Репозиторий Университета

© 2021, The Author(s). Background: The acute phase response (APR) to CNS insults contributes to the overall magnitude and nature of the systemic inflammatory response. Aspects of this response are thought to drive secondary inflammatory pathology at the lesion site, and suppression of the APR can therefore afford some neuroprotection. In this study, we examined the APR in a mouse model of traumatic spinal cord injury (SCI), along with its relationship to neutrophil recruitment during the immediate aftermath of the insult. We specifically investigated the effect of IL-1 receptor antagonist (IL-1RA) administration on the APR and leukocyte recruitment to the injured spinal cord. Methods: Adult female C57BL/6 mice underwent either a 70kD contusive SCI, or sham surgery, and tissue was collected at 2, 6, 12, and 24 hours post-operation. For IL-1RA experiments, SCI mice received two intraperitoneal injections of human IL-1RA (100mg/kg), or saline as control, immediately following, and 5 hours after impact, and animals were sacrificed 6 hours later. Blood, spleen, liver and spinal cord were collected to study markers of central and peripheral inflammation by flow cytometry, immunohistochemistry and qPCR. Results were analysed by two-way ANOVA or student’s t-test, as appropriate. Results: SCI induced a robust APR, hallmarked by elevated hepatic expression of pro-inflammatory marker genes and a significantly increased neutrophil presence in the blood, liver and spleen of these animals, as early as 2 hours after injury. This peripheral response preceded significant neutrophil infiltration of the spinal cord, which peaked 24 hours post-SCI. Although expression of IL-1RA was also induced in the liver following SCI, its response was delayed compared to IL-1β. Exogenous administration of IL-1RA during this putative therapeutic window was able to suppress the hepatic APR, as evidenced by a reduction in CXCL1 and SAA-2 expression as well as a significant decrease in neutrophil infiltration in both the liver and the injured spinal cord itself. Conclusions: Our data indicate that peripheral administration of IL-1RA can attenuate the APR which in turn reduces immune cell infiltration at the spinal cord lesion site. We propose IL-1RA treatment as a viable therapeutic strategy to minimise the harmful effects of SCI-induced inflammation.

© 2020, LLC Science and Innovations. Pancreatic cancer (PC) is one of the most fatal types of oncological disease in the world and is an extremely aggressive cancer with a poor prognosis. The objective of this review was to analyze the domestic data of the incidence of PC in the Russian Federation and to analyze the protocols that are used for the management of this group of patients in Russian clinical centers. For the analysis of the literature sources, the data in the elibrary.ru database published in the period from 2015 to 2019 were used. The methodology that was used in each study was examined in order to ensure its reliability, and these data were selected as potential sources of evidence for the preparation of national recommendations. The study results influence the level of evidence assigned to the publication. Updates to the national recommendations are conducted at least once every three years, and these updates depend on new information about the diagnosis and management of patients with PC.

© 2020, LLC Science and Innovations. Pancreatic cancer (PC) is one of the most fatal types of oncological disease in the world and is an extremely aggressive cancer with a poor prognosis. The objective of this review was to analyze the domestic data of the incidence of PC in the Russian Federation and to analyze the protocols that are used for the management of this group of patients in Russian clinical centers. For the analysis of the literature sources, the data in the elibrary.ru database published in the period from 2015 to 2019 were used. The methodology that was used in each study was examined in order to ensure its reliability, and these data were selected as potential sources of evidence for the preparation of national recommendations. The study results influence the level of evidence assigned to the publication. Updates to the national recommendations are conducted at least once every three years, and these updates depend on new information about the diagnosis and management of patients with PC.

