published_or_final_version / abstract / Physiology / Master / Master of Philosophy

published_or_final_version / abstract / Physiology / Master / Master of Philosophy

published_or_final_version / Physiology / Doctoral / Doctor of Philosophy

Vertigo is the presenting symptom of some peripheral vestibular disorders, like Benign Positional Vertigo (BPV), Ménière's disease, and vestibular neuritis, and for many other clinical conditions as well. Some clinicians from the Christchurch Public Hospital suspect that there is a significant need to improve the diagnostic accuracy and overall management of patients presenting with complaints of "acute vertigo or dizziness", especially BPV and Ménière's disease. The final diagnosis of many such patients treated for these conditions in the past has been suspected to be somewhat incomplete or inappropriate. These patients were commonly referred to various other departments, where they underwent a number of investigations, particularly medical imaging [head CT (Computed Tomography) / MRI (Magnetic Resonance Imaging) scans, which were in many cases not necessary. Such delays in the process led to an extra or unnecessary burden on the limited health funds available to the hospital or to the patient. Another drawback was an elevated patient stress and anxiety as critical time was lost with the increased number of admissions, or in transferring the patient between various departments without any conclusive diagnosis and treatment. It was proposed to conduct a retrospective study on the accuracy of diagnosis of those patients admitted to Christchurch Public Hospital with complaints of acute vertigo, particularly for suspected peripheral vestibular disorders (mainly BPV and Ménière's disease) over the period of 2004-2005. Implementation of a more specific and detailed management approach at the level of the initial clinical examination or diagnostic investigations (specifically, by an early Otolaryngology/Audiology intervention) was planned for the year 2006. The two groups of patients (2004-2005 and 2006) were compared to verify the final achievements concerning the diagnostic accuracy and at various other levels with the newly implemented changes in 2006.

Background: Sit-to-stand is a challenging task as it requires the transition from a large 3-point base of support to a small 2-point base of support while simultaneously controlling anteroposterior and vertical body acceleration. Age-related morphological changes in both the visual and vestibular system could impair the ability to extract and interpret sensory information necessary for motor control in older adults, which can increase instability and the risk of falls. The purpose of this study is to understand the effects of aging on visual-vestibular interaction for maintaining stability during sit-to-stand. Methods: Fifteen younger (age=22.5±1.1) and fifteen older (age=73.9±5.3) healthy adults were asked to stand from a sitting position as quickly as possible. Vestibular input was manipulated using percutaneous bipolar galvanic vestibular stimulation where threshold intensity was individually calculated for each participant during quiet stance with eyes closed. Galvanic vestibular stimulation was applied at both threshold (1xGVS) and 2-times the participant’s threshold intensity (2xGVS). Visual conditions included eyes opened, wearing custom-made vision blurring goggles, or eyes closed. Outcome measures included a global measure of performance (transition phase duration), mediolateral stability (peak-to-peak trunk roll angle, mediolateral center of mass displacement, mediolateral center of pressure displacement) and anteroposterior stability (peak braking force, peak-to-peak trunk pitch angle, and peak anteroposterior center of mass velocity). Results: When vision was suboptimal (blurring goggles), older adults had significantly longer transition phase duration than younger adults (p<0.05). Older adults demonstrated greater mediolateral instability than younger adults. When vision was absent, trunk roll angle was significantly greater with 1xGVS than 2xGVS (p<0.05). Mediolateral center of mass displacement was greater when vision was absent than when vision was available, irrespective of age (p<0.05). No effects of age, vision or galvanic vestibular stimulation were seen in peak braking force, trunk pitch angle, and peak anteroposterior center of mass velocity (p>0.05). Conclusion: Regardless of age, visual inputs were more critical to maintain stability during sit-to-stand than vestibular inputs. Differences between younger adults and older adults were only seen in the mediolateral direction. Despite having greater mediolateral instability, older adults utilized similar strategies as younger adults to overcome sensory perturbations during sit-to-stand. / Thesis (Master, Rehabilitation Science) -- Queen's University, 2013-09-20 23:22:16.695

