МЕТОДИКА ОБРАБОТКИ ЭКСПЕРИМЕНТАЛЬНЫХ ДАННЫХ ПРИ МОДЕЛИРОВАНИИ ДИСПЕРСИИ ИМПЕДАНСА БИОЛОГИЧЕСКИХ ТКАНЕЙ С ПОМОЩЬЮ СХЕМЫ ЗАМЕЩЕНИЯ ФРИКЕ

Purpose. Modeling the dispersion of the biological tissue impedance of vegetable and animal origin using the Fricke equivalent circuit; development of a technique for experimental data processing to determine the approximation coefficients of the dispersion of the biological tissue impedance for this equivalent circuit; study of the features of the equivalent circuit at modeling the dispersion of the impedance, resistance, and reactance; the definition of the frequency domain in which using of the equivalent circuit is correct; revealing and generalization of the main regularities of dissipation of biological tissue impedance of vegetable and animal origin. Methodology. The technique is based on the scientific provisions of theoretical electrical engineering – the theory of the electromagnetic field in nonlinear media in modeling the dispersion of the biological tissue impedance. Results. The electric circuit of the Fricke equivalent circuit allows modeling the dependences of the impedance module of biological tissues, active and reactive components of impedance with acceptable accuracy for practical purposes in the frequency domain from 103 to 106 Hz. The equation of impedance of the Fricke equivalent circuit for biological tissues makes it possible to approximate the frequency dependences of the impedance modulus, active and reactive parts of the total resistance only by using the approximation coefficients corresponding to each part. The developed method for determining the values of the approximation coefficients of the impedance equation for the Fricke equivalent circuit for biological tissues allows to determine these values with high accuracy for various biological tissues. It is shown that the frequency dependences of the active component of the total resistance for tissues of vegetable and animal origin are similar. Originality. The developed technique operates with the normalized values of the impedance modulus of the Fricke equivalent circuit, the active and reactive components of the impedance as a function of frequency, which allows a comparative analysis of the dependencies of these parameters of various biological tissues of plant and animal origin. Practical value. The approximate dependences of the absolute impedance modulus, active and reactive components of the impedance allow modeling processes occurring in biological tissues with the passage of a current of different frequency. Dependence of the impedance of biological tissue can be applied to the design of diagnostic and control equipment to determine the properties of tissues of animal and vegetable origin, including developing more effective medical equipment.Разработана методика обработки экспериментальных данных для определения коэффициентов аппроксимации импеданса биологических тканей растительного и животного происхождения при моделировании дисперсии импеданса с помощью схемы замещения Фрике. Проведен анализ свойств схемы замещения Фрике, ее возможностей и особенностей при моделировании дисперсии импеданса, резистанса и реактанса. Показано, что при нормировании дисперсии активные составляющие импеданса для тканей растительного и животного происхождения подобны

Sustained microglial depletion with CSF1R inhibitor impairs parenchymal plaque development in an Alzheimer's disease model.

Many risk genes for the development of Alzheimer's disease (AD) are exclusively or highly expressed in myeloid cells. Microglia are dependent on colony-stimulating factor 1 receptor (CSF1R) signaling for their survival. We designed and synthesized a highly selective brain-penetrant CSF1R inhibitor (PLX5622) allowing for extended and specific microglial elimination, preceding and during pathology development. We find that in the 5xFAD mouse model of AD, plaques fail to form in the parenchymal space following microglial depletion, except in areas containing surviving microglia. Instead, Aβ deposits in cortical blood vessels reminiscent of cerebral amyloid angiopathy. Altered gene expression in the 5xFAD hippocampus is also reversed by the absence of microglia. Transcriptional analyses of the residual plaque-forming microglia show they exhibit a disease-associated microglia profile. Collectively, we describe the structure, formulation, and efficacy of PLX5622, which allows for sustained microglial depletion and identify roles of microglia in initiating plaque pathogenesis

Association of polymorphisms of genes SLC30A8 and MC4R with the prognosis of the development of type 2 diabetes mellitus