© 2021, The Author(s). Background: The morphometric analysis of the individual bones of the human skeleton can be used to estimate the sex of unidentified corpses. Our aims were as follows: to test whether thyroid cartilage can be used for forensic purposes as a predictor of biological sex; to establish the level of sexual dimorphism of the thyroid cartilage in a sample of adult subjects from a population of European Russia; and to test the accuracy of the morphometric parameters obtained from the thyroid cartilage. Results: The thyroid cartilage from 100 adults of known age (50 males and 50 females) was obtained during forensic examination; morphometric tests were conducted using Vernier Digital ROKTOOLS ABS DIN 862 0-200/6 inch with measurement accuracy ± 0.01 mm. The measured parameters were N = 31 for each subject. Intra- and inter-observer reproducibility was tested. Multivariate statistical analysis was applied to the measurements. To check the data set for normal distribution, the Kolmogorov-Smirnov test was used. Finally, to estimate the sex of the observed individuals, a stepwise discriminant analysis was conducted, using the Wilks’ lambda selection method. The most significant parameters were the outer distance between bases of inferior horn; the inner distance between distal ends of inferior horns; distance between distal ends of left superior and inferior horns; left superior horn length (distance between left superior horn distal end and base); distance between superior and inferior notches; thyroid angle; left lamina height (vertical line along left lamina middle); horizontal distance between anterior intermedium line and the right lamina posterior edge; distance between inferior thyroid notch and line connecting left and right thyroid laminae; and left superior horn thickness at mid-line. The stepwise discriminant analysis resulted in an equation with ten parameters. Conclusions: The results of the current study indicated that in the European Russian population, the equation obtained in the stepwise discriminant analysis makes it possible to predict sex with a probability of 100% on the validation set. On the test set, the resultant accuracy was 100% for females and 100% for males. Our findings confirm the scientific evidence that the thyroid cartilage has a pronounced sexual dimorphism.

© 2021, The Author(s). Background: The morphometric analysis of the individual bones of the human skeleton can be used to estimate the sex of unidentified corpses. Our aims were as follows: to test whether thyroid cartilage can be used for forensic purposes as a predictor of biological sex; to establish the level of sexual dimorphism of the thyroid cartilage in a sample of adult subjects from a population of European Russia; and to test the accuracy of the morphometric parameters obtained from the thyroid cartilage. Results: The thyroid cartilage from 100 adults of known age (50 males and 50 females) was obtained during forensic examination; morphometric tests were conducted using Vernier Digital ROKTOOLS ABS DIN 862 0-200/6 inch with measurement accuracy ± 0.01 mm. The measured parameters were N = 31 for each subject. Intra- and inter-observer reproducibility was tested. Multivariate statistical analysis was applied to the measurements. To check the data set for normal distribution, the Kolmogorov-Smirnov test was used. Finally, to estimate the sex of the observed individuals, a stepwise discriminant analysis was conducted, using the Wilks’ lambda selection method. The most significant parameters were the outer distance between bases of inferior horn; the inner distance between distal ends of inferior horns; distance between distal ends of left superior and inferior horns; left superior horn length (distance between left superior horn distal end and base); distance between superior and inferior notches; thyroid angle; left lamina height (vertical line along left lamina middle); horizontal distance between anterior intermedium line and the right lamina posterior edge; distance between inferior thyroid notch and line connecting left and right thyroid laminae; and left superior horn thickness at mid-line. The stepwise discriminant analysis resulted in an equation with ten parameters. Conclusions: The results of the current study indicated that in the European Russian population, the equation obtained in the stepwise discriminant analysis makes it possible to predict sex with a probability of 100% on the validation set. On the test set, the resultant accuracy was 100% for females and 100% for males. Our findings confirm the scientific evidence that the thyroid cartilage has a pronounced sexual dimorphism.

In the search for anti-SARS-CoV-2 drugs, much attention is given to safe and widely available native compounds. The green tea component epigallocatechin 3 gallate (EGCG) is particularly promising because it reportedly inhibits viral replication and viral entry in vitro. However, conclusive evidence for its predominant activity is needed. We tested EGCG effects on the native virus isolated from COVID-19 patients in two independent series of experiments using VERO cells and two different treatment schemes in each series. The results confirmed modest cytotoxicity of EGCG and its substantial antiviral activity. The preincubation scheme aimed at infection prevention has proven particularly beneficial. We complemented that finding with a detailed investigation of EGCG interactions with viral S-protein subunits, including S2, RBD, and the RBD mutant harboring the N501Y mutation. Molecular modeling experiments revealed N501Y-specific stacking interactions in the RBD-ACE2 complex and provided insight into EGCG interference with the complex formation. Together, these findings provide a molecular basis for the observed EGCG effects and reinforce its prospects in COVID-19 prevention therapy.

