Effects of Combined Exposure to Carbon Ions and Protons on the Pool of MCF-7 Breast Cancer Stem Cells In Vitro.

We studied the effects of single and combined action of protons and carbon ions 12C6+ on the pool of MCF-7 human breast cancer stem cells. Single irradiation with a beam of protons or carbon ions had no significant effects on the relative number of cancer stem cells (CSC). The effects of combined irradiation in a total equieffective dose of 4 Gy depended on the sequence of exposure to ionizing radiations: the relative number of CSC did not change after irradiation with carbon ions and then with protons, but increased in the case of the reverse sequence. The most favorable result, i.e. a decrease in the CSC pool, was observed in the case of sequential irradiation with carbon ions and protons and their equal contribution to total equieffective dose. In this case, the absolute number of CSC decreased by on average 2.1 times in comparison with the control (p<0.05). The revealed regularities are of interest for the further development of new methods of radiation therapy.

[A longitudinal study of pediatric-onset multiple sclerosis in the Voronezh region]. / Prospektivnyi analiz klinicheskogo techeniya rasseyannogo skleroza s debyutom v detskom i podrostkovom vozraste v Voronezhskoi oblasti.

OBJECTIVE: To study the clinical course, the rate of progression and the results of the disease modifying treatment (DMT) in pediatric-onset multiple sclerosis (POMS) patients in the Voronezh region. MATERIAL AND METHODS: The clinical characteristics of the course of relapsing-remitting multiple sclerosis (MS) were analyzed among 51 POMS patients and 51 patients with the adult-onset MS (AOMS). The clinical course was assessed based on the Expanded Disability Status Scale (EDSS) score, the average annual frequency of exacerbations and the rate of disease progression before and during DMT. RESULTS: There were no statistically significant differences in EDSS scores 11 years after the onset of MS between the groups: POMS patients achieved moderate disability by the age of 25, and AOMS patients showed stabilization of their condition during DMT by the age of 36. During changing first-line drugs in patients with POMS, there was again an increase in disability with the transition of 25% of patients to the group with secondary progression of MS on average after 8 years of DMT. CONCLUSION: The onset of the disease in children and adolescents leads to a significant decrease in their quality of life and the deterioration of all activities throughout their lives. To prevent the progression of the disease it seems appropriate to transfer patients with POMS immediately to second-line DMT when signs of a suboptimal response to first line DMT appear, and in the case of a rapidly progressive course to start therapy with second-line drugs.

Characterization of CoCas9 nuclease from Capnocytophaga ochracea.

Cas9 nucleases are widely used for genome editing and engineering. Cas9 enzymes encoded by CRISPR-Cas defence systems of various prokaryotic organisms possess different properties such as target site preferences, size, and DNA cleavage efficiency. Here, we biochemically characterized CoCas9 from Capnocytophaga ochracea, a bacterium that inhabits the oral cavity of humans and contributes to plaque formation on teeth. CoCas9 recognizes a novel 5'-NRRWC-3' PAM and efficiently cleaves DNA in vitro. Functional characterization of CoCas9 opens ways for genetic engineering of C. ochracea using its endogenous CRISPR-Cas system. The novel PAM requirement makes CoCas9 potentially useful in genome editing applications.

DISEASES OF THE ORAL MUCOSA IN PATIENTS IN THE POST-COVID PERIOD.

The impact of SARS-CoV-2 (severe acute respiratory syndrome-related coronavirus-2) on the entire human body causes irreversible changes in all organs and systems. Complications in the form of chronic diseases require the treatment of clinicians in various fields of medicine. Dentists are faced with diseases of the oral mucosa in apparently healthy patients who are not predisposed to them but have undergone COVID-19. Purpose of the study - to assess the impact of the coronavirus infection (COVID-19) on the course of diseases of the oral mucosa. We examined 51 patients aged 20 to 75 who had undergone COVID-19 with various diseases of the oral mucosa. The study used clinical and laboratory methods. The features of the clinical course of certain diseases of the oral mucosa were revealed, the dynamics of the local immune defense of the oral cavity in the post-covid period was determined.

Clinical and Genetic Characteristics of Preeclampsia.

