Abstract To investigate the turnover of type IV collagen in skeletal muscle in conditions where muscle function is impaired, type IV collagen and proteins regulating its degradation were studied during 1, 3 and 7 days of immobilization, 3- and 10-day glucocorticoid treatment and in neuromuscular diseases. In addition, fibrillar type I and III collagens were studied during immobilization and in neuromuscular diseases. The mRNA levels of type I, III and IV collagens were decreased during immobilization and during 10-day dexamethasone treatment. Gene expression and quantity of (pro)MMP-2 was increased during immobilization but decreased during dexamethasone treatment. The expression of TIMP-2 was decreased both during immobilization and dexamethasone treatment. Decreased gene expression and increased degradation caused decreased concentration of type IV collagen, suggesting net degradation of type IV collagen during immobilization. While the gene expression and degradation were decreased during dexamethasone treatment, the amount of type IV collagen was not changed. Dexamethasone thus seemed to slow down the turnover of type IV collagen. Decreased mRNA levels of collagens and prolyl 4-hydroxylase suggest decreased biosynthesis of collagens during immobilization. The mRNA levels of collagens I, III and IV were increased in polyneuropathy and polymyositis. The concentration and staining intensity of type IV collagen was increased in polyneuropathy, as was also the quantity and staining intensity of (pro)MMP-9. The results suggest accumulation of type IV collagen in the basement membranes of muscle cells and capillaries in polyneuropathy muscles. Lengthened position during immobilization partly prevented the atrophy and changes in collagen metabolism in plantarflexors. Endurance running was effective in preventing muscle atrophy during dexamethasone treatment, but exercise did however fail to prevent the changes observed in type IV collagen synthesis and degradation.

Les maladies neuromusculaires regroupent des pathologies engendrant un dysfonctionnement de l'unité motrice, d'évolution et de gravité hétérogène. Leur point commun est l'apparition d'une diminution de la force musculaire, notamment des muscles respiratoires conditionnant le pronostic vital. La survenue d'une insuffisance respiratoire est en général progressive et insidieuse. Son diagnostic repose sur des examens cliniques et para-cliniques. Pour la plupart de ces pathologies, il n’existe aucun traitement curatif. Seule la ventilation mécanique associée à une prise en charge cardiaque adaptée permet, pour certaines pathologies, une survie prolongée avec une qualité de vie satisfaisante. Son indication au long cours peut se poser de différentes manières : soit au décours d'une décompensation respiratoire aiguë révélatrice de la maladie ou survenant en l'absence de suivi, soit de façon programmée (le cas le plus fréquent) dans le cadre d’un suivi pluridisciplinaire. Les critères d'indication retenus sont l’existence d’au moins un signe clinique évoquant une atteinte respiratoire, associée à une PaCO2 > 45 mmgH ou à une CV < 50% ou à une désaturation nocturne. Toutefois ces indications sont à nuancer en fonction de la pathologie et de la clinique. D’autre part, il existe également très peu d'études ayant pu démontrer l'efficacité de la ventilation sur la survie, ceci est dû à la rareté de ces pathologies et de la durée nécessaire des études. En outre, l'utilisation de la trachéotomie comme technique de ventilation reste discutée. Les objectifs de ce travail sont : dans un premier temps, de décrire l'évolution de la prise en charge respiratoire chez les patients atteints d'une maladie neuromusculaire et d'identifier les facteurs prédictifs de mise sous ventilation invasive. Ensuite d'analyser les facteurs influençant l’observance de la ventilation non invasive et de mesurer l’impact de celle-ci sur la survie des patients atteints d'une dystrophie myotonique de type 1. Enfin, d'analyser l'impact de la ventilation mécanique invasive lorsque la ventilation non invasive est inefficace sur la survie des patients atteints d'une myopathie de Duchenne de Boulogne. / Neuromuscular diseases include pathologies causing a malfunction of a motor unit with an evolution and gravity heterogeneous. Their common point is the appearance of a decrease in muscle strength, especially respiratory muscles conditioned the vital prognosis. Generally, the occurrence of respiratory failure is progressive and insidious. Its diagnosis is based on clinical and para- clinical exams. For all of these diseases, there is no cureOnly mechanical ventilation coupled with a cardiac treatment allows certain conditions for prolonged survival with a satisfactory quality of life. Its long-term indication can be indicated in different ways: either as a result of acute respiratory decompensation (revealing the disease or due at absence of follow-up) or programmed during of multidisciplinary monitoring (the most frequent case). The consensual indication criteria used are the existence of a clinical sign suggestive of respiratory impairment associated with a PaCO2> 45 mmgH or a CV <50% or a nocturnal desaturation. However, these indications must be classified according to the pathology and the clinic. On the other hand, there are also very few studies which have demonstrated the effectiveness of ventilation on survival, this is due to the rarity of these pathologies and to the necessary duration of the studies. In addition, the use of tracheotomy as a ventilation technique remains controversial. The objectives of this work were: in first part, analyzed the evolution of respiratory management in patients with neuromuscular disease and the identification of predictive factors for invasive ventilation. We then analyzed the factors influencing the respect of noninvasive ventilation and the impact of the master on the survival of myotonic mystery patients 1. Finally, we analyzed of the impact of invasive ventilation on the survival of patients with Duchenne de Boulogne myopathie. when noninvasive ventilation was ineffective.