© 2020 by the authors. The success of using soft tissue transplants is enough for their spreading in the clinic, but the need to cover the surface, where the transplant was taken from, can be forgotten. It can lead to long-term discomfort of the patient in real life, in some cases to complications alike bleeding; We performed the analysis of the use of different new xenogenic resorbable membranes created within our University in compare with the natural healing of oral mucosa defects in the experiment in vivo on 36 rabbits after performing of the surgical wound on the palatine side (5x5 mm). All animals were separated (divided) for 3 groups: #1 group of control and main groups #2 and #3, where we used pericardium and collagen film for covering mucous defects. We assessed the edema, hyperemia in the operation side, the pain according to animal behavior, the histological picture after animals completion of the experiment (on 3rd, 6th and 10th days); The decrease of clinical signs of inflammation in groups of collagen and pericardium films use (p<0.05) was statistically confirmed. Analysis of histologic investigation of biopsy specimens has shown the faster and massive growth of soft tissue in the donor site after application of pericardium and collagen films (p<0.05). An analysis of the experiment results allows recommending their possible use for closing the donor site after taking a free gingival graft or in the zone of postoperative wound defect in the oral mucosa in clinical oral surgery after specific clinical trials.

© 2020 The Authors Congenital malformations of blood vessels, including arteriovenous malformations (AVMs), are a less common pathology, which remains one of the most diagnostically and therapeutically complex diseases for treatment. Patients with vascular abnormalities often receive an erroneous diagnosis and inadequate treatment. Depending on the abnormality, such improper treatment can lead to potential long-term functional and cosmetic consequences. Existing treatment options include surgical resection, endovascular embolization, and a combination of these methods. To date, there is no pharmacotherapy available that allows you to radically treat this pathology. Despite recent advances, AVMs are rarely cured and may require multi-stage therapy throughout life. The article presents a clinical case of successful endovascular treatment of extra-intracranial arteriovenous malformation of the frontoparietal region in a young girl with a more pronounced extracranial component of AVM on the front and frontoparietal region with cosmetic and functionally significant defect. We performed double-stage embolization of AVMs with a combination of non-adhesive liquid embolic agents with high and low viscosity. We got good angiographic, clinical and cosmetic treatment results.

© 2020 Objective: The association between the most severe types of placenta accreta spectrum disorders and caesarean scar pregnancy (CSP) poses the question of whether early diagnosis may impact the clinical outcome of these anomalies. The aim of this study is to report the outcome of cesarean scar pregnancy (CSP) diagnosed in the early (≤9 weeks) versus late (>9 weeks) first trimester of pregnancy. Study design: Medline, Embase and Clinicaltrail.gov databases were searched. Studies including cases of CSP with an early (≤9 weeks of gestation) compared to a late (>9 weeks) first trimester diagnosis of CSP, followed by immediate treatment, were included in this systematic review. The primary outcome was a composite measure of severe maternal morbidity including either severe first trimester bleeding, need for blood transfusion, uterine rupture or emergency hysterectomy. The secondary outcomes were the individual components of the primary outcome. Random-effect meta-analyses were used to combine data. Results: Thirty-six studies (724 women with CSP) were included. Overall, composite adverse outcome complicated 5.9 % (95 % CI 3.5−9.0) of CSP diagnosed ≤9 weeks and 32.4 % (95 % CI 15.7−51.8) of those diagnosed >9 weeks. Massive hemorrhage occurred in 4.3 % (95 % CI 2.3−7.0) of women with early and in 28.0 % (95 % CI 14.1−44.5) of those with late first trimester diagnosis of CSP, while the corresponding figures for the need for blood transfusion were 1.5 % (95 % CI 0.6−2.8) and 15.8 % (95 % CI 5.5−30.2) respectively. Uterine rupture occurred in 2.5 % (95 % CI 1.2−4.1) of women with a prenatal diagnosis of CSP ≤ 9 weeks and in 7.5 % (95 % CI 2.5−14.9) of those with CSP > 9 weeks, while an emergency intervention involving hysterectomy was required in 3.7 % (95 % CI 2.2−5.4) and 16.3 % (95 % CI5.9−30.6) respectively. When computing the risk, early diagnosis of CSP was associated with a significantly lower risk of composite adverse outcome, (OR: 0.14; 95 % CI 0.1−0.4 p < 0.001). Conclusions: Early first trimester diagnosis of CSP is associated with a significantly lower risk of maternal complications, thus supporting a policy of universal screening for these anomalies in women with a prior cesarean delivery although the cost-effectiveness of such policy should be tested in future studies.

