Thesis (Ph.D.) - University of Queensland, 2006. / Includes bibliographical references.

A candidate protein from the venom gland of parasitoid wasp, Habrobracon hebetor, predicted to be responsible for the paralysis of lepidopteran caterpillars, was produced in baculovirus and bacterial expression systems. The function of both recombinant protein variants was confirmed by in vivo tests in Galleria mellonella larvae.

Orientador: Jorge Rizzato Paschoal / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-17T07:18:50Z (GMT). No. of bitstreams: 1 Tessitore_Adriana_D.pdf: 12454982 bytes, checksum: 981e89f52f8f84566e6227b2354f5d34 (MD5) Previous issue date: 2010 / Resumo: A Paralisia Facial (PF) tem sido progressivamente, objeto de estudo dos fonoaudiólogos que trabalham com motricidade e reabilitação orofacial. A terapia visa a reabilitação das funções orais - sucção, deglutição, mastigação, fala e expressividade facial. Na paralisia facial periférica (PFP), a diminuição dos movimentos faciais e seqüela estética resultantes podem ter repercussões emocionais importantes, além do déficit funcional. A reabilitação orofacial favorece a recuperação de movimentos e a adequação e/ou a adaptação das funções orofaciais e de expressividade, mediante atuação no tônus muscular. Entretanto, quantificar os resultados terapêuticos na tentativa de aferição do tônus muscular é tarefa difícil. O objetivo geral desta tese foi avaliar a mudança do ACL a partir de um protocolo específico aplicado em pacientes com paralisia facial periférica. Os objetivos específicos foram estudar a variação do ACL, entre o início e o final do tratamento de reabilitação e avalia a confiabilidade da variação desse ângulo como elemento quantificador da eficácia terapêutica. Foram estudados 20 pacientes com PFP (grau IV), encaminhados para reabilitação orofacial do Ambulatório de Paralisia Facial do Hospital de Clínicas da Unicamp, num ensaio longitudinal prospectivo. A constatação da evolução funcional favorável baseou-se na melhora do tônus muscular com a reabilitação. A variação do tônus foi aferida mediante modificação no ACL. O estudo foi feito nas imagens da documentação fotográfica pré (após quinze dias de instalação da paralisia facial) e pós-tratamento de um ano. Para comprovação da eficácia da reabilitação, comparou-se o ACL pré e pós-reabilitação. O grupo estudado foi comparado a um grupo controle composto de nove sujeitos com paralisia facial grau IV, não submetidos a reabilitação orofacial. Os dados foram analisados estatisticamente pelo teste emparelhado das amostras (T-Student). A confiabilidade da medida do ACL foi aferida através do teste de coeficiente de correlação de Pearson. A média da idade dos pacientes estudados foi 47,65 anos, com desvio padrão (DP) 13,50. A média do ACL pré-reabilitação foi 101,70 e, pós-reabilitação, diminuiu para 93,80 (DP = 4,3). O teste estatístico revelou diferença estatisticamente significativa (p< 0, 001). A análise de confiabilidade demonstrou que existe uma alta correlação entre as medidas de ângulos para os três juízes, sendo estatisticamente significante (p<0,001). O teste estatístico T-Student aplicado para comparação entre o grupo estudado e o grupo controle revelou que a média do ACL no grupo controle foi 100.9, não tem diferença com a média das medidas iniciais do grupo estudado (p=0,723). Em contrapartida apresentou significância estatística na comparação dos valores pós tratamento (p=0.001). Concluímos que o ACL é um marcador antropométrico que nos permite avaliar objetivamente a modificação do tônus da musculatura facial na PFP. Esse protocolo de reabilitação permitiu incremento marcante do tônus muscular, com melhora significativa da simetria do rosto no repouso facial / Abstract: Facial Paralysis has progressively been object of study by speech therapists Who work with motor skills and orofacial rehabilitation. The objective of the therapy is to rehabilitate oral functions - suction, swallowing, mastication, speech and facial expressiveness. The impairment of facial movements and aesthetical sequelae as a consequence of peripheral facial paralysis (PFP) have important emotional repercussions besides functional deficit. Orofacial rehabilitation improve recuvery of movements and adjustment and/or adaptation of the orofacial functions by acting on muscular tonus. However quantifying the therapeutic results in an attempt to valuate muscular tonus is a hard task. The general objective of this thesis was to assess the change on the LCA from a specific protocol applied to patients with peripheral facial paralysis. The specific objectives were to study the LCA variation between the beginning and end of rehabilitation treatment and to assess the reliability of this angle's variation as a quantifying element of therapeutic efficacy. Twenty patients with PFP (HB IV) were studied. They were refered for orofacial rehabilitation from the Facial Paralysis Ambulatory of the Hospital das Clínicas da UNICAMP. This is a prospective longitudinal study. The study was based on the photographically documentation images before (after fifteen days of facial paralysis onset) and one year after treatment. The value of LCA was compared before and one year after treatment. The patients were compared to a control group of nine pacients with PFP - HB IV Who were did not undergo orofacial rehabilitation. The data were analyzed statistically using a T-student test. The reliability of the measurement of the LCA was verifiedusing a Pearson correlation coefficient test. The average age of the patients was 47.65 years, with a standard deviation (SD) of 13.50. The LCA average before rehabilitation was of 101.7o and, after rehabilitation, it 93.8o (SD = 4.3). The statistical test showed a statistically significant difference (P < 0.001). The reliability analysis showed that there is a high correlation among the three angle measurements for the three judges, therefore being statistically significant (p<0.001). The statistical T-test applied to compare the group which was studied with the control groups has revealed that the average LCA in the control group was 100.9, and there is no difference with the average of the initial measurements in the group which was studied (p = 0.723). On the other hand, there is a statistical significance in the comparison of post-treatment values (p=0.001). We concluded that the LCA is an anthropometric marker which seems to allow objectively assessment the muscular tonus modification on facial muscles in patients with PFP. Our protocol of rehabilitation improved the muscular tonus, and facial functions / Doutorado / Ciencias Biomedicas / Doutor em Ciências Médicas

