Made available in DSpace on 2014-12-17T15:55:07Z (GMT). No. of bitstreams: 1 SandraMLB.pdf: 485730 bytes, checksum: 2d9d8cd23c72f730b56737d606b11e82 (MD5) Previous issue date: 2006-08-30 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior / The rapid growth of the Brazilian cities in the latest years has brought a series of problems regarding housing policies and, therefore, the provision of dwellings for the low-income class people. Following the pattern of other capital cities, Natal has repeated the pattern of urbanization practiced in the country, which concentrates the low-income class inhabitants in specific zones of the city known as peripheries or even in a dwelling place for less-favored classes such as Felipe Camar?o, which is one of ten boroughs belonging to the western administrative zone, a region which has historically received less attention from the public administrators towards infrastructure investments. Based on those aspects, the general objective of this work is to investigate which main social-environmental alterations have resulted from the processes of urbanization and field occupation in that area. The specific objectives are concerned with verifying 1) the process of urbanization and the process of dividing urban soil from the 1960s; 2) the current configuration of the public spaces in the borough; 3) the process of the deprivation of the original landscape characteristics of Environmental Protection Zones; 4) the dynamics of land occupation which are predominant in dune areas; 5) the dynamics of land occupation which are predominant in mangrove areas; 6) and the destruction of green covering on the land with its consequent alteration of the local floristic pattern. The methodology consisted of in-loco visits; the application of questionnaires as community research; a survey of bibliography published by the organisms and institutions in charge of carrying out the city hall s environmental and housing policies; and descriptive statistics of the collected data. Concerning the pattern of occupation which is predominant in the borough, the treatment of space dispensed by the local dwellers has culminated in the emergence and consolidation of environmental alterations which are clearly different from common occurrence in both the building area represented by housing complexes and in the green areas represented by dunes and mangroves. The data show that there was the predominance of the irregular land occupation process over the official housing policy during the population settlement which contributed with a series of frequent and foreseeable problems in the dynamics of urbanization of poverty such as invasions and appropriations of land parcels, the beginning of irregular arrangement of streets, the formation of villages and slums, which are full of self-constructed housing units, and the occupation and degradation of susceptibly fragile environmental areas such as the dune slopes and the mangroves / O r?pido crescimento das cidades brasileiras nos ?ltimos anos trouxe uma s?rie de problemas relacionados com as pol?ticas de habita??o e conseq?entemente com a provis?o de habita??es para as classes de renda baixa. Seguindo o exemplo de outras capitais, Natal repetiu o modelo de urbaniza??o praticado no pa?s, concentrando as popula??es de baixa renda em zonas espec?ficas da cidade classificadas como periferias, ou lugar de habita??o das classes menos favorecidas como ocorre em Felipe Camar?o, um dos dez bairros que integram a zona administrativa oeste, regi?o que historicamente recebeu pouca aten??o por parte dos poderes p?blicos em termos de investimentos em infra-estrutura. Fundamentados nesses aspectos, o objetivo geral deste trabalho ? averiguar quais as principais altera??es s?cio-ambientais decorrentes do processo de urbaniza??o e ocupa??o na ?rea. Constituem-se os objetivos espec?ficos verificar: o processo de urbaniza??o e parcelamento do solo a partir de 1960; a configura??o atual dos espa?os p?blicos do bairro; o processo de descaracteriza??o das Zonas de Prote??o Ambiental; as din?micas de ocupa??o predominantes nas ?reas de dunas e de manguezal e a destrui??o da cobertura vegetal com conseq?ente altera??o do padr?o flor?stico local. A metodologia compreendeu: 1) visitas a campo; 2) aplica??o de question?rios pesquisa comunit?ria; 3) levantamento da bibliografia publicada pelos ?rg?os e institui??es encarregados de executar as pol?ticas de meio ambiente e habita??o no munic?pio; e 4) estat?stica descritiva dos dados coletados. No que se refere ao modelo de ocupa??o predominante no bairro, constatou-se que o tratamento dispensado pelos moradores ao espa?o culminou com o aparecimento e consolida??o de altera??es ambientais distintas de comum ocorr?ncia na ?rea edificada representada pelos conjuntos habitacionais e nas ?reas verdes representadas respectivamente pelas dunas e pelo mangue. Os dados demonstram que durante o povoamento, houve predomin?ncia do processo de ocupa??o irregular sobre a pol?tica oficial de habita??o, colaborando com uma s?rie de problemas freq?entes e previs?veis nas din?micas de urbaniza??o da pobreza como: invas?es e apropria??es de lotes; abertura de arruamentos irregulares; forma??o de vilas e favelas, repletas de unidades habitacionais auto-constru?das e ocupa??o e degrada??o de ?reas de fragilidade ambiental, como as encostas de dunas e os manguezais

