of pelvic and femoral arteries, with a risk of iatrogenic injury/trauma for those patients undergoing pelvic, gluteal and thigh surgical procedures. An understanding of the variability of the pelvic arteries in relation to a coexistent sciatic artery will provide an appropriate background for clinicians. The present study proposes a new theory of sciatic artery development and persistence, as well as new theories for the superior and inferior gluteal, internal pudendal and obturator arteries. The thesis is in two parts: first an anatomical study on the dissection of 171 cadavers including the pelvic, gluteal and thigh regions to observe (i) the patterns of the arteries these regions, and (ii) the course of the sciatic nerve. With variable course of sciatic nerve, there is a variability of its blood supply. Moreover, it includes a new classification of sciatic nerve with respect to clinical implications. The thesis clarifies the origins of the sciatic artery and its course. The second part is a literature review of sciatic artery aneurysm cases in 171 patients, which clarifies the risk of aneurysm, together with its incidence with respect to pathologic finding and associated disorders. Radiologists have to be aware of the internal iliac artery classifications to be able to alert general surgeons, orthopaedic surgeons, obstetricians, gynecologists, and urologists so that they can improve patient management.
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Crighton, Keith S. "Designing, producing and evaluating a multimedia computer based education system for teaching red eye diagnosis." Thesis, Queensland University of Technology, 1998. https://eprints.qut.edu.au/36744/1/36744_Digitised%20Thesis.pdf.
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The aim of this research thesis was to develop principles for the production of a computer based education (CBE) system designed to teach the diagnosis of 'red eyes' to undergraduate optometry students. The topic of 'red eyes' was chosen as the subject matter for this research because of an increasing movement by Australian optometrists towards using therapeutic agents for the treatment of 'red eyes'.
Based upon the results of an extensive literature review on CBE and effective teaching strategies, a series of four separate tutorials on 'red eye' diagnosis was developed. The first tutorial was initially programmed and evaluated in a pilot study. Results from this evaluation were incorporated into the design of a further three tutorials which increased in difficulty and decreased in feedback from tutorial one to four. Assessment of the four tutorials was then conducted using nine final year students and one recent graduate.
Qualitative evaluation of the tutorials indicated that the teaching strategies that were applied were successful in teaching most of the concepts considered important in 'red eye diagnosis'. Of note was the feeling of the students that they had increased their understanding of the topic and their enthusiasm for the usefulness of the tutorials and for CBE in general.
As a result of this research process, a structure was developed for teaching the topic of 'red eye' diagnosis that breaks the learning process down into four stages: 1. Recognition and Nomenclature 2. Signs & Symptoms/Differential Diagnosis 3. Simulated Controlled Examinations 4. Simulated Uncontrolled Examinations. Each of these four stages needs to be assessed in a similar manner to that used in the research and described in this thesis.
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Skelton, Sarah Anne. "Combined and additive effects of assembly tasks and constrained body postures." Thesis, Rhodes University, 2007. http://hdl.handle.net/10962/d1005185.
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Despite extensive research into musculoskeletal disorders (MSDs) they continue to plague workers. Manual materials handling (MMH), in particular the concurrence of load manipulation and awkward body posture, has been identified as a key factor in the onset of MSDs. Only a few studies have looked at the interaction between manipulation tasks and working posture during assembly tasks and as a result their relationship has not been widely explored. Assessing the stresses resulting from individual task factors and body posture in isolation and adding them together may be too simplified to estimate an overall risk profile, since this does not take into account that there may be a non-linear interaction in strain responses when manipulation task and body posture interact. Therefore, the present study investigated biophysical, physiological and psychophysical responses to combined tasks, rather than individual tasks of body posture and manipulative tasks. The objective of the research was to establish the interactive effects of constrained body postures and manipulative tasks and to identify whether a cumulative or compensatory reaction occurs during this interaction. Nine conditions were assessed in a laboratory setting, which included combinations of three working postures (standing, sitting and stooping) and three assembly tasks (torque wrenching, precision and no task). Thirty-six subjects were required to complete all nine conditions, with each condition lasting ninety seconds. Muscle activity was recorded for seven muscles from the upper extremity, trunk and lower extremity regions and was complemented by physiological (heart rate, tidal volume, minute ventilation, oxygen consumption, energy expenditure and breathing frequency) and psychophysical (body discomfort) data. At the completion of all nine conditions subjects completed a retrospective psychophysical rating questionnaire pertaining to discomfort felt during the conditions. Responses obtained for the different task and posture combinations revealed compensatory reactions (additive > combined) for most of the conditions assessed for the biomechanical and physiological responses. In the majority of cases for muscle activity, no significant differences were found between the combined and the additive effects (p < 0.05), while for the physiological responses there were mostly significant differences observed. Psychophysical responses indicated that there was a significant difference overall between the additive and combined effects. The results of this study demonstrate that in order to identify risk areas, manipulation tasks and constrained working postures may be considered either in isolation and added together (additive) or as a combined task, since there were very few significant differences observed between these two effects. Further studies are required, however, to provide conclusive evidence.
