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Copyright of Czecho-Slovak Pediatrics / Česko-Slovenská Pediatrie is the property of Czech Medical Association of JE Purkyne and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Based on toxicological evidence, children's exposure to phthalates may contribute to altered neurodevelopment and abnormal regulation of brain-derived neurotrophic factor (BDNF). We analyzed data from five aligned studies of the Human Biomonitoring for Europe (HBM4EU) project. Ten phthalate metabolites and protein BDNF levels were measured in the urine samples of 1148 children aged 6-12 years from Italy (NACII-IT cohort), Slovakia (PCB-SK cohort), Hungary (InAirQ-HU cohort) and Norway (NEBII-NO). Serum BDNF was also available in 124 Slovenian children (CRP-SLO cohort). Children's total, externalizing and internalizing behavioral problems were assessed using the Child Behavior Checklist at 7 years of age (only available in the NACII-IT cohort). Adjusted linear and negative binomial regression models were fitted, together with weighted quantile sum (WQS) regression models to assess phthalate mixture associations. Results showed that, in boys but not girls of the NACII-IT cohort, each natural-log-unit increase in mono-n-butyl phthalate (MnBP) and Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) was cross-sectionally associated with higher externalizing problems [incidence rate ratio (IRR): 1.20; 95% CI: 1.02, 1.42 and 1.26; 95% CI: 1.03, 1.55, respectively]. A suggestive mixture association with externalizing problems was also observed per each tertile mixture increase in the whole population (WQS-IRR = 1.15; 95% CI: 0.97, 1.36) and boys (IRR = 1.20; 95% CI: 0.96, 1.49). In NACII-IT, PCB-SK, InAirQ-HU and NEBII-NO cohorts together, urinary phthalate metabolites were strongly associated with higher urinary BDNF levels, with WQS regression confirming a mixture association in the whole population (percent change (PC) = 25.9%; 95% CI: 17.6, 34.7), in girls (PC = 18.6%; 95% CI: 7.92, 30.5) and mainly among boys (PC = 36.0%; 95% CI: 24.3, 48.9). Among CRP-SLO boys, each natural-log-unit increase in ∑DINCH concentration was associated with lower serum BDNF levels (PC: -8.8%; 95% CI: -16.7, -0.3). In the NACII-IT cohort, each natural-log-unit increase in urinary BDNF levels predicted worse internalizing scores among all children (IRR: 1.15; 95% CI: 1.00, 1.32). Results suggest that (1) children's exposure to di-n-butyl phthalate (DnBP) and di(2-ethylhexyl) phthalate (DEHP) metabolites is associated with more externalizing problems in boys, (2) higher exposure to DINCH may associate with lower systemic BDNF levels in boys, (3) higher phthalate exposure is associated with higher urinary BDNF concentrations (although caution is needed since the possibility of a "urine concentration bias" that could also explain these associations in noncausal terms was identified) and (4) higher urinary BDNF concentrations may predict internalizing problems. Given this is the first study to examine the relationship between phthalate metabolite exposure and BDNF biomarkers, future studies are needed to validate the observed associations.

Information about the effects of phthalates and non-phthalate substitute cyclohexane-1,2-dicarboxylic acid diisononyl ester (HEXAMOLL ® DINCH) on children's neurodevelopment is limited. The aim of the present research is to evaluate the association between phthalate/HEXAMOLL ® DINCH exposure and child neurodevelopment in three European cohorts involved in HBM4EU Aligned Studies. Participating subjects were school-aged children belonging to the Northern Adriatic cohort II (NAC-II), Italy, Odense Child Cohort (OCC), Denmark, and PCB cohort, Slovakia. In each cohort, children's neurodevelopment was assessed through the Full-Scale Intelligence Quotient score (FSIQ) of the Wechsler Intelligence Scale of Children test using three different editions. The children's urine samples, collected for one point in time concurrently with the neurodevelopmental evaluation, were analyzed for several phthalates/HEXAMOLL ® DINCH biomarkers. The relation between phthalates/HEXAMOLL ® DINCH and FSIQ was explored by applying separate multiple linear regressions in each cohort. The means and standard deviations of FSIQ were 109 ± 11 (NAC-II), 98 ± 12 (OCC), and 81 ± 15 (PCB cohort). In NAC-II, direct associations between FSIQ and DEHP's biomarkers were found: 5OH-MEHP+5oxo-MEHP (β = 2.56; 95% CI 0.58-4.55; N = 270), 5OH-MEHP+5cx-MEPP (β = 2.48; 95% CI 0.47-4.49; N = 270) and 5OH-MEHP (β = 2.58; 95% CI 0.65-4.51; N = 270). On the contrary, in the OCC the relation between DEHP's biomarkers and FSIQ tended to be inverse but imprecise ( p -value ≥ 0.10). No associations were found in the PCB cohort. FSIQ was not associated with HEXAMOLL ® DINCH in any cohort. In conclusion, these results do not provide evidence of an association between concurrent phthalate/DINCHHEXAMOLLR DINCH exposure and IQ in children.

