Molecular effects of cardiac contractility modulation in patients with heart failure of ischemic aetiology uncovered by transcriptome analysis.

Cardiac contractility modulation (CCM) is based on electrical stimulation of the heart without alteration of action potential and mechanical activation, the data on its fundamental molecular mechanisms are limited. Here we demonstrate clinical and physiological effect of 12 months CCM in 29 patients along with transcriptomic molecular data. Based on the CCM effect the patients were divided into two groups: responders (n = 13) and non-responders (n = 16). RNA-seq data were collected for 6 patients before and after CCM including 3 responders and 3 non-responders. The overall effect of CCM on gene expression was mainly provided by samples from the responder group and included the upregulation of the genes involved in the maintenance of proteostasis and mitochondrial structure and function. Using pathway enrichment analysis, we found that baseline myocardial tissue samples from responder group were characterized by upregulation of mitochondrial matrix-related genes, Z disc-protein encoding genes and muscle contraction-related genes. In summary, twelve months of ССM led to changes in signaling pathways associated with cellular respiration, apoptosis, and autophagy. The pattern of myocardial remodeling after CCM is associated with initial expression level of myocardial contractile proteins, adaptation reserves associated with mitochondria and low expression level of inflammatory molecules.

Tuberculosis incidence and its socioeconomic determi-nants: developing a parsimonious model.

Background: Tuberculosis is a widespread communicable disease, which is one of the top 10 causes of demise globally. Several regression models have been built, and then utilized for the Tuberculosis incidence projections. However, when fitting a multiple linear regression model, an analysis must account for multicollinearity aspects. The present study aimed to develop a parsimonious model that produces unbiased results based on socioeconomic variables as predictors of Tuberculosis incidence. Study design: Ecological study. Methods: Data were collected from the Karaganda Regional Center of Phthisio-pulmonology and Bureau of National Statistics. By multiple linear regression model, we investigated associations between Tuberculosis incidence rate and socioeconomic determinants in Karaganda region, Kazakhstan, during 2001-2019. A Principal components analysis was performed on the socioeconomic variables with oblique rotation. Furthermore, associations of Tuberculosis incidence with the principal components derived from the Principal components analysis were assessed. Results: The incidence of Tuberculosis in Karaganda region decreased over the period of 2001-2019. Economic development and healthcare capacity were negatively correlated with Tuberculosis incidence. A multiple linear regression equation on Tuberculosis incidence (y) was developed with economic development (x1) and healthcare capacity (x2) clustering two components (utilizing Principal components analysis) to eliminate collinearity: y = 1442 - 454.3x1 - 211.4x2. The incidence of Tuberculosis decreased with the increase of economic development and healthcare capacity. Conclusions: In conclusion, the study indicated that economic development and healthcare capacity are closely associated with the incidence of Tuberculosis. The findings support the implementation of optimal preventive measures for Tuberculosis control, including improving the level of economic status, increasing social protection, health expenditure, and strengthening health sector capacity, which are key determinants of the incidence of Tuberculosis.

System dynamics modeling for general practitioner workforce forecasting in Kazakhstan.

Background: Primary health care has been proven to be a highly effective and efficient way to address the main causes and risks of poor health and well-being today, as well as handling the emerging challenges that will threaten health and well-being tomorrow. In our study we used the System Dynamics approach to develop a model for the population and General Practitioner workforce to include multiple inputs and their relationships in the equations for each stock and flow. Methods: We built the model in the Any Logic software to cover the flow of medical workers, demographic data of the population and the prevalence of the disease over time. Three scenarios were examined for forecasting primary health care personnel resources. The base year for forecasting was 2018, and the modeling was carried out until 2030. Results: All of three scenarios indicate that with the current number of graduated General Practitioners, the shortage of primary care physicians will be exacerbated. In general, the shortage can reach more than 2,000 on a population of 18.3 million (2018). Conclusion: The projected shortage of doctors in the primary health care system requires special attention to human resource planning. Only one third of medical graduates in Kazakhstan go to work in the primary health care system. The government needs to develop measures to stimulate and support young medical doctors to become general practitioners.

[Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia].

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (Mg BP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (Mg D) (185±90 mg/day). RESULTS: Mg supply was adequate (Mg BP >0.80 mmol/L, Mg D >300 mg/day) in not more than 6 % of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95 % confidence interval [CI] 10-25, р=0.0006). Mg deficit (Mg BP.

Nonlinear analyses of heart rate variability in hypertension.