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Acharyya, Swarnali. "Elucidating molecular mechanisms of muscle wasting in chronic diseases." Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1180096565.
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Hott, Morgan E. "Cartilage tissue engineering: uses of injection molding and computer aided design for the fabrication of complex geometries with high dimensional tolerances: a dissertation." eScholarship@UMMS, 2007. https://escholarship.umassmed.edu/gsbs_diss/325.
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Cartilage Tissue Engineering. Joint pain and functional impairment due to cartilage damage from osteoarthritis and other means is a major source of disability for adults the world over. Cartilage is an avascular tissue with a very limited capacity for self repair. Current medical and surgical approaches to cartilage repair also have limited efficacy, and in all cases fail to completely restore a normal, healthy cartilage phenotype. Tissue engineering is a relatively new approach to cartilage repair that seeks to fabricate a replacement tissue, indistinguishable from healthy, native tissue.
The basic idea of the tissue engineering approach is to seed tissue synthesizing cells into a shapeable, biocompatible/bioabsorbable scaffold that serves as a temporary extracellular matrix with a localized source of bioactive molecules to direct the development of new tissue. The challenge of tissue engineering is to identify cells, scaffolds, and growth conditions that will be optimal for tissue regeneration. The goal of the current studies was to evaluate one aspect of all three of the major components of cartilage tissue engineering: cell source, scaffolding material and preparation, and controlled growth factor delivery.
We evaluated the chondrogenic potential of human nasal chondrocytes grown in calcium alginate in an in vivo culture system, the potential of computer-aided design and injection molding with calcium alginate to reliably reproduce complex geometries with high dimensional tolerances, and the potential for the controlled release of TGF-β1 from calcium alginate modified by the covalent addition of a recently discovered TGF-β binding peptide.
We found that adult human nasal chondrocytes show significant chondrogenic potential when grown within an alginate scaffold. We also found that alginate is readily amenable to an injection molding process that utilizes precision made molds from computer-aided design and solid free form fabrication, allowing for the fabrication of tissue engineered constructs with very precise shape fidelity. Additionally, we found that calcium alginate could be reliably modified by the covalent addition of peptides, and that the addition of a newly discovered TGF-β binding peptide delayed the release of pre-loaded TGF-β1. Together these results show some of the encouraging prospects for cartilage tissue engineering.
`Menière’s Syndrome.Menière’s syndrome is an inner ear disorder characterized by idiopathic endolymphatic hydrops with associated periodic tinnitus, vertigo, and progressive sensorineural hearing loss. It affects approximately 0.2% of the population, for whom it can be quite devastating. In addition to progressive hearing loss people with Menière’s syndrome are prone to sudden attacks of vertigo and tinnitus that are severe enough that they can lead to falls and potentially serious injury. People subject to frequent attacks are unable to drive, with obvious consequences on standard of living.
In the current studies we evaluated the standard animal model of Menière’s syndrome by comparing cochlear turn specific hearing thresholds and the degree of hydrops in that turn. A positive correlation between these had previously been established in the study of human temporal bones from people with Menière’s syndrome, but had not been reported in the animal model.