BACKGROUND: The prevalence of Type 2 diabetes mellitus (T2DM) has reached epidemic proportions and it is estimated to affect over 400 million people worldwide. Moreover, the incidence of diabetes is expected to continue to rise and it is projected to affect nearly one of the three individuals by the year 2050. These alarming projections suggest that there is an urgent need for the development and implementation of novel prevention and treatment strategies to combat the rise in T2DM.AIM: To study the possibility of using polymorphisms of genes SLC30A8 and MC4R as markers for predicting the development of T2D in the population of Novosibirsk.MATERIALS AND METHODS: On the basis of prospective follow-up of a representative population sample of residents of Novosibirsk (The HAPIEE Project), 2 groups were formed according to the “case-control” principle (case — people who had diabetes mellitus 2 over 10 years of follow-up, and control — people who did not developed disorders of carbohydrate metabolism). T2D group (n = 443, mean age 56.2 ± 6.7 years, men — 29.6%, women — 70.4%), control group (n = 532, mean age 56.1 ± 7.1 years, men — 32.7%, women — 67.3%). DNA was isolated by phenol-chloroform extraction. Genotyping was performed by the method of polymerase chain reaction with subsequent analysis of restriction fragment length polymorphism, polymerase chain reaction in real time. Statistical processing was carried out using the SPSS 16.0 software package.RESULTS: Genotype TT rs13266634 of the SLC30A8 gene was associated with the risk of developing T2D (relative risk — RR 1.51, 95% confidence interval — CI 1.11–2.05, p =0.008). The CC genotype rs13266634 of the SLC30A8 gene was associated with a protective effect against T2D (RR 0.57, 95% CI 0.35–0.92, p=0.026). No significant effect of rs17782313 of the MC4R gene on the risk of developing T2D was found.CONCLUSION: The rs13266634 polymorphism of the SLC30A8 gene confirmed its association with the prognosis of the development of T2D, which indicates the possibility of considering it as a candidate for inclusion in a diabetes risk score. The association between polymorphisms rs17782313 of the MC4R gene and the prognosis of the development of T2D was not found

Analytic review of the factors influencing on of the stomatologic status of sportsmen

Учитывая, что сегодня в занятия физической культурой и спортом вовлекаются все более широкие массы населения различного возраста, уровня здоровья и подготовленности, достижения оздоровительного эффекта и высокой стабильности результатов становятся лишь при полном соответствии нагрузок спорта физическими возможностями организма. Установлена связь между' показателями иммунной защиты и проявлениями заболеваний пародонта в полости рта. Considering, that in employment of physical training and sports is involved today more and broader masses of the various age, health and readiness level achievement of improving effect and high stability of the results become only at full conformity of loadings of sports physical possibilities of the organism. It is established the connection between indicators of immune protection and displays the periodontal diseases in an oral cavity

Significance of Input Correlations in Striatal Function

The striatum is the main input station of the basal ganglia and is strongly associated with motor and cognitive functions. Anatomical evidence suggests that individual striatal neurons are unlikely to share their inputs from the cortex. Using a biologically realistic large-scale network model of striatum and cortico-striatal projections, we provide a functional interpretation of the special anatomical structure of these projections. Specifically, we show that weak pairwise correlation within the pool of inputs to individual striatal neurons enhances the saliency of signal representation in the striatum. By contrast, correlations among the input pools of different striatal neurons render the signal representation less distinct from background activity. We suggest that for the network architecture of the striatum, there is a preferred cortico-striatal input configuration for optimal signal representation. It is further enhanced by the low-rate asynchronous background activity in striatum, supported by the balance between feedforward and feedback inhibitions in the striatal network. Thus, an appropriate combination of rates and correlations in the striatal input sets the stage for action selection presumably implemented in the basal ganglia

Retinoic Acid Functions as a Key GABAergic Differentiation Signal in the Basal Ganglia

Retinoic acid (RA) is essential for the generation of GABAergic inhibitory neurons in the mouse forebrain, and RA treatment of embryonic stem cells induces the production of GABAergic neurons

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Hermeneutik der Intersubjektivität : der Wahrheitsbegriff der philosophischen Hermeneutik bei Hans-Georg Gadamer und Karl-Otto Apel (russische tekst)

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