Submitted by Nadir Basilio (nadirsb@uninove.br) on 2018-07-20T20:38:01Z No. of bitstreams: 1 Mariana dos Anjos Furtado de Sá.pdf: 757823 bytes, checksum: c621e732da266331642bb34898bd1ee0 (MD5) / Made available in DSpace on 2018-07-20T20:38:01Z (GMT). No. of bitstreams: 1 Mariana dos Anjos Furtado de Sá.pdf: 757823 bytes, checksum: c621e732da266331642bb34898bd1ee0 (MD5) Previous issue date: 2018-03-07 / Objective: Study I: Identify the evaluation instruments utilized to measure the Functional Capability (FC) and the performance in the activities of daily living (ADL) of people with Parkinson’s disease (PD) in clinical trials in the field of physiotherapy. Study II: Analyze the reproducibility of the ADL test – Glittre in individuals with Parkinson’s disease (PD) and analyze the minimum detectable change in this test results in subjects with PD. Methods and Materials: Study I: A systematic review was carried out with a search in four databases. Extracted terms from Descritores em Ciências da Saúde (DeCS) and Medical Subject Headings (MeSH) were utilized. The terms were Parkinson’s disease, Physiotherapy, Daily Activities, Functional Capability and randomized clinical trials, including the suggested synonyms, in the Portuguese, English and Spanish language. Clinical trials were included in which the outcome were Functional Capability (FC) and/or the Physical Activities of Daily Living (ADL) from subjects with PD submitted to Physical Therapy. Two independent evaluators selected studies based on the eligibility criteria of the PEDro scale. A third evaluator analyzed the differences between the evaluators that selected the studies. Study II: Population sample composed of 30 subjects with PD, mean age 62±9 years old, both sexes (17 men), 8 (26,6%) at the Stage 1 of the Hoehn and Yahr classification, 11 (36,7%) at Stage 2 and 11 (36,7%) at Stage 3. The Glittre test (GT), was made in the intra-rater analysis twice, by the same rater, with a 30-minute interval, and in the inter-rater analysis both tests were made, by two distinct raters, with an interval of 1 to 7 days. The Intraclass correlation coefficient (ICC) was used to the reproducibility analysis and the proposed test by Bland and Altman to agreement analysis. Results: Study I: 10 studies were found, all using the total UPDRS or their II and III domains to evaluate, respectively, the performance of physical activities of daily living and the motor performance. The Timed Up and Go (TUG), was utilized in two out of the ten selected studies, was the only utilized instrument to evaluate the proposed outcomes, already validated to PD, in addition to UPDRS. Several other general measures, such as the 6-minute walk Test (6WT) and the Activity Card Sort (ACS) were cited as tools developed to other clinical populations, with the objective of evaluate the FC and/or ADL. Study II: The results demonstrated that the Glittre test execution time was significantly shorter in the retest (Intra-rater) with ICC= 0,92 (95%, CI= 0,83-0,96; P<0,0001). The results of the second evaluator were significantly shorter ICC= 0,86 (95%, CI = 0,71-0,93; P<0,0001). The MDC was 0,24 minutes (Intra-raters) and 0,62 minutes (Inter-raters). Conclusion: The study I results suggest that validation studies of other instruments are necessary to be utilized, as alternatives, to the evaluation of these outcomes. In the study II, the presented differences among the evaluators demonstrate the best results at the second test, pointing that at least two repetitions are necessary to obtain reliable evaluations. / Objetivo: Estudo I: Identificar os instrumentos de avaliação utilizados para mensurar a capacidade funcional (CF) e o desempenho nas atividades de vida diária (AVD´s) de pessoas com doença de Parkinson (DP) em ensaios clínicos na área da fisioterapia. Estudo II: Analisar a reprodutibilidade do teste de AVD - Glittre em indivíduos com a doença de Parkinson (DP) e analisar a mínima mudança detectável nos resultados deste teste em indivíduos com DP. Materiais e métodos: Estudo I: Foi realizada uma revisão sistemática com uma busca em quatro bases de dados. Foram utilizados termos extraídos dos Descritores em Ciências da Saúde (DeCS) e Medical Subject Headings (MeSH). Os termos foram Doença de Parkinson, fisioterapia, Atividades Diárias, Capacidade Funcional e ensaios clínicos randomizados, incluindo os sinônimos sugeridos, nos idiomas português, inglês e espanhol. Foram incluídos ensaios clínicos em que os desfechos eram a Capacidade Funcional (CF) e/ou as Atividades de Vida Diária (AVD´s) de pessoas com DP submetidas à Fisioterapia. Dois revisores independentes selecionaram os estudos baseados nos critérios de elegibilidade da escala PEDro. Um terceiro revisor avaliou as diferenças entre os revisores que selecionaram os estudos. Estudo II: Amostra populacional composta por 30 indivíduos com DP, idade média 62±9 anos, ambos os sexos (17 homens), 8 (26,6%) no estágio 1 da classificação de Hoehn e Yahr, 11 (36,7%) no estágio 2 e 11 (36,7%) no estágio 3. O teste Glittre (TG) foi realizado duas vezes, pelo mesmo avaliador, com intervalo de 30 minutos, para análise intra-avaliador e na análise interavaliadores os dois testes foram realizados por dois avaliadores distintos, com intervalo de 1 a 7 dias. Utilizou-se o coeficiente de correlação intraclasse (CCI) para análise da reprodutibilidade e o teste proposto por Bland e Altman para análise de concordância. Resultados: Estudo I: 10 estudos foram encontrados, todos utilizaram a UPDRS total ou os seus domínios II e III para avaliar, respectivamente, o desempenho nas atividades de vida diária e o desempenho motor. O Timed Up and Go (TUG) foi utilizado em dois dos dez estudos selecionados, foi o único instrumento utilizado para avaliar os desfechos propostos, já validado para DP, além da UPDRS. Diversas outras medidas genéricas, como o Teste de caminhada de 6 minutos (TC6) e o Activity Card Sort (ACS) foram citadas como ferramentas desenvolvidas para outras populações clínicas, com o objetivo de avaliar a CF e/ou AVD. Estudo II: Os resultados demonstraram que o tempo de execução do teste Glittre era significativamente menor no reteste (intra-avaliador) com CCI= 0,92 (95%, IC= 0,83-0,96; P<0,0001). Resultados do segundo examinador foram significativamente mais baixos CCI=0,86 (95%, IC = 0,71-0,93; P<0,0001). A MMD foi de 0,24 minutos (intra-avaliadores) e de 0,62 minutos (interavaliadores). Conclusão: Os resultados do estudo I sugerem que estudos de validação de outros instrumentos são necessários para serem utilizados, como alternativas, para a avaliação destes desfechos. No estudo II, as diferenças apresentadas entre os avaliadores mostram os melhores resultados no segundo teste, apontando que pelo menos duas repetições são necessárias para obter avaliações confiáveis.

