Curvature suppresses the Rayleigh-Taylor instability

The dynamics of a thin liquid film on the underside of a curved cylindrical substrate is studied. The evolution of the liquid layer is investigated as the film thickness and the radius of curvature of the substrate are varied. A dimensionless parameter (a modified Bond number) that incorporates both geometric parameters, gravity, and surface tension is identified, and allows the observations to be classified according to three different flow regimes: stable films, films with transient growth of perturbations followed by decay, and unstable films. Experiments and theory confirm that, below a critical value of the Bond number, curvature of the substrate suppresses the Rayleigh-Taylor instability

Impact of stromal cell components of tumor microenvironment on epithelial-mesenchymal transition in breast cancer cells

Background: Cell and tissue homeostasis results from the dynamic balance of cell – cell and cell – extracellular component crosstalk that regulates proliferation, differentiation, and apoptosis of cells as well as secretion and activation of soluble factors and/or deposition of extracellular matrix (ECM) components. Aim: The aim of the work was to study the crosstalk between tumor cells and stromal cell components using noncontact co-cultivation in vitro system. Materials and Methods: Human and rat breast cancer (BC) cell lines, normal human fibroblasts (NHF) and endothelial cells, and aspirates of bone marrow (BM) of BC patients with different clinical course of the disease (groups “Remission” (BM-R) and “Progression” (BM-P)) were used in noncontact co-cultivation system in vitro. The cell growth, expression of epithelial-mesenchymal transition (EMT) and tumor stem cell markers (E-cadherin, vimentin, CD44), Ki-67, p21 and Slug were investigated using immunocytochemical analysis. Results: Analysis of expression of E- and N-cadherin, vimentin and Slug in BC cells has shown that T-47D and MRS-T5 cells possess mesenchymal phenotype, while MCF-7 and MRS cells possess mostly epithelial phenotype with a part of cells with mesenchymal patterns. Upon noncontact co-cultivation of fibroblasts with Т-47D or MRS-Т5 cells, BC cells acquired higher proliferative activity compared to the control cells (р < 0.05) or MCF-7 and MRS cells co-cultivated with fibroblasts. Upon noncontact co-cultivation of Т-47D cells with normal fibroblasts and BM cells from BC patients from group “Progression” there were observed increased quantity of CD44+ Т-47D cells (by 26%), decreased quantity of Е-cadherin+ Т-47D cells, and appearance of vimentin-positive cells. In co-cultivation variant Т-47D + NHF + BM-R (“Remission“) the quantity of CD44+ Т-47D cells significantly decreased (р < 0.005) and E-cadherin expression remained unaltered compared to control cells. At the same time, in NHF cell population (co-cultivation variant Т-47D + NHF + BM-P) there was detected significant increase of quantity of р21+-cells (р < 0.005), cytoplasmic localization of p21, and nuclear localization of Slug. Expression of vimentin did not alter in any variant of co-cultivation. Conclusion: The new integration cell system for investigation of the mechanisms of interaction between tumor cells and the tumor microenvironment in vitro was developed. The significant changes in proliferative activity of TC dependently on its ­ЕМT-status were detected after their interaction with fibroblasts and endothelial cells in noncontact co-cultivation system. BM cells of BC patients had different modifying influence on TC dependent on clinical BC course. The activation of ЕМT program was revealed in TC upon noncontact co-cultivation with BM cells of BC patients with progression of the disease. Key Words: breast cancer, epithelial-mesenchymal transition, microenvironment, bone marrow, co-cultivation

Disse index and free fatty acids as markers of insulin resistance and their association with hospital outcomes of coronary bypass surgery in patients with different glycemic status