© 2020 Bone age is used widely by pediatricians to assess the skeletal maturity of a child and predict growth potential. This entails measuring the size of secondary ossification centers (SOCs), which develop with age in the ends of long bones, which are initially cartilaginous. However, little is presently known about the developmental biology, evolution and functional role of these skeletal elements. Here, we summarize the knowledge currently available in this area and discuss potential primary functions of the SOC.

© 2020 Bone age is used widely by pediatricians to assess the skeletal maturity of a child and predict growth potential. This entails measuring the size of secondary ossification centers (SOCs), which develop with age in the ends of long bones, which are initially cartilaginous. However, little is presently known about the developmental biology, evolution and functional role of these skeletal elements. Here, we summarize the knowledge currently available in this area and discuss potential primary functions of the SOC.

© 2020 Bone age is used widely by pediatricians to assess the skeletal maturity of a child and predict growth potential. This entails measuring the size of secondary ossification centers (SOCs), which develop with age in the ends of long bones, which are initially cartilaginous. However, little is presently known about the developmental biology, evolution and functional role of these skeletal elements. Here, we summarize the knowledge currently available in this area and discuss potential primary functions of the SOC.

© 2020, The Author(s). Background: Currently, no data is available regarding the association between professional experience or limb dominance and the prevalence of asymptomatic knee joint lesions in adult professional male soccer players. Hypothesis: The prevalence of the accumulated changes increases with training experience. This is especially true for the dominant leg, which is involved in a large proportion of the athletes’ movements. Study Design: Level 2 cross-sectional cohort study Methods: MRI was used to assess the condition of 94 knee joints in 47 adult professional male soccer players (mean age 25.7 ± 4.6 years, BMI 22.8 ± 1.4). Previous surgery on joints was an exclusion criterion. No football player had knee injuries (including fresh bruises) for at least 3 months before the examination. All the scans were performed using a 1.5T MRI scanner and a slice thickness of 3 mm. The images were blindly analyzed by two experienced radiologists. We analyzed all the three compartments of the knee joint. We consider a chondral lesion already from grade I in modified Noyes and Stabler classification system. To assess the influence of soccer training experience, all players were divided into two groups: group 1 formed from players with less than 20 years of experience and group 2 with more than 20 years of experience. Results: One hundred percent of the soccer players had at least one chondral and meniscal lesion. In both legs, the posterior horn of the medial meniscus (95.6%) was the most frequent site of injury. Most of the injuries were classified as grade II injuries (73.3% for the dominant and 75.6% for the non-dominant leg). Experience and age of the athletes significantly increased the probability of subcortical bone lesions. They were significantly positively correlated with the grades of patellar lesions and lesions of the patellar surface of the femur and significantly negatively correlated with the grades of lesions of posterior horn of lateral meniscus and anterior horn of medial meniscus. No statistically significant differences in the prevalence and grades of cartilage and meniscal lesions in the dominant and non-dominant limb were observed. Conclusion: Soccer practice is associated with the increased prevalence of asymptomatic chondral and meniscal lesions. The probability of subcortical bone lesions significantly increases with training experience and age. These factors are also positively correlated with the grades of patellar lesions and lesions of the patellar surface of the femur. The prevalence and grade of asymptomatic chondral and meniscal lesions is independent of leg dominance.

