Репозиторий Университета

© 2019, Springer Science+Business Media, LLC, part of Springer Nature. Objectives. To study the expression of various neurotransmitter transporters (glutamate, aspartate, lactate, choline) in cultures of astrocytes from different part of the brain (cortex, hippocampus, and brainstem) in rats aged three and 11 days. Materials and methods. An experimental study was performed using 24 Rattus norvegicus rats aged three (n = 12) and 11 days (n = 12). High-throughput sequencing results were analyzed. Results. Expression of the glutamate and aspartate transporters in the brainstem in three-day-old rats was greater than in other areas, though the reverse pattern was seen in rats aged 11 days. Expression of the lactate transporter with age was identical to that in the cortex. Conclusions. The data obtained here demonstrated the nature of neuroastrocyte relationships and the role of astrocytes in the process of signal transmission. The results of the study, carried out using original methods of investigating neurotransmitter transporters, allow them to be recommended for monitoring the processes of neurogenesis and neurohomeostasis, including in cerebrovascular and neurodegenerative diseases.

© 2019 Nanodiamonds (ND) are one of the most attractive carbon materials for nanotechnology. The impregnation of NDs into the polymer capsule shell in the form of the single nanoparticles insures the control over the thermal conductivity of the capsule shell and increases their sensitivity to the external microwave irradiation. The polymer shell of the polyelectrolyte capsules was modified with NDs by electrostatic adsorption technique. The sensitivity of the capsules with embedded NDs to the external microwave irradiation was demonstrated by scanning electron microscopy leading to the shell rupture and release of the encapsulated agents.

© Mary Ann Liebert, Inc., publishers 2019. The pathological processes developing after spinal cord injuries often lead to formation of cysts. Existing surgical and medical methods are insufficient for treatment of post-traumatic spinal cord cysts. One of the emerging tools is cell therapy. Olfactory ensheathing cells (OECs) are perspective cells for cell therapy. In this study, we demonstrated that human OEC transplantation is effective in experimental spinal cysts. For our experiments, we selected animals only at the intermediate stage of recovery with scores from 8 to 13 according to the Basso, Beattie, and Bresnahan (BBB) scale. Cells were transplanted in different quantities (0.75 and 1.5 million) into the fully formed cysts and in the areas of injury without cysts. Improvement of limb mobility after human OEC transplantation into post-traumatic cysts was shown. In the group of rats with cysts, time-dependent increase in the BBB score was observed in subgroups treated with 0.75 and 1.5 million OECs with no statistically significant time-dependent dynamics of BBB values in the control group. When all three subgroups (control and two OEC doses) were compared, the Kruskal-Wallis test showed the presence of differences between subgroups after 1, 3, and 4 weeks of treatment with evidence of divergence increase. There was no statistically significant difference between the two doses of OEC treatment. The human OECs in the experiments without cysts were not effective. It was also shown that PKH26-labeled human OECs survive throughout the experiment and migrate to nearby areas of the cyst. Therefore, it was found that it is effective to transplant human OECs into fully formed cysts. In the future, autologous OECs can be used to personalize the treatment of patients with spinal cysts.

© 2019 Elsevier B.V. Human populations are chronically exposed to mixtures of toxic chemicals. Predicting the health effects of these mixtures require a large amount of information on the mode of action of their components. Xenobiotic metabolism by bacteria inhabiting the gastrointestinal tract has a major influence on human health. Our review aims to explore the literature for studies looking to characterize the different modes of action and outcomes of major chemical pollutants, and some components of cosmetics and food additives, on gut microbial communities in order to facilitate an estimation of their potential mixture effects. We identified good evidence that exposure to heavy metals, pesticides, nanoparticles, polycyclic aromatic hydrocarbons, dioxins, furans, polychlorinated biphenyls, and non-caloric artificial sweeteners affect the gut microbiome and which is associated with the development of metabolic, malignant, inflammatory, or immune diseases. Answering the question ‘Who is there?’ is not sufficient to define the mode of action of a toxicant in predictive modeling of mixture effects. Therefore, we recommend that new studies focus to simulate real-life exposure to diverse chemicals (toxicants, cosmetic/food additives), including as mixtures, and which combine metagenomics, metatranscriptomics and metabolomic analytical methods achieving in that way a comprehensive evaluation of effects on human health.