Background Hair cells (HCs) are the sensory receptors in both the auditory and the vestibular organs of the inner ear. Supporting cells (SCs) are non-sensory cells embracing the HCs. Injuries of the HCs by aging, acoustic trauma or ototoxic drugs (mainly aminoglycosides, e.g. gentamicin) and cisplatin, often cause permanent impairment of hearing and balance. Birds and amphibians can regenerate their auditory and vestibular HCs after injury through proliferation of SCs or direct transdifferentiation of a SC into a HC. For mammals this ability is limited and spontaneous HC regeneration occurs only in the vestibular sensory epithelia. The utricle is one of the five vestibular organs and contributes to our balance by registering linear acceleration and head tilts. The aim of this PhD thesis was to investigate morphological and morphometric events during spontaneous HC regeneration following gentamicin exposure in neonatal rat utricular explants. Methods Long-term organ culture of macula utriculi, which is stable and reproducible for up to 28 days in vitro (DIV), was used in all papers in the thesis. HC damage was induced by gentamicin. On 2 DIV the explanted utricular maculae were divided into two groups, a control group and a gentamicin-exposed group. In the latter group macular explants were exposed to gentamicin for 48 hours during 2-3 DIV and then allowed to recover. Morphologic and morphometric evaluations were done from utricles harvested at various time points during 28 DIV. Imaging techniques used were light microscopy, including immunohistochemistry, and transmission electron microscopy. Results In the control group the epithelia were well preserved with a slight decline in HC density after 14 DIV. In the gentamicin-exposed group there was an initial substantial decline in HC density and thereafter the proportion of HCs in relation to SCs increased significantly. Using BrdU as a proliferation marker and myosin 7a as a HC marker, we found no cells that were double marked. At the ultrastructural level, the apical occlusion of the explanted epithelia was intact in both the control and the gentamicin exposed group during the entire in vitro period. Cells that seemed to be in a transitional state, transforming from SCs into HCs were observed in the gentamicin-exposed group. These cells had cytoplasmic extensions basally i.e. foot processes, an assembly of mitochondria basally in the cell or in these foot processes, and often apical SC extensions covering the HC. HCs classified as transitional cells had an increased number of SC connections to their basal parts compared to mature HCs. Conclusions  In these neonatal rat utricular explants: - The morphological structure of the sensory epithelia was well preserved during long-term culture. - The renewal of hair cells after gentamicin exposure occurred through direct transdifferentiation of supporting cells into hair cells. - There was also a proliferative response by the supporting cells, but this supporting cell proliferation did not contribute to the generation of new hair cells. - Cells in a transitional state, showing a characteristic morphology, were observed during the process of transdifferentiation from supporting cells into hair cells. - The tight junctional seal of the epithelia stayed morphologically intact also after gentamicin exposure. - Gap junctions were observed in between supporting cells but not found in between hair cells and supporting cells or between transitional cells and supporting cells.

The theoretical part focuses on vestibular system - the formation and role of vestibular information in the control of bipedal locomotion, and processes issues of gait control with respect to walking speed and the use of sensory feedback. The experimental part deals with the effect of rotational stimulation of labyrinth on the ability to maintain straight walking direction with the exclusion of visual control at various speeds - slow walking, fast walking and running. Two groups were tested - younger group aged 21 - 30 years (29 people) and older group aged 41 - 55 years (15 people). The difference between deviations from a straight direction before stimulation (with the exclusion of visual control) and after stimulation appeared to be significant (p < 0.05) for slow walking, fast walking and running, but only in the younger group. In the younger group there was also a statistically significant difference between deviation for slow walking after rotational stimulation and deviations for fast walking and running after stimulation. In the older group there were statistically insignificant differences between deviations before and after stimulation and between various speeds. Younger and older group differed statistically significantly in response to rotational stimulation at slow walking. The results...

