Thesis (Ph.D.)--University of Delaware, 2008. / Principal faculty advisor: Thomas W. Kaminski, Dept. of Health, Nutrition, and Exercise Sciences. Includes bibliographical references.

Thesis (Ph. D.)--University of Hong Kong, 1998. / Includes bibliographical references (leaves 166-193).

Worldwide there was a growing trend towards the recognition of Chiropractic, but little was known of this recognition in South Africa. However, with regards to the Western Region of Johannesburg, it was unclear how the medical profession viewed Chiropractic and how effective they viewed Chiropractic in the treatment of neuromusculoskeletal conditions. This study attempted to establish how medical doctors viewed Chiropractic and to determine how Chiropractors compared to physiotherapists in the opinion of the medical profession in the treatment of common neuromusculoskeletal conditions. A questionnaire was hand-delivered to the consulting rooms of each general practitioner, orthopedic surgeon and neurologist/neurosurgeon in the Western Region of Johannesburg. The researcher with the aid of a statistical consultant drew up the questionnaire. The data was analysed using the SPSS 13 (2005), SPSS Incorporated, Chicago using descriptives and frequencies. To compare Chiropractic treatment to physiotherapy, statistical significance was calculated using a Paired Samples Test (T-Test). The results of this study found that the doctors had a positive view of Chiropractic as a profession. When comparing Chiropractic to physiotherapy, statistical analysis revealed that physiotherapy was seen as more effective. Physiotherapists were also more likely to receive referrals from medical doctors than Chiropractors. The results of this study were in accordance with worldwide trends in that Chiropractic was growing in recognition and was viewed as beneficial in the health care system. However, more education of the medical profession with regards to Chiropractic and more research comparing Chiropractic effectiveness compared to physiotherapy were needed. / Dr. M. Moodley Dr. J. Mitchell

A method for modeling and simulating neural action potential (AP) propagation along the length of an axon containing a number of Ranvier nodes is proposed in this dissertation. A system identification approach is adopted to represent node of Ranvier (NR) response to current pulse stimulus in the form of transfer function representations for NR excitability. Segments of myelinated internodal (IN) and NR regions are cascaded, representing the remaining downstream axon after a site-of-stimulus introduction of an external current pulse. This cascading network is used to simulate "cable" properties and signal propagation along the length of the axon. This work proposes possible solutions to attenuation losses inherited in the classical myelinated cable models and accounts for neuronal AP velocity as well as introducing signal attenuation and transient delays associated with internodal demyelination. This model could aide as a predictive tool for the diagnosis and analysis of axonal signal integrity associated with demyelination pathology. Possible applications could include functional stimulation control methodologies for axon bundles that may exhibit signal fidelity issues associated with demyelination. It is further proposed that this model may serve as an instructive tool for further development and incorporation of other axon dynamic behaviors such as: relative refractory periods of AP generation, NR AP recovery mechanisms and responses to varied current stimulus input. / by George Jason Morales. / Thesis (Ph.D.)--Florida Atlantic University, 2011. / Includes bibliography. / Electronic reproduction. Boca Raton, Fla., 2011. Mode of access: World Wide Web.

No description available.

No description available.

Thesis (Ph.D.)--University of Western Australia, 2006.