Introdução: A privação de sono (PdS) tem sido utilizada como um estratégia alternativa para o tratamento do Transtorno Depressivo Maior (TDM), contudo sua eficácia e efetividade carecem de estudos homogêneos e de bom delinemento para dar um grau de evidência científica para seu uso na prática diária. Assim sendo, desde a primeira publicação, em 1971, num relato de caso de um paciente com TDM grave tipo melancólico, por Plug e Tölle, o mesmo estava assintomático no dia seguinte à privação total de sono. Contudo, na noite seguinte de sono seus sintomas depressivos retornaram. Nestes quase 40 anos desde esta publicação houve dezenas de estudos em sua maioria relatos de caso, série de casos ou até estudos abertos só que misturando pacientes com TDM com Depressão Bipolar sem mesmo distinguir se tipo I ou II. A cafeína com seu efeito estimulador poderia ser uma alternativa para facilitar a privação de sono. No entanto, não há dados sobre o sua potencial influência no efeito antidepressivo da PdS. O objetivo deste estudo é avaliar o efeito da cafeína na PdS em pacientes deprimidos unipolares moderados a graves não psicóticos. Métodos: Ensaio Clínico randomizado, duplo cego, cruzado, comparando cafeína contra placebo em pacientes deprimidos moderados a graves submetidos à privação total de sono (PdS). Os pacientes foram avaliados por itens da escala de Lader, HAMD- 6 itens, CGI Severidade e Melhora Global. Resultados: Foram avaliados 20 pacientes. Os pacientes que usaram cafeína mantiveram o mesmo escore de energia pré e pós-privação de sono (item energético-letárgico da escala de Lader) enquanto os do grupo placebo diminuíram o escore de energia pós-privação de sono. (p = 0,0045). Não houve diferença entre o grupo cafeína e placebo nos demais itens da escala de Lader. Conclusão: O uso combinado de cafeína e PdS pode ser uma estratégia útil para manter os pacientes mais acordados sem o prejuízo do cansaço da PdS em pacientes ambulatoriais deprimidos. Contudo, mais estudos envolvendo pacientes que tenham 10 respondido à PdS são necessários para verificar se a cafeína também não interfere nos resultados deste grupo. / Introduction: Sleep deprivation (SD) has been used as an alternative approach to treat major depressive disorder (MDD), however the efficacy and the effectiveness needs studies with homogeneity and better delineament to strengthen the evidence based medicine to the use in the practical daily use. Besides, since the 1° puplication in 1971 of a case report, by Plug and Tölle, in that one patient with severe melancholic depressive disorder achieved remission in the next day after a total sleep deprivation. However his depressive sintomtology was back after the next night of sleep. Since this almost 40 years, a lot of papers were puplished, and the majority where case report, case reports and open trials with patients with MDD, bipolar depression without make difference between tipe I or II. Caffeine, due to its stimulating effect, could be an alternative to promote sleep deprivation. However, there are no data about its potential influence on the antidepressive effect of SD. The objective of this study is to assess the effect of caffeine on SD in non-psychotic patients with moderate to severe unipolar depression. Methods: Randomized, double-blind, crossover clinical trial comparing caffeine and placebo in moderate to severe depressed patients who underwent total sleep deprivation (SD). The patients were assessed with items of the Bond-Lader Scale, the 6-item Hamilton Depression Rating Scale (HAMD-6), and the Clinical Global Impression (CGI)-Severity/Improvement. Results: Twenty patients participated in this study. The patients who consumed caffeine presented the same score of energy before and after sleep deprivation (lethargicenergetic item of the Bond-Lader scale), while the patients in the placebo group had a reduced score of energy after sleep deprivation (p = 0.0045). There was no difference between the caffeine and placebo groups in the other items of the Bond-Lader scale. Conclusion: The combined use of caffeine and SD can be a useful strategy to keep the 12 patient awake without impairing the effect of SD on depressed outpatients. However, further studies involving patients who have responded to SD are needed in order to verify if caffeine also does not interfere with the results in this group.

