Dissertations / Theses on the topic 'Syndrome MARCH'

Les désordres du système nerveux central sont des pathologies qui peuvent se développer dès le neurodéveloppement du fœtus jusqu'à la mort de l'individu. La capacité d'évaluer la façon dont les cellules humaines reprogrammées (iPSCs) peuvent se développer et s'autoorganiser en trois dimensions en se transformant en organoïdes cérébraux a le potentiel de révolutionner notre approche à la fois de la recherche scientifique fondamentale et du traitement des maladies neurologiques humaines qui s'avèrent désormais comme la première cause de morbidité mondiale Nous avons exploré ce potentiel pour modéliser deux de ces pathologies : le syndrome MARCH, un syndrome neurodéveloppemental caractérisé par une hydranencéphalie, et la maladie d'Alzheimer, pathologie neurodégénérative. Nous décrivons la mise en place de ces modèles pathologiques ainsi que leurs avantages pour reproduire les symptômes physio-pathologiques associés, tout en soulignant les limites inhérentes à l'utilisation de cellules souches pluripotentes pour modéliser ces pathologies complexes
Central nervous system disorders are pathologies that can develop from fetal neurodevelopment through to individual death. The ability to assess how reprogrammed human cells (iPSCs) can develop and self-organize in three dimensions into brain organoids has the potential to revolutionize our approach to both basic scientific research and the treatment of human neurological diseases, now emerging as the leading cause of overall disease burden in the world. We have explored this potential to model two of these pathologies: MARCH syndrome, a neurodevelopmental syndrome characterized by hydranencephaly, and Alzheimer's disease, a neurodegenerative pathology. We describe the set-up of these pathological models and their advantages in reproducing the associated physio- pathological symptoms, while highlighting the inherent limitations of using pluripotent stem cells to model these complex pathologies

Les néoplasies myéloprolifératives (NMP), non BCR-ABL1, regroupent principalement la polyglobulie de Vaquez (PV), la thrombocytémie essentielle (TE) et la myélofibrose primitive (MFP).Ces pathologies partagent, dans des proportions variables, une mutation commune, la mutation JAK2 V617F. La protéine JAK2 mutée a une activité tyrosine kinase constitutive, impliquée dans le développement de la maladie. Cette mutation, seule, n’explique pas l’hétérogénéité phénotypique au sein des NMP. L’avènement des techniques de séquençage haut débit a permis de mieux appréhender la physiopathologie. Notre travail avait pour objectif l’identification de mutations additionnelles au sein de deux cohortes suivies au long cours en lien avec un risque d’aggravation de la maladie, l’une regroupant des patients en phase chronique (TE et PV JAK2 V617F), la seconde regroupant des patients avec une myélofibrose traitée par interféron. A l’instar d’autres travaux récents, nous avons montré que le nombre de mutations et la présence de mutations additionnelles sont associés à l’évolution de la maladie, voire à la réponse au traitement.Parmi les mutations identifiées, certaines pourraient influencer l’épissage. La deuxième partie de ce travail a donc consisté à étudier l’épissage alternatif en fonction des mutations présentes, et en particulier la mutation JAK2 (V617F) et de manière globale dans les TE. Un saut de l’exon 14 de JAK2 a été décrit chez des patients NMP présentant, ou non, la mutation JAK2 V617F. Cette mutation du gène JAK2 est prédite pour altérer un site de fixation de la protéine SRSF6 régulatrice de l’épissage. Nous observons que le saut de l’exon 14 est un événement peu fréquent chez les patients, modulé en partie par l’expression des protéines SR. L’analyse transcriptomique montre une grande hétérogénéité entre les patients en termes d’expression et d’épissage, ce qui ne nous a pas permis de mettre en évidence de profil caractéristique. Ces résultats soulignent l’importance de l’identification des mutations additionnelles au diagnostic et au cours du suivi.Nous avons pu, en outre, identifier quelques transcrits alternatifs associés à la présence de ces mutations. Le rôle fonctionnel de ces variants reste à définir
Polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) are a group of Philadelphia-negative myeloproliferative neoplasm (MPN). These diseases share a common mutation, JAK2 V617F, in varying proportions. The mutated JAK2 protein has a constitutive tyrosine kinase activity, implicated in the physiopathology of MPN. This mutation alone does not explain the phenotypic heterogeneity within MPN.High throughput sequencing techniques helped understanding the physiopathology. This work aimed to identify additional mutations in two patient cohorts related to the aggravation risk of the disease. The first one consisted of patients in chronic phase (JAK2 V617F ET and PV), the second consisted in patients with myelofibrosis treated with interferon. Like other studies, we have shown that the number of mutations and the presence of additional mutations are associated with disease progression or with response to treatment. Some identified mutations could influence splicing. The second part of this work aimed at studying the putative impact of the JAK2 V617F mutation, on alternative splicing (AS).We also analyzed global AS profiles in ET. JAK2 exon 14 skipping has been described in NMP patients with or without the JAK2 V617F mutation.This mutation was predicted to alter the binding site of the SRSF6 splice-regulating protein. We observed that exon 14 skipping was an uncommon event in patients, in part related to SR protein expression. In addition, our transcriptomic-wide analysis showed a great heterogeneity between the patients with respect to both gene expression and splicing. This prevented us from identifying any characteristic profile. These results underscore the importance of identifying additional mutations at diagnosis and during follow-up. We have also been able to uncover some alternative transcripts associated with the presence of these mutations.The functional role of these variants remains to be defined

Orientador: Alan Stewart Hazell
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
Made available in DSpace on 2018-08-25T22:16:15Z (GMT). No. of bitstreams: 1 FaimFerreira_Samantha_M.pdf: 1383020 bytes, checksum: 557a29a1393de153dfad4f2c4815defa (MD5) Previous issue date: 2014
Resumo: A neurotoxicidade por manganês (Manganismo) leva a uma disfunção neurológica caracterizada pelo desenvolvimento de ataxia, hipocinesia, rigidez e tremores. Evidências sugerem que os astrócitos desempenham um papel importante na disfunção cerebral nesta desordem, pois acumulam manganês e sequestram o metal na mitocôndria, o que inibe a oxidação fosforilativa. A exposição aguda ao manganês leva ao acúmulo focal do metal e perda neuronal no cerebelo. No entanto, a relação entre esta deposição localizada de manganês e as manifestações neurológicas não são claras. Neste estudo, foram caracterizados os efeitos do manganês na marcha e no equilíbrio após um tratamento subagudo em ratos adultos da linhagem Sprague-Dawley (CEMIB ¿ UNICAMP). Os animais foram divididos em três grupos: Controle; tratado com Mn e tratado com Mn + NAC (N - acetilcisteína), um anti-oxidante. Os ratos do grupo Mn receberam cloreto de manganês (II) (50 mg/kg de peso corporal, i.p.) diariamente durante 4 dias, enquanto os ratos do grupo Mn + NAC foram co-tratados diariamente com o cloreto de manganês (II) e NAC (163 mg/kg, i.p.). Na análise da marcha o grupo tratado com Mn demonstrou alteração na marcha, vizualizados pela diminuição da área da impressão plantar (comprimento x largura), do comprimento da passada e da base de suporte. Apesar das alterações observadas nesses parâmetros, os animais não apresentaram mudanças na pressão exercida pela pata durante a marcha. O grupo co-tratado com NAC não demonstrou essas alterações, apresentando-se semelhante ao controle. Nos estudos de imonohistoquímica, imunofluorescência, histoquímica e Western blotting o grupo tratado com Mn apresentou morte neuronal, aumento da reatividade astrocítica na camada granular, desarranjo na camada das células de Purkinje e aumento na expressão do transportador de glutamato GLT-1a. Estes resultados corroboram com as importantes alterações na função motora de animais tratados com Mn. O co-tratamento com o antioxidante NAC foi capaz de impedir parcialmente esses danos, exercendo uma ação protetora na área do cerebelo e na função motora. Em conclusão, demonstramos que a intoxicação por manganês gera alterações morfo-funcionais no cerebelo, as quais podem ser principalmente revertidos pelo uso do antioxidante NAC
Abstract: Manganese (Mn) neurotoxicity (Manganism) leads to a neurological disorder characterized by the development of ataxia, hypokinesia, rigidity and tremors. Evidence suggests that astrocytes play an important role in brain dysfunction in this disorder because accumulate manganese and sequester metal in the mitochondria, where it inhibits oxidative phosphorylation. Acute exposure to manganese leads to focal accumulation of the metal and neuronal loss in the cerebellum. However, the relationship between this localized deposition of manganese and neurological manifestations are unclear. In this study, we characterized the effects of manganese in gait and balance after a subacute treatment in Sprague - Dawley rats (CEMIB - UNICAMP). The animals were divided into three groups: control, treated with Mn and Mn + treated with NAC (N - acetylcysteine). The rats from manganese group were administered with manganese (II) chloride (50 mg / kg body weight , ip) daily for 4 days, whereas rats of the group Mn + NAC daily were co- treated with manganese chloride (II) and NAC (163 mg / kg , ip). In Catwalk test group treated with manganese showed changes in gait and balance, leading to a reduction of the area of the paw (length and width), the stride length and the base of support. Despite the changes observed in these parameters, the animals showed no changes in pressure exerted by the leg during gait. The group co-treated with NAC showed no such changes, keeping similar to the control group. In studies of immunohistochemistry, immunofluorescence, western blotting and histochemistry group treated with showed neuronal death, an increase in signal astrocytic reactivity in the granular layer, a derangement in the Purkinje cell layer and an increase in the expression of glutamate transporter GLT - 1a. These results suggest significant changes in motor function in animals treated with Mn. The co - treatment with the antioxidant NAC was able to partially prevent this damage, exerting a protective action in the area of the cerebellum and motor function. In conclusion, we demonstrated that manganese poisoning produces morphological and functional changes in the cerebellum, which can principally be reversed by the use of the antioxidant NAC
Mestrado
Fisiopatologia Médica
Mestra em Ciências

