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Introduction: Pleural tuberculosis (PlTB), the most common site of extrapulmonary TB, is characterized by a paucibacillary nature and a compartmentalized inflammatory response in the pleural cavity, both of which make diagnosis and management extremely challenging. Although transcriptional signatures for pulmonary TB have already been described, data obtained by using this approach for extrapulmonary tuberculosis and, specifically, for pleural tuberculosis are scarce and heterogeneous. In the present study, a set of candidate genes previously described in pulmonary TB was evaluated to identify and validate a transcriptional signature in clinical samples from a Brazilian cohort of PlTB patients and those with other exudative causes of pleural effusion., Methods: As a first step, target genes were selected by a random forest algorithm with recursive feature elimination (RFE) from public microarray datasets. Then, peripheral blood (PB) and pleural fluid (PF) samples from recruited patients presenting exudative pleural effusion were collected during the thoracentesis procedure. Transcriptional analysis of the selected top 10 genes was performed by quantitative RT-PCR (RT-qPCR)., Results: Reanalysis of the public datasets identified a set of candidate genes ( CARD17, BHLHE40, FCGR1A, BATF2, STAT1, BTN3A1, ANKRD22, C1QB, GBP2 , and SEPTIN4 ) that demonstrated a global accuracy of 89.5% in discriminating pulmonary TB cases from other respiratory diseases. Our validation cohort consisted of PlTB ( n = 35) patients and non-TB ( n = 34) ones. The gene expressions of CARD17 , GBP2 , and C1QB in PF at diagnosis were significantly different between the two (PlTB and non-TB) groups ( p < 0.0001). It was observed that the gene expressions of CARD17 and GBP2 were higher in PlTB PF than in non-TB patients. C1QB showed the opposite behavior, being higher in the non-TB PF. After anti-TB therapy, however, GBP2 gene expression was significantly reduced in PlTB patients ( p < 0.001). Finally, the accuracy of the three above-cited highlighted genes in the PF was analyzed, showing AUCs of 91%, 90%, and 85%, respectively. GBP2 was above 80% (sensitivity = 0.89/specificity = 0.81), and CARD17 showed significant specificity (Se = 0.69/Sp = 0.95) in its capacity to discriminate the groups., Conclusion: CARD17 , GBP2 , and C1QB showed promise in discriminating PlTB from other causes of exudative pleural effusion by providing accurate diagnoses, thus accelerating the initiation of anti-TB therapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Corrêa, Leal-Calvo, Mafort, Santos, Leung, Pinheiro, Rufino, Moraes and Rodrigues.)

Although several cohort studies have raised the important association between diabetes mellitus (DM) and latent tuberculosis infection (LTBI), evidences are limited and controversial. Furthermore, it is well documented that the poor glycemic control may exacerbate the risk for active TB. Thus, the monitoring of diabetic patients living in high-incidence areas for TB is an important concern in views of available diagnostic tests for LTBI. In this cross-sectional study, we estimate the association of DM and LTBI among diabetic patients classified as type-1 DM (T1D) or type-2 DM (T2D) living in Rio de Janeiro, RJ, Brazil - considered a high TB burden region of these country. Non-DM volunteers were included as endemic area healthy controls. All participants were screened for DM using glycosylated-hemoglobin (HbA 1c ) and for LTBI using the QuantiFERON-TB Gold in Tube (QFT-GIT). Demographic, socioeconomic, clinical and laboratorial data were also assessed. Among 553 included participants, 88 (15.9%) had QFT-GIT positive test, of which 18 (20.5%) were non-DM, 30 (34.1%) T1D and 40 (45.4%) T2D. After adjustments for potential baseline confounders, age, self-reported non-white skin color and an active TB case in the family were significantly associated with LTBI among the studied population by using a hierarchical multivariate logistic regression analysis. Additionally, we verified that T2D patients were able to produce significant increased interferon-gamma (IFN-γ) plasma levels in response to Mycobacterium tuberculosis -specific antigens, when compared to non-DM individuals. Altogether, our data showed an increased prevalence of LTBI among DM patients, albeit non-statistically significant, and point out to important independent factors associated with LTBI, which deserve attention in monitoring patients with DM. Moreover, QFT-GIT test seems to be a good tool to screening LTBI in this population, even in a high TB burden area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Torres, Corrêa, Bevilacqua, do Prado, Bandeira, Rodrigues and Gomes.)

