Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-04-03T23:16:39Z No. of bitstreams: 1 RafaelFranzonBenz_DISSERT.pdf: 10736405 bytes, checksum: ca4d2c8372c3631326a624f5404a7a3e (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-04-11T23:43:23Z (GMT) No. of bitstreams: 1 RafaelFranzonBenz_DISSERT.pdf: 10736405 bytes, checksum: ca4d2c8372c3631326a624f5404a7a3e (MD5) / Made available in DSpace on 2017-04-11T23:43:23Z (GMT). No. of bitstreams: 1 RafaelFranzonBenz_DISSERT.pdf: 10736405 bytes, checksum: ca4d2c8372c3631326a624f5404a7a3e (MD5) Previous issue date: 2016-09-20 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior (CAPES) / Salicilato, o principal composto de diversos medicamentos, como a Aspirina, ? conhecido por causar zumbido se consumido em altas doses ou de forma cr?nica (para o tratamento de osteoporose, por exemplo). Zumbido ? o ouvir ou a percep??o de um som quando nenhum est?mulo f?sico est? presente. O zumbido n?o ? uma doen?a em si, mas um sintoma presente em diversas doen?as, e est? associado ? ansiedade e outros dist?rbios de humor. Apesar de estar diretamente ligado ao sistema auditivo, o zumbido n?o ? gerado a partir de uma regi?o espec?fica do c?rebro. Al?m disso, alguns estudos mostraram que o salicilato afeta v?rias regi?es cerebrais al?m do sistema auditivo, como o estriado, amigdala e o hipocampo. Estudos iniciais atribu?ram uma fun??o unit?ria ao hipocampo: processamento de memorias declarativas. Entretanto, estudos mais recentes mostraram que o hipocampo n?o s? possui outras fun??es, como processamento emocional, mas tamb?m pode ser dividido em ventral e dorsal, e a parte ventral desempenha um papel essencial no processamento emocional. A oscila??o mais estudada do c?rebro ? o r?tmo teta, e ela pode ser encontrada em todo o hipocampo. Dois tipos de teta podem ser distinguidos: o teta tipo 1, que ? resistente a atropina, possui uma frequ?ncia mais alta (7 a 10 Hz) e est? relacionado com comportamentos de padr?o motor; e o teta tipo 2, que ? sens?vel a atropina, possui uma frequ?ncia mais baixa (4 to 7 Hz) e ocorre durante anestesia, estado de imobilidade vigilante e situa??es de alta ansiedade. O presente estudo investigou os efeitos eletrofisiol?gicos do salicilato no hipocampo ventral de camundongos em estado de comportamento. Atrav?s da inje??o de salicilato foi gerado teta tipo 2 no hipocampo ventral. Tamb?m foi encontrado que o salicilato leva a comportamentos de ansiedade. / Salicylate, the main compound of many medications as Aspirin, is known to cause tinnitus if consumed in high doses or in a chronic way (for the treatment of osteoporosis, for example). Tinnitus is the hearing or perception of a sound when no physical stimulus is present. Tinnitus is not a disease itself, but a symptom present in some diseases, and is associated with anxiety and other mood disorders. Despite being directly related with auditory system, tinnitus is not generated from one specific region of the brain. Additionally, some studies showed that salicylate affects various brain regions besides the auditory system, as the striatum, amygdala and the hippocampus. Early studies have ascribed a unitary function to the hippocampus: declarative memory processing. However, more recent studies showed that the hippocampus not only has other functions, as emotional processing, but also can be divided into ventral and dorsal, and the ventral part plays an essential role in emotional processing. The most studied oscillation of the brain is the theta rhythm, and it can be found in the entire hippocampus. Two types of theta can be distinguished: the type 1, that is atropine resistant, has a higher frequency (7 to 10 Hz) and is related with motor pattern behaviors; and the type 2 theta, that is atropine sensitive, has a lower frequency (4 to 7 Hz) and occur during anesthesia, alert immobility and high arousal situations. The present study investigated the electrophysiological effects of salicylate in the ventral hippocampus of behaving mice. Through salicylate injection we generated type 2 theta in the ventral hippocampus. We also found that salicylate led to anxietylike behavior

Temporomandibular joint disorders (TMD) are defined as a collective term embracing clinical problems that involve the masticatory musculature, the temporomandibular joint and associate stuctures. These disorders are primarily characterized by pain, joint sounds, and irregular or limited function. Other common complaints are headache, jaw-ache, ear-ache, facial pain or tinnitus [Chyba! Nenalezen zdroj odkazů.,Chyba! Nenalezen zdroj odkazů.,Chyba! Nenalezen zdroj odkazů.,Chyba! Nenalezen zdroj odkazů.]. Carlsson [Chyba! Nenalezen zdroj odkazů.] reported in a review of the epidemiologic literature that the need for treatment of TMD is with a range 5% and 13% among adults. At present, the majority of authors propose a multifactor aetiology for TMD, considering that acute trauma, degenerative articular disorders, psychological factors and functional mandibular overload are involved [Chyba! Nenalezen zdroj odkazů.,Chyba! Nenalezen zdroj odkazů.,Chyba! Nenalezen zdroj odkazů.,Chyba! Nenalezen zdroj odkazů.]. Although the diagnosis of TMD is based mainly on the detailed patient's history and clinical examination, in some cases it is necessary to complete these routine procedures through imaging methods that can help to find out the cause of a patient's pain [Chyba! Nenalezen zdroj odkazů.,Chyba! Nenalezen...