We also evaluated the potential of aminoguanidine, a relatively specific inhibitor of the inducible isoform of nitric oxide synthase, as a neuroprotective therapeutic agent for preservation of hearing in animals with surgically induced endolymphatic hydrops.
We found, for the first time, a partial correlation between cochlear turn specific hydrops and hearing thresholds in the most commonly used animal model of Menière’s syndrome, helping to validate the utility of this animal model for future studies. We also found that aminoguanidine did indeed partially preserve hearing in animals with surgically induced Menière’s syndrome. This encouraging result appears to be the first report of a medical intervention protective against hearing loss in an animal model of Menière’s syndrome, and may help us to understand the etiology pathology seen in Menière’s syndrome.
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Ni, Chih-Wen. "Discovery of mechanosensitive microrna and messenger RNA in mouse arterial endothelium and in cultured endothelial cells." Diss., Georgia Institute of Technology, 2010. http://hdl.handle.net/1853/34674.
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Atherosclerosis is a major contributor to cardiovascular disease and accounts for an estimated one third of deaths overall. In order to address the hemodynamic components of disease pathogenesis, researchers have focused on mechanotransduction of flow-dependent shear stress in the vascular endothelium as a source of novel pathological mechanisms. Understanding how unidirectional, laminar blood flow protects vessels from atherogenesis, while disturbed, oscillatory blood flow promotes it, stands to provide enormous insight into disease pathogenesis and may provide powerful, specific new therapies for cardiovascular disease intervention.
The overall objective of this dissertation was to determine which microRNAs (miRNAs) and mRNAs are regulated by different flow conditions in vascular endothelial cells in vitro and in mouse carotid artery endothelium in vivo, and to identify which miRNAs mediate flow-dependent vascular inflammation. The overall hypothesis of this project was that oscillatory shear (OS) and laminar shear (LS) stress differentially alter the expression of mechanosensitive miRNAs each capable of regulating complex networks of gene expression, which in turn leads to inflammation in endothelial cells. This hypothesis was tested using both in vitro and in vivo approaches, high throughput microarray analyses, and functional validation of specific targets by PCR.
The findings from the partial carotid ligation model show that acute exposure to disturbed flow results in accelerated endothelial dysfunction and atherosclerosis in vivo. High-throughput microarrays reveal distinct expression profiles of both miRNAs and mRNAs in mouse endothelium exposed to disturbed flow suggesting the regulatory mechanisms by which miRNAs regulate mRNAs resulting in EC inflammation, the earliest stage of atherosclerosis. This in vivo study provides new insight into the mechanisms of flow induced atherosclerosis. In particular, the upregulation of miR-663 due to OS in HUVEC causes monocyte adhesion, but not endothelial apoptosis, in an ICAM-1 dependent manner. miR-663 regulates a group of genes including transcriptional factors and inflammatory genes which may also mediate OS-induced EC inflammation. Collectively, revealing the profiles of miRNAs and mRNAs regulated by hemodynamic flow provides a better understanding in vascular diseases and provide potential target for developing effective preventative therapeutic approaches in cardiovascular diseases.
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Roos, Annerine. "Validation of a rating scale for bedside cognitive assessment." Thesis, Stellenbosch : Stellenbosch University, 2004. http://hdl.handle.net/10019.1/50219.
