Linking Kindling to Increased Glutamate Release in the Dentate Gyrus of the Hippocampus Through the STXBP5/tomosyn-1 Gene

Introduction: In kindling, repeated electrical stimulation of certain brain areas causes progressive and permanent intensification of epileptiform activity resulting in generalized seizures. We focused on the role(s) of glutamate and a negative regulator of glutamate release, STXBP5/tomosyn-1, in kindling. Methods: Stimulating electrodes were implanted in the amygdala and progression to two successive Racine stage 5 seizures was measured in wild-type and STXBP5/tomosyn-1−/− (Tom−/−) animals. Glutamate release measurements were performed in distinct brain regions using a glutamate-selective microelectrode array (MEA). Results: Naïve Tom−/− mice had significant increases in KCl-evoked glutamate release compared to naïve wild type as measured by MEA of presynaptic release in the hippocampal dentate gyrus (DG). Kindling progression was considerably accelerated in Tom−/− mice, requiring fewer stimuli to reach a fully kindled state. Following full kindling, MEA measurements of both kindled Tom+/+ and Tom−/− mice showed significant increases in KCl-evoked and spontaneous glutamate release in the DG, indicating a correlation with the fully kindled state independent of genotype. Resting glutamate levels in all hippocampal subregions were significantly lower in the kindled Tom−/−mice, suggesting possible changes in basal control of glutamate circuitry in the kindled Tom−/−mice. Conclusions: Our studies demonstrate that increased glutamate release in the hippocampal DG correlates with acceleration of the kindling process. Although STXBP5/tomosyn-1 loss increased evoked glutamate release in naïve animals contributing to their prokindling phenotype, the kindling process can override any attenuating effect of STXBP5/tomosyn-1. Loss of this “braking” effect of STXBP5/tomosyn-1 on kindling progression may set in motion an alternative but ultimately equally ineffective compensatory response, detected here as reduced basal glutamate release

IMMUNOSUPPRESSION AS A COMPONENT OF MULTIPLE ORGAN DYSFUNCTION SYNDROME FOLLOWING CARDIAC SURGERY

Aim. To defne the role of myeloid-derived suppressor cells in the development of persistent multiple organ dysfunction followed cardiac surgeries with cardiopulmonary bypass.Methods. 40 patients who have undergone cardiac surgery were included in the study. Granulocyte myeloid-derived suppressor cells (G-MDSC) were defned as cells with the HLA-DR– / CD11β+ / CD15+ / CD33+ phenotype, and monocytic MDSC (M-MDSC) as cells with the HLA-DR– / CD11β+ / CD14+ / CD33+ phenotype using flow cytometry. Levels of cytokines, IL-1β, IL-6, TNF-α, and IL-10 were measured with an enzyme immunoassay. All patients were assigned to three groups: Group 1 – patients with the uncomplicated postoperative period (n = 14), Group 2 – patients with non-persistent MODS and its early resolution (n = 16), and Group 3 – patients with persistent MODS at day 7.Results. We observed an increase in M-MDSCs and G-MDSC at day 1 following cardiac surgery. The most pronounced increase was found in monocytic-myeloid derived suppressor cells, i.e. an 8-fold increase in M-MDSCs in all study groups at day 1 after surgery. The number of M-MDSCs remained high in patients with persistent MODS at day 7 after cardiac surgery. Levels of IL-6 and IL-10 increased at day 1 after surgery. IL-6 reached its peak level, signifcantly exceeding baseline levels. By day 7, blood levels of all cytokines have decreased, except IL-10 levels, which remained above the baseline in patients with persistent MODS.Conclusion. An increase in M-MDSCs and elevated serum levels of the anti-inflammatory cytokine IL-10 have been found in patients regardless of the presence or absence of the complications in the early postoperative period after cardiac surgery with cardiopulmonary bypass. Persistent MODS with the SOFA scoring > 5 scores at day 7 after cardiac surgery, is associated with an increase in M-MDSCs and elevated levels of the anti-inflammatory cytokine IL-10, related to higher rate of hospital infections, prolonged intensive care unit stay and higher mortality.Aim. To defne the role of myeloid-derived suppressor cells in the development of persistent multiple organ dysfunction followed cardiac surgeries with cardiopulmonary bypass.Methods. 40 patients who have undergone cardiac surgery were included in the study. Granulocyte myeloid-derived suppressor cells (G-MDSC) were defned as cells with the HLA-DR– / CD11β+ / CD15+ / CD33+ phenotype, and monocytic MDSC (M-MDSC) as cells with the HLA-DR– / CD11β+ / CD14+ / CD33+ phenotype using flow cytometry. Levels of cytokines, IL-1β, IL-6, TNF-α, and IL-10 were measured with an enzyme immunoassay. All patients were assigned to three groups: Group 1 – patients with the uncomplicated postoperative period (n = 14), Group 2 – patients with non-persistent MODS and its early resolution (n = 16), and Group 3 – patients with persistent MODS at day 7.Results. We observed an increase in M-MDSCs and G-MDSC at day 1 following cardiac surgery. The most pronounced increase was found in monocytic-myeloid derived suppressor cells, i.e. an 8-fold increase in M-MDSCs in all study groups at day 1 after surgery. The number of M-MDSCs remained high in patients with persistent MODS at day 7 after cardiac surgery. Levels of IL-6 and IL-10 increased at day 1 after surgery. IL-6 reached its peak level, signifcantly exceeding baseline levels. By day 7, blood levels of all cytokines have decreased, except IL-10 levels, which remained above the baseline in patients with persistent MODS.Conclusion. An increase in M-MDSCs and elevated serum levels of the anti-inflammatory cytokine IL-10 have been found in patients regardless of the presence or absence of the complications in the early postoperative period after cardiac surgery with cardiopulmonary bypass. Persistent MODS with the SOFA scoring > 5 scores at day 7 after cardiac surgery, is associated with an increase in M-MDSCs and elevated levels of the anti-inflammatory cytokine IL-10, related to higher rate of hospital infections, prolonged intensive care unit stay and higher mortality