Bakgrund: Parkinsons Sjukdom (PS) är en kronisk progressiv neurodegenerativ sjukdom som ger både motoriska och icke-motoriska symtom. Ett vanligt icke-motoriskt symtom vid PS är depression. Depression påverkas, enligt forskning, positivt av fysisk aktivitet (FA) men stark evidens saknas för sambandet mellan dem. Syfte: Syftet med studien var att undersöka sambandet mellan FA och depression hos personer med PS. Metod: Femtioåtta deltagare rekryterades till denna tvärsnittsstudie. The International Physical Activity Questionnaire modified for the elderly (IPAQ-E) användes som mätmetod för FA, och var angiven i form av låg, måttlig och hög fysisk aktivitetsnivå samt i MET-minuter/vecka. Montegomery-Åstrand Depression Rating Scale (MADRS-S) användes för depression och angavs i totalpoäng. Frågeformulärerna sammanställdes till en webbenkät varifrån datan samlades in. Sambandet beräknades med Spearmans rangkorrelation. Resultat: Av samtliga deltagare hade 15 (26%) låg fysisk aktivitetsnivå, 18 (31%) måttlig och 25 (43%) hade hög fysisk aktivitetsnivå. Bland deltagarna hade 15 (26%) ingen depression, 27 (47%) mild, 14 (24%) måttlig och 2 (3%) svår depression. Sambandet mellan låg, måttlig och hög fysisk aktivitetsnivå enligt IPAQ-E och totalpoäng i MADRS-S visade r = -0.2 och p = 0.14. Sambandet mellan MET-minuter/vecka enligt IPAQ-E och totalpoäng i MADRS-S visade r = -0.15 och p = 0.26. Konklusion: Resultaten visade ett svagt negativt samband men sannolikheten att resultatet beror på slumpen är hög. Det krävs fler studier i framtiden för att säkerställa sambandet mellan FA och depression hos personer med PS. / Background: Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease with both motor and non-motor symptoms. Depression is a common non-motor symptom in PD. According to research, physical activity (PA) has a positive effect on depression; however, strong evidence supporting the relation between them is lacking. Purpose: The purpose of this study was to examine the relation between PA and depression in patients with PD.  Method: Fifty-eight participants were recruited to this cross-sectional study. The International Physical Activity Questionnaire modified for the elderly was used to measure PA, presented in low, moderate and high physical activity levels and MET-minutes/week. Montegomery-Åstrand Depression Rating Scale was used to assess depression and was presented in total score. The questionnaires were formed into a survey from which the data was collected. Spearman’s rank correlation was used to calculate the relation.  Results: Among the participants, 15 (26%) had a low level of PA, 18 (31%) moderate and 25 (43%) high level of PA. Further, 15 (26%) were non-depressed, 27 (47%) had mild depression, 14 (24%) moderate and 2 (3%) severe depression. Evaluating the relation using the two different presentations of PA along with depression scores, results showed r= -0.2 (p= 0.26) and r= -0.15 (p= 0.26), respectively. Conclusion: The result showed a weak negative relation, but the probability of the result being due to coincidence is high. To ensure the relation between PA and depression in patients with PD, further studies are needed in the future.

