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Antipsychotics (APs) are psychotropic drugs that generally have a psycholeptic effect, capable of reducing psychotic symptoms and psychomotor agitation. This class of drugs is widely used in psychiatric practice, especially for the treatment of psychosis in schizophrenia and other psychotic disorders. Most APs pass through a biotransformation process, or metabolism, after they enter the body before being eliminated. There are three phases of AP metabolism. Cytochrome P450 (CYP) monooxygenase (mixed-function oxidase) plays a central role in most AP biotransformation. CYP’s functional activity depends on gene–drug and drug–drug interaction and influences on the occurrence of adverse drug reactions (ADRs). So, it is extremely important for a practicing psychiatrist to know the oxidation pathway of APs, since most of them are metabolized in the liver. This is important both to prevent ADRs and to avoid unwanted drug–drug interactions, which will undoubtedly increase the effectiveness and safety of AP therapy.

The aim of this review was to analyze domestic and foreign publications reflecting the main existing theories of tension-type headache (TTH) development and the search for common pathogenetic links of TTH with arterial hypertension (AH) as potential triggers for the development of the clinical TTH and AH phenotype.Methods. We searched for articles in databases (eLibrary.ru, Web of Science, Scopus, PubMed, Clinical Case) by keywords. Search depth – 2006–2021.Results. The analysis allowed us to identify the leading theories underlying the development of TTH: psychogenic, vascular, myofascial, biochemical and neurogenic. At the same time, a neurobiological theory has been considered: it combines some of the mechanisms of previously studied pathogenetic theories of TTH. In addition, there are the most important (from the clinical point of view) mechanisms of the comorbidity of TTH and AH, which underlie the development of the TTH + AH phenotype. In terms of these mechanisms, in recent years, it is of scientific interest to study the role of nitric oxide (NO) and NO-synthases, since they play an important role not only in the development of the comorbidity of two diseases simultaneously existing in one patient (phenotype «TTH and AH», but also in modulating the response to drugs for the treatment of TTH and AH. Modulators of NO and NO-synthases, which have been developed in recent years, can improve the efficacy and safety of therapy for this phenotype.Conclusion. New approaches to predicting and disease-modifying therapy of the TTH and AH phenotype can increase the efficiency and safety of treatment, and improve the quality of life of patients, and reduce the risk of cardiovascular complications.

Th e condition of collagen fi bres in the skin directly aff ects its mechanical properties, which in turn aff ects the external condition of the skin, refl ecting the age of a person. Th at is why the genetic aspects of the synthesis, functioning and degradation of collagen fi bres are of great interest in cosmetology and dermatology. Quite a large number of patients turn to cosmetologists in order to correct the external manifestations of aging. Classically, procedures are carried out to correct collagen synthesis, but development of personalised pathogenetically based therapy of involutional skin changes requires understanding of features of the main links of exchange in collagen fi bres, including the processes of collagen degradation. Knowing clinical and genetic features of collagen metabolism in a particular subject, it is possible to assess the risk of premature skin ageing and develop a personalised patient management scheme. Th is review is devoted to genetic aspects of functioning of skin collagen fi bres and the features of their degradation.

Th e convulsive syndrome is an urgent and potentially life-threatening condition in neurological, pediatric and general medical practice. Over the past decade, there has been a reconsideration of the definition of epilepsy and epileptic syndromes, including the convulsive syndrome. Additionally, the arsenal of pharmaceuticals for the relief of seizures in children and adults has expanded. In this connection, this lecture was created in two parts: this second part will consider treatment of convulsive syndrome at the pre-hospital and the hospital stages. Th e lecture is intended for neurologists, pediatricians, general practitioners, emergency doctors, anesthesiologists. In the system of continuing medical education, convulsive syndrome is considered within the framework of the postgraduate training program for doctors of these specialties.

Alzheimer’s disease (AD) is the most common cause of dementia in the population. Late onset AD has a classic clinical picture with short-term memory deficit, apraxia and agnosia. Patients with early-onset AD may have an atypical clinical picture which complicates diagnosis. Atypical AD variants include the logopenic variant of primary progressive aphasia, posterior cortical atrophy, behavioral, biparietal, and cortico-basal variants. These variants have pathomorphological signs similar to classical AD, but at an early stage they are characterized by focal atrophy which explains their clinical polymorphism. This article provides a review of the current literature on atypical types of AD and presents a clinical case of a 62-year-old patient in whom the disease debuted with prosopagnosia due to focal atrophy of the temporo-occipital regions of the non-dominant hemisphere.