AIM: to analyze various indices of insulin resistance and plasma free fatty acid (FFA) levels, and their association with the preoperative status and in-hospital complications after coronary artery bypass grafting (CABG) in normoglycemic patients and patients with carbohydrate metabolism disorders (CMD).MATERIALS AND METHODS: The study included 708 patients who underwent CABG. The glycemic status, preoperative parameters, the specifics of surgical intervention, in-hospital complications were analyzed. The patients were divided into 2 groups: Group 1 (n=266) — patients with CMD (type 2 diabetes mellitus (T2DM) and prediabetes); Group 2 (n=442) — patients without CMD. Plasma FFA and fasting plasma insulin levels were determined, the Disse index, the quantitative insulin sensitivity check index (QUICKI), revised QUICKI were estimated in 383 patients.RESULTS: Screening prior to CABG increased the number of patients with T2DM from 15.2% to 24.1%, prediabetes – from 3.0% to 13.4%, with any CMD – from 18.2% to 37.5%.Patients with CMD showed a higher percentage of significant hospital complications (25.2% vs 17.0%, p=0.007), progression of renal failure (6.3% vs 2.9%, p=0.021), multiple organ failure (4.5% vs 1.7%, p=0.039), sternal wound complications (6.3% vs 2.9%, p=0.018), renal replacement therapy (3.7% vs 1.1%, p=0.020), surgery on peripheral arteries (1.5% vs 0%, p=0.039).According to the results of multivariate analysis, the Disse index turned out to be a significant predictor of the end point (hospital stay &gt;10 days or any significant complication CABG) in several regression models (OR 1.060 in one of the models; 95% CI 1.016–1.105; p=0.006). Independent predictors of the end point were: female gender, age, body mass index, cardiopulmonary bypass duration, left atrium size, left ventricular end diastolic dimension, T2DM, FFA levels (OR 3.335; 95% CI 1.076–10.327; p=0.036), average postoperative glycemia on the 1st day after CABG, failure to achieve the target range of perioperative glycemia.CONCLUSION: Screening for CMD prior to CABG can significantly increase the number of patients with diagnosed CMD. Significant in-hospital complications after CABG tend to be more prevalent in patients with CMD compared with normoglycemic patients. Insulin resistance index Disse, FFA, postoperative glycemia are independent predictors of prolonged hospital stay or postoperative complications of CABG

The role of newly diagnosed diabetes mellitus for poor in-hospital prognosis of coronary artery bypass grafting

Background: The management of coronary artery disease in patients with type 2 diabetes (T2DM) who need myocardial revascularization is a great challenge. Aims: To study the role of newly diagnosed T2DM in the development of in-hospital adverse outcomes after coronary artery surgery (CABG). Methods: 708 consecutive patients underwent CABG were included. All patients without history of T2DM and with border fasting hyperglycemia underwent an oral glucose tolerance test. Results: The screening allowed to diagnose T2DM in 8.9% and prediabetes in 10.4% of the study population. The the number of patients with T2DM increased from 15.2% to 24.1%, and with prediabetes from 3.0% to 13.4%. The total number of patients with carbohydrate metabolism disorders increased from 18.2% to 37.5%. The trend towards higher rate of in-hospital complications after CABG was defined among patients with newly diagnosed and previously diagnosed T2DM. The regression analysis demonstrated the presence of the relationships between the previously diagnosed T2DM and the total number of significant complications (odds ratio (OR) 1.350, 95% confidence interval (CI): 1.0571.723, p=0.020) and prolonged in-hospital stay (OR 1.609, 95%CI 1.2022.155, p=0.001). The significance of these relationships increased with the addition of newly diagnosed T2DM to the regression model (for in-hospital complications: OR 1.731, 95% CI 1.1312.626, p=0.012; for prolonged in-hospital stay: OR 2.229, 95%CI 1.4123.519, p0.001). Moreover, additional associations between T2DM and the risk of developing multiple organ dysfunction (OR 2.911, 95% CI 1.0727.901, p=0.039), urgent lower extremity surgery (OR 1.638, 95%CI 1.00915.213, p=0.020) and the need for extracorporeal correction of hemostasis (OR 3.472, 95%CI 1.04211.556, p=0.044) have been defined. Importantly, the presence of these associations would not have been identified without including newly diagnosed DM in the regression model. Conclusion: The newly diagnosed T2DM affects the prognosis of CABG as well as the previously diagnosed T2DM. The obtained results suggest the importance of active preoperative T2DM screening

Первый опыт применения электромиостимуляции при ранней реабилитации реципиента донорского сердца с осложненным послеоперационным периодом