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Thesis (MMed)--University of Stellenbosch, 2004.ENGLISH ABSTRACT: Numerous tests exist for the assessment of general cognitive functioning. Most of these tests were developed within the discipline of psychology. Neuropsychological tests are very useful, but have some limitations. Administration of the tests is limited to a psychologist, is very timeconsuming in that it can take 3-8 hours to administer and often need specialized equipment. At the other end of the continuum are very brief screening tests. General practitioners, psychiatrists and occupational therapists, in addition to psychologists, also use these tests. Although useful, the short tests only provide limited information. An intermediate level test streamlining the assessment process between the very short and longer neuropsychological tests is therefore introduced by this study. The Bedside Cognitive Assessment Battery (BCAB) was developed in 1995 and are since used, at Tygerberg Hospital's Memory Clinic, to assess patients and teach students. The test comprehensively assesses the six main classes of cognitive functioning, namely attention and concentration, speech, memory, motor functioning, perceptual functioning and executive functioning. Approximately 35-45 minutes is required for administration and training is needed to administer the BCAB. No specialized equipment is needed for administration. The battery can therefore be used at the bedside, in the office or at old age homes. The aims of this study were to validate the BCAB for use with people aged eighteen years and older, and provide normative values for use in clinical settings. The test was revised in 1997 and 2001, and extensively so in 2002, but was never formally evaluated for validity. Well-known single tests were used to compile the BCAB. Most of these tests have proven validity and reliability, but only for foreign populations. In addition, some items were reformulated and others created by the researchers. The introduction of normative values would also be useful to assist in the delineation of cognitively intact and impaired individuals. This study succeeded in providing a table of normative values. One-hundred-and-sixty Afrikaans and English participants, and fourteen Xhosa participants were assessed in their mother tongue language. This project thus also introduced a Xhosa version of the BCAB. The purpose of the Xhosa version was to address the lack of culturally relevant cognitive assessment instruments. Results were evaluated for the effects of the variables' language, gender, age and education. The effect of language was most noticeable in the Xhosa group. Gender did not affect results as dramatically as age and especially, education. These significant effects on the aforementioned variables have been described in previous reports. The BCAB is thus relevant and useful as a detector of mild to moderate impairment. It can also be used to identify specific impairment. This can narrow down the investigation of psychologists, thus saving time and money. In addition, medical and nonmedical staff can use the BCAB. Some limitations were also identified. The sample used may limit the generalization of results. Some test items also need revision, along with further validation studies. Clinicians are therefore advised to use the BCAB only in addition to complete clinical examinations when making decisions regarding a patient's cognitive status. The BCAB appears to be a valid tool for bedside assessment. However, this study could only set the stage for further research, especially studies concerned with establishing normative values.
