published_or_final_version / Medicine / Doctoral / Doctor of Philosophy

published_or_final_version / abstract / Humanities / Doctoral / Doctor of Philosophy

published_or_final_version / Nursing Studies / Master / Master of Nursing

published_or_final_version / Nursing Studies / Master / Master of Nursing

published_or_final_version / Anatomy / Doctoral / Doctor of Philosophy

Ischemic stroke is a leading cause of death and long-term disability in the world. Although many pathological aspects of mechanisms are considered to be involved in the stroke, accumulating evidences implicated that inflammation accounts for its progression and complications. Tumor necrosis factor-alpha (TNF-α) and nitric oxide are considered as key mediators produced by cells like microglia in the pathogenesis of the disease. Therefore, the development of therapies targeting at the suppression of nitric oxide and TNF-α productions may ameliorate the severity of ischemic stroke. Gastrodia and Uncaria Decoction (GUD) is a traditional herbal decoction that is commonly used in the therapy of post-ischemic stroke in China. Although it shows great efficacy in clinical treatment, few studies have been conducted to investigate the mechanisms of action of GUD. Furthermore, GUD contains a complex mixture of constituents and the effects of these compounds are unknown. In this study, individual herbs from GUD were extracted and the bioactive fractions were further separated using liquid-liquid partition, silica gel chromatography and high performance liquid chromatography (HPLC). The inhibitory effect of the extracts on lipopolysaccharide (LPS)-stimulated nitric oxide production in BV-2 microglial cells was utilized as the biological marker for the screening. After several rounds of purification, a purified bioactive compound was isolated. After spectroscopic analysis by nuclear magnetic resonance and gas chromatography-mass spectrometry, the compound was identified as genipin (1R,4aS,5,7aS-tetrahydro-1-hydroxy-7-(hydroxymethyl)-cyclopenta[c]pyran-4-carboxylic acid, methyl ester). Mechanisms of the suppressive action on signaling pathways were investigated in the LPS-activated BV-2 cells. Our results demonstrated that genipin can dose-dependently inhibit LPS-stimulated nitric oxide overproduction. It can also suppress mRNA levels and protein expressions of inducible nitric oxide synthase (iNOS) and TNF-αupon LPS-induction. In addition, the phosphorylations of phosphoinositide-3 kinase (PI3K) and protein kinase B (Akt) were suppressed. In contrast, the phosphorylations of mitogen-activated protein kinases (MAPKs), nuclear translocation of nuclear factor-κB (NF-κB) p65 and degradation of inhibitory κB-α (IκB-α) were not affected by genipin. Finally, genipin protected murine Neuro-2a neuroblast against neurotoxicity stimulated by the conditioned media transferred from LPS-challenged BV-2 cells. In conclusion, the anti-inflammatory effects of genipin are via the modulation of PI3K/Akt signaling pathway. Genipin and its synthetic analogues may have great potential for developing into new drugs in treating ischemic stroke. In addition, genipin can be used as the chemical marker to standardize the extract of Eucommia ulmoides Oliver as anti-inflammatory agents for treating inflammatory conditions associated with ischemic stroke. / published_or_final_version / Paediatrics and Adolescent Medicine / Master / Master of Philosophy

A short report submitted to the Faculty of Medicine, University of the Witwatersrand in partial fulfilment of the requirements for the degree of Master of Medicine in Nuclear Medicine / 19 patients were selected, from the patients screened, for investigation within 48 hours of the onset of an ischaemic cerebrovascular accident. Clinical neurulogical scoring, computerized tomography lCT) scans and single photon emission computed tomography (SPECT) scans were performed on day 1, day 10 and day 30. SPECT scan data was analysed by 5 semi-quantitative methods, and findings were compared with neuroloyical clinical scores on each respective day. It was found that day 1 SPECT scans are of value for early localization of the acute ischaemic infarction. A multiple regression model was developed using both the day 30 Defect Volume index and segmental analysis score which related to the day 30 clinical scores. The day 1 model was unsatisfactory and no such model was found relating day 10 SPECT semi-quantitative methods to day 10 clinical scoring. Changes in semi-quantitative scores from day 1 to day 30 did not correlate with clinical changes. Longer follow up may be required for there to be value in performing SPECT scans in stroke trials. A prognostic equation was derived by multiple regression analysis of day 1 SPECT scan scores and day 30 clinical scores. / Andrew Chakane 2019

Thesis advisor: Ellen K. Mahoney / Purpose: The purpose of this qualitative descriptive study was to investigate the experiences of post stroke survivors (PSSs) during transition from hospital discharge home during the first four weeks. Background: PSSs describe the transition from hospital to home as an important time in recovery and stress various physical and cognitive concerns early within the recovery period. Research to date fails to adequately reflect PSSs' experiences early after discharge home. This gap in research limits the ability to create interventions for PSSs during this critical time period. Methods/analysis: Semi-structured telephone interviews were conducted with 31 participants, recruited from a large metropolitan hospital in the northeastern United States. The use of in-vivo codes lead to the development of themes that described PSSs' experiences during the four week transitional period. Credibility and transferability of findings were strengthened through memoing, field notes, reflexivity of analysis, member checking, and peer review throughout the analysis process by qualitative experts. Results: The five major themes were: (a) the shock of a stroke interrupting a normal day, (b) transition to an unfamiliar home, (c) experiencing a life riddled with uncertainty, (d) a journey to a new sense of self, and (e) adjusting to a new sense of self. Throughout their journey all PSSs had to cope with uncertainty and adjust to a new sense of self. PSSs that experienced less uncertainty were able to return to their prior daily routine, knew how to prevent another stroke, had a helpful support system, and had frequent follow-up and communication with health care professionals. Conclusion: All PSSs are at risk for complications regardless of stroke severity. To address PSSs complex needs, nurses can provide care beyond symptom management by fostering a dynamic intentional relationship to support recovery. The framework resulting from this study can provide the platform for advanced neuroscience nurses to engage with PSSs to improve their recovery and adjustment to a new sense of self as they transition from hospital to home. / Thesis (PhD) — Boston College, 2014. / Submitted to: Boston College. Graduate School of Arts and Sciences. / Discipline: Philosophy.

Várias são as propostas para reabilitação da disfagia orofaríngea, sendo a eletroestimulação neuromuscular (EENM) uma nova modalidade de tratamento. Poucos são os trabalhos que comprovam a eficácia deste tratamento na reabilitação da disfagia e ainda não foram encontrados estudos que verificaram o efeito da EENM em idosos em fase tardia do acometimento vascular encefálico. Assim, o objetivo do presente trabalho foi verificar o efeito, a curto e médio prazo, da terapia da deglutição com EENM sensorial em idosos com sequelas de acidente vascular encefálico (AVE) que foram submetidos à terapia fonoaudiológica convencional sem sucesso, quanto ao nível de ingestão oral, ao quadro de disfagia orofaríngea e à qualidade de vida relacionada à deglutição. Para isto 10 indivíduos idosos, pósacidente vascular encefálico (AVE), que já haviam realizado terapia fonoaudiológica convencional foram classificados quanto ao nível de ingestão oral na escala funcional de ingestão oral (FOIS), submetidos à avaliação instrumental (videofluoroscopia) da deglutição utilizando-se líquido, alimento na consistência de pudim e sólido, a partir da qual foi analisado o grau da disfagia orofaríngea por meio da escala Dysphagia Outcome and Severity Scale (DOSS), realizada a classificação na escala de penetração e aspiração e na escala de resíduos. Também foi realizada a aplicação do protocolo de qualidade de vida relacionado à deglutição SWAL-QOL e aos procedimentos terapêuticos propostos, sendo que os exames foram repetidos imediatamente e três meses após a reabilitação. As sessões de terapia foram realizadas três vezes por semana e distribuídas em quatro semanas, totalizando 12 sessões. Cada sessão consistiu em duas etapas de 10 minutos de exercício, nas quais os pacientes foram solicitados a deglutirem a saliva com esforço, ou umapequena quantidade de água a cada 10 segundos durante a EENM. imediatamente após e três meses após as 12 sessões de terapia, todos os indivíduos foram submetidos novamente às avaliações iniciais. Os resultados demonstram que houve melhora da classificação da deglutição para 4 dos 10 pacientes imediatamente após a intervenção e, após três meses, um paciente ainda melhorou em mais um nível. Na análise estatística foi confirmada diferença significante na classificação da escala DOSS (0,023) entre os períodos. Além disso, houve diferença estatisticamente significante na somatória dos pontos do questionário de qualidade de vida relacionado à deglutição (p=0,008) entre os períodos pré e pós 3 meses de terapia com EENM. Não foram encontradas diferenças entre os períodos da reabilitação quanto ao nível de ingestão oral, classificação da penetração e aspiração, aos resíduos na faringe e aos tempos de trânsito oral e faríngeo (p>0,005). Portanto, a aplicação da eletroestimulação neuromuscular em nível sensorial em idosos acometidos por AVE resultou em diminuição do grau da disfagia em curto e médio prazo, além de melhora na qualidade de vida relacionada à deglutição após três meses de terapia. / There are several proposals for rehabilitation of oropharyngeal dysphagia, and the neuromuscular electrical stimulation (NMES) is a new type of treatment. There are few studies proving the efficiency of this treatment in oropharyngeal dysphagia, and studies verifying the effect of NMES in the elderly in late stage of cerebrovascular impairment haven´t been found yet. Thus, the objective of this study is to verify the short- and medium-term effect of the deglutition therapy with sensorial NMES in elderly patients with stroke sequelae, who underwent conventional speech therapy with no success, regarding the level of oral intake, the oropharyngeal dysphagia condition and the quality of life related to deglutition. In order to achieve such objective, 10 poststroke elderly patients, who had already undergone conventional speech therapy, were classified regarding the level of oral intake according to the functional oral intake scale (FOIS). They underwent swallowing instrumental assessment (fluoroscopy) with liquid, solid food and food in the consistency of pudding, their level of oropharyngeal dysphagia was analyzed by means of the Dysphagia Outcome and Severity Scale (DOSS), and they were rated by means of the penetration and aspiration scale and the waste scale. The SWAL-QOL outcomes tool was also applied regarding the quality of life in deglutition and the therapeutic procedures proposed. The sessions were performed three times per week for 4 weeks, a total of 12 sessions. One session consisted of two 10 minutes exercises with a 2 minutes rest period provided between exercises. Patients were asked to forcefully swallow their saliva or a small amount of water every 10 seconds during stimulation. The exams were repeated immediately and three months after rehabilitation. The results show there was an improvement in the deglutition rating for 4 out of the 10 patients immediately after the intervention and, after three months, one patient improved in one more level. In the statistical analysis, a significant difference was confirmed in the rating of the scale DOSS (0.023) between the periods. Furthermore, there was a statistically significant difference in the sum of the scores of the quality of life questionnaire related to deglutition (p=0.008) between the periods before and after 3-month therapy with NMES. No differences were found between the rehabilitation periods regarding the level of oral intake, the penetration and aspiration rating, the waste in the pharynx and oral and pharyngeal transit times (p>0.005). Therefore, the application of neuromuscular electrical stimulation in sensory level in elderly patients who had stroke resulted in the lowering of the dysphagia level in short- and long- term, in addition to the improvement in the quality of life related to deglutition after three months of therapy.