Orientador: Sergio Rocha Piedade
Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas
Made available in DSpace on 2018-08-11T10:38:39Z (GMT). No. of bitstreams: 1 Reis_JuliaGuimaraes_M.pdf: 2248238 bytes, checksum: 945fbd990c61ac6b327c4c18556ee2e0 (MD5) Previous issue date: 2008
Resumo: Das anormalidades que envolvem a articulação do joelho, a disfunção do aparelho extensor é um dos problemas mais freqüentemente encontrados na prática ortopédica. Para abranger toda a complexidade de investigação da locomoção necessita-se de informações qualitativa e quantitativa da cinética (momentos e forças) e cinemática (ângulos). O objetivo do estudo foi identificar e analisar as alterações biomecânicas dos indivíduos com instabilidade patelofemoral objetiva durante a marcha. A amostra foi composta de 10 indivíduos com instabilidade patelofemoral (grupoI), média de idade de 25,6 (±7,6) anos, média de altura de 1,63 (±0,06) m e média de peso de 63,3 (±13,52) kg; e, 14 indivíduos sem história de lesão músculo-esquelética (grupo controle ou grupo II), com média de idade de 24,14 (±2,71) anos, média de altura de 1,63 (±0,05) m e média de peso de 59,43 (±10,02) kg. Ambos os grupos foram submetidos a uma análise cinemática e cinética, onde os mesmos caminharam em velocidade livre, numa passarela de 10 m de comprimento. As imagens foram filmadas por seis câmeras do sistema Qualysis, que capturou os sinais de marcadores reflexíveis posicionados no membro inferior das voluntárias. Paralelamente, aplicou-se no grupo I uma avaliação clínica do grau de funcionalidade dos joelhos lesados, onde a pontuação os classificou como funcionalmente ruins; e, um exame físico, onde ambos os membros apresentaram-se estatisticamente semelhantes. A análise dos dados cinemáticos e cinéticos foi realizada pelo programa Qgait que mostrou menor flexão de joelho, nas fases de apoio e balanço (p<0,0001); menor momento extensor de joelho, no apoio (p<0,0001); e, maior força de reação do solo (p=0,4094), no grupo de pacientes em relação ao controle. Foram avaliados também parâmetros espaços-temporais como velocidade (p=0,0053), cadência (p=0,0376) e comprimento da passada (p=0,0021), onde o grupo I apresentou valores inferiores comparado ao grupo controle. Já no período de apoio (p=0,1186), o grupo I superou o grupo II. Estes resultados sugerem que o grupo I utilizou várias estratégias durante a marcha, na tentativa de reduzir a dor e a pressão na articulação patelofemoral. Entretanto, a força de reação do solo não foi reduzida, o que poderá resultar em danos a outras articulações, em longo prazo, devido a cargas repetitivas na articulação tíbiofemoral
Abstract: Abnormalities involving knee joint, the dysfunction of the extensor apparatus, it is one of the problems most often found in orthopaedic practice. To cover the full complexity of of locomotion research, it is necessary qualitative and quantitative information of kinetic (moments and forces) and kinematics (angles). The objective of the study was to identify and analyse the biomechanical changes of individuals with objective patellofemoral instability during gait. The sample was composed of 10 individuals with patellofemoral instability (group I), mean age of 25.6 (± 7.6) years, the average height of 1.63 (± 0.06) m and mean weight of 63.3 (± 13 , 52) kg; and 14 individuals with no history of musculo-skeletal injury (control group or group II), with an average age of 24.14 (± 2.71) years, the average height of 1.63 (± 0.05) m and mean weight of 59.43 (± 10.02) kg. Both groups were subjected to an analysis kinematics and kinetics, where they walked naturally on a 10 m walkway. The images were filmed by six cameras Qualysis system, which captured the signs of reflective markers placed on the lower limb of the volunteers. Paralely, was applied in the group I a functional clinical assessment of the degree functionality in the knee injured that classified it as bad functionally; and, physical examination, where both limbs showed up statistically similar. The analysis of kinematic and kinetic data was performed by the Qgait program that showed less of knee flexion, in the stance and balance phase (p <0.0001), less knee extensor moment, in support (p <0.0001); and, greatest ground reaction force (p = 0.4094) in the group of patients with respect to control. They were also assessed spatiotemporal parameters such as speed (p = 0.0053), cadence (p = 0.0376) and stride length (p = 0.0021), where the group I showed lower values compared to control group. Already in the support period (p = 0.1186), group I overcame the group II. These results suggest that the group I used several strategies during gait, in an attempt to reduce the pain and pressure in patellofemoral joint. However, the ground reaction force was not reduced, which could result in damage to other joints, in the long term, due to repetitive loads in tibiofemoral joint
Mestrado
Pesquisa Experimental
Mestre em Cirurgia