Background: The largest radiological accident to occur in any urban area happened in Goiânia, Brazil, in 1987., Objective: To evaluate the association between breast cancer incidence and ionizing radiation levels., Design and Setting: Ecological study among residents of the city of Goiânia, Brazil., Methods: The central region of Goiânia, with seven major sources of contamination from cesium-137, was defined as the study area. The addresses of women diagnosed with breast cancer were identified between 2001 and 2010. The data were geographically referenced and, using census data, the annual averages of crude incidence rates were estimated. The existence of clusters of new cases was ascertained by means of the Moran index. Correlations of radiometric measurements with the incidence were assessed using unconditional linear regression., Results: A total of 4,105 new cases were identified, of which 2,233 were in the study area, and of these, 1,286 (57.59%) were georeferenced. The gross rates of total and referenced cases were 102.91 and 71.86/100,000 women, respectively. These were close to the average for Brazilian state capitals, which is 79.37/100,000 women. The cluster analysis showed slight correlations in three small sets of census tracts, but these were far from the sources of contamination. The scatter plot of points and the R2 value close to zero indicated that there was no association between the variables., Conclusion: This study reinforces the hypothesis that the ionizing radiation levels to which women living in Goiânia are now exposed to are not associated with the onset of new cases of breast cancer.

Objective:  To assess the daily dietary intake and energy contribution of ultra-processed foods among women who are positive and negative for the human immunodeficiency virus (HIV) during pregnancy., Methods:  This case-control study included 77 HIV-positive and 79 HIV-negative puerperal women between 2015 and 2016. The socioeconomic and maternal demographic data were assessed, and a food frequency questionnaire (FFQ) adapted for pregnant women was applied. The Fisher exact test and the Mann-Whitney test were applied to detect differences between the groups. Linear regression was used to assess the associations between the intake of ultra-processed food and energy, macro- and micronutrients, with values of p  < 0.05 considered significant., Results:  The HIV-positive group was older ( p  < 0.001) and had lower income ( p  = 0.016) and level of schooling ( p  < 0.001) than the HIV-negative group. Both groups presented similar average food intake: 4,082.99 Kcal/day and 4,369.24 Kcal/day for the HIV-positive and HIV-negative women respectively ( p  = 0.258).The HIV-positive group consumed less protein ( p  = 0.048), carbohydrates ( p  = 0.028) and calcium ( p  = 0.001), and more total fats (p  = 0.003). Ultra-processed foods accounted for 39.80% and 40.10% of the HIV-positive and HIV-negative groups' caloric intake respectively ( p  = 0.893). The intake of these foods was associated with a higher consumption of carbohydrates ( p  < 0.001), trans fat ( p  = 0.013) and sodium ( p  < 0.001), as well as lower protein ( p  < 0.001) and fiber intake ( p  = 0.022)., Conclusion:  These findings demonstrate that the energy consumption and ultra-processed food intake were similar in both groups, which reinforces the trend toward a high intake of ultra-processed food in the general population. The intake of ultra-processed food was positively associated with the consumption of carbohydrates, trans fat and sodium, and negatively associated with the consumption of protein and fiber., Competing Interests: The authors have none to declare., (Thieme Revinter Publicações Ltda Rio de Janeiro, Brazil.)