<p>  </p> <p>Disfluencies are a commonly reported speech symptom associated with Parkinson disease (PD), though the cause remains unknown. Studies have consistently reported that people with PD experience more disfluencies, particularly atypical disfluencies compared to healthy controls. One proposed theory, known as the dualistic model of dopamine levels and stuttering, posits that abnormally high or low levels of dopamine may cause an increase in disfluencies. The aim of the current study is to examine how levodopa medication and deep-brain stimulation affect fluency in people with PD. Twenty-seven participants with PD underwent testing before (on and off medicine) and six months after deep-brain stimulator implant surgery (optimally medicated, on and off stimulation). Participants read a passage aloud and provided a 2-minute monologue. Speech samples were transcribed. The number of typical and atypical disfluencies were identified auditorily and using a wide-band spectrogram. After surgery, most participants reduced their levodopa equivalency dose from pre-implant levels. Results demonstrated no significant differences in frequency of disfluencies across time (pre-surgery, post-surgery) or condition (on/off medication/stimulation). Overall, participants produced more typical than atypical disfluencies and more disfluencies in the monologue task than the reading task. Results do not support the dualistic model of dopamine, but instead support a more nuanced and individualized role for dopamine in speech fluency. For example, patterns within individual subjects suggest changes in dopamine may play a role in speech fluency for individual patients with PD. Data support the effect of cognition and language formulation in the production of disfluencies, particularly typical disfluencies.</p>

<p dir="ltr">Papilledema is the swelling of the optic disc resulting from increased cranial pressure. The diagnosis of papilledema is important not only to treat pathologies of the eye, but it also can be an important indicator for underlying brain pathology since the subarachnoid space surrounding the optic nerve is contiguous with the brain. Therefore increased pressure from the brain from pathologies such as hydrocephalus can be transmitted to the posterior eye. To study papilledema, a reproducible post hemorrhagic hydrocephalic rat model was used to study the changes of the retina, optic disc and optic nerve when exposed to high intracranial pressure. Multiple changes were noted in the post hemorrhagic hydrocephalic model including decreased thickness of the ganglion cell complex, decreased retinal thickness in the periphery in females, increased retinal thickness close to the optic nerve in males, increased optic disc width and diameter along with a decrease number of retinal ganglion cells. These findings were similar to findings in human patients with papilledema. Therefore, future studies are indicated using the post hemorrhagic hydrocephalic rat model to further understand the mechanism of papilledema progression and the use of possible therapeutics.</p>

In people with neuromotor deficits of trunk and lower extremities, maintaining and regaining balance is a difficult task. Many undergo rehabilitation to improve their movement capabilities, health, and overall interactions with their environment. Rehabilitation consists of a set of interventions designed to improve the individual’s mobility and independence. These strategies can be passive, active or task-specific and are dependent on the type of injury, how the individual progresses, and the intensity of the activity. Some of the common rehabilitation interventions to strengthen muscles and improve coordination are accomplished either by the manual assistance of a physical therapist, bodyweight suspension systems or through robotic-assisted training. There are several types of rehabilitation robotic systems and robotic control strategies.However, there are few robotic studies that compare their robotic device’s control strategy to common rehabilitation interventions. This dissertation introduces robotic strategies centered around rehabilitation ones and characterizes human motion in response to the robotic forces. Two cable-driven robotic systems are utilized to implement the robotic controllers for different tasks. Further details of the two cable-driven systems are discussed in Chapter 1. The validation and evaluation of these robotic strategies for standing rehabilitation is discussed in Chapter 2. A case study of a robotic training paradigm for individuals with spinal cord injury is presented in Chapter 3. Chapter 4 introduces a method to redistribute individuals’ weight using pelvic lateral forces. Chapter 5 and 6 characterizes how young and older groups respond to external perturbations during their sit-to-stand motion. This dissertation presents robotic strategies that can be implemented as rehabilitation interventions. It also presents how individuals’ biomechanics and muscle responses may change depending on the force control paradigm.These robotic strategies can be utilized by training individuals to improve their reactive and active balance control and thus reduce their risk of falling.

