The Journal of V. N. Karazin Kharkiv National University, series "Medicine"

Entropy of frequency domain of heart rate variability

Oleksandr Martynenko — 2022-11-28

Introduction. The heart rate variability (HRV) is based on measuring (time) intervals between R-peaks (of RR-intervals) of an electrocardiogram (ECG) and plotting a rhythmogram on their basis with its subsequent analysis by various mathematical methods which are classified as Time-Domain (TD), Frequency-Domain (FD) and Nonlinear [1, 2]. There are a number of popular Nonlinear methods used in HRV analysis, such as entropy-based measures that mostly applied for TD. Spectral Entropy (SE) is using for Frequency-Domain: it is defined to be the Shannon entropy of the power spectral density (PSD) of the data. An important characteristic of Frequency-Domain studies is sympatho-vagal balance, which has been overlooked by entropy-based analysis. This is due to the fact that good entropy analysis restricted the number of existing HRV data, which is shrinking in FD and also in total spectrum parts. Aim of the research. The goal of this paper is to provide a reliable formula for calculating entropy accurately for Frequency-domain of standard 5-min. HRV records and to show the advantages of such approach for analyzing of sympatho-vagal balance for healthy subjects (NSR), Congestive Heart Failure (CHF) and Atrial Fibrillation (AF) patients. Materials and Methods. We used MIT-BIH long-term HRV records for Normal Sinus Rhythm (NSR), Congestive Heart Failure (CHF) and Atrial Fibrillation (AF). The generalized form of the Robust Entropy Estimator (EnRE) for Frequency-domain of standard 5-min. HRV records was proposed and the key EnRE futures was shown. The difference between means of the two independent selections (NSR and CHF, before and after AF) has been determined by a t-test for independent samples; discriminant analysis and statistical calculations have been done by using the statistical package IBM SPSS 27. The results of the study. We calculate entropy for all valuable for HRV spectral interval, namely 0–0.4 Hz and to compare with existing results for Spectral Entropy: qualitatively we receive the same distribution number as [14] and significant difference (p < 0.001) between entropy averages for NSR and CHF or AF patients. We define low-frequencies (LF) power spectrum components in the range of 0.04–0.15 Hz and high-frequencies (HF) power spectrum components in the range of 0.15–0.4 Hz [1]. The sympatho-vagal balance is a simple ratio LF/HF [1]. Then, we define an entropy eLF of the LF power spectrum components, an entropy eHF of the HF power spectrum components and entropy based sympatho-vagal balance as a ratio eLF/eHF. The difference between NSR and CHF groups are significant in both cases LF/HF and eLF/eHF with p < 0.001, but in case of eLF/eHF the results are quite better (t = -4.8, compared to LF/HF where t = -4.4). The discriminant analysis shows total classification accuracy for eLF/eHF in 79.3 % (χ² = 19.4, p < 0.001) and for LF/HF in 72.4 % (χ² = 16.6, p < 0.001). We applied entropy-based Frequencies-domain analyzing for AF patients and showed that ratio eLF/eHF is significantly higher during AF than before AF (p < 0.001). This is opposite to ordinary LF/HF where difference is insignificant due to high variation of this ratio. Conclusion. Proposed in the article is generalized form for Robust Entropy Estimator EnRE for Frequencies-domain, which allows, for time series of a limited length (standard 5-min. records), to find entropy value of HRV power spectrum (total spectrum, low- and high- frequencies bands). Using the proposed EnRE for MIT-BIH database of HRV records, we show for standard 5 min. HRV records the usage of EnRE of HRV power spectrum and entropy-based sympatho-vagal balance of Normal Sinus Rhythm (NSR) and Congestive Heart Failure (CHF) cases. It is demonstrated, that, entropy-based Frequencies-domain analyzing is applicable for case of Atrial Fibrillation (AF) even during AF episodes. We showed the significant difference (p < 0.001) before and during AF for entropy of total spectrum, as well as for sympatho-vagal balance in form of eLF/eHF.

