Mutation and over-expression of Receptor Tyrosine Kinases (RTKs) or the proteins they regulate serve as oncogenic drivers in diverse cancers. RTKs catalyze the transfer of phosphate from ATP to the hydroxyl group on tyrosine. The proximal stretch of amino acids including this post translational modification is then able to be recognized by SH2 and PTB domains. Chapter 1 details our work to better understand RTK signaling and its link to oncogenesis using protein microarrays to systematically and quantitatively measure interactions between virtually every SH2 or PTB domain encoded in the human genome and all known sites of tyrosine phosphorylation on 40 out of the 53 Receptor Tyrosine Kinases. Chapter 2 expands upon this work to study the next layer of binding among SH2 and PTB domain-containing adaptor proteins themselves. We found that adaptor proteins, like RTKs, have many high affinity bindings sites for other adaptor proteins. In addition, proteins driving oncogenesis, including both receptors and adaptor proteins, tend to be highly interconnected via a network of SH2 and PTB domain-mediated interactions. Our results suggest that network topological properties such as connectivity can be used to prioritize new drug targets in these well-studied signaling networks. Despite the extensive work presented here on experimentally determining interactions, we nevertheless are unable to keep up with the discovery of new sites of tyrosine phosphorylation by high throughput mass spectrometry as well as their mutation in cancer discovered by next generation tumor sequencing approaches. Chapter 3 introduces work in progress to build a unified predictive model of SH2 domain interactions via integration of diverse data sets of binding as well as crystal structures of domain-peptide interactions. This model will enable researchers discovering new phosphorylation events or mutations to be able to predict potential interaction partners and thereby elucidate novel functional mechanisms. / Chemistry and Chemical Biology

No description available.

Introduction: Conventional suture repair of peripheral nerves following injury is associated with several limitations such as technical difficulty, intra- and extra-neural scar formation, axonal escape and the leakage of neurotrophic factors. These limitations are particularly relevant following nerve grafting when regenerating axons must traverse two coaptation sites. Outcomes following suture repair are notoriously poor, providing large impetus for the development of alternative methods. Photochemical tissue bonding (PTB) uses visible light to create sutureless, non-thermal bonds between two closely apposed tissue surfaces stained with a photoactive dye. When used with a human amnion nerve wrap for end-to end nerve repair, this technique results in superior functional and histological outcomes in comparison to conventional epineurial suture. When initially applied to large gap injury and nerve grafting, outcomes were unsuccessful due to proteolytic degradation of amnion and photochemical bonds during extended periods of recovery. Chemical crosslinking of nerve wraps prior to PTB may improve wrap durability and efficacy of technique. This thesis provides a comprehensive three-phase assessment of the efficacy of this novel approach when applied to the repair of large gap injuries with nerve grafts. Phase 1 assesses the ex vivo biomechanical properties of nerve wraps and light activated bonds in addition to the in vivo performance of photochemically sealed crosslinked nerve wraps against several other clinically relevant fixation methods in a rodent sciatic nerve isograft model. Following major multi-limb injury and amputation, demand for autogenous nerve graft may exceed that which can be supplied by the patient. Acellular nerve allograft (ANA) is an alternative option in these circumstances although outcomes are typically inferior to autograft. Phase 2 assesses the performance of the optimum repair strategy from phase 1 against conventional epineurial suture when applied to ANA. Most studies investigating the efficacy of novel repair techniques tend to perform repairs immediately following injury, a situation that rarely occurs clinically. Delays of weeks or months are not uncommon and have been shown to have a detrimental effect on regeneration and outcome. Phase 3 assesses the efficacy of PTB when applied to delayed nerve grafting. Additional work investigating a novel imaging technique for visualizing nerve revascularisation following injury and repair has been included. Optical frequency domain imaging (OFDI) uses low power infrared light to provide real time in vivo imaging of tissue microvasculature and flow characteristics. Originally applied to the study of tumour biology, this technique may prove useful for outcome assessment in preclinical research and eventually for the assessment of nerve viability in the clinical setting. Experiments investigating the early development of