© 2018, Springer Science+Business Media, LLC, part of Springer Nature. The objective of the present study was to assess the impact of ethnicity on hair trace element content in Han and aboriginal inhabitants of Hualien in Taiwan. Fifty Han (female/male = 35/15) and 50 aboriginal (female/male = 40/10) Hualien inhabitants aged 40–60 years were involved in the present study. Anthropometric data and dietary patterns were recorded. Hair mineral, essential, and toxic trace element levels were assessed using inductively coupled plasma mass spectrometry at NexION 300D (PerkinElmer Inc., USA) equipped with ESI SC-2 DX4 autosampler (Elemental Scientific Inc., USA). No group difference in gender, age, body weight, height, or physical activity was observed. Fish intake was more frequent in Han inhabitants, whereas aborigines consumed significantly more nuts. Indigenous people were characterized by higher hair Al (45%), Ca (threefold), Co (71%), Fe (twofold), I (74%), K (60%), Mg (2.5-fold), Na (62%), P (6%), Sn (78%), and V (46%) content. In turn, Han Hualien inhabitants had higher hair Be (twofold), Li, Se, Si levels as compared to indigenous counterparts. Multiple regression analysis demonstrated that ethnicity was significantly associated with hair Ca (β = 0.302), Mn (β = 0.284), P (β = 0.387), and Se (β = − 0.310) levels after adjustment for other confounders. At the same time, the overall models were significant for Ca, Mn, Se, and As. The obtained data may provide a background for monitoring and correction of trace element status in patients of different ethnic groups. However, further detailed studies are required to highlight the mechanisms underlying the observed associations.

© 2019 Elsevier Ltd The negative societal impacts associated with the increasing prevalence of violence and aggression is increasing, and, with this rise, is the need to understand the molecular and cellular changes that underpin ultrasound-induced aggressive behavior. In mice, stress-induced aggression is known to alter AMPA receptor subunit expression, plasticity markers, and oxidative stress within the brain. Here, we induced aggression in BALB/c mice using chronic ultrasound exposure and examined the impact of the psychoactive anti-oxidant compounds thiamine (vitamin B1), and its derivative benfotiamine, on AMPA receptor subunit expression, established plasticity markers, and oxidative stress. The administration of thiamine or benfotiamine (200 mg/kg/day) in drinking water decreased aggressive behavior following 3-weeks of ultrasound exposure and benfotiamine, reduced floating behavior in the swim test. The vehicle-treated ultrasound-exposed mice exhibited increases in protein carbonyl and total glutathione, altered AMPA receptor subunits expression, and decreased expression of plasticity markers. These ultrasound-induced effects were ameliorated by thiamine and benfotiamine treatment; in particular both antioxidants were able to reverse ultrasound-induced changes in GluA1 and GluA2 subunit expression, and, within the prefrontal cortex, significantly reversed the changes in protein carbonyl and polysialylated form of neural cell adhesion molecule (PSA-NCAM) expression levels. Benfotiamine was usually more efficacious than thiamine. Thus, the thiamine compounds were able to counteract ultrasound-induced aggression, which was accompanied by the normalization of markers that have been showed to be associated with ultrasound-induced aggression. These commonly used, orally-active compounds may have considerable potential for use in the control of aggression within the community. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.