OBJETIVO: Avaliar o padrão eletromiográfico em hemiface normal e hemiface afetada nos casos de paralisia facial, em seus dois extremos de evolução; musculatura sem aporte neural e musculatura após a regeneração neural aberrante. MATERIAL E MÉTODO: Foram selecionados indivíduos com paralisia facial periférica unilateral de qualquer etiologia, Idade entre 18 e 69 anos, de ambos os sexos, sem histórico de paralisias faciais prévias ou congênita e sem lesões faciais que interfirissem no contato dos eletrodos. Trinta e quatro indivíduos preencheram os critérios. O grupo controle foi constituído de 20 indivíduos voluntários sem história de paralisia facial, traumas de face ou anomalias craniofaciais. A avaliação da atividade elétrica dos músculos da face foi realizada por meio de registro eletromiográfico, usando equipamento MIOTEC com software MIOTOOL 400, de 04 canais, filtro Passa Baixa, com eletrodos de superfície descartáveis do tipo: Ag-AgCI mini med Kendal. Para a avaliação eletromiográfica foram solicitados os seguintes movimentos: elevação da testa, fechamento de olhos, protrusão labial e retração labial. Além disso, foram registradas as atividades eletromiográficas em outros canais correspondentes aos outros grupos musculares durante a atividade primária a fim de identificar a presença de sincinesias, sendo a atividade dos lábios durante fechamento forçado dos olhos, a atividade dos olhos durante protrusão labial e a atividade dos olhos durante retração labial. A análise estatística foi realizada utilizando-se o software Statistical Package for Social Sciences (SPSS) for Mac versão 16.0 (SPSS Inc, Chicago, IL). Foi considerada como atividade eletromiográfica de cada segmento das hemifaces avaliadas (testa, olho e lábio) durante cada movimento (franzimento a testa, fechamento ocular, protrusão labial e retração labial) o valor médio obtido durante os 8 segundos de registro (em V). O índice da atividade eletromiográfica (IEMG) foi calculado através da divisão da atividade eletromiográfica do lado acometido pela atividade do lado normal para o grupo em estudo e através da divisão da atividade eletromiográfica do lado esquerdo pelo lado direito no grupo controle. RESULTADOS: Houve diferença estatisticamente significante entre os grupos em todos os movimentos analisados. Nas sincinesias no lábio durante o fechamento ocular a totalidade de indivíduos será identificada corretamente (com 100% de verdadeiros positivo e 0% de falsos negativos) utilizando-se o valor de IEMG de 1,62 como ponto de corte. Para a identificação da sincinesia no olho durante a protrusão labial o valor do IEMG no ponto de corte que apresenta ao maior sensibilidade (93,3%) e especificidade (95,9%) é 1,79. CONCLUSÃO: O padrão da atividade eletromiográfica mostrou ser estatisticamente diferente entre os grupos em fase flácida e fase de seqüelas; a relação entre as duas hemifaces é rebaixada nos pacientes em fase flácida e pode tanto mostrar valores normais, elevados ou rebaixados em indivíduos em fase de seqüelas; o IEMG mostrou ser de alta sensibilidade e especificidade na identificação das sincinesias / OBJECTIVE: To evaluate the electromyographic profile in the normal and the affected faces in cases of facial paralysis, in its two extremes of evolution; musculature without neural input and musculature after regeneration neural aberrant. METHODS: Subjects with peripheral facial paralysis unilateral of any etiology, with age ranging from 18 to 69 years, of both sexes, without a history of prior facial paralysis or without congenital facial lesions that would interfere with the contact of electrodes selected. Thirty-four subjects met the criteria. The control group was composed of 20 volunteers without history of facial paralysis, trauma or face craniofacial anomalies. The electromyographic assessment of the facial muscle was performed by means of a MIOTEC equipment with software MIOTOOL 400, 04 channels, low-pass filter, with disposable surface electrodes type: Ag-AgCI mini med Kendal. For the evaluation electromyographic were requested the following movements: lifting the forehead, closure of eyes, protrusion labial and labial retraction. In addition, Eletromyographic activities were recorded in other channels corresponding to the other groups during the primary activity in order to identify the presence of synkinesis, the activity of the lips during strong eye closure, the activity of the eyes during protrusion labial and the activity of eyes during labial retraction. The statistical analysis was performed usingsoftware Statistical Package for Social Sciences (SPSS) version is Mac 16.0 (SPSS Inc, Chicago, IL). The mean value of the RMS during 8 seconds of register (in V) was considered as the electromyographic activity of each segment of hemifaces evaluated (forehead, eye and lip) during each movement. The electromyographic index IEMG was obtained from the division of electromyographic activity (on) of the left side by the right side in the control group. RESULTS: There was a statistically significant difference between the groups in all movements analyzed. The lip synkinesiss during the eye closure in all patients must be correctly identified (with 100% true positive and 0% false negative) using (a) the IEMG value of 1.62 as cutoff point. In order to detect synkinesis in the eye or eye synkinesis during lip protrusion the IEMG at the cutoff point is 1,79 with (a) 93.3% of sensivity and 95,9% of specificity . CONCLUSION: The pattern of electromyographic activity showed to be statistically different between the flaccid and the sequelae groups; the relationship between the two hemifaces is below normal levels in patients at the flaccid stage whereas in patients at the stage of sequelae it can either show normal values, above or below normal levels; the IEMG showed to be of high sensitivity and specificity in the identification of synkinesis

