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The emergence and international spread of neurovirulent circulating vaccine-derived polioviruses (cVDPVs) across multiple countries in Africa and Asia in recent years pose a major challenge to the goal of eradicating all forms of polioviruses. Approximately 90% of all cVDPV outbreaks are caused by the type 2 strain of the Sabin vaccine, an oral live, attenuated vaccine; cVDPV outbreaks typically occur in areas of persistently low immunization coverage (1). A novel type 2 oral poliovirus vaccine (nOPV2), produced by genetic modification of the type 2 Sabin vaccine virus genome (2), was developed and evaluated through phase I and phase II clinical trials during 2017-2019. nOPV2 was demonstrated to be safe and well-tolerated, have noninferior immunogenicity, and have superior genetic stability compared with Sabin monovalent type 2 (as measured by preservation of the primary attenuation site [domain V in the 5' noncoding region] and significantly lower neurovirulence of fecally shed vaccine virus in transgenic mice) (3-5). These findings indicate that nOPV2 could be an important tool in reducing the risk for generating vaccine-derived polioviruses (VDPVs) and the risk for vaccine-associated paralytic poliomyelitis cases. Based on the favorable preclinical and clinical data, and the public health emergency of international concern generated by ongoing endemic wild poliovirus transmission and cVDPV type 2 outbreaks, the World Health Organization authorized nOPV2 for use under the Emergency Use Listing (EUL) pathway in November 2020, allowing for its first use for outbreak response in March 2021 (6). As required by the EUL process, among other EUL obligations, an extensive plan was developed and deployed for obtaining and monitoring nOPV2 isolates detected during acute flaccid paralysis (AFP) surveillance, environmental surveillance, adverse events after immunization surveillance, and targeted surveillance for adverse events of special interest (i.e., prespecified events that have the potential to be causally associated with the vaccine product), during outbreak response, as well as through planned field studies. Under this monitoring framework, data generated from whole-genome sequencing of nOPV2 isolates, alongside other virologic data for isolates from AFP and environmental surveillance systems, are reviewed by the genetic characterization subgroup of an nOPV working group of the Global Polio Eradication Initiative. Global nOPV2 genomic surveillance during March-October 2021 confirmed genetic stability of the primary attenuating site. Sequence data generated through this unprecedented global effort confirm the genetic stability of nOPV2 relative to Sabin 2 and suggest that nOPV2 will be an important tool in the eradication of poliomyelitis. nOPV2 surveillance should continue for the duration of the EUL.

The transcription factor Forkhead box M1 (FoxM1) is overexpressed in breast cancers and correlates with poor prognosis. Mechanistically, FoxM1 associates with CBP to activate transcription and with Rb to repress transcription. Although the activating function of FoxM1 in breast cancer has been well documented, the significance of its repressive activity is poorly understood. Using CRISPR–Cas9 engineering, we generated a mouse model that expresses FoxM1-harboring point mutations that block binding to Rb while retaining its ability to bind CBP. Unlike FoxM1-null mice, mice harboring Rb-binding mutant FoxM1 did not exhibit significant developmental defects. The mutant mouse line developed PyMT-driven mammary tumors that were deficient in lung metastasis, which was tumor cell-intrinsic. Single-cell RNA-seq of the tumors revealed a deficiency in prometastatic tumor cells and an expansion of differentiated alveolar type tumor cells, and further investigation identified that loss of the FoxM1/Rb interaction caused enhancement of the mammary alveolar differentiation program. The FoxM1 mutant tumors also showed increased Pten expression, and FoxM1/Rb was found to activate Akt signaling by repressing Pten. In human breast cancers, expression of FoxM1 negatively correlated with Pten mRNA. Furthermore, the lack of tumor-infiltrating cells in FoxM1 mutant tumors appeared related to decreases in pro-metastatic tumor cells that express factors required for infiltration. These observations demonstrate that the FoxM1/Rb-regulated transcriptome is critical for the plasticity of breast cancer cells that drive metastasis, identifying a prometastatic role of Rb when bound to FoxM1. Significance: This work provides new insights into how the interaction between FoxM1 and Rb facilitates the evolution of metastatic breast cancer cells by altering the transcriptome.

Although progress is evident in the effective treatment of joint replacement-related infections, it still remains a serious issue in orthopedics. As an example, the local application of antibiotics-impregnated bone grafts supplies the high drug levels without systemic side effects. However, antibiotics in the powder or solution form could be a risk for local toxicity and do not allow sustained drug release. The present study evaluated the use of an antibiotic gel, a water-in-oil emulsion, and a PLGA microparticulate solid dispersion as depot delivery systems impregnating bone grafts for the treatment of joint replacement-related infections. The results of rheological and bioadhesive tests revealed the suitability of these formulations for the impregnation of bone grafts. Moreover, no negative effect on proliferation and viability of bone marrow mesenchymal stem cells was detected. An ex vivo dissolution test of vancomycin hydrochloride and gentamicin sulphate from the impregnated bone grafts showed a reduced burst and prolonged drug release. The PLGA-based formulation proved to be particularly promising, as one-day burst release drugs was only 15% followed with sustained antibiotics release with zero-order kinetics. The results of this study will be the basis for the development of a new product in the Tissue Section of the University Hospital for the treatment of bone defects and infections of joint replacements.

The glucocorticoid receptor (GR) is a nuclear receptor that controls critical biological processes by regulating the transcription of specific genes. There is a known allosteric cross-talk between the ligand and coregulator binding sites within the GR ligand-binding domain that is crucial for the control of the functional response. However, the molecular mechanisms underlying such an allosteric control remain elusive. Here, molecular dynamics (MD) simulations, bioinformatic analysis, and biophysical measurements are integrated to capture the structural and dynamic features of the allosteric cross-talk within the GR. We identified a network of evolutionarily conserved residues that enables the allosteric signal transduction, in agreement with experimental data. MD simulations clarify how such a network is dynamically interconnected and offer a mechanistic explanation of how different peptides affect the intensity of the allosteric signal. This study provides useful insights to elucidate the GR allosteric regulation, ultimately providing a foundation for designing novel drugs.

Circulation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the human population leads to further viral evolution. The new variants that arise during this evolution are more infectious. Our data suggest that newer variants have shifted from utilizing both cathepsin/endosome- and TMPRSS2-mediated entry mechanisms to rely on a TMPRSS2-dependent entry pathway. Accordingly, only the early lineages of SARS-CoV-2 are capable of infecting and forming syncytia in Vero/ACE2 cells which lack TMPRSS2 expression. The presence of an intact multibasic furin cleavage site (FCS) in the S protein was a key requirement for cell-to-cell fusion. Deletion of FCS makes SARS-CoV-2 more infectious

Tyrosine kinase inhibitors were found to be clinically effective for treatment of patients with certain subsets of cancers carrying somatic mutations in receptor tyrosine kinases. However, the duration of clinical response is often limited, and patients ultimately develop drug resistance. Here, we use single-cell RNA sequencing to demonstrate the existence of multiple cancer cell subpopulations within cell lines, xenograft tumors and patient tumors. These subpopulations exhibit epigenetic changes and differential therapeutic sensitivity. Recurrently overrepresented ontologies in genes that are differentially expressed between drug tolerant cell populations and drug sensitive cells include epithelial-to-mesenchymal transition, epithelium development, vesicle mediated transport, drug metabolism and cholesterol homeostasis. We show analysis of identified markers using the LINCS database to predict and functionally validate small molecules that target selected drug tolerant cell populations. In combination with EGFR inhibitors, crizotinib inhibits the emergence of a defined subset of EGFR inhibitor-tolerant clones. In this study, we describe the spectrum of changes associated with drug tolerance and inhibition of specific tolerant cell subpopulations with combination agents., It has been proposed that resistance to targeted therapies in non-small cell lung carcinoma (NSCLC) is due to a nonhomogeneous cell population. Here the authors analyse preclinical NSCLC models using single-cell RNA-seq and identify drug tolerant cell states and subpopulations, as well as associated genes.

A chimeric Eilat/ Chikungunya virus (EILV/CHIKV) was previously reported to replicate only in mosquito cells but capable of inducing robust adaptive immunity in animals. Here, we initially selected C7/10 cells to optimize the production of the chimeric virus. A two-step procedure produced highly purified virus stocks, which was shown to not cause hypersensitive reactions in a mouse sensitization study. We further optimized the dose and characterized the kinetics of EILV/CHIKV-induced immunity. A single dose of 108 PFU was sufficient for induction of high levels of CHIKV-specific IgM and IgG antibodies, memory B cell and CD8+ T cell responses. Compared to the live-attenuated CHIKV vaccine 181/25, EILV/CHIKV induced similar levels of CHIKV-specific memory B cells, but higher CD8+ T cell responses at day 28. It also induced stronger CD8+, but lower CD4+ T cell responses than another live-attenuated CHIKV strain (CHIKV/IRES) at day 55 post-vaccination. Lastly, the purified EILV/CHIKV triggered antiviral cytokine responses and activation of antigen presenting cell (APC)s in vivo, but did not induce APCs alone upon in vitro exposure. Overall, our results demonstrate that the EILV/CHIKV vaccine candidate is safe, inexpensive to produce and a potent inducer of both innate and adaptive immunity in mice.