The prognosis of a patient suffering from severe chronic heart failure is determined by the impairment of cardiac and skeletal muscles. More evidence has recently emerged on the use of electrical muscle stimulation (EMS) as a method of rehabilitation in patients admitted to the intensive care units. Nevertheless, evidences on the use of this type of rehabilitation in patients after heart transplantation are still limited. This article presents the first experience of using EMS in the patient who underwent heart transplantation. Sessions of electric muscle stimulation of the quadriceps allowed maintaining muscle mass according to the ultrasound findings, as well as muscle strength and endurance. The EMC was safe, had no proarrhythmogenic effect and did not affect the pacing of the temporary pacemaker. Further data accumulation, systematization and analysis on the use of EMC in this group of patients is required.Прогноз пациента, страдающего тяжелой хронической сердечной недостаточностью, определяется не только поражением сердца, но и состоянием скелетных мышц. В течение последних лет все больше появляется информации о применении в качестве средства реабилитации пациентов отделений реанимации и интенсивной терапии электростимуляции скелетных мышц (ЭМС), однако информация о применении такого вида реабилитации у пациентов после трансплантации сердца недостаточна. В настоящей статье представлен первый опыт применения ЭМС у пациента, перенесшего трансплантацию сердца. Проведенный курс электростимуляции четырехглавой мышцы бедра позволил сохранить мышечную массу по данным ультразвукового исследования, а также силу и выносливость мускулатуры. Проведенная ЭМС была безопасной, не имела проаритмогенного эффекта и не сказывалась на работе временного электрокардиостимулятора. Необходимо дальнейшее накопление, систематизация и анализ данных о применении ЭМС у данной категории больных

Связь индексов инсулинорезистентности с периоперационным статусом и ближайшим прогнозом у пациентов с нарушениями углеводного обмена и нормогликемией, подвергающихся коронарному шунтированию