Les contraintes physiologiques cérébrales rendent le cerveau humain vulnérable à l'hypoxie, qu’elle soit environnementale (haute altitude) ou en lien avec une pathologie hypoxémiante. Parmi ces pathologies, et en raison de sa forte prévalence dans la population générale, le syndrome d'apnées obstructives du sommeil (SAOS) est un modèle physiopathologique reconnu des effets délétères de l'hypoxie sur le cerveau. Les épisodes cycliques d'apnées et d'hypopnées survenant au cours du sommeil qui caractérisent le SAOS entraînent une hypoxie intermittente, une fragmentation du sommeil et des fluctuations de la pression intra-thoracique, tous trois facteurs déclenchant des mécanismes intermédiaires contribuant au développement de maladies cardio-métaboliques ainsi que des répercussions cérébrales (troubles cognitifs et accidents vasculaires cérébraux (AVC)). Ce travail de thèse explore la relation bidirectionnelle entre les syndromes d’apnées du sommeil (SAS) et le cerveau. Le premier axe se concentre sur les conséquences neurocognitives du SAOS au travers du contrôle de la marche. Les répercussions neurocognitives du SAOS sont à ce jour bien décrites et des troubles de la marche ont récemment été mis en évidence, avec une relation de type dose-réponse entre la gravité du SAOS et la sévérité des troubles de la marche. Il a ainsi été suggéré que la marche pouvait représenter un marqueur des répercussions cérébrales du SAOS. Les effets du traitement par pression positive continue (PPC) sur le contrôle de la marche ont été investigués au cours de ce travail de Thèse, avec des résultats contrastés. Dans une première étude prospective contrôlée, 8 semaines de traitement par PPC entraînaient une amélioration du contrôle de la marche chez des patients atteints de SAOS sévère (Baillieul et al., 2018, Plos One). Afin de valider ces résultats et d'étudier les corrélats neurophysiologiques du lien entre marche et SAOS, nous avons mené un essai contrôlé randomisé étudiant l'impact de 8 semaines de traitement par PPC comparativement à la Sham-PPC (Baillieul et al., 2020, Soumis). Contrairement à notre hypothèse, nous n'avons constaté aucune amélioration du contrôle de la marche dans le groupe PPC, résultat corroboré par l'absence d'impact de la PPC sur les déterminants du contrôle de la marche. Le deuxième axe est centré sur les répercussions cérébro-vasculaires des SAS. SAS et AVC sont deux pathologies graves et étroitement liées, le SAS pouvant être à la fois cause et conséquence potentielle des AVC. Le présent travail est axé sur l'identification des traits phénotypiques de SAS chez les patients post-AVC, afin d'en améliorer le diagnostic (Baillieul et al., en préparation). Le dépistage du SAS post-AVC est crucial en raison du risque élevé de morbi-mortalité et de conséquences fonctionnelles associées au SAS après AVC, mais il ne peut être effectif sans une identification plus précise des patients à risque de SAS. Le troisième axe a été conçu comme une perspective qui servira au développement du deuxième axe. Dans ce dernier axe, le potentiel de l'imagerie cérébrale et en particulier de l'imagerie par résonance magnétique pour développer des marqueurs de récupération et étudier les mécanismes physiopathologiques des déficiences liées aux AVC sont présentés, au travers de la marche et de son contrôle. Les corrélats neuronaux de la marche comme activité post-AVC sont mis en évidence, en utilisant une approche de type Voxel-based lesion-symptom mapping (Baillieul et al., 2019, Hum. Mov. Sci.). Les marqueurs d'imagerie basés sur l’utilisation du Diffusion tensor imaging pour prédire la récupération de la marche post-AVC sont également présentés (Soulard et al., 2019, Neurology). Ces travaux sur les marqueurs d'imagerie cérébrale de la récupération post-AVC serviront à développer des outils pour les recherches à venir sur les corrélats neuronaux des SAS post-AVC
The human brain is a perfect example of our dependence on oxygen. Brain physiological constraints render it vulnerable to hypoxia, such as encountered in environmental conditions (high altitude exposure) or pathological hypoxemic conditions. Among those pathological conditions, and due to its high prevalence in general population and the various levels of hypoxia resulting of the different degrees of severity of the pathology, obstructive sleep apnoea syndrome (OSAS) is a pathophysiological model of choice to investigate the detrimental effects of hypoxia on the brain. The cyclical, repeated episodes of apnoea and hypopnea during sleep that characterize OSAS result in intermittent hypoxia, sleep fragmentation and fluctuations in intrathoracic pressure, which are stressors that triggers mechanisms contributing to the initiation and progression of life-threatening cardiometabolic diseases, as well as several brain repercussions, such as cognitive impairment and stroke. This Thesis work explores the bidirectional relationship between sleep apnoea syndromes (SAS) and the brain. The first axis is focused on the neurocognitive consequences of OSAS through the lens of gait control. The neurocognitive signature of OSAS has been thoroughly investigated but recently, gait impairments have been highlighted in severe OSAS, with dose-response relationship between OSAS severity and the magnitude of gait impairments. As gait control relies at least partly on frontal lobe functions, it has been suggested that gait could represent a marker of OSAS brain repercussions. We investigated the effects of continuous positive airway pressure (CPAP) treatment on gait control, with contrasting results. In a first prospective controlled study, eight weeks of CPAP improved gait control in severe OSAS patients (Baillieul et al., 2018, Plos One). In order to validate those results and investigate the neurophysiological correlates of the link between gait control and OSAS, we conducted a randomized controlled trial which investigated the impact of an 8-week CPAP treatment compared to sham-CPAP on gait control in severe OSAS patients (Baillieul et al., 2020, Submitted). Contrary to our hypothesis, we found no improvement in gait control in the CPAP group and this result is substantiated by the absence of impact of CPAP on the determinants of gait control, further illustrating the complexity of the OSAS-neurocognitive relationship. The second axis is focused on the cerebrovascular repercussions of SAS. SAS and stroke are both severe intertwined conditions, SAS being both cause and potentially consequence of stroke. The present work is focused on the identification of phenotypic traits of SAS in post-stroke patients, to improve diagnosis of SAS following stroke (Baillieul et al., in preparation). Screening stroke patients for SAS is crucial due to the high risk of morbimortality and functional consequences associated to SAS following stroke but cannot be achieved without a more accurate identification of patients at risk to develop SAS following stroke. The third axis has been conceived as a perspective that will serve the development of the second axis. In this last axis, the potential of brain imagery and in particular magnetic resonance imagery to develop markers of stroke recovery as well as investigate the pathophysiological mechanisms underlying stroke-related deficiencies are presented, with a specific focus on gait and walking activity. The neural correlates of walking activity following stroke are highlighted, using a voxel-based lesion-symptom mapping approach (Baillieul et al., 2019, Hum. Mov. Sci.). Imagery markers of walking recovery following stroke using diffusion tensor imaging are also presented (Soulard et al. 2019, Neurology). This work on brain imagery markers of stroke recovery will further serve the development of investigations focused on the neural correlates of SAS following stroke

Made available in DSpace on 2014-12-17T15:16:07Z (GMT). No. of bitstreams: 1 ThayseLM.pdf: 2358410 bytes, checksum: 2b6dfd18cdd5c0c7624aef8c0dfc4278 (MD5) Previous issue date: 2009-11-09
Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
Background: Down syndrome (DS) is a genetic alteration characterized by being a nonprogressive congenital encephalopathy. Children with DS have hypotonia and developmental delays that interfere in the movement`s acquisition for these children. Objective: Analyze the effects of treadmill inclination on angle and spatiotemporal gait characteristics of these individuals. Methodology: We studied 23 subjects of both sexes, with ages ranged between 05 and 11 years, they presented ability to walk on level 5 classified according to the Functional Ambulation Category (FAC). Initially held a subjective evaluation of balance through a questionnaire (Berg Balance Scale-BBS) then the kinematic gait analysis was realized on a treadmill first, without inclination and then, with inclination of 10%, using the motion system analysis Qualisys System. Data analysis was done using BioStat 5.0 attributing significance level of 5%. Normality of data was verified using D'Agostino test and later was applied paired t-test to compare data in two experimental conditions. Results: There was a statistically significant difference in the spatiotemporal variables: reduction in the cadence (from 108.92 ? 39.07 to 99.11 ? 27.51, p <0.04), increase in cycle time (from 1.24 ? 0.27 to 1.36 ? 0.34, p = 0.03 ) and increase in time to take stock (from 0.77 ? 0.15 to 0.82 ? 0.18, p <0.001). Angular variables that showed statistically significant increasing were: the hip in the initial contact (12.23 ? 4.63 to 18.49 ? 5.17, p <0.0001) and max. flexion in balance (12.96?4:32 to 19.50 ? 4.51, p <0.0001 ), knee in the initial contact (15.59 to ? 6.71 to 21.63 ? 6.48, p <0.0001), the ankle in the initial contact (-2.79 ? 9.8 to 2.25 ? 8.79, p <0.0001), max dorsiflexion in stance (4.41 ? 10.07 to 7.13 ? 11.58, p <0.0009), maximum plantar flexion in the pre-assessment of the ankle joint (increase of -6.33 ? 8.77 to -2.69 ? 8.62, p <0.0004).Conclusions: The inclination acts in a positive way for angular and spatiotemporal features gait of children with Down syndrome, demonstrating possible benefit of using this surface in the gait rehabilitation of children with Down Syndrome
Contextualiza??o: A s?ndrome de Down (SD) ? uma altera??o gen?tica caracterizada por ser uma encefalopatia cong?nita n?o progressiva. As crian?as com SD apresentam hipotonia muscular e atraso no desenvolvimento neuropsicomotor que dificultam a aquisi??o da marcha para estas crian?as. Objetivo: Analisar os efeitos da inclina??o da esteira na marcha de crian?as com SD. Metodologia: Foram avaliados 23 sujeitos ( 9 do g?nero feminino e 14 do g?nero masculino), com m?dia de idade de 8,43 ?2,25 anos, com capacidade de deambular classificada em n?vel 5 de acordo com a Categoria de Deambula??o Funcional (FAC Functional Ambulatory Category). Inicialmente realizou-se avalia??o subjetiva de equil?brio atrav?s de question?rio (Escala de Equil?brio de Berg- BBS) em seguida, a an?lise cinem?tica da marcha em esteira el?trica sem inclina??o e com inclina??o de 10%, utilizando o sistema de an?lise do movimento Qualisys System. Para an?lise dos dados foi utilizado o programa Bioestat 5.0 atribuindo-se n?vel de signific?ncia de 5%. A normalidade dos dados foi verificada pelo teste D`Agostino e posteriormente foi aplicado o teste t-pareado para comparar os dados nas duas condi??es experimentais. Resultados: Observou-se diferen?a significante estatisticamente nas vari?veis espa?o-temporais: redu??o na cad?ncia ( de 108,92 ? 39,07 para 99,11 ? 27,51, p< 0,04) , aumento no tempo do ciclo (de 1,24 ? 0,27 para 1,36 ? 0,34, p=0,03) e aumento no tempo de balan?o (de 0,77 ? 0,15 para 0,82 ? 0,18, p< 0,001) . As vari?veis angulares que demonstraram aumento estatisticamente significante foram: quadril no contato inicial (de 12,23+4,63 para 18,49+ 5,17, p<0,0001) e m?x. flex?o no balan?o (de 12,96 ? 4,32 para 19,50 ? 4,51, p<0,0001); joelho no contato inicial (de 15,59 ? 6,71 para 21,63 ? 6,48, p< 0,0001); e tornozelo no contato inicial (de 2,79 ? 9,8 para 2,25 ? 8,79, p<0,0001), m?x. dorsiflex?o no apoio (de 4,41 ?10,07 para 7,13 ? 11,58, p<0,0009), m?x. flex?o plantar no pr?-balan?o (de 6,33 ? 8,77 para 2,69 ? 8,62, p<0,0004). Conclus?es: A inclina??o atua de forma positiva nas caracter?sticas angulares e espa?o-temporais da marcha de crian?as com S?ndrome de Down, demonstrando poss?vel benef?cio da utiliza??o deste tipo de superf?cie na reabilita??o da marcha desta popula??o