The aim of the study was to develop an ECG hardware and software system for monitoring electrical instability of the myocardium and to assess the diagnostic and prognostic capabilities of this setup in a cardiology clinic. Materials and Methods. The Intecard 7.3 software and hardware system developed in this study makes it possible to measure fluctuations of the ECG amplitude-time parameters using the beat-to-beat mode. Intecard 7.3 evaluates a number of ECG markers that reflect electrical instability of the myocardium. Among them are the fragmented QRS complex, the spatial QRS-T angle, the T-wave alternans, the duration, and dispersion of the QT interval, the turbulence and acceleration/deceleration of the heart rhythm. Clinical trials of Intecard 7.3 were carried out with 734 patients with ischemic heart disease or cardiomyopathy and 112 healthy individuals. Results. Intecard 7.3 reliably identifies fragmented QRS complexes by detecting short spikes of 0%) than that in healthy controls (p

To compare the neointima structure in conduits for coronary bypass grafting, bioprosthetic heart valves, tissue-engineered vascular grafts, and metal stents.The objects of the study were the fragments of the human internal thoracic artery, experimental biodegradable vascular prostheses, leaflets of xenopericardial bioprostheses of heart valves, and fragments of stented vessels. Tissue samples were fixed in formalin and post-fixed in osmium tetroxide. After dehydration and epoxy resin embedding, the samples were ground and polished. Samples were counterstained with uranyl acetate and lead citrate and visualized by means of backscattered scanning electron microscopy.Neointimal pattern in all samples was similar. Neointima was comprised of endothelial cells, smooth muscle cells, fibroblasts, and the extracellular matrix. Endothelial cells showed significant diversity both between different elements of the circulatory system and within the same tissue, having either elongated or polygonal shape. Adhesion of leukocytes testified to the endothelial cell activation. In the absence of inflammation in the superficial layer of the neointima, the arrangement of smooth muscle cells and extracellular matrix fibers was parallel to the endothelium. Clusters of foam cells were frequently detected around the neointimal layers with solid inclusions (metal stents or calcium deposits). Thickening of the neointima was accompanied by the presence of capillaries and capillary-like structures.Neointima formation is a typical response to the damage inflicted to the elements of the circulatory system. Neointima underwent a constant remodeling characterized by an altered cellular composition, macrophage invasion, neovascularization, and calcification.Выполнить сравнительную оценку строения неоинтимы кондуитов для коронарного шунтирования, биопротезов клапанов сердца и искусственно созданных сосудистых протезов и металлических стентов.Объектами исследования послужили участки внутренней грудной артерии человека, экспериментальные биодеградируемые сосудистые протезы, створки ксеноперикардиальных биопротезов клапанов сердца и фрагменты стентированных сосудов. Образцы фиксировали в формалине и постфиксировали в тетраокиси осмия. После обезвоживания в спиртах и ацетоне, заключения в эпоксидную смолу образцы шлифовали и полировали до нужной глубины. Образцы контрастировали уранилацетатом и цитратом свинца и просматривали в сканирующем электронном микроскопе в режиме обратно рассеянных электронов.Во всех образцах обнаружили наличие неоинтимы сходного строения, состоящей из эндотелия, гладкомышечных клеток, фибробластов и внеклеточного матрикса. Эндотелиальный слой демонстрировал большое разнообразие как в составе различных элементов системы кровообращения, так и в пределах одной и той же анатомической структуры. Клетки могли иметь уплощенную либо более округлую форму. Встречались участки эндотелия с адгезированными лейкоцитами. При отсутствии воспаления в поверхностном слое неоинтимы гладкомышечные клетки и волокна были расположены параллельно эндотелию. Кроме гладкомышечных клеток в этом слое присутствовали клетки фибробластического ряда. Вблизи слоев неоинтимы, содержащих твердые включения (металлические стенты или кальциевые депозиты), встречались скопления пенистых клеток. В образцах с утолщенной неоинтимой наблюдали капилляроподобные структуры и настоящие капилляры.Образование неоинтимы является универсальной реакцией организма на повреждение участков элементов кровеносной системы. Сформировавшаяся неоинтима находится в постоянном процессе ремоделирования: изменяется клеточный состав, появляются макрофаги, образуются капилляры и кальциевые депозиты.

Background: A number of studies have reported elevated incidence of 25-OH-vitamin D deficiency among patients with multiple myeloma (MM). Several studies have found association between vitamin D levels and factors associated with survival, including ISS stage at diagnosis. However, the impact of vitamin D deficiency on MM prognosis is not entirely clear. Also, in general, both the incidence and the impact of vitamin D deficiency differ substantially by race. Here, we investigate the impact of vitamin D deficiency on prognosis in a large and racially heterogenous patient population with MM in the Veterans Affairs (VA) system. Methods: We used the VA's nationwide Corporate Data Warehouse to identify patients diagnosed with symptomatic MM from 1999 to 2017. Various demographic and laboratory data was collected including age, race, 25-OH-vitamin D levels, and ISS stage at diagnosis as well as survival outcome data. Details of therapies received was also available which indicted similar access to all newer agents approved for myeloma for both African American (AA) and Caucasian patients. Results: We identified 15,717 patients diagnosed with MM (3353 AA and 9070 Caucasian), of whom 6675 had vitamin D measurements within 2 months of diagnosis (1959 AA and 4398 Caucasian). Median serum vitamin D levels were significantly lower among AA patients (21.8 ng/mL) than Caucasians (28.6 ng/mL; p We evaluated the ability of serum vitamin D level to predict overall survival (OS) in patients with MM using a cut-off of 20ng/mL. Patients with vitamin D deficiency ( The analyses were repeated for AA and Caucasian patients separately. Among AA patients, serum vitamin D was not a significant predictor of OS in univariate (P=0.5096) or multivariate analysis (P=0.6923), while it was still a strong predictor among Caucasian patients in both univariate (HR 1.38; P=0.0006) and multivariate analysis (HR 1.45; P=0.0048). Median OS is 3.54 years (95% CI 2.99-5.52; n=255) for AA patients with vitamin D deficiency and 3.95 years (3.25-5.35; n=296) with normal levels. Among Caucasians, median OS is 2.71 years (2.18-3.47; n=273) for deficient and 3.87 years (3.59-4.42; n=885) for normal. Kaplan-Meier plots (Fig. 1B and 1C) illustrate the observed OS curves for the two subgroups. Since levels of vitamin D were lower in AA patients, a lower cut-off of 10 ng/mL was also tested. Even using this lower cutoff, vitamin D deficiency was not a statistically significant predictor of OS in univariate (HR 1.33; P=0.0781) or multivariate analysis (HR 1.09; P=0.7039), though the number of AA patients with vitamin D Conclusions: Vitamin D deficiency is a significant predictor of survival among patients diagnosed with MM, even after accounting for race, age, and ISS stage. However, this relationship is only observed in Caucasian patients and not observed among AA patients. Studies are ongoing to evaluate impact of Vitamin D deficiency of disease presentation including bone disease as well as genetic characteristics. This investigation highlights the need to assess the underlying biological mechanism responsible for the observed impact of vitamin D deficiency across race in MM. Download : Download high-res image (145KB) Download : Download full-size image Disclosures Yellapragada: Novartis: Employment; Celgene: Research Funding; Takeda: Research Funding. Munshi: OncoPep: Other: Board of director.

ObjectiveTo describe and assess the effectiveness of a neurology resident quality improvement curriculum focused on development of practical skills and project experience.MethodsWe designed and implemented a quality improvement curriculum composed of (1) a workshop series and (2) monthly resident-led Morbidity, Mortality, & Improvement conferences focused on case analysis and project development. Surveys were administered precurriculum and 18 months postcurriculum to assess the effect on self-assessed confidence with quality improvement skills, attitudes, and project participation. Scholarship in the form of posters, presentations, and manuscripts was tracked during the course of the study.ResultsPrecurriculum, 83% of neurology residents felt that instruction in quality improvement was important, but most rated their confidence level with various skills as low. Following implementation of the curriculum, residents were significantly more confident in analyzing a patient case (odds ratio, 95% confidence interval) (2.4, 1.9–3.1), proposing system changes (3.1, 2.3–3.9), writing a problem statement (9.9, 6.2–13.5), studying a process (3.1, 2.3–3.8), identifying resources (3.1, 2.3–3.8), identifying appropriate measures (2.5, 1.9–3.0), collaborating with other providers to make improvements (4.9, 3.5–6.4), and making changes in a system (3.1, 2.3–3.8). Project participation increased from the precurriculum baseline (7/18, 39%) to the postcurriculum period (17/22, 77%; p = 0.023). One hundred percent of residents surveyed rated the curriculum positively.ConclusionsOur multifaceted curriculum was associated with increased resident confidence with quality improvement skills and increased participation in improvement projects. With adequate faculty mentorship, this curriculum represents a novel template for preparing neurology residents for meeting the expectations of improvement in practice and offers scholarship opportunities.

Large-scale functional connectivity is an important indicator of the brain’s normal functioning. The abnormalities in the connectivity pattern can be used as a diagnostic tool to detect various neurological disorders. The present paper describes the functional connectivity assessment based on artificial intelligence to reveal age-related changes in neural response in a simple motor execution task. Twenty subjects of two age groups performed repetitive motor tasks on command, while the whole-scalp EEG was recorded. We applied the model based on the feed-forward multilayer perceptron to detect functional relationships between five groups of sensors located over the frontal, parietal, left, right, and middle motor cortex. Functional dependence was evaluated with the predicted and original time series coefficient of determination. Then, we applied statistical analysis to highlight the significant features of the functional connectivity network assessed by our model. Our findings revealed the connectivity pattern is consistent with modern ideas of the healthy aging effect on neural activation. Elderly adults demonstrate a pronounced activation of the whole-brain theta-band network and decreased activation of frontal–parietal and motor areas of the mu-band. Between-subject analysis revealed a strengthening of inter-areal task-relevant links in elderly adults. These findings can be interpreted as an increased cognitive demand in elderly adults to perform simple motor tasks with the dominant hand, induced by age-related working memory decline.

Diseases of the endocrine system are an urgent medical and social problem in connection with their widespread prevalence and negative growth trend throughout the world; they often accompany other chronic diseases and can lead to disability.Aim: to study the trends in the structure and characteristics of the morbidity of the population in the Republic of Tatarstan with diseases of the endocrine system.The study was based on the materials of the official statistics in the Republic of Tatarstan for the period 2014-2019, the methods of descriptive statistics and linear regression analysis were used. The indicators of the primary morbidity and prevalence of the endocrine system diseases among various age groups in the Republic of Tatarstan were studied.The retrospective analysis of the incidence of the endocrine system diseases in the population in the Republic of Tatarstan indicates the formation of stable negative trends in the growth of the prevalence of thyroid diseases, diabetes and obesity among all the groups under study. There is an increase in the primary incidence and prevalence of thyroid diseases among children (growth rate in 2019 compared to 2014 of 198.6 and 50.1% respectively) and adolescents (growth rate of 244.9% and 114.3% respectively), as well as an increase in the prevalence of type 2 diabetes in these groups (growth rate of 500% and 269,2% respectively); an increase in both the primary incidence (growth rate of 200%) and the prevalence of hypothyroidism among children (growth rate of 183.5%), an increase in the prevalence of thyroiditis among adults (growth rate of 24.3%).The rate of increase in the primary incidence of obesity, over 6 years of observation, among children was 74.7%, among adolescents - 171.1%; among the adult population - 21.2%.To reverse negative trends in morbidity, we believe it is necessary to strengthen preventive work among all age groups to form healthy eating habits, maintain a normal body weight, take legislative decisions on mass prevention of iodine deficiency in endemic regions, as well as conduct some research aimed at assessing the impact of risk factors caused by the impact of endocrine disruptors on the health of the population of the Republic.

Structural characterization of the SARS-CoV-2 full length nsp1 protein will be an essential tool for developing new target-directed antiviral drugs against SARS-CoV-2 and for further understanding of intra- and intermolecular interactions of this protein. As a first step in the NMR studies of the protein, we report the 1H, 13C and 15N resonance backbone assignment as well as the Cβ of the apo form of the full-lengthSARS-CoV-2 nsp1 including the folded domain together with the flaking N- and C- terminal intrinsically disordered fragments. The 19.8 kD protein was characterized by high-resolution NMR. Validation of assignment have been done by using two different mutants, H81P and K129E/D48E as well as by amino acid specific experiments. According to the obtained assignment, the secondary structure of the folded domain in solution was almost identical to its previously published X-ray structure as well as another published secondary structure obtained by NMR, but some discrepancies have been detected. In the solution SARS-CoV-2 nsp1 exhibited disordered, flexible N- and C-termini with different dynamic characteristics. The short peptide in the beginning of the disordered C-terminal domain adopted two different conformations distinguishable on the NMR time scale. We propose that the disordered and folded nsp1 domains are not fully independent units but are rather involved in intramolecular interactions. Studies of the structure and dynamics of the SARS-CoV-2 mutant in solution are on-going and will provide important insights into the molecular mechanisms underlying these interactions.

An association between high serum calcium/phosphate and cardiovascular events or death is well-established. However, a mechanistic explanation of this correlation is lacking. Here, we examined the role of calciprotein particles (CPPs), nanoscale bodies forming in the human blood upon its supersaturation with calcium and phosphate, in cardiovascular disease. The serum of patients with coronary artery disease or cerebrovascular disease displayed an increased propensity to form CPPs in combination with elevated ionised calcium as well as reduced albumin levels, altogether indicative of reduced Ca2+-binding capacity. Intravenous administration of CPPs to normolipidemic and normotensive Wistar rats provoked intimal hyperplasia and adventitial/perivascular inflammation in both balloon-injured and intact aortas in the absence of other cardiovascular risk factors. Upon the addition to primary human arterial endothelial cells, CPPs induced lysosome-dependent cell death, promoted the release of pro-inflammatory cytokines, stimulated leukocyte adhesion, and triggered endothelial-to-mesenchymal transition. We concluded that CPPs, which are formed in the blood as a result of altered mineral homeostasis, cause endothelial dysfunction and vascular inflammation, thereby contributing to the development of cardiovascular disease.

In this paper, we used an EEG system to monitor and analyze the cortical activity of children and adults at a sensor level during cognitive tasks in the form of a Schulte table. This complex cognitive task simultaneously involves several cognitive processes and systems: visual search, working memory, and mental arithmetic. We revealed that adults found numbers on average two times faster than children in the beginning. However, this difference diminished at the end of table completion to 1.8 times. In children, the EEG analysis revealed high parietal alpha-band power at the end of the task. This indicates the shift from procedural strategy to less demanding fact-retrieval. In adults, the frontal beta-band power increased at the end of the task. It reflects enhanced reliance on the top–down mechanisms, cognitive control, or attentional modulation rather than a change in arithmetic strategy. Finally, the alpha-band power of adults exceeded one of the children in the left hemisphere, providing potential evidence for the fact-retrieval strategy. Since the completion of the Schulte table involves a whole set of elementary cognitive functions, the obtained results were essential for developing passive brain–computer interfaces for monitoring and adjusting a human state in the process of learning and solving cognitive tasks of various types.

In order to achieve a persistent hypotensive effect in primary open-angle glaucoma, a modification of the sinustrabeculectomy operation - modified sinustrabeculectomy with basal iridectomy combined with deep sclerectomy involving drainage of the anterior chamber and suprachoroidal space have been developed at the Department of Eye Diseases of the People's Friendship University of Russia.Development of a new method of surgical treatment of primary open-angle glaucoma based on sinustrabeculectomy with basal iridectomy in combination with deep sclerectomy involving drainage of the anterior chamber and suprachoroidal space by autosclera, and evaluation of the surgical outcomes.The study analyses the results of surgical treatment of 19 patients (19 eyes) with glaucoma, who underwent sinustrabeculectomy with basal iridectomy in combination with deep sclerectomy and drainage of the anterior chamber and suprachoroidal space.The level of intraocular pressure (IOP) on the first day after surgery decreased from 14 mm Hg to 17.5 mm Hg in the late postoperative period (after 12 months), IOP of 18 patients had normalized and stabilized (IOP averaged 17.0±1.8 mm Hg); in 1 case there was an increase in IOP level, for which hypotensive therapy was prescribed (β-blockers).Modified sinustrabeculectomy with basal iridectomy in combination with deep sclerectomy and drainage of the anterior chamber and suprachoroidal space by autosclera helps achieve a persistent hypotensive effect and does not require the use of donor material.Для достижения стойкого гипотензивного эффекта при первичной открытоугольной глаукоме (ПОУГ) нами на кафедре глазных болезней Российского университета дружбы народов разработана модификация традиционной операции синус-трабекулэктомии (СТЭК) — модифицированная СТЭК с дренированием передней камеры и супрахориоидального пространства собственной склерой пациента.Разработка нового метода хирургического лечения ПОУГ на основе СТЭК с базальной иридэктомией в сочетании с глубокой склерэктомией и дренированием передней камеры и супрахориоидального пространства аутосклерой, оценка результатов хирургического лечения пациентов.Изучены результаты хирургического лечения у 19 пациентов (19 глаз) с ПОУГ, которые были прооперированы с использованием метода модифицированной СТЭК с базальной иридэктомией, дренированием передней камеры и супрахориоидального пространства аутосклерой.В первые сутки после операции уровень внутриглазного давления (ВГД) составил 14—17,5 мм рт.ст. В отдаленном послеоперационном периоде (через 12 мес) у 18 пациентов наблюдались нормализация и стабилизация офтальмотонуса (ВГД составило в среднем 17,0±1,8 мм рт.ст.), в одном случае отмечено повышение уровня ВГД, по поводу чего была назначена гипотензивная терапия (бета-блокаторы).Модифицированная СТЭК с базальной иридэктомией в сочетании с глубокой склерэктомией, дренированием передней камеры и супрахориоидального пространства аутосклерой позволяет достичь стойкого гипотензивного эффекта и не требует применения донорского материала.

Factors that affect on the sexual behavior of leeches not only in nature, but also in artificial conditions remain largely unexplored. We did not find data on the behavior of medicinal leeches, which are not placed in time from the aquatic environment in the peat-soil conditions after the appearance of clitella on their bodies. Therefore, the study of this problem has become relevant. For the study, four experimental animals groups were formed: 1 control - medicinal leeches (H. verbana), which were allowed to breed immediately after the appearance of clitella; 2 experimental - medicinal leeches (H. verbana), which were kept in an aqueous medium after the appearance of clitella for a month and then allowed to breed; 3 control - medicinal leeches (H. medicinalis), which were allowed to breed immediately after the appearance of clitella; 4 experimental - medicinal leeches (H. medicinalis), which were kept in an aqueous medium after the appearance of fertilization belts for a month then allowed to breed. The 400 sexually mature healthy medical leeches of two types aged 1.5-2 years were used in experiments. Initially, four individuals were placed into 4-liter containers for sexual intercourse, and after the appearance of differentiated fertilization zones, the control groups were immediately allowed to breed in a peat-soil environment. The experimental groups were left in the same containers for a month and then the survived leeches were allowed to breed. As a result of our research, we found mortality in the experimental groups. From the first week, we found that mortality before breeding of H. verbana was 15.6 ± 2.1% and of H. medicinalis - 14.3 ± 1.5%. Also, 92 ± 0.9% leeches from experimental group died in pet-soil environment sometimes even without cocoon deposition. The experimental group had defective cocoons, but mostly dead offspring.