Pseudomonas aeruginosa (PA) is a gram-negative bacillus well known for colonizing human respiratory airways and causing opportunistic infections. Children with neuromuscular disease (NMD) including cerebral palsy (CP) and severe upper airway obstruction who get infected with PA, their chances of experiencing a severe illness, being admitted to a pediatric intensive care unit, and extended or repeated hospital stays increase dramatically. These patients often need a surgical procedure called tracheostomy which act as a channel for microbes to enter lower respiratory tract and increase infections, despite its well documented impact as an opportunistic pathogen comprehensive investigation into the diversity of PA in such vulnerable populations is limited. To fill this gap in knowledge we perform whole genome sequencing (WGS) and phenotypic analysis of 40 PA isolates from the respiratory tract of this susceptible population with and without tracheotomies. Pangenome analysis showed highly variable genome content with 16,212 total genes of which 2326 are core genes. MLST revealed diverse sequence types (STs) among the studied population with 21 known and 10 new STs. Genotypic analysis revealed moderate variations in the antimicrobial resistance determinants and virulence factors among all isolates. In total 8 serogroups were identified, with serogroups O6 and O11 accounting for 70% of all the isolates. Genotypic diversity was observed in overall population however comparative analysis among tracheostomized and non-tracheostomized patient groups showed significant similarity which aligns with the phenotypic analysis revealing significant similarity with minor differences in biofilm formation, motility, hemolysis production, and pigment production. Last, we explored putative healthcare transmission and identified three potential transmission events. These findings provide insight into how WGS along with phenotypic analysis can help us better understand population dynamics, epidemiology, virulence profile and antibiotic resistance profile of PA contributing to respiratory infections which has valuable therapeutic implications for epidemiology and disease management.

