[Modern concept of treatment of adolescents with Class III malocclusion]. / Sovremennaya kontseptsiya lecheniya podrostkov s mezial'noi okklyuziei.

OBJECTIVE: Aim of the work is to increase the effectiveness of complex treatment in patients with mesial occlusion during active skeletal growth. mproving the effectiveness of complex treatment of patients with mesial occlusion during active skeletal growth. MATERIAL AND METHODS: Clinical and radiological examination and comprehensive treatment of 30 patients with skeletal anomalies according to sagittale were carried out (average age 15 years). Orthodontic treatment of patients was performed using the Damon self-ligating bracket system («Ormco¼, USA), H4 («OC Orthodontics¼ USA) with a sequential change of arches. According to the indications, orthodontic mini screws, removable, non-removable dilators, a facial mask, occlusal pads for disconnecting the bite, in the retention period, non-removable retainers in the anterior part of the dentition, a removable retention device at night «Corrector¼, or removable plate devices were used. RESULTS: Rapid palatal expansion was performed according to the traditional method, based on the stages of formation of the median palatine suture (the first algorithm is the stage of formation of the palatine suture A-B). In patients with narrowing of the HF with the stage of formation of the median palatine suture C, the beginning of stage D, the use of the proposed expansion scheme with the use of piezocorticotomy to eliminate the buttresses of the upper jaw, the use of laser corticotomy and the protocol of activation and deactivation of the screw to relax the bone and achieve skeletal expansion of the upper jaw was effective. The change in the dental alveolar height, normalization of the incisor overlap height improved harmony in the gnatic part of the facial skull of patients. In the process of orthodontic treatment, the inclination of the occlusal plane was normalized, the profile of the face improved. Changes in the soft tissues of the profile consisted in an increase in the thickness of the upper lip by 2.27±0.48 mm (p<0.05) and its length by 1.45±0.39 mm (p<0.05), the total length of the lower lip and chin by 3.16±0.45 mm (p<0.05). The position of the lips relative to the aesthetic plane has changed most significantly. An algorithm was developed for the treatment of patients with dental anomalies in the sagittal plane, with a narrowing of the upper jaw during the bite of permanent teeth 12-17 years. CONCLUSION: The method of complex treatment is designed to increase the effectiveness of orthodontic treatment of patients with skeletal abnormalities during active skeletal growth and is aimed at changing skeletal growth, as well as to prevent the development of skeletal malocclusion during permanent bite, which is necessary to prevent the development of more pronounced skeletal deformity at the stage of complete skeletal maturation.

[The use of fixed expanders with orthodontic miniscrews support in children with mesial occlusion]. / Ispol'zovanie nes"emnykh rasshiritelei s vnutrikostnoi oporoi u detei s mezial'noi okklyuziei.

OBJECTIVE: Prevention of the development of pronounced skeletal abnormalities in patients with mesial occlusion. MATERIALS AND METHODS: Biometric analysis of control and diagnostic models of dentition was performed in 60 patients with dental anomalies before and after treatment in 3 mutually perpendicular planes to identify violations in the formation of dental arches by sagittal and transversal dimensions, and alveolar processes - by vertical dimensions (methods of A. Pont, G. Korkhaus). Measurements of 23 parameters of TRG and sections of CBCT were carried out using the modified Nad-Ars technique with analysis of skeletal parameters before and after treatment. Treatment was carried out using dilators for the upper jaw in combination with a facial mask and further dynamic observation using active retention devices. RESULTS: The results of treatment showed an increase in the length of the anterior segment of the upper dental arch by 2.8±0.55 mm (p<0.05 mm); expansion in the area of temporary molars by 2.85±0.65 mm (p<0.05); in the area of permanent molars by 2.75±0.55 mm (p<0.05); in the area of the apical basis of HF by 3.82±0.45 mm (p<0.05). The length of the lower dental arch in the anterior segment has not changed. Analysis of TRG parameters showed a significant increase in the values of

[Visual deficit as a marker of cognitive impairment.]