STUDENT SOCIO-PSYCHOLOGICAL EXPECTATIONS FROM STUDYING IN HIGHER EDUCATION INSTITUTION: SATISFACTION DEGREE AND IMPLEMENTATION EVALUATION

O objetivo do estudo é analisar a implementação das expectativas dos alunos de estudar na Universidade. O método principal para o estudo desse problema é o método do questionário, que permite o estudo mais qualitativo e aprofundado das expectativas dos jovens em relação ao ensino superior. É revelado que os problemas existentes têm um impacto negativo na atitude dos alunos em relação à sua instituição educacional e, consequentemente, reduzir sua imagem aos olhos dos futuros alunos e do público em geral. Os dados obtidos neste trabalho podem ser utilizados nas áreas de psicologia da educação, psicologia da idade, psicologia social, pedagogia, sociologia, bem como para o desenvolvimento teórico adicional desta questão.El objetivo del estudio es analizar la implementación de las expectativas de los estudiantes al estudiar en la Universidad. El método principal para el estudio de este problema es el método del cuestionario, que permite el estudio más cualitativo y profundo de las expectativas de los jóvenes en relación con la educación superior. Se revela que los problemas existentes tienen un impacto negativo. sobre la actitud de los estudiantes hacia su institución educativa y, en consecuencia, reducir su imagen ante los futuros estudiantes y el público en general. Los datos obtenidos en este trabajo pueden utilizarse en psicología de la educación, psicología de la edad, psicología social, pedagogía, sociología, así como para un mayor desarrollo teórico de este tema.The aim of the study is to analyze the implementation of students' expectations from studying at the University. The leading method for the study of this problem is the method of the questionnaire, which allows the most qualitative and in-depth study of the expectations of young people in relation to higher education.. It is revealed that the existing problems have a negative impact on the attitude of students to their educational institution and, consequently, reduce its image in the eyes of future students and the public as a whole. The data obtained in this work can be used in the psychology of education, age psychology, social psychology, pedagogy, sociology, as well as for further theoretical development of this issue

Features of <i>ESCHERICHIA COLI</i> samples from patients with diarrheal syndrome in the Republic of Guinea

