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Relevance. Self-development is a recognized existential value of the modern personality. This process requires taking into account many factors, including the influence of motivation and discipline. However, people do not fully realize the difference between them within the framework of self-development, which affects its effectiveness. The purpose of this work is to study the role of motivation and discipline in personal self-development, as well as a comparative assessment of their contribution to the formation of the meaningfulness of self-development of a person’s personality. Research methods: analysis of scientific literature from the field of psychology, pedagogy and sociology, observation, comparative analysis. Results. The study showed that many consider the contribution of motivation to the process of personal self-development more significant than discipline. The authors consider disciplined self-development to be more rational and effective for achieving success in any activity and self-development.

Relevance. The process of forming a student’s readiness for future professional activity requires a developed motivational sphere of personality. Professional motivation is the leading driving factor of successful learning. The actual needs of the individual here should have a close connection with their satisfaction through the solution of educational tasks related to the chosen field of activity. However, the authors note that the motives of admission to university for first-year students do not sufficiently coincide with the motives of learning a particular profession. The aim of the work was to pose the problem of insufficient use of the axiological approach in teaching as a condition for professional development. The research methodology is related to the substantiation of a value-based approach to choosing and obtaining a profession. Results. Analysis of the data obtained during the survey of 310 students showed that for the vast majority of them, higher education is an important factor for getting a high-paying job, but many also believe that even without higher education, a person is able to get a good job in life and get a prestigious profession. It is characteristic that respondents mostly consider their choice to be independent, positively affecting a person’s personal growth, however, almost a third of them prefer not to think about the fact that they will need to work according to the chosen profile. Such a choice cannot be called fully conscious. As a result, the motivation to learn and the quality of the educational result decreases. The authors come to the conclusion that the axiological approach in the learning process already in the first years allows them to direct their value orientations towards showing more interest in the chosen profession.

The urgency of the problem of formation and improvement of the level of financial literacy of the population is beyond doubt. By far, the most vulnerable social group here is the older generation. However, young people also need this competence. Purpose: this article describes the study of the level of financial literacy of generation Z and Y on the subject of knowledge of the operations of the gold and foreign exchange market; representations and concepts of modern economics; banking transactions; the subject of international trade, as well as international currency. Methods that were used in the research process: comparative analysis and synthesis, dialectical approach, sociological survey. Results: the authors conclude that Generation Z is less educated in terms of having and using financial knowledge than Millennials, and this is explained by the following facts: less life experience, focus only on the present, low interest in finance as a source of self-development opportunities.

The article has an interdisciplinary character related to the influence of the integration of medicine and pedagogy on the possibilities of studying Latin by medical students. The aim of the work is to analyze the transformation of the traditional principles of learning Latin in a medical university in the context of modernizing modern education. Concerning the methods of the study, the researchers relied on the principles of dialectics, general scientific methods of generalization, analysis and systematization, as well as questionnaires. SWOT-analysis was used for the first time in the work to achieve this goal. Results. The study showed that the traditional principles and methods of teaching Latin at a medical university are not able to fully ensure the formation of the necessary competencies, primarily general cultural ones. The advantages of traditional principles were highlighted: providing a rich terminological stock and knowledge of grammatical norms. The identified disadvantages include insufficient development of students’ horizons, a narrow professional perspective and a large amount of memorized material and low educational motivation. It is described that many innovative technologies are quite applicable here, but little in demand. The threat to slowing down their use is an increase in the load on the teacher, uncontrolled independent work of students and a decrease in the school’s general cultural base of future students.

Abstract Cystic fibrosis (CF, MIM# 219,700) is an autosomal recessive disease caused by pathogenic variants within the CFTR gene. It was shown that genetic variants located in cis can affect disease severity or treatment response because of additive or epistatic effects. Studies on the prevalence of complex alleles in Russian CF patients have just begun. Aim To evaluate frequencies and genetic background of complex alleles carrying c.1521_1523delCTT (F508del) and c.1399C>T (L467F), c.2562T>G (T854=) or c.4389G>A (Q1463=) in cis; to determine clinical consequences of complex allele c.[1399C>T;1521_1523delCTT] ([L467;F508del]) in Russian CF patients. Methods Sequencing of coding regions of CFTR gene and analysis of polymorphic markers in CF patients carrying F508del variant. Comparing of clinical features in two groups patients having genotypes [L467F;F508del];[F508del] (group 1) and [F508del];[F508del] (group 2). Results Frequency of [L467F;F508del] allele linked to 2–2–21–6–17–13 haplotype was 4.42%, of [F508del;T854=;Q1463=] allele linked to haplotype 1–2–21–6–17–13 – 2.2% in F508del chromosomes. No differences in disease severity in patients carrying complex allele [L467F;F508del] and patients homozygous for F508del was found. Conclusion The frequency of complex alleles associated with F508del was at least 6.6% in Russian CF patients, which should be taken into account for the decision on optimal treatment options with CFTR modulators.