AFRIKAANSE OPSOMMING: Verskeie toetse bestaan vir die evaluering van algemene kognitiewe funksionering, waarvan die meeste ontwikkel is binne die sielkunde. Neuro-sielkundige toetse is baie bruikbaar, maar het sekere beperkings. Administrasie van die toetse is beperk tot sielkundiges, maar tydrowend weens 'n tydsduur van drie tot agt uur, en verg dikwels gespesialiseerde toerusting. Aan die ander kant is heelwat kart siftings-toetse beskikbaar. Aigemene praktisyns, sielkundiges en arbeidsterapeute, asook sielkundiges, gebruik dit. Hoewel bruikbaar, bied die kart toetse beperkte inligting. 'n lntermediere vlak toets om die evaluerings-proses tussen kart en langer neuro-sielkundige toetse te integreer word met hierdie studie beoog. Die Bedkant Kognitiewe Evaluasie Battery (BKEB) is in 1995 ontwikkel en gebruik in die Geheue-kliniek van die Tygerberg Hospitaal om pasiente te evalueer en studente op te lei. Die toets is gerig op die omvattende evaluering van die ses hoof-klasse van kognitiewe funksionering. Hierdie klasse omvat aandag en konsentrasie, spraak, geheue, motoriese funksionering, perseptuele funksionering en uitvoerende funksionering. Sowat 35 tot 45 minute word benodig vir administrasie terwyl opleiding vereis word vir die neem van die toets. Geen gespesialiseerde toerusting is nodig nie. Die battery kan dus by die bedkant, in die kantoor of in ouetehuise gebruik word. Die doelwitte van hierdie studie is om die BKEB te evalueer in gebruik by 18-jariges en ouer, en normatiewe waardes te bepaal vir gebruik in kliniese omgewings. Die toets is in 1997 en 2001 hersien. In 2002 is dit uitvoerig hersien, maar nooit ge-evalueer vir geldigheid nie. Bekende enkel-toetse is gebruik am die BKEB saam te stel. Dit is as geldig en betroubaar bewys, hoewel slegs onder buitelandse bevolkingsgroepe. Hierbenewens is sekere items herformuleer en ander bygewerk deur die navorsers. Normatiewe waardes sal oak handig wees in die afbakening van kognitief normaal-funksionerende en kognitief-ingekorte individue. Hierdie studie het daarin geslaag am 'n tabel van normatiewe waardes daar te stel. Een-honderd-en-sestig Afrikaans- en Engels-sprekendes, en 14 Xhosa-sprekendes is tydens hierdie studie in hulle moedertaal ge-evalueer. Hierdie projek het dus oak 'n Xhosaweergawe van die BKEB geskep. Die doel van die Xhosa-weergawe was am die gebrek aan 'n kultureel toepaslike kognitiewe instrument te beklemtoon. Resultate is ge-evalueer gedagtig aan veranderlikes soos taal, geslag, ouderdom en opleidingsvlak. Taal het die grootste invloed gehad op uitslae van Xhosa-deelnemers. Geslag het nie die uitslae so dramaties bernvloed soos ouderdom, en veral opleidingsvlak nie. Literatuur het meestal die groot uitwerking van hierdie veranderlikes bevestig. Die BKEB is dus relevant en handig in die naspeuring van ligte tot matige kognitiewe ingekortheid. Dit kan ook gebruik word om spesifieke kognitiewe ingekortheid te identifiseer. Die kan die omvang van ondersoek deur sielkundiges vernou, wat kan lei tot In groot besparing in tyd en geld. Hierbenewens kan mediese en nie-mediese personeel aangewend word in die gebruik van die BKEB. Sekere tekortkominge is ge·,dentifiseer. Die steekproef mag egter die veralgemening van die uitslae beperk. Sekere toets-items mag ook hersiening vereis, tesame met verdere geldigheid-studies. Kliniese praktisyns word daarom aangeraai om die BKEB slegs in aanvulling tot omvattende kliniese ondersoeke te gebruik vir besluite m.b.t. In pasient se kognitiewe status. Die BKEB kom voor as In geldige instrument vir bedkant evaluering. Hierdie studie kon egter slegs die tafel dek vir verdere ondersoek, veral t.o.v. studies wat poog om normatiewe waardes daar te stel.
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Roach, Denise Margaret. "Upregulation of matrix metalloproteinases -2 and -9 and type IV collagen degradation in skeletal muscle reperfusion injury." Title page, contents and abstract only, 2002. http://web4.library.adelaide.edu.au/theses/09MD/09mdr6281.pdf.
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Includes bibliographical references (leaves 292-352) Determines the role of matrix metalloproteinases, MMP-2 and MMP-9 in reperfusion injury following skeletal muscle ischaemia; and, whether inhibition of MMPs by doxycycline protects against tissue damage.
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Thomas, Saralene Iona. "Genetic markers in the differential diagnosis in a family setting of episodic loss of consciousness." Thesis, Stellenbosch : Stellenbosch University, 2000. http://hdl.handle.net/10019.1/51777.
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Bigordà, Sagué Albert. "Diseño y validación de una aplicación informática de sospecha de patología del aparato locomotor en el hombro." Doctoral thesis, Universitat de Lleida, 2017. http://hdl.handle.net/10803/405802.