A síndrome da dor patelofemural é uma das disfunções mais comuns que acometem o joelho, principalmente mulheres jovens fisicamente ativas. No entanto, o tratamento permanece desafiador por carecer de bases científicas que direcionem sua reabilitação. Distúrbios no alinhamento estático e dinâmico dos membros inferiores, como a pronação excessiva do retropé, têm sido associados na clínica e embasados teoricamente como fatores de risco para a disfunção. No entanto, estudos experimentais que embasem esta relação ainda são controversos. O objetivo geral deste estudo foi verificar a influência da síndrome da dor patelofemural no alinhamento postural do retropé e joelho, assim como na distribuição da pressão plantar durante a fase apoio do descer escadas e em três subfases do apoio da marcha. Foram estudados 77 adultos jovens de ambos os sexos, divididos em grupo controle (GC=47) e grupo síndrome da dor patelofemural (GSPF=30). Para responder a questões científicas específicas, foram realizados três experimentos. O experimento 1 teve o objetivo específico de verificar a associação entre a síndrome da dor patelofemural e o alinhamento postural dos membros inferiores (n=77; GC=47,GSPF=30). Para tanto, foram avaliadas três medidas clínicas: o ângulo do retropé, o ângulo Q (fotogrametria digital) e a orientação médiolateral da patela (método adaptado de Mc Connell). O experimento 2 teve como objetivo específico investigar a distribuição da pressão plantar de indivíduos com e sem diagnóstico de síndrome da dor patelofemural durante o descer escadas, e avaliar a dor dos sujeitos com essa disfunção antes e após a tarefa proposta (n=74; GC=44,GSPF=30). Para tanto, avaliouse a distribuição da pressão plantar por meio de palmilhas capacitivas (Pedar X System) na fase de apoio do descer escadas e a dor referida pelos sujeitos pela escala analógica visual de dor antes e depois da tarefa motora. O experimento 3 (n=57; GC=35,GSPF=22) buscou especificamente avaliar a influência da síndrome da dor patelofemural na distribuição da pressão plantar durante o contato inicial, médio-apoio e propulsão da fase de apoio da marcha. Os principais resultados demonstraram que não houve influência da disfunção no alinhamento postural do retropé e joelho. No entanto, durante o descer escadas, a síndrome da dor patelofemural esteve associada à um contato medialmente direcionado no retropé e médio-pé, assim como menores sobrecargas plantares, provavelmente associadas ao aumento significativo da dor relatada pelos sujeitos após a tarefa. Na marcha, os sujeitos com a disfunção realizaram novamente um contato inicial medialmente direcionado no retropé e uma propulsão mais lateralizada no antepé. Os resultados deste estudo mostram que a síndrome da dor patelofemural não esteve relacionada ao alinhamento postural do retropé e joelho, mas influenciou o padrão dinâmico da distribuição da pressão plantar tanto na marcha como no descer escadas. Estes achados confirmam a importância da avaliação dinâmica durante a reabilitação dos indivíduos com esta disfunção.
Patellofemoral pain syndrome is one of the most common dysfunctions of the knee, particularly among young physically active females. Its treatment remains challenger due to the lack of scientific rationales bases to guide its rehabilitation. Static and dynamic misalignment of the lower extremity, like excessive rearfoot pronation has been clinically and theoretically associated as risk factors for this dysfunction. However, scientific studies to confirm this association are still controversial. The general purpose of this study was to verify the influence of patellofemoral pain syndrome on rearfoot and knee postural alignment as well as on plantar pressure distribution during the stance phase of stair descent and three sub phases of stance gait. 77 young adults of both sexes divided in to control group (GC=47) and patellofemoral pain goup(PFPG=30) were studied. Three experiments were realized in order to respond the specific scientific questions. The experiment 1 had the specific purpose of verify the association between patellofemoral pain syndrome and postural alignment of rearfoot and knee (n=77; CG=47, PFPG=30). Therefore, three clinical measurements were evaluated: rearfoot angle, Q angle (digital photogrammetry) and the medio-lateral orientation of the patella (adapted from McConnell). The experiment 2 aimed specifically to investigate plantar pressure distribution in subjects with and without patellofemoral pain syndrome, during the stair descent, and evaluate the pain referred by the subjects before and after the motor task (n=74;CG=44,PFPG=30), plantar pressure distribution was evaluated with capacitive insoles(Pedar X System) during the stance phase of stair descent as well as the pain referred by the subjects by Visual Analogue Scale before and after the task. The experiment 3 intended specifically to verify the influence of patellofemoral pain syndrome on plantar pressure distribution during initial contact, midstance and propulsion of the gait stance (n=57; GC=35, GSPF=22). The principal results of this study showed that there was no influence of the dysfunction on postural alignment of rearfoot and knee. However, patellofemoral pain syndrome during the stair descent was related to a medially directed contact at the rearfoot and midfoot and lower plantar loads probably due to the increase in pain observed after the task. During gait, the subjects with the dysfunction showed again an initial contact medially directed at the rearfoot and laterally directed propulsion on forefoot. The results of this study show that patellofemoral pain syndrome was not associated to postural alignment but influenced the plantar pressure distribution during gait as well as stair descending task. These findings confirm the importance of the dynamic evaluation of subjects with this dysfunction during their rehabilitation.

