Background: Rosacea is a chronic inflammatory disorder characterized by flushing, erythema, papules/pustules, and telangiectasia. Several clinical studies have investigated the efficacy of botulinum neurotoxin A (BoNT/A) in the treatment of rosacea, but its mechanism of action remains unclear. Objective: This study aims to examine the potential role of BoNT/A in a mouse model of rosacea-like skin lesions induced by the 37-amino acid C-terminal cathelicidin peptide (LL-37). Methods: Mice were randomly divided into 4 groups: Control, LL-37, LL-37 + BoNT/A, and LL-37 + dexamethasone. Results: BoNT/A treatment alleviated skin damage, reduced skin thickness, and decreased mast cell infiltration. Furthermore, BoNT/A improved redness score severity and redness area while enhancing skin barrier function by suppressing transepidermal water loss and increasing skin hydration. At the molecular level, BoNT/A decreased the mRNA levels of interleukin (IL)-6 and tumor necrosis factor-α, which are known as pro-inflammatory cytokines. It also downregulated the expression of pyrin domain-containing protein 3, caspase-1, and IL-1 beta in the LL-37-injected dorsal skin. Furthermore, BoNT/A prevented LL-37-mediated upregulation of neurovascular-associated factors, including CD31, transient receptor potential vanilloid 1, calcitonin-related polypeptide alpha, vascular endothelial growth factor, chymase 1, and tryptase alpha/beta 1. Conclusion These results indicate that BoNT/A effectively alleviates inflammatory and vascular responses in a rosacea mouse model, highlighting its potential as a promising preventive approach for rosacea.

Conventional aryl hydrocarbon receptor (AhR) antagonists, which play a critical role in modulating tumor immune evasion, have shown limited clinical translation due to poor solubility, restricted systemic exposure, and dose-limiting toxicities. To overcome these limitations, we developed SB5794, a phosphate prodrug of the potent AhR antagonist SB2617, designed to improve aqueous solubility and pharmacokinetic properties. SB5794 exhibited markedly enhanced solubility and achieved more than six-fold higher systemic exposure in mice compared with SB2617, while fully retaining its in vitro AhR antagonistic activity. In syngeneic tumor models, SB5794 significantly inhibited tumor growth, and its combination with anti–PD-1 therapy further enhanced antitumor efficacy. However, repeated-dose studies revealed dose-dependent histopathological changes in the gastrointestinal tract, liver, and immune organs. Collectively, these findings demonstrate that SB5794 possesses improved drug-like properties and strong immunomodulatory activity, supporting its potential as a next-generation AhR-targeted immunotherapeutic candidate.

Background: The distribution of bacteria isolated from bloodstream infections and cumulative antimicrobial susceptibility data are the basis for empirical decisions regarding antibiotics as an initial treatment. Therefore, it is important to consistently collect blood culture results of individual patients and analyze them correctly. Methods: The blood culture results of patients at a university hospital from 2016 to 2020 were analyzed retrospectively to determine the bacterial distributions and antibiotic resistance patterns. Duplicates were eliminated by including only the first isolate of each species per patient. Results: Escherichia coli (27.1%) was the most commonly isolated bacterium from blood cultures, followed by Klebsiella pneumoniae (10.1%) and Staphylococcus aureus (8.6%). The methicillin resistance rate of S. aureus was 49.2%, and the vancomycin resistance rate of Enterococcus faecium was 39.5%; with no significant changes over the study period. The cefotaxime, ciprofloxacin, and ertapenem resistance rates of E. coli were 35.0%, 46.8%, and 0.7%, respectively. Seventeen carbapenem-resistant E. coli strains were isolated, of which 11 produced carbapenemase. The cefotaxime, ciprofloxacin, and ertapenem resistance rates of K. pneumoniae were 29.5%, 31.7%, and 5.4%, respectively. Forty-eight carbapenem-resistant K. pneumoniae strains were isolated, of which 37 produced carbapenemase. The imipenem resistance rates of Acinetobacter baumannii and Pseudomonas aeruginosa were 72.3% and 23.4%, respectively. Conclusion In the blood culture results from 2016 to 2020, the isolation frequency of E.coli, K. pneumoniae, and E. faecium showed an increasing trend, whereas that of S. aureus was stable. Over the 5 year study period, the ciprofloxacin resistance rate of E. coli and P.aeruginosa and ampicillin/sulbactam resistance rate of A. baumannii significantly increased.

