Modeling of temperature fields of details during laser hardening using the method of polyargument systems

Представлено дані математичного моделювання теплового стану ріжучого інструменту в умовах лазерного загартування. Розглядаються особливості реалізації методу поліаргументних систем для розв’язання тривимірної задачі теплопереносу з локалізованим рухомим джерелом лазерного нагріву. Наводяться дані числових досліджень щодо встановлення закономірностей впливу радіуса плями нагріву на температурний режим зміцнюваного інструменту. Показано, що варіювання даного параметра може використовуватися як ефективний спосіб впливу на тепловий стан ріжучого інструменту в процесі його загартування променем лазера. Представлено результати моделювання температурних режимів інструмента в широкому практично важливому діапазоні зміни його кута заточки.The data of mathematical modeling of the thermal state of a cutting tool under conditions of laser hardening are presented. The features of the implementation of the method of polyargument systems for solving the three-dimensional heat transfer problem with a localized movable laser heating source are considered. The data of numerical studies to establish patterns of the influence of the radius of the heating spot on the temperature regime of the hardened tool are presented. It is shown that varying this parameter can be used as an effective way of influencing the thermal state of a cutting tool during its hardening by a laser beam. The results of modeling the temperature conditions of the tool in a wide practically important range of changes in its sharpening angle are presented.Представлены данные математического моделирования теплового состояния режущего инструмента в условиях лазерной закалки. Рассматриваются особенности реализации метода полиаргументных систем для решения трехмерной задачи теплопереноса с локализованным подвижным источником лазерного нагрева. Приводятся данные численных исследований по установлению закономерностей влияния радиуса пятна нагрева на температурный режим упрочняемого инструмента. Показано, что варьирование данного параметра может использоваться в качестве эффективного способа воздействия на тепловое состояние режущего инструмента в процессе его закалки лучом лазера. Представлены результаты моделирования температурных режимов инструмента в широком практически важном диапазоне изменения его угла заточки

Klotho protein in men with type 2 diabetes mellitus blood and its association with cardiometabolic risk factors

The aim of the study was to investigate Klotho protein levels in men with type 2 diabetes blood and its associations with several cardiometabolic risk factors. Material and methods. The study included 37 men with diabetes and 141 men without diabetes. Fasting blood samples were collected to measure Klotho protein levels and some biochemical parameters. Results and its discussion. The Klotho protein level in men with diabetes was significantly lower than in men without diabetes (374 [117; 500] and 515 [315; 1009] pg/dl, p<0.0001). Among the examined men with diabetes with a glomerular filtration rate of less than 60 ml/min/1.73 cm2, the concentration of Klotho protein was 4 times lower than in the comparison group (104 [93; 118] and 413 [147; 535] pg/dl, p = 0.014) In men with diabetes, the Klotho protein was inversely correlated with the ratio of waist to hip circumference (-0.329; p = 0.047). But with multivariate analysis, only a tendency towards a negative association of the Klotho protein with abdominal obesity was determined (-0.385, p = 0.078). Conclusion. The content of Klotho protein in men with diabetes is significantly lower, especially in middle-aged men and in those with a reduced glomerular filtration rate. In men with diabetes, the Klotho protein has a negative correlation with the presence of abdominal obesity. In a multivariate analysis among men with diabetes, the Klotho protein tends to be inversely associated with the presence of abdominal obesity

Searching for new genes associated with the familial hypercholesterolemia phenotype using whole-genome sequencing and machine learning