OBJECTIVE: The autonomic nervous system plays an important role in blood pressure regulation and in the development of hypertension. Heart rate variability (HRV) may be of importance in identifying subjects at higher risk of developing hypertension. In the present study, comparative analysis of HRV for normal and hypertension subjects using nonlinear indices has been carried out. PATIENTS AND METHODS: We analyzed the data from 24 patients with essential hypertension aged 45-55 (HG). All the subjects in this group had a confirmed diagnosis of the first- or second-stage essential hypertension. The control group for these subjects included 32 healthy volunteers of the same age group (CG). We analyzed the whole 5minutes of the ECG recording. Nonlinear indices D2, K2 and lagged Poincaré plot indices were calculated. RESULTS: Values of D2 and K2 in hypertension state is statistically significantly lower than in healthy. Poincaré plot indices SD1 and SD2 in healthy volunteers are statistically higher than in hypertensive patients for all lags (P<0,05). SD1/SD2 ratio is also higher in healthy subjects, but the difference is statistically significant only for l=5 and 6. CONCLUSION: The heart rhythm in groups with hypertension is more regular, its dynamics are less complex and less "chaotic," compared to healthy ones. This is expressed in lower values of entropy and correlation dimension. The HR stabilization is observed at both short and long time intervals, but mainly due to the decrease in the difference of the "neighboring" R-R intervals.

Biochemical markers of hypertension, prehypertension.

OBJECTIVE: There are insufficient researches aimed at evaluating biochemical markers of mechanisms of formation of AH and lesion of target organs in hypertension and prehypertension. The aim of that research was to study the level of endothelial dysfunction markers and damage to the cardiovascular system in hypertension and prehypertension. PATIENTS AND METHODS: A cross-sectional study was performed among 938 people aged 18 to 65 years. All respondents were surveyed, blood pressure measured, for glucose, cholesterol, interleukin-6, sFAS, LIGHT, hFABP, NT-ProBNP and an Endocan concentrations were tested. Depending on the level of blood pressure participants were splitted into groups with normotension, prehypertension and hypertension. RESULTS: Comparing the markers of inflammation, apoptosis and target organ damage in the prehypertensive group, the level of the LIGHT protein was Me=265.2pg/ml (Q25-Q75: 197.7-444.3), in the control group - Me=251.1pg/ml (Q25-Q75: 176.6-376.6), the Endocan level was Me=660.6pg/ml (Q25-Q75: 419.6-867.4) and in the control group Me=587.5pg/ml (Q25-Q75: 401.9-838.1). In the AH group, the level of the LIGHT Me=273.1pg/ml (Q25-Q75: 195.1-455.2), Endocan Me=668.2pg/ml (Q25-Q75: 434.8-977.3), heart-type fatty-acid-binding protein Me=2233.1pg/ml (Q25-Q75: 1518.4-3391.1) exceeded the control group. CONCLUSION: Thus, the development of prehypertension and hypertension is characterized by an increase in the activity of biochemical markers of endothelial dysfunction and damage to target organs, more expressed in the presence of hypertension.

Functional Orientation of Biochemical Processes in Female Beluga × Sterlet (Acipenser ruthenus Linnaeus, 1758 × Huso huso Linnaeus, 1758) Hybrids in the Reproductive Cycle.

The article reports data on the dynamics of blood parameters and parameters of protein, fat, and water-salt metabolism in female starlet × beluga hybrids kept under artificial conditions in the period of reproductive cycle. Gonad maturation in female hybrids in the artificial environment causes clear changes in the biochemistry of blood and of urine.

Deficit of Magnesium and States of Hypercoagulation: Intellectual Analysis of Data Obtained From a Sample of Patients Aged 18-50 years From Medical and Preventive Facilities in Russia.

The states characterized by pronounced hypercoagulable components (deep vein thrombosis, cardio- and cerebro-vascular pathologies) are caused by multiple pathophysiological factors, including insufficient supply of magnesium (Mg) and other micronutrients. AIM: to present results of analysis of the Institute of Microelements Data Base (IMDB) performed from point of view of interrelationships of Mg deficit and hypercoagulable states in adults treated in medico-preventive facilities of Central, Northwestern, Northern, and Siberian federal districts of Russia. METHODS: The analysis was realized as analysis of data obtained in a cross-sectional study. In the cohort of patients (n=1453) formed from the IMBD adequacy of Mg supply was assessed by magnesium levels in blood plasma (MgBP) (0.69±0.15 mmol/L) and estimates of daily Mg consumption according to dietary diaries (MgD) (185±90 mg/day). RESULTS: Mg supply was adequate (MgBP >0.80 mmol/L, MgD >300 mg/day) in not more than 6% of patients. Presence of "Hypercoagulation" label in data base was associated with greater number of chronic diseases (2.3±2.1 and 0.83±0.8 with and without this label, respectively, р=0.0006) and elevated risk of the presence on 4 comorbid pathologies (odds ratio [OR] 18, 95% confidence interval [CI] 10-25, р=0.0006). Mg deficit (MgBP.

