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No description available.

No description available.

The first stage of mammalian auditory processing occurs within the dorsal and ventral divisions of the cochlear nucleus. The dorsal cochlear nucleus (DCN) is remarkable in that it shares striking similarities with the cerebellum in terms of its development, gene expression patterns, and anatomical organization. Notably, principal cells of the DCN integrate auditory nerve input with a diverse array of signals conveyed by a mossy fiber- granule cell system. Yet how the elaborate cerebellum-like circuitry of DCN contributes to early auditory processing has been a longstanding puzzle. The work in this thesis shows that, in mice, that the DCN functions to cancel responses to self-generated sounds. While the DCN and ventral cochlear nucleus (VCN) neurons respond similarly to externally-generated acoustic stimuli, sounds generated by licking behavior evoke much weaker responses in DCN than in VCN. Recordings in deafened mice revealed non- auditory signals related to licking in Purkinje-like neurons of DCN. Moreover, silencing somatosensory mossy fiber inputs revealed prominent DCN responses to sounds generated by licking, suggesting that these inputs normally function to cancel responses to self-generated sounds. Finally, I show that this cancellation is not fixed, but involves an adaptive process whereby neural responses correlated with the animal’s own behavior are gradually reduced. Together, these findings suggest that the fundamental process of distinguishing self-generated from external stimuli begins at the very first stage of mammalian auditory processing. Related adaptive filtering functions have been described for cerebellum-like sensory structures in fish and hypothesized for the mammalian cerebellum. Hence our findings also suggest that, despite their wide phylogenetic separation, different cerebellum-like structures and the cerebellum itself may all perform a similar computation.

This thesis cover two separate topics related to the function of the mammalian inner ear. Acoustic sensitivity of the vestibular system. Data are presented showing facilitation of the auditory startle response by tones outside the range of the mouse cochlea. The sensation of these low frequency tones is demonstrated to be mediated via the acoustically sensitive sacculus of the vestibular system by data collected from Nox3-/- mice. These mice lack the otoconia of the vestibular system and, unlike the wild-type mice, only show facilitation to tones within the range of the mouse cochlea, and not in response to tones <4 kHz. The mechanical properties of the tectorial membrane (TM). The mechanical properties of the TM are investigated using a laser interferometer-based method for tracking the longitudinal propagation of a radially shearing travelling wave in segments of TM isolated from the basal and apical regions of the wild-type cochlea. The properties of these travelling waves (wave propagation velocity and wave amplitude decay) are tracked over a range of stimulus frequencies (1-20 kHz). The viscoelastic properties, shear storage modulus (G') and shear viscosity (η), are estimated over this frequency range and are found to be lower in the apical TM segments compared to the basal TM segments, indicating the apical region of the TM is less stiff than the basal region. These data are compared to data collected from TM segments isolated from the basal cochlear region of three mutant groups, each lacking expression of TM-specific proteins; α-tectorin (TectaY1870C/+), β-tectorin (Tectb-/-) and otoancorin (OtoaEGFP/EGFP), using the same laser interferometer-based method. The viscoelastic properties are estimated for each of the mutants and indicate varying degrees of loss of structural integrity in their respective TM segments. Reflective difference between the wild-types and mutants are also observed and compared.

