One of the currently assumed causes of impaired social interaction exhibited by children with autism spectrum disorders (ASD) is dysfunction of the mirror neuron system (MNS), which is responsible for imitation, understanding the intentions and emotions of other people. Desynchronization of sensorimotor rhythms is considered to be the indicator of MNS activation. This study aimed to analyze the specific patterns of reactivity of the μ-rhythm in an individually determined frequency range and β-rhythm on the EEG in children with ASD during independent movements, observation, imitation and auditory perception of similar movements performed by another person. The data collected were compared to those describing normally developing children. The study involved right-handed children with ASD aged 5–10 (n = 10) and normally developing children (n = 10). In the independent movements exercise, β-rhythm desynchronization was more pronounced in children with ASD, with difference becoming significant in the P4 locus (p = 0.03). In the movements imitation exercise, the groups showed significant differences in the EEG μ-rhythm in the locus C3 (p = 0.03). Auditory perception of movements revealed significant differences in the ranges of both μ-rhythm (loci F3 and Fz (p = 0.02), F4 (p = 0.04), Cz (p = 0.009)) and β-rhythm (loci Fz (p = 0.01), F4 (p = 0.02)). In these situations, children with ASD exhibited synchronization of sensorimotor rhythms, while normally developing children showed desynchronization. The assumption is that the specific patterns revealed are the consequences of disruption of functions of MNS and anti-mirror system. The data obtained can be used in development of EEG biofeedback training protocols for children with ASD.
VIEWS 3479
 Antiviral system of innate immunity includes two main components: the mitochondrial antiviral sensor — the mitochondrial outer membrane protein and peripheral blood neutrophils capable of forming neutrophilic extracellular traps. Depending on the activation pathway of the mitochondrial antiviral sensor (MAVS), two possible variants of cells death, apoptosis or cellular degeneration with necrotic changes, develop during cell infection with an RNA-containing virus. The development of virus-induced apoptosis of infected cells causes the formation of neutrophilic extracellular traps, the secretion of inflammatory cytokines, ROS generation, tissue damage, hemocoagulation and the development of an acute inflammatory process with the development of COVID-19 pneumonia. Violation of the prion-like reaction of MAVS in response to viral infection of the cell triggers an alternative pathway for activating autophagy. Cells under conditions of prolonged activation of autophagy experience necrotic changes and are eliminated from the organism by monocytes/macrophages that secrete anti-inflammatory cytokines. This type of reaction of the antiviral system of innate immunity corresponds to the asymptomatic course of the disease. From the most significant aspects of the pathogenesis of the coronavirus infection COVID-19 given, recommendations for the prophylactic treatment of this dangerous disease follow. The proposed treatment can significantly decrease the severity of COVID-19 disease and reduce mortality.
VIEWS 3643
The term “chronic critical illness” (CCI) refers to patients with prolonged dependence on intensive care. In most patients, CCI is triggered by severe brain injury. Ever more studies researching the microbiota in pathologic conditions are published every year, but a lot is yet to be elucidated about the composition of the gut microbiota in CCI. The aim of this study was to investigate possible correlations between changes in the taxonomic abundance of the gut microbiota, levels of proinflammatory and neurological serum biomarkers and the severity of central nervous system injury in patients with CCI. Our prospective observational pilot study included 29 patients with CCI. Using real-time PCR allowed us to detected changes in the taxonomic abundance of the gut microbiota. The correlation analysis of serum biomarkers and the taxonomic composition of the gut microbiota revealed statistically significant correlations between cortisol levels and the abundance of F. prausnitzii (r = ‒0.62; p < 0.05) and B. thetaiotaomicron (r = ‒0.57; p < 0.05) in vegetative state patients; between the CRP/albumin ratio and the abundance of S. aureus (r = 0.72; p < 0.05); between the abundance of B. fragilis group/F. prausnitzii and S100 levels (r = 0.45; p <0.05) in conscious patients; between Glasgow coma scale scores and the abundance of Enterococcus spp. (r = ‒0.77; p <0.05) in both groups. Thus, the association between the changes in the taxonomic composition of the gut microbiota and the severity of neurologic deficit can be evaluated using PCR-based diagnostic techniques and blood serum biomarkers. This approach will help to optimize antibacterial treatment regimens and/or develop alternative strategies to minimize the aggressive effect of antibiotics on the gut microbiota.
