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The study aimed to conduct a meta-analysis of studies comparing pharmacogenetically guided dosing of antidepressants with empiric standard of care. Publications referring to genotype-guided antidepressant therapy were identified via PubMed, Google Scholar, Scopus, Web of Science, Embase, and Cochrane databases from the inception of the databases to 2021. In addition, bibliographies of all articles were manually searched for additional references not identified in primary searches. Studies comparing clinical outcomes between two groups of patients who received antidepressant treatment were included in meta-analysis. Analysis of the data revealed statistically significant differences between the experimental group receiving pharmacogenetically guided dosing and the empirically treated controls. Specifically, genotype-guided treatment significantly improved response and remission of patients after both eight and twelve weeks of therapy, whereas no effect on the development of adverse drug reactions was observed. This meta-analysis indicates that the use of preemptive genotyping to guide dosing of antidepressants might increase treatment efficacy.

The subject of the study is the novelties introduced by the legislator into the criminal procedure legislation in 2016 on the possibility of termination of criminal prosecution against persons who have committed crimes of small and medium gravity for the first time, with the simultaneous application of another criminal law measure against them, a judicial fine. The object of the study is the emerging law enforcement practice arising in connection with the application of the norms on the judicial fine. The article pays special attention to the practical applicability of the rules on the judicial fine in relation to persons who have committed crimes of small and medium gravity for the first time, with the so-called formal (non-investigative) composition, as well as those who have committed attempted crimes. Various aspects of practical compensation by such defendants (suspects, defendants) for the harm caused by the crime are considered. The main result of the conducted research is the author's conclusion that a real proportionate compensation for any harm caused by a crime, as required by law, should be an indispensable condition for the application of the rules on a judicial fine, regardless of what kind of crime is in question: with a formal composition or material. The novelty of the research lies in the fact that the author analyzed statistical data on the application of novels about a court fine for the last 3 years, the existing trends in the application of a criminal law measure, a court fine against persons accused (suspects, defendants) of committing crimes with the so-called formal composition, as well as attempted crimes.

Diazepam is one of the most commonly prescribed tranquilizers for the therapy of alcohol withdrawal syndrome (AWS). However, diazepam therapy often turns out to be ineffective, and some patients experience dose-dependent adverse drug reactions. Previous studies have shown that the metabolism of diazepam involves the CYP2C19 isoenzyme, whose activity is highly dependent on polymorphism of the encoding gene.The study aimed to investigate the effects of CYP2C19*17 genetic polymorphisms on plasma and saliva concentrations of diazepam as well as its impact on the efficacy and safety rates of therapy in patients with AWS.The study was conducted on 100 Russian male patients suffering from the AWS who received diazepam injections at a dosage of 30.0 mg/day for 5 days. Genotyping was performed by real-time PCR with allele-specific hybridization. The efficacy and safety assessment was performed using psychometric scales.Based on the results of the study, we revealed differences in the efficacy and safety of therapy in patients with different CYP2C19 -806CT genotypes. Therapeutic drug monitoring revealed the statistically significant difference in the levels of diazepam plasma concentration: (CC) 251.76 (214.43; 310.61) vs. (CT+TT) 89.74 (54.18; 179.13); P = 0.003, and diazepam saliva concentration: (CC) 3.86 (3.22; 5.12) vs. (CT+TT) 0.79 (0.44; 1.56); P = 0.003.Our study showed the effects of CYP2C19*17 genetic polymorphisms on the efficacy and safety rates of diazepam. Furthermore, we revealed the statistically significant differences in plasma and saliva concentration levels of diazepam in patients carrying different genotypes.

Aims: To study the readiness of Russian physicians with experience and younger physicians undergoing clinical residency and postgraduate education to apply pharmacogenetic testing in their clinical practice. Materials & methods: The sociological study involved physicians (n = 378) living in different regions of the Russian Federation, as well as residents and graduate students (n = 185) of the Russian Medical Academy of Continuing Professional Medical Education. The survey consisted of 35 questions, and 23 were created on the online platform of professional surveys, Testograf.ru. Results: Every second respondent was willing to use pharmacogenetic testing in clinical practice to predict the efficacy and safety of medications in patients with cardiovascular disease (p = 0.06). Factors impeding the clinical implementation of pharmacogenetic testing in Russia were identified: physicians' ignorance of pharmacogenetics (p = 0.015), a lack of pharmacogenetic testing in clinical guidelines and treatment standards (p = 0.175) and a lack of economic justification for using pharmacogenetic testing (p = 0.320). Conclusion: Russian physicians have a positive attitude toward pharmacogenetic testing. However, the level of test implementation remains low.

Background: Previous studies have shown that haloperidol biotransformation is mainly metabolized by CYP2D6. The CYP2D6 gene is highly polymorphic, contributing to inter-individual differences in enzymatic activity, and may impact haloperidol biotransformation rates, resulting in variable drug efficacy and safety profiles. Objective: The study aimed to investigate the correlation of the CYPD6 activity with haloperidol's efficacy and safety rates in patients with alcohol-induced psychotic disorders. objective: To investigate the correlation of the CYPD6 activity with the efficacy and safety rates of haloperidol in patients with alcohol-induced psychotic disorders. Method: One hundred male patients received 5-10 mg/day haloperidol by injections for 5 days. The efficacy and safety assessments were performed using PANSS, UKU, and SAS-validated psychometric scales. Results: No relationship between haloperidol efficacy or safety and the experimental endogenous pharmacometabolomic marker for CYP2D6 activity, urinary 6-НО-ТНВС/pinoline ratio was identified. In contrast, we found a statistically significant association between haloperidol adverse events and the most common CYP2D6 loss-of-function allele CYP2D6*4 (p Conclusion: Evaluation of the single polymorphism rs3892097 that defines CYP2D6*4 can predict the safety profile of haloperidol in patients with AIPD, whereas metabolic evaluation using an endogenous marker was not a suitable predictor. Furthermore, our results suggest haloperidol dose reductions could be considered in AIPD patients with at least one inactive CYP2D6 allele.