This study was undertaken to investigate the preoperative incidence and severity of intimal hypertrophy, as well as the level of blood supply of arterial and venous conduits for coronary artery bypass grafting.Segments of the internal thoracic artery and great saphenous vein (n=13) were harvested pairwise during coronary artery bypass grafting and were then visualized by scanning electron microscopy in back-scattered electrons. The analysis of the incidence and thickness of intimal hypertrophy, as well as the calculation of the number and the area of the vasa vasorum were performed using the programme ImageJ.Intimal hypertrophy was more characteristic for the great saphenous vein as compared with the internal thoracic artery (9/13 (69.2%) and 7/13 (55.8%), respectively), although this difference did not reach statistical significance. The maximal-to-minimal neointimal thickness ratio correlated with the percentage of stenosis (r=0.875, p0.0001), the area (r=0.45, p=0.023) and the number (r=0.47, p=0.015) of the vasa vasorum in the conduits, thus confirming the hypothesis on possible participation of these vessels in the development of intimal hypertrophy, with the area of the vasa vasorum being greater in the vessels with10% stenosis (p=0.051). The number of the vasa vasorum in the great saphenous vein exceeded that in the internal thoracic artery (p=0.0005), with this difference remaining significant after adjustment for the area of the adventitia (p=0.027). The number of the vasa vasorum per the percentage of stenosis in the great saphenous vein also exceeded that in the internal thoracic artery (p=0.039) and more strongly correlated with intimal hypertrophy in the great saphenous vein as compared with that in the internal thoracic artery (r=0.53 and r=0.27, respectively).Intimal hypertrophy correlates with the area and number of the vasa vasorum in conduits. The great saphenous vein is characterised by a larger number and higher density of the vasa vasorum as compared with the internal thoracic artery. The number of the vasa vasorum is correlated with stenosis of the great saphenous vein more closely than with stenosis of the internal thoracic artery. This may be suggestive of significant predisposition of the great saphenous vein to the onset of adventitial inflammation followed by the development of intimal hypertrophy.Цель исследования – изучить предоперационные распространенность и выраженность гипертрофии интимы, а также уровень кровоснабжения артериальных и венозных кондуитов для коронарного шунтирования. Материалы и методы. Сегменты внутренней грудной артерии и большой подкожной вены (n=13) были попарно получены в процессе коронарного шунтирования и далее визуализированы сканирующей электронной микроскопией в обратно-рассеянных электронах. Анализ распространенности и толщины гипертрофии интимы, а также подсчеты числа и площади vasa vasorum выполнялись в программе ImageJ. Результаты. Гипертрофия интимы была более характерна для большой подкожной вены в сравнении с внутренней грудной артерией (9/13 (69,2%) и 7/13 (53,8%) соответственно), хотя это различие не достигало статистической значимости. Отношение наибольшей толщины неоинтимы к наименьшей коррелировало с процентом стеноза (r=0,875, p0,0001), площадью (r=0,45, p=0,023) и количеством (r=0,47, p=0,015) vasa vasorum в кондуитах, подтверждая гипотезу о возможном участии этих сосудов в развитии гипертрофии интимы, при этом площадь vasa vasorum была больше в сосудах c10% стенозом (p=0,051). Количество vasa vasorum в большой подкожной вене превышало таковое во внутренней грудной артерии (p=0,0005), причем это различие оставалось значимым после поправки на площадь адвентиции (p=0,027). Количество vasa vasorum на процент стеноза в большой подкожной вене также превышало таковое во внутренней грудной артерии (p=0,039) и сильнее коррелировало с гипертрофией интимы в большой подкожной вене по сравнению с внутренней грудной артерией (r=0,53 и r=0,27 соответственно). Выводы. Гипертрофия интимы коррелирует с площадью и количеством vasa vasorum в кондуитах. В сравнении с внутренней грудной артерией большая подкожная вена характеризуется большим количеством и плотностью vasa vasorum. Количество vasa vasorum связано со стенозом большой подкожной вены сильнее, чем со стенозом внутренней грудной артерии. Это может свидетельствовать о значительной предрасположенности большой подкожной вены к возникновению адвентициального воспаления с последующим развитием гипертрофии интимы.

Aim To evaluate economic results of using omega-3 acid ethyl esters 90 for primary prevention of cardiovascular catastrophes in patients with residual hypertriglyceridemia (HTG).Material and methods The economic evaluation of using the medicine omega-3 acid ethyl esters 90 in the system of drug provision of the population of the Russian Federation was performed by analyzing the effect on the budget using a pharmacoeconomic model developed with the Microsoft Office Excel 2016 software. The effect of omega-3 acid ethyl esters 90 was evaluated in 555 643 patients with residual HGT (Moscow). The study lasted for one year. Results of the meta-analysis by A.A. Bernasconi et al. (2020) were used as a source of efficacy data. The following direct and indirect medical expenses for treatment of cardiovascular complications of residual HTG were taken into account in this study: expenses for drug therapy; expenses for therapy and rehabilitation for nonfatal complications; expenses for fatal outcomes; state support for disability; foregone per capita gross domestic product resulting from losses of earnings due to temporary incapacity to labor by people of work-able age; and salary payments for temporary incapacity to work.Results Using omega-3 acid ethyl esters 90 in 555 643 patients with residual HTG will allow preventing 1 437 fatal ischemic cardiovascular complications (including 564 deaths from ischemic heart disease and 1 128 cases of myocardial infarction (MI), including 558 fatal cases of MI). Furthermore, the difference in expenses compared to the high-dose statin treatment alone will be 359 252 253 rubles or 0.32 %.Conclusion The results of this comprehensive pharmacoeconomical study showed that the use of omega-3 acid ethyl esters 90 in patients with residual HGT is an economically preferrable strategy compared to high-dose statin treatment alone and does not influence significantly the budgetary expenses as a part of the State Guarantee of Free Medical Care to the Citizens of the Russian Federation (increase in expenses by 0.32 % compared to the current practice). At the same time, the use of omega-3 acid ethyl esters 90 results in a 10% decrease in the number of fatal ischemic cardiovascular complications.

Increasing neurological disease burden and advancing treatment options require clinical trials to expand the evidence base of clinical care. We aimed to characterize neurology clinical trials registered between October 2007 and April 2018 and identify features associated with early discontinuation and results reporting.We compared 16,994 neurology (9.4%) and 163,714 non-neurology comparison trials registered to ClinicalTrials.gov. Trials therapeutic focus within neurology was assigned via combination programmatic and manual review. We performed descriptive analyses of trial characteristics, cox regression of early discontinuation, and multivariable logistic regression for results reporting within 3 years of completion.Most neurology trials were academic-funded (58.5%) followed by industry (31.9%) and US-government (9.6%). Neurology trials focused more on treatment than prevention compared to non-neurology studies. Of neurology trials, 11.3% discontinued early, and 32.2% of completed trials reported results by April 30, 2018. In multivariable analysis accounting for time-to-event, neurology trials were at lower risk of discontinuation than non-neurology trials (adjusted hazard 0.83, p 0.0001). Both academic and government-funded trials had greater risk of discontinuation than industry (adjusted hazard 0.57 and 0.46, respectively). Among completed trials, government-funded studies (adjusted odds ratio 2.12, p 0.0001) had highest odds of results reporting while academic trials reported less (adjusted odds ratio 0.51, p 0.0001).Funding source is associated with trial characteristics and outcomes in neurology. Improvements in trial completion and timely dissemination of results remain urgent goals for the field.

5621 patients with MI and emergency PCI were retrospectively selected from the database of the City Clinical Hospital No.13 (Nizhny Novgorod, Russia); among them, there were 3935 men (70%) and 1686 women (30%), their mean age was 61.5±10.8 years. CMVO was recorded in 201 (4%) patients (the blood flow in the infarction-related artery after PCI was less than 3 points according to TIMI flow grade). The following input parameters were assessed: age, gender, past history of coronary artery disease, previous revascularization, presence of ST-segment elevation, a class of acute heart failure, a fact of systemic thrombolytic therapy administration and its effectiveness, symptom-to-balloon time, severity of coronary thrombosis and atherosclerosis, the number of stents and the number of operated coronary arteries. The sampling was divided into a training group (n=4060), a testing group (n=717), and an independent validation group (n=844).We developed an artificial neural network by a fully connected multilayer perception with forward signal propagation and two hidden layers (the area under the ROC curve - 0.69) to predict CMVO based on the subsampling for training and testing. The network model was tested on an independent subsampling (the area under the ROC curve - 0.64, negative predictive value - 97.4%, positive predictive value - 14.6%).The developed artificial neural network enables to use the parameters routinely available in an operating room when choosing a surgical approach and predict CMVO development during PCI in MI patients with accuracy sufficient for practical use.

Alphavirus nsP3 proteins contains long, intrinsically disordered, hypervariable domains, HVD, which serve as hubs for interaction with many cellular proteins. Here, we have deciphered the mechanism and function of HVD interaction with host factors in alphavirus replication. Using NMR spectroscopy, we show that CHIKV HVD contains two SH3 domain-binding sites. Using an innovative chemical shift perturbation signature approach, we demonstrate that CD2AP interaction with HVD is mediated by its SH3-A and SH3-C domains, and this leaves the SH3-B domain available for interaction with other cellular factor(s). This cooperative interaction with two SH3 domains increases binding affinity to CD2AP and possibly induces long-range allosteric affects in HVD. Our data demonstrate that BIN1, CD2AP and SH3KBP1 play redundant roles in initiation of CHIKV replication. Point mutations in both CHIKV HVD binding sites abolish its interaction with all three proteins, CD2AP, BIN1 and SH3KBP1. This results in strong inhibition of viral replication initiation.