Magister Scientiae (Physiotherapy) - MSc(Physio) / Bell’s palsy (BP), a fairly common disorder predominantly prevalent in the adult age group, affects nerves and muscles in the face causing paralysis or dropping of one side of the face. Clients with Bell’s palsy face many challenges, including psychological, physical and emotional. A long recovery period and/or delayed complete healing could lead to a negative effect on many aspects of an individual's life. How society perceives the person could negatively influence the client’s self-confidence. The management of Bell’s palsy depends on the individual case and may include medication, physiotherapy and as a last option, surgery. The aim of the study was to investigate the management of Bell’s palsy at primary health care level in the Cape Metropolitan District of the Western Cape. The study specific objectives was to investigate the management or treatment protocol of clients with Bell’s palsy, to determine the tendency for referral for physiotherapy, to determine whether an association exists between the type of management or treatment received and the recovery of clients with Bell’s palsy and to explore the impact Bell's Palsy has on the clients. The over-arching design of the study was the sequential explanatory mixed methods design where qualitative data was used to assist in explaining and interpreting the findings of a primarily quantitative study. Stratified random sampling was done proportionately to ensure equal representation. A self-administered questionnaire, comprising of four sections, was used to collect quantitative data that was analysed using SPSS version 21. Descriptive statistics was employed to summarise the data on the socio-demographic information of the clients. Inferential statistics was used to determine the distributions of cases in the various groups. Significant differences tested for using the Chisquare test and effect size through Cramer’s V tests. A semi-structured interview guide was developed based on the results of the analysis of the quantitative data. Focus group discussions were employed to a sub-sample of the clients with Bell’s palsy. Permission an ethical clearance will be obtained from Senate Higher Degrees Committee at the University of the Western Cape (UWC), the Western Cape Department of Health and the facility managers of the participating CHCs.

Hyperkalemic periodic paralysis, HyperKPP, is an inherited progressive disorder of the muscles caused by mutations in the voltage gated sodium channel (NaV1.4). The objectives of this thesis were to develop a technique for measurement symptoms in vivo using electromyography (EMG) and to determine the mechanism by which Ca2+ alleviates HyperKPP symptoms, since this is unknown. Increasing extracellular [Ca2+] ([Ca2+]e) from 1.3 to 4 mM did not result in any increases in45Ca2+ influx suggesting no increase in intracellular [Ca2+] ([Ca2+]i) acting on an intracellular signaling pathway or on an ion channel such as the Ca2+sensitive K+ channels. HyperKPP muscles have larger TTX-sensitive22Na+ influx than wild type muscles because of the defective NaV1.4 channels. When [Ca2+] was increased from 1.3 to 4 mM, the abnormal 22Na+ influx was completely abolished. Thus, one mechanism by which Ca2+alleviates HyperKPP symptoms is by reducing the abnormal Na+ influx caused by the mutation in the NaV1.4 channel.