La mort soudaine inattendue (SUDEP) est fréquemment rapportée chez les patients qui souffrent d'épilepsie et compte pour près de 17% des décès dans cette population. Bien que son étiologie soit restée longtemps incertaine, des études menées sur des cas de victimes de SUDEP suggèrent fortement l'implication de l'apnée post-ictale dans la survenue de ce type de décès. Afin d'élucider les mécanismes physiopathologique de la SUDEP, il était nécessaire de mettre en place un modèle animal qui présente à la fois des crise spontanées récurrentes comme dans le syndrome épileptique et des altérations respiratoires. Dans une première partie, nous mettons en évidence la présence d'altérations respiratoires (RAs) chez 30 à 50% des rats qui présentent une épilepsie suite à un état de mal épileptique (SE) induit par l'administration de pilocarpine. Ces RAs, que nous avons assimilées à des apnées, ont été mises en évidence par thermochimie respiratoire et se traduisent par une diminution de la consommation en oxygène, dont la durée peut varier entre 20 secondes et 13 minutes. La présence des RAs est associée à des altérations du système sérotoninergique au niveau du tronc cérébral, où sont concentrés la majorité des groupes de neurones impliqués dans la régulation et dans la modulation de la fonction respiratoire. Nous montrons que de nombreux gènes du système sérotoninergique sont dérégulés lors de la mise en évidence des RAs ; toutefois, seules les altérations touchant le récepteur 5-HT2c semblent être associées au maintien des RAs. Ce résultat est d'autant plus important qu'il avait été montré que la délétion de ce récepteur chez les souris peut conduire à un arrêt respiratoire fatal suite à une crise épileptique, provoquée ou spontanée. Dans une seconde partie, nous montrons que la surface de la zone présentant un hypersignal T2 dans le système limbique ventral des rats épileptiques est prédictive de la présence de RAs. En outre, des différences d'expression du récepteur 5-HT2c similaires à celles qui avaient été observées dans le tronc cérébral sont retrouvées entre les rats épileptiques selon qu'ils présentent ou pas des RAs. Les résultats de cette thèse impliquent donc le récepteur 5-HT2c dans la survenue et/ou le maintien des altérations respiratoires associées à l'épilepsie. Dans le contexte de la SUDEP, nos résultats ouvrent comme première perspective clinique celle de développer des traitements permettant de cibler spécifiquement le récepteur 5-HT2c chez les patients qui présenteraient un risque de survenue de la SUDEP. La seconde perspective clinique serait de pouvoir identifier ces patients à risque à partir de biomarqueurs tels que les anomalies de signal T2 que nous avons identifiées dans la région limbique ventrale qui inclut notamment l'insula, dont il a été montré qu'elle contribue à la modulation de la fonction respiratoire / Pas de résumé anglais

The aim of this dissertation is to find out the effect of alterations on market value of he property, specifically apartments in concrete-block buildings. Evaluation is made chiefly on factors influencing layout. First of all brief information about the subject is given. Secondly market influences are determined for the purpose of eliminating them by differential index and unifying input data. Afterwards, market values of apartments with alternations are compared with ones without alternations from database. At the end of the thesis alternations are calculated and recovery of the costs are detected.

Das vom endonasalen Neuroepithel der Rima olfactoria entstandenen Aesthesioneuroblastom gehört zu den seltenen malignen Tumoren der Rhinobasis. Eine generelle Therapieempfehlung für die Behandlung dieses Tumors gibt es nicht, da bis heute etablierte, durch umfassende onkologische Studien untermauerte diagnostische und therapeutische Standards fehlen und der klinische Verlauf oft unberechenbar ist. Die Aufgabe der vorliegenden Arbeit bestand in der Überprüfung des chirurgischen Konzeptes bei der Therapie von Aesthesioneuroblastomen und in der erstmaligen molekularzytogenetischen Charakterisierung von Aesthesioneuroblastomen. Dazu wurden 18 Patienten mit Aesthesioneuroblastomen, die im Zeitraum zwischen 1988 und 2001 in der HNO-Klinik (17 Patienten) sowie in der Neurochirurgischen Klinik des Klinikums Fulda operiert wurden, untersucht. Die daraus resultierenden 22 Aesthesioneuroblastome wurden alle mit Hilfe der Vergleichenden Genomischen Hybridisierung (CGH) analysiert. Nach derzeitigem Kenntnisstand besteht die optimale Therapie der Aesthesioneuroblastome in der chirurgischen Resektion des Tumors mit nachfolgender stereotaktischer Bestrahlung. Für die operative Sanierung der Aesthesioneuroblastome und auch anderer Malignome der vorderen Schädelbasis ist das nachfolgende neue Fuldaer Konzept empfehlenswert: 1) Endonasale Resektion, wenn keine intrakranielle bzw. orbitale Tumorinfiltration vorliegt; 2) Subfrontaler Zugang, bei Infiltration des Gehirns; 3) Midfacial