Latent Mycobacterium tuberculosis infection presents one of the largest challenges for tuberculosis control and novel antimycobacterial drug development. A series of pyrano[3,2- b ]indolone-based compounds was designed and synthesized via an original eight-step scheme. The synthesized compounds were evaluated for their in vitro activity against M. tuberculosis strains H37Rv and streptomycin-starved 18b (SS18b), representing models for replicating and nonreplicating mycobacteria, respectively. Compound 10a exhibited good activity with MIC 99 values of 0.3 and 0.4 μg/mL against H37Rv and SS18b, respectively, as well as low toxicity, acceptable intracellular activity, and satisfactory metabolic stability and was selected as the lead compound for further studies. An analysis of 10a -resistant M. bovis mutants disclosed a cross-resistance with pretomanid and altered relative amounts of different forms of cofactor F 420 in these strains. Complementation experiments showed that F 420 -dependent glucose-6-phosphate dehydrogenase and the synthesis of mature F 420 were important for 10a activity. Overall these studies revealed 10a to be a prodrug that is activated by an unknown F 420 -dependent enzyme in mycobacteria.

Thymol is a substance with a great therapeutic potential possessing antibacterial and antifungal activity, with a characteristic odour that remains long after application but is not pleasant at higher concentrations. In this study, attention has been focused on describing the chemical and biological properties of the simply prepared trimethylsilyl ether of thymol (kubicin). Interestingly, kubicin has similar volatility as thymol, undergoes hydrolysis in the water (moisture; forming thymol and trimethylsilanol) and can be used at 6,000 times higher concentration than thymol without any negative and irritating odour. Kubicin showed diverse fungistatic and fungicidal activities when tested by direct contact assay, or in vapour phase. The volatile vapour of kubicin was effective on all tested fungal strains. These results suggest that vapours of kubicin might provide an alternative way to fight against fungal contamination., Competing Interests: The authors declare there are no competing interests., (©2020 Kubinec et al.)

Flow injection analysis-tandem mass spectrometry has become widely used for analysis of many biomarkers in various biological matrices. To improve the sensitivity, the compounds are often determined as their butylesters. Since the concentration of urinary excreted compounds are generally reported after normalization to creatinine, the aim of this study was to investigate the possibility of creatinine determination in urine samples which underwent butylation. The impact of derivatization on urinary creatinine determination was investigated by measuring of underivatized and derivatized samples. The 10% creatine to creatinine conversion was observed during butylation, what above 700 μmol creatine/mmol creatinine caused significant creatinine overestimation. In that case, correction for creatine conversion rate was done. QC samples at six concentration levels were examined and precision and accuracy values fulfill the European Medicine Agency validation requirements. The elaborated method was applied for determination of creatinine in 41 real human urine samples. Determined creatinine concentrations were in the range of 0.27-22.3 mmol/L, linearity was confirmed within the concentration range of 0.27-31.7 mmol/L. Obtained results highly correlated with routinely used enzymatic assay for all tested samples and proposed method provide reliable determination of creatinine in butylated urine in a single run with butylesters of other analytes of interest., (Copyright © 2018 Elsevier Inc. All rights reserved.)

A newly designed needle trap device with Carbopack X as a sorbent material is used for sampling, preconcentration and injection of volatile analytes benzene, toluene, ethylbenzene and xylenes (BTEX) into gas chromatograph. The closed system of stripping the analytes from water samples was used. An injection port with a modified metal liner was used to desorb analytes trapped in needle trap device. The main advantage of needle trap device consists in the simple methodology and easiness and rapidity of the analysis. Needle trap device is suitable for sampling in field. The experimental parameters as breakthrough volume of stripping gas, linearity, repeatability and limit of detection (LOD) and quantification (LOQ) were investigated. LOD ranges from 0.05 to 0.07 microgL(-1) and relative standard deviation ranges from 0.5% to 11.6% at concentrations 5 and 0.1 microgL(-1), respectively.