Orientadores: Anamarli Nucci, Luis Alberto Magna / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-14T03:53:48Z (GMT). No. of bitstreams: 1 Iwabe_Cristina_D.pdf: 1754354 bytes, checksum: 4d6a8aa043ff9b54a822122861754044 (MD5) Previous issue date: 2009 / Resumo: Os objetivos do estudo foram: traduzir a escala francesa Medida da Função Motora (MFM) para o português; identificar a confiabilidade de sua aplicação intra e interexaminador; validar a versão em português da MFM (MFM-P) em pacientes brasileiros com doenças neuromusculares; estudar a aplicabilidade da MFM-P na desproporção congênita de tipos de fibras (DCTF), em associação com ressonância magnética de músculo, e na distrofia miotônica (DM-1), correlacionando o grau de força. Métodos: tradução e retrotradução da escala foram realizadas, resultando em texto consensual. Na análise da confiabilidade, a aplicação da MFM-P foi documentada em vídeo em 58 pacientes de 6 a 60 anos, e diversos diagnósticos de doenças neuromusculares. O autor realizou o teste e re-teste e outros três fisioterapeutas analisaram os vídeos para avaliação estatística interexaminador dos resultados, através dos coeficientes de Kendall, kappa e Pearson. Para a validação da escala, 65 pacientes foram examinados pela escala MFM-P, Índice de Barthel (IB) e escala de Vignos. Na análise estatística utilizou-se o coeficiente de correlação de Spearman, com valor de p < 0,05. Para a aplicabilidade da MFM-P na DCTF, examinou-se pai e dois filhos da mesma família, submetidos a ressonância magnética de músculo. Na DM-1, verificou-se a correlação entre a MFM-P e a força muscular, através do coeficiente de correlação de Pearson. Resultados: os coeficientes de concordância de Kendall para a análise interexaminador e os coeficientes kappa e de Pearson para o teste e re-teste foram estatisticamente significativos (p-valor < 0.0001) nos 32 itens da escala e no escore total. Na validação da MFM-P observou-se alta correlação significativa com IB (r= 0,980; p <0,001) e com a escala de Vignos (r= -0,894; p<0,001). Os pacientes com DCTF apresentaram limitações nas atividades da dimensão 1 (em pé e transferências) da MFM-P, devido à fraqueza muscular mais acentuada em membros inferiores em concordância com os dados da ressonância magnética de músculo. No estudo dos pacientes com DM-1, obser-vou-se fraqueza simétrica dos membros inferiores, superiores e região axial, sendo que o segmento distal foi o mais deficitário. A correlação da força com as funções motoras na DM-1 demonstrou que a fraqueza muscular (grau igual ou inferior a 4) ocasiona prejuízo na execução das atividades funcionais, tornando o individuo dependente para suas atividades de vida diária. Concluiu-se pelo estudo da validade e confiabilidade, que a MFM-P mostrou-se eficaz como instrumento de avaliação em doenças neuromusculares / Abstract: The objective of this study were: to translate the French version of Motor Function Measure (MFM) into the Portuguese language; to describe the inter and intraexaminer reliability of the Portuguese MFM version (P-MFM); to validate the PMFM in Brazilian patients with neuromuscular disease; to analyzed the applicability of the P-MFM in congenital fibre type disproportion (CFTD), associated with muscle magnetic resonance image, and in Myotonic Dystrophy type 1 (MD-1), correlating with the strength. Methods: for the accomplishment of the Portuguese MFM version scale, two MFM translations were produced separately by proficient neurologists in French, resulting in a consensual text after evaluation by authors. For assessment of reliability of P-MFM, 58 patients, aged to 6 from 60 years, and several diagnostics neuromuscular disease were documented on video tape. The test-retest examiner (intrarater) and three other physiotherapists (interrater) analyzed the video tape, and the results were calculated by Kendall, kappa and Pearson coefficients. For validation of the scale, 65 patients were analyzed by the P-MFM, Barthel Index (BI) and Vignos scale. Statistical analyzes were conducted using Spearman correlation coefficients, p-value < 0,05. For the applicability of the P-MFM in CFTD it was evaluated from the same family, father and two sons, associated to the analysis of the muscle magnetic resonance. In the MD-1, it was analyzed the correlation between the P-MFM and muscle strength, using the