Mais de 2 bilhões de pessoas em todo o mundo encontram-se infectadas com Toxoplasma gondii. Na região endêmica de Erechim, RS, cerca de 90% da população é soropositiva e cerca de 18% destes indivíduos apresentam lesões oculares com manifestações clínicas. A estrutura genética das populações do T. gondii tem sido bastante investigada, a despeito da infecção ter se espalhado pelo mundo, do grande número de hospedeiros intermediários e da capacidade do parasita de se reproduzir sexualmente. Linhagens de T. gondii com atípica ou nova combinação de alelos têm sido isoladas de animais não domésticos ou em outros continentes, como América do Sul e África, e de pacientes com apresentações clínicas incomuns. Em modelos murinos, as linhagens com o genótipo tipo I são altamente virulentas, em contraste às cepas tipo II e tipo III que são menos virulentas. Este trabalho propõe a caracterização fenotípica da resposta imune do hospedeiro frente a infecção por diferentes cepas de T. gondii, bem como o isolamento e a caracterização genotípica das linhagens de T. gondii que infectam indivíduos de Erechim no Rio Grande do Sul. Para a caracterização fenotípica utilizamos duas cepas de T. gondii já bem estabelecidas, a cepa RH (tipo I) e a ME49 (tipo II), e uma cepa isolada a partir de gatos domésticos do Brasil, chamada TgCatBr71. Sendo assim, através da fenotipagem das células dendríticas de camundongos C57Bl/6 infectados com as cepas citadas, foi possível observar que essas cepas induzem expressão das moléculas de superfície CD40, CD80, CD86 e MHC classe II em DCs CD11c+, porém sem significativa diferença entre as cepas. Com relação as células CD4+ e células CD8+, observamos o aumento das células CD8+ no decorrer da infecção pelas cepas RH e ME49, indicando a importância deste tipo celular na resposta protetora contra T. gondii. Avaliamos também a produção de citocinas IL-12, IFN-g e IL-10 em células esplênicas de camundongos infectados pelas três cepas no decorrer da infecção e detectamos que camundongos infectados pela cepa tipo II (ME49) apresentam síntese maior dessas citocinas do que camundongos infectados pela cepa tipo I (RH) e pela cepa TgCatBr71. Assim, concluímos que esta cepa TgCatBr71 se assemelha bastante a cepa do tipo I (RH), tanto em relação a evolução da doença no camundongos como nos padrões da resposta imune do hospedeiro. E que apesar dessas duas cepas diferirem da cepa tipo II (ME49), resultando em graus diferentes de patologia em camundongos C57Bl/6, todas a três cepas parecem produzir semelhante resposta imune protetora do hospedeiro. / More than 2 billion people are infected with Toxoplasma gondii around the world. In the endemic region of Erechim, RS, Brazil, about 90% of the population is soropositive and about 18% of these individuals have ocular lesions with clinical manifestations. The genetic structure of strains of T. gondii has been investigated, despite the infection has spread throughout the world, the large number of intermediate hosts and the ability to reproduce sexually. Strains of T. gondii with atypical or new combination of alleles have been isolated from wild animals and other continents, such as South America and Africa, and also from patients with unusual clinical presentations. In murine models, the type I genetic lineage are highly virulent, in contrast to strains type II and type III.Our work proposes the phenotypic characterization of the host immune response against the infection by different strains of T. gondii, and the isolation and genetic strains characterization of T. gondii that infect individuals of Erechim in RS, Brazil. In the phenotypic characterization were used two strains of T. gondii already well established, the strain RH (type I) and ME49 (type II), and a strain isolated from domestic cats from Brazil, called TgCatBr71 (type BrI). Thus, by phenotyping dendritic cells of C57BL/ 6 mice infected with the strains mentioned, we observed that these strains upregulated the expression of surface molecules such as CD40, CD80, CD86 and MHC class II in DC CD11c+ although with no significant difference between the strains. With respect to the CD4+ and CD8+ cells, the observed increase in CD8+ T cells during the infection by strains RH and ME49, indicating the importance of this cell type in the protective response against T. gondii. We also evaluated the production of cytokines IL-12, IFN-g and IL-10 from spleen cells and found that mice infected by the strain type II (ME49) have increased synthesis of these cytokines than mice infected by the strain type I (RH) and the strain type BrI (TgCatBr71). Thus, we concluded that type BrI (TgCatBr71) strain is similar to type I (RH) strain, both for the evolution of the disease and also concerning the immunological parameters evaluated. Besides, despite these two strains differ from the strain type II (ME49), resulting in different degrees of pathology in mice C57BL / 6, all three strains seem to produce similar protective immune response of the host.