Introduction: Selective serotonin reuptake inhibitors have a common and increasing use for the treatment of patients diagnosed with depressive disorders. Some of them do not respond adequately to therapy, and numerous previous studies have indicated an increased risk of type A adverse drug reactions. Objective: The objective of our study was to evaluate the effect of 1846G>A polymorphism of CYP2D6 on the concentration/dose ratio of paroxetine. Material and methods: The study enrolled 267 patients with depressive episode (average age, 40.3 ± 14.3 years). Therapy included paroxetine in an average daily dose of 25.1 ± 9.5 mg per day. The efficacy and safety rates of treatment were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Therapeutic drug monitoring has been performed using high-performance liquid chromatography mass spectrometry (HPLC-MS/MS). Results: Our study revealed the statistically significant results in terms of treatment efficacy (Hamilton Depression Rating Scale scores): ( GG) 2.0 [1.0; 3.0] and ( GA) 4.0 [2.0; 5.0], p Conclusion The effect of CYP2D6*4 genetic polymorphism on the efficacy profile of paroxetine was demonstrated in a group of 267 patients with depressive disorder.

ABCB1 gene polymorphisms are associated with rivaroxaban distribution changes and adverse reactions but the data are controversial.To evaluate the influence of ABCB1 (rs1045642 and rs4148738) gene polymorphisms on rivaroxaban pharmacokinetics in patients aged 80 years and older with nonvalvular atrial fibrillation (NAF).128 patients aged 80 years and older (median [Me] age 87.5 [83.0-90.0] years) with NAF were included. We performed ABCB1 (rs1045642 and rs4148738) genotyping, measured the trough steady-state plasma concentration (CCC genotype carriers had no differences in CABCB1 (rs1045642 and rs4148738) polymorphisms didn't influence rivaroxaban pharmacokinetics in patients aged 80 years and older with NAF. TT carriers developed CRNMB more frequently compared with the CC rs1045642 and the CC and CT rs4148738 genotypes. The haplotype TT-TT haplotype was associated with a higher frequency of CRNMB.

Relativistic rotation causes a change of QCD critical temperatures. Various phenomenological and effective models predict a decrease of the critical temperatures in rotating QCD. Nevertheless, lattice simulations showed that the critical temperature in gluodynamics increases due to rotation. We extend the lattice study to the theory with dynamical fermions. We present the first lattice results for rotating QCD with $N_f=2$ dynamical clover-improved Wilson quarks. We also study separately the effect of rotation on gluonic and fermionic degrees of freedom. It is shown that separate rotations of gluons and fermions have opposite effects on the critical temperatures. In aggregate, the pseudo-critical temperatures in QCD increase with angular velocity. Dependence of the results on the pion mass is also discussed., Comment: 10 pages, 5 figures, Proceedings of the 39th International Symposium on Lattice Field Theory, 8th-13th August, 2022, Bonn, Germany

This article deals with installations with complex and nonstandard executive instrument movement. Having analyzed the technical implementation and operational features of cold-rolling pipe mills, the research team formulated the problem of synthesizing electric drives of auxiliary mechanisms. It is shown that the conditions for choosing a mechanical converter are associated with the oscillation of the processes of the electric drive system. The finite element method and the gradient descent method are used for structural analysis of solids and electromagnetic calculations. The data of the specific cost of semiconductor converters were analyzed using a linear least-squares regression technique. The advantages of a synchronous reluctance motor of independent excitation for the electric drives of auxiliary mechanisms are given and substantiated. The optimization of the geometrical parameters of the electromechanical converter was carried out according to the maximum developed electromagnetic torque. Modern semiconductor technology in the design of special-purpose electric drives leads to a revision of the principles for determining the optimal number of phases and the structure of the motor power supply. The rationale for the use of multilevel frequency converters is given. Taking into account an in-depth preliminary analysis and an integrated approach, these tasks were successfully completed, which was confirmed experimentally at the implementation of the developed system.

Purpose The aim of this study was to determine the impact of ABCB1 (MDR1) rs1045642 polymorphisms on the efficacy and safety of amlodipine in Caucasian patients. Patients and methods The 12-week study included 100 patients. Patients with the newly diagnosed stage I–II hypertension (HT) were recruited to complete genotyping of the rs1045642 single-nucleotide polymorphism (SNP). The study design did not include a control group. Before treatment, all patients either did not undergo antihypertensive treatment at all or did not receive regular antihypertensive therapy. The initial dose was 5 mg/day. Four office blood pressure measurements, two 24-hour noninvasive ambulatory blood pressure measurements, and questionnaires of Tsvetov were used to evaluate the efficacy and safety of amlodipine. Results and conclusion The highest antihypertensive effect in combination with the lowest incidence of adverse reactions was observed in the TT group, while patients with the CC genotype showed a low antihypertensive effect and the highest incidence of adverse effects. Patients with the CC genotype presented with adverse effects predominantly in the form of edema. A total of 33 patients reached the target blood pressure (SBP