Background: Cytokines have been shown to be involved in traumatic brain injury (TBI). We investigated the independent association between serum levels of IL-10 and TNF-α and hospital mortality of patients with severe TBI. Methods: Serum IL-10 and TNF-α levels were determined after a median period (interquartile range (IQ) 25–75) of 10 h (IQ 5–18) after severe TBI in 93 consecutive patients and in randomly selected patients with mild (n = 18) and moderate (n = 16) TBI. In patients with severe TBI, additional blood samples were analyzed 30 h (IQ 22–37) and 68 h (IQ 55–78) after TBI. Age, gender, computed tomography findings, Glasgow Coma Scale score (GCS) and pupil reactions at admission, associated trauma and hospital mortality were collected. Results: Elevated serum levels of IL-10, but not TNF-α, correlated significantly with GCS severity (R² coefficient, p < 0.0001) and were found to be associated with hospital mortality in patients with severe TBI. Elevated IL-10 remained associated with mortality (p = 0.01) in a subset of patients with isolated severe TBI (n = 74). Multiple logistic regression analysis showed that higher IL-10 levels (>90 pg/ml) at 10 or 30 h after TBI were 6 times (odds ratio (OR) 6.2, 95% confidence interval (CI) 1.2–25.1, p = 0.03) and 5 times (OR 5.4, 95% CI 1.2–25.1, p = 0.03), respectively, more frequently associated with hospital mortality than lower levels (<50 pg/ml), independently of age, GCS as well as pupil reactions at admission and associated trauma. Conclusions: Serum IL-10 levels may be a useful marker for severe TBI prognosis.

g Nanoenabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with Mycobacterium tuberculosis and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation and inhibits M. tuberculosis growth by enhancing intracellular drug bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular M. tuberculosis and cell-free bacteria, indicating that NPs directly interact with the bacterium. Taken together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra-and intracellular mycobacteria, which could actively enhance chemotherapy during active TB.

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Surface and secreted mycobacterial proteins play a major role on the infection process by mediating macrophage-bacteria interactions as well as the fate of cell’s death. We have previously described a secreted 13-kDa lectin (sMTL-13) in Mycobacterium tuberculosis (Mtb), encoded by Rv1419 gene, and although a possible importance for this protein as a major mycobacterial antigen was shown in tuberculosis patients, the importance of such lectin during infection has not been formally addressed. We have generated an Rv1419 knockout Mtb (ΔRv1419) to investigate a possible role of this gene during infection. In silico analysis of the protein as well as its detection on Mtb surface suggest that sMTL-13 may participate during bacteria entry in the host macrophage. This was confirmed by binding experiments performed in either murine or human derived macrophages. In addition, lower levels of TNF were detected in ΔRv1419-infected cells, indicating that this lectin may be important for pathogen recognition. Importantly, ΔRv1419 displays higher intracellular growth than the WT bacteria. Thus, although binding of Mtb to macrophages is decreased in the absence of Rv1419 gene, cells exposed to the knockout Mtb display higher bacterial replication rate and cell death. These data suggest that sMTL-13 expressed on Mtb regulates macrophage entry and perhaps cell fate, which could serve as a pathogen survival strategy, allowing bacterial growth without leading host cells to a premature death.

Background: The Rapid Molecular Test (RMT) Gene Xpert is widely used as a control strategies and surveillance for tuberculosis (TB). In the region of the Americas TB incidence is slowly increasing, owing to an upward trend in Brazil, which is among the high TB burden countries (HBCs) ranking the 19th position. In this context, we aimed to: (i) describe the implementation and history of RMT-TB (Xpert® MTB/RIF and Xpert® MTB/RIF Ultra) in Brazil; (ii) to evaluate the national RMT-laboratory distribution and TB and RIF detection by RMT-TB equipment (by year, by federal units and by region); and (iii) to correlate these data the Brazilian TB incidence. Methods: For this, we collected the quantitative data of Xpert® MTB/RIF and Xpert® MTB/RIF Ultra assays, performed in the pulmonary TB investigation from 2014 to 2020, provided by the Brazilian Ministry of Health. A spatial visualization using ArcGIS software was performed. Results: The Southeast region allocated about double RMT-laboratories from 39.4% - 45.9% of the total value over five which is the number of regions. Regarding the federal units, the São Paulo state allocated alone from 20.2% to 34.1% (5.0 to 8.5 times the value) of RMT-laboratories depending on the year observed. There were significant differences (p < 0.0001) in the frequency of RMT-laboratory in all years of the historical series. There was an unequal distribution of RMT-laboratory between Brazilian regions and federal units. Conclusions: This alerts for the surveillance of rapid molecular detection of TB in different parts of the country, with the possibility of improving the distribution of tests in areas of higher incidence to achieve the disease control recommended by national and worldwide authorities.