The majority of patients with alcohol dependence syndrome suffer from sleep disorders, particularly insomnia, associated with a number of critical clinical aspects, increased suicide risk, anxiety and depression. The authors of relevant publications indicate associations between polymorphic melatonin genes and melatonin metabolism and symptoms of sleep disorders. However, the literature review failed to reveal any studies on the role of genetic polymorphism of circadian rhythm regulators in sleep disorders in patients with alcohol dependence.Objective: to determine the associations of polymorphic variants of genes HTR2A, MTNR1A, MTNR1B, CLOCK, DRD2 with sleep disorders risk in alcohol dependence syndrome.Patients and methods. 307 patients with alcohol dependence syndrome were screened, including 61 women (21%) and 246 (79%) men (mean age – 41.92±7.9 years). The presence and severity of sleep disorders were assessed by the Insomnia Severity Index. In addition, 10 ml of venous blood sample was obtained from all participants. Genotyping of single nucleotide variants of HTR2A (rs6313), MTNR1A (rs34532313), MTNR1B (rs10830963), CLOCK (rs1801260), DRD2 (rs1800497) genes was performed using real-time polymerase chain reaction. Statistical analysis of the data was conducted using parametric and nonparametric methods.Results and discussion. The carriage of the *G allele of the polymorphic variant of the MTNR1B (rs10830963) gene, and its genotypes are associated with a greater risk of insomnia than the carriage of *С/*С genotype. The carriage of the *С allele of the polymorphic variant of the CLOCK (rs1801260) gene, as well as the *С/*Т genotype, are associated with the presence of sleep disorders. No associations between polymorphic variants of the HTR2A (rs6313), DRD2 (rs1800497) genes and insomnia risk were detected in patients with alcohol dependence syndrome.Conclusion. The found associations reveal prospects for future research on melatonin's role in the pathophysiology of sleep disorders in patients with alcohol dependence and pathogenetic therapy for insomnia.

The International Classification of Functioning, Disability and Health (ICF) is a globally recognized classification for health components and health-related factors, which has been recommended by the World Health Organization for use in medical rehabilitation. In the practice of a rehabilitation doctor dealing with patients suffering from juvenile myoclonic epilepsy (JME), the ICF is used to establish a rehabilitation diagnosis and formulate the goal of rehabilitation, as well as to implement its basic principles. It provides better insight into a range of difficulties patients with JME might face at the level of personal health and in everyday life.

Individuals who have suffered from novel coronavirus disease (COVID-19) are at risk for developing post-COVID neuropsychiatric disorders, which are an integral part of the Long COVID syndrome. Depression and/or anxiety are considered the most common psychiatric disorders after experiencing COVID-19. Certain antiepileptic drugs, notably, carbamazepine (CMZ), are effective in the treatment of mood disorders, especially as mood stabilizers in bipolar affective disorder (BAD), but the efficacy of CMZ in Long COVID remains to be established. The aim of the review was to investigate pharmacogenetic predictors of safety and efficacy of CMZ in patients with depressive symptoms of Long COVID during the post-infection period.We carried out a systematic search for publications in English and Russian on the safety and efficacy of CMZ in depressive disorders of different etiologies in the PubMed, Web of Science, Springer, Clinical Keys, Google Schooler, E-Library databases using keywords and combined word searches (carbamazepine, COVID-19, depression, epilepsy, post-COVID-syndrome) for the period from January 01,2020 to June 10, 2022.We review the main adverse drug reactions (ADRs) associated with CMZ, drug-drug interactions, and genetic predictors of the development of ADR. Here, we consider as risk factors, candidate genes for CMZ metabolism, CMZ transport, immunohistocompatibility genes, and candidate genes for QT prolongation.The choice of antidepressant treatment for patients with Long COVID is fraught because of the frequent occurrence of subclinical (interictal) epileptiform activity in the EEG. Consequently, antidepressant medications with a proconvulsant effect are contraindicated for Long COVID patients. CMZ may be a promising alternative for the treatment of depressive disorders in Long COVID states, given its mood-stabilizer, antidepressant, and antiepileptic profile.

Antipsychotic-induced parkinsonism (AIP) is one of the prognostically unfavorable complications of psychopharmacotherapy in patients with schizophrenia. Many studies have investigated various drugs that are used to treat this neurological side effect. This review analyzes drugs that are used and may be perspective for the treatment of AIP. We searched for full-text publications in Russian and English in the following databases: E-Library, PubMed, Web of Science, Springer, using keywords and combined word searches over the past decade (2011—2020). The review covers drugs that are promising for the correction of AIP, including anticholinergic drugs; NMDA receptor antagonists; dopamine receptor agonists; selective inhibitors of monoamine oxidase B; catecholamine transferase inhibitors; melatonin preparations; melatonin receptor agonists; benzodiazepines; herbal preparations traditionally used for the prevention and correction of extrapyramidal syndrome of various etiologies. Currently, a small number of medications are used in clinical practice for the treatment of AIP. However, not all of them are registered in the Russian Federation. Along with the differences in the mechanisms of AIP pathogenesis in specific patients, the limited choice of AIP treatments makes it difficult to solve the problem of adverse neurological complications of psychopharmacotherapy in schizophrenia.

Introduction : Hyaluronic acid (hyaluronan, HA) has become the most popular tool for improving the skin condition during aging, correcting wrinkles and other cosmetic defects. Objective : Analysis of the results of studies that reflect the pharmacogenomics of the synthesis, degradation, and reception of HA. Materials and methods : We searched for full-text publications in Russian and English in the E-Library, PubMed, Springer, Clinical keys, Google Scholar databases, using keywords and combined word searches (hyaluronic acid, hyaluronan, synthesis, degradation, reception, receptor, genetics), over the past decade. In addition, the review included earlier publications of historical interest. Despite our comprehensive searches of these commonly used databases and search terms, it cannot be excluded that some publications may have been missed. Results : The lecture examines: the role of ha in normal and aging human; genes involved in the synthesis ( HAS1, HAS2, HAS3 ), degradation ( HYAL1, HYAL2, HYAL3 ) and reception of ha ( CD44, HARE, RHAMM ); as well as the expression of their encoded proteins and enzymes in the skin. Conclusion : Expanding our knowledge of the pharmacogenomics of endogenous ha and increasing the exogenous HA drugs (used in anti-aging therapy and medical cosmetology) on the pharmaceutical market requires taking into account individual, including genetically determined, characteristics of the body of each individual patient to ensure an optimal balance of effectiveness/safety of exogenous HA from the point of view of personalized medicine

Antipsychotic drugs are a critical modality in managing of schizophrenia. Although medications can be highly effective, response varies and some patients derive considerably less benefit than others. Long-term use of antipsychotic drugs is associated with the development of adverse reactions. Te safety advantages of the atypical drugs havebeen questioned because of their propensity to induce weight gain and alter glucose and lipid metabolism. Antipsychotic-induced weight gain is a common cause of self-discontinuation of treatment and a significant deterioration in the quality of life in patients with schizophrenia. Te severity of adverse reactions when taking antipsychotics in different patients varies, which be associated with genetic factors. Antipsychotic induced weight gain is a major health concern and unfortunately, there is no predictive tool to identify who are high risk individuals. Te LEP, LEPR and NRY genes represents a compellings candidates for genetic studies of antipsychotic-induced weight gain. Candidate gene selection should rely on current knowledge on the molecular pathways to weight gain, antipsychotic pharmacokinetics and pharmacodynamics, as well as possible disease-related genetic links to the side effects under study. Pharmacogenetics will provide rational treatment based on matching antipsychotics to a patient’s DNA profile, thus, potentially providing effective treatment with minimal side effects to outliers and mean responders to a given antipsychotic medication.

Dabigatran etexilate is a prodrug of dabigatran, a oral direct inhibitor of thrombin. Pharmacokinetics of dabigatran etexilate doesn’t have the disadvantages of vitamin K antagonists. However, pharmacokinetics and pharmacogenetics of dabigatran are variable. This can affect both effectiveness and safety of anticoagulant therapy. It is considered that CES1 enzyme and P-glycoprotein (CES1 and ABCB1 genes accordingly) play important role in pharmacokinetics of dabigatran etexilate. UDP-glucuronosyltransferase enzymes UGT2B15, UGT1A9, UGT2B7 (UGT2B15, UGT1A9, UGT2B7 genes accordingly) take part in the metabolism of active dabigatran. Presence of these gene’s single-nucleotide variants (SNV) can affect effectiveness and safety of dabigatran etexilate usage. The goal of this review is analysis of associated researches of SNV genes CES1 and ABCB1 and search for new candidate genes that reveal effectiveness and safety of dabigatran etexilate usage.Materials and methods. The search for full-text publications in Russian and English languages containing key words “dabigatran etexilate”, “dabigatran”, “pharmacokinetics”, “effectiveness”, “safety” was carried out amongst literature of the past twenty years with the use of eLibrary, PubMed, Web of Science, OMIM data bases. Pharmacokinetics and pharmacogenetics of dabigatran etexilate are considered in this review. The hypothesis about UDP-glucuronosyltransferase enzymes influence on dabigatran metabolism was examined. Nowadays more than 2000 SNV CES1 and ABCB1 genes are identified, but their potential influence on pharmacokinetics of dabigatran etexilate and its active metabolite (dabigatran) in clinical practice needs to be further researched. Role of SNV UDP-glucuronosyltransferase genes (UGT2B15, UGT1A9, UGT2B7) in dabigatran’s effectiveness and safety is not explored enough. However, UGT2B15 gene can be a potential candidate gene for research on safety of this drug.

The aim of this study was to assess the dynamics of interhemispheric coherence (IC) as an indicator of integration of different areas of the brain and their participation in the performance of certain functions before and after wrist tapping (WT), using the author's method in juvenile myoclonic epilepsy (JME). Methods and Results: The study included 81 subjects of working age, including 51 clinically healthy volunteers (median age of 39[21;56] years) and 30 patients (median age of 27[23;38] years) with JME. Analysis of IC in the electrode pairs Fp1-Fp2, F3-F4, C3-C4, T3-T4 was performed using a computer encephalographic complex. A coherent EEG analysis was used to identify and evaluate the relationships between different areas of the brain. Based on the change in the coherence coefficients (CCs), the level of integrative activity of brain structures was quantified. In healthy volunteers, before and after WT, we observed a statistically significant decrease in CCs for the beta-1 band in the pairs Fp1-Fp2, F3-F4, and C3-C4 (P0.05). At the same time, a statistically significant decrease in CCs in the alpha band was found only in the frontal regions in the pairs Fp1-Fp2 and F3-F4 (P

General practitioners, therapists, and cardiologists do not have formal education (training) regarding cerebrocardial syndrome, primarily heart rhythm and conduction disorders in epilepsy and sudden unexpected death in epilepsy (SUDEP), as well as the potential arrhythmogenic effect of antiepileptic drugs. This lecture presents important elements of knowledge about the genetic predictors of cerebrocardial syndrome and SUDEP in juvenile myoclonic epilepsy, which is the most common form of genetic generalized epilepsy.

Convulsive syndrome is an urgent, potentially life-threatening condition in neurological, paediatric and general practice. Over the past decade, reconsideration has been committed in relation to the defi nition of epilepsy, epileptic syndromes, including convulsive syndrome with simultaneous expansion of the arsenal of medicinal products for cessation of convulsive seizures in children and adults. In this connection, we have prepared this lecture comprising two parts: the first part considers the defi nition, pathogenesis, aetiology and diagnosis of the convulsive syndrome. The lecture is designed for neurologists, paediatricians, general practitioners, ambulance physicians and anaesthesiologists-reanimatologists. Th e system of continuing medical education (CME) considers convulsive syndrome within the framework of the programme for postgraduate training of physicians in these specialities.

At the present time, the 4P concept (predictive, preventive, personalised and participatory) is a prospective trend in development of clinical medicine. The concept is being actively introduced into diff erent medical specialities. However, the development of personalised approach in medical cosmetology as a speciality at the intersection of medical sciences (dermatology, maxillofacial surgery, plastic surgery, restorative medicine, general practice, psychiatry, clinical pharmacology, etc.) is at the stage of discussion. The concept of 4P medicine suggests, among other things, analysis of genetic risks and development of preventive procedures based thereon that would decrease the risk of cosmetological complications development. The review includes analysis of literature dated 2010-2020. The following databases in Russian and foreign languages were searched using the keywords and advanced search builders: E-Library, PubMed, Springer, Clinicalkeys, Google Scholar. In this paper, we introduce a novel compilation of the known gene polymorphisms that may be used for determination of the genetic risks in cosmetological patients.

Tension-type headache (TTH) is the most common form of primary headache. The aim of the review is to analyse research on epidemiology and triggers of TTH. The search for full-text articles in Russian and English languages published within the past decade was performed in E-Library, PubMed, Springer, ClinicalKey and Google Scholar databases. A total of seven Russian and forty-two foreign epidemiological studies have been analysed. Thus, the global prevalence of TTH amounts to 32% (4.4% among these cases are chronic TTH). In Russia, its prevalence is 52.4%. The leading TTH triggers are stress and anxiety-depressive disorders. Insomnia, clinical and meteorological conditions, the ethnos and culture are possible triggers as well. Despite the high occurrence of this primary form of headache in clinical pictures of nervous diseases, it remains insufficiently considered to the date. The issue of TTH requires further investigation.

Objective: To study the effect of hand tapping on the synchronization of the alpha rhythm in healthy adults. Materials and Methods: The study included 51 clinically healthy volunteers of working age. Results: We have shown that under the influence of wrist tapping in a state of sensory deprivation in healthy adults there is a statistically significant change in the peak frequency (p = 0.0006) and peak power of the alpha rhythm (p = 0.0003), but the width of the peak plateau remains unchanged (p = 0.2). This effect of wrist tapping indicates the potential for clinical use in JME, since it was previously shown that if the selected external frequencies enter into resonance with the neurons of the antiepileptic system, then an antiepileptic effect can be obtained.

Background: The aim of this study was to assess the effect of wrist tapping (WT), according to the author's method, on the synchronization of alpha activity in healthy adults and patients with juvenile myoclonic epilepsy (JME). Methods and Results: The study included 71 people of working age, including 51 clinically healthy volunteers (median age - 39[21;56] years) and 20 patients with JME (median age 27[23;35] years). Under the influence of WT in a state of sensory deprivation, statistically significant changes in the alpha peak frequency (APF) (P

Edoxaban is a new generation of oral anticoagulant; it is selective, direct and reversible inhibitor of activated blood coagulation factor X (F Xa), serine protease responsible for thrombin formation. Edoxaban is used to prevent stroke in non-valvular atrial fibrillation, to treat deep vein thrombosis and pulmonary embolism. The purpose of the review is to analyze the associative studies of OHB of CYP3A4 / 5 and ABCB1 genes, as well as to search for new candidate genes reflecting the efficacy and safety of edoxaban. The search for full-text publications in Russian and English over the past two decades was carried out in eLibrary, PubMed, Web of Science, OMIM databases using the following keywords: edoxaban, pharmacokinetics, pharmacogenetics, efficacy, and safety. The review covers pharmacokinetics of edoxaban, as well as pharmacogenetic features of the drug metabolism in details. Candidate genes influencing concentration of edoxaban are genes encoding key enzymes of its metabolism – CES1, CYP3A4 / 5, ABCB1, and, to a lesser extent, SLCO1B1. By present day, numerous NVS of candidate genes have been identified. They potentially affect pharmacokinetics of edoxaban, but their role in real clinical practice requires further study

Amyotrophic lateral sclerosis (ALS) is an incurable chronic progressive neurodegenerative disease with the progressive degeneration of motor neurons in the motor cortex and lower motor neurons in the spinal cord and the brain stem. The etiology and pathogenesis of ALS are being actively studied, but there is still no single concept. The study of ALS risk factors can help to understand the mechanism of this disease development and, possibly, slow down the rate of its progression in patients and also reduce the risk of its development in people with a predisposition toward familial ALS. The interest of researchers and clinicians in the protective role of nutrients in the development of ALS has been increasing in recent years. However, the role of some of them is not well-understood or disputed. The objective of this review is to analyze studies on the role of nutrients as environmental factors affecting the risk of developing ALS and the rate of motor neuron degeneration progression. Methods: We searched the PubMed, Springer, Clinical keys, Google Scholar, and E-Library databases for publications using keywords and their combinations. We analyzed all the available studies published in 2010–2020. Discussion: We analyzed 39 studies, including randomized clinical trials, clinical cases, and meta-analyses, involving ALS patients and studies on animal models of ALS. This review demonstrated that the following vitamins are the most significant protectors of ALS development: vitamin B12, vitamin E > vitamin C > vitamin B1, vitamin B9 > vitamin D > vitamin B2, vitamin B6 > vitamin A, and vitamin B7. In addition, this review indicates that the role of foods with a high content of cholesterol, polyunsaturated fatty acids, urates, and purines plays a big part in ALS development. Conclusion: The inclusion of vitamins and a ketogenic diet in disease-modifying ALS therapy can reduce the progression rate of motor neuron degeneration and slow the rate of disease progression, but the approach to nutrient selection must be personalized. The roles of vitamins C, D, and B7 as ALS protectors need further study.

We studied the complex effect of genetic and non-genetic factors on the formation of opioid-associated resistance using machine learning methods in patients with chronic pain syndrome against the background of pancreatic cancer. Fifty-seven factors for predicting the realization of pharmacoresistance were studied in all examined Caucasian patients. The most significant predictive factors were determined and a software-analytical complex "Algorithm for assessing the significance of clinical and pathogenetic factors for predicting the safety of opioid therapy" was developed.

PERSONALIZED CHOICE OF OPIOID THERAPY IN A PATIENT WITH CHRONIC PAIN SYNDROME ON THE BACKGROUND OF PANCREAS CANCER: CLINICAL CASE REPORT

(1) Background: The purpose of this review is to analyze domestic and foreign studies on the role of collagen-encoding genes polymorphism in the development of intervertebral discs (IVDs) degeneration in humans. (2) Methods: We have carried out a search for full-text articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier and Google Scholar databases. The search was carried out using keywords and their combinations. The search depth was 5 years (2016–2021). In addition, this review includes articles of historical interest. Despite an extensive search, it is possible that we might have missed some studies published in recent years. (3) Results: According to the data of genome-wide and associative genetic studies, the following candidate genes that play a role in the biology of IVDs and the genetic basis of the processes of collagen degeneration of the annulus fibrosus and nucleus pulposus of IVDs in humans are of the greatest interest to researchers: COL1A1, COL2A1, COL9A2, COL9A3, COL11A1 and COL11A2. In addition, the role of genes COL1A2, COL9A1 and others is being actively studied. (4) Conclusions: In our review, we summarized and systematized the available information on the role of genetic factors in IVD collagen fibers turnover and also focused on the functions of different types of collagen present in the IVD. Understanding the etiology of impaired collagen formation can allow doctors to prescribe pathogenetically-based treatment, achieving the most effective results.

Regular physical activity in cyclic sports can influence the so-called “angiogenic switch”, which is considered as an imbalance between proangiogenic and anti-angiogenic molecules. Disruption of the synthesis of angiogenic molecules can be caused by local changes in tissues under the influence of excessive physical exertion and its consequences, such as chronic oxidative stress and associated hypoxia, metabolic acidosis, sports injuries, etc. A review of publications on signaling pathways that activate and inhibit angiogenesis in skeletal muscles, myocardium, lung, and nervous tissue under the influence of intense physical activity in cyclic sports. Materials: We searched PubMed, SCOPUS, Web of Science, Google Scholar, Clinical keys, and e-LIBRARY databases for full-text articles published from 2000 to 2020, using keywords and their combinations. Results: An important aspect of adaptation to training loads in cyclic sports is an increase in the number of capillaries in muscle fibers, which improves the metabolism of skeletal muscles and myocardium, as well as nervous and lung tissue. Recent studies have shown that myocardial endothelial cells not only respond to hemodynamic forces and paracrine signals from neighboring cells, but also take an active part in heart remodeling processes, stimulating the growth and contractility of cardiomyocytes or the production of extracellular matrix proteins in myofibroblasts. As myocardial vascularization plays a central role in the transition from adaptive heart hypertrophy to heart failure, further study of the signaling mechanisms involved in the regulation of angiogenesis in the myocardium is important in sports practice. The study of the “angiogenic switch” problem in the cerebrovascular and cardiovascular systems allows us to claim that the formation of new vessels is mediated by a complex interaction of all growth factors. Although the lungs are one of the limiting systems of the body in cyclic sports, their response to high-intensity loads and other environmental stresses is often overlooked. Airway epithelial cells are the predominant source of several growth factors throughout lung organogenesis and appear to be critical for normal alveolarization, rapid alveolar proliferation, and normal vascular development. There are many controversial questions about the role of growth factors in the physiology and pathology of the lungs. The presented review has demonstrated that when doing sports, it is necessary to give a careful consideration to the possible positive and negative effects of growth factors on muscles, myocardium, lung tissue, and brain. Primarily, the “angiogenic switch” is important in aerobic sports (long distance running). Conclusions: Angiogenesis is a physiological process of the formation of new blood capillaries, which play an important role in the functioning of skeletal muscles, myocardium, lung, and nervous tissue in athletes. Violation of the “angiogenic switch” as a balance between proangiogenic and anti-angiogenic molecules can lead to a decrease in the functional resources of the nervous, musculoskeletal, cardiovascular, and respiratory systems in athletes and, as a consequence, to a decrease in sports performance.

