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Background and objectiveIncidence and predictors of endobronchial tuberculosis (EBTB) remain unknown because of the lack of prospective studies. Our objective was to assess the incidence and predictors of concomitant EBTB in patients with active pulmonary tuberculosis (PTB).MethodsWe prospectively performed routine bronchoscopic examination in all patients with PTB to detect EBTB. Clinical and bronchoscopic findings were analyzed to elucidate predictors of EBTB.ResultsBronchoscopies of 429 PTB patients were performed at a tertiary referral hospital in Korea. Among those, 233 patients (54.3%) had EBTB. Female gender (odds ratio (OR) 4.35, 95% confidence interval (CI) 1.78–10.63), longer symptom duration (>4 weeks; OR 1.86, 95% CI 1.05–5.46), and no previous history of tuberculosis (OR 4.16, 95% CI 1.22–14.18) were found to be the independent predictors of concomitant EBTB in patients with active PTB. Most of the EBTB/PTB patients had mild stenosis, and more than 20% of them had severe stenosis at the time of diagnosis. Patients with EBTB had follow-up bronchoscopy to evaluate persistent airway stenosis. Persistent bronchostenosis with the lumen narrowed by more than one third occurred in 20.7% (30/145) of patients. The involvement length and decreased forced expiratory volume in 1 s were the risk factors for persistent bronchostenosis.ConclusionsIn patients with active PTB, 50% or more have EBTB. Female gender and longer duration of symptoms are the main predictors of concomitant EBTB. Immediate diagnostic bronchoscopy in patients with active PTB should be considered in selected patients for detection of brocnhostenosis.Summary at a GlanceWe performed a prospective study to elucidate incidence and clinical predictors of EBTB. More than 50% of patients with PTB have EBTB. Female gender and longer duration of symptoms are the main predictors of concomitant EBTB.

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Autophagy is an important antimicrobial effector process that defends against Mycobacterium tuberculosis (Mtb), the human pathogen causing tuberculosis (TB). MicroRNAs (miRNAs), endogenous noncoding RNAs, are involved in various biological functions and act as post-transcriptional regulators to target mRNAs. The process by which miRNAs affect antibacterial autophagy and host defense mechanisms against Mtb infections in human monocytes and macrophages is largely uncharacterized. In this study, we show that Mtb significantly induces the expression of MIR144*/hsa-miR-144-5p, which targets the 3'-untranslated region of DRAM2 (DNA damage regulated autophagy modulator 2) in human monocytes and macrophages. Mtb infection downregulated, whereas the autophagy activators upregulated, DRAM2 expression in human monocytes and macrophages by activating AMP-activated protein kinase. In addition, overexpression of MIR144* decreased DRAM2 expression and formation of autophagosomes in human monocytes, whereas inhibition of MIR144* had the opposite effect. Moreover, the levels of MIR144* were elevated, whereas DRAM2 levels were reduced, in human peripheral blood cells and tissues in TB patients, indicating the clinical significance of MIR144* and DRAM2 in human TB. Notably, DRAM2 interacted with BECN1 and UVRAG, essential components of the autophagic machinery, leading to displacement of RUBCN from the BECN1 complex and enhancement of Ptdlns3K activity. Furthermore, MIR144* and DRAM2 were critically involved in phagosomal maturation and enhanced antimicrobial effects against Mtb. Our findings identify a previously unrecognized role of human MIR144* in the inhibition of antibacterial autophagy and the innate host immune response to Mtb. Additionally, these data reveal that DRAM2 is a key coordinator of autophagy activation that enhances antimicrobial activity against Mtb.

Toxoplasma gondii is an obligate intracellular protozoan parasite that induces antitumor activity against certain types of cancers. However, little information is available regarding the immunologic mechanisms that regulate these effects. For this purpose, C57BL/6 mice were administered either the T. gondii Me49 strain orally or Lewis lung carcinoma (LLC) cells intramuscularly. Survival rates, tumor size, histopathology, and immune responses were determined for each group, and angiogenesis was evaluated by in vivo Matrigel plug assay. Toxoplasma-infected (TG-injected) mice survived the entire experimental period, whereas cancer cell-bearing (LLC-injected) mice died within six weeks. Mice injected with both T. gondii and cancer cells (TG/LLC-injected group) showed significantly increased survival rates, CD8+ T-cell percentages, IFN-γ mRNA expression levels, serum IgG2a titers, and CTL responses as compared to the LLC-injected mice. In addition, angiogenesis in the TG/LLC-injected mice was notably inhibited. These effects in TG/LCC-injected mice were similar or were increased by the addition of an adjuvant, Quil-A. However, TG/LLC-injected mice showed decreased percentages of CD4+ and CD8+ T-cells, IFN-γ mRNA expression levels, and serum IgG1 and IgG2a titers as compared to TG-injected mice. Taken together, our results demonstrate that T. gondii infection inhibits tumor growth in the Lewis lung carcinoma mouse model through the induction of Th1 immune responses and antiangiogenic activity.

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The roles of gut microbiota on the natural course of atopic dermatitis (AD) are not yet fully understood. We investigated whether the composition and function of gut microbiota and short-chain fatty acids (SCFAs) at 6 months of age could affect the natural course of AD up to 24 months in early childhood. Methods: Fecal samples from 132 infants were analyzed using pyrosequencing, including 84 healthy controls, 22 transient AD and 26 persistent AD subjects from the Cohort for Childhood Origin of Asthma and Allergic Diseases (COCOA) birth cohort. The functional profile of the gut microbiome was analyzed by whole-metagenome sequencing. SCFAs were measured using gas chromatography-mass spectrometry. Results: Low levels of Streptococcus and high amounts of Akkermansia were evident in transient AD cases, and low Clostridium, Akkermansia and high Streptococcus were found in children with persistent AD. The relative abundance of Streptococcus positively correlated with scoring of AD (SCORAD) score, whereas that of Clostridium negatively correlated with SCORAD score. The persistent AD group showed decreased gut microbial functional genes related to oxidative phosphorylation compared with healthy controls. Butyrate and valerate levels were lower in

Spotlight on etching: (11-22) semipolar GaN plane light-emitting diodes (LEDs) are demonstrated using a wet-etching process. A trigonal prism cell structure with a (0001) c plane and nnn{10-10} m planes is formed after KOH wet etching, and leads to a better ohmic contact and enhanced light extraction. LEDs fabricated by wet etching show excellent output performance 1.89 times higher than that of the reference LEDs.