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Currently, the treatment of pituitary adenomas is inextricably linked with transsphenoidal neurosurgical intervention. Modern technologies used in surgery for this pituitary pathology, such as endoscopy using angled optics, as well as the use of specialized instruments, sealing and hemostatic materials, increase the effectiveness of surgical treatment of pituitary adenomas and reduce the incidence of intraand postoperative complications. The development of radiation methods of diagnostics, such as MRI, makes it possible to more accurately identify the formation of the pituitary gland, assess its size, direction of growth, and the degree of invasion of surrounding tissues. The authors of the article described in detail the modern technique of transsphenoidal removal of pituitary adenoma using an endoscope. Each stage of the operation is described step by step, taking into account various anatomical features and illustrated. This article discusses the MRI characteristics of pituitary adenomas: size of the tumor, the direction of its growth, the degree of invasion of the cavernous sinuses, the compression effect on the structures of the chiasmal-sellar region. The use of treatment methods, knowledge of the features of MRI diagnostics described in this article greatly increase the effectiveness of the treatment of patients with pituitary adenomas and reduce the risk of complications after neurosurgical intervention in such patients.

Background. The indication for radiotherapy in oncological practice are metastases of differentiated thyroid cancer after thyroidectomy, the presence of distant metastases, or stage N1b, or negative dynamics of blood thyroglobulin levels after thyroidectomy for thyroid cancer. The mechanism of action of radiotherapy is based on provoking double-stranded DNA breaks. It is important to study the role of polymorphisms of NFKB1, ATM, ATG16L2 and ATG10 genes, products of which are involved in the processes of DNA damage response pathway and autophagy, in the formation of resistance to radioiodine therapy of thyroid cancer patients. Aim. To examine the association between NFKB1, ATM, ATG16L2 and ATG10 polymorphisms and resistance to radioiodine therapy in thyroid cancer patients. Materials and methods. The study included 181 patients (37 men, 144 women; mean age 53.515.7 years) with histologically confirmed thyroid cancer and a history of thyroidectomy who received radioiodine therapy. Carriage of single-nucleotide polymorphisms (rs230493) NFKB1, (rs11212570) ATM, (rs10898880) ATG16L2 and (rs10514231, rs1864183, rs4703533) ATG10 was determined by real-time PCR using TaqMan kits. Results. Among 181 patients, resistance to radioiodine therapy was observed in 11 (6.1%) cases. No significant associations between the individual polymorphisms and resistance to radioiodine therapy were obtained, p0.05. Haplotype analysis showed that carriage of the C-C ATG10 rs10514231-rs1864183 haplotype was associated with an increased risk of developing resistance to radioiodine therapy, p=0.04. Conclusion. Further studies on large samples of radioiodine therapy-resistant patients using whole-genome sequencing methods are required to specify the role of genetic factors in the response to 131I therapy.

Acromegaly is a severe neuroendocrine disease caused by chronic excessive production of somatotropic hormone (STH), characterized by specific changes in appearance, metabolic disorders. In 95% of cases, the cause of pathology is STH-producing pituitary adenomas. The priority method of treatment for acromegaly is transnasal transsphenoidal adenomectomy. If it is impossible to carry out neurosurgical intervention, in order to prevent the progression of the disease and the development of complications, patients are recommended drug therapy with long-acting somatostatin analogues, and if their effectiveness is low, additional radiation therapy may be applied to the neoplasm area. The usage of a relatively new group of drugs, antagonists of STH receptors, namely Pegvisomant for the purpose of drug treatment of acromegaly demonstrates high efficacy even in cases of aggressive forms resistant to other types of treatment. In this article we present two clinical cases of hereditary acromegaly, when the initiation of Pegvisomant therapy led to the achievement of clinical and laboratory remission of acromegaly in patients with an aggressive form of the disease, accompanied by continued growth of residual neoplasm tissue and preservation of its secreting ability even after surgical interventions, radiatiotherapy and long-term drug treatment with somatostatin analogues. The results of the above clinical cases confirm the success of mono- or combined (in cases with continued growth of the neoplasm) therapy with a growth hormone receptor antagonist, Pegvisomant, especially in the case of aggressive acromegaly.

Background. Gastrointestinal (GI) tract cancer includes a broad spectrum of tumors with generally high prevalence and poor prognosis. Over the past decade sarcopenia (skeletal muscle depletion), myosteatosis, sarcopenic obesity were all shown to have a negative prognostic impact in patients with various malignancies. However, the role of myosteatosis in patients with GI tumors remains controversial. Aim. To summarize recent literature regarding the impact of myosteatosis on the surgical treatment of patients with GI malignancies. Materials and methods. PubMed, Cochrane Library and ClinicalTrials.gov databases were searched for relevant original studies published between Jan. 2011 and Dec. 2021. The risk of bias of the included studies was assessed using Newcastle-Ottawa Scale (NOS). Results. 34 studies comprising 15 295 patients were included. Patients with myosteatosis had significantly poorer overall survival (hazard ratio 0,506, 95% confidence interval 0,4310,595; p0,05). There was no significant influence of myosteatosis on recurrence-free survival (hazard ratio 0,658, 95% confidence interval 0,3891,112; p0,05). Myosteatosis was significantly associated with the occurrence of major postoperative complications in 6 studies. However, only 3 studies supported the impact of myosteatosis on mortality. Conclusion. This meta-analysis demonstrates that patients with preoperative myosteatosis have poor long-term survival following treatment for GI malignancy. Therefore, myosteatosis might be used as a prognostic tool. However, more studies with standardized definitions and cut-offs are required.

The paper is devoted to the modeling of high-performance multiprocessor architecture for data processing systems used to solve problems with an expandable calculations' area. The proposed system is characterized by high reliability and high energy efficiency. The system contains a separate reconfigurable network for the exchange of data between computing nodes, managed switches. The system also provides network booting nodes and redundancy mechanism of key components.