The purpose of this study was to explore the relationship between psycho-physiological markers of human health and dermatoglyphic indicators in young people. Materials and Methods: The study included 920 healthy volunteers aged between 18 and 21 years. All volunteers underwent the following examinations: EEG, an assessment of the anxiety level according to the BAI, and dermatoglyphic scanning. Results: According to the data obtained, there was a statistically significant strong negative correlation between the stress load indicator and dermatoglyphic data, such as the summary delta index (DI) and summary ridge count. A strong positive correlation was found between the percentage of whorls and stress (r=0.88). The predominant increase in anxiety is characteristic of persons with total ridge count (TRC) on the thumb of the right hand in the range from 19 to 23. Conclusion: Results demonstrate the interrelationships (association) between psycho-physiological (anxiety level, stress load indicator) and dermatoglyphic markers (DI, TRC and whorl pattern type) in young healthy people.

Dabigatran, rivaroxaban, apixaban, and edoxaban are direct oral anticoagulants (DOACs) that are increasingly used worldwide. Taking into account their widespread use for the prevention of thromboembolism in cardiology, neurology, orthopedics, and coronavirus disease 2019 (COVID 19) as well as their different pharmacokinetics and pharmacogenetics dependence, it is critical to explore new opportunities for DOACs administration and predict their dosage when used as monotherapy or in combination with other drugs. In this review, we describe the details of the relative pharmacogenetics on the pharmacokinetics of DOACs as well as new data concerning the clinical characteristics that predetermine the needed dosage and the risk of adverse drug reactions (ADRs). The usefulness of genetic information before and shortly after the initiation of DOACs is also discussed. The reasons for particular attention to these issues are not only new genetic knowledge and genotyping possibilities, but also the risk of serious ADRs (primarily, gastrointestinal bleeding). Taking into account the effect of the carriership of single nucleotide variants (SNVs) of genes encoding biotransformation enzymes and DOACs metabolism, the use of these measures is important to predict changes in pharmacokinetics and the risk of ADRs in patients with a high risk of thromboembolism who receive anticoagulant therapy.

Chronic pain syndromes are an important medical problem generated by various molecular, genetic, and pathophysiologic mechanisms. Back pain, neuropathic pain, and posttraumatic pain are the most important pathological processes associated with chronic pain in adults. Standard approaches to the treatment of them do not solve the problem of pain chronicity. This is the reason for the search for new personalized strategies for the prevention and treatment of chronic pain. The nitric oxide (NO) system can play one of the key roles in the development of peripheral pain and its chronicity. The purpose of the study is to review publications devoted to changes in the NO system in patients with peripheral chronical pain syndromes. We have carried out a search for the articles published in e-Library, PubMed, Oxford Press, Clinical Case, Springer, Elsevier, and Google Scholar databases. The search was carried out using keywords and their combinations. The role of NO and NO synthases (NOS) isoforms in peripheral pain development and chronicity was demonstrated primarily from animal models to humans. The most studied is the neuronal NOS (nNOS). The role of inducible NOS (iNOS) and endothelial NOS (eNOS) is still under investigation. Associative genetic studies have shown that single nucleotide variants (SNVs) of NOS1, NOS2, and NOS3 genes encoding nNOS, iNOS, and eNOS may be associated with acute and chronic peripheral pain. Prospects for the use of NOS inhibitors to modulate the effect of drugs used to treat peripheral pain syndrome are discussed. Associative genetic studies of SNVs NOS1, NOS2, and NOS3 genes are important for understanding genetic predictors of peripheral pain chronicity and development of new personalized pharmacotherapy strategies.