Pearson correlation coefficient for statistical analysis. Results: the Kendall coefficients for the inter-examiner analysis and kappa and Pearson coefficients for the test-retest were statistically significant (p-value < 0,001) for the 32 items on the scale and total score. The P-MFM validation observed highly significant correlation with BI (r = 0,980; p < 0,001) and with the Vignos scale (r= - 0,894; p < 0,001). The patients with CFTD showed limitations in the activities of dimension 1 (standing and transfers) of the P-MFM, due more weakness in lower limbs, confirmed with those data in muscle magnetic resonance. In patients with MD-1, observed symmetrical weakness in the lower, upper limbs and axial region, with the most deficient in the distal segment. The correlation between strength and motor function in the MD-1 showed the strength reduction (score equal or less than 4) cause damage in the functional activities performance, reducing the independence for activities of daily living. In conclusion, with the reliability and validity of the PMFM, this scale can be used as useful tool in neuromuscular disease. The scale allowed monitoring the progress of the clinical in patients with CFTD. In patients with MD-1, observed the correlation between strength and motor function, mainly in distal segment / Doutorado / Ciencias Biomedicas / Doutor em Ciências Médicas

The retromer is a protein complex whose function is to mediate the recycling of proteins from the endosome to either the plasma membrane or the trans-Golgi network. A deficit in retromer function has been associated with multiple neurodegenerative disorders, including Alzheimer’s disease (AD) and Parkinson’s disease (PD). In both AD and PD, deficiencies have been found in retromer expression both in patient tissues and in animal models of disease. Furthermore, mutations in the retromer and in retromer-associated genes have been strongly linked with both diseases. Despite ample evidence of the link between the retromer and neurodegeneration, little is known about the retromer in the context of amyotrophic lateral sclerosis (ALS), another common neurodegenerative disorder. ALS is an adult-onset neurodegenerative disorder of the upper and lower motor neurons (MNs) characterized by muscle wasting and weakness leading to death within 3-5 years after diagnosis. To date, the most commonly used model of ALS is a transgenic (Tg) mouse that overexpresses an ALS-causing G93A mutation in the human superoxide dismutase 1 (SOD1) gene. In this study, I first establish a link between the retromer and ALS by showing that cells from ALS patients as well as tissues and cells from SOD1G93A-Tg mice express lower protein levels of the retromer core components—vacuolar protein sorting 35 (Vps35), Vps26a, and Vps29. I then establish that deficiencies in retromer core proteins have functional consequences in an in vitro model of ALS. Having found significant deficiencies in the retromer in SOD1G93A-Tg mice, I then followed the model of studies performed in mouse models of other neurodegenerative disorders by investigating whether repletion of retromer levels, either virally or pharmacologically, in SOD1G93A-Tg mice confers a therapeutic benefit. Surprisingly, I find that rather than ameliorating disease, repletion of retromer levels in SOD1G93A-Tg mice exacerbates it, resulting in a faster decline in motor performance, earlier mortality, and a decrease in MNs in the spinal cord. Finally, since retromer repletion causes deleterious effects on SOD1G93A-Tg mouse disease progression, I study the effect of a single allele deletion of Vps35 in SOD1G93A-Tg mice and find that this depletion of the retromer results in amelioration of disease, including delayed onset of symptomatology, slower decline of motor deficits, delayed mortality, and an increase in MNs in the spinal cord. Altogether, the findings reported herein, support the notion that a mild defect in retromer develops over the course of the disease, which, rather than being deleterious may be therapeutic in mutant SOD1-induced MN degeneration. Perhaps this unexpected outcome may be explained by the fact that the observed mild nature of the defect is not sufficient to kill MNs but enough to alter the trafficking of specific cargos such as AMPA receptors, allowing MNs to better withstand the neurodegenerative process.