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S'exposa una demora significativa per accedir a tractament de fisioteràpia en els afectats per dolor d'espatlla. Es proposa millorar-la amb el disseny i validació d'una aplicació informàtica autoadministrada per a la sospita de patologia. Es van reclutar usuaris amb dolor de més de 6 setmanes d'evolució en serveis de rehabilitació i traumatologia. S'ha realitzat una revisió bibliogràfica, una prova de viabilitat, una revisió per avaluadors experts segons la metodologia Delphi, una prova pilot amb anàlisi de la fiabilitat i una prova de validació en 250 pacients. Els valors de validesa van ésser: CP+ 7,8 i CP- 0,1 per a la radiculopatia; CP+ 4,1 i CP- 0,4 per a l’artrosi glenohumeral; CP+ 15,5 i CP- 0,2 per a la inestabilitat; CP+ 17,2 i CP- 0,2 per a la ruptura massiva del manegot rotador; CP+ 6,2 i CP- 0,2 per a la retracció capsular; CP+ 4,0 i CP- 0,3 per al síndrome subacromial; i CP+ 2,5 i CP- 0,6 per a l’artropatia acromioclavicular. S'ha obtingut un coeficient de Kappa del 0,67 i una mitja de correcta classificació del 84% per a un mateix pacient. Els factors que van influir negativament en la precisió van ser la ruptura massiva del manegot rotador, l'artropatia acromioclavicular, una edat superior a 55 anys i una intensitat del dolor (EVA) superior a 8 (p> 0,05). S'exposa una bona fiabilitat, una acceptable validesa per a algunes patologies, però una insuficient capacitat per a sospitar la totalitat del quadre clínic en un mateix pacient.Se expone una demora significativa para acceder a tratamiento de fisioterapia en los aquejados por dolor de hombro. Se propone mejorarla con el diseño y validación de una aplicación informática autoadministrada para la sospecha de patología. Se reclutaron usuarios con dolor de más de 6 semanas de evolución en servicios de rehabilitación y traumatología. Se ha realizado una revisión bibliográfica, una prueba de factibilidad, una revisión por evaluadores expertos según la metodología Delphi, una prueba piloto con análisis de la fiabilidad y una prueba de validación en 250 pacientes. Los valores de validez fueron: CP+ 7,8 y CP- 0,1 para la radiculopatía, CP+ 4,1 y CP- 0,4 para la artrosis glenohumeral, CP+ 15,5 y CP- 0,2 para la inestabilidad, CP+ 17,2 y CP- 0,2 para la rotura masiva del manguito rotador, CP+ 6,2 y CP- 0,2 para la retracción capsular, CP+ 4,0 y CP- 0,3 para el síndrome subacromial, y CP+ 2,5 y CP- 0,6 para la artropatía acromioclavicular. Se ha obtenido un coeficiente Kappa del 0,67 y una media de correcta clasificación del 84% para un mismo paciente. Los factores que influyeron negativamente en la precisión fueron la rotura masiva del manguito rotador, la artropatía acromioclavicular, una edad superior a 55 años y una intensidad del dolor (EVA) superior a 8 (p>0,05). Se expone una buena fiabilidad y una aceptable validez para algunas patologías, pero una insuficiente capacidad para la sospecha de la totalidad del cuadro clínico en un mismo paciente.
There is a significant delay in accessing physiotherapy treatment for those patients with shoulder pain. It is proposed to improve it with the design and validation of a self-administered computer application for suspected pathology. Patients with pain for more than six weeks in rehabilitation and traumatology services were recruited. A bibliographic review, a feasibility test, a review by expert evaluators according to the Delphi methodology, a pilot test with reliability analysis and a validation test in 250 patients were carried out. Validity values were: LR+ 7,8 and LR- 0,1 for radiculopathy; LR+ 4,1 and LR- 0,4 for glenohumeral osteoarthritis; LR+ 15,5 and LR- 0,2 for instability; LR+ 17,2 and LR- 0,2 for massive rotator cuff tear; LR+ 6,2 and LR- 0,2 for capsular retraction; LR+ 4,0 and LR- 0,3 for subacromial syndrome; and LR+ 2,5 and LR- 0,6 for acromioclavicular arthropathy. A kappa coefficient of 0,67 and an average of correct classification for the same patient of 84% were obtained. Factors that negatively influenced precision were massive rupture of the rotator cuff, acromioclavicular arthropathy, age over 55 years and pain intensity (VAS) over 8 (p> 0,05). The result were good reliability and acceptable validity, but insufficient capacity to suspect whole clinical state in the same patient.
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Rauch, Hanz Frederick. "The development of a system that emulates percussion to detect the borders of the liver." Thesis, Stellenbosch : University of Stellenbosch, 2009. http://hdl.handle.net/10019.1/2331.
