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9-Substituted 6,6-dimethyl-11-oxo-6,11-dihydro-5H-benzo[b]carbazoles were discovered as highly selective and potent anaplastic lymphoma kinase (ALK) inhibitors by structure-based drug design. The high target selectivity was achieved by introducing a substituent close to the E(0) region of the ATP binding site, which has a unique amino acid sequence. Among the identified inhibitors, compound 13d showed highly selective and potent inhibitory activity against ALK with an IC(50) value of 2.9 nM and strong antiproliferative activity against KARPAS-299 with an IC(50) value of 12.8 nM. The compound also displayed significant antitumor efficacy in an established ALK fusion gene-positive anaplastic large-cell lymphoma (ALCL) xenograft model in mice without body weight loss.

The spread of COVID-19 pandemic may have affected antibiotic consumption patterns and the prevalence of colonized or infected by multidrug-resistant (MDR) bacteria. We investigated the differences in the consumption of antibiotics easily prone to resistance and the prevalence of MDR bacteria during the COVID-19 pandemic (March 2020 to September 2021) compared to in the pre-pandemic period (March 2018 to September 2019). Data on usage of antibiotics and infections caused by methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA) were obtained from hospitalized patients in four university hospitals. The consumption of penicillin with β-lactamase inhibitors (3.4% in ward, 5.8% in intensive care unit (ICU)), and carbapenems (25.9% in ward, 12.1% in ICU) increased during the pandemic period. The prevalence of MRSA (4.7%), VRE (49.0%), CRE (22.4%), and CRPA (20.1%) isolated in clinical samples from the ward and VRE (26.7%) and CRE (36.4%) isolated in clinical samples from the ICU were significantly increased, respectively. Meanwhile, only the prevalence of CRE (38.7%) isolated in surveillance samples from the ward increased. The COVID-19 pandemic is associated with increased consumption of antibiotics and has influenced the prevalence of infections caused by MDR isolates.

Reliable results of serologic positivity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody before and after AstraZeneca (AZ) vaccination are essential to estimate the efficacy of vaccination. We assessed the positivity rates and associated factors using five SARS-CoV-2 antibody assays. A total of 228 paired serum samples (456 samples) were obtained from 228 participants. After baseline sampling, the second sampling was conducted between 11-28 days after the first dose of AZ. Sera were tested using five SARS-CoV-2 antibody assays, including two surrogate virus neutralization tests. A questionnaire on symptom, severity, and duration of adverse reactions was completed by all participants. The overall positive rates for SARS-CoV-2 antibody were 84.6% for Roche, 92.5% for Abbott, 75.4% for Siemens, 90.7% for SD Biosensor, and 66.2% for GenScript assays after the first dose of AZ vaccination. The positive rates and antibody titer of sera obtained between 21-28 days were significantly higher than those obtained between 11-20 days in all five assays. More severe and longer duration of adverse reactions were related to higher SARS-CoV-2 antibody levels. The agreements and correlations among the applied assays were substantial (к=0.73-0.95) and strong (ρ=0.83-0.91). A single dose of AZ vaccination led to high positivity rates based on the five assays. Days after vaccination and adverse reactions could help estimate serologic conversions. The results should be interpreted cautiously considering the applied assays and cutoffs. Our findings could inform decisions regarding vaccination and laboratory settings and, thus, contribute to the control of the spread of SARS-CoV-2 infection.