Made available in DSpace on 2016-12-06T17:06:48Z (GMT). No. of bitstreams: 1 Lisiane Piazza.pdf: 1405416 bytes, checksum: 55ba3d2e707b8e4658ae86707f239905 (MD5) Previous issue date: 2012-02-16
Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
The purpose of this study was to understand the biomechanical patterns adopted by subjects with and without PFPS during perform five daily living activities (walking on a flat surface, up and down stairs and ramp). Participated of this study 65 individuals, females, of which 57 were selected: 26 with PFPS (PFPSG) and 31 clinically healthy (CG), matched by age, height and body mass. The data were collected in the Biomechanics Lab at the University of Passo Fundo RS. Initially, was applied an evaluation form to characterize the subjects and the Kujala Questionnaire to assess the symptoms and functional limitations related to the patellofemoral joint. Was evaluated plantar pressure distribution (peak pressure, contact area and contact time) in six regions (medial forefoot, lateral forefoot, midfoot, medial rearfoot, central rearfoot and lateral rearfoot) through the Pedar-X during perform five daily living activities. Kinematic analysis was also carried out (maximum angle of rearfoot eversion and % of support phase in which this angle has been reached) using the APAS (Ariel Performance Analysis System) as well as isokinetic evaluation (peak torque and work concentric/concentric) of the knee flexors and extensors in two speeds (180°/s and 60°/s) using the Biodex Multi Joint System 3. The order of the assessments was randomized. Pain intensity before and after perform the activities was assessed by Visual Numeric Scale (VNS). Data were analyzed using descriptive and inferential statistics (U- Mann Whitney test, independent T-test, Wilcoxon and ANOVA 2x6), with a significance level of p ≤ 0.05.The PFPSG had a lower score on the Kujala Questionnaire in relation to CG (p=0,01). There were no differences between groups in peak pressures, contact area and contact time in six plantar regions analyzed during the five daily living activities. Additionally, there were no differences between groups regarding the magnitude of the maximum angle of rearfoot eversion. There was also increased pain after perform the five daily living activities (p = 0.01) and isokinetic evaluation at 180 ° / s (p = 0.007) and 60 ° / s (p = 0.01). The results of this study, in the experimental conditions used, suggested that there isn t a behavior pattern in the plantar pressure distribution that differentiate subjects with and without PFPS during perform five daily living activities proposed in this study. However, subjects with PFPS reach maximum rearfoot eversion in early stance phase of walking on a flat surface, suggesting a strategy to avoid a possible appearance or worsening of their symptoms and have low knee flexors and extensors peak torque and knee extensors work compared to asymptomatic subjects.
Este estudo teve como objetivo compreender os padrões biomecânicos adotados por sujeitos com e sem SDPF na realização de cinco atividades funcionais (marcha em superfície plana, subir e descer escadas e rampa). Participaram 65 indivíduos do gênero feminino, dos quais foram selecionados 57: 26 com SDPF (GSDPF) e 31 clinicamente saudáveis (GC), pareados em idade, estatura e massa corporal. Os dados foram coletados no Laboratório de Biomecânica da Universidade de Passo Fundo-RS. Inicialmente foi aplicada uma ficha de avaliação para caracterização dos sujeitos e o Questionário de Kujala para avaliação dos sintomas e limitações funcionais relativos à articulação patelofemoral. Foi avaliada a distribuição da pressão plantar (pico de pressão, área de contato e tempo de contato) em seis regiões plantares (antepé medial, antepé lateral, médio pé, retropé medial, retropé central e retropé lateral) por meio do Pedar-X durante a realização das cinco atividades funcionais. Foram realizadas também a análise cinemática (ângulo máximo de eversão do retropé e % da fase de apoio em que este ângulo foi atingido) através do APAS (Ariel Performance Analysis System) e avaliação isocinética (pico de torque e trabalho concêntrico/concêntrico) dos flexores e extensores do joelho nas velocidades de 180°/s e 60°/s através do dinamômetro isocinético Biodex Multi Joint System 3. A ordem de realização das avaliações foi randomizada. A intensidade da dor dos sujeitos antes e após as atividades foi avaliada pela Escala Visual Numérica (EVN). Os dados foram analisados por meio da estatística descritiva e inferencial (Testes U de Mann Whitney, T-independente, Wilcoxon e Anova 2x6), com nível de significância de p≤0,05. O GSDPF apresentou menor pontuação no Questionário de Kujala em relação ao GC (p=0,01). Não foram observadas diferenças entre os grupos no pico de pressão, área de contato e tempo de contato nas seis regiões plantares analisadas durante as cinco atividades funcionais. Adicionalmente, não foram constatadas diferenças entre os grupos em relação à magnitude do ângulo máximo de eversão do retropé. No entanto, o GSDPF atingiu este ângulo mais cedo na fase de apoio da marcha que o GC (p=0,01). A avaliação isocinética evidenciou menor pico de torque dos flexores (p=0,005 e p=0,03) e extensores (p=0,006 e p=0,004) do joelho nas velocidades de 180°/s e 60°/s e menor trabalho da musculatura extensora do joelho (p=0,05 e p=0,01) em ambas velocidades do teste isocinético no GSDPF. Houve também exacerbação da dor dos sujeitos após a realização das cinco atividades funcionais (p=0,01) e avaliação isocinética a 180°/s (p=0,007) e 60°/s (p=0,01). Sendo assim, os resultados do presente estudo, nas condições experimentais utilizadas, sugerem que não existe um padrão de comportamento da distribuição da pressão plantar que diferencie sujeitos com e sem SDPF durante a realização das cinco atividades funcionais propostas no estudo. No entanto, sujeitos com SDPF alcançam a eversão máxima do retropé mais cedo na fase de apoio da marcha em superfície plana, sugerindo uma estratégia para evitar um possível surgimento ou agravo dos seus sintomas, além de apresentar menor torque dos flexores e extensores do joelho e trabalho dos extensores do joelho em relação a sujeitos assintomáticos.

Les flux financiers internationaux ont connu un développement accéléré au cours des quatre dernières décennies, et le rôle du secteur bancaire dans la transformation de ces flux en moyens de financer la demande s’est accru. Or le passage d’un choc de flux, à un choc de revenu, puis à un choc de demande, génère des ajustements de type «Syndrome Hollandais»; avec variation des prix relatifs et ajustement de la structure de production, mouvement des facteurs de production, et variation des rémunérations absolues et relatives de ces facteurs. Le phénomène est d’importance pour les petites économies ouvertes preneuses de prix et exposées aux chocs exogènes. Nous conceptualisons la transmission du choc et les ajustements sur différents horizons temporels pour une économie à deux secteurs; l’un produisant des biens échangeables et l’autre des biens non-échangeables. L’économie dispose de deux facteurs de production, le travail et le capital, substituables et mobiles avec le temps. Nous testons ce cadre conceptuel sur le Liban, le Luxembourg, et l’Islande; trois pays bénéficiant de larges flux financiers internationaux avant la crise de 2008 et ayant des secteurs bancaires de tailles importantes. Nous trouvons que la direction et l’intensité des ajustements de moyen terme vont dépendre du différentiel d’intensité capitalistique entre secteurs. Sur le long terme, l’offre des facteurs va se modifier. Nous testons aussi l’impact des politiques de réserves et du marché de la monnaie et du crédit, et des politiques fiscales et structurelles. La combinaison de mesures produit de meilleurs résultats sans toutefois mettre le poids de l’atténuation des ajustements sur un seul instrument
Foreign financial inflows have developed quickly in the past 40 years. These inflows have increased the ability of the banking sector to further finance domestic demand. The transformation of foreign financial inflows into an income and demand shock generates Dutch Disease adjustments; with change in relative prices and adjustments in the productive system, resources movement, and change in the absolute and relative remunerations of factors of production. The phenomenon is of great importance in the case of small open economies that are price takers in the international market and exposed to exogenous shocks. We conceptualize the transmission of the shock and the adjustments over different time horizons for an economy composed of two sectors; one producing traded goods and the other producing non-traded goods. This economy is endowed with two factors of production, labor and capital, substitutable and mobile as time elapses. We experiment this conceptual framework in the cases of Lebanon, Luxemburg, and Iceland; the three economies having large banking sectors and benefiting from large foreign financial inflows prior to the 2008 crisis. We find that the direction and intensity of adjustments over the medium term depend on the differential of capital intensity between sectors. Over the longer term, the supply of factors of production would change. We also simulate the impact of policy choices, with focus on reserves policies, policies of money and credit, fiscal policies, and structural policies. The combination of measures leads to better results without putting the burden of the mitigation of adjustments on one single policy instrument