In the conclusion of the council of experts (list of participants see text) the following issues are discussed: regional specifics of diagnostics and therapy of patients with ischemic heart disease (IHD) and / or peripheral arterial disease (PAD), methods of risk assessment in patients with stable course of atherosclerotic disease, pathogenetic validity of simultaneous inhibition of coagulation and platelet thrombus formation, as well as clinical significance of a novel therapeutic approach – combined use of rivaroxaban and acetylsalicylic acid (ASA). Possible problems and ways to their solution at implementation in clinical practice of the novel scheme of antithrombotic therapy are presented. Importance of multidisciplinary approach to management of patients with IHD and concomitant diseases is stressed. Experts have noted that after registration of the corresponding indication therapy with rivaroxaban 2.5 mg twice daily and ASA 75–100 mg once daily might be recommended to majority of patients with atherosclerotic involvement of blood vessels. In real clinical practice prescription of this therapy is appropriate first of all in patients with IHD and high risk of complications – with multifocal atherosclerosis, with history of myocardial infarction after stoppage of dual antiplatelet therapy, – patients with concomitant diabetes, heart failure, and other prognosis worsening comorbid diseases. Experts express hope that in the nearest time combined antithrombotic therapy will be included into corresponding national clinical recommendations.

The understanding of neurophysiological mechanisms responsible for motor imagery (MI) is essential for the development of brain-computer interfaces (BCI) and bioprosthetics. Our magnetoencephalographic (MEG) experiments with voluntary participants confirm the existence of two types of motor imagery, kinesthetic imagery (KI) and visual imagery (VI), distinguished by activation and inhibition of different brain areas in motor-related α- and β-frequency regions. Although the brain activity corresponding to MI is usually observed in specially trained subjects or athletes, we show that it is also possible to identify particular features of MI in untrained subjects. Similar to real movement, KI implies muscular sensation when performing an imaginary moving action that leads to event-related desynchronization (ERD) of motor-associated brain rhythms. By contrast, VI refers to visualization of the corresponding action that results in event-related synchronization (ERS) of α- and β-wave activity. A notable difference between KI and VI groups occurs in the frontal brain area. In particular, the analysis of evoked responses shows that in all KI subjects the activity in the frontal cortex is suppressed during MI, while in the VI subjects the frontal cortex is always active. The accuracy in classification of left-arm and right-arm MI using artificial intelligence is similar for KI and VI. Since untrained subjects usually demonstrate the VI imagery mode, the possibility to increase the accuracy for VI is in demand for BCIs. The application of artificial neural networks allows us to classify MI in raising right and left arms with average accuracy of 70% for both KI and VI using appropriate filtration of input signals. The same average accuracy is achieved by optimizing MEG channels and reducing their number to only 13.

The presence of high-frequency velocity fluctuations in aneurysms have been confirmed by in-vivo measurements and by several numerical simulation studies. Only a few studies have located and recorded wall vibrations in in-vitro experiments using physiological patient models. In this study, we investigated the wall fluctuations produced by a flowing perfusion fluid in a true-to-scale elastic model of a cerebral fusiform aneurysm using a laser Doppler vibrometer (LDV). The model was obtained from patient data. The experimental setup reproduced physiologically relevant conditions using a compliant perfusion system, physiological flow parameters, unsteady flow and a non-Newtonian fluid. Three geometrically identical models with different wall elasticities were used for measurements. The influence of five different flow rates was considered. Wall vibrations were predominantly found at frequencies in the range 40–60 Hz and 255–265 Hz. Their amplitude increased with increasing elasticity of the model, but the spectral peaks remained at about the same frequency. Varying the flow rate produced almost no changes in the frequency domain of the models. The frequency of the spectral peaks varied slightly between points at the lateral wall and at the bottom of the aneurysm. Indeed, embedding the model in a fluid during measurements produced higher and smoother amplitude fluctuations.

MutYH-associated polyposis is the only polyposis syndrome with an autosomal recessive type of inheritance, often phenotypically similar to a weakened form of familial adenomatous polyposis. For the development of the disease mutations in both alleles of the gene are required, but an increased risk of developing colorectal cancer in carriers of monoallelic mutations is noted. The diagnosis of MutYH-associated polyposis should be suspected in a patient with colorectal cancer over 45 years old on the background of polyps in the colon. The review presents modern algorithms for diagnostic and treatment of the disease.

With the advent of generative adversarial networks, synthesizing images from textual descriptions has recently become an active research area. It is a flexible and intuitive way for conditional image generation with significant progress in the last years regarding visual realism, diversity, and semantic alignment. However, the field still faces several challenges that require further research efforts such as enabling the generation of high-resolution images with multiple objects, and developing suitable and reliable evaluation metrics that correlate with human judgement. In this review, we contextualize the state of the art of adversarial text-to-image synthesis models, their development since their inception five years ago, and propose a taxonomy based on the level of supervision. We critically examine current strategies to evaluate text-to-image synthesis models, highlight shortcomings, and identify new areas of research, ranging from the development of better datasets and evaluation metrics to possible improvements in architectural design and model training. This review complements previous surveys on generative adversarial networks with a focus on text-to-image synthesis which we believe will help researchers to further advance the field., Published at Neural Networks Journal, available at https://www.sciencedirect.com/science/article/pii/S0893608021002823

Fungal species of genus Sepedonium are rich sources of diverse secondary metabolites (e.g., alkaloids, peptaibols), which exhibit variable biological activities. Herein, two new peptaibols, named ampullosporin F (1) and ampullosporin G (2), together with five known compounds, ampullosporin A (3), peptaibolin (4), chrysosporide (5), c(Trp-Ser) (6) and c(Trp-Ala) (7), have been isolated from the culture of Sepedonium ampullosporum Damon strain KSH534. The structures of 1 and 2 were elucidated based on ESI-HRMSn experiments and intense 1D and 2D NMR analyses. The sequence of ampullosporin F (1) was determined to be Ac-Trp1-Ala2-Aib3-Aib4-Leu5-Aib6-Gln7-Aib8-Aib9-Aib10-GluOMe11-Leu12-Aib13-Gln14-Leuol15, while ampullosporin G (2) differs from 1 by exchanging the position of Gln7 with GluOMe11. Furthermore, the total synthesis of 1 and 2 was carried out on solid-phase to confirm the absolute configuration of all chiral amino acids as L. In addition, ampullosporin F (1) and G (2) showed significant antifungal activity against B. cinerea and P. infestans, but were inactive against S. tritici. Cell viability assays using human prostate (PC-3) and colorectal (HT-29) cancer cells confirmed potent anticancer activities of 1 and 2. Furthermore, a molecular docking study was performed in silico as an attempt to explain the structure-activity correlation of the characteristic ampullosporins (1–3).

The unfolded protein response (UPR) is associated with hepatic metabolic function, yet it is not well understood how endoplasmic reticulum (ER) disturbance might influence metabolic homeostasis. Here, we describe the physiological function of Cysteine-rich with EGF-like domains 2 (Creld2), previously characterized as a downstream target of the ER-stress signal transducer Atf6. To this end, we generated Creld2-deficient mice and induced UPR by injection of tunicamycin. Creld2 augments protein folding and creates an interlink between the UPR axes through its interaction with proteins involved in the cellular stress response. Thereby, Creld2 promotes tolerance to ER stress and recovery from acute stress. Creld2-deficiency leads to a dysregulated UPR and causes the development of hepatic steatosis during ER stress conditions. Moreover, Creld2-dependent enhancement of the UPR assists in the regulation of energy expenditure. Furthermore, we observed a sex dimorphism in human and mouse livers with only male patients showing an accumulation of CRELD2 protein during the progression from non-alcoholic fatty liver disease to non-alcoholic steatohepatitis and only male Creld2-deficient mice developing hepatic steatosis upon aging. These results reveal a Creld2 function at the intersection between UPR and metabolic homeostasis and suggest a mechanism in which chronic ER stress underlies fatty liver disease in males.

For centuries, crop plants have represented the basis of the daily human diet. Among them, cereals and legumes, accumulating oils, proteins, and carbohydrates in their seeds, distinctly dominate modern agriculture, thus play an essential role in food industry and fuel production. Therefore, seeds of crop plants are intensively studied by food chemists, biologists, biochemists, and nutritional physiologists. Accordingly, seed development and germination as well as age- and stress-related alterations in seed vigor, longevity, nutritional value, and safety can be addressed by a broad panel of analytical, biochemical, and physiological methods. Currently, functional genomics is one of the most powerful tools, giving direct access to characteristic metabolic changes accompanying plant development, senescence, and response to biotic or abiotic stress. Among individual post-genomic methodological platforms, proteomics represents one of the most effective ones, giving access to cellular metabolism at the level of proteins. During the recent decades, multiple methodological advances were introduced in different branches of life science, although only some of them were established in seed proteomics so far. Therefore, here we discuss main methodological approaches already employed in seed proteomics, as well as those still waiting for implementation in this field of plant research, with a special emphasis on sample preparation, data acquisition, processing, and post-processing. Thereby, the overall goal of this review is to bring new methodologies emerging in different areas of proteomics research (clinical, food, ecological, microbial, and plant proteomics) to the broad society of seed biologists.