OBJETIVO: Avaliar a responsividade da escala de avaliação funcional para pacientes com distrofia muscular de Duchenne (FES-DMD-D4), sentar e levantar do solo, no período de um ano. MÉTODO: Estudo observacional, longitudinal e retrospectivo. Foi estudada, utilizando o software FES-DMDDATA, uma amostra com 25 pacientes na atividade sentar no solo e 28 pacientes para a atividade levantar do solo. As avaliações ocorreram a cada três meses no período de um ano. Para análise estatística da capacidade de resposta foram utilizados índices de tamanho de efeito, como, effect size (ES) e Standardized Response Mean (SRM). RESULTADOS: A responsividade da atividade de sentar no solo foi considerada baixa a moderada em intervalos de três meses (ES de 0.28 a 0.54 e SRM de 0.38 a 0.71), moderada a alta em intervalos de seis meses (ES de 0.69 a 1.07 e SRM de 0.86 a 1.19), alta em intervalos de nove meses (ES de 1.3 a 1.17 e SRM de 1.26 a 1.55) e doze meses (ES de 1.9 e SRM de 1.72). Na atividade levantar do solo, a responsividade variou em baixa, moderada e alta em intervalos de três meses (ES de 0.21 a 0.33 e SRM de 0.45 a 0.83), baixa a alta em intervalos de seis meses (ES de 0.46 a 0.59 e SRM de 0.73 a 0.97), moderada a alta em intervalos de nove meses (ES de 0.76 a 0.88 e SRM de 1.03 a 1.22) e alta em doze meses (ES de 1.14 e SRM de 1.25). CONCLUSÃO: Para detectar alterações clinicamente significativas e consistentes nas atividades funcionais sentar e levantar do solo recomendamos a utilização da FES-DMD-D4 em intervalos a partir de seis meses, pois foi neste período de tempo que a capacidade de resposta variou de moderada a alta / OBJECTIVE: To evaluate responsiveness of functional scale for Duchenne muscular dystrophy - sitting and standing from the ground (FES-DMD - D4) in three months evaluation intervals in a one year follow up. METHODS: Observational, longitudinal and retrospective study. It was studied, using FESDMD- DATA software, films of sample of 25 patients performing sitting on the activity of soil and 28 patients performing the activity of from the ground. The evaluations were performed every three months within one year. The analysis for statistical responsiveness of the instrument we use effect size (ES) and Standardized Response Mean (SRM) tests. RESULTS: The responsiveness of the activity of sitting on the ground was considered low to moderate every three months (ES 0.28 to 0.54 and 0.38 to 0.71 SRM), moderate to high in intervals of six months (ES 0.69 the 1.07 and the 1.19 0.86 SRM), High at intervals of nine months (1,3 ES of the 1.17 and the 1.55 1.26 SRM), and twelve months (ES SRM 1.9 and 1.72). In raising from the ground activity, the responsiveness varied at low, moderate and high in intervals of three months (ES 0.21 to 0.33 and 0.45 to 0.83 SRM), low to high in intervals of six months (ES 0.46 to 0.59 and 0.73 to 0.97 SRM), moderate to high at intervals of nine months (ES 0.76 to 0.88 and 1.03 to 1.22 SRM ) and high in twelve months (ES 1.14 and SRM 1.25). CONCLUSION: To detect clinically significant changes and consistent in functional activities of sitting and standing from the ground we recommend using the FES-DMD-D4 at intervals from six months because it was at this time that the responsiveness was moderate to high

A Distrofia Muscular dos cães Golden Retriever (GRMD) é uma miopatia degenerativa causada pela ausência da proteína distrofina na superfície da membrana da célula muscular. É geneticamente homóloga à distrofia muscular de Duchenne (DMD) que acomete os humanos, portanto, estes cães são considerados modelos experimentais para estudos que buscam tratamentos para pacientes vitimados pela doença. A maior causa de morte na DMD é a insuficiência respiratória ou infecção pulmonar que ocorre em cerca de 75% dos casos. Os músculos respiratórios são sempre afetados e, juntamente com as cifoescolioses e deformidades torácicas, diminuem marcadamente a função respiratória. O padrão respiratório é de respiração rápida e superficial, com volume corrente diminuído, e está associado com a presença de alterações nas pressões parciais dos gases sanguíneos. A complacência pulmonar diminui, resultante de microatelectasias. Os músculos intercostais internos e abdominais, que auxiliam a expiração, também são acometidos, reduzindo a efetividade da tosse e dificultando a eliminação de secreções. Na fase préterminal da doença, nota-se uma redução na pressão parcial de oxigênio arterial associada com a