degloving, bei weit lateraler Tumorausbreitung; 4) Laterale Rhinotomie nur bei der Notwendigkeit der simultanen Exenteratio orbitae (bei orbitaler Tumorinfiltration). Aesthesioneuroblastomen sind durch ein typisches genetisches Muster charakterisiert, das Deletionen im Bereich der chromosomalen Arme 1p, 2q, 3p/q, 4p/q, 5p/q, 6q, 8p/q, 9p, 10p/q, 11p, 12q, 13q, 18q und 21q sowie Amplifikationen der Chromosomen 1p, 7q, 9q, 11q, 14q, 16p/q, 17p/q, 19p/q, 20p/q und 22p/q umfasst. Die beim Aesthesioneuroblastom häufigen DNA-Verluste im Bereich der chromosomalen Banden 1p21-p31 scheinen mit der Prognose dieser Tumoren assoziiert zu sein. Die Tumoren aller in der vorliegenden Studie am Malignom verstorbenen Patienten zeigten eine Kombination aus 1p21-p31-Deletion, dem Vorliegen des klinischen Stadiums C oder D sowie gleichzeitig einer schlechten Differenzierung (Grad III oder IV). Vermittels der CGH ist es möglich, eine klonale Zuordnung von Metastasen bzw. auch Rezidiven zu ihren primären Aesthesioneuroblastomen vorzunehmen. Die vorliegende Arbeit zeigt nicht nur neue Ansätze in der chirurgischen Therapie von Aesthesioneuroblastomen sondern auch die erste umfassende molekularzytogenetische Analyse dieser Tumorentität, auf dem Weg, das biologische Verhalten dieser Malignome genauer charakterisieren zu können. / Esthesioneuroblastoma (ENB) is a very rare malignant neoplasm arising from the olfactory epithelium which is recognized for its propensity for local recurrence and distant dissemination. Therapeutic management approaches for this neoplasm lack uniformity. The present study describes therapeutic management in ENB: Complete surgical resection combined with adjuvant stereotactic radiation therapy. Thereby, a new surgical concept is recommended: 1) Endonasal approach in cases without tumor infiltration of the orbit and/or the brain; 2) Subfrontal approach in cases with extended tumor infiltration of the intradural space or of the brain; 3) Midfacial degloving in cases with far lateral tumor spread, particularly fossa pterygoidea or pterygopalatina; 3) Lateral rhinotomy in all cases where an exenteratio orbitae is needed. Secondarily, the study characterizes the specific chromosomal alterations of ENB analyzed using Comparative Genomic Hybridization (CGH). ENB show frequently deletions of chromosoms 1p, 2q, 3p/q, 4p/q, 5p/q, 6q, 8p/q, 9p, 10p/q, 11p, 12q, 13q, 18q and 21q as well as DNA gains of chromosoms 1p, 7q, 9q, 11q, 14q, 16p/q, 17p/q, 19p/q, 20p/q and 22p/q. Deletions of the chromosomal region 1p21-p31 could be associated with bad prognosis since the tumors of all patients who died were of stage C or D and grade III or IV, and showed 1p21-p31 deletions. The analysis of primary ENB and their corresponding metastases shows clonality by a high concordance of alterations between the tumor pairs. For the first time, this study presents the specific chromosomal alterations of ENB pathogenesis and progression.

No description available.

Made available in DSpace on 2014-07-29T15:13:52Z (GMT). No. of bitstreams: 1 Tese_Marcelo_Roza.pdf: 1255109 bytes, checksum: 0fed736dcde7d2550d7d1cd31a009acb (MD5) Previous issue date: 2009-06-22 / Eleven dogs and four cats with buccodental alterations, treated in the Centro Veterinário do Gama, in Brasilia, DF, Brazil, were submitted to cone beam computed tomography. The exams were carried out in a i-CAT tomograph, using for the images acquisition six centimeters height, 40 seconds time, 0,2 voxel, 120 kilovolts (kV) and 46,72 milliampéres per second (mAs). The ideal positioning of the animal for the exam was also determined in this study and it proved to be fundamental for performing the exam, which required a simple and safe anesthetic protocol due to the relatively short time necessary in obtaining the images. Many alterations and diseases had been identified, with extreme accuracy of the images, becoming the cone beam computed tomography as a safe, accessible and feasible imaging method which could be included in the small animals dentistry routine diagnosis / A tomografia computadorizada é uma modalidade de diagnóstico utilizada na odontologia desde a década de 90, que apresenta uma série de vantagens sobre outros exames de imagem, como menor exposição à radiação ionizante, menor tempo na aquisição das imagens, dispensa do processamento químico e menor custo. O exame tomográfico de feixe cônico é empregado na odontologia humana, mas não foram encontrados na literatura consultada trabalhos científicos sobre o assunto. Este estudo teve por objetivo padronizar a tomografia de feixe cônico visando sua utilização na rotina da clínica veterinária de pequenos animais, utilizando pacientes atendidos na rotina clinica odontológica. Na padronização desenvolveu-se primeiramente um dispositivo que possibilitou o posicionamento dos pacientes no tomógrafo de feixe cônico e permitiu a aquisição das imagens de forma correta e sem repetições. Na seqüência estudaram-se os aspectos morfofuncionais da cabeça em cães e gatos e, num segundo momento avaliaram-se alterações dentárias em cães e gatos e temporomandibulares em gatos. O dispositivo desenvolvido e o exame tomográfico de feixe cônico mostraram-se apropriados para avaliar alterações buco dentarias em cães e gatos, podendo ser recomendado para essa finalidade diagnóstica