Glaucoma and cataract continue to be the leading causes of visual deficits, especially in older age groups, but the association of visual deficits with cognitive impairments has not been sufficiently studied. The aim of this study is to study visual impairment as a marker of cognitive impairment in patients with cataracts and glaucoma. The study included 326 elderly patients with cataracts and 318 elderly patients with primary open-angle glaucoma. The degree of cognitive impairment was determined using the Mini-Mental State Examination (MMSE) scale. Visual deficit was assessed by visual acuity without correction and maximum corrected visual acuity, and the severity of visual deficit was assessed by the scale we proposed. It was found that with low visual deficit (visual acuity without correction 0,51-0,60 and over 0,61) in the examined patients, the average score on the MMSE scale varied from 28,4±0,6 to 28,7±0,8 points (p>0,05), corresponding to subjective cognitive disorders. However, with a pronounced visual deficit (visual acuity without correction to 0,20 and 0,21-0,30), the average score is 13,9±0,3 and 16,5±0,4 (p<0,001), which indicates moderate dementia. Practically similar patterns about the association of cognitive impairments with the magnitude of visual deficit were also obtained when assessing visual deficit by maximum corrected visual acuity. The associativity of cognitive impairment with visual defect in patients with cataract and glaucoma was confirmed by the correlation method, according to which the correlation coefficient with visual acuity without correction is r=+0,428 (p<0,05), and with maximum corrected visual acuity - r=+0,385 (p<0,05). The results of the study allow us to consider visual deficit as a marker of cognitive impairment.

[Effect of Usnic Acid-Derived Tyrosyl-DNA Phosphodiesterase 1 Inhibitor Used as Monotherapy or in Combination with Olaparib on Transplanted Tumors In Vivo].

Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a DNA repair enzyme that removes various adducts from the 3' end of DNA. Such adducts are formed by enzymes that introduce single-strand breaks in DNA during catalysis (for example, topoisomerase 1) and a number of anticancer drugs with different mechanisms of action. Poly(ADP-ribose) polymerase 1 (PARP1) is an enzyme that catalyzes posttranslational modification (PARylation) of various targets and thus controls many cell processes, including DNA repair. Tdp1 is a PARP1 target, and its PARylation attracts Tdp1 to the site of DNA damage. Olaparib is a PARP1 inhibitor used in clinical practice to treat homologous recombination-deficient tumors. Olaparib inhibits PARylation and, therefore, DNA repair. The Tdp1 inhibitor OL7-43 was used in combination with olaparib to increase the antitumor effect of the latter. Olaparib cytotoxicity was found to increase in the presence of OL7-43 in vitro. OL7-43 did not exert a sensitizing effect, but showed its own antitumor and antimetastatic effects in Lewis and Krebs-2 carcinoma models.

Functioning of P-Glycoprotein during Pregnancy in Rabbits.

The level P-glycoprotein (Pgp) in organs of pregnant rabbits and its content and activity in the placental barrier at different stages of pregnancy were studied. An increase in Pgp content in the jejunum on days 7, 14, 21, and 28 of pregnancy in comparison with this parameter non-pregnant females was revealed by ELISA; in the liver, Pgp content was higher on day 7 and tended to increase on day 14; in the kidney and cerebral cortex, Pgp content was higher on day 28 of pregnancy in parallel with an increase in serum progesterone concentration. We also observed a decrease in Pgp content in the placenta on days 21 and 28 of pregnancy in comparison with day 14 and a decrease in Pgp activity in the placental barrier, which was confirmed by enhanced penetration of fexofenadine (Pgp substrate) through the barrier.

[Myocardial revascularization in chronic coronary artery disease. State of art].

The review addresses debatable issues of myocardial revascularization in chronic forms of ischemic heart disease, shows major differences between percutaneous coronary intervention and coronary artery bypass grafting in terms of long-term prognosis, and the dependence of the results on the clinical profile of the disease. The review of current publications demonstrates advantages of open surgery in long-term survival and prevention of adverse outcomes in target groups of patients.

[The structure of pathogenic germline variants in colorectal cancer in Moscow patients]. / Struktura patogennykh germinal'nykh variantov pri kolorektal'nom rake v vyborke patsientov Moskvy.