retenção do gás carbônico, podendo observar-se um quadro de cianose, papiloedema e falhas respiratórias. A ventilação nãoinvasiva com pressão positiva (VNIPP) consiste em um método de assistência ventilatória em que uma pressão positiva é aplicada à via aérea do paciente através de máscaras ou outras interfaces sem a utilização da intubação traqueal. Este estudo teve como escopo avaliar possibilidades de terapia respiratória em cães afetados pela GRMD submetidos à VNIPP, identificar os fatores associados ao sucesso ou ao insucesso da VNIPP; caracterizar os padrões de resposta a VNIPP e complicações associadas. Os conhecimentos específicos das modalidades ventilatórias a serem usadas, assim como dos parâmetros ventilatórios a serem empregados na terapia foram fundamentais para a realização deste trabalho. A monitorização das concentrações dos gases sangüíneos, e da saturação de oxigênio, são essenciais para que possam ser estabelecidos parâmetros ventilatórios seguros e confortáveis aos animais e, assim, viabilizar a terapia. No experimento proposto foram estudados cães Golden Retriever, afetados pela distrofia muscular, submetidos à ventilação mecânica não-invasiva com pressão positiva. Para tanto foi consideradas na avaliação respiratória, a gasometria arterial e a oximetria. Apesar do desconforto respiratório e sinais de hipoventilação, clinicamente observado nos animais, não houve confirmação de Insuficiência Respiratória. Portanto concluímos que o suporte ventilatório não-invasivo (Bipap) falhou em demonstrar melhora nas funções respiratórias dos cães da raça Golden Retriever afetados pela distrofia muscular quando usado sob a forma profilática. / The Muscular Dystrophy Golden Retriever dogs (GRMD) is a degenerative myopathy caused by the absence of dystrophin protein on the surface of the membrane of muscle cells. It is genetically counterpart to Duchenne muscular dystrophy (DMD) which affects humans, so these dogs are considered experimental models for studies that seek treatments for patients affected by the disease. The biggest cause of death in DMD is respiratory failure or lung infection that occurs in about 75% of cases. The respiratory muscles are always affected and, together with the cifoescolioses and chest deformities, the markedly reduced respiratory function. The breathing pattern is rapid and superficial, with tidal volume decreased, and is associated with the presence of changes in the partial pressure of blood gases. The lung compliance decreases, resulting from microatelectasias. The intercostal muscles and internal abdominal, which help the expiration, are also affected, reducing the effectiveness of cough and hampering the removal of secretions. In the preterminal disease, there is a reduction in the partial pressure of oxygen blood associated with the retention of carbon dioxide, with a framework of cyanosis, papilloedema and respiratory failure. The non-invasive ventilation with positive pressure (VNIPP) is a method of ventilatory assistance at a positive pressure that is applied to air the patient through masks or other interfaces without the use of intubation. This study was to objective evaluate the potential of respiratory therapy in dogs affected by GRMD submitted to VNIPP, identify the factors associated with the success or failure of VNIPP; characterize the patterns of response to VNIPP and associated complications. The specific knowledge of how to use ventilation and the ventilatory parameters to be used in therapy were fundamental for this work. The monitoring of blood concentrations of the gases, and the saturation of oxygen, are essential in order to be established ventilatory parameters safe and comfortable for animals and thereby facilitate the therapy. In the proposed experiment studied dog Golden Retriever, affected by muscular dystrophy, submitted to non-invasive mechanical ventilation with positive pressure. To do so was considered in assessing breathing, blood gases and oximetry. Despite the signs of respiratory discomfort and hypoventilation, clinically observed in animals, there was no confirmation of respiratory failure. So we find that the non-invasive ventilatory support (Bipap) failed to show improvement in respiratory functions of the breed dogs Golden Retriever affected by muscular dystrophy when used in the form prophylactic.

Thesis (doctoral)--Rijksuniversiteit te Utrecht, 1985. / "Stellingen": leaves inserted. Vita. Includes bibliographical references.

