Comparison of Extended-Spectrum Beta-Lactamase-Producing Escherichia coli Isolates From Rooks (Corvus frugilegus) and Contemporary Human-Derived Strains: A One Health Perspective.

During winter, a large number of rooks gather and defecate at the park of a university clinic. We investigated the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli in these birds and compared recovered isolates with contemporary human isolates. In 2016, fecal samples were collected from 112 trap-captured rooks and investigated for presence of ESBL producers using eosin methylene blue agar supplemented by 2 mg/L cefotaxime; 2,455 contemporary human fecal samples of patients of the clinics sent for routine culturing were tested similarly. In addition, 42 ESBL-producing E. coli isolates collected during the same period from inpatients were also studied. ESBL genes were sought for by PCR and were characterized by sequencing; E. coli ST131 clones were identified. Epidemiological relatedness was determined by pulsed-field gel electrophoresis and confirmed using whole genome sequencing in selected cases. Thirty-seven (33%) of sampled rooks and 42 (1.7%) of human stools yielded ESBL-producing E coli. Dominant genes were bla CTX-M-55 and bla CTX-M-27 in corvid, bla CTX-M-15 and bla CTX-M-27 in human isolates. ST162 was common among rooks. Two rook-derived E. coli belonged to ST131 C1-M27, which was also predominant (10/42) among human fecal and (15/42) human clinical isolates. Another potential link between rooks and humans was a single ST744 rook isolate grouped with one human fecal and three clinical isolates. Despite possible contact, genotypes shared between rooks and humans were rare. Thus, rooks are important as long-distance vectors and reservoirs of ESBL-producing E. coli rather than direct sources of infections to humans in our setting.

Discovery of BAY-985, a Highly Selective TBK1/IKKε Inhibitor.

The serine/threonine kinase TBK1 (TANK-binding kinase 1) and its homologue IKKε are noncanonical members of the inhibitor of the nuclear factor κB (IκB) kinase family. These kinases play important roles in multiple cellular pathways and, in particular, in inflammation. Herein, we describe our investigations on a family of benzimidazoles and the identification of the potent and highly selective TBK1/IKKε inhibitor BAY-985. BAY-985 inhibits the cellular phosphorylation of interferon regulatory factor 3 and displays antiproliferative efficacy in the melanoma cell line SK-MEL-2 but showed only weak antitumor activity in the SK-MEL-2 human melanoma xenograft model.

The Short-term Effects of ASPIRA: A Web-based, Multimedia Smoking Prevention Program for Adolescents in Romania: A Cluster Randomized Trial.

INTRODUCTION: Although web-based, multimedia smoking prevention programs have been tested in several high-income countries, their efficacy in Central and Eastern Europe is unknown. The aim of this trial was to assess the short-term effects of ASPIRA, among Romanian and Hungarian speaking ninth graders in Tirgu Mures, Romania. ASPIRA is the Romanian acronym for the translated and adapted version of ASPIRE, "A Smoking Prevention Interactive Experience," an evidence-based smoking prevention program originally developed to prevent tobacco use among high school students in the United States. METHODS: Sixteen high schools in Tirgu Mures, Romania were randomized to receive five weekly sessions of the ASPIRA web-based, multimedia program or to a control condition. Socio-demographic data, psychosocial characteristics, and smoking behavior were collected from students at baseline and at 6 months. A hierarchical logistic regression analysis was conducted to test the efficacy of the intervention on smoking initiation and current smoking among 1369 students. RESULTS: Never-smoker students in the intervention arm were 35% less likely to report smoking initiation 6 months after the baseline assessment (OR = 0.65, 95%CI: 0.44-0.97). Reduced smoking initiation was observed most notably among students who were exposed to at least 75% of the ASPIRA program. There was no statistically significant effect of the intervention on current tobacco use (OR = 0.80, 95%CI: 0.44-1.46). CONCLUSIONS: ASPIRA, an adapted version of the evidence-based, multimedia ASPIRE program that was originally developed and tested in the United States may decrease smoking initiation among multi-ethnic adolescents in Central and Eastern Europe. IMPLICATIONS: (1). Web-based, multimedia smoking prevention programs may be effective tools to prevent smoking initiation among multi-ethnic adolescent communities in Central and Eastern Europe. (2). The degree of exposure is critical, only high exposure to the multimedia smoking prevention program is associated with reduced smoking initiation.