Since February 24, 2022, invasion of Ukraine by Russia has affected the entire population of Ukraine, including the scientific community. The attack by Russian forces has resulted in the destruction of infrastructure of Ukrainian cities, including universities, research centers, and educational institutions. Millions of people, including educators and scientists, have been displaced from their homes, their futures uncertain. This conflict is unfolding in a country with a large and diverse scientific community and a rich history of higher education and scientific research. The global research community has provided effective and timely response by offering research opportunities and fellowships for displaced Ukrainian academic faculty and students. However, many of these opportunities were primarily targeted to individuals capable of leaving the country. Many Ukrainian scholars remaining in the country need the help of the international community to help find short- or long-term employment. Moving forward, we hope to increase collaboration, provision of training provided by educational organizations worldwide, and spur rapid advancements in science and technology that will lead and expedite the postwar reconstruction of Ukraine.

Odontoreparation is fundamental to ensure the functional efficiency, high aesthetics and durability of fixed prostheses. At present, with fixed prosthetics of defects in hard tissues of teeth and dentition, various types of artificial crowns are widely used [1, 2]. Purpose of the study: to determine the angular deviations of the vertical surfaces of molars, prepared by students of the 3rd year. Based on the data obtained, calculate the average value for the group and identify which surfaces of the stump are most prone to errors during odontopreparation. Materials and methods. Frasaco® phantom teeth (mandibular molars) were used as research materials. Preparation for metal-ceramic crowns was carried out according to the traditional method by thirteen third-year students of the Samara State Medical University of the Ministry of Health of Russia. In this work, 6° was taken as the optimal angle of convergence of the vertical walls (3° on each of the two opposite surfaces). During the preparation, a fissure bur d = 1,6 mm was used. Conclusion. The average time spent on preparation is quite long, which indicates an insufficient level of manual skills. The revealed phenomena of wall divergence also indicate that the preparation skills are insufficient. In addition, divergence was found mainly on the distal surface, which is explained by more difficult access and limited visibility of the prepared surface.

Objectives Timolol maleate is used for the treatment of glaucoma and metabolized by cytochrome CYP2D6 in the liver. The aim of this study was the evaluation of the influence of CYP2D6*4 and CYP2D6*10 gene polymorphisms on the safety of medications containing 0.5% of timolol maleate as glaucoma treatment in patients with primary open-angle glaucoma (POAG). Methods 105 patients with POAG were prescribed glaucoma medications, containing 0.5% timolol maleate. The safety of glaucoma treatment was determined by electrocardiography (ECG) (to assess heart rate (HR) and PQ interval) and blood pressure (BP) measurements. The real-time polymerase chain reaction method was used for the detection of single nucleotide polymorphisms (SNP). Results The risk of adverse drug reactions was higher in patients with the CYP2D6*4 GA genotype compared with GG: mean HR change at 1 month (2.88 ± 4.68 and 6.44 ± 5.57, pCYP2D6*10 CT genotype compared with CC: mean HR change at 1 month (2.94 ± 4.65 and 6.34 ± 5.66, p Conclusions CYP2D6*4 and CYP2D6*10 gene polymorphisms may affect a higher risk of timolol-induced bradycardia and increased PQ interval of treatment medications containing 0.5% of timolol maleate in patients with POAG.

Modern digital technologies and their software open up new possibilities in dentistry. For example, the use of computed tomography is becoming more and more affordable. Almost every dental tomograph has the necessary software for 3D planning of dental procedures. Dental implantation has developed significantly in our country. The available surgical equipment make it possible to put dental implants even with the deficit of bone tissue. The purpose of this article was to summarize various methods to plan the placing the dental implant and to manufacture surgical templates. Dentistry has always been closely associated with other areas of science and industry, it tends to use a large number of modern innovations and developments. In this article, we have collected materials to demonstrate how the treatment process is changing in response to the integration of computer diagnostics and manufacturing (CAD / CAM) technologies. Consequently, we have more efficient and less traumatic dental implant planning systems based on the accurate data and computer calculations that minimize technological and human negative factors.

Antipsychotics are a first-line treatment for psychotic disorders. The cytochrome P450 isoenzymes CYP3A4/5 and CYP2D6 metabolize most antipsychotics. The activity of these isoenzymes in children changes with maturation, so it is different from that in adults. Objective: to study the associations of CYP3A and CYP2D6 isoenzyme activity parameters with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode. Patients and methods. The investigation enrolled 53 adolescents with an acute psychotic episode who took antipsychotics. The observation period lasted 14 days. The CGAS, PANSS, UKU SERS, SAS, and BARS scales were used to evaluate the efficiency and safety of the therapy on day 14. The activity of CYP3A and CYP2D6 isoenzymes was measured by determining the metabolic ratios of the concentrations of endogenous substrates of the isoenzymes and their metabolites in a morning urine sample on days 1 and 14 of the study. The activity of CYP3A was assessed by the 6-beta hydroxycortisol/cortisol ratio; that of CYP2D6 was measured by the 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline/pinoline ratio. The influence of carriage of polymorphic variants CYP2D6*4,*9,*10, CYP3A4*22, CYP3A5*3 on the activity of isoenzymes was excluded by removing their carriers from the analysis. Results and discussion. The investigators revealed an association of certain antipsychotic-induced undesirable symptoms with CYP3A and CYP2D6 activity parameters. On day 1, a lower CYP2D6 activity was initially observed in patients with tremor (0.54 [0.34; 1.34] vs 1.25 [0.91; 1.75]; p=0.023). Also, patients with any documented adverse reaction (ARs) to therapy had initially a decreased CYP3A activity (1.2 [0.85; 2.29] vs 2.55 [1.44; 4.83]; p=0.047) and an enhanced CYP3A activity during therapy (the activity difference between day 14 and day 1 was 0.28 [-0.28; 2.32] vs -1.3 [-3.47; 0.66]; p=0.042). Conclusion. The initially reduced activity of CYP2D6 and CYP3A isoenzymes is a significant predictor of antipsychotic-induced ARs in adolescents with an acute psychotic episode. The predictive role of CYP2D6 and CYP3A activity levels in the efficacy of antipsychotics has not been confirmed.