Introdução: As particularidades da anatomia e a localização topográfica da orelha a tornam uma estrutura única no corpo humano, existindo diversas situações clínicas em que a sua reconstrução (total ou parcial) pode ser necessária. Devido à dificuldade técnica, as complicações pós-operatórias são freqüentes. Objetivos: Realizar análise epidemiológica dos pacientes submetidos à reconstrução de orelha devido a causas congênitas (microtia) e adquiridas (trauma, queimaduras e outras), com avaliação comparativa dos resultados, para definir qual grupo teria menores índices de complicações. Método: Realizada análise retrospectiva de 279 casos de reconstrução de orelha realizados de 1994 a 2004 na Disciplina de Cirurgia Plástica da Faculdade de Medicina da Universidade de São Paulo. Os pacientes foram separados em portadores de deformidades congênitas ou adquiridas e analisados comparativamente. Resultados: O sexo masculino foi mais prevalente tanto entre os pacientes portadores de deformidades congênitas (61,3%) quanto entre aqueles com deformidades adquiridas (68,75%). A média de idade no início dos procedimentos cirúrgicos foi de 14,3 anos nos pacientes com deformidades congênitas e 29,5 nas deformidades adquiridas. Trauma foi a principal causa de deformidade adquirida (55% dos casos adquiridos), seguido pelas queimaduras (29% dos casos adquiridos) e a única deformidade congênita observada no estudo foi a microtia. Em média, os pacientes dos grupos necessitaram de 4,2 cirurgias, mas aqueles com seqüelas de queimaduras foram submetidos a um número significativamente maior de procedimentos (5,9 - p < 0,01). As principais complicações foram a exposição de cartilagem (15,1% do total de casos), sem diferença entre os grupos, e a brida retroauricular (16,5% do total de casos), sendo esta última mais freqüente nos casos de microtia e seqüelas de queimaduras. Conclusões: Os casos de perda traumática mostraram menor índice de complicações quando comparados àqueles submetidos a reconstrução por microtia ou após queimadura. / Introduction: The distinctive anatomic features and topography render the ear unique in the human body. Total or partial reconstruction of the ear may be required in many clinical conditions, but because technical difficulties are common, the rate of postoperative complications increases. Objectives: To analyze the epidemiologic data of patients who underwent surgery for reconstruction of the ear due to congenital conditions (microtia) or acquired deformities (trauma, burns and others), and to compare the results in order to define which group had the lowest rate of complications. Methods: A retrospective analysis was conducted with 279 cases of ear reconstruction performed between 1994 and 2004 by the Discipline of Plastic Surgery of the University of São Paulo Medical School. The patients were initially separated in two groups, according to their condition (congenital or acquired), to compare their data. Results: Male was the prevailing gender in both groups of ear deformities: congenital (61.3%) and acquired conditions (68.7%). The patients with congenital deformities had a mean age of 14.3 years at the beginning of the treatment, whereas the patients with acquired deformities were 29.5 years old, in average. The major causes of acquired deformities were trauma (55% of the cases in this group) and burns (29%). The only cause of congenital deformity observed was microtia. Patients required an average of 4.2 surgical procedures. However, those with sequelae of burn injuries were submitted to a significantly higher number of procedures (5.9 - p < 0.01). Cartilage exposure (15.1% of the total) and postauricular bridles (16.5%) were the major complications observed in this study. The latter was more common among those cases with microtia and sequelae of burns. Conclusions: Patients with traumatic injuries had a better outcome after surgery than those with microtia or burn injuries, because of a lower rate of complications.

Thesis (M. Sc.)--University of Hong Kong, 2006. / Title proper from title frame. Also available in printed format.