a brain body interface system (BBI) for upper limb reanimation following spinal cord injury (SCI) have also been included. The ultimate aim of this project is to restore autonomous motor control in a non-human primate (NHP) using cortically driven stimulation of peripheral nerves via implantable nerve cuffs. The experiments reported in this thesis detail the development of a selective, reversible paralysis model of elbow flexion in a NHP and demonstrate selective fascicular stimulation using acute and chronically implanted nerve cuffs in rodent and murine models. Methods: Phase 1: Three candidate nerve wraps (human amnion (HAM), crosslinked human amnion (xHAM), crosslinked swine intestinal sub-mucosa (xSIS)) and 3 fixation methods (suture, fibrin glue, PTB) were investigated. Crosslinking was performed using (1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC)/N-hydroxysuccinimide (NHS). Biomechanical tests were performed using a tensiometer. Ex vivo wrap durability was assessed using a type- 2 collagenase degradation assay. Under isoflurane anaesthesia, 110 inbred male Lewis rats had 15mm left sciatic nerve defects created and repaired with reversed isografts. 9 groups (n=10) had isografts secured by one of the aforementioned wrap/fixation combinations. PTB repairs had nerve wraps and nerve ends stained with photoactive dye (Rose Bengal) and, once nerve ends were apposed and wrapped circumferentially, the interface was illuminated with a 532nm laser. Fibrin repairs had nerve ends apposed, wrapped circumferentially and secured with Tisseel fibrin glue. Suture repairs had nerve ends apposed, wrapped circumferentially and then secured with two 10-0 nylon sutures at each coaptation site (one either side of each repair). Positive and negative control groups (n=10) were repaired with graft+suture (10-0 nylon) and no repair respectively. Phase 2: 20 sciatic nerves were harvested from Sprague Dawley rats and sent to AxoGen Inc. for decellularisation. An additional 20 male inbred Lewis rats were randomized into 2 groups (n=10). All rats had 15mm left sciatic nerve defects created and repaired with processed ANA. 1 group had nerves secured using conventional epineurial suture. The remaining group had ANA secured using photochemically sealed amnion wraps. Phase 3: 40 inbred male Lewis rats were randomized into 4 groups (n=10). All 40 rats had 15mm left sciatic nerve gaps created and reconstructed with reversed isografts harvested from donor Sprague Dawley rats. In groups 1 and 2, nerve gaps were repaired immediately with either conventional epineurial suture or photochemically sealed amnion wraps, respectively. In groups 3 and 4, repair took place 30- days following injury using either conventional epineurial suture or photochemically sealed amnion wraps, respectively. All outcomes were assessed using walking track analysis and calculation of sciatic function index (SFI). Walking track analysis and SFI was performed pre-operatively, after the 30-day delay (phase 3) and at 30-day intervals following surgery. Following sacrifice after 5-months, left (experimental) and right (control) gastrocnemius muscles were excised and weighed for calculation of muscle mass retention. Nerves were excised for histomorphometric analysis including axon count, fiber diameter, axon diameter, myelin thickness and G-ratio. For all in vivo experiments, statistical analysis was performed using ANOVA, repeated measures ANOVA and the post hoc Bonferroni test. Optical Frequency Domain Imaging (OFDI) pilot study: eight rodents were randomized into 4 groups (n=2): (1) crush injury, (2) transection and end-to-end repair, (3) transection and repair of 10mm nerve gap using contralateral autograft, (4) transection and repair of 10mm nerve gap using ANA. Under ketamine/xylazine anaesthesia, all rodents had sciatic nerves exposed through hind limb dorsolateral incisions. Imaging was performed immediately pre-injury, immediately post-injury and on post-operative days 1, 3, 5 and 7. Rodents were secured firmly to polystyrene platforms in order to reduce movement artifact during imaging Brain-Body Interface (BBI) experiments: In the upper limb of a Rhesus macaque nonhuman primate, the median nerve branch to brachialis and radial nerve branch to brachioradialis were transected, leaving elbow flexion entirely reliant on the musculocutaneous nerve. The musculocutaneous nerve was transposed into a subcutaneous position. Ultrasound guided nerve block resulted in a highly selective, reversible paralysis of elbow flexion. Under ketamine/xylazine anaesthesia, Sprague Dawley rats (n=5) and C57 Black 6 mice (n=5) had sciatic nerves exposed through dorsolateral, muscle splitting incisions. 8-channel stimulating cuff electrodes were wrapped around sciatic nerves and connected to a Tucker14 Davies stimulation/recording system. Electromyography (EMG) needle electrodes were inserted into the tibialis anterior (TA) and gastrocnemius (G) muscles to record muscle activity.

