No description available.

No description available.

Background: Amyotrophic Lateral Sclerosis (ALS) is a fatal neurodegenerative disease characterized by the loss of motor neurons. Preference-based measures (PBMs) of health-related quality of life (HRQL) can be utilized for cost-effectiveness analyses of interventions in individuals with ALS. However, current measures are generic (GPBMs) and the psychometric properties of these measures have not yet been evaluated in ALS. Purpose: The purpose of this thesis was to evaluate the psychometric properties of GPBMs in ALS by 1) conducting a systematic review of the psychometric properties of GPBMs, and 2) assessing the content and convergent validity of GPBMs in ALS. Methods: Two studies were conducted. First, a systematic review was performed, and four databases were searched to identify studies that used and reported on the psychometric properties of GPBMs in ALS. Second, participants were recruited from three clinical sites across Canada and outcome measures were administered through an online or hardcopy survey. Areas of importance to the HRQL of individuals with ALS were identified using the Patient Generated Index (PGI), mapped against GPBMs to determine their coverage and scores were compared to determine convergent validity. Results: For the first study, the EQ-5D-3L was found to be the most commonly used GPBMs in ALS. It demonstrated convergent and known-groups validity however, significant floor effects were observed. For the second study, results indicated that the majority of GPBMs identified approximately half of the areas impacted by ALS. In addition, there were several domains not identified by GPBMs. Conclusion: This thesis highlights the importance of complete psychometric evaluation of measures in ALS. There is the need for the development of an ALS specific preference-based measures that reflects the health concerns of individuals with ALS; as GPBMs used in ALS were evaluated and deemed to be lacking in support for their usage in ALS. / Thesis / Master of Science Rehabilitation Science (MSc) / Amyotrophic Lateral Sclerosis (ALS) is a fatal disease that causes individuals to lose their strength and eventually the ability to speak, eat, move and breathe. Questionnaires can be used to understand the health-related quality of life (HRQL) of individuals with ALS however these measures do not always reflect the experiences of these individuals. The goal of this dissertation was to identify whether measures truly capture areas important to individuals with ALS. In our studies, we found that there is little proof in the accuracy of measures used. In addition, the measures do not fully capture the areas of life important to individuals with ALS. This is important to help researchers and health care professionals understand the effects of ALS on HRQL. These results will help them determine which treatments are worthwhile and the best to use in practice and provide recommendations for future research.

No description available.

Yes / Despite intense attention from biomedical and chemical researchers, there are few approved treatments for amyotrophic lateral sclerosis (ALS), with only riluzole (Rilutek) and edaravone (Radicava) currently available to patients. Moreover, the mechanistic basis of the activity of these drugs is currently not well-defined, limiting the ability to design new medicines for ALS. This Letter describes the synthesis of triazole-containing riluzole analogues, and their testing in a novel neuroprotective assay. Seven compounds were identified as having neuroprotective activity, with two compounds having similar activity to riluzole.