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Thesis (MScEng (Mechanical and Mechatronic Engineering))--University of Stellenbosch, 2009.Percussion is a centuries old bedside diagnostic technique that is used to diagnose various conditions of the thorax and abdomen, among these, abnormalities of the liver. The physician taps the patient’s skin in the area of interest to determine the qualities or presence of the underlying tissue or organ, by listening to the generated sound. The research contained in this thesis views percussion as a system identification method which uses an impulse response to identify the underlying system. A design employing an electromagnetic actuator as input pulse generator and accelerometer as impulse response recorder was motivated and built. Tests were performed on volunteers and the recorded signals were analysed to find methods of identifying the presence of the liver from these signals. The analyses matched signals to models or simply extracted signal features and matched these model parameters or signal features to the presence of the liver. Matching was done using statistical pattern recognition methods and the true presence of the liver was established using MR images. Features extracted from test data could not be matched to the presence of the liver with sufficient confidence which led to the conclusion that either the test, apparatus or analysis was flawed. The lack of success compelled a further test on a mock-up of the problem – a silicone model with an anomaly representing the organ under test. Results from these tests showed that signals should be measured further from the actuator and the approach followed during this test could lead to the successful location of the anomaly and discrimination between subtle differences in the consistency thereof. It is concluded that further research should aim to first validate percussion as performed by the physician and increase complexity in a phased manner, validating results and apparatus at each step. The approach followed was perhaps too bold in light of the lack of fundamental understanding of percussion and the underlying mechanisms.
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Hashmi, Sumaiya F. "A DNA Computer for Glioblastoma Multiforme Diagnosis and Drug Delivery." Scholarship @ Claremont, 2013. http://scholarship.claremont.edu/cmc_theses/799.
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Glioblastoma multiforme (GBM) is a debilitating malignant brain tumor with expected patient survival of less than a year and limited responsiveness to most treatments, often requiring biopsy for diagnosis and invasive surgery for treatment. We propose a DNA computer system, consisting of input, computation, and output components, for diagnosis and treatment. The input component will detect the presence of three GBM biomarkers: vascular endothelial growth factor (VEGF), caveolin-1α (CAV), and B2 receptors. The computation component will include indicator segments for each of these genes, and ensure that output is only released if all the biomarkers are present. The output component will consist of the therapeutic agent interleukin-12 (IL-12).
This study will designate four groups of animals: untreated tumor-free (control), tumor-inoculated (RG2), treated and tumor-free (DNA), and treated and tumor-inoculated (RG2/DNA). In the RG2 and RG2/DNA groups, we will inoculate adult male Fischer rats with RG2 cells into the striatum to induce tumor growth. Rats in the DNA and RG2/DNA groups will be implanted with the DNA system at the same location via recombinant adeno- associated viral vectors. The effectiveness of the DNA system will be evaluated through tumor size measurements, collected from brain slices stained with hematoxylin and eosin, and survival curve. Additionally, IL-12 localization will confirm the release of the output component.
We anticipate that the DNA treatment will result in a decrease in tumor size, leading to smaller tumor size in the RG2/DNA group versus the RG2 group. The control group is expected to survive the longest, followed by the DNA group, then the RG2/DNA group, and finally the RG2 group. In the DNA group, IL-12 is expected to stay localized to the implantation site, remaining in its unreleased stem-loop form. On the other hand, it is expected to be released and active in the RG2/DNA group.
This study provides a proof of concept to demonstrate the viability and effectiveness of a DNA system using VEGF, CAV, and B2 receptors as biomarkers and IL-12 as a therapeutic output component in the RG2 model. Further research may include varying several of the parameters used in this study, including amount of RG2 administered, choice of biomarkers, quantity and choice of output component, and choice of animal model. This system provides a promising and innovative new approach that is less invasive than surgery yet is still effective in diagnosing, targeting, and treating GBM.
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Van, der Merwe Ruben Gerhard. "The development of a novel fluorescentmarker phage technology system for the early diagnosis of tuberculosis disease." Thesis, Stellenbosch : Stellenbosch University, 2012. http://hdl.handle.net/10019.1/71908.
