The Bacillus subtilis lutABC operon encodes three iron-sulfur-containing proteins required for Llactate utilization and involved in biofilm formation. The transcriptional regulator LutR of the GntR family negatively controls lutABC expression. The lutP gene, which is situated immediately upstream of lutR, encodes an L-lactate permease. Here, we show that lutP expression can be strongly induced by L-lactate and is subject to partial catabolite repression by glucose. Disruption of the lutR gene led to a strong derepression of lutP and no further induction by L-lactate, suggesting that the LutR repressor can also negatively control lutP expression. Electrophoretic mobility shift assay revealed a LutR-binding site located downstream of the promoter of lutA or lutP and containing a consensus inverted repeat sequence 59-TCATC-N 1 -GATGA-39. Reporter gene analysis showed that deletion of each LutR-binding site caused a strong derepression of lutA or lutP. These results indicated that these two LutR-binding sites can function as operators in vivo. Moreover, deletion analysis identified a DNA segment upstream of the lutP promoter to be important for lutP expression. In contrast to the truncated LutR of laboratory strains 168 and PY79, the full-length LutR of the undomesticated strain RO-NN-1, and probably many other B. subtilis strains, can directly and negatively regulate lutP transcription. The absence or presence of the N-terminal 21 aa of the full-length LutR, which encompass a small part of the predicted winged helix-turn-helix DNA-binding motif, may probably alter the DNA-binding specificity or affinity of LutR.

Background: Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has also imposed a substantial economic and social burden on the health care system. In Taiwan, a nationwide COPD pay-for-performance (P4P) program was designed to improve the quality of COPD-related care by introducing financial incentives for health care providers and employing a multidisciplinary team to deliver guideline-based, integrated care for patients with COPD, reducing adverse outcomes, especially COPD exacerbation. However, the results of a survey of the effectiveness of the pay-for-performance program in COPD management were inconclusive. To address this knowledge gap, this study evaluated the effectiveness of the COPD P4P program in Taiwan. Methods: This retrospective cohort study used data from Taiwan's National Health Insurance claims database and nationwide COPD P4P enrollment program records from June 2016 to December 2018. Patients with COPD were classified into P4P and non-P4P groups. Patients in the P4P group were matched at a ratio of 1:1 based on age, gender, region, accreditation level, Charlson Comorbidity Index (CCI), and inhaled medication prescription type to create the non-P4P group. A difference-in-difference analysis was used to evaluate the influence of the P4P program on the likelihood of COPD exacerbation, namely COPD-related emergency department (ED) visit, intensive care unit (ICU) admission, or hospitalization. Results:The final sample of 14,288 patients comprised 7144 in each of the P4P and non-P4P groups. The prevalence of COPD-related ED visits, ICU admissions, and hospitalizations was higher in the P4P group than in the non-P4P group 1 year before enrollment. After enrollment, the P4P group exhibited a greater decrease in the prevalence of COPD-related ED visits and hospitalizations than the non-P4P group (ED visit: −2.98%, p<0.05, 95% confidence interval [CI]: −0.277 to −0.086; hospitalization: −1.62%, p<0.05, 95% CI: −0.232 to −0.020), whereas no significant difference was observed between the groups in terms of the changes in the prevalence of COPD-related ICU admissions. Conclusion:The COPD P4P program exerted a positive net effect on reducing the likelihood of COPD exacerbation, namely COPD-related ED visits and hospitalizations. Future studies should examine the long-term cost-effectiveness of the COPD P4P program.

Background: To date, no data are available regarding the effect of chronic obstruction pulmonary disease (COPD) and COPD with acute exacerbation (COPDAE) on survival in patients with lung squamous cell carcinoma (SCC) receiving definitive concurrent chemoradiotherapy (CCRT). Patients and methods: We enrolled 3986 patients with clinical stage IIIA–IIIB, unresectable lung SCC, who had received standard definitive CCRT, and categorized them into two groups based on their COPD status to compare overall survival outcomes. We also examined the effects of COPD severity (0, 1, or ≥2 hospitalizations for COPDA within 1 year before CCRT). Results: In the inverse probability of treatment weighting (IPTW)-adjusted model, the adjusted hazard ratio (aHR) (95% confidence interval (CI)) of all-cause death for COPD was 1.04 (1.01, 1.16), compared no COPD in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. In the IPTW-adjusted model, the aHRs (95% CIs) of 1 and ≥ 2 hospitalizations for COPDAE within 1 year before CCRT were 1.32 (1.19, 1.46) and 1.81 (1.49, 2.19) respectively, compared with no hospitalization for COPDAE. Conclusion: COPD and its severity are significant independent risk factors for all-cause death in patients with stage IIIA–IIIB lung SCC receiving definitive CCRT. Hospitalization for COPDAE within 1 year before CCRT is the significant independent risk factor for lung cancer death in the patients with stage IIIA–IIIB lung SCC receiving definitive CCRT.

Some patients with severe asthma experience exacerbations despite receiving multiple therapy. The risk of exacerbation and heterogeneous response to treatment may be associated with specific inflammatory molecules that are responsive or resistant to corticosteroids. We aimed to identify the independent factors predictive for the future risk of exacerbation in patients with severe asthma. In this multi-center prospective observational study, 132 patients with severe asthma were enrolled and divided into exacerbation (n = 52) and non-exacerbation (n = 80) groups on the basis of exacerbation rate after a 1-year follow-up period. We found that previous history of severe-to-serious exacerbation, baseline blood eosinophil counts (≥ 291cells/μL), and serum tryptase (≤ 1448 pg/mL) and thrymic stromal lymphopoietin (TSLP) levels (≥ 25 pg/mL) independently predicted the future development of exacerbation with adjusted odds ratios (AOR) of 3.27, 6.04, 2.53 and 8.67, respectively. Notably, the patients with high blood eosinophil counts and low tryptase levels were likely to have more exacerbations than those with low blood eosinophil counts and high tryptase levels (AOR 16.9). TSLP potentially played the pathogenic role across different asthma phenotypes. TSLP and tryptase levels may be implicated in steroid resistance and responsiveness in the asthma inflammatory process. High blood eosinophil counts and low serum tryptase levels predict a high probability of future asthma exacerbation.

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