Les altérations mnésiques associées au trouble de stress post-traumatique (TSPT) constituent un aspect fondamental de la symptomatologie de cette pathologie. Cette altération qualitative de la mémoire inclut à la fois une hypermnésie, c’est-à-dire une intensification de la mémoire vis-à-vis du coeur de l’événement traumatique, et une amnésie de type déclaratif pour les éléments contextuels péri-traumatiques. Les données chez l’Homme suggèrent que ces altérations mnésiques pourraient être sous-tendues par une hyper-activation amygdalienne et un dysfonctionnement hippocampique, respectivement. Cependant, les bases neurobiologiques, et en particulier moléculaires, du TSPT restent largement méconnues. Un modèle comportemental développé chez la souris au laboratoire et basé sur un conditionnement aversif permet précisément de comparer une mémoire de peur normale, c’est-à-dire « contextualisée » et adaptée, à une mémoire pathologique de type TSPT, c’est-à-dire « décontextualisée » et focalisée sur un élément saillant du trauma. Dans la mesure où il a été montré que le développement d’une mémoire de peur contextuelle implique certaines modifications épigénétiques spécifiques, nos travaux ont eu pour objectif de déterminer les altérations des modifications post-traductionnelles d’histones qui sous-tendent le développement d’une mémoire traumatique au lieu d’une mémoire de peur normale. Nos résultats révèlent (1) que des profils spécifiques différents des états d’acétylation/méthylation de l’histone H3 dans le réseau hippocampo-amygdalien sont associés à une mémoire de peur normale et à une mémoire traumatique de type TSPT. Spécifiquement, une mémoire de peur normale est associée à une forte acétylation de H3K9 hippocampique, tandis qu’une mémoire traumatique de type TSPT s’accompagne d’une hyperméthylation de H3K9 dans l’hippocampe, traduisant une répression transcriptionnelle, ainsi que d’une diminution de la tri-méthylation de H3K27 dans l’amygdale latérale, caractéristique d’une activation transcriptionnelle. De plus, nos travaux montrent (2) qu’une modulation pharmacologique de la balance des états d’acétylation/méthylation de H3K9 dans l’hippocampe permet de promouvoir ou de prévenir le développement d’une mémoire traumatique. Enfin, (3) une dernière série d’expériences révèle (i) qu’un stress prénatal est un facteur de risque au développement d’une mémoire traumatique, (ii) que cette dernière est associée à des profils épigénétiques spécifiques, et (iii) qu’une telle vulnérabilité peut se transmettre de manière intergénérationnelle. / Memory alterations associated with post-traumatic stress disorder (PTSD) are a fundamental feature of this pathology. PTSD is characterized both by hypermnesia for simple salient trauma-related stimuli and amnesia for peri-traumatic contextual cues. In humans, this disorder is associated with hippocampal hypofunction and amygdalar hyperfunction, which may underlie such paradoxical memory pattern. However, neurobiological bases of PTSD, particularly at the molecular level, remain largely unknown. A behavioral model based on aversive conditioning was developed in mice by our team. This model allows the comparison between a normal, i.e. “contextualized” and adaptive, fear memory, and a PTSD-like pathological fear memory, i.e. “decontextualized” and focused on a salient cue of the trauma. Since specific epigenetic alterations have been involved in the development of contextual fear memory, our aim was the identification of the alterations in post-translational histone modifications underlying the development of traumatic memory instead of normal fear memory. Our results first reveal that normal and PTSD-like fear memory are associated with distinct acetylation/methylation profiles of histone H3 in the hippocampal-amygdalar network. Specifically, we show that, compared to normal fear memory, PTSD-like memory is associated with a switch from H3K9 hyperacetylation (marker of transcriptional activation) to H3K9 hypermethylation (marker of transcriptional repression) in hippocampal CA1, as well as a significant reduction of H3K27 trimethylation, which results in an increased transcription, in the lateral amygdala. Second, we show that the pharmacological manipulation of the acetylation/methylation balance of H3K9 in the hippocampus can prevent or promote the development of PTSD-like memory. Finally, a last series of experiments shows that (i) prenatal stress is a risk factor for the development of PTSD-like memory, (ii) which is associated with specific epigenetic alterations and (iii) that such vulnerability to stress can be transmitted to subsequent generations.