One of the most common congenital metabolic disorders is familial hypercholesterolemia. Familial hyper-cholesterolemia is a condition caused by a type of genetic defect leading to a decreased rate of removal of low-density lipoproteins from the bloodstream and a pronounced increase in the blood level of total cholesterol. This disease leads to the early development of cardiovascular diseases of atherosclerotic etiology. Familial hypercholesterolemia is a monogenic disease that is predominantly autosomal dominant. Rare pathogenic variants in the LDLR gene are present in 75–85 % of cases with an identified molecular genetic cause of the disease, and variants in other genes (APOB, PCSK9, LDLRAP1, ABCG5, ABCG8, and others) occur at a frequency of < 5 % in this group of patients. A negative result of genetic screening for pathogenic variants in genes of the low-density lipoprotein receptor and its ligands does not rule out a diagnosis of familial hypercholesterolemia. In 20–40 % of cases, molecular genetic testing fails to detect changes in the above genes. The aim of this work was to search for new genes associated with the familial hypercholesterolemia phenotype by modern high-tech methods of sequencing and machine learning. On the basis of a group of patients with familial hypercholesterolemia (enrolled according to the Dutch Lipid Clinic Network Criteria and including cases confirmed by molecular genetic analysis), decision trees were constructed, which made it possible to identify cases in the study population that require additional molecular genetic analysis. Five probands were identified as having the severest familial hypercholesterolemia without pathogenic variants in the studied genes and were analyzed by whole-genome sequencing on the HiSeq 1500 platform (Illumina). The whole-genome sequencing revealed rare variants in three out of five analyzed patients: a heterozygous variant (rs760657350) located in a splicing acceptor site in the PLD1 gene (c.2430-1G>A), a previously undescribed single-nucleotide deletion in the SIDT1 gene [c.2426del (p.Leu809CysfsTer2)], new missense variant c.10313C>G (p.Pro3438Arg) in the LRP1B gene, and single-nucleotide deletion variant rs753876598 [c.165del (p.Ser56AlafsTer11)] in the CETP gene. All these variants were found for the first time in patients with a clinical diagnosis of familial hypercholesterolemia. Variants were identified that may influence the formation of the familial hypercholesterolemia phenotype

NEW METHOD OF PERSONIFIED EVALUATION OF RISK OF CARDIOVASCULAR DISEASES BY THE COEFFICIENT OF ATHEROGENICITY

The aim of the work is to develop a new atherogenic coefficient as a personalized method for assessing cardiovascular risk in patients with dyslipidemia. Materials and methods. The subject of the study was a sample of men and women ( n = 100 people) with lipid metabolism disorders aged 50-70 years (mean age 58.7 ± 3.2 years) without documented cardiovascular pathology, diabetes mellitus, hereditary dyslipidemia. As a result of the research, a new CA was created and tested, including additional non-lipid risk factors, which was calculated using the formula: risk SCOREЧ(non-HDL-C/HDL-C). Results and discussion. Positive correlation of coefficient values with conventional factors of cardiovascular risk: age, levels of TC and LDL cholesterol, systolic blood pressure, lipid coefficient of atherogenicity, and estimated risk for SCORE, the latter being the strongest. Negative, reliable correlation of the new CA was found with the female sex of patients. Important for clinical practice is the fact that it does not require invasive intervention and significant time and material costs for an additional examination

Analysis of association of rs9536314 of the KL gene with anthropometric and biochemical indicators in men of Novosibirsk (West Siberia)

Purpose of the study. To determine the frequency of the rs9536314 (F325V) polymorphism of the KL gene and the association of this variant with a number of biochemical and anthropometric parameters in men of the study group and in the Caucasian population of Western Siberia. Materials and methods. The study group (69 men, average age 61.2 ±11.5 years) was randomly formed from a sample of persons who applied to the clinic and polyclinic of NIITPM - a branch of the ICG SB RAS and GBUZ NSO Hospital of war veterans No. 3 (178 men, aged 50-65 years old and over 80 years old). The population group was randomly selected (219 people) from the sample surveyed within the framework of the International Multicenter Project "Risk Factors for Cardiovascular Diseases in Eastern Europe" HAPIEE (9360 participants, 45–69 years old, mean age 53.8±7 years old, Caucasians > 90 %). Biochemical parameters were determined by standard enzymatic methods. Serum concentration of Klotho protein was measured by ELISA. Genomic DNA was amplified by polymerase chain reaction in a standard reaction mixture and further digested with TaqI B restriction enzyme. Results. The frequency of genotypes (TT, TG, and GG) and alleles (T and G) rs9536314 of the KL gene in the study group corresponds to the data in the population of Western Siberia, as well as the population of Western and Eastern Europe. There were no statistically significant differences in the mean values of the studied clinical and biochemical parameters depending on the rs9536314 genotypes of the KL gene in the study group and in the population. In the study group, the level of Klotho protein in the blood and the glomerular filtration rate in men with coronary heart disease and arterial hypertension did not differ in the autosomal dominant and autosomal recessive models for the rs9536314 KL gene. Conclusion. Thus, the frequency of the rs9536314 polymorphism of the KL gene in the study group corresponds to the frequency of the rs9536314 polymorphism of the KL gene in the Caucasian population of Western Siberia. Biochemical and anthropometric parameters, as well as the Klotho protein, do not have statistically significant differences depending on the genotypes of rs9536314 of the KL gene in the examined men