The telemedicine’s capabilities are rapidly expanding due to technological advances in a smarphone development. The goal of this thesis was to suggest the architecture and prepare the design providing acquisition, processing and synchronization of voice para- meters recorded by patients with Parkinson’s disease and to implement such system. The architecture was completed successfully, it consists of the mobile application able to record patient’s calls, the server application introducing an interface to store and synchronize the data and to provide them to the web application, where doctors can see the data and analyze it. Implementation of the server application was finished according to the design and to the requirements for robustness and security as well as the web application. By an extension of the existing mobile application for recording voice calls there was developed a huge system for the analysis of this disease.

This master’s thesis takes aim with the use of statistical methods for progression evaluation of Parkinson’s disease. There is a brief description of Parkinson’s disease. It is further stated processing and evaluation of values of speech parameters which are affected by Parkinson’s disease. The thesis describes the process using the values of classification and regression trees and evaluate results using the mean absolute error and estimated error. Processing and evaluation of values was done in MATLAB software.

Parkinson's disease (PD) is a progressive disorder that affects movement, muscle control and balance. Second only to Alzheimer's disease, PD is one of the most common neurodegenerative disorders in the United States (Lai & Tsui, 2001:135), affecting approximately one million people in the U.S. alone (Parkinson's disease Foundation [PDF], 2009). While the cause of Parkinson's disease remains unknown, there are certain known risk factors associated with the disease. One of the risk factors is increasing age. PD is most frequently associated with older adulthood, affecting one in 100 Americans 60 years and older (PDF). Over the next five decades, the incidence of PD is expected to triple, as the average age of the population increases (Lai & Tsui, 2001:135). Parkinson's disease is a chronic, progressive disorder, with no known cause or promising cure. While substantial information is known about the medical aspect of Parkinson's disease, little is known about the illness experience of living with the disease. The goal of this study was to explore and describe the experiences of people living with Parkinson's disease. The guiding research question was: What are the experiences of people living with Parkinson's disease? A qualitative research approach was followed, with a collective case study research design. The population for this study included people who are in the late stage of Parkinson's disease, thus being diagnosed with Parkinson's disease before 2012 and who are receiving support services from Parkinson's Association of South Africa (PASA). Non-probability purposive sampling was utilized to generate a sample. Ten participants who met the criteria were selected for this study. Semi-structured individual interviews were conducted with participants. Interviews were voice recorded with the permission of the participants and were transcribed. The data gathered were analysed by the researcher and themes and sub-themes were identified. The research findings were presented and critically discussed. Literature control and verbatim quotes were used to support the findings. The conclusions of this study reflected that the experiences of people living with Parkinson's disease are complex. Throughout the study it was found that Parkinson's disease impacts significantly on the physical, psychological and social well-being of people living with this disease in a number of ways. The recommendations offered by this study can be used by professionals working in the field of chronic, geriatric and neurodegenerative illnesses to understand the experiences of people living with Parkinson's disease. / Mini Dissertation (MSW)--University of Pretoria, 2016. / Social Work and Criminology / MSW / Unrestricted