La pronation et les pieds plats ont longtemps été considérés conjointement, notamment dans leur relation avec la blessure. Or, cette relation, au regard des résultats divergents de la littérature, a été remise en question. Récemment, la dissociation entre la typologie et la fonctionnalité du pied a permis de mettre en évidence une possible association entre la pronation et la lombalgie. L’étude de la locomotion de sujets pronateurs identifiés par des tests fonctionnels pourrait exposer les facteurs de risques biomécaniques associés à la lombalgie. L’objectif général était d’identifier et d’étudier l’impact cinématique et baropodométrique de la pronation à la marche. Puis d’évaluer l’effet de traitements préventifs visant à limiter la biomécanique à risque dans un but de prévention primaire. Trois études ont été menées. Une étude de concordance entre différents tests d’identification de la pronation a été réalisée, dans des conditions différentes, afin de sélectionner un test approprié à l’étude de la marche. La cinématique et la baropodométrie de la marche de 159 sapeurs-pompiers professionnels, pronateurs vs non-pronateurs, ont été comparées. Deux protocoles d’un mois visant à réduire la pronation (renforcement musculaire du pied ou port de semelles) ont été proposés chez les sujets pronateurs. La concordance des différents tests de fonctionnalité a été jugée faible. Une combinaison de tests fonctionnels a été utilisée pour affiner le diagnostic de pronation. Les sujets pronateurs ont exposé des différences baropodométriques et cinématiques de l’avant et de l’arrière-pied, du genou et du bassin à la marche. Cette cinématique pourrait constituer un facteur de risque de lombalgie. La pronation a été réduite par les deux protocoles préventifs et accompagnée de modifications cinématiques du pied et de la hanche. Bien que nos protocoles préventifs ne témoignent pas d’une incidence sur le bassin, ils exposent une modification cinématique du membre inférieur, qui pourrait modifier la biomécanique du bassin et constituer un moyen de prévention des lombalgies
Pronation and flat feet have, for a long time, been associated, particularly in their relationship to injury. However, this relationship has been questioned in view of the divergent results in writings. Recently, the dissociation between foot-type and foot-function has highlighted a possible link between pronation and low back pain. The study of pronator subjects' way of moving, identified by foot function tests, could highlight the biomechanical risk factors associated with low back pain. The general objective was to identify and study the kinematic and plantar pressure impact of pronation while walking. Then to evaluate the effect of preventive treatments aimed aimed to limit the biomechanics at risk while keeping primary prevention in mind. Three studies were conducted. A concordance study between different pronation identification tests, under different conditions, was carried out in order to select an appropriate test for the study of gait. Gait kinematic and baropodometric analyses of 159 pronator vs non-pronator professional firefighters were then compared. Then, the effects of two one-month protocols aimed at reducing pronation (foot muscle strengthening or wearing insoles) were suggested to pronator subjects. Agreement between the different tests of foot-function identification was found to be low. A combination of functional tests was used to refine the identification of pronation. Pronator subjects showed plantar pressure and kinematic differences in the forefoot, hindfoot, knee and pelvis. These kinematic effects may reflect a risk factor for low back pain. Pronation was reduced by both preventive protocols wich were accompanied by kinematic changes in the foot and hip. Although our preventive protocols do not show an impact on the pelvis, they do show a kinematic change in the lower limb that could modify the biomechanics of the pelvis and provide a mean of preventing low back pain

La schizophrénie est une pathologie caractérisée par des symptômes positifs (idées délirantes et hallucinations), des symptômes négatifs (émoussement affectif, alogie, apragmatisme, retrait social) et des symptômes de désorganisation (cognitifs et affectifs). Cette pathologie est également associée à des altérations cognitives, perceptuelles et de la qualité de vie. La physiopathologie de la schizophrénie reste mal connue. Récemment, des travaux ont mis en avant le rôle central des processus inflammatoires chroniques dans la physiopathologie de ce trouble psychiatrique. En particulier, il a été montré que la CRP (Protéine C-Réactive), marqueur inflammatoire chronique aspécifique et facile à doser dans une prise de sang, est augmentée dans la schizophrénie. La CRP est reliée à la symptomatologie clinique et aux altérations cognitives des patients souffrant de schizophrénie. Mais le lien entre altérations perceptuelles et de la qualité de vie et CRP reste à explorer
Schizophrenia is an illness characterized by positive symptoms (delusions and hallucinations), negative symptoms (reduced emotional expression, alogia, apragmatism, reduced social engagement) and disorganized symptoms (cognitive and affective). This pathology is also associated to cognitive and perceptual alterations and to quality of life alterations. The physiopathology of schizophrenia is still unclear. Recently, papers put forward the central role of chronic inflammatory process in pathophysiology of this psychiatric disorder. In particular, CRP (C-Reactive Protein), a nonspecific marker of chronic inflammation and easy to measure with blood sample, was shown to be increased in schizophrenia. CRP is connected to clinical symptomatology and to cognitive alterations in patients with schizophrenia. However the connection between alterations of perception, quality of life and CRP remains to be explored