© 2020 Age estimation is an important procedure in the forensic practice, especially when it comes to the criminal imputability of juvenile offenders. This study aimed to compare two radiographic methods for dental age estimation in a population of subadults from Northeast Brazil considering their performance on allocating individuals below or above the age threshold of 18 years. A cross-sectional observational study was designed. The sample consisted of 1200 panoramic radiographs of Northeastern Brazilian females (n = 600) and males (n = 600) aged between 16 and 21 years. Dental age estimation was performed using the London Atas technique and Cameriere's third molar maturity index (I3M). Statistical tests were performed to assess the sensitivity, specificity and accuracy of the two methods on distinguishing individuals below or above the legal age threshold of 18 years. Considering the total sample, the London Atlas technique reached sensitivity of 92.3%, specificity of 56% and accuracy of 79.9%. I3M revealed sensitivity of 94.1%, specificity of 55.4% and accuracy of 79.8%. Specificity rates systematically decreased when the sample was progressively stratified based on age groups that narrowed close to 18 years. The methods performed very similar (0.878). The combination of methods did not improve the performance on dental age estimation. The London Atlas and the I3M methods similarly distinguished Brazilian individuals as minors or not. Their performance, however, was suboptimal because of the low rates of specificity that could negatively influence on Court decisions. In other words, the methods could wrongly classify minors into the age of legal majority (culminating in false positives). In practice, the misleading classification could restrict individual rights (in the civil scenario) or even support more severe penalties (in the criminal scenario).

© 2020 Elsevier B.V. Fe/Fe3O4 nanoparticles have been deposited on the surfaces of ultrathin CoFeB film and CoFeB/Ta/CoFeB hetero-structure to be detected due to the stray field generated by one particle or a cluster of particles. Exchange biased Fe/Fe3O4 core-shell nanoparticles have been used to stabilize the particles magnetization. Comparison between the Atomic Force and Magnetic Force Microscope images and subtraction of corresponding phase contrasts allows visualization of the film magnetization affected by the particles. Spectra of Ferromagnetic Resonance of the ultrathin films with deposited particles allow one to estimate particle/film dipolar interaction. The results will be useful for the development of lab-on-chip sensors of magnetically labeled cells. Estimation of particles number by magnetic response of the CoFeB heterostructure is demonstrated.

© 2020 Elsevier B.V. In a recent computational study, we revealed some mechanistic aspects of TRPV1 (transient receptor potential channel 1) thermal activation and gating and proposed a set of probable functionally important residues — “hot spots” that have not been characterized experimentally yet. In this work, we analyzed TRPV1 point mutants G643A, I679A + A680G, and K688G/P combining molecular modeling, biochemistry, and electrophysiology. The substitution G643A reduced maximal conductivity that resulted in a normal response to moderate stimuli, but a relatively weak response to more intensive activation. I679A + A680G channel was severely toxic for oocytes most probably due to abnormally increased basal activity of the channel (“always open” gates). The replacement K688G presumably facilitated movements of TRP domain and disturbed its coupling to the pore, thus leading to spontaneous activation and enhanced desensitization of the channel. Finally, mutation K688P was suggested to impair TRP domain directed movement, and the mutated channel showed ~100-fold less sensitivity to the capsaicin, enhanced desensitization and weaker activation by the heat. Our results provide a better understanding of TRPV1 thermal and capsaicin-induced activation and gating. These observations provide a structural basis for understanding some aspects of TRPV1 channel functioning and depict potentially pathogenic mutations.