Preeclampsia (PE) is a severe complication of pregnancy accompanied by arterial hypertension, edema, or proteinuria with impaired functioning of various organs and systems. It is also an important medical and social problem, which has been one of the leading causes of maternal and perinatal mortality and morbidity worldwide. Despite the achievements of modern medicine, the etiology of this pathology is still unknown. Recently, many scientists have especially focused on the study of genetic factors underlying the etiopathogenesis of PE, namely, the contribution of individual polymorphic loci of various candidate genes. The current study aimed to investigate the clinical characteristics of PE and the contribution of the polymorphic loci rs1042838 of Progesterone Receptor (PGR) gene and rs8068318 of the T-Box Transcription Factor 2 (TBX2) gene to the development of PE. The study was conducted on 219 women with PE with the mean±SD age of 26.52±5.51 years and 329 women with the physiological course of pregnancy as the control group with the mean±SD age of 26.27±4.88 years. In total, 64.20%, 68.29%, 16.44%, 98.63%, and 35.48% of women with PE had increased systolic and normal diastolic blood pressure (SBP and DBP) values, proteinuria, edema, and overweight (BMI≥25), respectively. In the control group, 100%, 1.53%, 1.12%, and 35.48% of cases had normal SBP values with no proteinuria, DBP>90 mm Hg, edema, and overweight (BMI≥25), respectively. An association was observed between the CC genotype of the rs8068318 polymorphism of the TBX2 gene with the risk of developing PE in women with PE (OR=2.12, 95%CI: 1.14-3.92, P=0.02). In addition, there was an association between the rs8068318 TBX2 polymorphic locus with lower SBP (Me=140, Q25 - Q75 130 - 142.5, P=0.01) and PBP (Me=50, Q25 - Q75 40 - 55, P<0.01). According to the GeneCards database, the TBX2 gene, a member of a phylogenetically conserved gene family, is located on the long arm of chromosome 17 and encodes the TBX2 T-box transcription factor protein, which is a regulator of the transcriptional activity of various genes (i.e., it suppresses the expression of CDKN2A (p19/ARF), inhibits cyclin-dependent kinase p21 Cip1 (CDKN1A), and affects the expression of MYC, RAS, BRCA1, and BRCA2 genes).

EVALUATION OF CHANGES IN THE PROFILE OF THE FACE DURING ORTHODONTIC TREATMENT OF DISTAL OCCLUSION CAUSED BY ANTEPOSITION OF THE UPPER JAW.

Distal occlusion of the dentition is one of the most common anomalies in the Eastern European population. The widespread use of conservative treatment methods creates the need to predict the results of tooth movement. The problem of the influence of orthodontic treatment on the configuration of the soft tissues of the face is of paramount importance for the orthodontist. Purpose of the study: to evaluate changes in the profile of the face during orthodontic treatment of distal occlusion due to anteposition of the upper jaw. 13 patients aged 18-30 years with distal occlusion caused by anteposition of the upper jaw were examined and treated. A standard examination was carried out, including clinical, anthropometric and radiological diagnostic methods. Orthodontic treatment of all patients was carried out, including the removal of individual teeth in the upper jaw. The study shows the features of changing the configuration of the soft tissue profile of the face in the treatment of patients with distal occlusion of the dentition. As a result of orthodontic treatment, the position of the jaws in the sagittal and vertical planes remained practically unchanged. The soft tissue profile of the face was affected by a change in the position of the incisors. A thorough diagnosis of dentoalveolar anomalies, identification of facial configuration features and knowledge of the changes that accompany orthodontic movements will lead not only to the normalization of occlusion and function, but also to the harmonization of the soft tissues of the face.

[Analysis of the quality of orthodontic care for children with partial defects of dentition in the dental organizations of various forms of ownership]. / Analiz kachestva ortodonticheskoi pomoshchi detyam pri chastichnykh defektakh zubnykh ryadov v stomatologicheskikh organizatsiyakh razlichnoi formy sobstvennosti.