Особенности содержания белка Клото в крови у мужчин с артериальной гипертонией и его ассоциации с кардиометаболическими факторами риска

Aim. To study serum levels of Klotho protein in men with arterial hypertension and to explore its association with some cardiometabolic risk factors.Methods. 134 men with hypertension aged 50-65 years old and over 80 years old were enrolled in a study. 44 men of the corresponding age without high blood pressure were enrolled in the control group. Serum levels of Klotho protein were measured using ELISA.Results. Both, the study and the control group, have similar serum levels of Klotho protein (464 [287; 849] and 458 [128; 1121] pg/dL, respectively; p>0.05). Significant differences in the serum levels of Klotho protein in the study groups are related to three risk factors: physical inactivity, obesity, and the presence of diabetes mellitus. A positive correlation between Klotho protein levels and regular physical activity has been found in men with arterial hypertension. Besides, negative correlations between Klotho proteins and diabetes mellitus and obesity have been stated. Multivariate analysis reports a positive association between Klotho protein and regular physical activity in men with hypertension regardless of their age, diabetes, lipid disorders, and obesity.Conclusion. Men with arterial hypertension and without it have similar Klotho protein levels. Serum Klotho protein levels are lower in obese men who are physically inactive. Klotho protein levels are lower in men with hypertension and concomitant diabetes mellitus. Klotho protein is positively associated with regular physical activity regardless of age and some cardiometabolic risk factors in men with arterial hypertension.Цель. Изучить уровень сывороточного белка Клото у мужчин с артериальной гипертонией и его ассоциации с кардиометаболическими факторами риска сердечно-сосудистых заболеваний.Материалы и методы. В исследование выключены 134 мужчины в возрасте 50-65 лет и старше 80 лет с диагнозом «гипертоническая болезнь». Группу сравнения составили 44 мужчины соответствующего возраста без повышенного артериального давления. Уровень сывороточного белка Клото измерен с помощью иммунофер-ментного метода.Результаты. У мужчин с артериальной гипертонией и в группе сравнения количество белка Клото оказалось одинаковым (464 [287; 849] и 458 [128; 1 121] пг/мл соответственно; p>0,05). Значимые различия уровня белка Клото между исследуемыми группами выявлены только в отношении трех факторов риска: сниженная физическая активность, ожирение и наличие сахарного диабета. В группе мужчин с артериальной гипертонией определена положительная корреляционная связь белка Клото с наличием регулярной физической активности и отрицательные корреляционные связи белка Клото с сахарным диабетом и ожирением. При многофакторном анализе сохранилась положительная ассоциация между белком Клото и наличием регулярной физической активности у мужчин с гипертонией вне зависимости от возраста, сахарного диабета, липидных нарушений и ожирения.Заключение. Уровень белка Клото у мужчин с артериальной гипертонией и без гипертонии не различается. Сывороточный белок Клото значительно ниже у мужчин с ожирением и без регулярной физической активности. Уровень белка Клото ниже у лиц при сочетании гипертонии с сахарным диабетом. У мужчин с артериальной гипертонией белок Клото положительно ассоциирован с наличием регулярной физической нагрузки вне зависимости от возраста и кардиометаболических факторов риска сердечно-сосудистых заболеваний

Implemented models and perspectives of managing lipid metabolism disorders. Concept of rare lipid disease centers

Despite the advances in lipidology over the past decade, the control of dyslipidemia at the population level in Russia, as in a number of European countries, remains unsatisfactory. The need for novel organizational approaches to solving the problem at the regional and federal levels is obvious. This publication provides an overview of the implemented projects and the successful practical experience of lipid centers in Russia, as well as the prospects for the development of novel models that will optimize the care provision for patients with lipid metabolism disorders at the population level