VIEWS 3697
Thrombogenicity and its causes in patients with ischemic stroke (IS) and pre-existing polycythemia vera (PV) is a significant clinical concern. The aim of this study was to identify the range of factors associated with increased thrombogenicity in patients with IS and pre-existing PV. We performed a physical examination and laboratory tests on 127 patients in the hyperacute stroke stage and 16-18 months after. Of them, 68 patients had PV (the main group) and 59 did not have this condition (the comparison group). Laboratory tests were conducted to evaluate blood rheology, hemostasis, endothelial function, angiogenesis, proinflammatory cytokine levels; we also tested patients for the presence of the V617F mutation in the JAK2 gene and analyzed the contribution of all studied parameters to the development of thrombotic and hemorrhagic complications. We found that the neurological picture did not differ between the groups: mean NIHSS scores were 12 and 13 points, respectively. Morphological and functional characteristics of red blood cells and platelets, hemostasis and cytokine profiles were compared between patients with IS and pre-existing PV and the comparison group. One of the key elements in potentiating thrombotic complications in patients with IS and PV was JAK2 V617F allele burden. The obtained data suggest the cumulative effect of the identified factors promoting thrombus formation in post-stroke patients with PV and overpowering the effect of antiplatelet therapy.
VIEWS 3433
Sustained-release drugs against tuberculosis are a promising approach to therapy since they positively affect patient compliance with long regimens, especially when it comes to the multidrug-resistant form of the disease. Conventional UV-visible spectroscopy does not work well with multicomponential culture media used for growing M. tuberculosis. The aim of this study was to develop a method for evaluating the kinetics of anti-tuberculosis drug released from bioresorbable polymeric carriers suitable for screening a wide range of encapsulated prolonged-release drugs and identifying the best performing candidate. While studying the growth dynamics of the laboratory susceptible strain M. tuberculosis H37Rv in the presence of different levofloxacin concentrations (from 0.03 to 0.4 μg/ml), we developed a model, which is essentially a set of 2 parallel experiments evaluating the kinetics of drug release into the culture medium. The results of these 2 experiments conducted on 3 encapsulated forms of levofloxacin loaded onto bioresorbable polymeric PLGA carriers (particles sized 50 μm and 100 μm and the matrix) revealed that release kinetics of the drug largely depended on the type of polymeric carrier. The best encapsulation of the antibiotic and its gradual release into the culture medium was observed for the matrix. All experiments were run in 3 replicates. The obtained data were analyzed using descriptive statistics.
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 Investigation of the triazole-derived drugs action mechanisms and understanding of their affinity and specificity molecular basis may contribute to the new drugs development. The study was aimed to investigate the triazoles class representative (fluconazole) complexes with amino acids using mass spectrometry, molecular dynamics and ab initio quantum chemistry calculations. During the experimental study, the fluconazole, alanine, lysine and threonine solutions were analyzed by electrospray ionization mass spectrometry and tandem mass spectrometry. The molecular dynamics modeling of the fluconazole–amino acid complexes was performed using the CHARMM force field. The quantum chemistry calculations of the complexes structure and energy parameters were carried out using the density-functional theory by B3LYP calculations (3-21G and 6-311++G** basis sets). Mass spectra indicated that fluconazole formed stable complexes with amino acids in the 1 : 1 stoichiometric ratio. In accordance with the tandem mass spectrometry with varying fluconazole–amino acid associates ion fragmentation energy, the following sequence was obtained: [Fluc + Ala + H]+ < [Fluc + Lys + H]+ < [Fluc + Thr + H]+. The fluconazole–amino acid interaction energy values resulting from the quantum chemistry calculations formed the sequence similar to that obtained by experiment. Thus, as seen in the case of fluconazole–amino acid complexes, it is possible to combine the experimental mass spectrometry studies with quantum chemical modeling for the complexes properties assessment.
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