THE AIM OF THE STUDY WAS: To conduct a comparative analysis of the quality of medical care for children and adolescents with dentoalveolar anomalies in dental medical organizations of different organizational and legal basis and forms of ownership. MATERIAL AND METHODS: The analysis of orthodontic records of children and adolescents with dentoalveolar anomalies and factors predisposing to their development in 1032 patients aged from 6 months to 18 years was carried out with the use of orthodontic patient records classification of L.S. Persin (2020). The effectiveness of orthodontic care for children and adolescents with various forms of anomalies of the dentition was analyzed. The draft clinical guidelines have been developed depending on the patient model. RESULTS: As shown by the data of orthodontic records of patients, 12% of patients applied during the formation of occlusion of deciduous teeth, 9.2% of children in the early mixed dentition phase, 66.5% of patients in the late mixed dentition phase, and 12.2% of patients first admitted in the permanent dentition phase. As for the analysis of the quality of orthodontic care for children and adolescents with dentoalveolar anomalies in dental organizations of various forms of ownership, the results are controversial. CONCLUSION: Most often in the orthodontic charts data on dentition anomalies were filled, followed by the anomalies of the teeth, anomalies of occlusion in the sagittal direction, anomalies of occlusion in the vertical direction and partial defects of the dentition. Anomalies of soft tissue attachment, anomalies of occlusion of molars on the right and left with palatoocclusion, and anomalies of occlusion of molars on the right and left with linguo-occlusion were less common in orthodontic charts.

CLINICAL AND RADIOGRAPHIC CHANGES FOLLOWING ORTHODONTIC INTRUSION OF OVERERUPTED MAXILLARY MOLARS WITH TWO MINI-IMPLANTS.

Objective - to evaluate clinical and radiographic changes of orthodontic intrusion of upper first molars with two mini-implants, using light intrusion forces, to create the space for prosthetic rehabilitation on the lower jaw. In 20 patients (aged between 26.8 and 45) with secondary deformities in the lateral region in the vertical direction, associated with partial absence of teeth in the lower jaw, and orthodontic preparation for subsequent prosthetics was performed. Each subject was missing 1-2 teeth in the lateral segment. All patients were divided into two groups: with intrusion mechanics with orthodontic implants (20 people) and intrusion with an orthodontic shape memory arch (20 people). The radiographic changes in male and female groups were assessed and compared based on the panoramic radiographs and CBCT data before and after intrusion. In the study 28 molars were fully intruded and their position was normalized with two mini-implants placed palatally and buccally. Mean extrusion time was 7.86±0.42 months (P<0.001), mean intrusion length was 2.97±0.15 mm (P<0.001), and mean change of mesial molar inclination was 2.02±0.44 degrees (P<0,005). The degree of root resorption was evaluated according to CBCT data in Multiplanar reconstruction (MPR); 50% of molars had grade 0 of resorption, 42.85% had grade 1, and 7.15% of molars had grade 2. There was no resorption in the trifurcation area. Intrusion of molars can be successfully accomplished with 2 mini-implants, placed palatally and buccally, with a light traction force (30-50 g) of an elastic chain.

BIOMECHANICS OF CHANGING THE POSITION OF PERMANENT TEETH WITH EARLY LOSS OF THE FIRST TEMPORARY MOLARS.

Premature removal of baby teeth is one of the main causes of deformation of the dentition. The loss of the first temporal molars is most often reported (39.9±4.8%), which leads to displacement of the teeth bordering on the defect, narrowing and shortening of the dental arch, which then leads to retention of premolars, cutting out permanent canines outside the dental arch, pathology of cutting out permanent molars. The aim of the study was to evaluate the biomechanics of permanent teeth migration in patients who prematurely lost their first temporal molars. An anthropometric study of jaw models and orthopantomograms was conducted in 25 patients (age 7-12 years) who had premature loss of the first temporal molars of the upper and lower jaws (age 7-12 years). Complications were evaluated, regularity was revealed and the biomechanics of permanent teeth displacement as a result of the prolonged absence of temporary molars were determined.

The Oral Mucosa Status and the Correlation between the Functional Parameters and the Level of Nitric Oxide Metabolites in Saliva among Patients with GERD.