Highlights. Patients with coronary artery disease undergoing coronary artery bypass grafting have a high prevalence of type 2 diabetes mellitus and prediabetes. The frequency of postoperative stroke and hospital stay is significantly higher in patients with impaired carbohydrate metabolism.Insulin resistance markers are associated with a variety of perioperative characteristics, but according to multivariate analysis, only free fatty acids and HOMA-IR were independent predictors of hospitalacquired complications and long-term hospital stayAim. To analyze insulin resistance markers and their association with the preoperative outcome and in-hospital complications of coronary bypass grafting (CABG) in patients with type 2 diabetes mellitus (DM 2), prediabetes and normoglycemia.Methods. The study included 383 consecutive patients undergoing CABG at the same center. Glycemic status, free fatty acids (FFA), fasting insulin, glucose, lipid profile of all patients were determined before surgery and the following insulin resistance indices (IR) were calculated: HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), QUICKI (Quantitative Insulin Sensitivity Check Index), Revised QUICKI, McAuley. Patients were divided into 2 groups: the group that included patients with carbohydrate metabolism disorders (CMD), type 2 diabetes mellitus and prediabetes (n = 192), and the group of patients without CMD (n = 191). Perioperative characteristics of patients, postoperative complications and their association with insulin resistance markers were analyzed.Results. FFA and calculated indices of insulin resistance such as HOMA-IR, QUICKI, RevisedQUICKI, and McAuley correlated with the following perioperative characteristics: the duration of surgical intervention and cardiopulmonary bypass, lipid levels, coagulation index, left ventricular dimension and myocardial diastolic function, etc. The analysis of in-hospital complications revealed that the frequency of postoperative stroke (p = 0.044) and hospital stay after CABG &gt;30 days (p = 0.014) was significantly higher in patients with CMD. According to the results of multivariate analysis, the predictors of the composite endpoint (hospital stay after CABG&gt;10 days and/or significant perioperative complication) were as follows: female sex (odds ratio (OR) 2.862, 95% confidence interval (CI) 1.062-7.712, p = 0.036); age (OR 1.085, 95%CI 1.027–1.147, p = 0.003); duration of cardiopulmonary bypass (OR 1.146, 95%CI 1.008–1.301, p = 0.035); body mass index (OR 1.125, 95% CI 1.035–1.222, p = 0.005), left atrial dimension (OR 5.916 95% CI 2.188–15.996, p&lt;0.001); any CMD (OR 1.436, 95%CI 1.029–2.003, p = 0.032), type 2 DM (OR 2.184, 95%CI 1.087–4.389, p = 0.027), FFA levels (OR 5.707, 95%CI 1.183–27.537, p = 0.029) and HOMA–IR index (OR 1.164, 95%CI 1.025–1.322, p = 0.019).Conclusion. FFA, HOMA-IR, QUICKI, Revised-QUICKI, and McAuley correlate with a variety of perioperative characteristics of patients undergoing CABG, but multivariate analysis revealed that only FFA levels and the HOMA-IR can be used as predictors of in-hospital complications and prolonged hospital stay.Основные положения. У пациентов с ишемической болезнью сердца, подвергающихся коронарному шунтированию, велика распространенность сахарного диабета 2-го типа и предиабета. Частота послеоперационного инсульта и пребывания в стационаре значимо выше у лиц с нарушениями углеводного обмена.Маркеры инсулинорезистентности показали корреляционные связи со множеством периоперационных характеристик, но в многофакторном анализе только уровень свободных жирных кислот и индекс HOMA-IR стали независимыми предикторами госпитальных осложнений и длительного пребывания в стационаре.Цель. Изучить маркеры инсулинорезистентности и их связь с предоперационным статусом и госпитальными осложнениями коронарного шунтирования (КШ) у пациентов с сахарным диабетом 2-го типа (СД 2), предиабетом и нормогликемией.Материалы и методы. В исследование включено 383 последовательных больных, перенесших КШ. Всем участникам исследован гликемический статус перед операцией, а также определены сывороточные свободные жирные кислоты, инсулин натощак, глюкоза, липидный профиль и рассчитаны индексы инсулинорезистентно-сти: HOMA-IR (Homeostasis Model Assessment of Insulin Resistance), QUICKI (Quantitative Insulin Sensitivity Check Index), Revised-QUICKI и McAuley. Пациенты разделены на две группы: лица с нарушениями углеводного обмена (НУО), включавшими СД 2 и предиабет (n = 192), и без НУО (n = 191). Проанализированы периоперационные характеристики, послеоперационные осложнения и их связь с маркерами инсулинорезистентности.Результаты. Свободные жирные кислоты и расчетные индексы инсулинорезистентности HOMA-IR, QUICKI, Revised-QUICKI, McAuley коррелировали с периоперационными характеристиками: длительностью операции и искусственного кровообращения, липидами, показателями коагулограммы, размерами левого предсердия, диастолической функцией миокарда и другими. При анализе госпитальных осложнений частота послеоперационного инсульта (p = 0,044) и пребывания в стационаре после КШ &gt;30 дней (p = 0,014) была значимо выше у пациентов с НУО. Предикторами комбинированной конечной точки (госпитализация после КШ &gt;10 дней и/или значимое периоперационное осложнение) по результатам многофакторного анализа стали женский пол (отношение шансов (ОШ) 2,862, 95% доверительный интервал (ДИ) 1,062–7,712; p = 0,036), возраст (ОШ 1,085, 95% ДИ 1,027–1,147; p = 0,003), длительность искусственного кровообращения (ОШ 1,146, 95% ДИ 1,008–1,301; p = 0,035), индекс массы тела (ОШ 1,125, 95% ДИ 1,035–1,222; p = 0,005), размеры  левого  предсердия  (ОШ  5,916,  95%  ДИ  2,188–15,996; р&lt;0,001), любое НУО (ОШ 1,436, 95% ДИ 1,029–2,003; p = 0,032), СД 2 (ОШ 2,184, 95% ДИ 1,087–4,389; p = 0,027), уровень СЖК (ОШ 5,707, 95% ДИ 1,183–27,537; p = 0,029) и индекс HOMA-IR (ОШ 1,164, 95% ДИ 1,025–1,322; p = 0,019).Заключение. Свободные жирные кислоты, индексы инсулинорезистентности HOMA-IR, QUICKI, Revised-QUICKI, McAuley коррелируют со множеством периоперационных характеристик пациентов, подвергающихся КШ, но в многофакторном анализе предикторами госпитальных осложнений и длительной госпитализации стали лишь уровень свободных жирных кислот и HOMA-IR