OBJECTIVE: Describe the structure of pathogenic germline variants and clinical and anatomical features in colorectal cancer patients in Moscow. MATERIAL AND METHODS: The whole genome sequencing results of patients with suspected hereditary cancer syndrome were evaluated. All identified genetic variants were validated using Sanger sequencing. RESULTS: The study included 238 patients with colorectal cancer, 41/238 (17.2%) patients have pathogenic germline variants associated with hereditary cancer syndromes or increased cancer risk. Lynch syndrome accounts for 8% of all colorectal cancer cases (19/238), and familial adenomatous polyposis - 1.7% (4/238). 5 new genetic variants were described for the first time in a Russian colorectal cancer patients: MLH1 c.1921dup (p.Leu641fs), APC c.2929C>T (p.Gln977Ter), PMS2 c.327del (p.Ala110LeufsTer2), MSH2 c.1857dup (p. Val620CysfsTer24), ATM c.895G>T (p.Glu299Ter). In 197 of 238 patients, no significant variants were identified or variants with an uncertain clinical underlying cause were identified. CONCLUSION: According to the results of the study, an earlier manifestation of a malignant neoplasm and a more frequent occurrence of high-grade carcinomas in the presence of pathogenic germline mutations were noted compared to the group of patients without clinically significant varianrs, while in the group with identified mutations, the frequency of regional and distant metastasis was not increased.

A COMPARATIVE REVIEW OF THE USE OF DANIO RERIO (ZEBRAFISH) AS A MODEL OBJECT IN PRECLINICAL STUDIES.

Danio rerio (Zebrafish) as a model object in preclinical studies have been widely used in recent years. This is facilitated by their morphological, physiological, biochemical, genetic, and embryological characteristics, as well as economic benefits and small-time costs of their breeding. The aim is to summarize the available data on the use of Danio rerio (Zebrafish) in preclinical studies. In this work a review of domestic and foreign articles on the use of Danio rerio in toxicological, pharmacological, embryological, and other research areas was carried out. Danio rerio (Zebrafish) can be used in many areas of preclinical studies of drugs. Their application in modeling novelty stress and experimental depression is especially interesting. Danio rerio are a versatile model object that allows cost-effective studies of various pharmacological drugs before they are tested on other models, particularly mammals.

[The use of intraosseous appliances considering the anatomical features of the hard palate]. / Ispol'zovanie vnutrikostnykh apparatov s uchetom anatomicheskikh osobennostei tverdogo neba.

OBJECTIVE: The aim of the study. To improve the effectiveness of patients' treatment with narrow upper jaw by improving the stability of intraosseous devices. MATERIALS AND METHODS: 40 patients with the narrow upper jaw, from 12 to 40 years old, were treated. 50 self-drilling orthodontic miniscrews of each manufacturer, i.e. «BioRay¼, Taiwan, «Turbo¼, Russia, a total of 100 items, were inserted into a palate. RESULTS: The greatest thickness of the cortical bone relative to the sagittal plane was observed at a distance of 6 mm from the incisor canal, which averages 6.32 mm. Relative to the transversal plane, the greatest bone thickness was observed 3 mm laterally from the median palatine suture and averages 7.62 mm. The smallest thickness of the mucous membrane of the hard palate is noted 6 mm distal from the incisor canal and 3 mm laterally from the palatine suture is on average 4.56 mm. CONCLUSION: The protocol for determining the individual position of the miniscrew for each patient, taking into account all his anatomical features, is a necessary tool for clinical success.

[The use of distal occlusion correctors during treatment on an individual lingual bracket system in adult patients]. / Primenenie korrektorov distal'noi okklyuzii pri lechenii s ispol'zovaniem individual'noi lingval'noi breket-sistemy u vzroslykh patsientov.

A case of treatment of a 35-year-old patient with a retroposition of the lower jaw, distal occlusion of the posterior teeth, deep incisal overlap, narrowing of the deformity of the dentoalveolar arches, protrusion of the lower incisors, crowded position of the teeth, mismatch between the incisor lines, absence due to extraction of tooth 3.6, with impacted dystopic tooth 3.8 is presented. Fixed individual orthodontic appliances of the WIN («DW Lingual Systems GmbH¼ Germany) were used. It was found that the use of the Herbst apparatus in combination with the WIN lingual bracket system in adult patients helps to achieve optimal functional and aesthetic results. The use of a distal bite correction device is an additional support for the mesialization of the molars of the lower jaw.