In vitro models of traumatic brain injury (TBI) help to elucidate the pathological mechanisms responsible for cell dysfunction and death. To simulate in vitro the mechanical brain trauma, primary neuroglial cultures were scratched during different periods of network formation. Fluorescence microscopy was used to measure changes in intracellular free Ca2+ concentration ([Ca2+]i) and mitochondrial potential (ΔΨm) a few minutes later and on days 3 and 7 after scratching. An increase in [Ca2+]i and a decrease in ΔΨm were observed ~10 s after the injury in cells located no further than 150–200 µm from the scratch border. Ca2+ entry into cells during mechanical damage of the primary neuroglial culture occurred predominantly through the NMDA-type glutamate ionotropic channels. MK801, an inhibitor of this type of glutamate receptor, prevented an acute increase in [Ca2+]i in 99% of neurons. Pathological changes in calcium homeostasis persisted in the primary neuroglial culture for one week after injury. Active cell migration in the scratch area occurred on day 11 after neurotrauma and was accompanied by a decrease in the ratio of live to dead cells in the areas adjacent to the injury. Immunohistochemical staining of glial fibrillary acidic protein and β-III tubulin showed that neuronal cells migrated to the injured area earlier than glial cells, but their repair potential was insufficient for survival. Mitochondrial Ca2+ overload and a drop in ΔΨm may cause delayed neuronal death and thus play a key role in the development of the post-traumatic syndrome. Preventing prolonged ΔΨm depolarization may be a promising therapeutic approach to improve neuronal survival after traumatic brain injury.

The problem of revealing age-related distinctions in multichannel electroencephalograms (EEGs) during the execution of motor tasks in young and elderly adults is addressed herein. Based on the detrended fluctuation analysis (DFA), differences in long-range correlations are considered, emphasizing changes in the scaling exponent α. Stronger responses in elderly subjects are confirmed, including the range and rate of increase in α. Unlike elderly subjects, young adults demonstrated about 2.5 times more pronounced differences between motor task responses with the dominant and non-dominant hand. Knowledge of age-related changes in brain electrical activity is important for understanding consequences of healthy aging and distinguishing them from pathological changes associated with brain diseases. Besides diagnosing age-related effects, the potential of DFA can also be used in the field of brain–computer interfaces.

Decades of insufficient control resulted in unprecedented spread of chikungunya virus (CHIKV) around the globe and millions already suffered from the highly debilitating disease. Nevertheless, the current understanding of CHIKV-host interactions and adaptability of the virus to replication in mosquitoes and mammalian hosts is still elusive. Our new study shows that four-and-a-half LIM domain protein (FHL1) is one of the host factors that interact with hypervariable domain (HVD) of CHIKV nsP3. Unlike G3BPs, FHL1 is not a pre-requisite of CHIKV replication, and many commonly used cell lines do not express FHL1. However, its expression has detectable stimulatory effect(s) on CHIKV replication, and the Fhl1 KO cell lines demonstrate slower infection spread. The NMR-based studies revealed that the binding site of FHL1 in CHIKV nsP3 HVD overlaps with that of another pro-viral host factor, CD2AP. The structural data also demonstrated that FHL1-HVD interaction is mostly determined by LIM1 domain of FHL1. However, it does not mirror binding of the entire protein, suggesting that other LIM domains are involved. In agreement with previously published data, our biological experiments showed that interactions of CHIKV HVD with CD2AP and FHL1 have additive positive effects on the efficiency of CHIKV replication. This study shows that CHIKV mutants with extensive modifications of FHL1- or both FHL1- and CD2AP- binding sites remain viable and develop spreading infection in multiple cell types. Thus, such modifications of HVD may improve live CHIKV vaccine candidates in terms of their safety and stability of the attenuated phenotype.IMPORTANCEReplication of chikungunya virus (CHIKV) is determined by a wide range of host factors. Previously, we have demonstrated that the hypervariable domain (HVD) of CHIKV nsP3 protein contains linear motifs that recruit defined families of host proteins into formation of functional viral replication complexes. Now, using NMR-based structural and biological approaches, we have characterized the binding site of cellular FHL1 protein in CHIKV HVD and defined the biological significance of this interaction. In contrast to previously described binding of G3BP to CHIKV HVD, the FHL1-HVD interaction was found to not be a prerequisite of viral replication. However, the presence of FHL1 has a stimulatory effect on CHIKV infectivity and subsequently, the infection spread. FHL1 and CD2AP proteins were found to have overlapping binding sites in CHIKV HVD and additive pro-viral functions. Elimination of FHL1-binding site in nsP3 HVD can be used for the development of stable, live attenuated vaccine candidates.

Studies in three mouse models of breast cancer identified profound discrepancies between cell autonomous and systemic Akt1 or Akt2 deletion on breast cancer tumorigenesis and metastasis. First, unlike systemic Akt1 deletion, which inhibits metastasis, cell autonomous Akt1 deletion does not. Second, systemic Akt2 deletion does not inhibit mammary tumorigenesis and metastasis, but cell autonomous Akt2 deletion eliminates ErbB2 expressing cells in the mammary gland and prevents tumorigenesis. However, the elevation in insulin by Akt2 systemic deletion hyperactivates tumor Akt, enabling ErbB2 expression, and exacerbates mammary tumorigenesis. Decreasing insulin level inhibits accelerated tumorigenesis by systemic Akt2 deletion. Single cell mRNA sequencing revealed that systemic Akt1 deletion maintains the pro-metastatic cluster within primary tumors but ablates pro-metastatic neutrophils. Systemic Akt1 deletion inhibits metastasis by impairing the survival and mobilization of tumor-associated neutrophils. Importantly, neutrophil-specific deletion of Akt1 is sufficient to exert resistance to metastasis. The results underscore the importance of determining systemic effects rather than cell autonomous effects as a proof of concept for cancer therapy.

Introduction: From May to December 2019, a literature review of the urinary system iatrogenic injury problem was performed. The most cited, representative articles in PubMed, Scopus, and WoS databases dedicated to this problem were selected. Urinary system iatrogenic injuries include ureter, bladder, urethra, and kidney traumas. It is widely thought that the main causes of such injuries are urological, obstetric, gynecological, and surgical operations on the retroperitoneal space, pelvis, or perineum. Methods: The purpose of the study is to describe all aspects of the iatrogenic injure problem, under the established scheme and for each of the most damaged organs: the urethra, bladder, kidney, and ureter. The treatment of confirmed iatrogenic injuries largely depends on the period of its detection. Modern medical procedures provide conservative or minimally invasive treatment. An untimely diagnosis worsens the treatment prognosis. “Overlooked” urinary system trauma is a serious threat to society and a particular patient. Thus, incorrect or traumatic catheterization can lead to infection (RR 95%) and urethral stricture (RR ≥11–36%), and percutaneous puncture nephrostomy can cause the risk of functional renal parenchyma loss (median 5%), urinary congestion (7%), or sepsis (0.6–1.5%). Results: Lost gain, profits, long-term and expensive, possibly multistage treatment, stress and depression, and the risks of suicide put a heavy financial, moral, and ethical burden on a person and society. Also, iatrogenic injury might have legal consequences. Discussion/Conclusion: Thus, the significant problem of urinary tract iatrogenic injuries is still difficult to solve. There is a need to implement mandatory examining algorithms for patients at risk, as well as the multidisciplinary principle for all pelvic surgery.

The aim of study is to evaluate the results of extraperitoneoscopic radical prostatectomy performed in the presence of various complicating factors.Materials and methods: This prospective study included 7 patients with a diagnosis of prostate cancer (T1-T2b, No, Mo) who underwent extraperitoneoscopic radical prostatectomy (ERPE).Results: Among all ERPEs performed on seven patients, the maximum duration of the surgery was 6 hours 30 minutes, and the minimum one was 3 hours 40 minutes. The average volume of blood loss did not exceed 350±20 ml; decline in hemoglobin level was in the range of 10-12 g/l. The urethral catheter was removed no earlier than 7 days after the surgery. Drainage from the space of Retzius was removed on the 3rd day. Postoperative complications occurred in 2 patients (28.57%). The maximum period of postoperative outpatient follow-up was 22 months. In 6 patients (85.71%), complete urinary retention up to 3 months was noted. One patient (14.29%) had mild urinary incontinence (PADtest - no more than one pad per day). In these cases, sexual potency was absent in 100% of patients. The maximum postoperative PSA level in the group reached 0.13 ng/ ml.Conclusions: Own experience of ERPE in patients on the background of previous transurethral resections and vaporization of the prostate demonstrated the effectiveness and safety of the method. More extensive studies with a larger number of cases are needed.