For more than 50 years, oral vitamin K antagonists were the choice of anticoagulant for the long-term treatment and prevention of arterial and venous thromboembolic events. In recent years, four direct oral anticoagulants (DOACs), dabigatran, rivaroxaban, apixaban and edoxaban have been compared with warfarin for thromboembolism prevention. These anticoagulants directly inhibit specific proteins within the coagulation cascade; in contrast, oral vitamin K antagonists inhibit the synthesis of vitamin K-dependent clotting factors. Dabigatran, a direct thrombin inhibitor, and rivaroxaban, apixaban and edoxaban, the factor Xa inhibitors, produce a more predictable, less labile anticoagulant effect. DOACs do not have limitations inherent vitamin K antagonists. DOACs have a predictable pharmacokinetic profile and are free of advers drugs reactions inherent in vitamin K antagonists. However, it is necessary to take into account the pharmacogenetic characteristics of the individual that can affect effectiveness and safety of use of DOACs. The results carried out to the present fundamental and clinical studies of DOACs studies demonstrate an undeniable the influence of genome changes on the pharmacokinetics and pharmacodynamics of DOACs. However, the studies need to be continued. There is a need to plan and conduct larger studies in various ethnic groups with the inclusion of sufficient associative genetic studies of the number of patients in each of the documented groups treatments with well-defined phenotypes.

The aim of our research was to study the multiphase response in a system of pro-inflammatory and anti-inflammatory cytokines due to the additive contribution of homozygous and heterozygous genotypes for the polymorphic allelic variants of the interleukin-1β (IL-1β) and interleukin-4 (IL-4) genes in patients with chronic adenoiditis (CA). Materials and Methods: The study included 388 children with CA. Associations between the IL1B gene (rs1143634) (C+3954T) SNP and the IL-4 gene (rs2243250) (C-589T) SNP and the clinical manifestations and clinical outcome of CA were investigated. Genotyping for the studied SNPs was performed using real-time PCR. The study of genotype-associated cytokine production in accordance with the level of concentration of IL-1β, IL-4 in blood serum with the method of solidphase EIA using horseradish peroxidase as an indicating enzyme was carried out. Results: The presence of homozygous or heterozygous genotypes of the studied SNPs of the IL-1β and IL-4 genes was characterized with genetically determined cytokine-production forming the phenotypical polymorphism. The conducted research into congenital immunity factors with an assessment of genetically determined cytokine production has revealed 5 options of the cytokine response and their corresponding frequencies. We extrapolated the results on clinical and functional outcomes of chronic adenoiditis, which allowed us to identify non-randomness in the nature of chronic adenoiditis as a multifactorial disease. Conclusion: The obtained data are evidence of the phenotypic-genetic heterogeneity of CA.

The aim of the present study was to assess the main characteristics of the tempo-rhythm in healthy adults. Materials and Methods: We examined 60 healthy adults without neurological and endocrinological pathology. Participants were divided into 2 groups. In Group 1 there were 33 adults without deviations on the scale of anxiety and depression were, and in Group 2, there were 27 persons with subclinically expressed anxiety according to the test results. The test was conducted using hospital anxiety and depression scale HADS. (6). The study was conducted using a modified original technique “Method of exogenous rhythmic stimulation influence on an individual human rhythm.” Results: We found that anxiety statistically significant affects the quantitative and qualitative parameters of wrist tapping (individual rhythm and rhythm stability) in healthy adults. Conclusion: The obtained data can be used in neurorehabilitation for patients with a wide range of neurological disorders, including epilepsy.

The purpose of our research was to study the association of the HTR2A T102C (rs6313) SNP with anthropometric and biochemical markers in patients treated with typical and atypical antipsychotics in monotherapy mode. Materials and methods: One hundred and seventeen white inpatients (95 men and 22 women) with F2 disorders (ICD-10, 1995) were enrolled in the study. All patients were divided into two groups by the antipsychotic class with which they were treated (Group 1 included 40 patients treated with typical antipsychotics; Group 2 included 77 patients treated with atypical antipsychotics) and two subgroups by weight change criteria during the study (Subgroup 1 included patients with weight change >6%; Subgroup 2 included patients with weight change 0.05). Kruskal-Wallis one-way analysis of variance between subgroups showed statistically significant differences between carbamide levels in the second visit in Group 2 (P=0.02). A Dunn post hoc test with Bonferroni adjustment showed statistically significant differences between TT and CT genotypes of the HTR2A T102C SNP: carbamide level was greater in TT carriers (P=0.02). The strength of associations and risks between alleles of the HTR2A T102C SNP and antipsychotic-induced weight change were as follows: ORC=0.49; CIC [0.25; 0.95]; RRC=0.58 CIC [0.35; 0.97]; ORT=2.03; CIT [1.05; 3.94]; RRT=1.7 CIT [1.02; 2.81]. Conclusion: Our results of the pilot pharmacogenetic studies show an association of the T allele carriage of the HTR2A T102C SNP with risk of antipsychotic-induced weight gain. The continuation of this study and an increase in the sample size will allow establishing valid pharmacogenetic markers for the risk of antipsychotic-induced weight gain.

Juvenile myoclonic epilepsy (JME) is a well-defined sub-syndrome of idiopathic generalized/genetic epilepsy, usually presenting in adolescence and characterized by myoclonic jerks, predominately in the arms, associated with tonic-clonic seizures and less often generalized absences. Although the evidence base for a relationship between JME and sleep disorders is weak, most experts regard sleep disorders as an actual comorbidity. This paper reviews the literature underpinning the development of sleep disorders in JME patients. Data that report associated causes of sleep problems in JME patients are discussed, as is the importance of counseling on lifestyle issues. Lastly, a practical approach to managing sleep disorders in young men and women with JME is summarized.