[ES] El síndrome de dolor regional complejo (SDRC) es un trastorno de dolor crónico debilitante que suele afectar a una extremidad, y se caracteriza por su compleja e incomprendida fisiopatología subyacente, lo que supone un reto para su diagnóstico y tratamiento. Para evitar el deterioro de la calidad de vida de los pacientes, la consecución de un diagnóstico y tratamiento tempranos marca un punto de inflexión. Entre los diferentes tratamientos, los bloqueos simpáticos lumbares (BSLs) tienen como objetivo aliviar el dolor y reducir algunos signos simpáticos de la afección. Este procedimiento intervencionista se lleva a cabo inyectando anestesia local alrededor de los ganglios simpáticos y, hasta ahora, se realiza frecuentemente bajo el control de diferentes técnicas de imagen, como los ultrasonidos o la fluoroscopia. Dado que la termografía infrarroja (TIR) ha demostrado ser una herramienta eficaz para evaluar la temperatura de la piel, y teniendo en cuenta el efecto vasodilatador que presentan los anestésicos locales inyectados, se ha considerado el uso de la IRT para la evaluación de los BSLs. El objetivo de esta tesis es, estudiar la capacidad de la TIR como una técnica complementaria para la evaluación de la eficacia en la ejecución de los BSLs. Para cumplir este objetivo, se han realizado tres estudios implementando la TIR en pacientes diagnosticados de SDRC de miembros inferiores sometidos a BSLs. El primer estudio se centra en la viabilidad de la TIR como herramienta complementaria para la evaluación de la eficacia ejecución de los BSLs. Cuando se realizan los BSLs, la colocación correcta de la aguja es crítica para llevar realizar el procedimiento técnicamente correcto y, en consecuencia, para lograr los resultados clínicos deseados. Para verificar la posición de la aguja, tradicionalmente se han utilizado técnicas de imagen, sin embargo, los BSLs bajo control fluoroscópico no siempre aseguran su exacta ejecución. Por este motivo, se han aprovechado las alteraciones térmicas inducidas por los anestésicos locales y se han evaluado mediante la TIR. Así, cuando en las imágenes infrarrojas se observaron cambios térmicos en la planta del pie afectado tras la inyección de lidocaína, se consideró que el BSL era exitoso. El segundo estudio trata del análisis cuantitativo de los datos térmicos recogidos en el entorno clínico a partir de diferentes parámetros basados en las temperaturas extraídas de ambos pies. Según los resultados, para predecir adecuadamente los BSLs exitosos, se deberían analizar las temperaturas de las plantas de los pies durante los primeros cuatro minutos tras la inyección del anestésico local. Así, la aplicación de la TIR en el entorno clínico podría ser de gran ayuda para evaluar la eficacia de ejecución de los BSLs mediante la evaluación de las temperaturas de los pies en tiempo real. Por último, el tercer estudio aborda el análisis cuantitativo mediante la implementación de herramientas de machine learning (ML) para evaluar su capacidad de clasificar automáticamente los BSLs. En este estudio se han utilizado una serie de características térmicas extraídas de las imágenes infrarrojas para evaluar cuatro algoritmos de ML para tres momentos diferentes después del instante de referencia (inyección de lidocaína). Los resultados indican que los cuatro modelos evaluados presentan buenos rendimientos para clasificar automáticamente los BSLs entre exitosos y fallidos. Por lo tanto, la combinación de parámetros térmicos junto con de clasificación ML muestra ser eficaz para la clasificación automática de los procedimientos de BSLs. En conclusión, el uso de la TIR como técnica complementaria en la práctica clínica diaria para la evaluación de los BSLs ha demostrado ser totalmente eficaz. Dado que es un método objetivo y relativamente sencillo de implementar, puede permitir que los médicos especialistas en dolor identifiquen los bloqueos realizados fallidos y, en consecuencia, puedan revertir esta situación. / [CA] La síndrome de dolor regional complex (SDRC) és un trastorn de dolor crònic debilitant que sol afectar una extremitat, i es caracteritza per la seua complexa i incompresa fisiopatologia subjacent, la qual cosa suposa un repte per al seu diagnòstic i tractament. Per a evitar la deterioració de la qualitat de vida dels pacients, la consecució d'un diagnòstic i tractament primerencs marca un punt d'inflexió. Entre els diferents tractaments , els bloquejos simpàtics lumbars (BSLs) tenen com a objectiu alleujar el dolor i reduir alguns signes simpàtics de l'afecció. Aquest procediment intervencionista es duu a terme injectant anestèsia local al voltant dels ganglis simpàtics i, fins ara, es realitza freqüentment sota el control de diferents tècniques d'imatge, com els ultrasons o la fluoroscopia. Atés que la termografia infraroja (TIR) ha demostrat ser una eina eficaç per a avaluar la temperatura de la pell, i tenint en compte l'efecte vasodilatador que presenten els anestèsics locals injectats, s'ha considerat l'ús de la TIR per a l'avaluació dels BSLs. L'objectiu d'aquesta tesi és, estudiar la capacitat de la TIR com una tècnica complementària per a l'avaluació de l'eficàcia