Analysed herein is the incidence rate of decompensated forms of venous insufficiency in patients who endured lower limb deep vein thrombosis and were prescribed either warfarin, rivaroxaban in therapeutic doses or rivaroxaban in a preventive dose. The study enrolled a total of 129 patients presenting with thrombotic lesions of deep veins of the lower limbs. The patients were divided into three groups depending on the anticoagulant therapy prescribed. Patients of the first and second groups for 6 months received warfarin and rivaroxaban, respectively, in therapeutic doses, and group three patients continued taking rivaroxaban in a therapeutic dose for a long time. RESULTS: Eighteen (36%) patients from the first group and two (4.5%) patients from the second group discontinued taking the anticoagulant before the scheduled date. Relapses of venous thromboembolic complications were observed in 11 (22%) group one patients and in 7 (15.9%) group two patients, with no relapses observed in the third group. Negative dynamics of the ultrasonographic picture was observed in two groups: 16% of group one patients and 9.1% of group two patients were found to develop signs of damage of previously unaltered veins or occlusion of a previously patent vein after endured thrombosis without clinical manifestation. Trophic disorders were observed in a third of patients of the first group and in one patient of the second group by the fourth year of follow up. None of the third group patients developed trophic ulcers. Statistically significant differences in the examined groups were obtained for such parameters as adherence to treatment and the degree of severity of venous insufficiency, in favour of rivaroxaban, with quality of recanalization being significantly better in the third group. A conclusion was drawn that prolonged preventive administration of new oral anticoagulants did not lead to the development of decompensated forms of venous insufficiency.Проанализирована распространенность декомпенсированных форм венозной недостаточности у пациентов, перенесших тромбоз глубоких вен нижних конечностей, которым были назначены варфарин, ривароксабан в лечебной и ривароксабан в профилактической дозах. Всего 129 участников исследования с тромботическим поражением глубоких вен нижних конечностей были разделены на три группы с учетом назначенной антикоагулянтной терапии. Пациенты первой и второй группы в течение 6 месяцев принимали варфарин и ривароксабан, соответственно, в лечебных дозах, больные третьей группы продолжили прием ривароксабана в профилактической дозе длительно. РЕЗУЛЬТАТЫ: 18 (36%) пациентов из первой группы и 2 (4,5%) пациента из второй прекратили прием антикоагулянта ранее установленного срока. Рецидив венозных тромбоэмболических осложнений в первой группе отмечен в 11 (22%) случаях, во второй у 7 (15,9%) пациентов, в третьей рецидивов не зарегистрировано. Отрицательная динамика ультразвуковой картины отмечена в двух группах: у 16% пациентов первой группы и 9,1% больных второй группы появились признаки поражения ранее неизмененных вен или окклюзия ранее проходимой вены после перенесенного тромбоза без клинической манифестации. Трофические расстройства отмечены у трети пациентов первой группы, у одного пациента второй группы к четвертому году наблюдения; в третьей группе ни у одного пациента не развились трофические изменения. Статистически значимые различия в группах были получены по таким параметрам как приверженность к лечению и степень тяжести венозной недостаточности, в пользу ривароксабана, качество реканализации было значимо лучше в третьей группе. Сделан вывод, что длительный профилактический прием новых оральных антикоагулянтов не приводит к развитию декомпенсированных форм венозной недостаточности.

The involvement of periostin in Th2-dependent allergic inflammation has been documented. However, the significance of periostin as a biomarker of local allergic inflammation in the nasal mucosa (NM) of patients with atopic bronchial asthma (BA) and allergic rhinitis (AR) is yet to be determined. The aim of the study was to determine the presence of periostin and evaluate its role as a non-invasive marker of allergic inflammation in the nasal secretions of children with atopic BA and AR. Materials and Methods. In 43 patients aged 4–17 years with atopic BA and AR, the NM was examined using nasal video-endoscopy and (if indicated) computed tomography; the amount of periostin in the nasal secretion was determined by the enzyme immunoassay. Results. Exacerbation of AR was accompanied by a statistically significant increase in the level of periostin in the nasal secretion: up to 0.84 [0.06; 48.79] ng/mg, whereas in remission, that was 0.13 [0.00; 0.36] ng/mg; p=0.04. This value increased progressively as the severity of AR increased from 0.16 [0.00; 0.36] ng/mg in the mild course to 0.20 [0.00; 9.03] ng/mg in AR of moderate severity, and to 10.70 [0.56; 769.20] ng/mg in most severe cases; p=0.048. Hypertrophy or polyposis of the nasal and/or paranasal mucosa was detected in 34.9% (15/43) of the examined patients. The concentration of periostin in the nasal secretion was lower in children without NM hypertrophy: 0.18 [0.001; 4.30] ng/mg vs 0.78 [0.13; 162.10] ng/mg in patients with NM hypertrophy; the differences were close to statistically significant: p=0.051. The level of nasal periostin depended on the clinical form of hypertrophy in the sinonasal mucosa, reaching 0.17 [0.00; 0.32] ng/mg in children with polyposis hyperplasia of NM and 21.6 [10.70; 1516.80] ng/mg — with hypertrophy of the NM in the medial surface of the concha; p=0.02. Conclusion. Exacerbation and increased severity of AR in patients with atopic BA are accompanied by an increased level of periostin in the nasal secretion. This allows us to consider the level of nasal periostin as a biomarker of local allergic inflammation in the NM of patients with atopic BA combined with AR. Hypertrophic changes in the sinonasal mucosa are generally accompanied by an increased level of nasal periostin; specifically, this level significantly depends on the clinical form of mucous membrane hypertrophy and requires additional studies.

Personality traits of users can affect the success in controlling brain-computer interfaces (BCIs), and the activity of right and left brain structures may differ depending on personality traits. Earlier, it was not known, how the success of BCI control with different personality traits is associated with interhemispheric asymmetry. In this work, the dependence of the success of imagination of movements, estimated by the success of recognition of EEG signals during imagination of hand movements compared to rest state, on the user's personal characteristics was studied. It is shown that in single control of BCI by naive subjects, recognition success in imagining right-hand (RH) movements was higher in expressive sensitive extroverts, and in imagining left-hand movements (LH) it was higher in practical, reserved, skeptical, and not very sociable persons. It is suggested that this phenomenon may be based on interhemispheric differences in dopamine level and in the way of encoding movement information.

Venezuelan equine encephalitis virus (VEEV) is one of the important human and animal pathogens. It forms replication enzyme complexes (RCs) containing viral nonstructural proteins (nsPs) that mediate the synthesis of virus-specific RNAs. The assembly and associated functions of RC also depend on the presence of a specific set of host proteins. Our study demonstrates that the hypervariable domain (HVD) of VEEV nsP3 interacts with the members of the FXR family of cellular proteins and also binds the Src homology 3 (SH3) domain-containing proteins CD2AP and SH3KBP1. Interactions with FXR family members are mediated by the C-terminal repeating peptide of HVD. A single short, minimal motif identified in this study is sufficient for driving efficient VEEV replication in the absence of HVD interactions with other host proteins. The SH3 domain-containing proteins bind to another fragment of VEEV HVD. They can promote viral replication in the absence of FXR-HVD interactions albeit less efficiently. VEEV replication can be also switched from an FXR-dependent to a chikungunya virus-specific, G3BP-dependent mode. The described modifications of VEEV HVD have a strong impact on viral replication in vitro and pathogenesis. Their effects on viral pathogenesis depend on mouse age and the genetic background of the virus. IMPORTANCE The replication of alphaviruses is determined by specific sets of cellular proteins, which mediate the assembly of viral replication complexes. Some of these critical host factors interact with the hypervariable domain (HVD) of alphavirus nsP3. In this study, we have explored binding sites of host proteins, which are specific partners of nsP3 HVD of Venezuelan equine encephalitis virus. We also define the roles of these interactions in viral replication both in vitro and in vivo. A mechanistic understanding of the binding of CD2AP, SH3KBP1, and FXR protein family members to VEEV HVD uncovers important aspects of alphavirus evolution and determines new targets for the development of alphavirus-specific drugs and directions for viral attenuation and vaccine development.

Protein glycation is usually referred to as an array of non-enzymatic post-translational modifications formed by reducing sugars and carbonyl products of their degradation. The resulting advanced glycation end products (AGEs) represent a heterogeneous group of covalent adducts, known for their pro-inflammatory effects in mammals, and impacting on pathogenesis of metabolic diseases and ageing. In plants, AGEs are the markers of tissue ageing and response to environmental stressors, the most prominent of which is drought. Although water deficit enhances protein glycation in leaves, its effect on seed glycation profiles is still unknown. Moreover, the effect of drought on biological activities of seed protein in mammalian systems is still unstudied with respect to glycation. Therefore, here we address the effects of a short-term drought on the patterns of seed protein-bound AGEs and accompanying alterations in pro-inflammatory properties of seed protein in the context of seed metabolome dynamics. A short-term drought, simulated as polyethylene glycol-induced osmotic stress and applied at the stage of seed filling, resulted in the dramatic suppression of primary seed metabolism, although the secondary metabolome was minimally affected. This was accompanied with significant suppression of NF-kB activation in human SH-SY5Y neuroblastoma cells after a treatment with protein hydrolyzates, isolated from the mature seeds of drought-treated plants. This effect could not be attributed to formation of known AGEs. Most likely, the prospective anti-inflammatory effect of short-term drought is related to antioxidant effect of unknown secondary metabolite protein adducts, or down-regulation of unknown plant-specific AGEs due to suppression of energy metabolism during seed filling.