[Orthodontic treatment as a stage of rational dental prosthetics]. / Ortodonticheskoe lechenie kak etap podgotovki k ratsional'nomu zubnomu protezirovaniyu.

OBJECTIVE: To improving the effectiveness of complex treatment of adult patients with the absence of individual teeth. MATERIAL AND METHODS: Clinical and radiological examination and comprehensive treatment of 37 patients with dental anomalies and the absence of individual teeth were carried out, 24 of them were women (average age 35 years), 13 men (average age 38 years). The patients were divided into two groups: the 1st group - 22 patients with distal occlusion; the 2nd group - 15 patients with mesial occlusion. RESULTS: The results of the developed algorithms for the complex treatment of patients with dental anomalies and the absence of individual teeth during the bite of permanent teeth are presented on a clinical example. The complex treatment included orthodontic treatment using a bracket system, functional fixed telescopic appliance, orthodontic mini screws for bone support and further rational prosthetics. After conducting a clinical and radiological examination and analyzing the data obtained, an individual patient treatment plan was developed, which included orthodontic and orthopedic stages. Orthodontic treatment made it possible to normalize the position of the teeth, the shape of the dental alveolar arches, occlusal planes, improve the bite, which made it possible to prepare the patient for rational prosthetics. The chosen treatment plan was optimal and correct for this patient: all the tasks were solved with changes not only at the dental alveolar level, a stable dental ratio was achieved and not only dental, but also facial parameters were improved. CONCLUSION: Orthodontic preparation of adult patients before orthopedic treatment significantly improves the quality of orthopedic treatment and allows to achieve the most stable functional and aesthetic results.

[The common morbidity of children population in conditions of propagation of new coronavirus infection COVID-19 in 2017-2019].

The health of children population is one of the indicators of the social and epidemiological well-being of society. The purpose of the study was to study main trends of propagation of various classes of diseases in children population in conditions of propagation of the new coronavirus infection. The data of Rosstat for the Udmurt Republic covering the pre-COVID period (2017-2019) and the period of COVID-19 propagation (2020-2021). The analytical method, descriptive statistics technique, the calculation of intensive and extensive indicators were applied. It is established that in 2017-2019, general morbidity of the children population aged 0-7 years decreased by 8.7%, while in conditions of higher propagation of COVID-19 (2020-2021) there was an increase by 11.0 %. In the children population aged 0-14 years, general morbidity decreased by 10%, and hereinafter it increased on 12.1%. At that, in the pre-COVID period in children population aged from 0 to 17 years, morbidity rate decreased for 14 classes of diseases, for 15 classes in children population aged from 0 to 14 years. During the period of higher propagation of COVID-19 morbidity rate for only 5 classes of diseases decreased in both age groups of children population.

[The functioning of call-center in conditions of COVID-19 pandemic].

In conditions of persisting high morbidity of COVID-19, issues related to prompt and timely medical care of population remains actual ones. The purpose of the study to analyze activities of the call-center of the Ministry of Health Care of the Udmurt Republic related to organization of medical care of COVID-19 patients in the Udmurt Republic. MATERIALS AND METHODS: The statistical (descriptive statistics) and descriptive methods were applied. The indicators of functioning of the call-center of the Ministry of Health Care of the Udmurt Republic in 2020-2022 were analyzed. The psychological characteristics of telephone counseling were studied. The satisfaction of medical organizations and citizens with services of call-center operators was assessed. THE RESULTS: The main principles of telephone counseling are confidentiality, maintenance of framework of working conversation, respect to personality of addressee. In 2020 the call center phone line received 34160 calls, in 2021 - 128339 calls, in 2022 - 65618 calls. In 25 months of operation the call-center operators received 228,117 calls from citizens related to issues of new coronavirus infection. The number of patient calls to the hot-line increases significantly when incidence of new coronavirus infection increases (r=0.885; p<0.05). Most frequently (25.1%) citizens contacted the call-center of the Ministry of Health Care of the Udmurt Republic due to inability to reach the polyclinic and on issues related to primary before-doctor care. The second place in terms of frequency (18.5%) took issues related to PCR-test results. The third place (14.1%) took issues related to duration of quarantine for patients and persons residing with them, possibility for children to attend preschool and educational institutions. The number of outgoing calling in 2020 was 16146, in 2021 - 89269 and in 2022 9936 calls. During 25 months of operation, call-center operators made 204,782 calls to citizens to monitor their health status and invite them to vaccinations and health screenings. More than half of outgoing calls (58.3%) were related to audio-monitoring of patients undergoing outpatient treatment with making-up of electronic protocol. CONCLUSIONS: During the period of increasing of COVID-19 morbidity, the call-center becomes an independent structural unit of organizing patient care. The medical organizations and citizens are satisfied with functioning of the call-center of the Ministry of Health Care of the Udmurt Republic organized in order of improving the organization of medical care of patients with COVID-19.