en l'execució dels BSLs. Per a complir aquest objectiu, s'han realitzat tres estudis implementant la TIR en pacients diagnosticats de SDRC de membres inferiors sotmesos a BSLs. El primer estudi avalua la viabilitat de la TIR com a eina complementària per a l'analisi de l'eficàcia en l'execució dels BSLs. Quan es realitzen els BSLs, la col·locació correcta de l'agulla és crítica per a dur a terme el procediment tècnicament correcte i, en conseqüència, per a aconseguir els resultats clínics desitjats. Per a verificar la posició de l'agulla, tradicionalment s'han utilitzat tècniques d'imatge, no obstant això, els BSLs baix control fluoroscòpic no sempre asseguren la seua exacta execució. Per aquest motiu, s'han aprofitat les alteracions tèrmiques induïdes pels anestèsics locals i s'han avaluat mitjançant la TIR. Així, quan en les imatges infraroges es van observar canvis tèrmics en la planta del peu afectat després de la injecció de lidocaIna, es va considerar que el BSL era exitós. El segon estudi tracta de l'anàlisi quantitativa de les dades tèrmiques recollides en l'entorn clínic a partir de diferents paràmetres basats en les temperatures extretes d'ambdós peus. Segons els resultats, per a predir adequadament l'execució exitosa d'un BSL, s'haurien d'analitzar les temperatures de les plantes dels peus durant els primers quatre minuts després de la injecció de l'anestèsic local. Així, l'implementació de la TIR en l'entorn clínic podria ser de gran ajuda per a avaluar l'eficàcia d'execució dels BSLs mitjançant l'avaluació de les temperatures dels peus en temps real. El tercer estudi aborda l'anàlisi quantitativa mitjançant la implementació d'eines machine learning (ML) per a avaluar la seua capacitat de classificar automàticament els BSLs. En aquest estudi s'han utilitzat una sèrie de característiques tèrmiques extretes de les imatges infraroges per a avaluar quatre algorismes de ML per a tres moments diferents després de l'instant de referència (injecció de lidocaïna). Els resultats indiquen que els quatre models avaluats presenten bons rendiments per a classificar automàticament els BSLs en exitosos i fallits. Per tant, la combinació de paràmetres tèrmics juntament amb models de classificació ML mostra ser eficaç per a la classificació automàtica dels procediments de BSLs. En conclusió, l'ús de la TIR com a tècnica complementària en la pràctica clínica diària per a l'avaluació dels BSLs ha demostrat ser totalment eficaç. Atés que és un mètode objectiu i relativament senzill d'implementar, pot ajudar els metges especialistes en dolor a identificar els bloquejos realitzats fallits i, en conseqüència, puguen revertir aquesta situació. / [EN] Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that usually affects one limb, and it is characterized by its misunderstood underlying pathophysiology, resulting in both challenging diagnosis and treatment. To avoid the patients' impairment quality of life, the achievement of both an early diagnosis and treatment marks a turning point. Among the different treatment approaches, lumbar sympathetic blocks (LSBs) are addressed to alleviate the pain and reduce some sympathetic signs of the condition. This interventional procedure is performed by injecting local anaesthetic around the sympathetic ganglia and, until now, it has been performed under different imaging techniques, including the ultrasound or the fluoroscopy approaches. Since infrared thermography (IRT) has proven to be a powerful tool to evaluate skin temperatures and taking into account the vasodilatory effects of the local anaesthetics injected in the LSB, the use of IRT has been considered for the LSBs assessment. Therefore, the purpose of this thesis is to evaluate the capability of IRT as a complementary assessment technique for the LSBs procedures performance. To fulfil this aim, three studies have been conducted implementing the IRT in patients diagnosed with lower limbs CRPS undergoing LSBs. The first study focuses on the feasibility of IRT as a complementary assessment tool for LSBs performance, that is, for the confirmation of the proper needle position. When LSBs are performed, the correct needle placement is critical to carry out the procedure technically correct and, consequently, to achieve the desired clinical outcomes. To verify the needle placement position, imaging techniques have traditionally been used, however, LSBs under radioscopic guidance do not always ensure an exact performance. For this reason, the thermal alterations induced by the local anaesthetics, have been exploited and assessed by means of IRT. Thus, the LSB procedure was considered successfully performed when thermal changes within the affected plantar foot were observed in the infrared images after the lidocaine injection. The second study deals with the quantitative analysis of the thermal data collected in the clinical setting through the evaluation of different temperature-based parameters extracted from both feet. According to the results, the proper LSB success prediction could be achieved in the first four minutes after the block through the evaluation of the feet skin temperatures. Therefore, the