A Distrofia Muscular dos cães Golden Retriever (GRMD) é uma miopatia degenerativa causada pela ausência da proteína distrofina na superfície da membrana da célula muscular. É geneticamente homóloga à distrofia muscular de Duchenne (DMD) que acomete os humanos, portanto, estes cães são considerados modelos experimentais para estudos que buscam tratamentos para pacientes vitimados pela doença. A maior causa de morte na DMD é a insuficiência respiratória ou infecção pulmonar que ocorre em cerca de 75% dos casos. Os músculos respiratórios são sempre afetados e, juntamente com as cifoescolioses e deformidades torácicas, diminuem marcadamente a função respiratória. O padrão respiratório é de respiração rápida e superficial, com volume corrente diminuído, e está associado com a presença de alterações nas pressões parciais dos gases sanguíneos. A complacência pulmonar diminui, resultante de microatelectasias. Os músculos intercostais internos e abdominais, que auxiliam a expiração, também são acometidos, reduzindo a efetividade da tosse e dificultando a eliminação de secreções. Na fase préterminal da doença, nota-se uma redução na pressão parcial de oxigênio arterial associada com a retenção do gás carbônico, podendo observar-se um quadro de cianose, papiloedema e falhas respiratórias. A ventilação nãoinvasiva com pressão positiva (VNIPP) consiste em um método de assistência ventilatória em que uma pressão positiva é aplicada à via aérea do paciente através de máscaras ou outras interfaces sem a utilização da intubação traqueal. Este estudo teve como escopo avaliar possibilidades de terapia respiratória em cães afetados pela GRMD submetidos à VNIPP, identificar os fatores associados ao sucesso ou ao insucesso da VNIPP; caracterizar os padrões de resposta a VNIPP e complicações associadas. Os conhecimentos específicos das modalidades ventilatórias a serem usadas, assim como dos parâmetros ventilatórios a serem empregados na terapia foram fundamentais para a realização deste trabalho. A monitorização das concentrações dos gases sangüíneos, e da saturação de oxigênio, são essenciais para que possam ser estabelecidos parâmetros ventilatórios seguros e confortáveis aos animais e, assim, viabilizar a terapia. No experimento proposto foram estudados cães Golden Retriever, afetados pela distrofia muscular, submetidos à ventilação mecânica não-invasiva com pressão positiva. Para tanto foi consideradas na avaliação respiratória, a gasometria arterial e a oximetria. Apesar do desconforto respiratório e sinais de hipoventilação, clinicamente observado nos animais, não houve confirmação de Insuficiência Respiratória. Portanto concluímos que o suporte ventilatório não-invasivo (Bipap) falhou em demonstrar melhora nas funções respiratórias dos cães da raça Golden Retriever afetados pela distrofia muscular quando usado sob a forma profilática. / The Muscular Dystrophy Golden Retriever dogs (GRMD) is a degenerative myopathy caused by the absence of dystrophin protein on the surface of the membrane of muscle cells. It is genetically counterpart to Duchenne muscular dystrophy (DMD) which affects humans, so these dogs are considered experimental models for studies that seek treatments for patients affected by the disease. The biggest cause of death in DMD is respiratory failure or lung infection that occurs in about 75% of cases. The respiratory muscles are always affected and, together with the cifoescolioses and chest deformities, the markedly reduced respiratory function. The breathing pattern is rapid and superficial, with tidal volume decreased, and is associated with the presence of changes in the partial pressure of blood gases. The lung compliance decreases, resulting from microatelectasias. The intercostal muscles and internal abdominal, which help the expiration, are also affected, reducing the effectiveness of cough and hampering the removal of secretions. In the preterminal disease, there is a reduction in the partial pressure of oxygen blood associated with the retention of carbon dioxide, with a framework of cyanosis, papilloedema and respiratory failure. The non-invasive ventilation with positive pressure (VNIPP) is a method of ventilatory assistance at a positive pressure that is applied to air the patient through masks or other interfaces without the use of intubation. This study was to objective evaluate the potential of respiratory therapy in dogs affected by GRMD submitted to VNIPP, identify the factors associated with the success or failure of VNIPP; characterize the patterns of response to VNIPP and associated complications. The specific knowledge of how to use ventilation and the ventilatory parameters to be used in therapy were fundamental for this work. The monitoring of blood concentrations of the gases, and the saturation of oxygen, are essential in order to be established ventilatory parameters safe and comfortable for animals and thereby facilitate the therapy. In the proposed experiment studied dog Golden Retriever, affected by muscular dystrophy, submitted to non-invasive mechanical ventilation with positive pressure. To do so was considered in assessing breathing, blood gases and oximetry. Despite the signs of respiratory discomfort and hypoventilation, clinically observed in animals, there was no confirmation of respiratory failure. So we find that the non-invasive ventilatory support (Bipap) failed to show improvement in respiratory functions of the breed dogs Golden Retriever affected by muscular dystrophy when used in the form prophylactic.