Cardiovascular disease associated with metabolic syndrome has a high prevalence, but the mechanistic basis of metabolic cardiomyopathy remains poorly understood. We characterised the cardiac transcriptome in a murine metabolic syndrome (MetS) model (LDLR−/−; ob/ob, DKO) relative to the healthy, control heart (C57BL/6, WT) and the transcriptional changes induced by ACE-inhibition in those hearts. RNA-Seq, differential gene expression and transcription factor analysis identified 288 genes differentially expressed between DKO and WT hearts implicating 72 pathways. Hallmarks of metabolic cardiomyopathy were increased activity in integrin-linked kinase signalling, Rho signalling, dendritic cell maturation, production of nitric oxide and reactive oxygen species in macrophages, atherosclerosis, LXR-RXR signalling, cardiac hypertrophy, and acute phase response pathways. ACE-inhibition had a limited effect on gene expression in WT (55 genes, 23 pathways), and a prominent effect in DKO hearts (1143 genes, 104 pathways). In DKO hearts, ACE-I appears to counteract some of the MetS-specific pathways, while also activating cardioprotective mechanisms. We conclude that MetS and control murine hearts have unique transcriptional profiles and exhibit a partially specific transcriptional response to ACE-inhibition.
The paper presents a possibility of estimating a human cardiac pacemaker using combined application of nonlinear integral transformation and fuzzy logic, which allows carrying out the analysis in the real-time mode. The system of fuzzy logical conclusion is proposed, membership functions and rules of fuzzy products are defined. It was shown that the ratio of the value of a truth degree of the winning rule condition to the value of a truth degree of any other rule condition is at least 3.
Background & Objective: The presented design attempt of building an advanced prosthetic lower limb has a vast requirement in these days to connect paralytic patients and elderly people with the external environment for a better lifestyle. The Recordings of Electromyography (EMG) patterns and other data analysis of the muscle signals has lightened the path of technology to a wide range of studies and experiments in the field of prosthesis of certain moveable body parts using the acquired EMG signal of muscles of lower limb. An effort has been made to acquire the EMG signal and study the signals with the incorporation of sufficient technology to build an artificial lower limb with the help of Flex-sensor and ‘Arduino Uno’ programming. The main aspect about the hardware circuitry of this practical work is its ease of use and applicability. The Bio-electrodes are attached on the specified location to acquire the muscle signals and also Laboratory Virtual Instrument Engineering Workbench (LabVIEW) to acquire the signals. In addition, the movements of certain joints of the lower limb can be replicated controlling the movement of a servo-motor for the implementation of the design of the artificial lower limb. Conclusion: The different output parameter changes can be measured according to the relaxation and the contraction of the Flex-sensor attached to the knee, and the ankle joints. The Servo-motors can further be utilized in the construction of the artificial lower leg to be moved externally without any voluntary motion of the subject. The measurement of dispersion has been introduced in the mathematical analysis.
Increasing evidence suggests that neuronal communication is a defining property of functionally specialized brain networks and that it is implemented through synchronization between population activities of distinct brain areas. The detection of long-range coupling in electroencephalography (EEG) and magnetoencephalography (MEG) data using conventional metrics (such as coherence or phase-locking value) is by definition contaminated by spatial leakage. Methods such as imaginary coherence, phase-lag index or orthogonalized amplitude correlations tackle spatial leakage by ignoring zero-phase interactions. Although useful, these metrics will by construction lead to false negatives in cases where true zero-phase coupling exists in the data and will underestimate interactions with phase lags in the vicinity of zero. Yet, empirically observed neuronal synchrony in invasive recordings indicates that it is not uncommon to find zero or close-to-zero phase lag between the activity profiles of coupled neuronal assemblies. Here, we introduce a novel method that allows us to mitigate the undesired spatial leakage effects and detect zero and near zero phase interactions. To this end, we propose a projection operation that operates on sensor-space cross-spectrum and suppresses the spatial leakage contribution but retains the true zero-phase interaction component. We then solve the network estimation task as a source estimation problem defined in the product space of interacting source topographies. We show how this framework provides reliable interaction detection for all phase-lag values and we thus refer to the method as Phase Shift Invariant Imaging of Coherent Sources (PSIICOS). Realistic simulations demonstrate that PSIICOS has better detector characteristics than existing interaction metrics. Finally, we illustrate the performance of PSIICOS by applying it to real MEG dataset recorded during a standard mental rotation task. Taken together, using analytical derivations, data simulations and real brain data, this study presents a novel source-space MEG/EEG connectivity method that overcomes previous limitations and for the first time allows for the estimation of true zero-phase coupling via non-invasive electrophysiological recordings.