© 2019 Elsevier Ltd Adhesion G protein-coupled receptor L3 (ADGRL3, LPHN3) has putative roles in neuronal migration and synapse function. Various polymorphisms in ADGRL3 have been linked with an increased risk of attention deficit/hyperactivity disorder (ADHD). In this study, we examined the characteristics of Adgrl3-deficient mice in multiple behavioural domains related to ADHD: locomotive activity, impulsivity, gait, visuospatial and recognition memory, sociability, anxiety-like behaviour and aggression. Additionally, we investigated the effect of Adgrl3-depletion at the transcriptomic level by RNA-sequencing three ADHD-relevant brain regions: prefrontal cortex (PFC), hippocampus and striatum. Adgrl3 −/− mice show increased locomotive activity across all tests and subtle gait abnormalities. These mice also show impairments across spatial memory and learning domains, alongside increased levels of impulsivity and sociability with decreased aggression. However, these alterations were absent in Adgrl3 +/− mice. Across all brain regions tested, the numbers of genes found to exhibit differential expression was relatively small, indicating a specific pathway of action, rather than a broad neurobiological perturbation. Gene-set analysis of differential expression in the PFC detected a number of ADHD-relevant pathways including dopaminergic synapses as well as cocaine and amphetamine addiction. The Slc6a3 gene coding for the dopamine transporter was the most dysregulated gene in the PFC. Unexpectedly, several neurohormone/peptides which are typically only expressed in the hypothamalus were found to be dysregulated in the striatum. Our study further validates Adgrl3 constitutive knockout mice as an experimental model of ADHD while providing neuroanatomical targets for future studies involving ADGRL3 modified models. This article is part of the Special Issue entitled ‘Current status of the neurobiology of aggression and impulsivity’.

© 2019 by the authors The present article reviews the clinical use of thiol-based metal chelators in intoxications and overexposure with mercury (Hg), cadmium (Cd), and lead (Pb). Currently, very few commercially available pharmaceuticals can successfully reduce or prevent the toxicity of these metals. The metal chelator meso-2,3-dimercaptosuccinic acid (DMSA) is considerably less toxic than the classical agent British anti-Lewisite (BAL, 2,3-dimercaptopropanol) and is the recommended agent in poisonings with Pb and organic Hg. Its toxicity is also lower than that of DMPS (dimercaptopropane sulfonate), although DMPS is the recommended agent in acute poisonings with Hg salts. It is suggested that intracellular Cd deposits and cerebral deposits of inorganic Hg, to some extent, can be mobilized by a combination of antidotes, but clinical experience with such combinations are lacking. Alpha-lipoic acid (α-LA) has been suggested for toxic metal detoxification but is not considered a drug of choice in clinical practice. The molecular mechanisms and chemical equilibria of complex formation of the chelators with the metal ions Hg2+, Cd2+, and Pb2+ are reviewed since insight into these reactions can provide a basis for further development of therapeutics.

© Copyright © 2019 Goryaynov, Okhlopkov, Golbin, Chernyshov, Svistov, Martynov, Kim, Byvaltsev, Pavlova, Batalov, Konovalov, Zelenkov, Loschenov and Potapov. Objective: This study is to analyze fluorescence sensitivity in the diagnosis of brain and spinal cord tumors. Material and methods: The authors conducted a multicenter retrospective analysis of data on 653 cases in 641 patients: 553 of them had brain tumors and 88 spinal cord tumors. Brain tumor resection was performed in 523 patients, of whom 484 were adults and 39 children. The analyzed series was presented by 320 gliomas, 101 meningiomas, and 72 metastases. A stereotactic biopsy was performed in 20 patients and endoscopic surgery in 10 patients. In all cases, 20 mg/kg of 5–Aminolaevulinic acid was administered orally 2-h before surgery. All surgical interventions were performed with a microscope BLUE 400 to visualize fluorescence, while endoscopic surgery—with an endoscope equipped with a fluorescent module. Fluorescence spectroscopy was conducted in 20 cases of stereotactic biopsies and in 88 cases of spinal cord tumors. Results: Among adult brain tumors operated by microsurgical techniques, meningiomas showed the highest 5-ALA fluorescence sensitivity 94% (n = 95/101), brain metastases 84.7% (n = 61/72), low-grade gliomas 46.4% (n = 26/56), and high-grade gliomas 90.2% (n = 238/264). In children the highest 5-ALA visible fluorescence was observed in anaplastic astrocytomas 100% (n = 4/4) and in anaplastic ependymomas 100% (n = 4/4); in low-grade gliomas it made up 31.8% (n = 7/22). As for the spinal cord tumors in adults, the highest sensitivity was demonstrated by glioblastomas 100% (n = 4/4) and by meningiomas 100% (n = 4/4); Fluorescence was not found in gemangioblastomas (n = 0/6) and neurinomas (n = 0/4). Fluorescence intensity reached 60% (n = 6/10) in endoscopic surgery and 90% (n = 18/20) in stereotactic biopsy. Conclusion: 5-ALA fluorescence diagnosis proved to be most sensitive in surgery of HGG and meningioma (90.2 and 94.1%, respectively). Sensitivity in surgery of intracranial metastases and spinal cord tumors was slightly lower (84.7 and 63.6%, correspondingly). The lowest fluorescence sensitivity was marked in pediatric tumors and LGG (50 and 46.4%, correspondingly). Fluorescence diagnosis can also be used in transnasal endoscopic surgery of skull base tumors and in stereotactic biopsy.