The choice of medical rehabilitation in patients with anal incontinence is impossible without diagnostic data revealing the mechanism of fecal incontinence. The most promising are programs of comprehensive physiotherapeutic rehabilitation based on biofeedback training. The rate of anal incompetence (AI) after hemorrhoidectomy is 1.3-12.5%. However, in addition to the organic cause (surgical trauma), functional disorders of the external sphincter and pelvic floor muscles may contribute to the pathogenesis of anal incontinence, aggravating the incontinence symptoms after surgery. Therefore, these functional disorders should be diagnosed before surgery. However, medical rehabilitation programs for anal incontinence after hemorrhoidectomy are not standardized, and functional outcomes have not been studied.To evaluate the outcomes of comprehensive rehabilitation in patients with AI after hemorrhoidectomy to improve quality of life after surgery.A retrospective study was carried out on 46 patients (mean age 53.8±15.4 years) after hemorrhoidectomy with fecal incontinence, 13 (28.3%) males and 33 (71.7%) females. The main group included 25 patients who received comprehensive rehabilitation, including biofeedback training and tibial neuromodulation (TNM) for 15 days. The control group consisted of 21 patients who received TNM at home also for 15 days. The severity of fecal incontinence was determined using the Wexner score. The functional state of the sphincter before and after surgery was assessed using the anorectal manometry (sphincterometry) (WPM Solar, the Netherlands).Comprehensive rehabilitation resulted in a statistically significant clinical improvement: a decrease in the Wexner score in both males and females. No significant differences in manometry results were observed: the anal sphincter tone increased by 16.0% in females and 10.6% in males, and contractility increased by 17.7% and 15.1%, respectively. Monotherapy with TNM in control group patients improved tone indices by 8.7% in females and 6.8% in males, and contractility by 6.2 and 5.4%, respectively, which was lower than in the main group.Contraindications to physiotherapeutic procedures based on electrical stimulation, extracorporeal magnetic stimulation, and magnetic translumbosacral neuromodulation determine the only possible choice of medical rehabilitation, which is the combination of biofeedback training and TNM (as superior to TNM monotherapy). If out-patient medical rehabilitation is not feasible, patients are recommended to complement the home course with a specially designed set of exercises for anal incontinence treatment.Выбор тактики консервативной реабилитации анальной инконтиненции, среди которой особый интерес представляют программы комплексной физиотерапевтической реабилитации с использованием тренировок по методу биологической обратной связи (БОС), невозможен без диагностических данных, выявляющих механизм недержания кишечного содержимого. Частота осложнений после геморроидэктомии в виде недостаточности анального сфинктера (НАС) составляет 1,3—12,5%. Однако в патогенезе анальной инконтиненции помимо органической причины (операционная травма), могут играть роль функциональные нарушения мышц наружного сфинктера и тазового дна, которые усугубляют клинические проявления недержания после операции, в связи с чем их необходимо диагностировать на предоперационном этапе. Вместе с тем реабилитационные программы для лечения анальной инконтиненции после геморроидэктомии не стандартизированы и функциональные результаты не изучены.Оценка результатов комплексной реабилитации у пациентов с НАС после геморроидэктомии с целью улучшения качества жизни в послеоперационном периоде.Ретроспективное исследование проведено у 46 пациентов (средний возраст 53,8±15,4 года) после геморроидэктомии с жалобами на недержание компонентов кишечного содержимого: 13 (28,3%) мужчин, 33 (71,7%) женщины. В основную группу включены 25 пациентов, которым проводили комплексную реабилитацию в объеме тренировок по методу БОС и тибиальной нейромодуляции (ТНМ), курс — 15 сут. Контрольную группу составил 21 пациент, получавший ТНМ в домашних условиях также в течение 15 сут. Клинически степень недержания компонентов кишечного содержимого определяли по шкале Векснера. Инструментально функциональное состояние сфинктерного аппарата до и после операции оценивали с помощью метода аноректальной манометрии (сфинктерометрии) (WPM Solar, Нидерланды).Комплексная реабилитация привела к статистически значимому клиническому улучшению — снижению оценки по шкале Векснера как у мужчин, так и у женщин. В то же время по манометрическим признакам достоверных различий не выявлено: зарегистрировано увеличение тонуса анального сфинктера на 16,0% у женщин и 10,6% у мужчин, сократительной способности — на 17,7 и 15,1% соответственно. Монотерапия ТНМ у пациентов контрольной группы позволила улучшить показатели тонуса на 8,7% у женщин и 6,8% у мужчин, сократительной способности — на 6,2 и 5,4% соответственно, что ниже, чем в основной группе.Наличие у пациентов противопоказаний к проведению физиотерапевтических процедур в виде электрической стимуляции, экстракорпоральной магнитной стимуляции и магнитной транслюмбосакральной нейромодулирующей терапии определяет единственно возможный выбор реабилитационного комплекса — тренировок по методу БОС и ТНМ (как более эффективного, чем монотерапия ТНМ). В случае невозможности прохождения курса реабилитации амбулаторно пациентам рекомендуется дополнять домашний курс специально разработанным комплексом упражнений для лечения анальной инконтиненции.

Advanced morphology analysis and image-based hemodynamic simulations are increasingly used to assess the rupture risk of intracranial aneurysms (IAs). However, the accuracy of those results strongly depends on the quality of the vessel wall segmentation. To evaluate state-of-the-art segmentation approaches, the Multiple Aneurysms AnaTomy CHallenge (MATCH) was announced. Participants carried out segmentation in three anonymized 3D DSA datasets (left and right anterior, posterior circulation) of a patient harboring five IAs. Qualitative and quantitative inter-group comparisons were carried out with respect to aneurysm volumes and ostia. Further, over- and undersegmentation were evaluated based on highly resolved 2D images. Finally, clinically relevant morphological parameters were calculated. Based on the contributions of 26 participating groups, the findings reveal that no consensus regarding segmentation software or underlying algorithms exists. Qualitative similarity of the aneurysm representations was obtained. However, inter-group differences occurred regarding the luminal surface quality, number of vessel branches considered, aneurysm volumes (up to 20%) and ostium surface areas (up to 30%). Further, a systematic oversegmentation of the 3D surfaces was observed with a difference of approximately 10% to the highly resolved 2D reference image. Particularly, the neck of the ruptured aneurysm was overrepresented by all groups except for one. Finally, morphology parameters (e.g., undulation and non-sphericity) varied up to 25%. MATCH provides an overview of segmentation methodologies for IAs and highlights the variability of surface reconstruction. Further, the study emphasizes the need for careful processing of initial segmentation results for a realistic assessment of clinically relevant morphological parameters.

Treatment of cerebral arteriovenous malformations (AVM)—the most common cause of stroke in the pediatric population—can be challenging due to the complexity of size, morphology, and location. There is a significant risk in comparison to AVM treatment among adults. Thus, AVM treatment in the pediatric population imposes unique challenges. Recent improvements include optimized catheter techniques and better embolization materials, such as Onyx, a non-adhesive liquid embolic agent used in the adult population. These improvements have increased the success rate of total and near-total obliteration of cerebral AVM. However, the use of Onyx causes significant distortion of the MR and CT images, which must be accounted for in any radiation treatment planning predicated on CT and MRI. These image distortions impact on the actual delivered dose to the nidus and behoove heterogeneity correction. Our group has previously shared a solution for heterogeneity correction in the adult population. The purpose of this study is to show our experience in this unique group of pediatric patients. This is a retrospective review of pediatric patients, who were undergoing combined endovascular embolization followed by SRS. The cohort consists of 14 patients undergoing SRS treatment in our institute between November 2006 and December 2012 with a mean follow-up of 49.9 months. Within this cohort, we retrospectively reviewed 12 consecutive pediatric patients who underwent a combined endovascular and SRS approach with a mean follow-up of 52.1 months and two patients receiving SRS-only treatment were excluded. In our cohort of 14 patients, 7 (50%) were male, with a mean age of 17.3 years (12.0–22.9) at the time of radiosurgery treatment. Mean age of beginning the combined modality treatment was 15.3 years (8.4–20). The median time from diagnosis to SRS was 24.3 months (11.1–64.4 months) in the complete cohort and 25.6 months (11.1–64.4) in the multimodality group. The overall median follow-up period was 49.9 months (range 12.8–118.8 months) in the complete cohort and 52.1 months (range 12.8–118.8 months) in the multimodality group. Eleven (78.6%) patients had at least one episode of hemorrhage prior to treatment. Spezler-Martin grades at baseline ranged from 2 to 5 (mean 3.2). Fifty percent had grade IV and V. Patients underwent a median of 2 (range 1–5) embolization procedures. The radiosurgical treatment dose to the margin of the angiography-based nidus: median prescription dose of 21.49 Gy (14.39–27.51) with a median max dose of 27.77 Gy (18.93–32.52). The median treatment volume was 0.6 cm3 (0.1–7.3 cm3). The Onyx embolization reduced the nidus target volume by a median of 66.7% (12.0–92.7%). We confirmed 10/14 (71%) complete closures. In 2/14 (14.2%) additional patients, a significant flow reduction was noted. In 1/14 (7.1%) patients, no significant change was noted during the observation period and two (14.2%) patients were without follow-up information. In two patients, post-treatment edema was noted; however, none was clinically significant and resolved without additional intervention or treatment. This cohort comprises the largest combined Onyx-SRS pediatric experience in the literature. In conjunction with our adult group study, we show that the use of Onyx reduces the SRS treatment target volume significantly. Importantly, we implemented the heterogeneity correction to avoid increased radiation exposure to normal surrounding brain tissue. The combined approach appears to be safe provided that the above-mentioned corrections are implemented.

A study on the Russian trotting breeds was conducted to assess the impact of horses' sporting results and the degree of accumulation of chemical elements in the hair. In the first phase of the research, the elemental composition of the mane hair of trotter horses (n = 215) was studied. Based on these studies, percentile intervals for the distribution of concentrations of chemical elements in the hair have been established, and the values of 25 and 75 percentile adopted as a "physiological standard" have been defined. In the second stage of the research into clinically healthy Russian trotting breeds (n = 56), it was estimated that the sporting results were dependent on the elemental status defined by the hair. The elemental composition of the hair was defined by 25 chemical elements using atomic emission and mass spectrometry. It is established that the mane hair is closely related to the sporting results of trotter horses. Thus, in animal wool with the highest sporting achievements, there were reliably less I, Cr, Co, Li, V, Al, Pb, and Cd, and reliably more Si than the low ones. Differences in individual elements exceeded 200%. As sporting performance diminished, the number of elements within the standard increased. For example, for mares with average speed, there were deviations from the physiological standard by 6 elements (P, Fe, Mn, I, Co, Si), with the low one by 13 elements (P, Fe, Cu, Mn, I, Co, Si, K, Cr, Ni, V, Al, Pb). A comparative estimate of the mineralization of the horses' mane measured by the sum of the amount of substances showed that there was a negative correlation between the accumulation of toxic elements and the speed (r = - 0.59). On the basis of the above, a conclusion is reached on the future use of the mane hair to assess the speed qualities of trotter horses.