The study involved 91 patients (48 women and 43 men), aged from 18 to 70 years with GERD. All patients underwent the clinical dental examination according to a single scheme including general clinical manifestations (nausea, single vomiting, belching, heartburn, pain in the epigastrium and around the navel, and poor appetite) and dental manifestations of GERD. The objective assessment of the dental status of the examined patients included the measurement of the functional parameters of the mixed saliva, buffer capacity (BC) of saliva, and the detection of the nitric oxide metabolites (NOx) content in saliva from the right parotid salivary gland ("SRPSG") and in blood serum using the indirect method based on the determination of the stable metabolites: nitrates and nitrites using the Griess reaction. It was established that salivation rate among patients with GERD with the prevailing of ACR and SACR was at the lower limit of normal values (0.32 + 0.19 ml/min), and the salivation rate among patients with the prevailing of SALCR was low (0.10 + 0.04 ml/min). The BC of saliva among patients with the prevailing of ACR and SACR was high (9.07 + 1.23 mmol eq/l and 9.40 + 1.71 mmol eq/l, respectively) and was reduced among patients with the prevailing of SALCR (7.63 + 0.18 mmol eq/l). The NOx level in SRPSG among patients with GERD was increased (especially in Group 3 (20.93 + 11.23 umol/l)). The direct correlation between the indicators of sialometry, the level of the BC of saliva, and the NOx level in SRPSG were established during the study.

Análisis de los Resultados nacionales obtenidos por grupos estatales de investigación del el cáncer ruso. Programa de Cribado de Enfermedades de la Mucosa Oral y Borde Bermellón / Analysis of The Results Obtained by National Research Groups with The Russian State Cancer Program for The Screening of Diseases of The Oral Mucosa and The Vermillion Border

This article analyzes the results obtained by national research groups in the implementation of the Russian State Cancer Program. From 2015 to the first half of 2019, specialists studied the epidemiology and structure of oncological and precancerous diseases of the oral mucosa and the vermillion border in 486,059 persons aged 18-92 years living in Tula, the Tula region, Moscow and Noyabrsk as a result of screening and medical aid appealability. In this period, the productivity of the research group from Tula grew by the factor of 18.92. The results of the research confirm low cancer alertness of practicing dentists. An individual patient registration card has been developed to systematize data and create a diagnostic register for the screening of cancer and precancerous diseases of the oral mucosa and the vermillion border.

[Implementation of the national program of cancer screening of oral precancerous and oncological diseases in the Russian Federation]. / Realizatsiia natsional'noi programmy onkoskrininga predrakovykh i onkologicheskikh zabolevanii slizistoi obolochki rta u naseleniia Rossiiskoi Federatsii.

The aim of the study is to implement the national project created within the framework of the state task of the Ministry of Education and Science of the Russian Federation 'Development of the program of screening of cancer and precancerous diseases of the oral mucosa and red border of the lips'. For its approbation and implementation, national research groups have been created at the bases of the Department of Therapeutic Dentistry of the Moscow State Medical and Dental University, the Tula regional dental clinic, City dental clinic in Noyabrsk City (Yamal-Nenets autonomous district), which in the period from 2015 to the first half of 2018 studied the epidemiology of cancer and precancer of the oral mucosa and the vermilion among 217 806 people aged 18-92 years. Over three and a half years, the effectiveness of the research team increased by 8.45 times. The results of the study confirmed the low oncological alertness of dentists. Educational working program for dentists training 'Screening of diagnostics of precancerous diseases and cancer of the oral mucosa - AFS-D Set' was developed by coordinators of the project and implemented for training of 574 dentists within continuous medical education programs.

HDAC inhibitors induce apoptosis but not cellular senescence in Gadd45α-deficient E1A+Ras cells.