Introduction. Diarrheal diseases are a global public health issue and cause 15% of deaths in children under 5 years old, of which about 80% occur in the regions of Africa and Southeast Asia. According to the Global Enteric Multicentre Study (GEMS) conducted in a number of African countries, one of the leading pathogens of high risk of death in infants and young children is diarrheagenic E. coli (DEC). In recent decades, antimicrobial resistance (AMR) has become globally ubiquitous. The Republic of Guinea urgently needs large-scale studies devoted to assessing DEC distribution and antibiotic resistance. The purpose of the study is to assess the pattern of E. coli infections and to test the susceptibility to antibiotics in strains of diarrheagenic E. coli sampled from individuals residing in the Republic of Guinea. Materials and methods. From 2019 to 2022, we studied 724 samples of faeces of patients with acute diarrhea, among them 72 (9.9%) children aged 1–5 years, 128 (17.7%) children aged 6–17 years, and 524 (72.4%) people aged 18 years and older; a method of polymerase chain reaction (PCR) was applied with the use of the AmpliSense® Escherichioses-FL reagent kit to identify the genetic determinants of DEC: EPEC, EHEC, ETEC, EIEC, and EAgEC (Central Research Institute of Epidemiology of Rospotrebnadzor, Russia). Susceptibility to 15 antimicrobial agents was found by the disc-diffusion method using Mueller–Hinton agar (Russia) and Oxoid discs (UK). Results were interpreted according EUCAST criteria, versions 2019–2022 (https://www.eucast.org/ast_of_bacteria/previous_versions_of_documents). Results. For the period from 2019 to 2022, the percentage of E. coli infections in the etiological pattern of acute intestinal infections amounted to 51.7%. In the age-related manner, DEC was significantly more common in young children aged 0–5 (96.9%, p 0.05) as compared to school age children aged 6–17 (53.9%) and adults (45.6%). In all years of observation, EAgEC strains prevailed, accounting for 38.4%. Other DEC pathotypes, EPEC, ETEC, EIEC and STEC, accounted for 27.2%, 17.5%, 11.8%, and 5.1%, respectively. DEC strains are susceptible to meropenem, amikacin, and nitrofurantoin. The activity of other antibiotics ranged from 11.3% for ampicillin, 28.3% for trimethoprim-sulfamethoxazole, and 34.0% for tetracycline to 73.6% for cephalosporins, 84.0% for aminoglycosides, and 98.1% for fluorinated quinolones. Conclusion. To reduce the burden of diarrheal diseases in the Republic of Guinea, it may be necessary to conduct targeted epidemiological and microbiological studies to identify DEC and monitor the development of antimicrobial resistance of E. coli infection pathogens in the population

Simulations of COMPASS vertical displacement events with a self-consistent model for halo currents including neutrals and sheath boundary conditions

The understanding of the halo current properties during disruptions is key to design and operate large scale tokamaks in view of the large thermal and electromagnetic loads that they entail. For the first time, we present a fully self-consistent model for halo current simulations including neutral particles and sheath boundary conditions. The model is used to simulate vertical displacement events (VDEs) occurring in the COMPASS tokamak. Recent COMPASS experiments have shown that the parallel halo current density at the plasma-wall interface is limited by the ion saturation current during VDE-induced disruptions. We show that usual magneto-hydrodynamic boundary conditions can lead to the violation of this physical limit and we implement this current density limitation through a boundary condition for the electrostatic potential. Sheath boundary conditions for the density, the heat flux, the parallel velocity and a realistic parameter choice (e.g. Spitzer's resistivity and Spitzer-Harm parallel thermal conductivity) extend present VDE simulations beyond the state of the art. Experimental measurements of the current density, temperature and heat flux profiles at the COMPASS divertor are compared with the results obtained from axisymmetric simulations. Since the ion saturation current density (Jsat) is shown to be essential to determine the halo current profile, parametric scans are performed to study its dependence on different quantities such as the plasma resistivity and the particle and heat diffusion coefficients. In this respect, the plasma resistivity in the halo region broadens significantly the Jsat profile, increasing the halo width at a similar total halo current

Understanding of Active and Passive Constructions in 7- to 10-Year-Old Russian-Speaking Children: Reliance on Inflections or Word Order

Background. The background of the present study includes analysis of the understanding of active and passive grammatical constructions (GCs) in Russianspeaking aphasic patients and in children aged 3, 4 and 5 years (Akhutina, 1989; Akhutina, Velichkovskiy, & Kempe, 1988). Data regarding the reorganization of the children’s strategies are further compared to GC understanding in children speaking different languages, and their interpretations. Objective. To analyze the variable mechanisms of understanding of reversible GCs in primary-school-age children, namely, to reveal individual differences in reliance on word order or case endings. Design. Ninety-three first-graders, 93 second-graders, and 63 third-graders underwent a neuropsychological assessment and computer-based sentence-topicture test of their understanding of reversible GCs of active/passive voice with direct/reverse word order. The “productivity” of understanding GCs (percent of correct responses) was analyzed through cluster analysis. Results. The cluster analysis divided the children into four clusters. Cluster 1 consisted of eight children with low productivity, who were excluded from further analysis. Cluster 2 was characterized by low productivity in passive direct constructions (Group 1); Cluster 3 comprised children who had low productivity in passive reverse sentences (Group 2). Cluster 4 included children with good understanding of all GCs (Group 3). Between-group differences in productivity and time of correct responses in GCs, as well as neuropsychological indexes, were revealed. Conclusion. The results are consistent with the following hypotheses: (a) Group 1 relies on the rule “The first noun is the agent”, whereas the other two groups use morphological marking; (b) Group 1 is the weakest neuropsychologically, and syntactic understanding processes involve a more diffuse activation of the brain in this group, compared to more successful children; (c) changes in response times from the first to the second grade are under the influence of cerebral changes induced by reading acquisition

Physico-chemical foundations underpinning microarray and next-generation sequencing experiments

Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next-generation sequencing (NGS). A physical understanding of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concentrations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinformatics and biostatistics, to theoretical and experimental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present knowledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico-chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized