Background and Aims : Subjects with familial hypercholesterolemia (FH) are characterized by an increased amount of LDL-C that promotes a development of early atherosclerosis. Our aim was to evaluate the effect of PCSK9-i on atherosclerosis damage analyzed by cardio-ankle vascular index (CAVI) in a cohort of FH subjects.Methods: In this prospective observational study, we included 54 FH subjects on moderate or high-intensity statins with or without ezetimibe. All subjects were placed on PCSK9-i therapy (Evolocumab 140 mg SC q2weeks) and biochemical analysis as well as CAVI evaluation at baseline and after twelve months of PCSK9-i therapy was obtained.Results: The mean age of the patients was 52.5±1.69 with DCLN of 7.98±0.3 and 70.3% with previous myocardial infarction or proven coronary disease. After 12 months there were a significant reduction of LDL-C (-3.21 mmol/l, 95% CI -2.49 to -3.92 mmol/l) and non HDL-C (-4.43 mmol/l, 95% CI -3.04 to -5.83 mmol/l). The proportion of patients reaching the target LDL levels according to the 2016 and 2019 ESC / EAS guidelines were 62.5% and 45% respectively. In the group taking double lipid lowering therapy (high intensity statin with PCSK9-i, n=30, 55.6%) and triple LLT (with ezetimibe, n=15, 27.8%) we noticed a profound improvement of CAVI which was more pronounced in the latest group (- 14.5% and 20.4%, p < 0.05).Conclusions: In addition to the reduction in atherogenic lipids and better achievment of targets, we also found a significant improvement in arterial stiffness among high-risk patients with FH. The observed effect depends on the intensity of lipid-lowering therapy. Background and Aims : Subjects with familial hypercholesterolemia (FH) are characterized by an increased amount of LDL-C that promotes a development of early atherosclerosis. Our aim was to evaluate the effect of PCSK9-i on atherosclerosis damage analyzed by cardio-ankle vascular index (CAVI) in a cohort of FH subjects. Methods: In this prospective observational study, we included 54 FH subjects on moderate or high-intensity statins with or without ezetimibe. All subjects were placed on PCSK9-i therapy (Evolocumab 140 mg SC q2weeks) and biochemical analysis as well as CAVI evaluation at baseline and after twelve months of PCSK9-i therapy was obtained. Results: The mean age of the patients was 52.5±1.69 with DCLN of 7.98±0.3 and 70.3% with previous myocardial infarction or proven coronary disease. After 12 months there were a significant reduction of LDL-C (-3.21 mmol/l, 95% CI -2.49 to -3.92 mmol/l) and non HDL-C (-4.43 mmol/l, 95% CI -3.04 to -5.83 mmol/l). The proportion of patients reaching the target LDL levels according to the 2016 and 2019 ESC / EAS guidelines were 62.5% and 45% respectively. In the group taking double lipid lowering therapy (high intensity statin with PCSK9-i, n=30, 55.6%) and triple LLT (with ezetimibe, n=15, 27.8%) we noticed a profound improvement of CAVI which was more pronounced in the latest group (- 14.5% and 20.4%, p < 0.05). Conclusions: In addition to the reduction in atherogenic lipids and better achievment of targets, we also found a significant improvement in arterial stiffness among high-risk patients with FH. The observed effect depends on the intensity of lipid-lowering therapy.

Background and Aims: The objective of this study was to evaluate if a polymorphism of several candidate genes were associated with the presence of carotid and peripheral atherosclerosis in 200 patients with angiographically proven coronary artery disease

Установлено регуляторное влияние лизинсодержащих пептидов Arg-Lys-Lys-Arg-Pro-Gly-Pro (RKKRPGP) и Lys-Arg-Lys-Pro-Gly-Pro (KRKPGP) на процессы свертывания крови животных. Многократное в течение 7 сут через каждые 24 ч пероральное или интраназальное введение пептидов в ежедневной дозе 100 мкг/кг массы тела крыс приводило к снижению антитромбоцитарной активности на 29 – 49 %, активности фактора XIIIa — на 15 – 49 %. При этом повышалась антикоагулянтная активность плазмы крови крыс по тесту активированного частичного тромбопластинового времени на 16 – 33 %, по тесту тромбинового времени — на 23 – 57 %. Кроме того, под влиянием пептида KRKPGP снижалась концентрация свертываемого тромбином фибриногена на 47 – 49 %. Поскольку оба пептида при пероральном и интраназальном применении в разной степени проявляли в здоровом организме антитромбоцитарную, антикоагулянтную активность и снижали активность фактора свертывания ХШа, сделан вывод, что лизинсодержащие пептиды участвуют в регуляции свертывания крови и могут считаться перспективными антитромботическими веществами.

Despite its high prevalence and negative impact, sleep-disordered breathing (SDB) remain commonly underdiagnosed and undertreated in stroke subjects. Multiple stroke comorbidities and risk factors, including obesity, hypertension, diabetes mellitus, ischemic heart disease, atrial fibrillation, and heart failure (H.F.) have been associated with SDB. This study aimed to examine associations of clinical and demographic characteristics with moderate-to-severe SDB (msSDB) in stroke patients and to develop a predictive score.Consecutive patients with ischemic stroke were enrolled in an open, prospective study. SDB was assessed using standard polysomnography. Clinical and demographic characteristics, as well as findings from echocardiography, entered the analysis. Multivariate logistic regression models were used to examine the associations with msSDB. Based on the results, an original score to predict msSDB was proposed and tested.120 patients with acute ischemic stroke (mean age: 64.0 ± 12.2 years, median NIHSS: 4) were included. Body-mass index (BMI), wake-up stroke onset (WUS), and diastolic dysfunction were independently associated with msSDB. A score allocating 1 point for BMI≥25 kg/m2 and <30 kg/m2, 2 points for BMI≥30 kg/m2, 1 point for WUS and 1 point for diastolic dysfunction resulted in an area under the curve of 0.81 (95% CI 0.71–0.90, p<0.001), sensitivity 82.9%, specificity 71.9% to identify stroke patients with msSDB.BMI, WUS, and diastolic dysfunction were associated with msSDB. A simple score might help to identify acute stroke patients with msSDB, who are usual candidates for positive airway pressure therapy.

We proposed a method to help researchers create novel research ideas using bibliometrics. Different concepts and techniques exist in different research areas, and when the fields are sufficiently similar, a salient combination of two different areas can lead to the development of novel research. We have assumed that two different research areas, sharing a high number of similar keywords, would be excellent candidates for integration. We combined link mining and text mining techniques to elucidate hidden but implicit opportunities among apparent, explicit research clusters. To demonstrate the effectiveness of our approach, we conducted a case study on fuel cells and ammonia synthesis. Fuel cells are a rapidly growing research field, while ammonia synthesis is relatively mature. Our results successfully extracted a plausible and post-mature research idea.

Temperature-responsive star-shaped poly(2-ethyl-2-oxazoline) (star-PETOX) and poly(2-isopropyl-2-oxazoline) (star-PIPOX) with arms grafted to the lower rim of thiacalix[4]arene were studied in solutions by viscometry, sedimentation velocity, light scattering, and small-angle neutron scattering. The experiments were carried out in water and tetrahydrofuran solutions. It was revealed that in tetrahydrofuran, the studied polymers were present only as individual molecules, while in aqueous solutions, in addition to individual molecules, large polymer aggregates were found. Molecular characteristics of the star-PETOX and star-PIPOX samples were estimated; their behavior in tetrahydrofuran and water was studied over a wide temperature range. It was established that a cloud point of the aqueous solution of star-PETOX (67 °C) is higher than that of a solution of star-PIPOX (35 °C). Comparison of the data obtained by dynamic light scattering and small-angle neutron scattering turned out to be fruitful in revealing all the structural levels of the organization of star-PETOX and star-PIPOX in aqueous solutions. They include the level of the individual macromolecules and the level of supramolecular organization with a star-like architecture.

1Московский государственный университет им. М.В. Ломоносова, Москва, e-mail: shubina.74@mail.ru; 2Институт молекулярной генетики РАН, Москва, e-mail: nfm@img.ras.ru В настоящем исследовании было установлено, что интраназальное многократное (7 раз) введение в малых дозах (50 мкг/кг) исследуемых пептидов Pro-Leu-Pro, Pro-Leu-Pro-Ala, Pro-Gly-Pro-Ala и Phe-ProLeu-Pro-Ala животным с метаболическим синдромом приводило к нормализации жирового и углеводного обменов. Эти различные по структуре регуляторные пептиды при данной патологии замедляли рост массы тела, максимальный эффект был отмечен при введении пептида Phe-Pro-Leu-ProAla. Они снижали уровень глюкозы крови, уровень общего холестерина, холестерина липопротеидов низкой плотности и триглицеридов. Следует отметить, что пептиды Pro-Leu-Pro-Ala и Phe-Pro-Leu-ProAla оказывали достоверные эффекты не только через 20 ч после последнего введения животным, но и спустя 7 сут. после отмены их применения животным, которые продолжали находиться на высококалорийной диете. Ключевые слова: метаболический синдром, липиды, глюкоза, регуляторные пептиды.

The paper justifies the specifics of the turning point in the world technological development and indicates the arising opportunity for Russia to change its positioning in the global econ omy.It demonstrates the role of the advanced manufacturing technologies as an important factor behind new industrialization and maintaining global competitiveness of an economy.The paper describes peculiarities of the modern world technological development and holds a comparative analysis of the level of manufacturing competitiveness, research potential and support provided to industrial and technological development in a number of countries.The authors detect main trends in the transformation of the world technological landscape, in cluding in the context of management of the manufacturing technologies development by the leading technologically advanced countries.

Target organ damage in hypertension / Atrial fibrillation obesity 759 represents myocardial perfusion pressure and the amount of the myocardial mass being perfused.Excessive lowering of DBP may compromise coronary blood flow (CBF) but this is independent of the other determinants of CBF.Purpose: To examine a model which integrates these three CBF determinants in management of patients with hypertension Methods: We developed non-parametric equations that incorporate fractional flow reserve (FFR) measured at the time of coronary angiography and left ventricular mass measured by echocardiography and diastolic blood pressure (DBP).To validate and extrapolate the utility of this approach, a retrospective case review was conducted from the electronic medical records of persons attending a Cardiology Clinic.A consecutive patient sample (N=81) with CAD documented by coronary angiogram or coronary computerized tomography angiogram (CCTA) without previous PCI or valvular heart disease and with echocardiographic assessment of LV mass, was evaluated.FFR was estimated from the degree of coronary stenosis on coronary angiogram or CCTA.Blood pressure was measured in the office by an automated device.Results: There was a highly significant correlation (r=0.565;p<0.01) between DBP and estimated CBF (ml/g LV mass/body surface area).This relationship was similar in patients with or without diabetes mellitus.In patients who had CCTA there was a highly significant (r=0.734,p<0.01) relationship between DBP and CBF.More severe coronary stenosis or greater LV mass also correlated with reduced CBF.Examining two variables showed the importance of considering LV mass was greater at DBP >70 mmHg while the absolute level of DBP became the most important consideration for CBF when DBP was less than 70 mmHg.The model equations permitted more precise assessment of CBF when considering all three variables.Conclusion: These data have validated a new approach in the antihypertensive treatment of patient with hypertension who have concomitant coronary artery disease.Measurement of the severity of CAD by CCTA or coronary angiography combined with LV mass from echocardiography, and the use of the assessment model, permits clinicians to guide the extent of, or target for DBP lowering to avoid seriously compromising coronary blood flow and producing myocardial ischemia.

Complexation of biologically active water-soluble flexible chain microassembled N-vinylpyrrolidone-N-vinylamine copolymers with ions was studied by complex chromatographic techniques (high-performance liquid chromatography and thin-layer chromatography). Constants of complex formation were evaluated (K-b=4.6x10(5)). Hydrodynamic behavior and molecular radii of the prepared metal-polymeric compounds were evaluated by molecular optics and hydrodynamic methods [viscosimetry, sedimentation diffusion analysis, dynamic light scattering, and flow birefringence (Maxwell effect)]. No significant changes in hydrodynamic properties of metal-polymeric complexes as compared with those of the pure copolymers were observed. Thus, the suggested approach seems to be promising for producing noninvasive metal-polymeric complexes for biological purposes.

Copolymers of 2-deoxy-2-methacrylamido-o-glucose with N,N-dimethyl aminoethyl methacrylate were synthesized. Triple copolymers containing N,N-dimethyl-N-dodecyl-N-methacryloyl oxyethyl ammonium iodide units were obtained by alkylation of tertiary amino groups. These copolymers were studied by hydrodynamic and optical methods in various solvents. It was revealed that polyelectrolyte effect in salt-free aqueous solutions is far less pronounced than that in dimethyl sulfoxide (DMSO) solutions. The values of equilibrium rigidity A of alkylated macromolecules in salt-free solutions obtained from viscosimetry data is equal to similar to (150 +/- 50) angstrom in aqueous solutions and to (750 +/- 250) angstrom in DMSO solutions. Change in intrinsic anisotropy of alkylated macromolecules in DMSO solutions demonstrated that in the concentration range from 2.5 to 0.5 g/dL, electrostatic interactions lead to isotropic increase in dimensions of macromolecular coils. In the concentration range from 0.5 to 0.02 g/dL, increase in equilibrium rigidity by almost a factor of 4 is observed. It was established that in water-salt solutions of copolymers which contain more than 10 mol.% of dodecyl groups, compact structure is formed; in this structure, intramolecular fragments of polymer chain are hindered. In dimethylsulfoxide solution, in the presence of a salt, the value of intrinsic viscosity [eta] increases by more than a factor of 6-8 as compared to that in water-salt solutions. The observed differences in conformation, optical and relaxation properties of the triple copolymers in aqueous and DMSO solutions are related to hydrophobic interactions between alkyl substituents. These interactions lead to the formation of hydrophobic "core" and shielding the charged quaternary ammonium groups (N+) in aqua solutions. (C) 2016 Elsevier Ltd. All rights reserved.

Ag 0 nanoparticles are prepared via the reduction of silver ions by copolymers of N , N -dimethylaminoethyl methacrylate and 2-deoxy-2-methacrylamido- D -glucose of various compositions in water at room temperature. It is found that an insignificant part of the macromolecules is involved in the reduction of Ag + to Ag 0 and stabilization of the resulting nanoparticles. As shown by flow-birefringence studies, the optical properties of solutions of stabilized silver nanoparticles change abruptly relative to the optical properties of the solutions of the initial copolymers.

Polarized luminescence and flow birefringence methods were used in the studies of structural and dynamic characteristics of 2-(diethylamino)ethyl methacrylate and 2-deoxy-2-methacrylamido-d-glucose copolymers with varied content of cationic monomer units while changing temperature, pH and ionic strength of solutions. It was demonstrated that with increasing temperature, nanosecond relaxation times τIMM (which characterize intramolecular mobility of fragments of copolymer chain in solution) increase over a relatively narrow temperature range. Increase in relaxation times indicates strengthening intramolecular interactions and the formation of intramolecular hydrophobic domains. From the obtained flow birefringence data, it follows that in the vicinity of the lower critical solution temperature (LCST) we have molecular dispersed diluted copolymer solutions. The influence of temperature and ionic strength of solutions on the transition temperature were also studied. The observed changes in intramolecular interactions are accompanied by insignificant changes in root-mean-square dimensions of macromolecular coils; however, coils retain their asymmetry.

Методами молекулярной гидродинамики (седиментация, диффузия, вискозиметрия), поляризованной люминесценции и двойного лучепреломления в потоке исследованы конформационные и релаксационные свойства образцов сополимеров N,N-диметиламиноэтилметакрилата и 2-деокси-2-метакриламидо-D-глюкозы в растворах. Получены уравнения Марка–Куна–Хаувинка и выполнена оценка длины статистического сегмента Куна при различных степенях протонирования аминогрупп. Установлена корреляция между длиной статистического сегмента Куна и внутримолекулярной подвижностью сополимеров.