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Thesis (PhD)--Stellenbosch University, 2012.Includes bibliography
ENGLISH ABSTRACT: Mycobacterium tuberculosis, the causative organism of tuberculosis (TB), is a major cause for mortality and morbidity world-wide with a death toll only second to HIV among infectious diseases. Drug resistance is widespread and cases of multiple drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) have emerged in several countries. Drug treatment is problematic and new drugs are not developed rapidly enough to offset the rapid drug resistance mutation rate of M. tuberculosis. Simple and effective diagnostics are required to contain the spread of the disease as current routine diagnostics are not fulfilling this role. Additionally, current rapid TB diagnostics are out of reach to resource poor settings due to infrastructure, cost and skill requirements. Novel TB diagnostics are thus required that meet these requirements. Mycobacteriophages are phages that infect mycobacteria and could offer a viable and cost effective alternative rapid TB diagnostics. In this study, an affinity-tagged fluorescent reporter mycobacteriophage is described, which was engineered to act as a TB diagnostic. Its performance proved favourable and superior to current existing mycobacteriophage-based TB diagnostics.
AFRIKAANSE OPSOMMING: Mycobacterium tuberculosis, die organisme verantwoordelik vir tuberkulose (TB), is `n groot bron van mortaliteit en morbiditeit wêreldwyd en slegs HIV is verantwoordelik vir groter getalle sterftes as gevolg van n aansteeklike siekte. Middelweerstandigheid is algemeen en gevalle van meervoudigemiddelweerstandige tuberkulose (MDR-TB) en uiters weerstandige tuberkulose (XDR-TB) kom in verskeie lande voor. Antibiotika behandeling is problematies en nuwe anti-TB middels word nie vinnig genoeg ontwikkel om die antibiotika weerstandigheid mutasie spoed van M. tuberculosis te bekamp nie. Doeltreffende diagnostiese toetse word benodig om die verspreiding van die siekte te beheer en bestaande roetine diagnostiese toetse voldoen tans nie aan hierdie vereiste nie. Behalwe hiervoor, is huidige vinnige TB diagnostiese toetse buite bereik van arm instansies weens vereistes aan infrastruktuur, meegaande kostes en werknemervaardigheid. Nuwe TB diagnostiese toetse is dus nodig om aan hierdie vereistes te voldoen. Mikobacteriofaage is fage wat mikobacteria infekteer en kan moontlik 'n lewensvatbare en koste-effektiewe alternatief bied vir vinnige TB diagnostiese toetse. In hierdie studie word 'n affiniteitgekoppelde fluoreserende rapporteringsmikobakteriofaag beskryf wat ontwerp is om op te tree as `n nuwe vinnige TB diagnostiese toets. Die werking hiervan vertoon gunstige en beter resultate as die huidige, mikobacteriofaaggebaseerde TB-diagnostiese toetse.
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Wang, Yee-moon Angela, and 王依滿. "Utility of cardiac biomarkers in end-stage renal disease patients on maintenance peritoneal dialysis." Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B41508968.
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Haga, Kristin Kerr. "The combined application of 'H MRI and '19F MRS to the study of cerebroprotection." Thesis, University of London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.312006.
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Oladele, Oluwafemi. "Characterization of feline borna disease virus /." Uppsala : Department of Biomedical Sciences and Veterinary Public Health, Swedish University of Agricultural Sciences, 2006. http://epsilon.slu.se/10454915.pdf.
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Galdun, John P. "A MECHANISTIC STUDY OF AN iPSC MODEL FOR LEIGH’S DISEASE CAUSED BY MtDNA MUTATAION (8993 T>G)." VCU Scholars Compass, 2016. http://scholarscompass.vcu.edu/etd/4411.
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Mitochondrial diseases encompass a broad range of devastating disorders that typically affect tissues with high-energy requirements. These disorders have been difficult to diagnose and research because of the complexity of mitochondrial genetics, and the large variability seen among patient populations. We have devised and carried out a mechanistic study to generate a cell based model for Leigh’s disease caused by mitochondrial DNA mutation 8993 T>G. Leigh’s disease is a multi-organ system disorder that depends heavily on the mutation burden seen within various tissues. Using new reprogramming and sequencing technologies, we were able to show that Leigh’s disease patient fibroblasts reprogrammed to induced pluripotent stem cells maintain the same level of mutation burden seen in the original patient cell line. Mutation burden was maintained through several passages and spontaneous differentiation. This cell based model could be useful for future pathogenesis studies, or therapeutic drug screenings in a patient and tissue specific manner.