Introdução: O bloqueio atrioventricular congênito isolado (BAVCi) é raro e tem múltiplas apresentações clínicas. O implante de marca-passo cardíaco permanente (MP) é o tratamento de escolha, resultando em evolução clínica satisfatória para a maioria dos casos, porém, aproximadamente 10% deles apresentam remodelamento ventricular e insuficiência cardíaca grave. Objetivos: Estudar a evolução tardia de crianças e adultos jovens com BAVCi e estimulação crônica do ventrículo direito (VD), visando determinar: a prevalência de sinais clínicos e laboratoriais de insuficiência cardíaca e de remodelamento ventricular; a capacidade funcional; a qualidade de vida e fatores preditores de alterações clínicas, funcionais ou ecocardiográficas. Métodos: Estudo transversal realizado em coorte de portadores de BAVCi e MP implantado antes de 21 anos de idade com estimulação no VD há mais de um ano. Todos os indivíduos foram submetidos a avaliação clínica e laboratorial, da capacidade funcional, da qualidade de vida e a ecocardiograma. Mães e sujeitos da pesquisa foram investigados para doenças reumatológicas. Os dados foram armazenados no sistema REDCap (Research Electronic Data Capture) e analisados pelos programas SAS (Statistical Analysis System), SPSS (Statistical Package for the Social Sciences) e R Studio. A análise dos dados incluiu: análise univariada para pesquisa de associações entre variáveis preditoras e desfechos, coeficiente de correlação de Pearson e modelo de regressão linear multivariado. Resultados: De março/2010 a dezembro/2013, foram avaliados 63 indivíduos, 68% do sexo feminino, com idade de 1 a 40 anos, com MP por 13,4 ± 6,5 anos e estimulação do VD por 10,0 ± 5,4 anos. O modo de estimulação era atrioventricular em 55,6%, o percentual de estimulação de VD de 97,9 ± 4,2% e a duração do complexo QRS estimulado de 152,4 ± 20,1 ms. A maioria (88,9%) era assintomática e não utilizava medicamentos de ação cardiovascular. Maior tempo de MP (P= 0,013), maior tempo de estimulação do VD (P= 0,005), maior idade na inclusão no estudo (P= 0,032) ou menor fração de ejeção do ventrículo (FEVE) (P= 0,013) associaram-se com a presença de classe funcional II (NYHA) e/ou uso medicamentos. Os valores do peptídeo natriurético tipo B foram normais em todos os exames laboratoriais, mas houve alteração da proteína C reativa ultrassensível, fator de necrose tumoral alfa e interleucina-6 em 66%, 34% e 13% exames, respectivamente. A distância média percorrida no teste de caminha de seis minutos foi de 546,9 ± 76,2 metros (91,0 ± 12,5% do valor predito). Os escores médios da qualidade de vida foram 78,1 ± 17,7 para o \"Sumário Físico\" e 76,6 ± 17,1 para o \"Sumário Mental\" do questionário Short Form 36 (SF-36) e de 77,4 ± 18,5, para o \"Sumário Físico\" e de 77,7 ± 21,6 para o \"Sumário Psicossocial\", do Child Health Questionnaire - Parent Form 50 (CHQ-PF50). Diminuição da FEVE foi detectada em 39,7% e aumento do diâmetro diastólico do ventrículo esquerdo (DDVE) em 22,2% dos indivíduos. A idade mais avançada no primeiro implante de MP se correlacionou negativamente com menor FEVE (r= -0,302; P= 0,016); a duração do complexo QRS estimulado (r= 0,447; P= 0,002) e maior tempo sob estimulação do VD (r= 0,416; P= 0,007) se correlacionaram positivamente ao aumento do DDVE. Foi detectada dissincronia ventricular em 60,3% dos indivíduos. O retardo da ativação eletromecânica intraventricular esquerda foi de 86,5 ± 56,9 ms e interventricular, de 141,9 ± 88 ms. Contudo, não houve correlação com os fatores estudados. Autoanticorpos anti-Ro/SSA foram detectados em 18 (32,1%) mães, com associação entre idade no momento do implante do MP (P= 0,032) e uso de MP ventricular no momento do estudo (P= 0,022). A regressão linear multivariada confirmou a correlação entre a idade no momento do implante do MP com a FEVE (P= 0,016), da duração do complexo QRS estimulado (P= 0,004) e do tempo sob estimulação do VD (P= 0,014) com o DDVE. Conclusões: A prevalência de manifestações clínicas e laboratoriais de insuficiência cardíaca foi baixa; por outro lado, a de remodelamento ventricular esquerdo foi elevada. A capacidade funcional foi satisfatória, assim como a qualidade de vida, nos aspectos físicos e emocionais. Idade mais avançada no primeiro implante de MP, maior tempo sob estimulação cardíaca e complexo QRS estimulado mais alargado foram fatores independentes de remodelamento ventricular e/ou de manifestação de insuficiência cardíaca
Introduction: Isolated congenital atrioventricular block (iCAVB) is a rare condition with multiple clinical presentations. Permanent cardiac pacing is the most effective therapy for this population resulting in satisfactory long-term outcomes. However, approximately 10% of patients may have ventricular remodeling and severe heart failure. Objectives: To study the long-term effects of chronic right ventricular (RV) pacing in children and young adults with iCAVB in order to determine: prevalence of clinical and laboratory signs of heart failure and ventricular remodeling, functional capacity, quality of life and predictors of clinical, functional or echocardiographic abnormalities. Methods: Cross-sectional study of a cohort of iCAVB patients with <= 21 years old at initial pacemaker (PM) implantation and single or dual-chamber pacing in a unique RV site for a minimum of one year. All subjects underwent clinical and laboratory assessment, functional capacity, quality of life and echocardiogram. Mothers and research subjects were investigated for rheumatic diseases. Data were stored in REDCap (Research Electronic Data Capture) system and analyzed by SAS (Statistical Analysis System), SPSS (Statistical Package for the Social Sciences) and R Studio programs. Data analysis included: univariate analysis for associations between predictor variables and outcomes, Pearson correlation coefficient and linear regression multivariate model. Results: Between March/2010 and December/2013, we evaluated 63 subjects aged 1-40 years old, 68% female, under PM for 13.4 ± 6.5 years and under RV pacing for 10.0 ± 5.4 years. Pacing mode was atrioventricular in 55.6%, percentage of RV pacing was 97.9 ± 4.2% and paced QRS duration was 152.4 ± 20.1 ms. Overall, the majority (88.9%) were asymptomatic and did not use cardiovascular drugs. Longer time under PM (P= 0.013), or even under RV pacing (P= 0.005), higher age at study inclusion (P= 0.032) and lower left ventricular ejection fraction (LVEF) (P= 0.013) were associated with functional class II (NYHA) and / or drug use. B-natriuretic peptide values were normal in all tests. C reactive protein ultrasensitive, tumor necrosis factor alfa and interleukin-6 were increased in 66%, 34% and 13% tests, respectively. The mean walked distance in the sex minute walk test was 546.9 ± 76.2 meters (91.0 ± 12.5% of the predicted value). Mean scores of quality of life were 78.1 ± 17.7 for \"Physical Summary\" and 76.6 ± 17.1 for \"Mental Summary\" in the Short Form 36 (SF-36) and 77.4 ± 18.5 for \"Physical Summary\" and 77.7 ± 21.6 for \"Psychosocial Summary\", of Child Health Questionnaire - Parent Form 50 (CHQ-PF50). Decreased LVEF was detected in 39.7% and increased left ventricular end-diastolic diameter (LVDD) in 22.2% of subjects. Higher age at the first PM implant was negatively correlated with lower LVEF (r= -0.302; P= 0.016); paced QRS duration (r= 0.447; P= 0.002) and time under RV pacing (r= 0.416; P= 0.007) were positively correlated with LVDD. Ventricular dyssynchrony was detected in 60.3 % of individuals. Intra-left ventricular electromechanical delay was 86.5 ± 56.9 ms and interventricular was 141.9 ± 88 ms. However, ventricular dyssynchrony was not correlated with the studied variables. Autoantibodies anti-SSA/Ro were detected in 18 (32.1%) mothers. There was association between age at PM implant (P= 0.032) and use of ventricular PM at the time of the study (P= 0.022) and presence of anti-SSA/Ro. Multivariate linear regression showed significant correlation between age at PM implant with LVEF (P= 0.016); and paced QRS duration (P= 0.005) and time under RV pacing (P= 0.014) with LVDD. Conclusions: Clinical and laboratorial manifestations of heart failure presented low prevalence in this population. On the other hand, the prevalence of left ventricular remodeling was high. Functional capacity was adequate, as well as quality of life, in both physical and emotional aspects. Higher age at first PM implant, longer time under pacing and wider paced QRS duration were independent factors of ventricular remodeling and/or manifestation of heart failure

Durant une infection pulmonaire, les porcs sont souvent infectés par plus d’un microorganisme. Actinobacillus pleuropneumoniae et le virus du syndrome reproducteur et respiratoire porcin (VSRRP) sont des pathogènes qui peuvent infecter de manière simultanée les porcs. L’objectif du présent projet est d’étudier l’interaction entre ces pathogènes. Les deux lignées cellulaires permissives au VSRRP utilisées sont les cellules « St-Jude porcine lung » (SJPL) et MARC-145. Les cellules ont été pré-infectées avec le VSRRP, puis infectées avec A. pleuropneumoniae. Un dosage de la lactate déshydrogénase a montré qu’une co-infection VSRRP-A. pleuropneumoniae comparée à une infection simple augmente significativement la cytotoxicité. Dans les mêmes conditions expérimentales, une pré-infection virale ne semble pas affecter l’adhérence d’A. pleuropneumoniae aux cellules. À l’aide de tests ELISA, il a été possible de démontrer la production d’IL-8 et d’INF-γ lorsqu’il y a infection des cellules. Pour ce qui est du TNF-α, d’IL-6 et d’IL-10, ces cytokines ne sont pas détectées en présence des pathogènes étudiés. Des expériences de pré-infection bactérienne suivie d’infection virale ont également été réalisées. Il a été démontré que la pré-infection avec A. pleuropneumoniae diminuait la réplication du VSRRP chez la lignée cellulaire SJPL, mais cela n’est pas observé avec la lignée cellulaire MARC-145. Les résultats préliminaires ont démontré que cette diminution de la réplication serait causée par une molécule de faible poids moléculaire sécrétée dans le surnageant bactérien et celle-ci serait résistante à la chaleur. Les lignées cellulaires SJPL et MARC-145 représentent de bons modèles pour l’étude des infections mixtes des voies respiratoires du porc.
The respiratory tract of pigs is often colonized by more than one pathogen during an infection. Actinobacillus pleuropneumoniae and the porcine reproductive and respiratory syndrome virus (PRRSV) are pathogens that can be associated with co-infection. The objective of this project was to study interactions between A. pleuropneumoniae and PRRSV during mixed infection. The PRRSV-permissive cell lines, St-Jude porcine lung (SJPL) and MARC-145 were used. In the first part, cells were pre-infected with PPRSV followed by an infection with A. pleuropneumoniae. Results obtained with a lactate dehydrogenase test showed that a co-infection resulted in a greater cytotoxicity then the single infections. The adherence of A. pleuropneumoniae to non-infected or PRRSV-infected cells was similar. Based on ELISAs tests, it was found that the cells produced IL-8 and IFN-γ when they were infected, but TNF-α, IL-6 and IL-10 were not detected. In the second part, cells were pre-infected with A. pleuropneumoniae followed by viral infection. The results showed that a pre-infection with A. pleuropneumoniae decreased PRRSV replication in SJPL cells, whereas A. pleuropneumoniae did not impair PRRSV replication in MARC-145 cells. Preliminary results indicate that a molecule secreted by A. pleuropneumoniae is the factor impairing PRRSV replication in SJPL cells. The factor is probably a small molecular weight molecule that is heat-resistant. In conclusion, both cell lines allowed the study of A. pleuropneumoniae and PRSSV interactions during a mixed-infection and these models could be adapted to study interactions of other swine pathogens.