Background: CD64 (FcγR1) is a high-affinity receptor for monomeric IgG1 and IgG3. Circulating neutrophils express very low amounts of CD64 on their surface., Objectives: Our primary aim was to investigate the utility of neutrophil CD64 surface expression as a biomarker of active pulmonary tuberculosis (TB). We hypothesised that elevated neutrophil CD64 expression in TB infection would be associated with interferon gamma (IFN-γ) as an inducer of CD64 expression., Methods: The expression level of CD64 per neutrophil (PMN CD64 index) was quantitatively measured with flow cytometry using a Leuko64 kit in samples from patients with TB and latent TB infection (LTBI) as well as healthy controls, as part of a prospective cohort study in Brazil., Findings: The PMN CD64 index in patients with TB was higher than that in healthy controls and LTBI. Receiver operating characteristic curve analyses determined that the PMN CD64 index could discriminate patients with TB from those with LTBI and healthy individuals. PMN CD64 index levels returned to baseline levels after treatment., Conclusions: The positive regulation of CD64 expression in circulating neutrophils of patients with active TB could represent an additional biomarker for diagnosis of active TB and could be used for monitoring individuals with LTBI before progression of TB disease.

Background: Pleural tuberculosis (PlTB) is the most common extrapulmonary manifestation of this infectious disease which still presents high mortality rates worldwide. Conventional diagnostic tests for PlTB register multiple limitations, including the lack of sensitivity of microbiological methods on pleural specimens and the need of invasive procedures such as pleural biopsy performance. In this scenario, the search for biological markers on pleural fluid (PF) has been the target of several studies as a strategy to overcome the limitations of PlTB diagnosis. This study aims to evaluate the use either isolated or in combination with adenosine deaminase (ADA), interferon-gamma (IFN-γ), interferon-gamma inducible protein of 10-kD (IP-10) levels on PF in order to guide an accurate anti-TB treatment in microbiologically non-confirmed cases., Methods and Findings: Eighty patients presenting pleural effusion under investigation were enrolled in a cross-sectional study conducted at Pedro Ernesto University Hospital, Rio de Janeiro, RJ, Brazil. Peripheral blood (PB) and PF samples collected from all patients were applied to the commercial IFN-γ release assay, QuantiFERON-TB Gold In-Tube, and samples were analyzed for IFN-γ and IP-10 by immunoassays. ADA activity was determined on PF by the colorimetric method. Based on microbiological and histological criteria, patients were categorized as follow: confirmed PlTB (n = 16), non-confirmed PlTB (n = 17) and non-PlTB (n = 47). The Mycobacterium tuberculosis antigen-specific production of IFN-γ and IP-10 on PB or PF did not show significant differences. However, the basal levels of these biomarkers, as well as the ADA activity on PF, were significantly increased in confirmed PlTB in comparison to non-PlTB group. Receiver operating characteristics curves were performed and the best cut-off points of these three biomarkers were estimated. Their either isolated or combined performances (sensitivity [Se], specificity [Sp], positive predictive value [PPV], negative predictive value [NPV] and accuracy [Acc]) were determined and applied to Venn's diagrams among the groups. Based on the confirmed PlTB cases, IFN-γ showed the best performance of them at a cut-off point of 2.33 IU/mL (Se = 93.8% and Sp = 97.9%) followed by ADA at a cut-off of 25.80 IU/L (Se = 100% and Sp = 84.8%) and IP-10 (Cut-point = 4,361.90 pg/mL, Se = 75% and Sp = 82.6%). IFN-γ plus ADA (cut-point: 25.80 IU/L) represent the most accurate biomarker combination (98.4%), showing Se = 93.7%, Sp = 100%, PPV = 100% and NPV = 97.9%. When this analysis was applied in non-confirmed PlTB, 15/17 (88.2%) presented at least two positive biomarkers in combination., Conclusion: IFN-γ, IP-10, and ADA in PlTB effusions are significantly higher than in non-PlTB cases. IFN-γ is an excellent rule-in and rule-out test compared to IP-10 and ADA. The combination of IFN-γ and ADA, in a reviewed cut-off point, showed to be particularly useful to clinicians as their positive results combined prompts immediate treatment for TB while both negative results suggest further investigation., Competing Interests: The authors have declared that no competing interests exist.