Background: The problem of vitamin D deficiency is particularly relevant for the entire territory of Russia, since most parts of the country are located above the 42nd geographical latitude and the residents are therefore at risk of vitamin D deficiency. Despite the urgency of the problem, a comprehensive study of the molecular and genetic mechanisms and exogenous factors of vitamin D deficiency in children living in various geographical areas of the Russian Federation has not been conducted. Different variants in the loci of the genes responsible for the synthesis, hydroxylation, and transport of vitamin D (such as DHCR7, CYP2R1, CYP24A1, and GC), as well as VDR gene polymorphisms may also be associated with the risk of vitamin D deficiency. The aim of this study was to analyze the influence of exogenous factors on the blood levels of 25-hydroxyvitamin D (25(OH)D) in children of three regions of the Russian Federation, as well as the relationship of blood 25(OH)D levels with polymorphic variants of cytochrome P450 genes and VDR gene.Methods: We conducted blood 25(OH)D level analysis in 333 healthy children and adolescents in three regions located in different geographical zones of the Russian Federation. We studied the polymorphic variants c.1075A>C (I359L, rs1057910, CYP2C9*3) and c.430C>T (R144C, rs1799853, CYP2C9*2) in the CYP2C9 gene, c.1334T>C (M445T, rs4986910, CYP3A4*3), and CYP3A4*1B (c.-392C>T, rs2740574) in the CYP3A4 gene, 1846G>A, (rs3892097, CYP2D6*4) in the CYP2D6gene, TaqI (NM_000376.2: c.1056T>C; rs731236), FokI (NM_000376.2:c.2T>C; (rs2228570), and BsmI (NM_000376.2: c.1024+283G>A; rs1544410) in the VDR gene. We also analyzed the influence of exogenous factors on the level of 25(OH)D in children of the three study regions, as well as the relationship of the level of 25(OH)D with variants CYP2C9*2 (c.430C>T; R144C), CYP2C9*3 (c,1075A>C; I359L), CYP2D6*4 (1846G>A), CYP3A4*3 (c.1334T>C), and CYP3A4*1B (c.-392C>T) and rs731236, rs2228570 and rs1544410 in the VDR gene.Results: We found that the blood level of 25(OH)D depended on the geographical location and the number of sunny days per year. The average blood level of 25(OH)D in adolescent boys was statistically significantly lower than in girls of this age group. The level of 25(OH)D also significantly depended on the prophylactic dose of cholecalciferol administered to the subjects. In the study, it was shown that a dose of cholecalciferol ≥1,000 IU per day can achieve a normal level of 25(OH)D in healthy children. We found no statistically significant association between single-nucleotide polymorphic variants of cytochrome P450 genes (CYP2C9*3, CYP3A4*3, CYP2C9*2, CYP2D6*4, and CYP3A4*1B) and blood level of 25(OH)D in the subjects. We also did not find a relationship between the TaqI, FokI, and BsmI polymorphisms of the VDR gene and serum 25(OH)D concentration.Conclusion: Exogenous factors (time of year, place of residence, and prophylactic administration of cholecalciferol), as well as endogenous factors (age and sex), play a determining role in the development of vitamin D deficiency and insufficiency; in contrast to genetic factors—polymorphic variants of the genes of xenobiotic phase 1 enzymes (CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and the VDR gene—which do not play such role. This study shows the need to create a diagnostic algorithm for Vitamin D deficiency based on the age, season of the year, and prophylactic dose of cholecalciferol.