L'épissage alternatif des pré-ARN messagers est un mécanisme qui permet de générer une très grande diversité protéique chez les eucaryotes supérieurs. La sélection des sites d'épissage permet ainsi de produire certains isoformes protéiques plutôt que d'autres dans des conditions précises. Cette modulation implique généralement la participation d'une multitude de facteurs aux propriétés parfois synergiques et/ou antagonistes. Dans le cas du pré-ARN messager hnRNP A1, au moins trois éléments distincts renforcent l'exclusion de l'exon 7B. Par contre, l'élément intronique conservé de 38 nt (CE9) situé en aval de l'exon 7B permet la répression du site d'épissage 3', ce qui entraînerait l'inclusion de l'exon 7B. La portion 5' de l'élément CE9 est liée par la protéine SRp30c et cette interaction est importante pour permettre l'activité de CE9 in vitro. Afin de déterminer les composantes essentielles à l'activité de répression de SRp30c, des sites de liaison de haute affinité pour cette protéine ont été identifiés à l'aide de la procédure"SELEX". Les résultats obtenus indiquent que plusieurs sites de haute affinité reproduisent l'activité de l'élément CE9 complet dans un essai d'épissage où deux sites d'épissage 3' sont en compétition pour un seul site d'épissage 5'. De plus, les résultats suggèrent une contribution de la portion 3' de CE9, en plus de la partie 5', pour la liaison de la protéine SRp30c. En utilisant la séquence complète de CE9 pour effectuer une chromatographie d'affinité, la protéine hnRNP UPTB a été isolée et identifiée par spectrométrie de masse. Cependant, nous avons été surpris de constater que la protéine recombinante PTB agit comme activateur du site d'épissage 3' en diminuant l'activité de répression de CE9. Ces résultats suggèrent donc un nouveau rôle pour la protéine PTB, c'est-à-dire comme anti-répresseure de l'activité d'inhibition de SRp30c. PTB pourrait donc être un nouveau facteur capable de contrôler l'épissage alternatif du pré-ARN messager de hnfP A1.

L'inactivation du chromosome X correspond au silence transcriptionnel de l'un des deux chromosomes X dans les cellules des mammifères femelles. Il s'agit d'un mécanisme de compensation du dosage du chromosome X qui assure un taux d'expression des gènes liés aux chromosomes X équivalent entre organismes mâles (XY) et femelles (XX). Elle débute par une accumulation de l'ARN Xist (X inactive specific transcript) sur le chromosome X qui sera inactivé (Xi). Elle est suivie très rapidement par des modifications des histones qui assurent l'établissement, le maintien et la transmission de l'état transcriptionnel inactif de la chromatine. L'ARN Xist comprend plusieurs régions d'éléments répétés et notamment la région des A-repeats, essentielle pour la mise en place de l'inactivation. Mes recherches se sont portées sur l'étude de cette région singulière : sa structure et ses interactions protéiques. La technique de FRET (Fluorescence Resonance Energy Transfer) appliquée à l'ARN nous a permis de confirmer la structure de cette région parmi 3 modèles possibles. Elle se structure en deux tiges-boucles formée par l'appariement 2 à 2 de 4 répétitions successives. Dans une seconde partie, j'ai caractérisé l'interaction de cette région avec certains de ses partenaires protéiques in vitro. La région des A-repeats interagit notamment de manière directe avec les protéines PTB, KSRP et ASF/SF2. Les 2 premières protéines pourraient avoir un rôle dans la stabilité de l'ARN tandis qu'ASF/SF2 serait impliquée dans la maturation de l'ARN X / X-chromosome inactivation is the transcriptional silencing of one of the two X chromosomes in female mammal cells. This mechanism of dosage compensation ensures an equal level of the X-linked genes expression between males (XY) and females (XX). It initiates with the accumulation of the Xist RNA (X inactive specific transcript) on the futur inactive X chromosome (Xi). It is followed by the apposition of epigenetic marks such as histone modifications, that ensure establishment, maintenance and transmission of the inactive state of the chromatin. Xist RNA comprises a number of repeated regions and, in particular to its 5' end the A region, absolutely necessary for the establishment of the X-inactivation. My research was focused on the study of this singular region: its structure and its protein interactions. The FRET method (Fluorescence Resonance Energy Transfer) applied to RNA allowed us to ascertain that the RNA is structured in two long stem-loop structures each including four repeats. In a second part, I characterized the in vitro interaction of this region with some of its protein partners. The A region interacts directly with PTB, KSRP and ASF/SF2 proteins. The first two proteins may have a role in RNA stability whereas ASF/SF2 could be involved in the splicing process

Made available in DSpace on 2015-03-03T19:30:55Z (GMT). No. of bitstreams: 0 Previous issue date: 28 / Universidade do Vale do Rio dos Sinos / A criação do Partido Trabalhista Brasileiro (PTB) marcou profundamente a política no Rio Grande do Sul no período 1945-64. Com uma tradição de bipolaridade, a política gaúcha daquele contexto se caracterizou pela oposição entre um campo mais progressista, representado pelo PTB, e outro conservador, liderado pelo Partido Social Democrático (PSD). Neste estudo buscamos analisar a atuação do PTB nas eleições estaduais de 1947, recorrendo para isso a elementos da teoria do campo político desenvolvida por Pierre Bourdieu. Procuramos compreender a trajetória inicial e o tipo de capital político que o partido então acumulou. As fontes utilizadas são os periódicos da época, artigos, entrevistas e depoimentos de lideranças partidárias, bem como um conjunto de cartas trocadas entre as mesmas. Uma possível contribuição do presente trabalho será evidenciar a importância que aquela disputa eleitoral assumiu no processo de formação do PTB gaúcho, especialmente por se tratar de um momento privilegiado para a criação de símb / The foundation of the Partido Trabalhista Brasileiro (PTB) – “Brazilian Labor Party” – deeply marked the politics in Rio Grande do Sul from 1945 to 1964. With bipolarity tradition the gaucha politics of those decades was defined by the conflict between a more progressive posture, represented by the PTB, and a more conservative one, leaded by the Partido Social Democrático (PSD) – “Social Democratic Party”. The present study intends to analyze the role PTB played at the gubernatorial elections of 1947, based on aspects from Pierre Bourdieu’s political field theory. This study also seeks understanding the initial trajectory and the political capital the party accumulated at that time. The sources were periodic newspapers, articles, interviews and declarations of leading parties and a set of letters traded between them as well. A possible contribution of this study might be proving the importance of that particular political dispute had in the foundation process of the “gaucho” PTB mainly for being such a propi

Submitted by PPG Ci?ncias Sociais (csociais-pg@pucrs.br) on 2018-10-25T19:12:11Z No. of bitstreams: 1 M?rcio_Soares_ Rodrigues_Dis.pdf: 1650077 bytes, checksum: f295f0bb4fc140f92ad684e3b5956a9d (MD5) / Approved for entry into archive by Sheila Dias (sheila.dias@pucrs.br) on 2018-10-26T13:46:49Z (GMT) No. of bitstreams: 1 M?rcio_Soares_ Rodrigues_Dis.pdf: 1650077 bytes, checksum: f295f0bb4fc140f92ad684e3b5956a9d (MD5) / Made available in DSpace on 2018-10-26T13:52:24Z (GMT). No. of bitstreams: 1 M?rcio_Soares_ Rodrigues_Dis.pdf: 1650077 bytes, checksum: f295f0bb4fc140f92ad684e3b5956a9d (MD5) Previous issue date: 2018-02-28 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / The main purpose of this research is to answer the following question: what were the factors that influenced the members of the MDB party to choose between PMDB or PDT when the multiparty system was restored in the late 1970? We intended to answer that question in two parts. First, we will do a historical analysis that goes from the multiparty system period - that began after the ?Estado Novo? regime - until the final moments of the bipartisanship system, in order to, as proposed by Panebianco (2005), prioritize the analysis of the foundation of the political parties, especially the sections of PTB and MDB from Rio Grande do Sul, as well as its development in such an unusual context as an opposing party, seeking to know how power were distributed in both organizations and the consequences of this interaction when the MDB party was extinguished. Then, we will analyze the political history of the MDB members from the elite of Rio Grande do Sul, searching for patterns in their political careers that may elucidate the choices between the two parties, highlighting the MDB leaders that have decided to join PMDB or PDT. Based on the journalistic coverage of the newspapers ?Zero Hora? and ?Folha da Tarde? from that period of time, we will also investigate how those leaders publicly justified their decision, in order to, considering the Panebianco (2005) study of the collective and selective incentives, verify if they use ideological and/or doctrinal arguments to explain their decisions, according to the narrative structured by the main leaders of those two political parties in that time: Leonel Brizola and Pedro Simon. / A presente disserta??o tem como objetivo principal responder ? seguinte quest?o: quais fatores colaboraram para a defini??o dos emedebistas ga?chos pelo PMDB ou PDT quando do retorno ao pluripartidarismo no final da d?cada de 1970? Buscamos responder das seguintes formas. Primeiro, faremos uma an?lise hist?rica do per?odo pluripartid?rio que se inicia ap?s o Estado Novo at? os momentos finais do bipartidarismo, visando assim, conforme proposto por Panebianco (2005), priorizar a an?lise do momento de nascimento das legendas, principalmente as se??es ga?chas do PTB e do MDB, bem como seu desenvolvimento em um contexto t?o at?pico para uma legenda oposicionista, buscando conhecer a estrutura e forma como o poder era distribu?do dentro de ambas ?s organiza??es, assim como a consequ?ncia desta intera??o no momento da extin??o do MDB. Segundo, atrav?s da an?lise da trajet?ria pol?tica da elite emedebista do Rio Grande do Sul, buscaremos encontrar padr?es de carreiras pol?ticas que possam elucidar a escolha da agremia??o a ser adotada com o retorno do pluripartidarismo, priorizando assim aqueles l?deres emedebistas que caminham para o PMDB ou o PDT. Com base na cobertura jornal?stica dos jornais Zero Hora e Folha da Tarde do per?odo, vamos analisar ainda como os l?deres emedebistas justificaram publicamente suas decis?es a respeito dos partidos adotados com a extin??o do MDB, visando assim, com base nos incentivos coletivos e seletivos de Panebianco (2005), verificar se estes utilizam de argumentos ideol?gicos e/ou doutrin?rios para explicar suas decis?es, conforme a narrativa constru?da pelos principais l?deres das duas legendas no per?odo, Leonel Brizola e Pedro Simon.