Анализ подходов к определению порогов готовности платить за технологии здравоохранения, установление их предельной величины на примере стран с развитой системой оценки технологий здравоохранения

The article reviews international methodological guidelines, regulatory documents and existing approaches to the determination of the costeffectiveness threshold (CeT), also known as the willingness-to-pay threshold (WTP), the threshold value of the incremental cost-effectiveness ratio (ICeR), in europe (england and Wales, Scotland, Ireland, France, Belgium, Denmark, the netherlands, Germany, Sweden, Finland, norway, Poland), America (the USA, Canada, Brazil), Asia (Japan, South korea, Taiwan, Thailand), in Australia and new Zealand. The CeT is commonly used to rationalize decision-making in health cost reimbursement. The present review demonstrates that just a few countries (englandandWales,Thailand,Poland,USA) have introduced the explicit value of CeT into their decision making. Some countries (Australia,Canada,new Zealand, thenetherlands,Sweden, andBrazil) use CeT in an implicit manner implying that no specific CeT value is defined by law. In other countries (Finland,Sweden,norway,France,Germany,Denmark,Japan,South korea,Taiwan), the role of the threshold in health reimbursement remains uncertain despite the presence of HTA systems. The CeT is expressed as additional cost per unit of incremental health benefit, which is represented by quality-adjusted life year (QALY) in most counties. However,PolandandBrazilallow using life years gained (LYG) as a measure of additional benefit neglecting the quality of life. In thenetherlandsandengland, different CeT values are applied to the health technology under assessment depending on the severity or rareness of the disease and some other factors.Проведен анализ зарубежных методических материалов, нормативно-правовых документов и существующей практики определения порогов готовности платить (ПГП) или порогового значения инкрементального отношения «затраты-эффективность» ICeR (costeffectiveness threshold, willingness-to-pay threshold, reference value of the ICeR) в странах Европы (Англия и Уэльс, Шотландия, Ирландия, Франция, Бельгия, Дания, Нидерланды, Германия, Швеция, Финляндия, Норвегия, Польша), Америки (США, Канада, Бразилия), Азии (Япония, Южная Корея, Тайвань, Таиланд), в Австралии и Новой Зеландии. ПГП широко используется для поддержки принятия решений о финансировании тех или иных медицинских технологий. Проведенный анализ показал, что лишь в некоторых странах (Англия и Уэльс, Таиланд, Польша, США) используется эксплицитный ПГП, то есть предельная величина показателя обозначена в нормативно-правовых документах, регламентирующих процедуру проведения оценки технологий здравоохранения (ОТЗ). В других странах (Австралия, Канада, Новая Зеландия, Нидерланды, Швеция, Бразилия) ПГП является имплицитным, то есть он учитывается при принятии решений, но его значение никак не закреплено на законодательном уровне. Во всех остальных изученных странах (Финляндия, Швеция, Норвегия, Франция, Германия, Дания, Япония, Южная Корея, Тайвань), несмотря на достаточное развитие систем ОТЗ, ПГП остается неопределенным. Проведенный анализ показал, что практически во всех странах, использующих ПГП, за исключением Польши и Бразилии, ПГП определяется за 1 год качественной жизни (Quality-Adjusted Life Years, QALY). В Польше и Бразилии ПГП рассчитывается за год сохраненной жизни (Life Years Gained, LYG). В таких странах, как Нидерланды и Англия, ПГП варьирует в зависимости от тяжести заболеваний, для лечения которых используются оцениваемые технологии

RISK FACTORS OF MAJOR CARDIOVASCULAR EVENTS IN LONG-TERM PERIOD OF CORONARY BYPASS IN PATIENTS WITH ISCHEMIC HEART DISEASE AND 2ND TYPE DIABETES MELLITUS