Aim. To search for new pharmacogenetic biomarkers of bleeding risk in patients taking rivaroxaban and dabigatran for different indications: atrial fibrillation, endoprosthesis of large joints of lower limbs.Material and methods. The study enrolled 29 patients (17 patients received dabigatran and 12 –rivaroxaban), who had hemorrhagic complications during taking direct oral anticoagulants. To find new pharmacogenetic biomarkers of bleeding risk, a next generation sequencing (NGS) was performed for selected candidate genes.Results. Among the patients with bleeding who received dabigatran, 13 variants of the nucleotide sequence showed statistically significant deviation from the population values: 11 in the CES1 gene and 2 in the ABCB1 gene. Among the patients with bleeding who received rivaroxaban, 7 variants of nucleotide sequence showed significant deviation: 4 in the ABCG2 gene, 2 in the CYP3A4 gene, and 1 in the ABCB1 gene.Conclusion. The identified in this study polymorphisms of candidate genes ABCB1, ABCG2, CES1, CYP3A4 were associated with the risk of bleeding in patients taking rivaroxaban and dabigatran. It makes an important contribution to the pharmacogenetics of direct oral anticoagulants and require additional assessment of clinical significance in further studies.

At the time of print, the evidence for using umifenovir in COVID-19 is mainly theoretical. The published clinical trials have contradicting results. The decision to use umifenovir in COVID-19 should be individualized, considering the “experimental” nature of this treatment.

Children and adolescents are more likely than adults to experience adverse side effects when taking antipsychotics. Pharmacogenetic testing allows one to more accurately choose the initial dose of a drug. The genes of pharmacokinetic factors have been shown to be of high prognostic value for the safety of antipsychotics in adults.Patients and methods. The study enrolled 36 adolescents (58.3% male) (mean age, 14.83±1.84 years). All the patients took an antipsychotic. The follow-up lasted 28 days. On 14 and 28 days of treatment, its efficiency and safety were evaluated using the Children's Global Assessment Scale (CGAS), the Positive and Negative Syndrome Scale (PANSS), the Udvalg for Kliniske Undersњgelser Side Effects Rating Scale (UKU-SERS), the Simpson-Angus Scale (SAS), and the Barnes Akathisia Rating Scale (BARS). The patients were genotyped for CYP3A4*22, CYP3A5*3, CYP2D6*4, *9, *10, ABCB1 1236C>T, 2677G>T/A, 3435C>T, DRD2 rs1800497, DRD4 rs1800955, and HTR2A rs6313.Results and discussion. The decrease in the mean score of the PANSS subscale “Productive symptoms” was more pronounced in carriers of the DRD2 rs1800497 polymorphic variant (-6.5 [-10.25; -3.75] vs -3 [-6.5; -2 ] on 14 day (p=0.028) and (-11 [-13; -9.5] vs -5 [-9; -3.5] on 28 day (p=0.001) compared to baseline. The carriage of ABCB1 3435CT+TT was associated with worse tolerance to pharmacotherapy on 14 day (the total score of the UKU-SERS M, 8 [3; 11.75] vs M, 2 [1; 6]; p=0.034). The carriers of DRD2 rs1800497 reported a greater severity of antipsychotic-induced neurological disorders (UKU-SERS subscale score M, 1 [0; 2.25] vs M 0 [0; 1]; p=0.029).Conclusion. The polymorphic variants DRD2 rs1800497 and ABCB1 3435C>T were established to be significantly associated with the efficacy and safety of antipsychotics in adolescents with an acute psychotic episode.

To ensure high-quality distance learning at the Department of Emergency Medicine of the National Medical Academy of Postgraduate Education named after P. L. Shupyk, a specialized course of thematic improvement is used, presented by digital lecture and practical material presented in limited access on an exchange server for students registered on the cycle. This form of education has a number of advantages both in terms of the convenience of the educational process for teachers and students, and the reduction of possible risks in case of adverse situations such as the epidemic threat of the COVID-19 pandemic. Distance education provides quality and comprehensive training of the student without separation from daily activities, taking into account the individually most convenient place and time to access the electronic knowledge base of the cycle. Existing technologies of distance learning through the use of modern digital platforms, high-quality content of educational web resources, the introduction of an effective quality control system of knowledge give us the opportunity to adapt to new realities of the educational process and ensure consistently high quality of postgraduate medical education.

The paper presents literary and original data on the problems of falling for elderly patients. The relationship between the occurrence of a fall and the initiation of drug therapy with a known negative effect on the risk of falling is considered. Data on the frequency and structure of falls by patients with cardiovascular diseases over the age of 75 who received treatment at a multidisciplinary hospital are presented. The data analysis showed a tendency of fall prevalence: a fall was observed in 33.8% of patients in the first 5 days of the hospital stay. This may be associated with a high drug burden and the prescription of new drugs to the patient. The study noted that the therapy was chosen on the first day. Additional drugs were often prescribed, which led to the polypharmacy state. Analysis of individual groups of drugs allowed reliable confirmation of the relationship between the prescription of drugs that increase the fall risk and occurrence in relation to the ophthalmic form of β-blockers (p = 0.04). Polypharmacy as a risk factor of falling in gerontological patients, which was described in the scientific literature, also confirmed the negative effect in our study. Thus, patients who are newly administered drugs known to have negative effect on fall development can be attributed to the risk group for falling.