Mes travaux ont porté sur l'étude de deux familles de protéines de liaison à l'ARN, la famille des ARE-BP (AU-rich elements binding protein) et la famille des PTB (Polypyrimidine tract binding protein) au cours du développement chez le xénope. L'étude de l'expression de cinq membres de la famille ARE-BP a mis en évidence une redondance d'expression tissulaire et temporelle entre quatre de ces ARE-BP (AUF1, KSRP, HuR et TIA1). A l'inverse, l'expression atypique de TTP a permis de suggérer son implication dans l'hématopoïèse. Mes travaux sur la famille PTB (PTBP1, PTBP2, PTBP3) ont montré que chacun des paralogues présente une expression spécifique ce qui suggère qu'elles aient des fonctions différentes lors du développement. Des résultats du laboratoire montraient que l'inactivation de PTBP1 ou de EXOSC9, un composant de l'exosome ARN, entraînait des défauts de morphogenèse de l'épiderme dorsal. Afin d'identifier l'origine moléculaire de ces défauts, j'ai réalisé l'analyse transcriptomique par séquençage à haut débit (RNA-Seq) des morphants PTBP1 et EXOSC9. J'ai produit des banques d'ADNc à partir des morphants ou d'embryons témoins et celles-ci ont été séquencées au Génoscope. L'analyse d'une cible connue de PTBP1 a montré que des modifications minoritaires de l'épissage étaient détectées à partir de ces données. De plus ces défauts d'épissage ne sont pas retrouvés dans les morphants EXOSC9, validant son utilisation comme crible additionnel permettant d'exclure les évènements d'épissage qui ne sont pas impliqués dans le défaut d'épiderme. Une approche gène candidat a été initiée afin de cibler l'analyse de transcrits impliqués dans la morphogenèse de l'épiderme dorsale.

This study emphasizes the exercise of power and its influence in society, based on two periodicals, Fôlha Trabalhista, linked to the Brazilian Labor Party Partido Trabalhista Brasileiro PTB, produced in the countryside of the State and Fôlha Popular, promoter of the actions of the political party PCB, that circulated in the capital from 1961 to 1964. It aims to understand the position of these periodicals in relation to the debate about the thinking and political actions of the forces such as the Left, (Laboring and Communism), focusing on the performance in the Sergipe State. This research is aimed by the methodology of the periodical criticism in its different parts, such as the social articles, newspaper articles, advertising, as well as the editorials focusing on national politics themes. This study emphasize that the press is the representation of reality and not the faithful portrait of reality, but of selected moments of reality, such as the process of selection of what is published in the newspapers is determined by their own journalistic criteria, which in turn are motivated by the political ideology in which the press is associated. It is important to emphasize that there were newspapers articles in 1962 that already denounced the eminence of a rightist coup. That would implement a terrorist dictatorship by the service of the most foreigner and national “infamous forces”, placing the economy in dependence on the United States. / Esse estudo enfatiza o exercício de poder e a sua influência na sociedade, a partir de dois periódicos, a saber, Fôlha Trabalhista, órgão do Partido Trabalhista Brasileiro (PTB), produzido no interior do Estado e a Fôlha Popular, divulgador das ações do partido político PCB, que circulava na capital /??/nos anos de 1961 e 1964. Busca-se compreender o posicionamento desses veículos em relação ao debate em torno do pensamento e das ações políticas das forças tidas como de esquerda (Trabalhismo e Comunismo), enfocando a atuação dessas forças em Sergipe. Essa pesquisa é norteada pela metodologia de crítica do jornal em suas diferentes partes, como as colunas sociais, classificados e propagandas, bem como os editoriais, desde que esses abordem temas da política nacional. Parte-se do pressuposto de que a imprensa é uma representação do real, ou seja, não é o retrato fiel da realidade, mas de momentos selecionados da realidade, visto que o processo de seleção do que publica-se nos jornais é determinado tendo em vista os próprios critérios jornalísticos que, por sua vez, são motivados pela ideologia política, a qual a imprensa está associada. Vale enfatizar que há matérias que já em 1962 denunciavam a eminência de um golpe da direita, que implantaria uma ditadura terrorista a serviço das mais “infames forças” estrangeiras e nacionais, colocando a economia na dependência dos Estados Unidos. / São Cristóvão, SE