The Incidence of Depression among the Population of Central Kazakhstan and Its Relationship with Sociodemographic Characteristics.

It has been established that the presence of depression is accompanied by an increased risk of morbidity and mortality in cerebrovascular and cardiovascular diseases and diabetes. The aim of this research was to estimate depressive symptom prevalence among the population in Central Kazakhstan and to define the relationship with social-demographic and behavioral factors. 1820 respondents of the population of Central Kazakhstan, aged 25 to 65, were performed. Participants included 777 urban and 1043 rural residents. Depressive symptoms assessed with the Patient Health Questionnaire (PHQ-9). The results showed that some degree of depressive symptoms was detected in 75.7% of the respondents. A minimal degree of depressive symptoms was observed in 28.51%, mild in 27.7%, moderate in 13.7%, and severe and very severe degree of depressive symptoms in 4.6% and 1.2%, respectively; the absence of depression symptoms was reported in 24.3% of the respondents. The study found a relationship between the prevalence of depressive symptoms and factors such as gender, education, income, presence of chronic diseases, and physical activity. We have not found a correlation between the frequencies of depressive symptoms with age, employment, character of labor, and marital status.

QPSK 3R regenerator using a phase sensitive amplifier.

A black box phase sensitive amplifier based 3R regeneration scheme is proposed for non-return to zero quadrature phase shift keyed formatted signals. Performance improvements of more than 2 dB are achieved at the presence of input phase distortion.

Photostructurable photo-thermo-refractive glass.

Photostructurable properties of photo-thermo-refractive glass are discovered for the first time. The etching kinetics in HF solutions for virgin photo-thermo-refractive glass and glass ceramics are investigated. The etching rate of the glass ceramics is shown to be more than ten times higher than that of glass. Future prospects of applying the chemical etching technology for developing various PTR glass-based photonic and mechatronic elements are discussed.

Numerical investigation of all-optical add-drop multiplexing for spectrally overlapping OFDM signals.

We propose a novel architecture for all-optical add-drop multiplexing of OFDM signals. Sub-channel extraction is achieved by means of waveform replication and coherent subtraction from the OFDM super-channel. Numerical simulations have been carried out to benchmark the performance of the architecture against critical design parameters.

[Correction of psycho-emotional state by the biofeedback method in patients with metabolic syndrome].

Metabolic syndrome is one of the important clinical problems of medicine. The aim of this study was to demonstrate the efficacy of heart rate variability biofeedback method in correction of mental and emotional state in patients with metabolic syndrome. For this task was set to study the dynamics of indicators of mental and emotional stress by biofeedback based hardware-software complex "Amblyocor" in patients with metabolic syndrome. Course of heart rate variability biofeedback passed 10 patients with the metabolic syndrome. During biofeedback sessions conducted tests that assess psycho-emotional state by 5 characters. Data processing was performed using software package «Statistica 8.0¼ and showed a statistically significant decrease in indicators of mental and emotional stress, that demonstrates the effectiveness of biofeedback in the correction of mental and emotional stress in patients with metabolic syndrome.

[The transtympanic administration of steroids for the treatment of acute sensorineural hearing impairment].

UNLABELLED: The objective of the present study was to compare the effectiveness of two methods (transtympanic and intravenous) administration of steroids and standard therapy for the treatment of the patients presenting with acute sensorineural hearing impairment (OSNHI). MATERIALS AND METHODS: The study included 56 patients with this pathology. 18 of them were given transtympanic injections of steroids; 10 others received steroids intravenously in the combination with standard therapy. 28 patients were treated by the standard therapy alone. The effectiveness of the treatment was estimated by means of tonal threshold audiometry. RESULTS: None of the patients in the first group enjoined total normalization of hearing. Its improvement by 10-29 dB was documented in 22 (78.6%) patients. In the second group hearing improved by 15-20 dB in 4 (40%) and by 5-10 dB in 6 (60%) patients. In the third group, 14 (77.7%) patients reported improvement of hearing and reduced noise as early as the first puncture. By the time of discharge from the hospital, their hearing improved by 30-40 dB while the 15-20 dB improvement was documented in 2 (11.1%) patients and the 5-10 dB improvement in another 2 (11.1%) patients. The study has demonstrated the high effectiveness of glucocorticoid therapy especially in the case of transtympanic administration of these steroids.

Regeneration limit of classical Shannon capacity.