Hyperkalemic periodic paralysis (HEPP) is an inherited, autosomal disorder characterized by myotonia and periodic paralysis in skeletal muscle. The hallmark of the disease is a severe sensitivity to the K+-induced force depression, the cause of the paralysis. Previous studies have provided evidence that the sensitivity to the K+-induced force depression can be alleviated when the Cl- conductance (GCl) is lowered. However, those studies were carried out at non-physiological temperatures (25°-30°C) and few stimulation frequencies. The overarching goal of this study was to examine whether manipulating GCl pharmacologically was a viable target for treating HEPP. This work sought to document the interactive effect of K+ and Cl- on force development in mouse skeletal muscle at 37°C, over a wide range of stimulation frequencies. Secondly, experiments were undertaken to determine if a reduction in GCl could protect against the severe K+ sensitivity in HEPP. The results show that in wildtype muscle, a reduction in GCl improved force generation at high [K+]e at stimulation frequencies that naturally occur in vivo for mouse EDL and soleus. While the effect in wildtype muscles was proof of principle that a reduction in GCl may be a potential approach to treat HEPP patients, the effects of reduced GCl at high [K+]e was quite variable in HEPP muscles. In a few cases, lowering GCl did improve force generation at high [K+]e. However, in most cases the decrease in GCl exacerbated the force depression at high [K+]e, suggesting that more studies will be necessary to understand the variability in the Cl- effect to conclude whether a decrease in GCl is a viable approach to treat HEPP patients.

Objectives. Acute flaccid paralysis (AFP) has recently emerged as a major central nervous system complication associated with West Nile virus (WNV) infection. The spectrum of clinical presentations of AFP in WNV infection and its sequelae have not been well-studied. Methods. We describe three patients with AFP due to WNV infection and review the clinical presentations of 56 patients with this complication derived from published studies. Results. Patients with AFP and WNV presented with a spectrum of illness ranging from single extremity paralysis to quadriparalysis with cranial nerve involvement. Patients commonly developed respiratory failure (54%) and bladder dysfunction (22%). While fever was nearly universal (92%), signs of meningismus were less common (17%). Cerebrospinal fluid (CSF) analysis generally revealed a modest pleocytosis, and imaging studies were not diagnositic. Persistent neurologic impairment occurred in all survivors; overall mortality rate was high (22%) and was associated with both the extent of paralysis and advanced age. Conclusion. AFP in the setting of WNV is associated with significant mortality and long-term morbidity.

Intracortical brain-computer interfaces (BCIs) provide the means to do something extraordinary: restore movement to patients with paralysis or amputated limbs. Realizing this potential requires the development of decode algorithms capable of accurately translating measurements of neural activity, in real time, into appropriate time-varying commands for an external device (e.g. prosthetic limb). This problem is fundamentally interdisciplinary, drawing on tools and insights from engineering, neuroscience, statistics, and computer science, among others. Decode algorithms that have been favored historically tend to be computationally efficient, but perform suboptimally, likely because their assumptions fail to fully and accurately capture the complexity in neural population responses. Recent work harnessing the power of contemporary machine learning methods has raised the performance bar, yet these methods can be computationally demanding and it is unclear what properties of neural and/or behavioral data they exploit. In this dissertation, we characterize properties of motor-cortex population geometry and let these properties dictate decoder design, resulting in methods that perform very well, yet retain the benefits of simpler methods. We use this approach to develop a closed-loop navigation BCI, and to design a highly accurate, general, and interpretable decoder. The properties described in this dissertation have implications for any BCI. By designing decoders to explicitly respect (and leverage) these properties, we can construct powerful yet practical BCIs that better meet the needs of patients.

Respiratory complications in dogs with cervical myelopathies can be life-threatening and are attributed to spinal cord morbidity secondary to cervical disease or decompressive surgery causing diaphragmatic dysfunction. However, diaphragmatic dysfunction in these dogs has not been described. Thirtyive client-owned dogs were recruited with 14 control and 21 test dogs. Dogs were evaluated for the presence of diaphragmatic dysfunction using radiography, M-mode ultrasonography, and fluoroscopy (gold standard) before and after an anesthetic or surgical event. Diaphragmatic dysfunction was observed more frequently in dogs with cervical disease prior to surgery (8/21 dogs, 38.1%) compared to control dogs (3/14 dogs, 21.4%) but was not statistically significant (odds ratio, 2.3; 95% confidence interval, 0.48-10.6; P = 0.30). Further, the frequency of diaphragmatic dysfunction did not significantly increase following surgical decompression in either group. Thus, dogs in this study with cervical disease and undergoing decompressive surgery were not considered to have a higher probability of diaphragmatic dysfunction compared to the control dogs.