With the worldwide increase in numbers of individuals infected with the human-immune deficiency virus (HIV) and acquired immune deficiency syndrome (AIDS), the need for more information became essential. The devastating influences and fatal outcome of this disease is inevitable. These individuals are confronted with mortality and various disabling conditions. One of these disabling conditions is the possible development of a hearing loss. Loss of hearing sensitivity related to HIV/AIDS is only one of numerous effects the virus may have on humans and their quality of life. Therefore increased awareness of HIV/AIDS and the influences of this disease is inevitable for the modern audiologist. The precise nature and the extent of the influence that HIV/AIDS and antiretroviral therapy (ART) has on the hearing ability of a person are unknown to date. Even though a relationship between hearing loss, HIV/AIDS and the administration of relevant medication is expected, no clear explanation is available to provide the public or clinicians with the necessary information on assessments, interventions and aural rehabilitation techniques. Without being able to identify the specific cause, symptoms and place of lesion of the hearing loss, it will be difficult to ensure appropriate monitoring and treatment. Information regarding the influences of HIV/AIDS and ART on hearing sensitivity had to be established to ensure appropriate intervention and rehabilitation options. The first part of this research project reviews the evidence available regarding the possible influences of HIV/AIDS on hearing. Throughout the research a cross-sectional design with quantitative and qualitative approaches were followed comprising of a structured interview, basic and specialized audiometric battery to obtain the necessary case history, as well as results for these different audiological tests that were conducted. The specialised tests included immittance measurements, distortion-product otoacoustic emission (DPOAE) and auditory brainstem response (ABR). The results of this study were discussed in terms of the three sub aims in accordance with the different audiological tests that were conducted. The results indicated that those participants with ART exposure had a significantly higher incidence of hearing loss. The pure tone averages were mainly found within normal limits but decreased with the progression of the final stages of HIV/AIDS. The high and low frequencies of the audiogram were often affected with loss of hearing sensitivity suggesting the presence of a high and low frequency slope. The final three stages of HIV/AIDS had a significantly higher incidence of bilateral hearing loss. ART exposure were associated with more severe degrees of hearing loss. The DPOAE and ABR indicated that cochlear and retro-cochlear damage existed often among these participants. Only 20% participants had abnormal tympanograms suggestive of conductive pathology. The results revealed that the type of pathology varied across the stages of HIV/AIDS. The conclusions and implications of this study are discussed. Recommendations incorporate the development of HIV/AIDS awareness campaigns that includes audiological information on the possible influences, where to refer or where to seek assistance; issues regarding the improvement of the modern audiologists’ knowledge in terms of the management of the audiological needs of individuals with HIV/AIDS and the application of these results in the industrial setting to utilize when they consider granting compensation claims. / Dissertation (MCommunication Pathology)--University of Pretoria, 2008. / Speech-Language Pathology and Audiology / unrestricted

The study of RNA-binding proteins has recently increased in importance due to discoveries of their larger role in cellular processes. One study currently conducted at Umeå University involves constructing a model that will be able to improve our knowledge about T-cells by explaining how these cells work in different diseases. But before this model can become a reality, Umeå Univerity needs to investigate the relation between RNA and RNA-binding proteins and find proteins of which highly contribute to the activity of the RNA-binding proteins. To do so, they have decided to use four penalized regression Machine Learning models to analyse protein sequences from CD4 cells. These models consist of a ridge penalized model, an elastic net model, a neural network model, and a Bayesian model. The results show that the models have a number of RNA-binding protein sequences in common which they list as highly decisive in their predictions.

The research objectives were to describe the age and gender of adult HIV positive clients on ART who received IPT; the incidence of tuberculosis among clients that received IPT and the defaulter rate among those that were commenced on IPT. Quantitative non-experimental descriptive retrospective cohort study was undertaken to ascertain the incidence of tuberculosis among adult HIV positive clients who received IPT. 104 clinic records of HIV positive adult clients accessing care at Isithebe Clinic, iLembe-South Africa who were commenced on IPT between 01 July 2010 and 30 November 2011 were analysed. The study found that 66 of 104 (63.5%) study respondents completed the course of IPT and the majority of those that defaulted were due to poor quality of care. Gender was statistically found to have played a role on whether a patient completes IPT. None of the study respondents that completed IPT was diagnosed with TB disease. / Health Studies / M.A. (Public Health)

The research objectives were to describe the age and gender of adult HIV positive clients on ART who received IPT; the incidence of tuberculosis among clients that received IPT and the defaulter rate among those that were commenced on IPT. Quantitative non-experimental descriptive retrospective cohort study was undertaken to ascertain the incidence of tuberculosis among adult HIV positive clients who received IPT. 104 clinic records of HIV positive adult clients accessing care at Isithebe Clinic, iLembe-South Africa who were commenced on IPT between 01 July 2010 and 30 November 2011 were analysed. The study found that 66 of 104 (63.5%) study respondents completed the course of IPT and the majority of those that defaulted were due to poor quality of care. Gender was statistically found to have played a role on whether a patient completes IPT. None of the study respondents that completed IPT was diagnosed with TB disease. / Health Studies / M.P.H.