© 2019, Indian Association of Surgical Oncology. The role of surgery in the management of metastatic gastric cancer (MGC) remains unclear. The aim of this study was to investigate the surgical and oncologic outcomes of gastrectomy in patients with MGC. The study included prospectively collected data of patients with MGC operated at four medical centers in Yerevan, Armenia, between 2000 and 2014. Armenian National Center of Oncology Registry and hospital records were used to obtain survival data. Factors associated with performing gastrectomy in patients with MGC were analyzed by using the logistic regression model. The Kaplan-Meier method was applied for survival analysis, and the Cox regression model with backward selection was used for multivariate analysis. A total number of 733 patients were operated for gastric cancer including 112 (15.3%) with MGC. Of those, 70 underwent gastrectomy, while 42 had exploratory laparotomy or bypass. Morbidity and mortality were similar after gastrectomy and exploratory laparotomy/bypass (18.6 vs 21.4%, p = 0.71 and 2.9 vs 7.1% p = 0.36, respectively). Female gender, involvement of N1 and/or N2 lymph node stations, and differentiated adenocarcinoma were associated with opting for gastrectomy. Gastrectomy with synchronous resection of distant metastases resulted in postoperative outcomes similar to those following gastrectomy without synchronous organ resection. Median follow-up was 6 months. Eighteen (16.1%) patients received chemotherapy. Median survival following gastrectomy and exploratory laparotomy/bypass were 7 and 4 months (p = 0.015), respectively. The use of chemotherapy following gastrectomy significantly improved survival compared with gastrectomy only (14 vs 6 months, p = 0.01). In the multivariable analysis, chemotherapy and nodal stage correlated with survival after gastrectomy. Gastrectomy for MGC is associated with satisfactory surgical outcomes and can be combined with synchronous resection of distant metastases in selected patients. Gastrectomy results in longer survival compared with exploratory laparotomy/bypass, especially when followed by chemotherapy.

© 2019 The Author(s). Background: Liver resection is a treatment of choice for colorectal and neuroendocrine liver metastases, and laparoscopy is an accepted approach for surgical treatment of these patients. The role of liver resection for patients with non-colorectal non-neuroendocrine liver metastases (NCNNLM), however, is still disputable. Outcomes of laparoscopic liver resection for this group of patients have not been analyzed. Material and methods: In this retrospective study, patients who underwent laparoscopic liver resection for NCNNLM at Oslo University Hospital between April 2000 and January 2018 were analyzed. Perioperative and oncologic data of these patients were examined. Postoperative morbidity was classified using the Accordion classification. Kaplan-Meier method was used for survival analysis. Median follow-up was 26 (IQR, 12-41) months. Results: Fifty-one patients were identified from a prospectively collected database. The histology of primary tumors was classified as adenocarcinoma (n = 16), sarcoma (n = 4), squamous cell carcinoma (n = 4), melanoma (n = 16), gastrointestinal stromal tumor (n = 9), and adrenocortical carcinoma (n = 2). The median operative time was 147 (IQR, 95-225) min, while the median blood loss was 200 (IQR, 50-500) ml. Nine (18%) patients experienced postoperative complications. There was no 90-day mortality in this study. Thirty-five (68%) patients developed disease recurrence or progression. Seven (14%) patients underwent repeat surgical procedure for recurrent liver metastases. One-, three-, and five-year overall survival rates were 85%, 52%, and 38%, respectively. The median overall survival was 37 (95%CI, 25 to 49) months. Conclusion: Laparoscopic liver resection for NCNNLM results in good outcomes and should be considered in patients selected for surgical treatment.