Thesis (MScPhysio)--Stellenbosch University, 2015. / ENGLISH ABSTRACT: Background: Pulmonary tuberculosis (PTB) remains a major concern worldwide. Although PTB is curable, both the disease and its treatment may have considerable medical, social and psychological consequences which may result in a decreased quality of life and functioning. Characterization of the functional capabilities of PTB patients post-treatment and the impact of PTB on their quality of life may identify a need for more holistic management of PTB treatment that extends beyond microbiological cure. Methods: Firstly, an in-depth scoping review was conducted using the following key words: Pulmonary tuberculosis (MESH term) and Health related quality of life (HRQoL), Pulmonary tuberculosis (MESH term) and Spirometry and Pulmonary tuberculosis (MESH term) and Six minute walk test or 6MWT to review the current literature reporting on the HRQoL, lung function measurements and exercise capacity of a PTB population (Chapter 2). Secondly, a cross-sectional, quantitative, descriptive study was conducted. The study setting included five primary health care facilities (PHCF) in the Breede Valley sub-district of the Cape Winelands East District, Western Cape, South Africa. Adult patients diagnosed with PTB, 18 years and older and who were successfully managed through the Cape Winelands District Health Care system were considered for the study if they had least two negative sputum sample results and had completed at least five months of anti-tuberculosis treatment. Post treatment bronchodilator lung function tests, health related quality of life using the BOLD core questionnaire and six minute walk test distance (6MWD) was measured. Findings: The comprehensive broad search of the literature yielded a total of 2446 articles. A total of 2422 articles were excluded since the title; abstract or full text article did not conform to the review question or were eliminated as duplicates across databases. Twenty-seven articles divided amongst the three subsections i.e. PTB and HRQoL (n=13), PTB and Spirometry (n=9) and PTB and exercise capacity (n=6), were included in the review. In the cross-sectional study, 328 names were obtained from the TB registers of the five included PHCF of which 45 patients were included in the study (56% male; mean age, 39.88±10.20 years). The majority of patients (n= 206; 63%) were not contactable, and could not be recruited. Approximately half the total sample, (n=23; 52%) presented with normal lung function while n=11 (25%) presented with a restrictive pattern, n=9 (21%) presented with an obstructive pattern and only n=1 (2%) presented with a mixed pattern (defined as FEV1<80% predicted, FVC<80% predicted and FEV1/FVC<0.7). The mean six minute walk distance (6MWD) was 294.5m±122.7m. Respondents scored poorly on all sub-domains of the SF-12v2 except vitality. Role emotional and role physical scored lowest with mean scores of 28.1 and 35.27 respectively, while vitality scored the highest with 52.78. Stellenbosch University https://scholar.sun.ac.za 4 | P a g e Conclusion The findings of this thesis suggest that even after microbiological cure, PTB patients may suffer from a decreased quality of life, impaired lung function and a decreased exercise capacity. Specific challenges to data collection in a rural region were identified; which included patient recruitment, field testing of exercise capacity (6MWD), and the generalizabilty of standardized questionnaires in rural regions. The findings of this pilot study serves to inform the planning of a larger observational study, in the rural Cape Winelands of the Western Cape, South Africa. / AFRIKAANSE OPSOMMING: Agtergrond Pulmonêre tuberkulose (PTB) wek wêreldwyd steeds groot kommer. Hoewel dit geneeslik is, kan die siekte sowel as die behandeling daarvan beduidende mediese, maatskaplike en sielkundige gevolge hê, wat lewensgehalte en funksionering kan knou. Die tipering van PTB-pasiënte se funksionele vermoëns ná behandeling sowel as die impak van PTB op hul lewensgehalte kan dalk dui op ’n behoefte aan die meer holistiese bestuur van PTB-behandeling, wat méér as blote mikrobiologiese genesing insluit. Metodes Eerstens is ’n diepgaande bestekstudie aan die hand van die volgende trefwoorde onderneem: pulmonêre tuberkulose (MeSH-term) en gesondheidsverwante lewensgehalte (HRQoL), pulmonêre tuberkulose (MeSH-term) en spirometrie, en pulmonêre tuberkulose (MeSH-term) en die ses minute lange stapafstandtoets (6MWT). Na aanleiding daarvan is die huidige literatuur oor die HRQoL, longfunksiemetings en oefenvermoë van ’n PTB-populasie bestudeer (hoofstuk 2). Tweedens is ’n kwantitatiewe, beskrywende deursneestudie onderneem. Die studie-omgewing het bestaan uit vyf fasiliteite vir primêre gesondheidsorg in die Breedevallei-subdistrik van die streek Kaapse Wynland-Oos, Wes-Kaap, Suid-Afrika. Volwasse pasiënte van 18 jaar en ouer wat met PTB gediagnoseer is en suksesvol deur die distriksgesondheidsorgstelsel van die Kaapse Wynland-streek bestuur word, is vir die studie oorweeg indien minstens twee van die pasiënt se sputummonsters TB-negatiewe resultate opgelewer het en die persoon reeds minstens vyf maande vir tuberkulose behandel is. Studiemetings het ingesluit brongodilator-longfunksietoetse ná behandeling, gesondheidsverwante beoordelings van lewensgehalte met behulp van die BOLD-vraelys, en die aflegging van ’n ses minute lange stapafstandtoets (6MWT). Bevindinge Die omvattende breë soektog van die literatuur het 'n totaal van 2446 artikels opgelewer. 'n Totaal van 2422 artikels is uitgesluit, aangesien die titel; abstrakte of volledige teks artikel het nie voldoen aan die navorsings vraag, of is uitgeskakel as duplikate oor databasisse. Sewe en twintig artikels verdeel tussen die drie onderafdelings, naamlik PTB en HRQoL (n = 13), PTB en Spirometrie (n = 9) en PTB en oefening kapasiteit (n = 6), is ingesluit in die oorsig. In die deursneestudie is 328 name uit die TB-registers van die vyf ondersoekpersele bekom. Altesaam 45 pasiënte (56% mans; gemiddelde ouderdom 39.88±10.20 jaar) is by die studie ingesluit. Die oorgrote meerderheid pasiënte (n = 206; 63%) kon nie bereik word nie, en dus ook nie gewerf word nie. Ongeveer die helfte van die algehele steekproef (n = 23; 52%) se longfunksie was normaal; n = 11 (25%) het ’n restriktiewe patroon getoon; n = 9 (21%) ’n obstruktiewe patroon, en slegs n = 1 (2%) ’n gemengde patroon (wat omskryf word as ’n FEV1-voorspellingswaarde van <80%, ’n FVC-voorspellingswaarde van <80%, en FEV1/FVC van <0.7). Die gemiddelde afstand wat in die ses minute lange staptoets afgelê is (6MWD), was 294,5 m±122,7 m. Respondente behaal swak Stellenbosch University https://scholar.sun.ac.za 6 | P a g e op al die sub-domein van die SF-12v2 behalwe vitaliteit. Rol emosionele en rol fisiese behaal laagste met die gemiddelde tellings van 28.1 en 35,27 onderskeidelik, terwyl vitaliteit behaal die hoogste met 52,78. Gevolgtrekking Die bevindinge van hierdie tesis gee te kenne dat PTB-pasiënte selfs ná mikrobiologiese genesing dalk swakker lewensgehalte, verswakte longfunksie en ’n afname in oefenvermoë ondervind. Bepaalde uitdagings vir data-insameling in ’n landelike omgewing is uitgewys, onder meer pasiëntewerwing, veldtoetsing van oefenvermoë (6MWD) en die veralgemeenbaarheid van gestandaardiseerde vraelyste in landelike gebiede. Die bevindinge van hierdie proefstudie kan gebruik word om die beplanning van ’n groter waarnemingstudie in die landelike Kaapse Wynland-streek in die Wes-Kaap, Suid-Afrika, te rig.