© 2020 Elsevier B.V. In a recent computational study, we revealed some mechanistic aspects of TRPV1 (transient receptor potential channel 1) thermal activation and gating and proposed a set of probable functionally important residues — “hot spots” that have not been characterized experimentally yet. In this work, we analyzed TRPV1 point mutants G643A, I679A + A680G, and K688G/P combining molecular modeling, biochemistry, and electrophysiology. The substitution G643A reduced maximal conductivity that resulted in a normal response to moderate stimuli, but a relatively weak response to more intensive activation. I679A + A680G channel was severely toxic for oocytes most probably due to abnormally increased basal activity of the channel (“always open” gates). The replacement K688G presumably facilitated movements of TRP domain and disturbed its coupling to the pore, thus leading to spontaneous activation and enhanced desensitization of the channel. Finally, mutation K688P was suggested to impair TRP domain directed movement, and the mutated channel showed ~100-fold less sensitivity to the capsaicin, enhanced desensitization and weaker activation by the heat. Our results provide a better understanding of TRPV1 thermal and capsaicin-induced activation and gating. These observations provide a structural basis for understanding some aspects of TRPV1 channel functioning and depict potentially pathogenic mutations.

© 2020 Elsevier B.V. A self-setting bone cement containing β-tricalcium phosphate (TCP) supplemented with boron nitride nanotubes (BNNTs, 1 wt%) was synthesized and analyzed in situ for its kinetics of hardening and selected physicochemical and biological properties. Moderately delayed due to the presence of BNNTs, the hardening reaction involved the transformation of the TCP precursor to the dicalcium phosphate (DCPD) product. In spite of the short-lived chemical transformations in the cement upon its hardening, the structural changes in it were extended. As a result, the compressive strength increased from day 1 to day 7 of the hardening reaction and the presence of BNNTs further increased it by ~25%. Fitting of the time-resolved energy-dispersive diffractometric data to the Johnson-Mehl-Avrami-Kolmogorov crystallization kinetics model conformed to the one-dimensional nucleation at a variable rate during the growth of elongated DCPD crystals from round TCP grains. For the first seven days of growth of human mesenchymal stem cells (hMSCs) on the cement, no difference in their proliferation was observed compared to the control. However, between the 7th and the 21st day, the cell proliferation decreased compared to the control because of the ongoing stem cell differentiation toward the osteoblast phenotype. This differentiation was accompanied by the higher expression of alkaline phosphatase, an early marker of hMSC differentiation into a pre-osteoblast phenotype. The TCP cement supplemented with BNNTs was able to thwart the production of reactive oxygen species (ROS) in hMSCs treated with H2O2/Fe2+ and bring the ROS levels down to the concentrations detected in the control cells, indicating the good capability of the material to protect the cells against the ROS-associated damage. Simultaneously, the cement increased the expression of mediators of inflammation in a co-culture of osteoblasts and macrophages, thus attesting to the direct reciprocity between the degrees of inflammation and stimulated new bone production.

© 2020 Elsevier Inc. The hypothalamus is the most important integrator of autonomic and endocrine regulation in the body and it also has a fundamental role in ageing development and lifespan control. In order to better understand the role of NO-ergic system in the hypothalamic regulation of ageing, the purpose of this study was to investigate the expression of neuronal nitric oxide synthase (nNOS) in the arcuate (ARC), ventromedial (VMH) and dorsomedial (DMH) hypothalamic nuclei in young (2-3-month-old) and old (24-month-old) male and female rats using immunohistochemistry and western blot analysis. In young animals, only single nNOS-immunoreactive (IR) neurons were detected in ARC, and nNOS-IR neurons were found in the VMH (19 ± 3.2% in females and 14.5 ± 2.6% in males) and DMH (17 ± 4.0% in females and 21 ± 2.8% in males). In aged animals, the number of nNOS-IR neurons increased in all studied nuclei, including ARC (36 ± 3.1% in females and 33.5 ± 3.7% in males), VMH (83 ± 4.3% in females and 58 ± 2.1% in males) and DMH (57 ± 1.9% in females and 54 ± 1.8% in males). The expression of nNOS also significantly increased in the ARC, VMH and DMH during ageing by western blot analysis. In conclusion, ageing is accompanied by increasing of nNOS expression in the hypothalamus and this process is related to regions involved in the control of feeding behavior.