© 2018, © 2018 Japan College of Rheumatology. Objective: The aim of this study was to analyze the efficacy and safety of etanercept (ETA) in children with juvenile idiopathic arthritis (JIA) under the age of 4 years and to compare the data with those for older age groups. Methods: Three groups comprising 34 patients each (total of 102 patients) were selected using the propensity score matching (PSM) method. The study group (patients under the age of 4 years; the Junior group (JNR)) was compared with patients of the older age groups, adjusted for criteria such as gender, JIA category, JIA severity, and either age at disease onset (the Reference by Age of disease Onset (RAO) group) or disease duration (the Reference by Disease Duration (RDD) group). Results: All three groups showed a good response to ETA therapy. During the follow-up period, only 4 (3.9%) patients failed to reach American College of Rheumatology (ACR) Pediatric criteria improvement at ACR50 level. In the JNR group, 82.4% of patients achieved ACR90 within a median time of 3 months (IQR, 3–6 months), which was a better result compared to the other two groups: 61.8% (RAO group) and 58.8% (RDD group) of patients achieved ACR90 within 6 (Interquartile Range (IQR), 3–9) months (p =.028). Three (9%) patients in the JNR group and none of the RDD and RAO groups discontinued treatment because of clinical remission (p =.045). Conclusion: An analysis of the ETA efficacy in different age groups comparable in terms of the diagnosis and disease severity demonstrated a higher efficacy of earlier ETA therapy in children of the same age at disease onset. In children at the early stage of arthritis (≤ 2.5 years long), ETA was more efficient in those with an earlier disease onset.

© 2019, © 2019 Informa UK Limited, trading as Taylor  &  Francis Group. The process of protein post-translational modifications (PTM) is one of the critical mechanisms of regulation of many cellular processes, which makes it an attractive target for various viruses. Since viruses cannot replicate on their own, they have developed unique abilities to alter metabolic and signaling cell pathways, including protein PTMs, to ensure faithful replication of their genomes. This review describes several ways of how lysine-specific PTMs are used by various viruses to ensure its successful invasion and replication. Covalent modifications like acetylation, ubiquitination, and methylation form a complex system of reversible and often competing modifications, which adds an additional level of complexity to the system of regulation of the activity of host proteins involved in viral replication and propagation. In furthering these, we also describe the manner in which PTM pathways can also be accosted by various types of viruses to neutralize the host’s cellular mechanisms for anti-viral protection and highlight key areas for future therapeutic targeting and design.

The article presents technique of calculation of the planned volume of outpatient care consumed by population of the subject of the Russian Federation considering demographic structure and level of morbidity. The formulas are presented developed for calculating financial costs of outpatient care and treatment in day hospital to be included into of mandatory health insurance program.

© 2019, Pediatria Ltd. All rights reserved. Acute kidney damage (AKD) is characterized by rapidly progressing organ dysfunction, which often results in development of chronic kidney disease. There are difficulties in diagnosing initial stages of kidney damage, which are usually reversible. Molecular diagnostics is a sensitive method that can detect early nephron changes that are not detectable by conventional methods (by assessing serum creatinine and urinary albumin in urine, diuresis) before renal filtration function decrease. The review examines markers of AKD development key stages: Ischemia (Kidney Injury Molecule-1 (KIM-1), Clusterin), hypoxia (Vascular Endothelial Growth Factor), Hypoxia Inducible Factor (HIF)), inflammation (Monocyte Chemoattractact Protein-1 (MCP-1), Interleukin 18 (IL18)), kidney tubule damage proximal (Beta-2-Microglobulin (B2M), Cystatin C, Neutrophil gelatinase associated lipocalin (NGAL)), distal (NGAL, Calbindin, Osteopontin). The study of these biomarkers in children's urine can be recommended for non-invasive screening, diagnosis and monitoring of AKD.