Background. The use of hypercaloric formulas in cystic fibrosis patients has the risks of negative effects on carbohydrate and lipid metabolism. Thus, it is interesting to analyze the efficacy of malnutrition correction and the safety of hypercaloric enteral products with a low glycemic index and with medium-chain triglycerides content of 50%.Objective. The aim of the study is analyze the efficacy of malnutrition correction with therapeutic hypercaloric product for enteral nutrition in children with cystic fibrosis.Methods. The study included patients aged from 3 to 18 years with malnutrition (BMI < 50 percentile) who were prescribed therapeutic hypercaloric formula to correct the malnutrition. Anthropometric indicators (height, body weight), actual nutritional status, pancreatin doses, lung function, carbohydrate metabolism rates, and cholestasis marker (bile acid concentration) were measured initially and after 1 month of using formula nutrition.Results. The children’ body weight (Me) has increased from 24.5 (21.2; 38.7) to 25.3 kg (21.6; 39.7) (p = 0.001), growth (Me) — from 133.5 (120.2; 146.5) to 136.5 cm (123.0; 148.5) (p < 0.001) after 1 month of using hypercaloric formula. The growth percentile increased from 33 to 40, the z-criterion values — from –0.5 to –0.3 SD (p < 0.001). There was no increase in BMI in dynamics due to the fact that the growth of children was ahead of body weight increase. The daily energy intake increased by an average of 450 kcal that was 21.8% regarding physiological need.Conclusion. The inclusion of hypercaloric formula in the diet of children with cystic fibrosis for 1 month significantly increases the indicators of linear growth and positively affects the overall physical development. There were no negative effect of formula on carbohydrate and lipid metabolism.

Cystic fibrosis (CF) is a genetically inherited disorder characterized by a wide range of clinical manifestations and genetic variations. This study focuses on the genetic and molecular epidemiology of CF in the Russian population, utilizing data from the national CF registry. The birth prevalence of CF in Russia has been analyzed over a span of years, revealing variations in frequency. The study delves into the genetic landscape of CFTR gene variants in Russian patients, showcasing a diverse spectrum with a predominance of severe variants, some of which are rare and distinct from global populations. A total of 233 variants have been documented, exhibiting frequencies ranging from 0.01% to 51.5%, with 47 of these variants remaining uncharted within international genetic databases. As of 2021, CFTR modulator therapy has been introduced for patients under 19 years, heightening the importance of genetic diagnosis. In 2023, more than 1,850 patients under 19 received CFTR modulator therapy. Notably, the impact of complex alleles on disease progression and response to targeted therapies is gaining recognition. Comparisons with European registries highlight distinctive features of the Russian population, such as differences in age distribution among patients. Additionally, the study emphasizes the need to ascertain clinical significance and pathogenicity of newly identified genetic variants, along with exploring their suitability for targeted therapies. The integration of genetic insights into the management of CF offers potential for enhanced personalized therapeutic interventions. In conclusion, this thorough analysis provides a comprehensive understanding of the genetic nuances within the Russian CF population. By illuminating the intricate relationship between genetic variations and disease manifestation, the study underscores the essential role of genetics in shaping therapeutic strategies and improving patient outcomes. Further research and ongoing genetic exploration are crucial for optimizing the care of individuals with CF in the era of evolving therapeutic options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Kondratyeva, Melyanovskaya, Sherman, Voronkova, Zhekaite, Krasovsky, Amelina, Kashirskaya, Shadrina, Polyakov, Adyan, Sсhagina, Starinova, Enina, Vasilyev, Marakhonov, Zinchenko and Kutsev.)

Complex alleles of the CFTR gene complicate the diagnosis of cystic fibrosis (CF), the classification of its pathogenic variants, affect the clinical picture of the disease and can affect the efficiency of targeted drugs. The total frequency of complex allele [L467F;F508del] in the Russian population of patients with CF is 0.74%, and in patients with the F508del/F508del genotype, its frequency reaches 8%. This article presents multi-faceted study of the complex allele [L467F;F508del] in a cohort of patients with genotypes [L467F;F508del]/class I (c.3532&#95;3535dup, c.1766+2T>C, W1310X, 712-1G>T), and data for a unique patient with the genotype [L467F;F508del]/[L467F;F508del]. Using the intestinal current measurement method, it was demonstrated the absence of CFTR function for [L467F;F508del]/class I and [L467F;F508del]/[L467F;F508del] genotypes. In intestinal organoids, it was shown that [L467F;F508del] in combination with class I variants and in the homozygotes abolishes the efficacy of both two-component (ivacaftor+lumacaftor; ivacaftor+tezacaftor) and three-component (ivacaftor+tezacaftor+elexacaftor) targeted drugs. When prescribing ivacaftor+tezacaftor+elexacaftor to three patients, they did not have a clinical effect after 6-12 months.