重症肌無力是由自身抗體在神經肌肉接頭特異性的結合乙酰膽鹼受體和肌肉特異性激酶引起的一種獲得性免疫性疾病。疾病的主要症狀是骨骼肌的軟弱無力和易疲勞性。這一症狀在運動後尤為顯著，休息後會有所緩解。重症肌無力在世界範圍的發病率是百萬分之三到三十。由於近年來患者的數量在不斷增加，重症肌無力引起了醫學界的廣泛關注。但是，目前的診斷和治療措施還不能完全滿足臨床病人的需要。在本課題研究中，我們希望運用代謝組學的手段建立一種新的更加有效可靠的方法用於重症肌無力的診斷。同時，我們希望在代謝物的水平上來闡釋強肌健力方（一種中藥復方）對重症肌無力的治療作用。 / 本研究所用樣本來自42個重症肌無力病人和16個健康志願者。樣本由廣州中醫藥大學第一附屬醫院於二零零七年到二零零八年收集所得。診斷後，病人每日口服一定劑量的強肌健力方接受治療，連續服藥兩個月。分別在服藥前和治療後對病人抽血採樣。進一步分離血清後，樣品進行質譜分析。多元統計學方法如主成分分析，正交偏最小二乘和正交偏最小二乘判別分析等用於質譜數據的分析。 / 通過和健康者比較分析，我們在重症肌無力病人的血液中找到142個顯著改變的離子。其中，14個離子得到鑒定，包括：γ-氨基丁酸，2-哌啶酸，鳥氨酸，5,8-十四碳二羧酸，精胺，己酰肉毒鹼，N-油酰基甘氨酸，鞘氨醇-1-磷酸，聯原膽酸，糞甾烷酸，植物鞘氨醇-1-磷酸，鵝去氧膽酸甘氨酸結合物，輔酶Q4和甘氨酸膽。基於以上142個離子建立的數學診斷模型在診斷重症肌無力時表現出很高的靈敏度和特異性，分別高達92.8%和83.3%。強肌健力方能夠逆轉由重症肌無力引起的特異性代謝變化，將病人體內被改變的代謝網絡恢復正常，特別是大部分的代謝標誌物在治療後都恢復到了相對正常水平，包括：γ-氨基丁酸，哌啶酸，鳥氨酸，5,8-十四碳二羧酸，精胺，己酰肉毒鹼，N-油酰甘氨酸，鞘氨醇-1-磷酸，聯原膽酸，輔酶Q4和甘氨酸膽。 / 本研究揭示了基於液質聯用的代謝組學方法適用於探索重症肌無力的代謝標誌物，並提供了一種可用於診斷重症肌無力的新方法。同時，本研究證實強肌健力方適用於重症肌無力的治療，且無明顯副作用。 / Myasthenia gravis (MG) is an acquired autoimmune disease caused by specific autoantibodies against acetylcholine receptors (AChRs) and muscle-specific kinase (MuSK) proteins at the neuromuscular junctions. The disease is characterized by weakness and fatigability of the voluntary muscles that gets worse with exertion and improves with rest. The global incidence rate of MG is about 3-30 cases per million per year. In recent years, the worldwide prevalence rate of MG is increasing as a result of increased awareness. However, current diagnostic measures and treatments are not conclusive and satisfactory for MG. In this study, a mass spectrometry-based metabolomic strategy was applied to develop a novel and reliable diagnostic measure for MG on the basis of metabolic analysis, and to explore the therapeutic effect of Qiangji Jianli Fang (QJF, a newly developed Chinese medicine formula) on MG at the metabolite level. / Total 42 MG patients (13 males and 29 females) and 16 volunteers (5 males and 11 females) were recruited at the First Affiliated Hospital of Guangzhou University of Chinese Medicine between March 2007 and March 2008. The patients took QJF once per day for 2 months. Peripheral blood from patients was collected at diagnosis and after 2-month treatment, respectively. Sera prepared from the blood samples were monitored by the liquid chromatography Fourier transform mass spectrometry (LC-FTMS). Mass spectral data were analyzed by multivariate statistical analyses, including principal component analysis (PCA), orthogonal partial least squares (OPLS), and orthogonal partial least squares discriminant analysis (OPLS-DA). / By comparing analysis with the healthy volunteers, 142 significantly changed ions from serum metabolic profile of MG patients were picked out as the potential biomarkers of MG. Among of them, 14 ions were temporarily identified. They were gamma-aminobutyric acid (GABA), pipecolic acid, ornithine, 5,8-tetradecadienoic acid, spermine, hexanoylcarnitine, N-oleoyl glycine, sphingosine-1-phosphate (S1P), bisnorcholic acid, coprocholic acid, phytosphingosine-1-P, chenodeoxycholylglycine, coenzyme Q4, and cholylglycine. The developed OPLS-DA diagnostic model based on the 142 special ions showed a high sensitivity (92.8%) and specificity (83.3%) in detecting MG. QJF showed a powerful action on MG by recovering the holistic serum