HDAC inhibitors (HDIs) induce irreversible cell cycle arrest and senescence in E1A+Ras expressing cells. Furthermore, HDIs activate Gadd45α/NF-κB signaling pathway to suppress apoptosis thereby promoting the cell survival. Here, to clarify the role of Gadd45α in realization of the antiapoptotic program, we compared wild-type E1A+Ras cells and the cells with knockout of gadd45α gene (Gadd45α-/- cells). As in Gadd45α-expressing E1A+Ras cells, HDIs induce irreversible cell cycle arrest in Gadd45α-/- cells, but the arrested cells do not senesce and eventually die due to activation of the apoptotic death program. These data suggest that the expression of Gadd45α is involved in maintaining the balance of pro- and anti-apoptotic stimuli, while lack or loss of Gadd45 directs the cells to apoptosis after HDIs treatment. Appropriately Gadd45α-deficient cells demonstrate a higher level of pro-apoptotic signals, whereas the anti-apoptotic program is suppressed. The elevated apoptotic background of Gadd45α-/- cells is accompanied by higher levels of Ser15-phosphorylated p53 and p21/Waf1 proteins that additionally commit the cells to HDIs-induced apoptosis. Additionally, loss of Gadd45α protein activates the DDR signaling pathway as demonstrated by nuclear pATM staining, accumulation of γH2AX foci and an increase of single-strand DNA breaks. Thus, in wild-type E1A+Ras cells the p53-dependent expression of Gadd45α is necessary not only for DNA repair and HDI-induced cellular senescence, but also to withstand to apoptosis after DNA damage and stress. Therefore the use of HDIs in combination with agents that block Gadd45α function may have promise for cancer therapy.

[Ontogenetic aspects of changing lysozyme activity under acute somatic pain].

OBJECTIVE: Ouraim was to study influence of acute somatic pain on lysozyme activity of rats of different age: newborn, rats after eye opening, rats at the age of a month, adult and old rats. METHODS: Lysozyme activity was checked before pain irritation and 2, 30, 60, 120, 180min afterwards using Dorofeychuk's method in our modification. Pain effect was modeling by electrical stimulation. RESULTS: activity of lysozyme was 0. 434±0. 01 units in intact newborn rats, It was higher than in adult rats - 0.260 ±0.01 units (p <0.001) and it was unchanged during the experiment. We found low lysozyme activity in rats after eye opening - 0.015±0.003 units and it was stable during the experiment. Rats at the age ofa month had diphasic reaction: lysozyme activity was 0.191±0.01 units in intact rats, it increased up to 0.378±0.01 units (p <0.001) in 2 min after painful irritation and it decreased up to 0.113±0.02 units (p <0.001) in 30 min. Lysozyme activity was 0.260±0.01 units. Single-phase reaction was determined after acute painful irritation: increase of lysozyme activity after acute somatic pain up to 0,450±0,014 units (p <0.001). Lysozyme activity was 0.246±0.02 units in blood plasma of old rats. It decreased up to 0.1701±0.01 units (p <0.01) after painful irritation and it was 0.387±0.01 (p <0.001) in the end of the experiment. CONCLUSION: Response on pain irritation has differences in different groups. The common vector of pain response was the increase of lysozyme activity in rats at the age of a month, adult rats, rats after eye opening and old rats. Reaction of increasing lysozyme activity was strongly detected in adult rats. The results demonstrate preventive lasozyme resistance to potential tissue damage or contamination.

[Investigation of actual nutrition and some factors of physical status in rugby players].

Physical status and nutrition and energy value of factual diets of 18 rugby players (15-30 years old) assessed during current medical observation were analyzed. Anthropometric data (height, body mass--BM, waist circumference/ hip circumference index, body mass index--BMI), body composition data and resting metabolic rate by bioimpedance method (analyzer ABC-01 "Medass") were determined. These indices were found to be normal except more high level of BMI due to high levels of lean and skeletal muscle mass, but not a result of obesity. Estimation of factual nutrition based on 1-day feeding (nutrition-screening questionnaire method) has demonstrate that it was not optimal both for energy and nutrition value for this group of physical activity. Energy value ranged from 1889 kcal to 3175 kcal (22.5-35.1 kcal/kg BM/day) with lower carbohydrate intake (46.9%) and higher fat intake (35.8%) were found. Nutrition value ranges: protein--67-144 g (0.71-1.38 kcal/kg BM/day), fat--75-140 g (0.88-1.51 kcal/kg BM/day), carbohydrate--173-420 g (2.17-4.66 kcal/kg BM/day) were observed. The findings suggest the need to pay more attention to in-depth study of dietary intake of athletes to maintain health and to create optimal conditions for a professional sports activities.

[Attraktive and aversive for intact individuals volatile excretion of male mice induced a thymus dependent antigen].

Immunization of male mice of the CBA and C57BL/6J strains with sheep red blood cells (SRBC) induce excretion of urinary volatile components (VC), modifying the behavioral reactions of intact males CBA strain. In early times after injection of 1 x 10(8) SRBC per mouse results in secretion of attractive VC, whereas injection of 1 x 10(9) cells per mice induces secretion of aversive VC. Regular for normal and the observed also in the early stages of attraction of intact males CBA to VC immunized syngeneic males CBA (relatively VC immunized with allogeneic C57BL/6) was lost from 3 to 14th day after the introduction of SRBC in the dose of 1 x 10(8) cells/mice and with the 9th on the 14th day after the introduction of SRBC in the dose of 1 x 10(9). The biological significance of the antigen induced chemosignaling in animals is discussed.

[Cerebral venous disorders in young patients with neurotic depression].

Authors examined 143 patients with neurotic depression using ultrasonic Doppler method. Disorders of the cerebral venous hemodynamics associated with clinical symptoms of the disease were found. It is recommended to use ultrasonic Doppler method for the diagnosis and objectification of functional changes in the cerebral blood circulation and for increasing treatment efficacy.

[Medical-biological approach to development of feeding ration for sportswomen--members of Russia weight lifting team].

Physical status of 12 sportswomen - member of Russia weight lifting team during training period was analiysed. Anthropometric, bioimpedance methods with analyzer ABC-01 "Medass" in observation [body weight Index (index Ketle-2), waist circle/hip circle index] and body compositions were used (adipose, bone and muscle tissues masse). Data obtained when bioimpedance method was used indicated: normal body weight and relative adipose mass to body weight - in 92%, surplus - in 8% of cases; body weight Index and normal level of adipose mass - in 75%, surplus - in 25%; active cellular mass and bone mass and general body liquid were found to be normal. 14-day feeding ration for sportswomen were analysed and 3 times per day food intakes was found to be not optimal. Data obtained let to recommend set of daily food products to compose optimal ration for present sportswomen group when energetic value of 4500 kKal and high nutritional value would be provided.

[Actual nutrition and physical state of athletes of the national sleigh team of Russia].

An assessment of actual nutrition and physical fitness of athletes of the Russian national sleigh team are presented, and the need to develop for them the individual well-balanced diet that will reimburse the amount of consumed energy and nutrients and help athletes to obtain high results.

Vasopressinergic neurons of the supraoptic nucleus in perinatal rats: reaction to osmotic stimulation and its regulation.

Osmotic stimulation (OS) of vasopressin (VP) neurons of the supraoptic nucleus (SON) promotes VP secretion and tyrosine hydroxylase (TH) expression in adult mammals. VP secretion is under a noradrenaline control, whereas the regulation of TH expression remains uncertain. This study was aimed to determine at what period of ontogenesis: (1) VP neurons begin to react to OS by modifying simultaneously VP and TH gene expression and synthesis, (2) the noradrenergic control of VP neurons is established. Rats on the 21st embryonic day (E), third postnatal day (P), P13 were salt loaded or salt loaded and treated with an antagonist (prazosin) or agonist (phenylephrine) of α1-adrenoreceptors. According to our immunocytochemical and in situ hybridization data, OS resulted in an increased amount of VP mRNA in each age group and of VP on E21 and P3. TH gene and synthesis was initially expressed under OS on P3. The number of TH-expressing neurons diminished by threefold in salt loaded rats from P3 to P13. OS combined with prazosin administration resulted in an increased level of VP mRNA on P3 and P13, but not on E21 suggesting the onset of the noradrenaline inhibitory control after birth. OS together with prazosin treatment stimulated TH expression on P3 and P13, whereas phenylephrine provided an opposite effect. Thus, VP neurons begin to react to OS by an increased VP synthesis at the end of fetal life and by the onset of TH expression shortly after birth; the expression of both substances appears to be under the inhibitory control of noradrenaline.