Background: Parkinson's disease (PD) is a debilitating progressive neurological disorder. The main clinical features of PD are: rigidity, bradykinesia, akinesia, and resting tremor. People living with PD often present with impaired gross- and fine upper-limb motor control and ocular tracking. The impaired motor control associated with PD results in difficulty performing basic- and instrumental activities of daily living (BADLs and IADLs). Virtual reality (VR) therapy is an emerging treatment strategy used to address movement impairment in people with neurological diseases, but has not been extensively researched in the rehabilitation of people with PD. This study aimed to determine the effectiveness of VR therapy as a treatment modality for the rehabilitation of upper-limb function during BADLs and IADLs and ocular tracking for people with PD, when compared to conventional physiotherapy. Methods: A single blind randomised control trial was done. Participants were randomly allocated to either the conventional therapy (control) or VR therapy (experimental) groups using the concealed opaque envelope method. Twenty-two participants who gave informed consent were included, if they met the following criteria: Confirmed PD diagnoses; scored above 24/30 for the Mini Mental State Examination; and did not suffer from uncontrolled co-morbid diseases. The control- and experimental groups underwent twelve intervention session of 45 minutes. The control group participated in conventional physiotherapy sessions and the experimental group used the X-box Kinect© VR apparatus during treatment. Participants were assessed at baseline and post-intervention (directly following the 12 session) with the: 9 Hole Peg Test (9HPT), Test d'Evaluation des Membres Superieurs De Personnes Agees (TEMPA) and the King Devick Test. Results: The TEMPA was used to determine unilateral- and bilateral upper-limb function during IADLs and BADLs. Three of the four items of the TEMPA that assessed bilateral upper-limb function indicated statistically significant improvement when the difference between the control and experimental groups were compared post-intervention (Task1 p=0.611; Task 2 p=0.0043; Task 3 p=0.0078; Task 4 p=0.0002). Similarly, three of the four items of the TEMPA that assessed unilateral upper-limb function indicated statistically significant improvement for the experimental group, when compared to the control- group post-intervention (Task 5 p=0.0151; Task 6 p=0.4118; Task 7 p=0.0064; Task 8 p=0.0009). The 9HPT assessed in-hand manipulation and fine upper-limb function. Results from the 9HPT for the left- and right hands of both groups showed clinically significant improvements from baseline to post-intervention, but there was no statistically significant difference between the two groups. The King Devick test was used to assess ocular tracking. The comparison of change between the two groups from baseline to post-intervention on the King Devick did not indicate clinically- or statistically significant change. Discussion and Conclusion: The findings from the bilateral IADL and BADL tasks as measured with the TEMPA are similar to findings in the literature. The results show that VR therapy improve motor control of the upper-limb significantly when both hands work together and when the upper-limbs are moving unilaterally. VR therapy might be more effective than conventional physiotherapy because it allowed for repetitive practice of functional activities, which aided the development of limb control and functional muscle strength. The VR therapy also allowed task-oriented training to occur repetitively. Task-oriented training is known to aid neural plasticity and facilitate functional rehabilitation. The insignificant differences between the groups on the 9HPT is an indication that the task performed for this outcome measure is not specific enough to detect hand function and grip strength. The King Devick test did not indicate change for the control- or experimental groups, which indicates that specific ocular tracking exercises should be included in therapy to address this impairment. / Dissertation (MPhysiotherapy)--University of Pretoria, 2016. / Physiotherapy / MPhysiotherapy / Unrestricted

Background In the as of yet uncurable Parkinson´s disease aggregation of α-syn is an accelerator of pathogenesis. Oligomers of α-synuclein is considered to be neurotoxic hence blocking the endocytosis of aggregated α-syn is possibly a way of preventing pathogenesis. With a protein construct of the Receptor X (RX) previously shown to bind α-syn, it can be possible to bind soluble aggregated α-syn and decrease neuron endocytosis.  Aim The aim of this study was to express, purify and trimerize two different protein constructs of RX to study the binding to α-syn monomers &amp; oligomers and if the proteins have higher affinity to α-syn oligomers. Methods In this study two RX constructs was produced with mammalian cell transfection and purified with Strep-Tactin affinity chromatography; D1, D123mut and D123 which affinity to α-syn monomers and oligomers were studied with ELISAs. Indirect ELISAs were optimized and conducted, a competitive ELISA with D123 was tested with poor reliability.  Results The results show that D1 could not be determined pure enough to examine its α-syn binding ability. D123mut was pure enough for ELISAs but did not show adequate binding to α-syn. D123 did show binding to α-syn in an indirect ELISA.  Conclusion The results were not as promising as expected and did not distinctly help strengthen the theory of a recombinant RX protein as a viable drug. Although there is potential, optimization of both protein constructs and methods used is essential for future studies of RX as a therapeutic protein.

No description available.