Le développement de la cochlée des mammifères est un phénomène complexe qui implique la coordination de nombreux gènes. La compréhension de la physiopathologie des surdités dorigine neurosensorielle ainsi que la mise au point de stratégies visant à restaurer la structure cellulaire de loreille interne ne nous paraît possible que grâce à la compréhension fine des processus qui régulent et sous-tendent son développement. Les connaissances actuelles, nous permettre en effet de constater que de nombreuses molécules qui contrôlent lorganogenèse au cours du développement sont souvent activées ou impliquées dans les phénomènes de régénération tissulaire après un traumatisme y compris à l'échelle de l'oreille interne (Levic et al., 2007). Lors de notre travail, nous avons montré que dans loreille interne, en labsence de Sox10, les cellules dérivées des crêtes neurales, à savoir les mélanocytes cochléaires et les cellules de Schwann du ganglion spiral étaient absentes, soulignant le caractère dépendant de ces cellules au gène Sox10. Au niveau du ganglion spiral, nous avons montré que contrairement aux neurones des ganglions rachidiens (Honore et al., 2003;Sonnenberg-Riethmacher et al., 2001), le développement et la survie embryonnaire des neurones auditifs étaient indépendants des cellules gliales et de Sox10. Par ailleurs, nous avons également montré que Sox10 napparaît pas comme un facteur indispensable à linduction et au développement de la placode otique, mais que son absence conduit à une diminution de la population de cellules progénitrices du canal cochléaire. Cette diminution aboutit à une réduction de la longueur de la cochlée, et suggère que Sox10 joue un rôle primordial dans le déterminisme du pool des progéniteurs de la portion auditive de loreille interne. Cependant, à des stades ultérieurs du développement, la structure parfaitement conservée de lorgane de Corti nous laisse penser que laction de Sox10 est compensée par dautres gènes du groupe SoxE, par exemple Sox9, dont nous avons mis en évidence lexpression dans les cellules de soutien de lorgane de Corti (Cook et al., 2005;Sock et al., 2001;Stolt et al., 2004;Wegner, 1999). Par ailleurs, nous avons montré quau cours du développement de lorgane de Corti, la première cellule identifiable était la cellule pilier interne. Cette cellule échapperait au système dinhibition latérale lié à Notch et pourrait avoir un rôle dans la différenciation des autres cellules de lorgane de Corti. La destruction des cellules ciliées provoque à plus ou moins long terme une dégénérescence rétrograde des neurones du ganglion spiral, un phénomène à lorigine de nombreuses surdités neurosensorielles (Bichler et al., 1983;Koitchev et al., 1982). Afin de mieux comprendre les signaux qui régulent la réponse neuronale suite à un traumatisme au cours de leur régénération, nous avons mis au point un modèle de culture organotypique de neurones déafférentés de rats postnataux. Cest dans ce modèle dexplants de ganglions spiraux en culture que nous avons évalué la mort neuronale lors des processus de déafférentation des neurones auditifs. Il a été démontré que les neurones auditifs survivent en partie grâce aux facteurs trophiques produits par leur cible périphérique, lorgane de Corti (Lefebvre et al., 1992) et que cette dépendance persiste à lâge adulte. Ce modèle de culture permet de conserver larchitecture du ganglion spiral, se rapprochant ainsi de la situation observée in vivo. Laissés seuls, en labsence de facteurs trophiques exogènes, le nombre de neurones auditifs chute drastiquement après 24 heures de culture. Lorgane de Corti, source de neurotrophines tant durant la période développementale quà lâge adulte (Oestreicher et al., 2000;Ylikoski et al., 1993), prévient significativement cette mort neuronale lorsquil reste associé au ganglion spiral à la mise en culture. Dans ce modèle de dégénérescence rétrograde, nous avons étudié lexpression de la périphérine et constaté que cette protéine était réexprimée dans les neurones auditifs de type I après lésion. De plus, létude de lexpression de la périphérine dans le ganglion spiral du rat a permis dobserver quelle était ubiquitaire dans la population neuronale en développement puis réduite seulement aux neurones de type II lors de la période postnatale. La périphérine serait donc une molécule susceptible dintervenir à la fois lors du développement embryonnaire et réactivée lors des phénomènes de lésions tissulaires cochléaires.

Objectives: To evaluate the effects of ear points pressing at ear meridian points on obesity-related parameters( body weight, body fat, body mass index, waist, hip circumferences, and WC/HC ratio) between treatment and control groups, and we also apply the Self-Determination Theory to discuss the relationship between motivation and performance of body weight control. Methods: The study was an cross over open-parallel randomized control trial and the sample consisted of 189 volunteers who were randomly divided into two groups and the baseline characteristics were similar. In the experimental (immediate treatment) group (n=93), ear points pressing at five ear meridian points and lifestyle education were applied, while volunteers in the control (delay treatment) group (n=96) just receive lifestyle education in the first 8 weeks. At baseline, 24th, 32nd and each week of the sixteen weeks study, the outcomes mentioned above were examined in all volunteers, and related SDT questionnaires were checked during the period of 32 weeks study. Results: The result showed a statistically significant drop in BW, BMI, Waist circumference and Hip circumference during the 32 weeks in experimental (immediate treatment) and control (delay treatment) group, and better effect while using ear points pressing in the same group. But, no significant differences were found between the two groups. A SEM analysis showed that autonomous support, relatedness and original autonomy can get better competence and was related to positive consequences in BW control. And it was relative an adequate model to test the self determination theory. Conclusion: Even though the result showed a statistically significant drop in BW, BMI, WC, HC during the 32 weeks treatment in experimental (immediate treatment) and control (delay treatment) groups, and better effect while using ear points pressing in the same group. But, no statistical significance change in BW related parameters were found between the two groups. Further studies are needed to detect the effect of ear points pressing and model fit of SDT application by increasing research time, and sample sizes.

Thesis (M. Communication Pathology)--University of Pretoria, 2003. / Summary in English and Afrikaans. Includes bibliographical references.