El texto completo de este trabajo no está disponible en el Repositorio Académico UPC por restricciones de la casa editorial donde ha sido publicado. / Objectives: Diagnosis of pleural tuberculosis (PT) is still a challenge, particularly in resource-constrained settings. Alternative diagnostic tools are needed. We aimed at evaluating the utility of Clinical Prediction Rules (CPRs) for diagnosis of pleural tuberculosis in Peru. Methods: We identified CPRs for diagnosis of PT through a structured literature search. CPRs using high-complexity tests, as defined by the FDA, were excluded. We applied the identified CPRs to patients with pleural exudates attending two third-level hospitals in Lima, Peru, a setting with high incidence of tuberculosis. Besides pleural fluid analysis, patients underwent closed pleural biopsy for reaching a final diagnosis through combining microbiological and histopathological criteria. We evaluated the performance of the CPRs against this composite reference standard using classic indicators of diagnostic test validity. Results: We found 15 eligible CPRs, of which 12 could be validated. Most included ADA, age, lymphocyte proportion and protein in pleural fluid as predictive findings. A total of 259 patients were included for their validation, of which 176 (67%) had PT and 50 (19%) malignant pleural effusion. The overall accuracy of the CPRs varied from 41% to 86%. Two had a positive likelihood ratio (LR) above 10, but none a negative LR below 0.1. ADA alone at a cut-off of ≥40 IU attained 87% diagnostic accuracy and had a positive LR of 6.6 and a negative LR of 0.2. Conclusion: Many CPRs for PT are available. In addition to ADA alone, none of them contributes significantly to diagnosis of PT.

京都大学 / 0048 / 新制・課程博士 / 博士(ｴﾈﾙｷﾞｰ科学) / 甲第20775号 / エネ博第360号 / 新制||エネ||71(附属図書館) / 京都大学大学院エネルギー科学研究科エネルギー基礎科学専攻 / (主査)教授 片平 正人, 教授 森井 孝, 教授 木下 正弘 / 学位規則第4条第1項該当 / Doctor of Energy Science / Kyoto University / DGAM

The Human Immunodeficiency virus-1 can stay undetected and unaffected by host immune surveillance and antiretroviral therapy. This phenomenon is called proviral latency and the cells harbouring such viruses are part of the latently infected cell reservoir. In this situation, the viral genome integrates into the host's genome upon infection, whereby infected cells exhibit either very low levels or no viral transcription, and hence no viral proteins or egress viruses are produced that can be detected by the immune system. However, viral transcription can be re-activated to produce infectious viruses under certain circumstances. Host-encoded retroviral restriction factors like APOBEC3 (A3) proteins are part of our intrinsic immune defences against retroviral infection, introducing mutations in viral replication intermediates. We hypothesize that low levels of G-to-A transition mutations in the HIV-1 LTR region, introduced by APOBEC3G/F, could lead to a latency-like phenotype. These latent viruses pose major hurdles for HIV-1 cure therapies. Our lab previously created a library of clones possessing mutations in the LTR introduced by A3G/F. Later, mutated LTRs were cloned into 3 types of plasmid backbones: 1) a pEGFP expression vector to study the transcriptional activity of the mutated promoter, 2) into non-replicative pNL4 ∆env ∆vif viral expression vector, and 3) into a replicative pNL4-CXCR4 viral vector to study infection and induction by latency reversal agent (LRA) treatment to better understand the mechanism of latency and transcriptional induction. Viruses produced from these plasmids carrying mutated promoters are referred to as latency-prone viruses or LPVs in this thesis. Characterizing the transcription, infection, and induction to PMA/I of the LPVs would essentially help in evaluating the role of A3 mutations in viral latency and further help in the development of new therapeutics.