Phenazepam is a benzodiazepine tranquilizer that is widely used in Russia. The drug is metabolized by cytochrome P450 3A (CYP3A) isozymes. Since their substrates have an affinity for P-glycoprotein, the polymorphic variants in the ABCB1 gene may affect the safety of this drug. Objective: to analyze associations between the CYP3A5, CYP2C9, CYP2C19, CYP2D6 and ABCB1 gene polymorphisms and the safety of phenazepam treatment for alcohol withdrawal syndrome (AWS). Patients and methods. The investigation enrolled 102 patients diagnosed with uncomplicated AWS (IDC-10 code F10.30). All the patients were followed up for 6 days within which they took phenazepam. 5-ml venous blood samples were collected from each patient for genotyping. The carriage of CYP3A4*22, CYP3A5*3, CYP2C19*2, CYP2C19*17, CYP2C9*2, ABCB1 3435C>T, 1236C>T, and 2677G>T/A polymorphic variants was determined by a real-time polymerase chain reaction assay. Therapy safety was evaluated using the UKU Side-Effect Rating Scale on day 6. Statistical analysis was carried out with SPSS Statistics 21.0. Haplotype and combinatorial analyses were performed using SNPStats. Results and discussion. The greater subjective severity of adverse reactions (ARs) was shown for the homozygotes of ABCB1 1236C>T CC (odds ratio (OR), 2.154; 95% confidence interval (CI), 1.271–3.650; p=0.014) and ABCB1 2677G>T GG (OR, 2.154; 95% CI, 1.271–3.650; p=0.014). On the contrary, a combinatorial analysis revealed the role of ABCB1 3435C>T, 1236C>T, and 2677G>T polymorphic alleles as predictors for the greater subjective severity of ARs. The following statistically significant polymorphic variant combinations were ABCB1 3435-1236–2677 and T-T-T-CYP3A5*3 isozymes (OR=5.03; 95% CI, 1.65–15.34; p=0.0056); T-T-T-CYP2C9*1 (OR=3.61; 95% CI, 1.31–9.92; p=0.015); T-T-T-CYP2C19*1 (OR=2.52; 95% CI, 1.05–6.08; p=0.042). Attention disorders were also established to be associated with the carriage of T-T-T-CYP2D6*1 (OR=2.58; 95 CI, 1.08–6.13; p=0.035). Conclusion. The carriage of ABCB1 3435-2677-1236 (T-T-T) haplotype is significantly associated with the greater severity of ARs in phenazepam-treated patients with AWS.

The study objective is to compare pre- and intraoperative characteristics, and the results of neurosurgical treatment in patients with Cushing’s disease, non-visualized adenoma and microadenoma of the pituitary gland.Materials and methods. The results of transsphenoidal adenomectomy were analyzed in 102 patients with non-visualized corticotropinomas and 360 patients with microcorticotropinomas. The pituitary genesis of endogenous ACTH-dependent hypercorticism in 182 patients was proved by the results of selective blood sampling from inferior petrosal sinus with stimulation desmopressin. The study included 369 women and 93 men aged 16 to 64 years. All patients were operated by transnasal approach using endoscopic techniques.Results. The group with non-visualized adenoma was dominated by men (p = 0.005) and patients with severe hypercorticism (p = 0.021). When comparing intraoperative characteristics in this group, invasive growth was statistically significantly more frequent (53 % vs 39 %) (p = 0.017), which in turn led to more aggressive intraoperative tactics (p Conclusion. Early results of primary transsphenoidal adenomectomy in patients with non-visualized pituitary adenoma were significantly worse in comparison with patients with microadenoma detected by 1.5 T magnetic resonance imaging, which have more frequently invasive growth, what leads to an increase in the volume of surgery and a possible increase in postoperative hypopituitarism.

Objective To analyse the frequency, structure and risk factors of adverse drug effects in adolescents with acute psychotic episode by the methods of global triggers - Paediatric All-Cause Harm Measurement Tool (PACHMT) and Global Assessment of Paediatric Patient Safety Tool (GAPPS). Patients and methods We used 151 completed case histories of patients who were admitted to a psychiatric hospital with acute psychotic episode. We applied Global Trigger Tool algorithm to each case retrospectively: we developed a special trigger list for psychiatric patients based on PACHMT, GAPPS and general Global Trigger Tool. We also calculated the Medical Appropriateness Index (MAI) for each case. We applied trigger tool analysis for calculation of treatment safety parameters. Statistical analyses included Pearson's Chi-square, Mann-Whitney U, and Kruskal-Walles tests. Results We identified a total of 261 triggers among 151 analysed cases, 51 of which were accompanied by adverse drug effects (ADEs) (overall positive prediction value = 19.54%). The value of ADEs per 1000 bed days was 4.73, ADEs per 100 admissions was 33.77%. Extrapyramidal reactions to antipsychotics (58.8%) were the most common ADEs, followed by an abrupt medication stop of one or more drugs due to ADEs (25.5%). Significant predictors of antipsychotic-induced extrapyramidal symptoms were age, MAI score and total number of hospital admissions. Conclusion We recommend three triggers, "Abrupt medication stop", "Prescribing of extrapyramidal symptoms corrector", and "Hospital readmission within 30 days", with reasonable positive predictive value for incorporation into routine systems for patient safety monitoring in adolescents with an acute psychotic episode. Antipsychotic-induced extrapyramidal symptoms were more prevalent in older adolescents and patients with fewer lifetime hospital admissions. These patients need to be carefully monitored to ensure patient safety.

Despite extensive preoperative imaging, intraoperative localization of liver lesions after systemic treatment can be challenging. Therefore, an image-guided navigation setup is explored that links preoperative diagnostic scans and 3D models to intraoperative ultrasound (US), enabling overlay of detailed diagnostic images on intraoperative US. Aim of this study is to assess the workflow and accuracy of such a navigation system which compensates for liver motion.Electromagnetic (EM) tracking was used for organ tracking and movement of the transducer. After laparotomy, a sensor was attached to the liver surface while the EM-tracked US transducer enabled image acquisition and landmark digitization. Landmarks surrounding the lesion were selected during patient-specific preoperative 3D planning and identified for registration during surgery. Endpoints were accuracy and additional times of the investigative steps. Accuracy was computed at the center of the target lesion.In total, 22 navigated procedures were performed. Navigation provided useful visualization of preoperative 3D models and their overlay on US imaging. Landmark-based registration resulted in a mean fiducial registration error of 10.3 ± 4.3 mm, and a mean target registration error of 8.5 ± 4.2 mm. Navigation was available after an average of 12.7 min.We developed a navigation method combining ultrasound with active liver tracking for organ motion compensation, with an accuracy below 10 mm. Fixation of the liver sensor near the target lesion compensates for local movement and contributes to improved reliability during navigation. This represents an important step forward in providing surgical navigation throughout the procedure.This study is registered in the Netherlands Trial Register (number NL7951).

The article is devoted to the study of the solution of the agrarian question in the Ukrainian State in 1918 and in modern Ukraine. The authors analyzed the content of the agrarian legislation in the Hetmanate period and on the basis of the study of sources and scientific literature, it was found out the common and different from the current agrarian legislation in Ukraine

Introduction The aim of this study is to assess the influence of gene CYP2C19, CYP3A4, CYP3A5 and ABCB1 polymorphisms on clopidogrel antiplatelet activity, rivaroxaban concentration equilibrium, and clinical outcomes among patients with acute coronary syndrome and non-valvular atrial fibrillation. Methods In the multicenter prospective registry study of the efficacy and safety of a combined antithrombotic therapy 103 patients with non-valvular atrial fibrillation both undergoing or not a percutaneous coronary intervention were enrolled. The trial assessed the primary outcomes (major bleeding, in-hospital death, cardiovascular death, stroke\transient ischaemic attack, death/renal insufficiency) and secondary outcomes (platelet reactivity units (PRU), rivaroxaban concentration). Results For none of the clinical outcomes when combined with other covariates, the carriership of polymorphisms CYP3A5*3 rs776746, CYP2C19*2 rs4244285;*17 rs12248560, ABCB1 3435 C>T, ABCB1 rs4148738 was significant. None of the markers under study (CYP3A5*3 rs776746, CYP2C19*2 rs4244285, *17 rs12248560, ABCB1 3435 C>T, ABCB1 rs4148738) has proven to affect rivaroxaban equilibrium concentration in blood plasma among patients with atrial fibrillation and acute coronary syndrome. Conclusion In situations of double or triple antithrombotic rivaroxaban and clopidogrel therapy among patients with atrial fibrillation and acute coronary syndrome, the genetic factors associated with bleeding complications risk (CYP2C19*17) may prove to be clinically relevant.

This study analyzes reports of the role of robot assistance in dentistry and the main pathways for its further development. We report a retrospective analysis of the construction of robotic and robot-assisted systems used in dental practice. The development of robot-assisted and robotic systems should be included in improvements to methods of intraoperative imaging, diagnostics, and improvements in surgical instrumentation and the introduction of new robotic developments.

One of the main causes for adverse reactions development is not taking into account the pharmacokinetics of drugs and the dose. Pharmacokinetics of drugs is mostly defined by the cytochrome P-450 isoenzymes activity, carboxylesterases and many other isoenzymes of drug metabolism, as well as ADME transporters (P-gp etc.) which take part in the process of drug metabolism. The activity of these isoenzymes is defined by the genetic aspects of patients and non-genetic aspects such as comorbidity and drug-drug interactions. The development of complex algorithms for personalization of therapy based on the results of pharmacogenetic studies and in the form of a decision support system will play an important role in reduction of adverse drug reactions. A lot can be achieved for personalization of Direct Oral Anticoagulants for treatment of cardiovascular diseases. New approaches are being developed based on the results of pharmacogenetic and pharmacokinetic testing that will help diminish adverse effects of drugs.

Introduction According to various data, 25–50% of all patients with schizophrenia suffer from treatment resistance. It is believed that patients with treatment-resistant schizophrenia (TRS) have reduced cognitive skills, compared to the patients with a more favourable type of schizophrenia. However, according to some authors, there is limited evidence-based research on this topic at present. Materials and methods The total number of patients included 130 patients with a diagnosis of schizophrenia (F20 according to ICD 10). All patients were examined according to the following scales: Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Brief Assessment of Cognition in Schizophrenia (BACS). Results Our results showed that patients with TRS as a whole had worse cognitive functions than nTRS patients (p = 0.357). In the group of patients with TRS, polymorphism CYP2D6*4 showed an effect on executive functions. Carriers of the heterozygous GA genotype had higher values of executive functions (p = 0.043). No association between the studied gene polymorphic variants and TRS was found in this research. Conclusion The polymorphic variant CYP2D6*4 showed an effect on cognitive function in the TRS group, regardless of their mental state and the effect of pharmacotherapy. In the future, it will be necessary to conduct larger prospective studies with a greater number of patients and a greater number of polymorphic variants of genes. Further identification of genetic predictors of cognitive impairment will improve researchers’ understanding of their causes and possibly move closer to more targeted therapy for schizophrenia.