Doctor of Philosophy / Biochemistry Interdepartmental Program / Antje Philine Wangemann / Mutations of SLC26A4 are the most common cause of the hearing loss associated with enlargement of the vestibular aqueduct. SLC26A4 encodes pendrin, an anion exchanger expressed in the cochlea, the vestibular labyrinth, and the endolymphatic sac of the inner ear. Slc26a4Δ/Δ mice, devoid of pendrin expression, develop an enlarged membranous labyrinth which leads to the failure to develop hearing, thereby recapitulating the human disease. Identifying the ionic composition of the endolymph and evaluating the importance of pendrin expression at various sites are initial steps towards developing strategies for preventing enlargement of the endolymph volume and subsequently restoring the inner ear functions. The major aims of the present study are 1) To determine the ionic composition of inner ear fluids during the developmental phase in which the enlargement of the endolymph volume occurs; 2) To test the hypothesis that pendrin expression in the endolymphatic sac is more important than its expression in the cochlea and the vestibular labyrinth. Here, we determined the Na+ and K⁺ concentrations in the cochlea and the endolymphatic sac with double-barreled ion-selective electrodes and generated a mouse model that restores pendrin expression in the endolymphatic sac while lacking expression in the cochlea and the vestibular labyrinth. High Na⁺ and low K⁺ concentrations were found in the cochlear endolymph during the embryonic stage. A rise of the K⁺ concentration along with a decline of the Na⁺ concentration occurred shortly before birth. The site-specific restoration of pendrin to the endolymphatic sac prevented enlargement and rescued hearing and balance. In conclusion, these data demonstrate that endolymph, in the phase of luminal enlargement during the embryonic development, is a Na⁺-rich fluid that is modified into a K⁺-rich fluid just before birth; restoration of pendrin in the endolymphatic sac is sufficient for developing normal inner ear function. Furthermore, these data suggest enlargement of endolymph volume caused by the loss of Slc26a4 is a consequence of disrupted Na⁺ absorption. Moreover, pharmacological strategies that correct fluid transport, as well as spatially and temporally limited restorations of pendrin, might restore normal inner ear functions in humans carrying mutations of SLC26A4.

A influência de avaliações em larga escala no currículo é bem conhecida e discutida amplamente. Contudo, a influência de avaliações vestibulares no mesmo tem sido deixada de lado, bem como a discussão sobre sua influência nos próprios exames governamentais. O presente texto tenta abrir este caminho, analisando a alteração nos tipos de questões elaboradas pelo vestibular, no sentido de arcar com uma responsabilidade social que lhe foi imposta. É feita uma análise do nível cognitivo exigido pelas questões - com base na taxonomia de Bloom (1983) e nas classes de exigência cognitiva de Zoller (2002), entre outras características - bem como outros detalhes relevantes, como interdisciplinaridade, área da química abordada, habilidades e competências envolvidas e o índice de discriminação, ao longo de onze anos (2003 - 2013). Os resultados demonstram uma crescente preocupação com o modo como se mede as capacidades dos alunos avaliados por tais exames. A partir de então, discute-se brevemente sobre o uso dos exames vestibulares como base para a construção do currículo, bem como o modo com que os exames são tratados pelo meio leigo e suas consequências / The influence of large scale assessment on the curriculum is well known and widely discussed. However, a influence of pre-entrance tests on it has been put aside, as well as the discussion about is influence on governmental assessment. The present work tries to clear that pass, analysing if there is any significant change on the types of questions made by these pre-entrance exams, in a perspective of living up to the social responsibility that was imposed on them. It is made an analysis around the cognitive level required by the questions - based on Bloom\'s taxonomy (1983) and in Zollers cognitive skills requirements (2002) - amongst other relevant details, such as interdisciplinarity, chemistry field addressed, skills and competences involved and the discrimination rate, over the period of eleven years (2003 - 2013). The results show a growing worry towards the way the student\'s capability is being measured by these exams. From that, it\'s briefly discussed the use of such exams as base to building the curriculum, as well as how the exams are treated by the non-academics and its consequences.

Em um contexto de disputa por uma vaga no Ensino Superior, diversos projetos têm surgido para auxiliar estudantes de baixa renda na preparação para os concorridos exames. Denominamos esses espaços como Cursinhos Populares (CPs), projetos que propõem uma Educação Popular que visa a superação solidária e coletiva das barreiras que impedem a entrada de estudantes de baixa renda nas universidades. Esta pesquisa investiga a proposta pedagógica e o trabalho dos professores de Geografia de três CPs de Porto Alegre, e analisa o desempenho dos estudantes nos exames. O objetivo principal deste trabalho é investigar e analisar as estratégias desenvolvidas por professores de Geografia dos CPs no que diz respeito às metodologias de ensino adotadas. / En un contexto de disputa por una vacante en la Enseñanza Superior, diversos proyectos han surgido para auxiliar a estudiantes de baja renta en la preparación para los concurridos exámenes. Denominamos esos espacios como Cursinhos Populares (CPs), proyectos que proponen una Educación Popular que busca la superación solidaria y colectiva de las barreras que impiden la entrada de estudiantes de baja renta en las universidades. Esta tesis investiga la propuesta pedagógica y el trabajo de los profesores de Geografía de tres CPs de Porto Alegre, y analiza el desempeño de los estudiantes en los exámenes. El objetivo principal de este trabajo es investigar y analizar las estrategias promovidas por profesores de Geografía de los CPs en lo que se refiere a las metodologías de enseñanza adoptadas.