implementation of IRT in the clinical setting might be of great help in assessing the LSBs performance by evaluating the plantar feet temperatures in real time. Finally, the third study addresses the quantitative analysis by implementing machine learning (ML) tools to assess their capability to automatically classify LSBs. In this study, a set of thermal features retrieved from the infrared images have been used to evaluate four ML algorithms for three different moments after the baseline time (lidocaine injection). The results indicate that all four models evaluated present good performance metrics to automatically classify LSBs into successful and failed. Therefore, combining infrared features with ML classification models shows to be effective for the LSBs procedures automatic classification. In conclusion, the use of IRT as a complementary technique in daily clinical practice for LSBs assessment has been evidenced entirely effective. Since IRT is an objective method and it is not very demanding to perform, it is of great help for pain physicians to identify failed procedures, and consequently, it allow them to reverse this situation. / Cañada Soriano, M. (2022). Infrared Thermography for the Assessment of Lumbar Sympathetic Blocks in Patients with Complex Regional Pain Syndrome [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/181699

In dieser Arbeit, wurden Endozytose und intrazellulären Transportwegen für zwei verschiedene biologisch relevante Nanopartikel (dendritisch Polyglycerolsulfat (dPGS-np) und Polyethylenimin beschichtete Goldnanopartikel (PEI-np)) mit Kryo-Röntgentomographie untersucht. Diese Untersuchungen zeigten, beide Nanopartikeln über Makropinozytose endozytiert werden und dass die meisten Nanopartikel in Endosomen, multivesikulären Körpern und Lysosomen lokalisiert sind. Trotz dieser Ähnlichkeiten im Verhalten beider Partikel gab es auch Unterschiede die zeigten. Im Gegensatz zu PEI-np, wurden einige dPGS-np in Lipidtröpfchen gefunden. Weiterhin verursachen die PEI-np bei einer Konzentration von 0,13 nM ein Zerplatzen von Lysosomen in erheblichem Ausmaß wodurch die Nanopartikel in das Zytoplasma entweichen und teilweise in den Zellkern eindringen. Im Unterschied dazu konnte kein Nachweis für ein Zerplatzen von Lysosomen durch dPGS-np erbracht werde. Interessanterweise wurde ein Wechsel des Endocytose-Weges von der Makropinozytose zu einer mutmaßlichen Caveolae-vermittelten Endozytose beobachtet, wenn die PEI-np-Konzentration um das Zehnfache reduziert wurde. Unter diesen Bedingungen induzierten PEI-np kein Zerplatzen von Lysosomen mehr. Das Ausbleiben von zerplatzten Lysosomen bei dieser niedrigeren Konzentration korreliert mit einer verringerten Zellschädigung und hat somit wichtige Auswirkungen auf die Verwendung von PEI beim Gentransfer. Überraschenderweise stellte sich heraus, dass beide Nanopartikelarten eine bisher nicht beobachtete umfassende zytoplasmatische Veränderungen in den Zellen induzierten. Insbesondere wurden nach der Inkubation mit beiden Diese zytoplasmatischen Veränderungen könnten wichtige physiologische Veränderungen widerspiegeln, jedoch ist hierzu zusätzliche Forschung erforderlich. Diese Beobachtungen deuten darauf hin, dass das Verhalten biologisch relevanter Nanopartikel in Zukunft vorhersehbarer werden kann durch weitere systematische Studien. / In this thesis, the endocytosis and trafficking pathways of two different biologically relevant nanoparticles, namely dendritic polyglycerol sulfate coated gold nanoparticles (dPGS-np) and polyethyleneimine coated gold nanoparticles (PEI-np) were investigated via cryo soft X-ray tomography. Both nanoparticles were found to be endocytosed predominantly via macropinocytosis, and most nanoparticles became localized to endosomes, multivesicular bodies and lysosomes. Despite these similarities in trafficking, there were also key differences. Some dPGS-np were found in lipid droplets but no PEI nanoparticles were found in this compartment. At a concentration of 0.13 nM, PEI-np were observed to induce extensive rupture of lysosomes, leading to significant levels of cytoplasmic escape and nuclear entry. In contrast, no evidence for lysosomal rupture with dPGS-np was detected, and concomitantly very low levels of cytoplasmic escape and no nuclear entry were found. Interestingly, when the PEI-np concentration was reduced by ten-fold, a switch in the endocytosis pathway from macropinocytosis to a putative caveolae-mediated endocytosis was observed. Importantly, under these conditions, PEI nanoparticles no longer induced lysosomal rupture. This lack of lysosomal rupture at the lower concentration was correlated with reduced cellular damage, and so has important implications for use of PEI in gene delivery. Most surprisingly, both nanoparticle types were found to induce similar global cytoplasmic alterations in the cells. These cytoplasmic alterations could reflect important physiological changes, but further work is required to determine this. Our observations suggest that the behavior of biologically relevant nanoparticles might become more predictable in the future by further application of systematic studies.