Entropy of DNA sequences and leukemia patients mortality

Oleksandr Martynenko — 2022-11-28

Introduction. Deoxyribonucleic acid (DNA) is not a random sequence of four nucleotides combinations: comprehensive reviews [1, 2] persuasively shows long- and short-range correlations in DNA, periodic properties and correlations structure of sequences. Information theory methods, like Entropy, imply quantifying the amount of information contained in sequences. the relationship between entropy and patient survival is widespread in some branches of medicine and medical researches: cardiology, neurology, surgery, trauma. Therefore, it appears there is a necessity for implementing advantages of information theory methods for exploration of relationship between mortality of some category of patients and entropy of their DNA sequences. Aim of the research. The goal of this paper is to provide a reliable formula for calculating entropy accurately for short DNA sequences and to show how to use existing entropy analysis to examine the mortality of leukemia patients. Materials and Methods. We used University of Barcelona (UB) leukemia patient’s data base (DB) with 117 anonymized records that consists: Date of patient’s diagnosis, Date of patient’s death, Leukemia diagnoses, Patient’s DNA sequence. Average time for patient death after diagnoses: 99 ± 77 months. The formal characteristics of DNA sequences in UB leukemia patient’s DB are: average number of bases N = 496 ± 69; min (N) = 297 bases; max(N) = 745 bases. The generalized form of the Robust Entropy Estimator (EnRE) for short DNA sequences was proposed and key EnRE futures was showed. The Survival Analysis has been done using statistical package IBM SPSS 27 by Kaplan-Meier survival analysis and Cox Regressions survival modelling. Results. The accuracy of the proposed EnRE for calculating entropy was proved for various lengths of time series and various types of random distributions. It was shown, that in all cases for N = 500, relative error in calculating the precise value of entropy does not exceed 1 %, while the magnitude of correlation is no worse than 0.995. In order to yield the minimum EnRE standard deviation and coefficient of variation, an initial DNA sequence's alphabet code was converted into an integer code of bases using an optimization rule for only one minimal numerical decoding around zero. Entropy EnRE were calculated for leukemia patients for two samples: 2 groups divided by median EnRE = 1.47 and 2 groups of patients were formed according to their belonging to 1^st (EnRE ≤ 1.448) and 4^th (EnRE ≥ 1.490) quartiles. The result of Kaplan-Meier survival analysis and Cox Regressions survival modelling are statistically significant: p < 0,05 for median groups and p < 0,005 for patient’s groups formed of 1^st and 4^th quartiles. The death hazard for a patient with EnRE below median is 1.556 times that of a patient with EnRE over median and that the death hazard for a patient of 1^st entropy quartile (lowest EnRE) is 2.143 times that of a patient of 4^th entropy quartile (highest EnRE). Conclusions. The transition from widen (median) to smaller (quartile) patients’ groups with more EnRE differentiation confirmed the unique significance of the entropy of DNA sequences for leukemia patient’s mortality. This significance is proved statistically by increasing hazard and decreasing of average time of death after diagnoses for leukemia patients with lower entropy of DNA sequences.

Large family genetic analysis: effects of variegated porphyria and hemophilia b on reproductive traits