This folio is comprised of nine electroacoustic compositions for multichannel presentation. They are linked together by their shared concern with micro- and macro-structural relationships between sonic layers, similar use of space (particularly Simon Emmerson’s ‘soundfield frames’), and exploitation of process departure or interruption. Chronic Pulsatile Tinnitus uses saxophone and percussion recordings to address the above compositional concerns. BCN comprises three works, Barbecued Spanish Builder, Cerveza Beer and Siren, which explore interactions between field recordings and those of bass guitar and drums. Mr President uses vocal recordings of phrases taken from Barack Obama’s election victory speeches to examine sequence verticality, while Nothing But Sky, BCN Metro, Digital Fun Pen and Ahlan Wa Sahlan offer approaches to field recordings within the contexts of the issues common throughout the folio. It is imperative that these pieces are listened to in their specified multichannel formats, as opposed to on a stereo system. This is to ensure the listener’s identification of sonic layers, which is not satisfactorily achievable over a headphone or two-speaker setup.

Decreases in overall well-being and daily functioning result from unpleasant and uncomfortable symptoms associated with physical health and mental health disorders. Neurofeedback training, rooted in the theory of operant conditioning, presents the possibility of increasing brain wave regulation, decreasing symptoms experienced from abnormal brain wave activity, and increasing overall well-being and daily functioning. The efficacy of neurofeedback for physical and mental health outcomes is unclear, contributing to confusion about the treatment and any potential benefits. In order to assess the efficacy of neurofeedback in the alleviation of physical health and mental health symptoms, a systematic review and meta-analysis of neurofeedback using a random effects model to generate the effect sizes was conducted on 21 studies with 22 comparisons that used neurofeedback to treat patients. The results showed that neurofeedback can be effective for physical and mental health outcomes, including for autism with an effect size of 0.29, tinnitus with an effect size of 0.77, schizophrenia with an effect size of 0.76, depression with an effect size of 0.28, insomnia with an effect size of 0.52, obesity with an effect size of 0.40, intellectual disability with an effect size of 0.73, and pain with an effect size of 0.30. Well-being and daily functioning for those with physical and mental health disorders can be improved. These findings have implications for clinical practice to help patients in treatment for physical and mental health problems, and also for social change by providing evidence for alternative health care options.

In 1993, the Neurofibromatosis type 2 gene product, merlin or schwannomin was identified by positional cloning and was mapped to chromosome 22q 12 (Rouleau et al., 1993; Trofatter et al., 1993). Individuals with mutations in this gene fail to produce normal merlin and develop the neural disorder, Neurofibromatosis type 2. The disease is characterized by growth of bilateral vestibular schwannomas with associated symptoms of tinnitus, hearing loss, balance dysfunction, meningiomas and other tumors of the nervous system (Ruggieri and Huson, 1999). To date, merlin's molecular mechanism of function as a tumor suppressor protein in cells is not known. In this thesis, we examined merlin's interaction with the epidermal growth factor receptor, erbB2, a receptor known to cause Schwann cell growth. Immunoprecipitation and indirect in vitro protein binding assay using total cell lysate from rat Schwann cells showed that merlin associates with erbB2. This association was further tested in a direct in vitro protein-protein binding assay, which showed that merlin binds directly to erbB2. This data places merlin in the erbB2 signaling pathway.