Experimental Study of Antitumor Activity of Pefagtal Addressed to αvß3 Integrins.

We studied the effect of a new targeted drug Pefagtal that represents a conjugate in which the MS2 phage filled with a substance toxic to cells (thallium salts) is covalently linked to peptides containing the RGD motif. The antitumor and pronounced antimetastatic effects of Pefagtal were demonstrated on transplanted mouse tumors differing in histological type and status of metastasis: Krebs-2 ascites adenocarcinoma of the mammary gland, Lewis lung adenocarcinoma, hepatoma-29, and lung adenocarcinoma. It is assumed that the RGD motif mediates primary binding of the construct to αvß3 and αvß5 integrins that are predominantly overexpressed in the endothelial cells of tumor blood vessels and in tumor and metastatic cells.

Effects of Heavy Metals on the Metabolome of Pinus sylvestris (Pinaceae).

The effects of Cu, Ni, and Cd on the Pinus sylvestris metabolome was studied in experimental conditions by gas chromatography-mass spectrometry (GC-MS). Structural changes in plant metabolite network became detectable on day 6 of exposure to the metals, 3-6 days earlier than visual signs of toxicity developed. Differences at the metabolome level arose earlier in a control group of plants, and specific effects of particular metals on the plant metabolome became distinct on day 9. Both nature and concentration of a metal equally contributed to the plant metabolome clustering. Plant responses (changes in concentrations of individual metabolites) to metal exposure substantially differed depending on the metal concentration (1 or 5 mM) and nature. The effects of Cd and Cu were generally similar, while the effect of Ni was often different. Dynamic changes visualized in plant metabolite matrix reflected the changes in its correlation structure, rather than depending on the set of particular compounds.

[Identification and chromatemass- spectrometry quantification of toxic chemicals (N-nitrosamines, phthalates) in baby foods].