The ECG features analysis in a patient born in 1946 led to repeated statement of misdiagnosis, particularly of myocardial infarction. About 2,500 patients’s ECGshave been analyzed for the three-year period of the patient’s observation. A Fourier analysis of the spectra of the ECGs of the patient 2506 allowed to assume that there exists an additional leading center in his myocardium, with a variable start phase of the myocardium relative to the phase of the fundamental frequency of contractions of the myocardium. Experimental confirmation of this hypothesis is in particular; found in the patient jump-like transition from synchronous phase daily changes in the function dynamics of the P wave width and the PQ segment to the antiphase ones, which reflects the change in the conditions for triggering the process of myocardial contraction. As a result, the coupling of the two leading frequencies of the myocardium, with a variable phase shift of the triggering, can be expressed both in the extra systoles appearance as well as in unusual cardio cycles not coinciding in the form and phase of cardio cycles of a single ECG. Cluster analysis of the entire set of collected patient’s ECGs in the similarity of their forms revealed 18 separate clusters of similarity. While cluster analysis of the ECG samples in other 4857 patients in most cases led to the identification of only one cluster characteristic for a certain patient’s ECG form. Mathematical modeling of the proposed hypothesis about the presence of more than one leading center of myocardial triggering which resulted in getting model patterns of split ECGs, qualitatively corresponding to the split forms of ECGs observed in the studied patient, confirmed its validity.
The paper presents the automated system intended to prevent industrial-caused diseases of workers, the basis of which is represented by algorithms of preventing several negative functional conditions (stress, monotony). The emergence of such state shall be determined based on an analysis of bioelectric signals, in particular, skin-galvanic reactions. Proceeding from the dynamics of the functional state, the automated system offers to perform an optimized set of measures to restore the health of the worker. Implementation of an automated system is presented in Visual Programming system LabVIEW.
Previously, the mathematical models (CoMPaS and CoM-III) of primary tumor (PT) growth and secondary distant metastases (sdMTS) growth of breast cancer (BC) considering TNM classification have been presented (Tyuryumina E., Neznanov A.; 2017, 2018). Goal: To detect the earliest diagnostics period of visible sdMTS via CoMPaS and CoM-III.
Material and methods. 122 patients had been scheduled for elective lumbar fusion in 2010-2016 was enrolled in a prospective study. Group K (n=19) underwent postoperative analgesia on-demand. Group PMA (n=21) was given preventive multimodal analgesia (PMA) including ketoprofen, paracetamol and morphine. At PMA+PG (n=20) and PMA+N (n=20) groups pregabalin and nefopam were used respectively; at PMA+E (n=22) epidural ropivacaine with morphine was combined; at PMA+I (n=20) continuous wound infiltration by ropivacaine with ketorolac was administered. Results and conclusions. Postoperative analgesia on-demand is not adequate during 5 postoperative days. PMA results in significant pain reduction during 3 postoperative days, enhancement of patient satisfaction, quicker recovery after surgery and fewer days of hospital stay. Patients receiving pregabalin or nefopam as well as epidural analgesia does not lead to better postoperative pain relief than at PMA, but shows a trend to increase the rate of adverse reactions. Wound infiltration with PMA is followed by significant pain relief during 6 postoperative hours, decrease in opioids consumption, rate of adverse reactions and duration of hospital stay (compared to PMA group).