The chemotherapeutic agents cisplatin and carboplatin are widely-used and highly-effective against a variety of malignancies. Unfortunately, these medications may sometimes cause ototoxicity. Cisplatin and carboplatin ototoxicity manifests as tinnitus and/or a permanent, bilateral and progressive hearing loss, leading to devastating consequences on the lives of cancer survivors. Earlier detection of ototoxicity during treatment allows clinicians to modify treatment plans, whenever possible, to prevent its progression. Audiological tests currently used for monitoring for platinum-induced ototoxicity are presented, as well as their advantages and disadvantages. A new paediatric evaluation method is also introduced, which uses patient-reported measures and could complement audiological testing in obtaining a more comprehensive assessment of ototoxicity.Different criteria are used in the literature in order to define ototoxicity, which makes comparison among studies difficult. A critical review was undertaken on commonly-used ototoxicity grading criteria. A retrospective chart review was also performed at the Montreal Children's Hospital, characterizing the incidence of long-term ototoxicity at our institution. Work done as part of this thesis led to the design of two novel studies: a prospective cohort study evaluating the pharmacogenomics of platinum-induced ototoxicity and a randomized controlled trial evaluating the efficacy of dexamethasone as a potential otoprotective agent. Comprehensive assessment of ototoxicity, including sensitive audiological tests, appropriate ototoxicity grading criteria, and self-reported outcomes, is urgently needed, in the clinic, in order to guide interventions, and in research, in order to gain greater understanding of the incidence and burden of platinum-induced ototoxicity. / Les anticancéreux cisplatine et carboplatine sont souvent utilisés et sont très efficaces contre une grande variété de cancers. Malheureusement, ces médicaments peuvent parfois causer l'ototoxicité. L'ototoxicité du cisplatine et du carboplatine consiste en acouphènes et/ou une perte auditive qui est souvent permanente, bilatérale et progressive, conduisant à des conséquences dévastatrices chez les survivants du cancer.Une détection plus précoce de l'ototoxicité permet aux cliniciens de modifier leurs plans de traitement, si possible, pour empêcher sa progression. Les examens audiologiques utilisés présentement pour la surveillance de l'ototoxicité induite par le platinum sont présentés, ainsi que leurs avantages et leurs inconvénients. Également, une nouvelle méthode d'évaluation pédiatrique est présentée. Celle-ci utilise des mesures auto déclarées, pouvant supplémenter les tests audiologiques pour obtenir une évaluation plus complète de l'ototoxicité. Différents critères sont utilisés pour définir l'ototoxicité, ce qui rend la comparaison entre études difficile. Une revue critique des critères les plus utilisés dans le classement de l'ototoxicité induite par le platinum a été menée. De plus, une étude rétrospective a été menée à l'Hôpital de Montréal pour Enfants pour caractériser l'incidence de l'ototoxicité au long-terme dans notre institution. Le travail effectué dans le cadre de cette thèse a conduit à la création de deux nouvelles études: une étude de cohorte prospective visant à évaluer la pharmacogénomique de l'ototoxicité induite par le platinum et un essai clinique évaluant l'efficacité de la dexamethasone tant qu'agent otoprotectif. Une évaluation globale de l'ototoxicité, incluant des tests audiologiques sensibles, des critères de classement appropriés, et des mesures auto déclarées, sont nécessaires, dans la clinique, afin de guider les interventions, et dans la recherche, afin d'acquérir une meilleure connaissance de l'incidence et les conséquences de l'ototoxicité induite par le platinum.