Aim. To summarize Russian studies using pharmacogenetic testing as applied to cardiology.Material and methods. The authors conducted an online search for articles in December 2018 using the following databases: PubMed, Google Scholar, eLIBRARY. The search was carried out by keywords: "Russia", "Russian", "cardiology" together with the terms associated with the polymorphic marker, including: «P450», «CYP2C19», «CYP2D6», «CYP2B1», «CYP2B6», «CYP2Е1», «CYP2C8», «CYP2C9», «CYP3A4», «CYP3A5», «CYP1A1», «CYP1A2», «CYP4F2», «CYP4F1», «ABCB1», «SLCO1B1», «VKORC1», «GGCX», «SULT1A1», «CULT1», «CES1», «gene», «genes», «pharmacogenetics», «pharmacogenomics», «ethnic group».Results. Generalization of information allowed to identify obscure genes that need to be investigated in pharmacogenetic studies. This information can be used for the development of dosing algorithms and the priority choice of drugs, considering the results of pharmacogenetic testing and planning future research.Conclusion. The results of the literature review indicate the importance of studying the most clinically valid and clinically useful pharmacogenetic markers (CYP2C19, CYP2C9, VKORC1, SLCO1B1) among various ethnic groups in the Russian Federation. With the accumulation of evidence of clinical validity and clinical utility of other pharmacogenetic markers (CES1, CYP2D6*4, etc.), the problem of interethnic differences in the carriage of clinically significant polymorphisms of these genes identified in previous studies in the Russian Federation increasingly requires attention. The most promising for the introduction into the clinical practice in the Russian Federation in the near future are polymorphic markers of the CYP2C19, CYP2C9, VKORC1 and SLCO1B1 genes.

Among the anomalies in the number of vessels of the umbilical cord,thesingle umbilical artery (SUA) is most often found. A significant impact of SUA on the course of such pregnancy and deliveries is expected. The article presents some peculiarities of the deliveries and condition of newborns after pregnancies with SUA compared with pregnant women with three umbilical cord vessels and physiological deliveries. The objective of the workwasto analyze the peculiarities of the perinatal period and deliveries after pregnancy with SUA, to conduct a comparative analysis of the revealed features with the corresponding indicators among pregnant women with two umbilical arteries and physiological births. Thestudygroupconsistedof 31 pregnant women with a SUA (study group)and control group – 62 pregnant women with 2 arteries of the umbilical cord. According to our data, pregnant womenwith SUA were hospitalized earlier and spent more time in the maternity hospital, although the terms of delivery did not differ between the two study groups, although there was a tendency to an earlier term of delivery in pregnant women with SUA. Among pregnant women with SUA, deliveries were premature in 4 women (12.9 %). No differences were found between pregnant women with SUA and control group in such indicators as early discharge of amniotic fluid, anthropometric indicators of pregnant women, entanglement of umbilical cord, pelvic presentation, rupture of the perineum or episiotomy during deliveries. The duration ofI, II and III periods of deliveries also did not differ significantly between the two study groups. Weakness of patrimonial activity was more often in women with SUA, accounting for 12.9 % of all deliveries, compared to 3.2 % in the control group. Fetal hypoxia in deliveries was observed in 25.8 % of cases among pregnant women with SUA, and in 4.8 % among pregnant women in the control group. Fetal distress in deliveries was estimated at 4 (12.9 %) and 4 caesarean sections were performed. Physiological childbirth occurred in all cases in the control group. In the SUA group, the infant weight was significantly lower than the control group children, but the Apgar score at 1 and 5 minutes did not differ between the two study groups. Cardio-respiratory depression, risk of neurological disorders, and congenital malformations (esophageal atresia, Gothic palate, and syndactylium) were more frequently reported in the SUA group. Long-term hospitalization of pregnant women, weakness in delivery, premature birth, fetal hypoxia in delivery, fetal distress and incidence of cesarean delivery are much more common in SUA group. The weight of newborns from pregnancies with SUA is significantly lower, however, the infants' status on the Agar scale after pregnancies with SUA did not differ from those of children in the control group. Cardiovascular depression, the risk of neurological disorders, and congenital malformations (esophageal atresia, Gothic palate, and syndactyly) were more common in the SUA group.

Deprescribing is the opposite of prescribing drugs, the purpose of which is to improve quality of life and reduce the risk of adverse drug reactions. The paper considers the process of deprescribing benzodiazepines. It analyzes relevant studies on this problem, as well as recommendations to help decide whether it is a need for deprescribing and how to accurately do this. There are also the results of original investigations demonstrating the tapering of benzodiazepine tranquilizers: comparison of simple tampering, use of psychotherapy, or replacement pharmacotherapy. The use of a deprescribing algorithm is the safest way to discontinue benzodiazepines in patients who do not have serious indications for their long-term use.

The realities of digitalization require changes in strategies for choosing educational technologies. The modern educational process is not possible without the use of digital technologies. Digital technologies have led to the arising and development of blended learning. However, its effectiveness is determined not only by technology. The human factor receives special attention in this direction. Analysis of the World Development Report 2016: Digital Dividends allows us to identify digital competence as a necessary condition for the successful use of digital technologies, and hence blended learning. Learning interactions designing in the process of implementing blended learning requires timely diagnosis of the level of digital competence. A popular tool for this is the Digital Competence Framework for Citizens. To clarify the peculiarities of its use was made an analysis of the experimental implementation results of blended learning in the industrial training in sewing for intended masters. During the research, it was revealed that the most important digital competence areas for the variable learning establishment in the training of future professionals are Information and data literacy, Communication and collaboration and Problem solving. In addition, competence for area Problem solving conduce to increase the level of competence for all other areas. The level of digital competence of the subjects mainly coincide to the characteristics of basic and secondary levels. The obtained data clarified the reasons for the difficulties, decrease motivation and cognitive activity that occur among students using distance courses-resources learning designed for blended learning. Thus, the use of the Digital Competence Framework for Citizens at the initial stage of implementing blended learning can make a rational choice of strategies for combining face-to-face and distance learning technologies.