Currently, assessing exposure to toxic chemicals detected in foodstuffs is a vital issue, especially regarding foods for babies and toddlers. The research goal was to identify and quantify toxic chemicals (N-nitrosamines, phthalates) in baby foods. Material and methods. Our research objects were 21 samples of canned meat and vegetable purees; 30 samples of juices. All samples were bought in retail outlets. We applied solid phase extraction to prepare the samples for the chromatographic analysis. Chemicals were identified in samples by a hybrid technique, gas chromatography and quadrupole mass spectrometry (GC-MS). The components were classified by comparing the mass spectra we obtained with spectra of specific chemicals and data from the following libraries: NIST 08.L, WILEY275.L and PMW_TOX2.L, AMDIS, USEPA (US Environmental Protection Agency) database with identification numbers of environmental pollutants; libraries containing mass spectra of narcotics, drugs, toxic pollutants and pesticides. Quantitative determination of phthalates in juice products by HPLC/MS was performed. Results. We identified three toxic chemicals in the analyzed canned meat and vegetable purees for babies. They belonged to the 1-3 hazard category and to different classes of organic compounds. Specifically, we identified nitrogen-containing chemicals (N-nitrosamines within a range of concentrations being 0.00077-0.0015 mg/kg with a 73% probability that a mass spectrum would match one taken from a library) in 52.9% of samples. These chemicals are not allowed in canned meat purees for babies by the Technical Regulations TR CU 021/2011 (<0.001 mg/kg). Next, we identified dibutyl phthalate and diethyl phthalate in 30.0% of samples; contents of these organic compounds in canned meat purees for babies are not stipulated by the TR CU 021/2011. We also identified an aromatic compound, namely furfural in 21.7% of samples, and a food additive, 2-butenoic acid (E570) in 5.3% of samples; their contents are regulated by the Technical Regulations TR CU 029/2012. Three toxic chemicals were identified in the analyzed juice samples. First, N-nitrosodiethylamine and N-nitrosodimethylamine were identified in 56.7% of samples (with a 73% probability that a mass spectrum would match one taken from a library, over a concentration range of 0.00045- 0.00077 mg/kg). Second, we identified phthalates (dibutyl phthalate, diethyl phthalate, and diisobutyl phthalate) in 30% of samples (in the concentration range from 0.4 to 59.26 mg/l). The contents of these compounds in juices for babies are not regulated by the TR CU 021/2011. We also detected furfural in 56.7% of samples (with a value of the coefficient of coincidence with library data of 90%), the use of which is regulated in TR CU 029/2012. Conclusion. We have developed and experimentally substantiated an algorithm of an analytical study with its focus on preparing food samples for further identification of chemicals in them. The algorithm involves using a complex technique that combines distillation, solid phase extraction, gas chromatography and mass spectrometry. This technique provides an opportunity to identify a component structure of complex chemical mixtures in food samples with high probability and reliability. It also provides solid evidence that organic compounds occur in food samples based on comparing analytical mass spectra with those taken from mass spectral libraries.

[Quantitative objective and subjective assessment of the quality of treatment of patients with distal occlusion]. / Kolichestvennaya ob"ektivnaya i sub"ektivnaya otsenka kachestva lecheniya patsientov s distal'noi okklyuziei zubnykh ryadov.

OBJECTIVE: The aim of the study is to evaluation of the quality of orthodontic treatment by comparing the severity of signs of distal occlusion before the start of orthodontic treatment and after its completion. MATERIAL AND METHODS: Quantitative assessment of the severity of distal occlusion in 83 patients aged 17 to 30 years before and after orthodontic treatment. Depending on the chosen treatment algorithms, the patients were divided into 3 groups. The first group - 34 people - treatment included the use of a functional non-removable orthodontic device (FNT). The second group - 21 people - the treatment was accompanied by the removal of individual teeth of the upper jaw and the retraction of a group of front teeth of the upper jaw. Patients of the 3rd group - 28 people - underwent combined orthodonto-surgical treatment. The severity of distal occlusion was assessed using 3D cephalometric analysis data. To obtain a subjective assessment of the quality of orthodontic treatment, patients were asked to fill out questionnaires before and after orthodontic treatment. RESULTS: The severity of distal occlusion decreased as much as possible as a result of treatment of the first group in 23.07% of patients and the third group (16.63%), which is interpreted by the formulation «significant improvement¼ of the dental anomaly. Patients of the first and third groups had a high degree of satisfaction with the result of treatment, according to the quantitative assessment of the questionnaire. The severity of distal occlusion in the second group was reduced to a lesser extent (55.5%), compared with the first and third groups, which is interpreted as «moderately improved¼. Patients noted an average degree of satisfaction with the result of treatment, as the implemented treatment plan did not meet their expectations in the aesthetic aspect. CONCLUSION: The use of FNT for the extension and normalization of the position of the lower jaw is justified in the case of refusal of patients from combined orthodonto-surgical treatment, as it allows to fully solve the functional, aesthetic and psychological problems of patients, which contributes to improving their quality of life.

[Algorithms for orthodontic treatment of patients with maxillary constriction based on the stages of formation of the palatal suture]. / Algoritmy ortodonticheskogo lecheniya patsientov s suzheniem verkhnei chelyusti na osnovanii stadii formirovaniya sredinnogo nebnogo shva.