This thesis examines the volatility forecasting performance of six commonly used forecasting models; the simple moving average, the exponentially weighted moving average, the ARCH model, the GARCH model, the EGARCH model and the GJR-GARCH model. The dataset used in this report are three different Nordic equity indices, OMXS30, OMXC20 and OMXH25. The objective of this paper is to compare the volatility models in terms of the in-sample and out-of-sample fit. The results were very mixed. In terms of the in-sample fit, the result was clear and unequivocally implied that assuming a heavier tailed error distribution than the normal distribution and modeling the conditional mean significantly improves the fit. Moreover a main conclusion is that yes, the more complex models do provide a better in-sample fit than the more parsimonious models. However in terms of the out-of-sample forecasting performance the result was inconclusive. There is not a single volatility model that is preferred based on all the loss functions. An important finding is however not only that the ranking differs when using different loss functions but how dramatically it can differ. This illuminates the importance of choosing an adequate loss function for the intended purpose of the forecast. Moreover it is not necessarily the model with the best in-sample fit that produces the best out-of-sample forecast. Since the out-of-sample forecast performance is so vital to the objective of the analysis one can question whether the in-sample fit should even be used at all to support the choice of a specific volatility model.

Objective: Degeneration of dopaminergic neurons in the substantia nigra projecting to the striatum is responsible for the motor symptoms in Parkinson’s disease (PD). Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is a well-established procedure to alleviate these symptoms in advanced PD. Yet the mechanism of action, especially the effects of STN-DBS on the availability of striatal dopamine transporter (DAT) as a marker of nigrostriatal nerve cell function, remains largely unknown. The aim of our study was therefore to evaluate whether 1) DAT availability changes within one year of STN-DBS and whether 2) the clinical outcome is predictable by DAT availability before surgical procedure (pre-op). Methods: Twenty-seven PD patients (age: 62.7 ± 8.9 years (y); duration of illness: 13.0 ± 4.9y; PD subtypes: akinetic-rigid n=11, equivalence n=13, tremor-dominant n=3) underwent [123I]FP-CIT single-photon emission computed tomography (SPECT) pre-op and one year after STN-DBS (post-op). DAT availability (specific-to-unspecific binding ratio, SBR) was assessed by volume of interest (VOI) analysis of the caudate nucleus and the putamen ipsilateral and contralateral to the clinically more affected side. Results: 1) Unified Parkinson’s Disease Rating Scale (UPDRS) III (pre-op on: on medication; pre-op off: off medication; post-op on/on: on medication/on stimulation; post-op on/off: on medication/off stimulation) improved significantly (pre-op on: 25.6 ± 12.3, pre-op off: 42.3 ± 15.2, post-op on/off: 41.4 ± 13.2; post-op on/on: 16.1 ± 9.4; pre-op on vs. post-op on/on: p = 0.006) while L-dopa equivalent daily dose (LEDD) was reduced (pre-op 957 ± 440 mg, post-op 313 ± 189 mg; p < 0.001). SBR did not differ significantly before and one year after DBS, regardless of PD subtypes. 2) Pre-op DAT availability was not related to the change in UPDRS III but the change in DAT availability was significantly correlated with the change in UPDRS III (contralateral head of the caudate VOI: p=0.014, contralateral putamen VOI: p=0.018). Conclusion Overall, DAT availability did not change significantly after one-year of STN-DBS. However, on an individual base, the improvement in UPDRS III was associated with an increase of DAT availability while DAT availability before STN-DBS surgery did not predict the clinical outcome. Whether a subtype-specific pattern of pre-op DAT availability can become a reliable predictor for successful STN-DBS has to be evaluated in larger study cohorts.:Introduction 2 1.1 Parkinson’s Disease Pathophysiology 2 1.2 Parkinson’s Disease Clinical Manifestation 4 1.2.1 Parkinson’s Disease Diagnosis 5 1.2.1.1 Unified Parkinson’s Disease Rating Scale 5 1.2.1.2 Imaging 6 1.2.2 Parkinson’s Disease Subtypes 6 1.3 Parkinson’s Disease Therapy 7 1.3.1 Pharmacologic Therapy 7 1.3.2 Surgical Therapy – Deep Brain Stimulation 9 1.3.2.1 Patient Selection 9 1.3.2.2 Operative Technique 9 1.3.2.3 Efficacy 10 1.3.2.4 Complications 11 1.3.2.5 Mechanism of action 11 2 Publication 15 3 Summary of Work 23 3.1 Background 23 3.2 DAT availability changes after STN-DBS 24 3.3 Pre-op DAT availability predicts the clinical outcome 25 3.4 DBS has a neuroprotective effect 25 3.5 Limitations and future direction 26 3.6 Conclusion 26 4 References 27 5 Attachments 35 5.1 Index of Abbreviations 35 5.2 List of figures 36 5.3 Academic Contribution 37 5.4 Declaration of the independent writing of this thesis 39 5.5 Declaration of Submission 40 5.6 Curriculum Vitae 41 5.7 Acknowledgements 43