Objectives To identify possible associations of CYP2D6, CYP3A4/5, and ABCB1 gene polymorphisms with the efficacy and safety of antipsychotics in adolescents with acute psychotic episodes. Methods We examined the associations of pharmacogenetic factors with the efficacy and safety of antipsychotics in 101 adolescents with acute psychotic episodes. The diagnosis on admission was “Brief psychotic disorder” (F23.0–23.9 by ICD-10). All patients were administered antipsychotics for 14 days. Treatment efficacy and safety were assessed using the PANSS, CGAS, CGI-S(I), UKU SERS, BARS, and SAS scales. Pharmacokinetic genotyping was performed for the CYP2D6*4, *10, ABCB1 1236C>T, 2677G>T, and 3435C>T genes. Results CYP2D6 intermediate metabolisers had “Micturition disturbances” more often than extensive metabolisers (24.2 vs. 7.4%; p=0.026). “Wild” homozygote ABCB1 3435C>T CC was associated with more prominent akathisia. Haplotype analysis of three ABCB1 polymorphisms revealed that the “wild” alleles “C-G-C” (ABCB1 1236-2677-3435) were associated with higher risk of “Reduced salivation” (OR=2.95; 95% CI=1.35–6.45; p=0.0078). Conclusions CYP2D6 intermediate metabolism was associated with the risk of urinary difficulties under treatment with antipsychotics. We found that “wild” homozygotes ABCB1 1236C>T, 2677G>T, and 3435C>T were predictors of adverse drug effects caused by treatment with antipsychotics.

Areas covered by seminatural grasslands have been in constant decline for decades in Europe. This trend is particularly strong for mountain territories, where such traditional agricultural practices as cattle grazing are no longer economically feasible. This study was conducted in the subalpine pasture of Cinte Tesino (TN, Italy), where local farmers have applied the following different management strategies: shorter and longer grazing durations during the season and a complete abandonment for the last 15 years. We aimed to study how these different management strategies impact the functioning and diversity of vegetation and the chemical and biological characteristics of the soil. Species richness was higher in plots subjected to longer grazing with a prevalence of D. caespitosa in terms of biomass share. A decline in species richness in abandoned plots was accompanied by an increase in the share of other graminoids in collected biomass. A concomitant increase in leaf N concentration and light availability in grazed plots resulted in higher photosynthetic efficiency in some species, as revealed by the δ13C of plant tissues. Soils under grazing were characterised by a higher concentration of total and extractable N, almost doubled microbial biomass C and increased extracellular enzymes activity, evidencing nutrient cycling mobilization. While the microbial pool was characterised by lower mineralization rates, C was lost from the soil with 15 years of abandonment. The longer grazing season demonstrated to be the most beneficial, promoting species richness, C accumulation and better soil microbial functioning. A change in soil pH from strongly acidic to moderately acidic with longer grazing is likely one of the important factors adding to the success in the functioning of primary producers and decomposers in this site.

Although MRI with hepatospecific contrast agents is a new standard diagnostic imaging for patients with liver cancer, there are no automated methods for detailed segmentation of the liver vasculature in cases with progressed tumors. This is due to the anatomical complexity, underlying disease and tunability of MRI image contrast, which challenge automatization. Here, we investigated the feasibility of liver vessel segmentation with three CNN architectures in combination with four different loss functions. In particular, a 3D Unet, a Vnet and its modification with an intra-layer dense block (DVnet) were evaluated. Dice-based loss, categorical cross entropy (CCE), weighed categorical cross entropy (WCCE) and focal loss (FL) were used as loss functions for training, the latter two to deal with the imbalanced class problem. A cohort of 90 patients (60 training, 10 validation and 20 testing) with progressed liver tumors were involved in this study, with manually annotated liver vasculature as a “gold standard”. Trained networks were evaluated by means of the Dice coefficient and centerline-based F1 score calculations. Models trained with balanced loss functions (FL,WCEE) performed the best for DVnet, while Vnet had the best performance for unbalanced loss functions. Vnet and DVnet architectures trained with an FL had the best overall segmentation accuracy (DC = 70%), while networks with a Dicebased loss had the lowest performance (max DC = 42%). In conclusion, the use of balanced loss functions, addition of an intra-layer dense block and drop-outs into the network architecture improved handling the unbalanced class problem in liver vessel segmentation.

In work considered using API-10S test system for diagnoctic and identification black rot pathogen, Xanthomonas campestris bacteria.

Experiments on the effects of femtosecond laser radiation on titanium targets in a liquid hydrocarbon medium were carried out. The structures obtained were investigated optical and scanning electron microscopy.

Objectives Prediction of the antipsychotic’s effectiveness is a relevant topic in the field of personalized medicine. Methods The research design of this study is a prospective observation with posthoc analysis of associations of genetic polymorphisms with safety parameters and effectiveness of antipsychotic therapy. We observed 53 adolescents with an acute psychotic episode which were prescribed antipsychotics for 14 days. We evaluated the effectiveness of antipsychotics with the Positive and Negative Symptoms Scale and the safety with the UKU Side Effects Rating Scale, Simpson-Angus Scale, and Barnes Akathisia rating scale. We genotyped CYP3A4*22 (rs2740574), CYP3A5*3 (6986A>G, rs7767746), CYP2D6*4, *9, *10 (rs3892097, rs1065852), ABCB1 1236C>T (rs1128503), 2677G>T/A (rs2032582), 3435C>T (rs1045642), DRD2 (rs1800497), DRD4 (rs1800955), HTR2A (rs6313) by the real-time polymerase chain reaction method. Results We found significantly more frequent “increased dream activity” between CYP2D6 intermediate metabolizers and normal metabolizers (54 vs. 22%; p=0.043). The «increased duration of sleep» was more often observed in homozygotes TT of ABCB1 2677G>T/A (50 vs. 15.8%, p=0.006) and TT of 3435C>T (41.7 vs. 8.2%, p=0.007). Conclusions We found that CYP2D6 and ABCB1 polymorphisms were associated with the safety of antipsychotics in adolescents with an acute psychotic episode.