THE AIM OF THE STUDY: Improving the effectiveness of complex orthodontic treatment of patients with constriction and deformation of the upper jaw during the period of replacement and permanent bite based on the analysis of cone-beam computed tomography (CBCT) data. MATERIALS AND METHODS: The results of complex treatment of 70 patients with constriction and deformation of the upper jaw during the period of temporary and permanent bite are presented. The patients were divided into groups according to the stage of formation of the midpalatal suture: 1st group - 40 patients with stage «A¼ and «B¼ (average age 11.5 years); 2nd group - 15 patients with stage «C¼ (average age 20.5 years); 3rd group - 15 patients with stage «D¼ and «E¼ (average age 24.5 years). Orthodontic treatment was carried out using palatine expanders with a dental and intraosseous type of fixation. The complex treatment consisted of: orthodontic treatment using a bracket system, transgingival laser corticotomy, piezocorticotomy, surgically assisted rapid palatal expansion, orthodontic appliances for the expansion of the upper jaw. After conducting a clinical X-ray examination of all patients and analyzing the data obtained, we developed algorithms for therapeutic measures. RESULTS: As a result of the diagnosis and treatment planning, the expansion of the upper jaw was achieved both at the dental alveolar and skeletal levels. Detailed algorithms of complex treatment were developed based on the analysis of CBCT data, the stage of formation of the midpalatal suture individually for each patient. CONCLUSION: It was found that the analysis of CBCT data makes it possible to choose the optimal treatment method for patients with skeletal deformities of the dentition complex, thereby increasing the effectiveness of orthodontic treatment.

[Antitumor Activity of the Combination of Topotecan and Tyrosyl-DNA-Phosphodiesterase 1 Inhibitor on Model Krebs-2 Mouse Ascite Carcinoma].

Topotecan is a cytostatic drug from the camptothecin group, it acts by inhibiting topoisomerase 1 (TOP1). Tyrosyl-DNA phosphodiesterase 1 (TDP1) is capable of interfering with the action of TOP1 inhibitors, reducing their therapeutic efficacy. Suppression of TDP1 activity may enhance the effects of topotecan. In this work, we investigated the effect of the antitumor drug topotecan alone and in combination with a TDP1 inhibitor, a hydrazinothiazole derivative of usnic acid, on Krebs-2 mouse ascites tumors. We have previously shown that this derivative efficiently inhibits TDP1. In the present work, we show that both topotecan and the TDP1 inhibitor have an antitumor effect when evaluated separately. The combination of topotecan and the TDP1 inhibitor additively reduces both the weight of the ascites tumor and the number of cells in ascites. In mice, the TDP1 inhibitor alone or in combination with topotecan eliminated the tumor cells. After the combined intraperitoneal administration of these two compounds, we observed cells in which lipid droplets occupied almost the entire cytoplasm and the accumulation of cell detritus, which was absent in the samples collected from mice treated with each compound separately.

[Comparative Analysis of MPTP Neurotoxicity in Mice with a Constitutive Knockout of the α-Synuclein Gene].

Aggregated forms of α-synuclein are core components of pathohistological inclusions known as Lewy bodies in substantia nigra (SN) neurons of patients with Parkinson's disease (PD). The role of α-synuclein in selective loss of SN dopaminergic neurons (DNs) in PD is studied in mice knocked out in the α-synuclein gene. The new mouse strain delta flox KO with a constitutive knockout of the α-synuclein gene models the end point of in vivo deletion of the α-synuclein gene in mice with a conditional knockout and has no foreign sequence in the modified genomic locus, thus differing from all other α-synuclein knockout mouse strains. The effect of the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), which is used to model PD, was compared between delta flox KO mice and mice of the well-known α-synuclein knockout strain AbKO. Subchronic MPTP administration, which models early PD, was found to reduce the dopamine content and to change the ratio of dopamine metabolites in the striatum to the same levels in delta flox KO, АbKO, and wild-type mice. Overt locomotor defects were not observed after MPTP treatment, but gait testing in a CatWalk XT (Noldus) system revealed identical gait deviations in mice of the two strains and control wild-type mice. Based on the findings, a similar mechanism of neurotoxic damage to DNs was assumed for delta flox KO and AbKO mice.