The article includes the observation of the cluster analysis of medical data on the example of the cardiac data. One of the main effective and commonly used Data Mining methods that applied to the large amounts of information (for example, mathematical economics) are clustering methods: the search for signs of similarity between objects in the study of the subject area and the subsequent merger of objects into subsets (clusters) according to the established affinity. The main purpose of the investigation is to examine the hypothesis of the possibility of diagnosing the patient health status, as well as identifying his pathologies, using the analysis of electrocardiogram (ECG) series and the allocation of similar clusters based on the results of this analysis. However, the subject of clustering techniques implementation to the ECG on the grounds of similarity of forms have not previously been extensively investigated. In the model of the heart, which is used in this study, the state of the heart is taken as a fixed oscillatory process of the phenomenon of the FPU auto-return. But, on the other hand, since the heart is an self-oscillating system and it has no need to start the oscillations by obtaining the energy of “perturbation”, the concept of FPU autoreturn is introduced in the study of the heart. The mathematical modeling of the heart work by using a decomposition of the Fermi-Pasta-Ulam (FPU) was investigated. The formal description of the mathematical model of the heart as a system of connected cells myocytes is presented. This represents a single oscillatory degree of freedom described by a system of coupled nonlinear differential equations of the second order equation of Van der Pol. Cluster analysis bases on the search of similar clusters of Fourier spectrum which are received by FPU recurrence. The current results that are obtained show that the hypothesis is confirmed. In mathematical modeling of the FPU heart modeling, which is based on the forms of Fourier spectra, were identified. Subsets were identified, among which various subsets of both forms of Fourier spectra with pathologies and forms of the Fourier spectrum of healthy people were formed. From this study it follows that the cluster analysis of the electrocardiogram may refer this ECG to any cluster and thereby diagnose the state of cardiac health of the patient.
Background. Predicting the efficacy of rGH therapy in patients with GH deficiency, based on the final achieved height (FAH) criterion, is an important tool for the clinician. It enables a personalized approach to the treatment of patients with GH deficiency: to recommend careful adherence to the regimen and dosage of the drug, evaluate the efficacy of therapy in different groups of patients, and clearly demonstrate the factors affecting the FAH indicator. Aim - to develop mathematical models for predicting FAH and its standard deviation score (SDS) in patients with GH deficiency in the Russian population. Material and methods. For simulation, we used the data of 121 patients diagnosed with GH deficiency who received rGH since the time of diagnosis to the time of final height and were followed-up at the Institute of Pediatric Endocrinology of the Endocrinology Research Centre in the period between 1978 and 2016. As model predictors, we used 11 indicators: the gender, chronological age at the time of GH deficiency diagnosis, puberty status, disease form, regularity of rGH therapy, height SDS at birth, height SDS at the time of GH deficiency diagnosis, bone age at the time of GH deficiency diagnosis, bone age/chronological index, SDS of a genetically predicted height, and maximum stimulated GH level in a clonidine test. To generate models, we used multiple linear regression, artificial neural networks (ANNs), and the Statistica 13 software. Results. The developed ANNs demonstrated a high accuracy of predicting FAH (the root-mean-square error was 4.4 cm, and the explained variance fraction was 76%) and a lower accuracy of predicting the FAH SDS (the root-mean-square error was 0.601 SDS, and the explained variance fraction was 42%). Linear regression models that were based on quantitative predictors only had a substantially worse quality. Free software implementation was developed for the best produced ANN. Conclusion. An ANN-based software-implemented model for predicting FAH uses indicators available for any clinician as predictors and can be used for individual prediction of FAH. In the future, the use of larger databases for simulation will improve the quality of predicting the efficacy of rGH therapy.
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Introduction. The concept of health-related quality of life as a key factor in patient-doctor interactions is an important basis for making managerial and medical decisions in many foreign health systems. In Russia, the concept of health-related quality of life is in its infancy: it is required the theoretical, methodological and scientific-practical foundations development.
Aims and objectives. The aim of this study is to assess the health- related quality of life for Russian population based on the EQ–5D questionnaire and to form the average health indicators.
Material and methods. The survey was conducted on a sample of 1,602 people aged 18 to 92 years. The final sample is representative for the country and federal districts. We use using the Russian-language version of the EQ–5D questionnaire which allows us to receive two indicators for each respondent – health profile and index based on visual analog scale EQ–VAS.
Results. The study revealed the following results: (1) the majority of the respondents among all ages have the problems in EQ-5D dimension “anxiety/depression”; (2) women tend to detect moderate problems in all dimensions more often than men; (3) EQ–5D descriptive results are decreased in all components with the respondents age; (4) the most infrequent population’s problems among the all dimensions are found in the "self-care" dimension; (5) the age changes related to a decrease of EQ–VAS are associated with the general tendency of a decrease in the dimensions.
