ABSTRACT
Resumo Fundamento Os limiares de corte para a "relação do ciclo completo de repouso" (RFR) oscilam em diferentes séries, sugerindo que as características da população podem influenciá-los. Da mesma forma, foram documentados preditores de discordância entre a RFR e a reserva de fluxo fracionado (FFR). O Estudo RECOPA, mostrou que a capacidade diagnóstica está reduzida na "zona cinzenta" da RFR, tornando necessária a realização de FFR para descartar ou confirmar isquemia. Objetivos Determinar os preditores de discordância, integrar as informações que eles fornecem em um índice clínico-fisiológico: a "RFR Ajustada", e comparar sua concordância com o FFR. Métodos Usando dados do Estudo RECOPA, os preditores de discordância em relação à FFR foram determinados na "zona cinzenta" da RFR (0,86 a 0,92) para construir um índice ("RFR Ajustada") que pesaria a RFR juntamente com os preditores de discordância e avaliar sua concordância com a FFR. Resultados Foram avaliadas 156 lesões em 141 pacientes. Os preditores de discordância foram: doença renal crônica, cardiopatia isquêmica prévia, lesões não envolvendo a artéria descendente anterior esquerda e síndrome coronariana aguda. Embora limitada, a "RFR Ajustada" melhorou a capacidade diagnóstica em comparação com a RFR na "zona cinzenta" (AUC-RFR = 0,651 versus AUC-"RFR Ajustada" = 0,749), mostrando também uma melhora em todos os índices diagnósticos quando foram estabelecidos limiares de corte otimizados (sensibilidade: 59% a 68%; especificidade: 62% a 75%; acurácia diagnóstica: 60% a 71%; razão de verossimilhança positiva: 1,51 a 2,34; razão de verossimilhança negativa: 0,64 a 0,37). Conclusões Ajustar a RFR integrando as informações fornecidas pelos preditores de discordância para obter a "RFR Ajustada" melhorou a capacidade diagnóstica em nossa população. Mais estudos são necessários para avaliar se os índices clínico-fisiológicos melhoram a capacidade diagnóstica da RFR ou de outros índices coronarianos.
Abstract Background Cutoff thresholds for the "resting full-cycle ratio" (RFR) oscillate in different series, suggesting that population characteristics may influence them. Likewise, predictors of discordance between the RFR and fractional flow reserve (FFR) have been documented. The RECOPA Study showed that diagnostic capacity is reduced in the RFR "grey zone", requiring the performance of FFR to rule out or confirm ischemia. Objectives To determine predictors of discordance, integrate the information they provide in a clinical-physiological index, the "Adjusted RFR", and compare its agreement with the FFR. Methods Using data from the RECOPA Study, predictors of discordance with respect to FFR were determined in the RFR "grey zone" (0.86 to 0.92) to construct an index ("Adjusted RFR") that would weigh RFR together with predictors of discordance and evaluate its agreement with FFR. Results A total of 156 lesions were evaluated in 141 patients. Predictors of discordance were: chronic kidney disease, previous ischemic heart disease, lesions not involving the anterior descending artery, and acute coronary syndrome. Though limited, the "Adjusted RFR" improved the diagnostic capacity compared to the RFR in the "grey zone" (AUC-RFR = 0.651 versus AUC-"Adjusted RFR" = 0.749), also showing an improvement in all diagnostic indices when optimal cutoff thresholds were established (sensitivity: 59% to 68%; specificity: 62% to 75%; diagnostic accuracy: 60% to 71%; positive likelihood ratio: 1.51 to 2.34; negative likelihood ratio: 0.64 to 0.37). Conclusions Adjusting the RFR by integrating the information provided by predictors of discordance to obtain the "Adjusted RFR" improved the diagnostic capacity in our population. Further studies are required to evaluate whether clinical-physiological indices improve the diagnostic capacity of RFR or other coronary indices.
ABSTRACT
Introduction: Paracoccidioidomycosis is an endemic systemic mycosis caused by Paracoccidioides brasiliensis, a thermally dimorphic fungus that in tissues and cultures at 37°C grows as a yeast while at lower temperatures (less than 24°C) it becomes a mold; however the genes that rule these processes and their expression are poorly understood. Objective: This research focused on the kinetic expression of certain genes in P. brasiliensis throughout the dimorphic process, one that involves the transition from the mycelium to yeast forms and the germination from the yeast to mycelium form. Materials and methods: A real-time quantitative polymerase chain reaction (RT-qPCR) was optimized to measure the expression of ten genes connected with diverse cellular functions including cell synthesis and wall structure, oxidative stress response, heat shock response, metabolism, proteins processing, solute transport across the cell membrane and signal transduction pathways at different time points during the mycelia to yeast transition, as well as in the yeast to mycelia germination processes. Results: Genes involved in cell synthesis and wall structure, metabolism and signal transduction were differentially expressed and highly up-regulated during the yeast to mycelia germination process; on the other hand, genes involved in heat shock response, cell synthesis and wall structure were highly up-regulated during the mycelia to yeast transition process. The remaining genes were differentially regulated during both processes. Conclusion: In this work the up-regulation of certain genes involved in the morphological changes occurring in P. brasiliensis yeast and mycelia forms were confirmed, indicating that these biological processes play an important role during the host-pathogen interactions, as well as in the fungus adaptation to environmental conditions.
Introducción. La paracoccidioidomicosis es una micosis sistémica causada por el hongo termodimorfo Paracoccidioides brasiliensis. En tejidos y cultivos a 37°C crece como levadura, mientras que a temperaturas menores de 24°C crece como un moho. Sin embargo, se conoce poco sobre los genes que regulan estos procesos. Objetivo. Se evaluó la cinética de expresión de algunos genes en P. brasiliensis mediante el proceso de dimorfismo incluida la transición del micelio a levadura y de la germinación de levadura a micelio. Materiales y métodos. Se optimizó una PCR cuantitativa en tiempo real (RT-qPCR) para medir la expresión de diez genes relacionados con diversas funciones celulares que incluyeron: síntesis de pared, respuesta al estrés oxidativo, respuesta al choque térmico, metabolismo, procesamiento de proteínas, trasporte de solutos a través de membranas y transducción de señales, todo ello a diferentes tiempos durante la transición de micelio a levadura, así como de la germinación de levadura a micelio. Resultados. Se encontró que los genes relacionados con síntesis de pared, metabolismo y transducción de señales, se expresaban de manera diferencial y con regulación positiva durante la germinaciónlevadura a micelio, mientras que algunos genes relacionados con respuesta a choque térmico y a síntesis de pared estaban sobreexpresados en la transición de micelio a levadura. Los genes restantes se regularon de manera diferencial en ambos procesos. Conclusiones. En este trabajo se confirma la regulación positiva de algunos genes relacionados con los cambios morfológicos de las fases levadura y micelio en P. brasiliensis, procesos biológicos que juegan un papel de importancia durante la interacción huésped-parásito y durante la adaptación del hongo al ambiente, respectivamente.