Made available in DSpace on 2016-08-10T10:38:40Z (GMT). No. of bitstreams: 1 ALEANDRO GERALDO ALVES.pdf: 687501 bytes, checksum: 815caf3ef15e76a3ef410c769760c097 (MD5) Previous issue date: 2011-08-11 / Amyotrophic lateral sclerosis (ALS) is a multifactorial disease that affects motor neurons. In most cases, the disease is sporadic, however, 5 to 10% of patients have a familial history (FALS). Among patients with FALS, 12 to 23% present with mutations in the SOD1 gene. Objectives: To present a systematic review about the mutations described in SOD1 gene in patients with FALS. Methods: The databases used in this study included PubMed, ISI Web of Science and Cochrane Library Virtual Health. After reading the abstracts, 71 articles were selected and systematically reviewed on this study. Results: The largest number of publications was found in 1997, and Japan was the country with the majority of published studies on the subject, with 23 articles. The majority of the mutations were described in éxons four and five of SOD1 gene, and A4V, I113T, I144F, D90A and L38V were the most commonly mutation described. More than 156 mutations in the SOD1 gene have been cataloged in patients with ALS-F and these data are deposited in ALS GENETICS ONLINE DATABASE, a database that contains specific information on mutations associated with amyotrophic lateral sclerosis. However, the articles reviewed in this study described 103 mutations. Conclusions: Several mutations in the SOD1 gene have been described in patients with ALS-F, however, the relationship between such mutations and the pathogenesis of ALS-F remains unclear, as well as the relationship between mutations and disease progression. Further studies are necessary in order to better explain such relationship. / A esclerose amiotrófica lateral (EAL) é uma doença multifatorial que afeta os neurônios motores. Na maioria dos casos, a doença é esporádica, entretanto, 5 a 10% dos pacientes apresentam história familiar (EAL-F). Dentre os pacientes com EAL-F, 12 a 23% apresentam mutações no gene SOD1. O objetivo deste trabalho foi realizar uma revisão sistemática acerca das mutações descritas no gene SOD1 em pacientes com EAL-F. As bases de dados consultadas incluíram Pubmed, ISI Web of Science e Cochrane Biblioteca Virtual em Saúde. Após a revisão dos resumos, 71 artigos foram selecionados descrevendo mutações no gene SOD1 em pacientes com EAL-F. O ano que apresentou o maior número de publicações foi 1997 e o Japão foi o país que mais publicou sobre o assunto, aparecendo em 23 artigos. O maior número de mutações foi descrito nos éxons 4 e 5 do gene SOD1 e as mutações A4V, I113T, I144F, D90A e L38V foram as mais comumente citadas. Até o momento 156 mutações no gene SOD1 já foram catalogadas em pacientes com EAL-F e esses dados encontram-se depositados no ALS ONLINE GENETICS DATABASE, um banco de dados que contém informações específicas sobre mutações associadas à esclerose amiotrófica lateral. Entretanto, os artigos revisados neste estudo descrevem 103 destas mutações. As causas relacionadas às mutações no gene SOD1 permanecem incertas, assim como a relação entre tais mutações e a evolução da doença, portanto, muito ainda deve ser estudado acerca desse tema.

Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 5 uppsatser. Även tryckt utgåva.

Lipids are important for structural and physiological functions of neuronal cell membranes. They exhibit a range of biological effects many are bioactive lipid mediators derived from polyunsaturated fatty acids such as sphingolipids, fatty acid ethanolamides (FA-EA) and endocannabinoids (EC). These lipid mediators and oxysterols elicit potent bioactive functions in many physiological and pathological processes of the brain and neuronal tissues. They have been investigated for biomarker discovery of ageing, neuroinflammation and neurodegenerative disorders. The n-3 fatty acids EPA and DPA are thought to exhibit a range of neuroprotective effects many of which are mediated through production of such lipid mediators. The aims of this study were to evaluate the effects of n-3 EPA and n-3 DPA supplementation on RBC membranes and in this way assess dietary compliance and to investigate brain sphingomyelin species of adult and aged rats supplemented with n-3 EPA and n-3 DPA to evaluate the effects and benefits on age-related changes in the brain. Furthermore, to study the effects of lithium on the brain FA-EAs and ECs to further understand the neuroprotective effects of lithium neuroprotective action on neuroinflammation as induced by LPS. Finally to examine if circulating oxysterols are linked to the prevalence of ALS and whether RBC fatty acids are markers of this action in relation to age and disease stages. These analytes were extracted from tissue samples and analysed with GC, LC/ESI-MS/MS and GC-MS. It was found that aged rats exhibited a significant increase in brain AA and decrease in Σn-3 and Σn-6 PUFAs when compared to adult animals. The observed increase of brain AA was reversed following n-3 EPA and n-3 DPA supplementation. Sphingomyelin was significantly increased when aged animals were supplemented with n-3 DPA. LPS treatment following lithium supplementation increased LA-EA and ALA-EA, while it decreased DHA-EA. Both oxysterols 24-OH and 27-OH increased in ALS patients and SOD1-mice. Eicosadienoic acid was different in ASL-patients compared to aged SOD1-mice. These studies demonstrated that dietary intake of n-3 EPA and n-3DPA significantly altered RBC fatty acids and sphingolipids in rat brain. They suggest that n-3 DPA can be a potential storage form for EPA, as shown by retro-conversion of n-3 DPA into EPA in erythrocyte membranes, ensuring supply of n-3 EPA. Also, n-3 EPA and n-3 DPA supplementation can contribute to an increase in brain sphingomyelin species with implications for age effects and regulation of brain development. Effects of lithium highlight novel anti-neuroinflammatory treatment pathways. Both 24-hydroxycholesterol and eicosadienoic acid may be used as biomarkers in ALS thereby possibly helping to manage the progressive stages of disease.