Valeriia Dorofieieva — 2022-11-28

Introduction. The relevance of the study of genetic pathologies is due to the growing prevalence in most countries, disability and mortality of persons, high costs of support and treatment. The modern classifications include various forms of porphyria and hemophilia. The study of pathologies in historical persons, when it is possible to collect information from different sources regarding members of a large family over a long period of time, is of interest for understanding the mechanisms of the development of the disease at the present time. Aim is to analyze the genetic characteristics of variegated porphyria and hemophilia B in a large family. Materials and methods. Data from current guidelines and clinical protocols, scientific literature and genetic databases (OMIM) on various forms of porphyria and hemophilia are analyzed. Information about 1362 people from the British royal family in 18–20^th centuries was collected from open sources and scientific literature. A pedigree of 10 generations, 27 nuclear families with persons with variegated porphyria and hemophilia B has been compiled. Genealogical, segregation, linkage, statistical analysis was performed. The results were used to study reproductive traits. Results. Genealogical analysis showed a family accumulation of porphyria – its prevalence among relatives in a large family was 1,8 %, which is three orders of magnitude higher than among the population of different countries. It was established that there is no statistically significant difference in the sex ratio among patients with the specified pathologies. Data from genealogical and segregation analysis and a penetration rate of 92 % suggest an autosomal dominant type inheritance with incomplete penetrance of disease which is consistent with the literature. The independent nature of inheritance of variegated porphyria and hemophilia B was established. It was found that in persons with porphyria reproductive traits are 3,3–4,1 times differ than the reproductive traits of persons with porphyria and hemophilia at the same time. A statistically significant difference was established between the analyzed traits of patients with porphyria, who at the same time are carriers of the mutation that causes hemophilia, and the indicators of healthy individuals.

Features of the formation of pathogenetic changes of the placental complex on the background of intra-uteronomy infection

Alisa Hoshovska — 2022-11-28

Abstract. One of the main complications during early embryogenesis and placentation is placental insufficiency. Under the influence of various factors, namely infectious factors, which, depending on the biological specificity, negatively affect the germ cells of the parents, the development of the embryo, the formation of the trophoblast and the placenta, which in turn leads to a violation of the function of the placental complex and gestational complications during pregnancy. Due to the expansion of diagnostic possibilities for detecting placental function disorders, as well as in connection with the emergence of new data on the mechanisms of blood circulation regulation in the placenta to assess the functional state of the feto-placental complex at the stage of the formation of primary placental insufficiency against the background of inflammatory diseases of the female genital organs, we were determined the dopplerometric pattern of blood flow (ovarian artery, intervillous space) in women of the main and control groups. Goal. To determine the dopplerometric pattern of blood flow characteristics (ovarian artery, chorionic volume, blood flow study in different areas of the chorion) in pregnant women against the background of inflammatory diseases of the female genital organs in the early trimester of pregnancy. Materials and methods. The main group consisted of 37 women with signs of inflammatory diseases of the female genital organs, the control group consisted of 30 practically healthy women. The results. Obtaining new data on the mechanisms of blood circulation regulation in the ovarian artery and intervillous space at the stage of formation of the placental complex in physiological and complicated pregnancy will allow to supplement the question of the pathogenesis of the development and prevention of placental insufficiency. Conclusions. The study of the blood flow of extraembryonic structures in the early stages of gestation allows to diagnose structural changes at the stage of placenta formation. Violation of blood flow in the first trimester of pregnancy against the background of an infectious factor that penetrates into various vascular links of the mother-placenta-fetus system with the deduction of blood flow volume indicators demonstrates the regularity of the formation of disturbed hemodynamics at the stage of formation of the placental complex. These indicators can serve as a criterion for the selection of women of the risk group for the formation of primary placental insufficiency.

Adropin and risk factors of arterial hypertension in patients with excess body weight and obesity

Nataliia Pokrovska — 2022-11-28

Introduction. Adropin is a hormone that is involved in the pathogenesis of arterial hypertension (AH) and diseases of the cardiovascular system and energy homeostasis, in particular, it reduces insulin resistance by controlling glucose synthesis in the liver. Aim. To investigate the level of adropin and its interaction with risk factors for AH in overweight and obese patients. Materials and methods. 70 patients with AH and overweight or obesity aged 62.4 ± 10.4 years were examined. 10 practically healthy people were selected for the control group. The level of adropin was determined by enzyme immunoassay (Finetest Elisa Kit) in blood serum. The inclusion criteria for participation in the study were: age of patients 40–75 years; arterial hypertension; BMI > 25 kg/m2. Results. It was established that the average level of adropin in patients with AH and comorbid obesity or excess body weight (n = 70) was 775.5 ± 311.7 pg/ml, which is significantly lower than the content of this peptide in practically healthy individuals (n = 10), which was 1084.6 ± 110.2 pg/ml (p < 0.01). A tendency towards a decrease in the level of the hormone in men was noted. It is probably associated with a much higher prevalence of smoking among this category of people, since when assessing the factors contributing to the development of AH and worsening its prognosis, a significant decrease in adropin was found in persons with a history of smoking (p < 0.01). In obese patients (BMI > 30 kg/m2), the level of adropin was significantly lower (p < 0.05), as well as in individuals with blood pressure > 150/90 mm Hg (p > 0.05). Conclusions. The level of serum adropin is significantly reduced in persons with AH and overweight and obesity compared to practically healthy persons. Factors contributing to a decrease in peptide concentration include smoking, obesity, and elevated blood glucose levels. Blood pressure indicators are not critical for changes in blood hormone concentration, which is probably due to medications used to treat AH.