Introduction. Les ultrasons (US) basse fréquence appliqués sur la peau pour en augmenter laperméabilité (sonophorèse) peuvent promouvoir le passage transcutané de molécules in vitroet in vivo chez l’animal. L’objectif de ce travail a été d’appliquer la sonophorèse à l’homme invivo.Méthodes. Trois essais cliniques randomisés ont été menés chez le volontaire sain : l’essai (1)évaluant la tolérance des US à différentes intensités versus placebo ; l’essai (2) évaluant lapénétration transcutanée de l’histamine après sonophorèse ; l’essai (3) comparant l’effetvasoconstricteur d’un dermocorticoïde sans et après sonophorèse. Les US étaient délivrés enmode pulsé, avec une sonde de 36 kHz, durant 5 minutes, à des intensités de 1,57 à 3,50W/cm2.Résultats. Dans l’essai (1), aucune toxicité (douleur > 40/100 ou nécrose) n’a été observéechez les 34 sujets inclus. Les effets secondaires étaient un érythème, et des acouphènesrégressifs dès l’arrêt des US. Dans l’essai (2), l’histamine a induit une papule chez 9/10 sujets,uniquement sur les zones préalablement traitées par US. Dans l’essai (3), sur les 15 sujets, lavasoconstriction induite par le dermocorticoïde était significativement plus importante sur leszones traitées par US, surtout avec une occlusion longue (2h).Conclusions. Ces essais démontrent qu’avec des intensités ultrasonores bien tolérées chezl’homme, la sonophorèse est efficace pour faire pénétrer l’histamine et améliorer l’efficacitédes dermocorticoïdes. / Introduction. Low-frequency ultrasound (US) applied on skin, called sonophoresis, havebeen investigated to enhance the transdermal transport of various drugs in vitro and in vivo inanimals. We aimed to investigate low-frequency sonophoresis in vivo in humans.Methods. Three randomized clinical trials have been conducted in healthy subjects: trial (1)aimed to assess skin toxicity of sonophoresis at different intensity levels compared to placebo;trial (2) aimed to investigate the transdermal penetration of histamine with sonophoresis; trial(3) aimed to investigate the clinical efficiency of sonophoresis in enhancing transdermalpenetration of topical steroids in human skin. US were applied in pulsed mode for 5 minutes,with a 36 kHz device. US intensities ranged from 1.57 to 3.50 W/cm2.Results. In trial (1), no toxicity, defined as a pain score > 40/100 or necrosis, was reported.The most frequent adverse events were erythema, and tinnitus, which ceased ondiscontinuation of US. In trial (2), arm zones without US showed no papules, whereas 9/10subjects receiving US showed papules. In trial (3), including 15 subjects, vasoconstrictionwas significantly higher with the topical steroid applied after US than without US, especiallyin the zone with 2-h occlusion.Conclusions. These clinical trials provide favourable exploratory results regarding toleranceof low-frequency sonophoresis on human skin in vivo. They confirm that sonophoresisenhances transdermal penetration of histamine and increases the efficiency of topical steroids.

Abstract Age-related hearing impairment is the most common type of hearing impairment among adults. Adult-onset hearing impairment is one of the leading causes of disease burden worldwide and it is associated with social isolation and depression. As the proportion of older people is increasing in Western countries, the socioeconomic importance of adult hearing impairment will increase notably. The aim of the present contribution was to study the epidemiological aspects of hearing and related factors among older adults. The prevalence of hearing impairment, defined either by audiometry or by a self-report, and the differences between these two were analyzed. Tinnitus and hyperacusis were also studied. Furthermore, the prevalence of ear diseases, otological risk factors, and noise exposure and their association with hearing thresholds were analyzed. In addition, audiogram configurations