The thesis research aims to further the study of human-robot interaction (HRI) issues, especially regarding the development of an assistive robot designed to help individuals possessing motor impairments. In particular, individuals with amyotrophic lateral sclerosis (ALS), represent a potential user population that possess an array of motor impairment due to the progressive nature of the disease. Through review of the literature, an initial target for robotic assistance was determined to be object retrieval and delivery tasks to aid with dropped or otherwise unreachable objects, which represent a common and significant difficulty for individuals with limited motor capabilities. This thesis research has been conducted as part of a larger, collaborative project between the Georgia Institute of Technology and Emory University. To this end, we developed and evaluated a semi-autonomous mobile healthcare service robot named EL-E. I conducted four human studies involving patients with ALS with the following objectives: 1) to investigate and better understand the practical, everyday needs and limitations of people with severe motor impairments; 2) to translate these needs into pragmatic tasks or goals to be achieved through an assistive robot and reflect these needs and limitations into the robot's design; 3) to develop practical, usable, and effective interaction mechanisms by which the impaired users can control the robot; and 4) and to evaluate the performance of the robot and improve its usability. I anticipate that the findings from this research will contribute to the ongoing research in the development and evaluation of effective and affordable assistive manipulation robots, which can help to mitigate the difficulties, frustration, and lost independence experienced by individuals with significant motor impairments and improve their quality of life.

Lipids are important for structural and physiological functions of neuronal cell membranes. They exhibit a range of biological effects many are bioactive lipid mediators derived from polyunsaturated fatty acids such as sphingolipids, fatty acid ethanolamides (FA-EA) and endocannabinoids (EC). These lipid mediators and oxysterols elicit potent bioactive functions in many physiological and pathological processes of the brain and neuronal tissues. They have been investigated for biomarker discovery of ageing, neuroinflammation and neurodegenerative disorders. The n-3 fatty acids EPA and DPA are thought to exhibit a range of neuroprotective effects many of which are mediated through production of such lipid mediators. The aims of this study were to evaluate the effects of n-3 EPA and n-3 DPA supplementation on RBC membranes and in this way assess dietary compliance and to investigate brain sphingomyelin species of adult and aged rats supplemented with n-3 EPA and n-3 DPA to evaluate the effects and benefits on age-related changes in the brain. Furthermore, to study the effects of lithium on the brain FA-EAs and ECs to further understand the neuroprotective effects of lithium neuroprotective action on neuroinflammation as induced by LPS. Finally to examine if circulating oxysterols are linked to the prevalence of ALS and whether RBC fatty acids are markers of this action in relation to age and disease stages. These analytes were extracted from tissue samples and analysed with GC, LC/ESI-MS/MS and GC-MS. It was found that aged rats exhibited a significant increase in brain AA and decrease in ¿n-3 and ¿n-6 PUFAs when compared to adult animals. The observed increase of brain AA was reversed following n-3 EPA and n-3 DPA supplementation. Sphingomyelin was significantly increased when aged animals were supplemented with n-3 DPA. LPS treatment following lithium supplementation increased LA-EA and ALA-EA, while it decreased DHA-EA. Both oxysterols 24-OH and 27-OH increased in ALS patients and SOD1-mice. Eicosadienoic acid was different in ASL-patients compared to aged SOD1-mice. These studies demonstrated that dietary intake of n-3 EPA and n-3DPA significantly altered RBC fatty acids and sphingolipids in rat brain. They suggest that n-3 DPA can be a potential storage form for EPA, as shown by retro-conversion of n-3 DPA into EPA in erythrocyte membranes, ensuring supply of n-3 EPA. Also, n-3 EPA and n-3 DPA supplementation can contribute to an increase in brain sphingomyelin species with implications for age effects and regulation of brain development. Effects of lithium highlight novel anti-neuroinflammatory treatment pathways. Both 24-hydroxycholesterol and eicosadienoic acid may be used as biomarkers in ALS thereby possibly helping to manage the progressive stages of disease. / Libyan Government