The pathogenic variant E92K (c.274G > A) of the CFTR gene is rare in America and Europe, but it is common for people with cystic fibrosis from Russia and Turkey. We studied the effect of the E92K genetic variant on the CFTR function. The function of the CFTR channel was studied using the intestinal current measurements (ICM) method. The effects of CFTR modulators on the restoration of the CFTR function were studied in the model of intestinal organoids. To assess the effect of E92K on pre-mRNA splicing, the RT-PCR products obtained from patients' intestinal organoid cultures were analyzed. Patients with the genetic variant E92K are characterized by an older age of diagnosis compared to homozygotes F508del and a high frequency of pancreatic sufficiency. The results of the sweat test and the ICM method showed partial preservation of the function of the CFTR channel. Functional analysis of CFTR gene expression revealed a weak effect of the E92K variant on mRNA-CFTR splicing. Lumacaftor (VX-809) has been shown to restore CFTR function in an intestinal organoid model, which allows us to consider the E92K variant as a promising target for therapy with CFTR correctors.

The presence of complex alleles in the CFTR gene can lead to difficulties in diagnosing cystic fibrosis and cause resistance to therapy with CFTR modulators. Tezacaftor/ivacaftor therapy for 8 months in a patient with the initially established F508del/F508del genotype did not lead to an improvement in her condition-there was no change in spirometry and an increase in the patient's weight, while there was only a slight decrease in NaCl values, measured by a sweat test. The intestinal current measurements of the patient's rectal biopsy showed no positive dynamics in the rescue of CFTR function while taking tezacaftor/ivacaftor. The assumption that the patient had an additional mutation in the cis position was confirmed by sequencing the CFTR gene, and the complex allele [L467F;F508del] was identified. Based on the rescue of CFTR function by elexacaftor/tezacaftor/ivacaftor obtained using forskolin-induced swelling on intestinal organoids, the patient was prescribed therapy with this targeted drug. The use of elexacaftor/tezacaftor/ivacaftor for 7 months resulted in a significant improvement in the patient's clinical condition.

In the cohort of Russian patients with cystic fibrosis, the p.[Leu467Phe;Phe508del] complex allele (legacy name [L467F;F508del]) of the CFTR gene is understudied. In this research, we present the results of frequency evaluation of the [L467F;F508del] complex allele in the Russian Federation among patients with a F508del/F508del genotype, its effect on the clinical course of cystic fibrosis, the intestinal epithelium ionic channel function, and the effectiveness of target therapy. The frequency of the [L467F;F508del] complex allele among patients with homozygous F508del was determined with multiplex ligase-dependent probe amplification followed by polymerase chain reaction and fragment analysis. The function of ionic channels, including the residual CFTR function, and the effectiveness of CFTR modulators was analyzed using intestinal current measurements on rectal biopsy samples and the forskolin-induced swelling assay on organoids. The results showed that the F508del/[L467F;F508del] genotype is present in 8.2% of all Russian patients with F508del in a homozygous state. The clinical course of the disease in patients with the F508del/[L467F;F508del] genotype is severe and does not vary from the course in the cohort with homozygous F508del, although the CFTR channel function is significantly lower. For patients with the F508del/[L467F;F508del] genotype, we can recommend targeted therapy using a combined ivacaftor + tezacaftor + elexacaftor medication.

In order to assess the effectiveness of the detection of cystic fibrosis (CF) patients by screening compared with diagnoses based on clinical manifestations, the data of the National CF Patient Registry (NCFPR) from the year 2012 (group I: children aged 6-9 years, diagnosed prior to the start of screening) were compared with the data in the NCFPR from the year 2015 (group II: children 6-9 years after the start of screening) for CF patients from the Moscow region. Homozygotes for c.1521&#95;1523delCTT (F508del) were separately compared in both groups. The average diagnosis age, genotype, body mass index, spirometry data, pulmonary infection, medications, and presence of complications were analyzed. This study demonstrated that in the c.1521&#95;1523delCTT (F508del) homozygote group, the patients diagnosed by screening had significant advantages over the patients born before the start of newborn screening in the diagnosis age, the number of patients with chronic Pseudomonas aeruginosa infection, the pulmonary function, and the growth in the percentiles. Newborn screening (NBS) detects nearly twice as many CF patients as the diagnostics based on clinical symptoms during the same time period. Importantly, patients will benefit from the early diagnosis of the disease and the early start of therapy., Competing Interests: Conflicts of InterestThe authors declare no conflict of interest., (© 2020 by the authors.)