and certain subject-related factors and their relation to hearing were assessed. The subjects were randomly sampled from the population register and they responded to an extensive questionnaire. Otological status was examined and pure tone audiometry was conducted. Data on 850 subjects aged 54–66 years were analyzed. Hearing impairment was found to be a highly common condition with a prevalence of 26.7% when defined by better ear and 42.2% when defined by worse ear. Men had worse hearing than women. High-frequency sloping audiogram configurations were common. Self-reported hearing difficulty and measured hearing impairment seem to be associated at high frequencies. At least one ear disease or otological risk factor for hearing impairment was found among 18.4% of the subjects and noise exposure among 46%, more often by men. Interestingly, noise exposure did not seem to associate with hearing levels among subjects screened for ear disease or otological risk factors. The results of the present study suggest that hearing impairment is a highly common condition among older adults and this should be taken into account when future hearing healthcare is planned. Furthermore, it seems that most of the subjects reporting hearing difficulty had no measured hearing impairment according to the criteria applied for eligibility for hearing aid fitting in Finland. Based on the results of the present study, the criteria for hearing impairment entitling persons for hearing aid fitting should be reconsidered. / Tiivistelmä Ikäkuulo on yleisin aikuisten kuulovian aiheuttaja, ja aikuisiän kuulovika on merkittävä terveydellinen haittatekijä. Kehittyneiden maiden ikäjakauman painottuessa vanhempiin ikäluokkiin aikuisten kuulovioista tulee merkittävä sosioekonominen rasite yhteiskunnille. Tutkimuksen tavoitteena oli selvittää aikuisten kuulovikojen epidemiologiaa ja kuulovikoihin liittyviä tekijöitä. Myös kuulovian vallitsevuus määriteltynä kuulokäyrän tai tutkittavan oman ilmoituksen perusteella selvitettiin. Samoin tutkittiin muita kuulemiseen liittyviä ongelmia, kuten tinnitusta ja ääniyliherkkyyttä. Edelleen arvioitiin erilaisten kuuloon vaikuttavien tekijöiden, kuten korvasairauksien, muiden kuulovian riskitekijöiden ja melulle altistumisen, vallitsevuutta väestössä sekä niiden assosiaatiota kuulemiseen. Näiden lisäksi tutkittiin kuulokäyrien muotoja ja niiden yhteyttä tutkittavan ilmoittamaan kuulo-ongelmaan. Tutkittavat valittiin satunnaisesti väestörekisteristä. He täyttivät laajan kyselylomakkeen, heidän korvansa tutkittiin lääkärin vastaanotolla ja lisäksi heille tehtiin kuulotutkimukset. Tutkimukseen osallistui 850 55–66-vuotiasta henkilöä. Tutkimus osoitti, että kuulovika on tässä ikäryhmässä hyvin yleinen löydös ja miehillä yleisempi kuin naisilla. Tutkittavan ilmoittama kuulovika ennusti mitattujen kuulokynnysten heikkenemistä korkeilla taajuuksilla (4–8 kHz). Samoin korkeille taajuuksille laskeva kuulokäyrän muoto oli yleisin. Erilaisia kuulovian riskitekijöitä raportoi 18.4 % tutkittavista. Tämän lisäksi 46 % kertoi merkittävästä altistumisesta melulle, miehet naisia useammin. Yllättäen melualtistumisella ei näyttänyt olevan yhteyttä kuulokynnyksiin siinä ryhmässä tutkittavia, joilla ei ollut korvaperäisiä riskitekijöitä kuulovialle. Tutkimustulokset osoittavat, että kuulovika on hyvin yleinen löydös tämän ikäisillä aikuisilla. Vanhenevat ikäluokat ovat merkittävä haaste kuulonhuollolle, ja tämä olisi otettava huomioon päätettäessä kuulonhuollon rahoituksesta. Useat niistä aikuisista, jotka kokivat kuulo-ongelmia, eivät kuulokäyrälöydöksensä mukaan täyttäneet Suomessa käytössä olevia kriteereitä kuulokojesovitukselle. Tämän tutkimuksen perusteella näyttääkin siltä, että kuntoutustarvetta arvioitaessa kuulovian kriteereitä tulisi kansallisesti tarkistaa ottamalla huomioon myös huonomman korvan kuulokynnykset sekä kuulon alenema korkeilla taajuuksilla.