Aim. To reveal the risk factors of major cardiovascular events (MCVE) in long-term period after CABG with DM2.Material and methods. Prospective study of 324 patients with CHD after CABG. Patients were selected into 2 groups: 148 with DM2 (median age 58 y., median of long-term follow-up 1,8 y.), 176 patients without DM and another disorders of carbohydrate metabolism (median age — 58 y., median follow-up 1,7 y.). As the long-term MCVE we used MI, stroke, cardiovascular death. An estimation of the freedom from MCVE was done by the method of multiplying estimations by KaplanMeier. To reveal risk factors for MCVE we used logistic regression.Results. Patients of both groups were comparable by the age (p=0,211), long-term outcome follow-up (p=0,132). Patients with DM2 had more often the MCVE (14,2% and 6,3%, respectively, p=0,028). By the Kaplan-Meier method we built the curves of the freedom from MCVE in the studied groups, with the test of Gekhan-Wilkokson we found differences (p=0,013). MCVE in long-term period after CABG was found in 4 patients with DM (2,7%) and in two — without DM (1,1%), p=0,529. By the results of multifactor analysis as the predictors for MCVE were DM2 (OR 3,30795% CI 1,372-7,968, р=0,007), female gender (OR 2,75295% CI 1,074-7,049, р=0,034), not related to age or renal function. Chance of MCVE in long-term period increased with the time of on-pump (OR 1,14595% CI 1,024-1,280, р=0,016 ) and with the decrease of LV EF (OR 1,04395% CI 1,001-1,087, р=0,041) with the presence of peripheral atherosclerosis the risk of long-term MCVE increased 5,5 times (OR 5,53995% CI 1,564-19,620, р=0,007) not related to gender, age, LV EF, GFR or statin intake. The level of fasting glucose at the moment of admittance after CABG was an independent predictor for MCVE (OR 1,144, р=0,037).Conclusion. The independent predictors of MCVE in long-term post-CABG period are DM2, female gender, peripheral atherosclerosis, duration of on-pump period, EF LV and glycemia before operation

Impact of Pre-Diabetes on the Rate of Major Adverse Cardiovascular Events in Patients Undergoing Coronary Artery Bypass Grafting

Aim. To assess  the  relationship between pre-diabetes/type 2 diabetes mellitus (type 2 DM) and  long-term adverse  prognosis in patients with coronary  artery disease (CAD) who underwent coronary  artery bypass grafting (CABG).Material and methods. 347 CAD patients who underwent CABG in the period from 2006 to 2009 were enrolled into the study. All patients were divided into 3 groups:  148 patients with type 2 DM (the median age – 58 years, the median follow-up – 1.8  years), 23 patients with pre-diabetes, i.e. impaired fasting glycemia and/or impaired glucose tolerance (the median age – 58 years, the median follow-up – 1.7  years); and 176 patients without diabetes and other carbohydrate metabolism disorders (CMD) (the median age – 58 years, the median follow-up – 1.7 years). The prognosis was considered as unfavorable in case of any major adverse  cardiovascular events  (MACEs) defined as myocardial infarction, stroke,  cardiovascular death. Logistic regression was used to identify the predictors of the unfavorable prognosis.Results. All patients in the study groups were comparable in age (p=0.345) and the median of the follow-up (p=0.134). The comparative assessment of the long-term prognosis showed the similar rate of major adverse  cardiovascular events in the groups  with CMD (the diabetes group  – 14.2% vs the  pre-diabetes group  – 13.0%), compared to 6.3% in patients without any CMD (p=0.028 for the  groups  with DM and  without CMD). The regression analysis reported that type 2 DM appeared to be a significant factor associated with the development of the long-term MACEs (odds ratio [OR] 3.307, 95% confidence interval [95%CI] 1.372-7.968, p=0.007). The addition of pre-diabetes as a potential predictor of the unfavorable prognosis increased 3.6-fold the risk of long-term MACEs (OR 3.617; 95%CI 1.557-8.403, p=0.001).Conclusion.  Pre-diabetes  significantly  affects  the  prognosis  of patients  after  CABG, similarly  to type  2 DM. The diagnosis  of CMD in  patients undergoing CABG is of significant clinical relevance