© 2019, Pediatria Ltd. All rights reserved. Attention deficit hyperactivity disorder (ADHD) is an urgent problem due to the high incidence rate, reaching 3–5% in the child population. The article discusses diagnostic criteria for ADHD and manifestation peculiarities in different age periods. It also duscusses etiopathogenesis of ADHD as a multifactorial developmental disorder; reviews main groups of drugs used for the pharmacological correction of the disease, among which nootropics, in particular aminophenylbutyric acid («Anvifen»), occupy a special place. Author discusses and justifies the need for an integrated approach to ADHD treatment, which should combine pharmacotherapy, neuropsychological correction and psychotherapy with a child, parents and teachers.

© 2019, Pediatria Ltd. All rights reserved. In the article the authors present relevant information on the criteria for assessing the activity of juvenile dermatomyositis (JDM) and modern approaches to its treatment. In clinical practice, various scales are currently used to assess the overall JDM activity and severity of damage to various organs, primarily muscles and skin. The article provides modern recommendations for JDM treatment: The use of glucocorticosteroids, disease-modifying antirheumatic drugs (methotrexate, calcineurin inhibitors, cyclophosphamide, mycophenolate mofetil, azathioprine, hydroxychloroquine, intravenous immunoglobulin), genetically engineered drugs (rituximab, infliximab, adalimumab, golimumab, certolizumab, etanercept), as well as promising new drugs and methods of maintenance therapy. The modern JDM treatment algorithm is described.

The article discusses issue of possibility of influence of religious organizations on the attitude of population to issues of human organ transplantation. The attitude of followers of different religions to key issues of bioethics related to organ donation and transplantation is analyzed. It is concluded that there are no definite prohibitions on implementing this kind of medical intervention in modern religious regulations. The study of results of questionnaire survey of two groups of respondents revealed certain part of population, whose decision on the issues of posthumous organ donation would be influenced by the opinion of representative of religious organization. It is established that every tenth respondent appealed to the Orthodox priest when making decision to sign consent paper concerning posthumous exempt of organ from relatives. It is concluded that it is possible to affect the formation in certain part of population understanding of need to support organ donation and transplantation in case of active work in this direction of representatives of religious organizations.

In recent years scientists actively study the influence of domestic violence on psychological status and occurrence of mental disorders in women and girls. Psychological, physical, sexual and other types of violence are distinguished, the consequences of which are studied in many countries under the auspices of WHO. In international studies the serious consequences of domestic violence for women are investigated. It was found out that women develop stressful disorders, depression and dependence on psychoactive substances. Negative influence of domestic violence at girls is expressed in formation of behavioral disorders, violations of sexual development, suicidal trends. At analysis of consequences of domestic violence by WHO was developed the concept of "cycle of violence" and cruelty inside family when in process of long influence of psychological traumatic factors at women and girls aggressive actions occurred so that victim and aggressor changed places. The objective of the study was to analyze the current state of the problem on the basis of the literature data, to study the data on the consequences of domestic violence and cruelty against women and girls, to identify gender-specific violations.

One demographic indicator is the structure of mortality by cause. Analysis of the causes of death allows you to define the fight against the disease, efforts should be focused to reduce mortality and on the effectiveness of measures against those or other diseases. The basis of information about the causes of death is a medical certificate of death, filling it depends on the correct diagnosis, the choice of the original cause of death, coding, as well as on policy documents aimed at reducing mortality from a particular cause. In the Russian Federation, in contrast to the countries of the European region, there is a fairly high proportion of inaccurately marked conditions, which account for 6.9% of all causes (in 2010 - 5%), the main reason for this is «old age», which ranks 4th among the leading causes of death (5% of all causes, in 2010 - 2.8%), as well as damage with uncertain intentions, which are on the 7th rank place of the leading causes of death (2.3% of all causes, in 2010 - 2%).