Discussion. To obtain the most accurate and objective assessments from the EQ–5D, it is necessary to conduct a study in accordance with established international protocols, compare the estimates with the average population indices and adhere to a thorough research design.
Conclusion. The study reveals the possibilities of using EQ–5D and the first health-related quality of life Russian population indicators that can be used as a basis for comparing between different population groups and patients.
Objective: to determine the influence of perioperative analgesia methods on the incidence of « failed back surgery syndrome» after intervertebral discal hernia removal. Material and methods: This prospective study was conducted from 2010 till 2013 and included 129 patients who underwent lumbar discectomy regarding intervertebral discal hernia. Patients of group GA+R (n=20) were operated on under general anesthesia (GA) and received «analgesia at request» (R) in postoperative period. Group SA+PMA included patients (n=23) who were operated under spinal anesthesia (SA) with the following usage of preventive multimodal analgesia (PMA) based on ketoprofen, paracetamol and nalbuphine. General anesthesia and PMA was used in GA+PMA (n=21) group; the additional wound infiltration by bupivacaine solution (I) was used in GA+PMA+I (n=21) group; application of corticosteroids (A) in the area of damaged spinal root - in GA+PMA+A (n=20) group; combination of wound infiltration by bupivacaine solution and application of corticosteroids - in GA+PMA+IA (n=24) group. The intensity of acute postoperative pain was assessed within 7 postoperative days. The phone interview was conducted in 6 months after operation with examination of long-term outcomes of surgical treatment. Results: The analgesia was inadequate in all patients of GA+R group within 4 postoperative days comparing with adequate analgesia in patients of GA+PMA group during whole period of observation. The pain syndrome within first 4 postoperative days had significantly lower intensity among patients of GA+PMA group comparing with GA+R group. Patients of SA+PMA group reported that pain intensity was significantly lower only during first 2 hours after operation comparing with GA+PMA group. Patients of GA+PMA+I and GA+PMA+IA groups had lower intensity pain within 2 postoperative days comparing with GA+PMA group. Studying the long-term outcomes of surgical treatment it was revealed that 60% of patients had back and/or lower extremity pain, among them 30% - lower extremity pain in 6 months after operation. The mean pain intensity was assessed as 2,85 (2; 3) according to numeric rating scale, 24% of patients suffered from chronic pain reported about sleep disturbances, 23% - significant reduction in the life quality, 25% of patients were были unable to work. There were no statistically significant differences between examined groups concerning incidence of chronic back and/or lower extremity pain as well as lower extremity pain (p=0,459 и p=0,903 consequently, x2test) and mean pain intensity (p=0,112, Kruskal-Wallis test ANOVA) in 6 months after operation. Conclusion: The usage of preventive multimodal analgesic schemes provides the adequate pain control within 7 postoperative days while the usage of analgesia at request does not allow solving this challenge within first 4 postoperative days after intervertebral discal hernia removal. The spontaneous release of pain intensity is seen after 4th postoperative day. The SA usage in patients with discal hernia provides the pain release only during first several hours after operations (within time of residual subarachnoid block) comparing with patients underwent surgery under GA. The usage of wound infiltration by bupivacaine solution allows achieving the lowering of pain intensity during first 2 postoperative days comparing with patie nts without wound infiltration. The 60% of patients suffered from back and/or lower extremity pain and 30% of patients - from lower extremity pain in 6 months after operation/ More over the chronic severe pain syndrome is observed in 23-25% of patients, accompanied by sleep disturbances, inability to work and significant reduction in the life quality The incidence of failed back surgery syndrome occurrence after intervertebral discal hernia removal is independent of perioperative analgesia schemes.
The risk factors for acute pain as well as chronic pain syndrome (CPS) in spine surgery have not been defined to date. Purpose — to define the prognostic parameters of acute pain severity and the risk of CPS in patients operated on for spinal diseases and injuries. Material and methods. The study included 291 patients operated on for degenerative diseases and injuries of the spine at the Sklifosovsky Research Institute of Emergency Medicine in 2010―2016. Sociodemographic and clinical data and the psychological status of patients were evaluated. A mechanical algometer was used to measure the pain threshold (PT) and pain tolerance. The movement pain intensity was assessed by using a visual analog scale (VAS) on the day of surgery. Pain was considered minor at a median score of 0―4 cm and severe at a median score of 5―10 cm. The presence of CPS was assessed during a telephone survey 5―7 months after surgery. Results. The gender, PT, dynamic pain intensity before surgery, and expectation of postoperative pain are risk factors for severe acute postoperative pain. A multinomial logit regression model (Hosmer—Lemeshow test ― 4.322; p=0.827) predicts minor dynamic pain on the 1postoperative day with an accuracy of 70% (95% CI 63—76). The age and dynamic pain intensity on the 1postoperative are the risk factors for CPS; the multinomial logit regression model (Hosmer—Lemeshow test ― 3.1; p=0.928) predicts CPS with an accuracy of 65% (95% CI 59—71) 5―7 months after surgery. Conclusion. The developed software in the form of MS Excel calculators provides a particular patient with preoperative assessment of the risk for minor acute dynamic pain on the 1postoperative day and CPS 5―7 months after surgery.
Background. Cushing's disease (СD) is а severe neuroendocrine disease that can rapidly progress with the development of severe complications of hypercorticism requiring immediate treatment. The main method of treatment is a neurosurgical operation, the effectiveness of which at the present time can reach 80% or more, however, about a quarter of patients after successful neurosurgical treatment experience reccurence. Aim. The analysis of prognostic factors potentially affecting the occurrence of recurrence of CD after successful primary transnasal adenomectomy. Material and methods. A retrospective monocenter comparative study of treatment outcomes in 219 patients (32 men, 187 women) with confirmed diagnosis of Cushing's disease who underwent endoscopic transsphenoidal adenomectomy between 2007 and 2014 was performed. The inclusion criteria were: the absence of previous pathogenetic treatment for this disease and the development of remission of the disease in the early postoperative period. The duration of follow-up period was three years and more. We used methods of statistical comparison of groups, including survival analysis and ROC-analysis. Results. Within 3 years the remission was preserved in 172 patients, the recurrence of Cushing's disease developed in 47 patients (21.5% [16%; 28%]). The probability of CD recurrence was associated with morning levels of ACTH and cortisol and evening ACTH in the early postoperative period. As a result of the ROC-analysis for morning ACTH and cortisol, the optimal cutting points were 7 pg/ml and 123 nmol/l respectively. In patients with ACTH level less than 7 pg/ml, three years recurrence appeared to be 7%, 95% CI [3%, 14%], while at the level of ≥7 pg/ml recurrence was observed in 31% [23%, 40%] cases, RR 0.22 [0.09; 0.51], ОR - 0.16 [0.06; 0.43]. In patients with cortisol level below 123 nmol/l the recurrence developed in 13% [9%, 20%] of cases, while in patients with cortisol level ≥123 nmol/l, recurrence was equal to 45% [32%, 59%], RR 0.29 [0.18; 0.50], ОR - 0.19 [0.09; 0.39]. Conclusion. The development of adrenal insufficiency (a decrease in ACTH level less than 7 pg/ml and cortisol level less than 123 nmol/l) statistically significantly reduces the probability of the recurrence of CD within three years after surgery.
The quality of the evidence on the efficacy and safety of therapeutic and preventive interventions is analyzed in health technology assessment procedure (including the development of reimbursement lists such as the List of Vital and Essential Drugs in Russian Federation) and during development of clinical guidelines. The traditional approach to assess the evidence quality is based on the well-known pyramid of research designs (from meta-analyses to case descriptions), and now it is obsolete. The modern approach is to take into account also the methodological quality of studies. The methodological quality depends on risks of biases and the risk of incorrect data analysis. The article proposes a scale based on combinations of designs and three levels of methodological quality (high, medium, poor) for each of them. The scale differentiates meta-analyses based on randomized controlled trials and comparative studies of other designs. In the scale, the new design of indirect comparisons is envisaged, its’ evidence is lower than for RCT that are used for indirect comparisons. The scale can be used for assessing the absolute and relative effectiveness and safety of medical and preventive medical technologies. At present, the scale is included in the guidelines for the complex assessment of pharmaceuticals.