An algorithm recommendation for the pharmacological management of allergic rhinitis in Ukraine: a consensus statement from an expert panel

Bogdan Bil — 2022-11-28

Allergic rhinitis (AR) is increasing at an alarming rate in Ukraine. The clinical picture of AR in modern conditions is changing towards more severe and mixed forms. Allergic rhinitis, especially moderate to-severe, has a negative impact on patient quality of life, productivity, direct, and indirect costs. Achieving adequate symptom control is essential for successful AR management, and relies mostly on pharmacotherapy. Most patients use multiple medications to control symptoms faster and better, but symptoms may persist. With the advent of new combination therapies, such as the intranasal formulation of azelastine hydrochloride and fluticasone propionate in a single device (MP-AzeFlu) like Dymista^®, most AR symptoms can be treated effectively. MP-AzeFlu acts synergistically and blocks two important pathophysiological pathways involved in the early- and late-phase reactions of the disease, providing rapid relief from all AR-associated symptoms. A total of 13 experts from Ukraine, Germany, and India participated in the development of this consensus statement. The lead author drafted the questions pertaining to diagnosis, management, treatment adherence, and real-life evidence of AR in Ukraine, and was agreed with the co-authors and expert panel. This consensus is obtained through guiding statements and recommendations based on literature evidences (recent research outcomes, randomized, and comparative studies), clinical practices and personal experience of using MP-AzeFlu in AR by allergist/ immunologists/ otolaryngologists from Ukraine. This consensus statement aimed to assist practitioners in selecting the appropriate treatment strategies, facilitate optimum use of MP-AzeFlu and provide symptomatic relief for patients with AR in the in Ukraine

Influence of the levels of thyroid hormones on the result of radiofrequency ablation for atrial fibrillation: literature review

Nataliia Bogun — 2022-11-28

Introduction. Atrial fibrillation is one of the most common, clinically significant cardiac arrhythmias and is associated with an increased risk of mortality, hospitalization, and deterioration in the quality of life. The prevalence of atrial fibrillation averages 1% and tends to increase with age. It is well known that aberrations of thyroid hormones have a proarrhythmogenic effect and increase the risk of cardiovascular disease. Currently, radiofrequency ablation is actively used to treat atrial fibrillation, which in most cases has high efficiency and lasting effect. However, recurrence of atrial fibrillation may occur in some patients even after radiofrequency ablation. It is known that thyroid function is closely related to the success of radiofrequency ablation and risk of relapse of atrial fibrillation after the procedure. The aim of this literature review is to determine what is already known about the effect of thyroid and thyroid-stimulating hormones levels on the outcome of radiofrequency ablation of atrial fibrillation and to analyze previous studies. Materials and methods. A complete review of the literature on atrial fibrillation and the relationship between thyroid and thyroid hormones and recurrence of atrial fibrillation after radiofrequency ablation was conducted to examine the effect of hormone levels on the success of radiofrequency ablation and recurrence of atrial fibrillation after the procedure. Results. Data from a significant number of studies suggest that the incidence of atrial fibrillation recurrence remains high after radiofrequency ablation and that thyroid hormones affect the success of radiofrequency ablation even within normal ranges. Evidence may also suggest that patients with thyroid dysfunction, even in the presence of subclinical forms, may require better monitoring of thyroid function prior to the procedure, which may reduce the incidence of atrial fibrillation recurrence. Conclusions. It should be noted that the assessment and correction of all modifying risk factors before radiofrequency ablation can prevent recurrence of supraventricular paroxysmal arrhythmias, improve the prognosis and overall quality of life in patients in this group.