This doctoral thesis describes unusual skin and soft-tissue tumors, which were the basis of the postgraduate study of Ladislav Hadravský, MD at Medical faculty in Pilsen of Charles University in Prague during 2013 - 2016. It contains documented cases of skin and soft-tissue tumors related to hereditary syndromes, unusual morphology, rare biological behavior, minor causal association with the respective disease, or different phenotypes. These cases were published in journals with the impact factor and in peer-reviewed journals. Regarding skin tumors, the study focused on sebaceous tumors of the skin, which may occur within Muir-Torre syndrome. In the retrospective study of sebaceous skin tumors, two unusual cases were found: the case of aggressive extraocular sebaceous carcinoma on the scalp in a patient with Muir-Torre syndrome and the case of multiple sebaceous skin tumors in a patient with MUTYH-associated polyposis of the colon mimicking Muir-Torre syndrome. As far as soft-tissue tumors are concerned, the study aimed at the morphological comparison of cases of myxoinflammatory fibroblastic sarcoma and pleomorhic hyalinizing angiectatic tumor.

Les récoltes de céréales sont souvent contaminées par des moisissures qui se développent pendant la récolte et l’entreposage et produisent des métabolites secondaires appelés mycotoxines. Le porc est reconnu pour être sensible au déoxynivalénol (DON). L’infection virale la plus importante chez le porc est causée par le virus du syndrome reproducteur et respiratoire porcin (VSRRP). Celui-ci provoque un syndrome grippal et des troubles de reproduction. L’objectif du présent projet était de déterminer l'effet in vitro de DON sur la réplication du VSRRP dans de lignées cellulaires permissives, MARC-145 et PAM, et déterminer in vivo l'impact de DON dans des aliments naturellement contaminés sur l’infection au VSRRP chez le porcelet. Tout d’abord, les cellules ont été incubées avec des doses croissantes de DON et ont été infectées avec du VSRRP pour évaluer la viabilité et la mortalité cellulaire, la réplication virale et l’expression de cytokines. Les résultats ont montré que les concentrations de DON de 560ng/ml et plus affectaient significativement la survie des cellules MARC-145 et PAM infectées par le VSRRP. En revanche, il y avait une augmentation significative de la viabilité et une réduction de la mortalité cellulaire à des concentrations de DON de 140 à 280 ng/ml pour les cellules PAM et de 70 à 280 ng/ml pour les cellules MARC-145 avec une réduction de l'effet cytopathique provoqué parle VSRRP. Au niveau in vivo, 30 porcelets divisés en 3 groupes de 10 porcelets et nourris pendant 2 semaines avec 3 différentes diètes naturellement ont été contaminées avec DON (0; 2,5 et 3,5 mg/kg). Les porcelets ont été subdivisés en 6 groupes, 3 groupes de 6 porcelets et ont été exposés au DON pendant 2 semaines et infectés par voie intratrachéale et intramusculaire avec le virus. Les 3 autres groupes de 4 porcelets servaient de contrôle non infectés. Les signes cliniques ont été enregistrés pendant 21 jours. La virémie a été évaluée par PCR. À la fin de l’expérimentation, les porcelets ont été euthanasiés et les lésions pulmonaires ont été évaluées. Les résultats ont montré que l’ingestion de DON à 3,5 mg/kg a augmenté l’effet du VSRRP sur la sévérité des signes cliniques, les lésions pulmonaires et la mortalité. L’ingestion de DON à 2,5 mg/kg a entrainé une augmentation de la virémie au jour 3 après l’infection mais sans impact sur les signes cliniques et les lésions pulmonaires. Mot clés: DON, VSRRP, MARC-145, PAM, effet cytopathique, cytokines, PCR
Cereal crops are often contaminated with moulds that grow during harvest and storage and produce secondary metabolites called mycotoxins. Pig is known to be sensitive to deoxynivalenol (DON). On the other hand, infection by porcine reproductive and respiratory syndrome virus (PRRSV) causes a flu-like syndrome and reproductive disorders. The objectives of this project were to determine the in vitro effect of DON on the replication of PRRSV in permissive cell lines, MARC-145 and PAM and the in vivo impact of DON-naturally contaminated feed on PRRSV infection in piglets. Firstly, cells were incubated with gradually increasing doses of DON and were infected with PRRSV to evaluate cytopathic effect and to assess cell viability, virus replication and cytokine mRNA expression on infected and uninfected cells. Results showed that DON concentrations of 560 ng/ml and higher were significantly detrimental to the survival of MARC-145 cells infected with PRRSV. In contrast, there was a significant increase of cell viability and decreased of cell mortality at DON concentrations within 140 to 280 ng/ml for PAM cells and 70 to 280 ng/ml ranges for MARC-145 showing a reduced cytopathic effect (CPE) caused by PRRSV. In vivo study was carried out on 30 piglets divided into 3 groups of 10 piglets fed naturally contaminated diets with different levels of DON; 0, 2.5 and 3.5 mg/kg. After 2 weeks, pigs were further divided into 6 subgroups, 3 subgroups of 6 piglets were infected intra tracheally and intramuscularly with PRRSV. The other 3 subgroups of 4 piglets were used as uninfected controls. Clinical signs were recorded for 21 days post-infection (p.i.). Sera were evaluated for viremia by PCR. At the end of the experiment, piglets were euthanized and pulmonary lesions were evaluated. Results showed that ingestion of diet highly contaminated with DON at 3.5 mg/kg increased the effect of PRRSV infection on the severity of clinical signs, weight loss, lung lesions and mortality. Diet with DON at 2.5 mg/kg showed an increase of viremia at day 3 but had not significant impact on clinical signs and lung lesions. Keywords: DON, PRRSV, MARC-145, PAM, cytopathic effect, cytokines, PCR

RESUMO: Objectivo: Este estudo tem como principal objectivo determinar perfis de fragilidade em pessoas idosas, residentes ma comunidade. Metodologia: Trata-se de um estudo de natureza não experimental, quantitativo, exploratório e descritivo, com uma amostra de conveniência, constituída por pessoas idosas (n=47), residentes na comunidade. As variáveis em análise foram o fenótipo de fragilidade, onde a força de preensão foi avaliada através de um dinamómetro portátil, a percepção de exaustão através da CES-D, a velocidade de marcha foi avaliada pelo Timed Up and Go Test, a actividade física através de uma escala simplificada, com base nos estudos de Grimby, e a perda de peso não intencional através de uma questão sobre perda de peso no último ano. As restantes variáveis foram avaliadas por questionário, à excepção da capacidade funcional, avaliada por uma escala com actividades básicas e instrumentais da vida diária assim como locomoção, e da força de membros inferiores, avaliada pelo teste de sentar e levantar da cadeira durante 30 segundos. Resultados: Verificou-se que a maioria da amostra era pré-frágil, com uma frequência próxima de fragilidade e uma quase inexistência de não fragilidade. Contribui para isto, essencialmente, a velocidade de marcha e perda de peso não intencional. Apesar de se encontrar uma grande presença de comorbilidade e independência com limitação nos indivíduos deste estudo, não se verifica uma relação de significância entre estas variáveis. Verificam-se relações significativas com a Hipertensão arterial e a percepção do estado de saúde. Conclusão: Não foi possível definir um perfil de fragilidade de forma consistente, devido à grande variabilidade de resultados encontrados e à não existência de correlações significativas, no que diz respeito à síndrome de fragilidade. -----------ABSTRACT: Objective: This study aims to determine profiles of fragility in elderly people, living in the community Methodology: This is a study of a non experimental, quantitative, exploratory and descriptive, with a convenience sample, consisting of elderly (n = 47), living in the community. The variables analyzed were the frailty phenotype where grip strength was measured using a handheld dynamometer, the perception of exhaustion through the CES-D, gait speed was assessed by the Timed Up and Go Test, physical activity through a simplified scale based on studies of Grimby and unintentional loss of weight through a question about weight loss in the last year.The remaining variables were assessed by questionnaire, with the exception of functional capacity assessed by a scale with basic and instrumental activities of daily living as well as locomotion, and lower limb strength, evaluated by sitting and rising from a chair for 30-second test. Results: It was found that most of the sample was pre-fragile with a frequency close to the fragility and almost no non-brittleness. Contribute to this, essentially, gait speed and unintentional weight loss. Despite being a large presence of comorbidity and independence in individuals with limitation of this study, no there is a significant relationship between this variables. There are significant relations with hypertension and the perception of health status. Conclusion: It was not possible to define a profile of fragility consistently, due to the great variability of results and the absence of significant correlations, with respect to the frailty syndrome.