metabolic profile from the disease level to the normal level. Especially, the levels of GABA, pipecolic acid, ornithine, 5,8-tetradecadienoic acid, spermine, hexanoylcarnitine, N-oleoyl glycine, S1P, bisnorcholic acid, coenzyme Q4, and cholylglycine in MG patients were regulated to a relatively normal level after QJF treatment. / My results first indicated that the LC-FTMS-based metabolomics was a useful tool in biomarkers exploration of MG, and it was potentially applicable as a new diagnostic approach for MG. Also, my results demonstrated that QJF was a good optional choice for the treatment of MG, with no reported side effects. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Lu, Yonghai. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2013. / Includes bibliographical references (leaves 113-129). / Abstract also in Chinese. / Thesis committee --- p.i / Declaration --- p.ii / Abstract (in English) --- p.iii / Abstract (in Chinese) --- p.vi / Acknowledgements --- p.viii / Table of contents --- p.ix / Abbreviations --- p.xiv / List of Tables --- p.xviii / List of Figures --- p.xix / Chapter 1: Introduction --- p.1 / Chapter 1.1 --- Myasthenia gravis --- p.1 / Chapter 1.1.1 --- History --- p.1 / Chapter 1.1.2 --- Epidemiology --- p.2 / Chapter 1.1.3 --- Clinical features --- p.2 / Chapter 1.1.4 --- Clinical classification --- p.4 / Chapter 1.1.5 --- Pathophysiology --- p.5 / Chapter 1.1.6 --- Diagnosis --- p.9 / Chapter 1.1.6.1 --- Physical examination --- p.9 / Chapter 1.1.6.2 --- Blood test --- p.10 / Chapter 1.1.6.3 --- Electrodiagnostic test --- p.10 / Chapter 1.1.6.4 --- Edrophonium test --- p.11 / Chapter 1.1.6.5 --- Imaging --- p.11 / Chapter 1.1.6.6 --- Pulmonary function test --- p.11 / Chapter 1.1.7 --- Treatment --- p.12 / Chapter 1.1.7.1 --- Medication --- p.12 / Chapter 1.1.7.2 --- Thymectomy --- p.12 / Chapter 1.1.7.3 --- Plasmapheresis and intravenous immunoglobulin --- p.13 / Chapter 1.2 --- Qiangji Jianli Fang --- p.14 / Chapter 1.2.1 --- Huang qi --- p.15 / Chapter 1.2.2 --- Dang shen --- p.16 / Chapter 1.2.3 --- Bai shu --- p.16 / Chapter 1.2.4 --- Dang gui --- p.17 / Chapter 1.2.5 --- Sheng ma --- p.17 / Chapter 1.2.6 --- Chai hu --- p.18 / Chapter 1.2.7 --- Chen pi --- p.18 / Chapter 1.2.8 --- Gan cao --- p.19 / Chapter 1.3 --- Metabolomics --- p.19 / Chapter 1.3.1 --- What’s metabolomics? --- p.20 / Chapter 1.3.1.1 --- Metabolites --- p.20 / Chapter 1.3.1.2 --- Metabolome --- p.21 / Chapter 1.3.1.3 --- Two terms: metabolomics and metabonomics --- p.21 / Chapter 1.3.2 --- How metabolomics works? --- p.22 / Chapter 1.3.2.1 --- Sample preparation --- p.22 / Chapter 1.3.2.1.1 --- Quenching --- p.23 / Chapter 1.3.2.1.2 --- Separating metabolites --- p.24 / Chapter 1.3.2.1.3 --- Sample concentration --- p.24 / Chapter 1.3.2.2 --- Analytical technologies (Sample analysis) --- p.25 / Chapter 1.3.2.3 --- Data analysis --- p.26 / Chapter 1.3.2.4 --- Database --- p.28 / Chapter 1.3.3 --- Why metabolomics? --- p.29 / Chapter 1.3.4 --- Metabolomics for human diseases --- p.30 / Chapter 1.3.5 --- Metabolomics for Traditional Chinese Medicine --- p.32 / Chapter 1.4 --- Objectives and significances of the present study --- p.34 / Chapter Chapter 2 --- Metabolic biomarkers of myasthenia gravis --- p.36 / Chapter 2.1 --- Introduction --- p.36 / Chapter 2.2 --- Materials and methods --- p.40 / Chapter 2.2.1 --- Chemicals --- p.40 / Chapter 2.2.2 --- Patients --- p.40 / Chapter 2.2.3 --- Volunteers --- p.42 / Chapter 2.2.4 --- Blood collection --- p.43 / Chapter 2.2.5 --- QC samples --- p.43 / Chapter 2.2.6 --- Sample processing --- p.43 / Chapter 2.2.7 --- Liquid chromatography-mass spectrometry --- p.44 / Chapter 2.2.8 --- Data analysis --- p.45 / Chapter 2.2.9 --- Metabolite identification --- p.45 / Chapter 2.3 --- Results --- p.46 / Chapter 2.3.1 --- Method validation --- p.46 / Chapter 2.3.2 --- An overall comparative analysis between 28 patients and 10 volunteers --- p.48 / Chapter 2.3.3 --- Classification of MG --- p.53 / Chapter 2.3.4 --- Comparative analysis of the metabolic changes in early- and late-stage MG patients respectively --- p.54 / Chapter 2.3.5 --- Biomarker identification --- p.56 / Chapter 2.4 --- Discussion --- p.58 / Chapter 2.5 --- Conclusion --- p.63 / Chapter Chapter 3 --- A novel diagnostic approach for myasthenia gravis --- p.64 / Chapter 3.1 --- Introduction --- p.64 / Chapter 3.2 --- Materials and methods --- p.68 / Chapter 3.2.1 --- Chemicals --- p.68 / Chapter 3.2.2 --- Patients and Volunteers --- p.69 / Chapter 3.2.2.1 --- Training set for establishment of diagnostic model --- p.69 / Chapter 3.2.2.2 --- Test set for evaluation of diagnostic model --- p.69 / Chapter 3.2.3 --- QC samples --- p.70 / Chapter 3.2.4 --- Sample processing --- p.71 / Chapter 3.2.5 --- Chromatography --- p.71 / Chapter 3.2.6 --- Mass spectrometry --- p.72 / Chapter 3.2.7 --- Data analysis --- p.72 / Chapter 3.3 --- Results --- p.72 / Chapter 3.3.1 --- Method validation --- p.73 / Chapter 3.3.2 --- Alterations in serum metabolic profile under MG --- p.74 / Chapter 3.3.3 --- Prediction of MG based on biomarkers --- p.74 / Chapter 3.3.4 --- Establishment of diagnostic model on the basis of metabolic profile --- p.77 / Chapter 3.3.5 --- Prediction of MG with diagnostic model --- p.79 / Chapter 3.4 --- Discussion --- p.80 / Chapter 3.5 --- Conclusion --- p.83 / Chapter Chapter 4 --- Qiangji Jianli Fang treatment for myasthenia gravis --- p.84 / Chapter 4.1 --- Introduction --- p.84 / Chapter 4.2 --- Materials and methods --- p.88 / Chapter 4.2.1 --- Chemicals --- p.88 / Chapter 4.2.2 --- Herbs --- p.88 / Chapter 4.2.3 --- Participants --- p.88 / Chapter 4.2.4 --- QC samples --- p.90 / Chapter 4.2.5 --- Sample processing --- p.90 / Chapter 4.2.6 --- Liquid chromatography-mass spectrometry --- p.90 / Chapter 4.2.7 --- Data analysis --- p.91 / Chapter 4.3 --- Results --- p.91 / Chapter 4.3.1 --- Method validation --- p.91 / Chapter 4.3.2 --- Symptomatic examination after QJF treatment --- p.92 / Chapter 4.3.3 --- Holistic metabolic responses to QJF treatment --- p.93 / Chapter 4.3.4 --- MG biomarkers changes after QJF treatment --- p.95 / Chapter 4.3.5 --- Drug-related biomarkers of QJF --- p.97 / Chapter 4.4 --- Discussion --- p.100 / Chapter 4.5 --- Conclusion --- p.103 / Chapter Chapter 5 --- Conclusions --- p.104 / Chapter Chapter 6 --- Perspectives --- p.107 / Chapter 6.1 --- Experimental autoimmune myasthenia gravis model --- p.107 / Chapter 6.2 --- Chemical composition of Qiangji Jianli Fang --- p.111 / References --- p.113 / Appendices --- p.130