Since Shannon derived the seminal formula for the capacity of the additive linear white Gaussian noise channel, it has commonly been interpreted as the ultimate limit of error-free information transmission rate. However, the capacity above the corresponding linear channel limit can be achieved when noise is suppressed using nonlinear elements; that is, the regenerative function not available in linear systems. Regeneration is a fundamental concept that extends from biology to optical communications. All-optical regeneration of coherent signal has attracted particular attention. Surprisingly, the quantitative impact of regeneration on the Shannon capacity has remained unstudied. Here we propose a new method of designing regenerative transmission systems with capacity that is higher than the corresponding linear channel, and illustrate it by proposing application of the Fourier transform for efficient regeneration of multilevel multidimensional signals. The regenerative Shannon limit--the upper bound of regeneration efficiency--is derived.

Optimization of cascaded regenerative links based on phase sensitive amplifiers.

We develop an analytical method for optimizing phase sensitive amplifiers for regeneration in multilevel phase encoded transmission systems. The model accurately predicts the optimum transfer function characteristics and identifies operating tolerances for different signal constellations and transmission scenarios. The results demonstrate the scalability of the scheme and show the significance of having simultaneous optimization of the transfer function and the signal alphabet. The model is general and can be applied to any regenerative system.

[Paralytic poliomyelitis in Russian Federation in 1998-2005].

From 1998 through 2005 3,294 cases of acute flaccid paralysis (AFP) including 93 cases with clinical picture of poliomyelitis were registered in Russian Federation. From the latter cases 91 were classified as vaccine-associated paralytic poliomyelitis (VAPP): 66 were VAPP cases in oral poliomyelitis vaccine (OPV) recipients and 25--VAPP cases in contacts. VAPP rate was 1 case per 1.6 million of distributed OPV doses, 1 case per 2.2 million doses for OPV recipients, and 1 case per 186,000 doses for recipients of 1st OPV dose in children aged < 1 year. Majority of VAPP cases in recipients occurred after 1st dose (89.4%) and in contacts--in non-vaccinated children (76%). Mean interval between OPV administration and onset of VAPP in recipients was 21 days. Children aged < 1 year were predominant among VAPP cases (92.4% among recipient VAPP cases, and 80% among contact VAPP cases). Majority of the patients had unfavorable health status including defects of immunity. Most of poliovirus strains isolated from VAPP cases belonged to type 3 (52.9%) whereas to type 2 and 1--29.8% and 17.4% of strains respectively. All VAPP cases were associated with vaccine-derived polioviruses. A highly diverged poliovirus type 1 (2.65% of nucleotide substitutions in VP1 region) was isolated from patient with contact VAPP. Formation of poliovirus-neutralizing serum antibodies in children with VAPP including persons with immunodeficiency reflects the ability of the organism to produce specific antiviral immune response.

[Life-style of medical personnel dwelling and working in agroindustrial area].

Results of sociological survey of medical personnel of typical agroindustrial area of Novgorod Oblast are presented. Data of self-registration of acute and chronic diseases and self-appraisal of one's health testify higher morbidity and health deterioration during last 3 years. Analysis of demographic characteristics, life-styles and labor conditions revealed complex of major factors impacting individual health and flow-out of professional medical personnel. Both amount of average monthly wage of physicians and paramedics, levels of their family income and welfare and as well degree of their inconsistence with cost of living of able-bodied population are established. Conditions of living and social maintenance, labor and off-labor activity, attitude to one's own health and spread of risk factors were analyzed. Management weaknesses of district and rural patient care institutions were established, including considerable exceeding of hygienic regulations established for medical personnel working load and higher spread of physical, chemical and biological risk factors of working environment harmful for health. Need in further enhancement of management of working process, occupational safety, labor remuneration and in increasing social safety, hygienic and curative activity of medical personnel is justified.

[Multiple sclerosis with childhood onset]. / Rasseiannyi skleroz s debiutom v detskom vozraste.

The clinical manifestations, magnetic resonance imaging (MRI) data, blood and cerebrospinal fluid (CSF) tests were analyzed in 19 patients with early-onset (before the age of 17 years) multiple sclerosis (MS) and in 100 patients with the definite diagnosis of MS with adult onset. Between group differences in sex ratio and initial neurological symptoms, with the prevalence of acute brainstem dysfunction (37%) and optic neuritis (37%) in the patients with early onset MS, were revealed. In childhood, the disease course was poorer with early disablement on the background of attendant unfavorable conditions. A sensitivity of various MRI parameters was analyzed and the essential proportion of the tumor-like acute inflammatory lesions was shown in early onset MS (29%). Immunological tests (albumin coefficient evaluation) revealed that in early onset MS hematoencephalic barrier dysfunction was registered more often, comparing to adult onset MS (100% vs 50%). The peculiarities of biases in concentrations of kappa-free and lambda-free light immunoglobulin chains in blood and CSF were detected. Higher levels of the kappa-free light chains concentrations in CSF were mostly found in the patients both with early and adult onset MS (86% and 99%, respectively) that confirmed the diagnostic value of this index. The results obtained may improve MS diagnosis in children.