Use of electronic cigarettes and alternative tobacco products among Romanian adolescents.

OBJECTIVES: To assess socio-demographic and smoking-related correlates of e-cigarette and alternative tobacco products (ATPs) use in a multi-ethnic group of adolescents in Tîrgu Mures, Romania. METHODS: The cross-sectional study included 1835 high school students from Tirgu Mures, Romania. Socio-demographic variables and data about smoking and e-cigarettes and ATP use were collected using an online questionnaire. Chi-square tests or one-way ANOVA were applied to compare never smokers, non-current smokers, and current smokers. Multiple logistic regression was conducted to determine the correlates of e-cigarettes and ATP use. RESULTS: The most frequently tried non-cigarette nicotine and tobacco products were e-cigarette (38.5 %), cigar (31.4 %) and waterpipe (21.1 %). Ever trying and current use of cigarettes were the most important correlates of e-cigarette and ATPs use. Sex, ethnicity, sensation seeking and perceived peer smoking were correlates of several ATPs use. CONCLUSIONS: The results of this study may inform the development of tailored tobacco control programs.

Optical resolution of 1-(1-naphthyl)ethylamine by its dicarboxylic acid derivatives: Structural features of the oxalic acid derivative diastereomeric salt pair.

Optical resolution methods were established for racemic 1-(1-naphthyl) ethylamine. The resolving agents were synthesized by N-derivatizing (R)-1-(1-naphthyl) ethylamine with dicarboxylic acids. Oxalic, malonic, and succinic acid derivatives were found to be suitable resolving agents. These resolutions are parallel to a series of optical resolutions of 1-phenylethylamine which had been previously performed by our research group using similar derivative resolving agents (Balint et al., Tetrahedron: Asymmetry 2001;12:1511-1518.) The comparison of the results of the enantiomer separations is performed. The diastereomeric salts formed with (R)-N-[1-(1-naphthyl)ethyl]oxalamic acid were investigated by single crystal X-ray diffraction. The crystal structures were compared with the previously published structures of the diastereomers of the phenyl-substituted analogue, namely (R)- and (S)-1-phenylethylammonium (R)-N-(1-phenylethyl)oxalamates (Balint et al., Tetrahedron: Asymmetry 2001;12:1511-1518).

Enantioseparation of secondary alcohols by diastereoisomeric salt formation.

A general method was found for the resolution of the racemic 1-phenyl-1-propanol (1) and 1-phenyl-2-propanol (2) with various resolving agents. Monoesters of the alcohols were prepared, which were then reacted with different chiral bases. Successful optical resolutions were achieved only with the maleic acid monoesters (3 and 6). Alcohol 1 has been resolved to >99% enantiomeric excess by diastereoisomeric salt formation via its maleic acid monoester (3) using cinchonidine (9) as resolving agent. Alcohol 2 has been obtained in 98% enantiomeric excess by diastereoisomeric salt formation via its the maleic acid monoester (6) using (+)-dehydroabietylamine (11) as resolving agent.

Optical resolution by crystallization from melt using enantiomer derivatives as resolving agents: nonlinear behavior of resolving agent mixtures.

Substituted racemic 1-phenylethylamine derivatives were reacted in molten phase with chiral N-substituted 1-phenylethylamine dicarboxylic acid derivatives (4-9), and their mixtures (e.g., 4+6, 7+8, etc.) in different ratios, and the crystalline quasi-racemic diastereomers so formed were separated. Nonlinear behavior of the mixtures of resolving agents having related structure and considerable positive and negative chiral-chiral interactions were observed.