Background: Previous studies that have examined functional status in relation to vascular events have focused on the short term after events and have measured functional status a limited number of times. The trajectories of functional status before and after vascular events are not well characterized, and the factors influencing these trajectories are not well known. Methods: A comprehensive, structured, narrative review was performed on the topic of trajectories of disability and cognition surrounding vascular events. Then using 2 large population-based epidemiologic cohorts, the Northern Manhattan Study (NOMAS) and the Cardiovascular Health Study (CHS), trajectories of functional status were examined. In Analysis A, in NOMAS, the effect of inflammatory biomarkers (interleukin-6 [IL6], tumor necrosis factor receptor-1 [TNFR1], C-reactive protein [CRP], and lipoprotein-associated phospholipase-A2 [LpPLA2]) on the intercept and slope of functional status was determined over a median of 13 years, measured with yearly assessments by the Barthel index. In Analysis B, in NOMAS, a similar modeling strategy was used to examine whether subclinical ischemic disease on brain MRIs, measured by subclinical brain infarct (SBI) and white matter hyperintensity volume (WMHV), was associated with functional trajectories. In Analysis C, in CHS, participants had yearly assessments of disability with a combined activities of daily living (ADL) and instrumental ADL scale. The slope of change in disability was compared before and after vascular events (stroke and myocardial infarction [MI]). Results: In Analysis A, CRP (-0.41 BI points per 1 SD increase, 95% CI -0.82 to 0.002) and LpPLA2 (-0.40, 95% CI -0.75 to -0.04) were associated with baseline BI but not change over time. TNFR1 was associated with baseline BI (-0.93, 95% CI -1.59 to -0.26) and change over time (-0.36 BI points per year, 95% CI -0.69 to -0.03). In Analysis B, functional change was -0.85 BI points per year (95%CI -1.01 to -0.69); among those with SBI there were -0.88 additional points annually (-1.44 to -0.32). In WMHV models, annual functional change was -1.04 points (-1.2 to -0.88), with -0.74 additional points annually per SD WMHV increase (-0.99 to -0.49). In Analysis C, stroke (0.88, 95% CI 0.57-1.20, p<0.0001) was associated with a greater acute increase in disability than MI (0.20, 0.06-0.35, p=0.006). The annual increase in disability before stroke (0.06 points per year, 0.002-0.12, p=0.04) more than tripled after stroke (0.15 additional points per year, 0.004-0.30, p=0.04). The annual increase in disability before MI (0.04 points per year, 0.004-0.08, p=0.03) did not change significantly after MI (0.02 additional points per year, -0.07-0.11, p=0.7). Conclusions: In these large population-based studies with repeated measures of functional status and disability over long-term follow-up, several trajectories were found. In Analysis A, TNFR1 predicted worse overall functional status as well as accelerated decline over time. In Analysis B, both SBI and WMHV were associated with accelerated decline. In Analysis C, there was a steeper decline in function after stroke but not MI. These findings help to elucidate the course and potential etiologies of long-term functional decline related to vascular events, and they suggest directions for future research in this area.