Background: Rapid antimicrobial susceptibility testing (RAST) is important for the appropriate treatment of bloodstream infections. The QMAC-dRAST system (QuantaMatrix Inc., Korea) can directly perform RAST using positive blood culture samples with microscopic imaging. This study aimed to evaluate the performance of the QMAC-dRAST system for AmpCβ-lactamase-producing Enterobacterales. Methods: Eighty isolates (20 Morganella morganii, 20 Serratia marcescens, 10 Klebsiella aerogenes, 10 Enterobacter cloacae, and 20 Citrobacter freundii) and 14 antimicrobial agents were included in the antimicrobial susceptibility testing (AST). The performance of the QMAC-dRAST system was evaluated by simulating the clinical blood culturing process. We conducted a comparative evaluation of the QMAC-dRAST and Vitek 2 systems (bioMérieux Inc., France). Broth microdilution tests were performed as the reference method to resolve any discrepancies in the AST results between the two systems. Results: For 20 M. morganii and 20 S. marcescens, the categorical agreement (CA) between the QMAC-dRAST and Vitek 2 systems increased from 55.4% to 83.8% after AST algorithm optimization. Moreover, the discrepancy rates decreased as follows: from 19.1% to 5.4% very major errors (VME), from 38.3% to 4.3% major errors (ME), and from 14.6% to 12.1% minor errors (mE) for the QMAC-dRAST system compared to the Vitek 2 system. For all 80 tested isolates, the QMAC-dRAST system showed 93.0% CA, 1.7% VME, 2.3% ME, and 4.9% mE. Conclusion The QMAC-dRAST system was comparable to the Vitek 2 system after AST algorithm optimization for AmpC β-lactamase-producers, which are major pathogens and require time to express the enzyme. However, further modifications of the AST algorithm are still warranted.

Purpose: This study aimed to compare and analyze the job stress of nurses with and without in COVID-19-related work. Methods: A structured self-reported questionnaire survey was conducted to assess job stress. The extent of job stress was compared between nurses with COVID-19 (COVID-19 group) and those without such experience (non-COVID-19 group). Multiple regression analysis was performed to identify the factors influencing job stress. Results: Job stress was higher in the COVID-19 group compared to the non-COVID-19 group (t=2.54, p=.12). In sub-categorical comparison, stress driven by a taxing work environment, relationship conflict, and work schedule was higher in the COVID-19 group than the non-COVID-19 group. Multiple regression analysis revealed the job stress was higher among nurses with COVID-19-related work experience than that of non-experienced nurses. The factors affecting job stress of nurses with COVID-19-related work experience included emergency room work, providing nursing assistant for COVID-patients, and caring for these patients. Conclusion Since COVID-19-related work experience is a major factor that affects nurses' job stress, it is imperative to provide various support measures for nursing assistants such as providing a break from working in an environment with high risk of infection, adjusting work schedules, resolving conflicts between personnel, and securing support.

Spinal epidural arteriovenous fistula (SEDAVF) is a rare vascular malformation. Due to the mass effect of enlarged epidural veins and venous hypertension, progressive radiculopathy and myelopathy are likely to occur. A 33-year-old female presented with right upper extremity weakness for a month. The cause of this symptom was a SEDAVF, which was located near the C5-6-7 foramens and compressed the nerve roots. In the absence of intradural venous drainage, endovascular treatment is often difficult because of the large venous pouch. We performed endovascular trapping of the vertebral artery (VA) and loose packing of the coil material on the AVF to minimize mass effects. Immediately after embolization, the fistula was occluded, but a small new feeder vessel developed a day later. An n-butyl cyanoacrylate embolization was performed, and the fistula was successfully occluded.

In Asia, the roots of Paeonia lactiflora and Astragalus membranaceus have been used as therapeutic agents for thousands of years. Once the medicinal plants are harvested, they are dried and their ingredients are extracted by heat-mediated reflux extraction. However, the condensed structure of organic products (especially roots) limits the extraction of bioactive components. In this study, we assessed the effect of the puffing method (using high temperature and pressure) before the extraction process in relation to the profile and antioxidant capacity of active ingredients. We demonstrated that the additional puffing process before extraction methods improves the yield of polyphenol concentrations and antioxidant activities from the roots of P. lactiflora and A.membranaceus.

Background: The rapid antimicrobial susceptibility testing (AST) performed on urine samples would guide the adequate choice of antibiotics for obtaining better treatment outcomes in patients. Our study aimed to evaluate the performance of the modified-EUCAST (European Committee on Antimicrobial Susceptibility Testing) rapid direct AST on urine samples. Methods: From >2,000 urine samples, a total of 128 urine samples containing bacterial counts of ≥2 × 10 4 CFU/mL with a uniform bacterial shape were initially included based on flow cytometry (Sysmex UF-1000i, Japan) and Gram staining, respectively. A total of 103 samples showing the presence of Enterobacteriaceae were finally selected in this study. The urine samples were directly inoculated on Mueller-Hinton agar, which was used in the current EUCAST rapid direct AST on blood samples. The size of the growth inhibition zones around antimicrobial disks was measured using a digital scanner (BIOMIC vision analyzer, Giles scientific, USA) and further confirmed by visualization with naked eyes after incubation for 4, 6, and 8 hours. The AST interpretations were compared to those of the conventional VITEK 2 AST system (bioMérieux, France) and the discrepancies between both tests were confirmed with the E-test. Results: The antibiotics, namely ampicillin, cefazolin, aztreonam, ceftazidime, cefotaxime, cefoxitin, cefepime, gentamicin, ciprofloxacin, and cotrimoxazole showed excellent correlations with modified-EUCAST rapid direct test and conventional ASTs with >0.75 weighted kappa values. The categorical agreement of the rapid direct AST was 1,442 (93.3%), with 76 (4.9%) minor error, 9 (0.6%) major error and 18 (1.2%) very major error, implicating the reliability of this method for clinical application. Conclusion Performing the modified-EUCAST rapid direct AST on urine samples can predict reliable AST results within 8 hours. The rapid direct AST can help the physicians to initiate adequate antimicrobial treatment for urinary tract infections.