In the article, the authors disclose the revisory measures of the Austro-German War in Ukrainian villages in February - March 1918. It shows the attitude of the Austro-Germanic authorities to the Ukrainian peasantry, the mechanism of imposing and recovering the continuities, as well as the attitude of the population towards such activity

The universally established method for effective and less-invasive reduction of the intraocular pressure (IOP) in patients with primary open-angle glaucoma (POAG) is a two-step method consisting of non-penetrating deep sclerectomy (NDSE) followed by laser goniopuncture of the Descemet's membrane (Descemet's goniopuncture; DGP). However, the hypotensive effect can diminish at different times during the follow-up due to excessive scarring in surgically formed outflow tracts (SFOT).To evaluate the condition of SFOT in dynamics with Visante OCT after one-step combined laser technique consisting of modified selective laser activation of the trabecula (MSLAT) and DGP in advanced POAG patients with normalized IOP who have pronounced pigmentation of the trabecular meshwork and stage II pseudoexfoliation syndrome (PES).OCT scans of 117 patients (117 eyes) were analyzed before laser treatments and after 1, 3, 6, 12 and 24 months. The study included 62 patients (62 eyes) comprising the main group who underwent MSLAT + DGP, and the control group consisting of 55 patients (55 eyes) who only underwent DGP.Visante OCT scans revealed that parameters of the filtration bleb (FB) and intrascleral cavity (ISC) in the main study group were more stable than in the control group during the whole follow-up. In the main study group there were less incorporations in the ISC and they had lower optical density, compared with the control group where there were denser incorporations in the ISC which gradually increased in count.According to Visante OCT, the growing count and the increase in density of incorporations in the ISC can be defined as adverse signs of an active proliferative process in SFOT. A one-step MSLAT with DGP help achieve both a long-lasting hypotensive effect, and decrease of active proliferative process signs in SFOT.Общепризнанным эффективным и малотравматичным методом снижения уровня внутриглазного давления (ВГД) при первичной открытоугольной глаукоме (ПОУГ) считается двухэтапный метод, состоящий из непроникающей глубокой склерэктомии (НГСЭ) с последующим проведением лазерной десцеметогониопунктуры (ДГП). Однако в разные сроки послеоперационного периода может снижаться гипотензивный эффект данного вмешательства ввиду избыточного рубцевания в зоне хирургически сформированных путей оттока (ХСПО). Цель - оценить динамику состояния ХСПО по данным ОСТ Visante после одномоментного комбинированного лазерного вмешательства, включающего модифицированную селективную лазерную активацию трабекулы (МСЛАТ) и ДГП, у пациентов с далекозашедшей стадией ПОУГ с выраженной пигментацией трабекулярной сети и псевдоэксфолиативным синдромом II стадии при нормализованном уровне ВГД. Материал и методы. Проанализированы сканограммы OCT Visante 117 пациентов (117 глаз) до лазерных вмешательств, а также через 1, 3, 6 мес, 1 и 2 года после лечения при нормализации офтальмотонуса. В основную группу вошли 62 пациента (62 глаза), которым было проведено одномоментное комбинированное лазерное вмешательство, в контрольную - 55 пациентов (55 глаз), которым была выполнена ДГП. Результаты. На протяжении всего срока наблюдения на сканограммах OCT Visante основной группы определяли более сохранные параметры фильтрационной подушки и интрасклеральной полости (ИСП) в сравнении с аналогичными показателями в контроле. В основной группе отмечали уменьшение количества включений в ИСП с преимущественно их невысокой оптической плотностью, тогда как в контроле визуализировали более плотные включения в ИСП с постепенным увеличением их количества. Заключение. По данным OCT Visante, нарастание количества включений в ИСП, увеличение их плотности являются неблагоприятными прогностическими признаками, указывающими на активность пролиферативного процесса в ХСПО. МСЛАТ, проводимая одновременно с ДГП, позволяет добиться не только продолжительного гипотензивного эффекта, но и уменьшения признаков активности пролиферативного процесса в ХСПО.

The article presents the literature and original data on the problems of falls in elderly patients. The connection of the fact of falling with initiation of therapy by a number of drugs known to have a negative impact on the risk of falling is considered. The article presents data on the frequency and structure of falls on the example of patients with cardiovascular diseases older than 75 years, treated in a multidisciplinary hospital. The analysis of the data showed a tendency of prevalence of the fact of falling in 1/3 patients (33,8%) in the first 5 days of hospital stay, which may be associated with high drug burden and the appointment of «new» drugs for the patient. The study noted that it was on the first day that the selection of therapy took place and additional drugs were often prescribed, leading to a state of polypragmasia. Analysis of individual groups of drugs was able to reliably confirm the relationship between the appointment of drugs that increase.В статье представлены литературные и оригинальные данные по проблемам падений у пациентов старческого возраста. Рассмотрена связь факта падения с инициацией терапии лекарственными средствами, известными негативным влиянием на риск падения. Представлены данные по частоте и структуре падений на примере пациентов с сердечно-сосудистыми заболеваниями старше 75 лет, получавших лечение в условиях многопрофильного стационара. При анализе полученных данных отмечена тенденция преобладания факта падения у 1/3 (33,8%) пациентов в первые 5 дней пребывания в стационаре, что может быть ассоциировано с высоким лекарственным обременением и назначением «новых» для пациента средств. В исследовании отмечено, что именно в первые сутки происходил подбор терапии и часто назначались дополнительные лекарственные средства, что приводило к состоянию полипрагмазии. Анализ по отдельным группам препаратов смог достоверно подтвердить взаимосвязь назначения лекарственных средств, повышающих риск падения, и развития падений в отношении офтальмологической формы бета-адреноблокаторов (p=0,04). Полипрагмазия как фактор риска падений у геронтологических пациентов, описанная в научной литературе, в нашей работе также подтвердила свое негативное влияние. Таким образом, пациентов, «новых пользователей» лекарств, известных по негативному влиянию развития падения, можно отнести в группу риска по падению.