碩士 / 中臺科技大學 / 護理系碩士班 / 103 / Objective: We conducted this study to investigate the associated factors and effect of the prevalence of head trauma patients with vestibular dysfunction (i.e., presenting dizziness, vertigo, tinnitus, nausea, vomiting, hearing impairment, visual impairment, neck pain, otorrhea or rhinorrhea) and unilateral neglect. Methods: A prospective cohort study that included 34 mild head trauma patients was conducted in a medical center. The visual analog scale checklist was used to identify vestibular dysfunction symptoms. Rivermead behavioral inattention conventional subtest (BITC) was used to identify unilateral neglect. Modified Barthel Index (MBI) and return-to-work were used to investigate outcomes. All patients were evaluated four times, as follows: within 3 days, and at 7, 14, and 28 days after the injury. Results: Prevalence within 3 days after injury was reported, and the symptoms were as follows: dizziness (69.7%), imbalance (56%), nausea (51.5%), neck pain (39.4%), vertigo (33.3%), vomiting (27.3%), tinnitus (21.2%), visual impairment (21.2%), hearing loss (18.2%), otorrhea (9.1%), and rhinorrhea (9.1%). Unilateral neglect may be 0%. Over time, the prevalence of all symptoms decreased. However, dizziness (30.8%), neck pain (19.2%), hearing loss (15.4%), vertigo (11.5%), and imbalance (5.3%) persisted until 28 days after the injury. Chi-square analysis results identified gender, age, occupation, history of hypertension or diabetes, diagnosis, and mechanism of injury as significantly associated factors of mild head trauma patients with vestibular dysfunction symptoms. Dizziness, nausea, and vomiting presented significant correlation. Vertigo and neck pain also showed significant correlation. A generalized estimating equation (GEE) model of linear analysis identified day 7, day 14, day 28, and imbalance as significant independent predictors of activities of daily living. A GEE model of ordinal analysis identified day 14, day 28, vertigo, and imbalance as significant independent predictors of return-to-work parameter. Conclusion: Results showed the prevalence of head trauma patients with vestibular dysfunction and unilateral neglect and the relationship between vestibular dysfunction symptoms and associated factors and impact. Future research should include an extended tracking time to assess the recovery process of the patients and prognosis of the situation. The prevalence of mild head trauma patients with unilateral neglect was possibly at 0%. Future research should include a different location, and researchers should choose the severity of cases to establish the prevalence of unilateral neglect and to check the association of unilateral neglect and vestibular dysfunction with vestibular symptoms. In addition, future research may include the development of vestibular rehabilitation to treat vestibular dysfunction symptoms.

[Truncated abstract] The present study investigated whether any of the characteristics of the compound action potential (CAP) waveform or the spectrum of the neural noise (SNN) recorded from the cochlea, could be used to examine abnormal spike generation in the type I primary afferent neurones, possibly due to pathologies leading to abnormal hearing such as tinnitus or tone decay. It was initially hypothesised that the CAP waveform and SNN contained components produced by the local action currents generated at the peripheral ends of the type I primary afferent neurones, and that changes in these local action currents occurred due to changes in the membrane potential of these neurones. It was further hypothesised that the lateral olivo-cochlear system (LOCS) efferent neurones regulate the membrane potential of the primary afferent dendrites to maintain normal action potential generation, where instability in the membrane potential might lead to abnormal primary afferent firing, and possibly one form of tinnitus. We had hoped that the activity of the LOCS efferent neurones could be observed through secondary changes in the CAP waveform and SNN, resulting from changes in the membrane potential of the primary afferent neurones. The origins of the neural activity generating the CAP waveform and SNN peaks, and the effects of the LOCS on the CAP and SNN were experimentally investigated in guinea pigs using lesions in the auditory system, transient ischemia and asphyxia, focal and systemic temperature changes, and pharmacological manipulations of different regions along the auditory pathway. ... Therefore, the CAP and SNN are altered by changes in the propagation of the action potential along the primary afferent neurones, by changes in the morphology of the tissues surrounding the cochlear nerve, and by changes in the time course of the action currents. If the CAP waveform is not altered, the amplitude of the 1kHz speak in the spontaneous SNN can be used as an objective measure of the spontaneous firing rate of the cochlear neurones. However, because the SNN contains a complex mixture of neural activity from all cochlear neurones, and the amplitude of the spontaneous SNN is variable, it would be difficult to use the spontaneous SNN alone as a differential diagnostic test of cochlear nerve pathologies. To record extratympanic electrocochleography (ET ECochG) from humans, a custom-designed, inexpensive, low-noise, optically isolated biological amplifier was built. Furthermore, a custom-designed extratympanic active electrode and ear canal indifferent electrode were designed, which increased the signal-to-noise ratio of the ECochG recording by a factor of 2, decreasing the overall recording time by 75%. The human and guinea pig CAP waveforms recorded in the present study appeared similar, suggesting that the origins of the human and guinea pig CAP waveforms were the same, and that experimental manipulations of the guinea pig CAP waveform can be used to diagnose the cause of abnormal human ECochG waveforms in cases of cochlear nerve pathologies.