The role of mechanisms of the onset of opioid-induced hyperalgesia in patients with chronic pain syndrome of oncological genesis is highlighted according to the review of results of the search for Russian and English articles in the scientific bases of PubMed, Scopus, Web of Science, eLibrary. The importance of genetic factors predetermining the development of opioid-induced hyperalgesia is shown. The key role of pharmacological preparations for relief of chronic pain in the conditions of opioid-induced hyperalgesia is presented.

This review is dedicated to the issue of non-pharmacological treatment of epilepsy in the adult population in Russia and other countries. A literature review was conducted using international databases for the period between 2010 and 2017. A total of 64 full-text editions were included in this review, which allowed us to reveal the basic non-pharmacological epilepsy treatment options. However, not all of these options have a sufficient evidence base, and some of them are not always safe. Particularly, methods with a low level of evidence include acupuncture and aromatherapy. Further studies are needed to explore the methods aimed at eliminating the dominant epileptic system through the development of a new, more powerful dominant system. One of the methods that can influence the pathogenesis of epilepsy is physical activity for patients with epilepsy, since epileptiform activity is reported to disappear from the EEG during exercises. The positive results of the application of music therapy are also described in the modern literature. Specifically, according to the results of some studies, the positive effect of reducing the frequency of seizures was achieved in epileptic patients who listened to music during sleep over a year. However, these studies are not numerous, so they cannot constitute a high level of evidence. Therefore, care should be exercised in applying these methods in epileptic patients.

The purpose of this study was to develop a sequential process of personalized valproic acid (VPA) prescription in patients with epilepsy. Materials and Methods: We randomly selected 167 patients with epilepsy receiving VPA, based on carriage of CYP2C9*2 and/or CYP2C9*3 and therapeutic drug monitoring. The patients’ CYP2C9 status was determined by CYP2C9 genotyping before the beginning of anticonvulsant therapy. Results: The sequence of personalized valproic acid prescription has been developed. Conclusion: Using the sequential process of personalized VPA prescription will allow neurologists, psychiatrists and general practitioners to select starting and maintenance dosages of VPA with respect to the individual patient’s pharmacogenetic profile and thereby, significantly improve the safety of pharmacotherapy in epilepsy patients.

This case report presents a 24-year-old man with a long history of arrhythmogenic convulsive syncope, which was managed as a cryptogenic generalized PRE. During complex examination of the patient within the framework of preoperative screening for the purpose of neurosurgical treatment of PRE, an idiopathic SSS was diagnosed. The clinical diagnosis was changed. The patient underwent emergency surgery at the center for cardiac surgery. ECP was implanted, the seizures stopped, resulting in dramatically improved quality of life.

Charcot-Marie-Tooth (CMT) disease, which encompasses several hereditary motor and sensory neuropathies, is one of the most common neuro-muscular disorders. 80% of patients having CMT disease are diagnosed with per cavus deformity. Orthosis is widespread and varies widely in forms. The paper arises the necessity of habilitation at the earliest possible stage as only a few patients use it. The meta-analysis of 412 scientific papers concerning this problem demonstrates the getting better gate, balance and the stopping CMT progression which is scientifically proven. It is also shown that patients with CMT use low prevalence of orthotics, and demonstrate low compliance of patients (for various reasons), high expectations from this habilitation technique.

Epileptic seizures are a common symptom in brain tumor patients. The aim of the study: to investigate the features of oncogenic epilepsy in women of the fertile age. Material and methods. The study included 352 women aged of from 15 to 49 years, suffering from epilepsy. The examination consisted of an EEG and a high-field MRI investigation of the brain (1.5 Tc) with a scan interval of 1-2 mm. Results and discussion. Epilepsy against the background of volumetric brain formations was found in 15/139 (10.8%) patients with symptomatic focal epilepsy. The age of a debut of oncogenic epilepsy ranged from 2 to 38 years, the median was 14 years. Astrocytomas, found in 40% of cases, prevailed in the etiology of volumetric formations. A considerable time interval between the epileptic seizure debut and the high-field MRI examination was noted to result in the diagnosis of volumetric brain formation: median was 10.5 [2; 15] years. In the clinical picture of epilepsy there were dominated simple and complex focal seizures. Secondary-generalized tonic-clonic seizures were stopped in 60% of cases. The pharmacoinduced remission of oncogenic epilepsy was achieved in 3/15 (20%) cases. Conclusion. The low alertness of primary care physicians in terms of diagnosis of neuroncology in women of childbearing age was noted. The therapy of symptomatic oncogenic epilepsy was characterized by certain difficulties, caused by the growth of volume formation and/or gross cicatricial postoperative changes in the brain substance.

The authors present a literature review using materials provided in the following databases: “MedLine”, “PubMed”, “Wiley Online Library”, “Web of Science”, “Oxford University Press”, “SAGE Premier”, dated 1995–2016. The paper describes the results of current international studies on the role of cytokine genes polymorphisms in the genesis of chronic cancer pain. We emphasize the role of inter-individual differences based on genetic polymorphism of cytokines and their receptors in personalized anesthetic care and accompanying therapy in oncology.