Circulating extracellular DNA (ecDNA) is known to worsen the outcome of many diseases. ecDNA released from neutrophils during infection or inflammation is present in the form of neutrophil extracellular traps (NETs). It has been shown that higher ecDNA concentration occurs in a number of inflammatory diseases including inflammatory bowel disease (IBD). Enzymes such as peptidyl arginine deiminases (PADs) are crucial for NET formation. We sought to describe the dynamics of ecDNA concentrations and fragmentation, along with NETosis during a mouse model of chemically induced colitis. Plasma ecDNA concentration was highest on day seven of dextran sulfate sodium (DSS) intake and the increase was time-dependent. This increase correlated with the percentage of cells undergoing NETosis and other markers of disease activity. Relative proportion of nuclear ecDNA increased towards more severe colitis; however, absolute amount decreased. In colon explant medium, the highest concentration of ecDNA was on day three of DSS consumption. Early administration of PAD4 inhibitors did not alleviate disease activity, but lowered the ecDNA concentration. These results uncover the biological characteristics of ecDNA in IBD and support the role of ecDNA in intestinal inflammation. The therapeutic intervention aimed at NETs and/or nuclear ecDNA has yet to be fully investigated.

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Dysgraphia (D) is a complex specific learning disorder with a prevalence of up to 30%, which is linked with handwriting issues. The factors recognized for assessing these issues are legibility and performance time. Two questionnaires, the Handwriting Proficiency Screening Questionnaire (HPSQ) for teachers and its modification for children (HPSQ-C), were established as quick and valid screening tools along with a third factor-emotional and physical well-being. Until now, in the Czechia, there has been no validated screening tool for D diagnosis. A study was conducted on a set of 294 children from 3rd and 4th year of primary school (132 girls/162 boys; M age 8.96 ± 0.73) and 21 teachers who spent most of their time with them. Confirmatory factor analysis based on the theoretical background showed poor fit for HPSQ [χ 2 (32) = 115.07, p < 0.001; comparative fit index (CFI) = 0.95; Tucker-Lewis index (TLI) = 0.93; root mean square error of approximation (RMSEA) = 0.09; standard root mean square residual (SRMR) = 0.05] and excellent fit for HPSQ-C [χ 2 (32) = 31.12, p = 0.51; CFI = 1.0; TLI = 1.0; RMSEA = 0.0; SRMR = 0.04]. For the HPSQ-C models, there were no differences between boys and girls [ χ 2 (7) = 12.55, p = 0.08]. Values of McDonalds's ω indicate excellent (HPSQ, ω = 0.9) and acceptable (HPSQ-C, ω = 0.7) reliability. Boys were assessed as worse writers than girls based on the results of both questionnaires. The grades positively correlate with the total scores of both HPSQ (r = 0.54, p < 0.01) and HPSQ-C (r = 0.28, p < 0.01). Based on the results, for the assessment of handwriting difficulties experienced by Czech children, we recommend using the HPSQ-C questionnaire for research purposes.

Methamphetamine (MA), as massively abused psychoactive stimulant, has been associated with many neurological diseases. It has various potent and neurotoxic properties. There are many mechanisms of action that contribute to its neurotoxic and degenerative effects, including excessive neurotransmitter (NEU) release, blockage of NEU uptake transporters, degeneration of NEU receptors, process of oxidative stress etc. MA intoxication is caused by blood-brain barrier disruption resulted from MA-induced oxidation stress. In our laboratory we constantly work on animal research of MA. Our current interest is to investigate processes of MA-induced alteration in neurotransmission, especially during development of laboratory rat. This review will describe current understanding in role of NEUs, which are affected by MA-induced neurotoxicity caused by altering the action of NEUs in the central nervous system (CNS). It also briefly brings information about NEUs development in critical periods of development.

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