Headache on the background of coronavirus infection: features of the clinical picture

Daryna Feshchenko — 2022-11-28

Introduction. Covid-19 has become a new problem of our time. Incidence in the world is rapidly increasing, and with it, attention to the study of the mechanisms of virus pathogenesis is increasing. New symptoms of SARS-CoV-2 persistence in the human body appear. It has been established that not only respiratory manifestations are observed in infected person, but neurological symptoms are increasingly coming to the fore. The main and common manifestation of Covid-19 infection is a headache in the pre- and post-Covid period. Determining the possible routes of entry of the pathogen into the nerve cell, establishing the specifics of Covid-associated headache remains an urgent problem in medicine. The aim of the study. To analyze the data of the world scientific literature regarding the possible mechanisms of invasion of the SARS-CoV-2 virus into the nervous system and their influence on the development of headache in the pre- and post-covid period. Materials and methods. A retrospective analysis of the literature of scientific databases Scopus, PubMed, MedLines, Web of Science for 2020-2022 was carried out. Results. The latest data of the researchers indicate the neurovirulence of the pathogen. SARS-CoV-2 infects humans using the angiotensin-converting enzyme 2 (ACE2) receptor, which is present in the olfactory region, cerebral cortex, basal ganglia, hypothalamus, brain stem, and endothelial cells. The detailed mechanisms of penetration into the central nervous system (CNS) have not yet been fully understood, but the following transmission routes are considered: through the olfactory nerve, the brain is subsequently affected, the second route is cellular invasion, infected monocytes and macrophages, which are a reservoir for the virus for further distribution to other tissues, the next mechanism is infection of endothelial cells of the blood-brain and epithelial blood-liquid barrier. The researchers explain the mechanism of the appearance of headache due to the direct invasion of the endings of the trigeminal nerve in the nasopharyngeal cavity, which leads to the activation of the trigeminal vascular system. Headache is observed at the beginning of the disease and can last more than 180 days after recovery. It is characterized as bilateral, compressive in nature, lasts for hours, resistant to conventional painkillers, intensifies in the morning, with coughing and physical activity. Conclusions. The SARS-CoV-2 virus causes infection using ACE2 receptors, some of which are localized in different parts of the central nervous system, causing neurological symptoms. Headache is one of the most pronounced symptoms of COVID-19, its characteristics and evolution may reflect various pathophysiological mechanisms, which makes their study necessary for a more thorough understanding of headache in the pre- and post-сovid period and the search for options for its elimination.

Modern aspects of short-term blood presssure variability in arterial hypertension

Olena Kanishcheva — 2022-11-28

Abstract. Arterial hypertension is an important public health problem worldwide due to its high incidence and associated risks of cardiovascular and renal diseases such as coronary heart disease, cerebrovascular disease, chronic kidney disease. The level of blood pressure is the main indicator of hypertension treatment effectiveness and leading cardiovascular risk factor. Blood pressure is one of the most dynamic physiological parameters, which is characterized by continuous and significant changes beat-to-beat, over 24 h, day-to-day, and visit-to-visit. Under physiological conditions, these blood pressure variations are mostly represent a response to environmental stimulation aimed at maintaining cardiovascular homeostasis. However, a persistent increase in the blood pressure variability may be the result of pathological changes in the mechanisms of cardiovascular regulation, which leads to alterations in cardiovascular system functioning with the subsequent development of cardiovascular diseases and complications. The phenomenon of blood pressure variability has been known for a long time. It was first described by the English physiologist Stephen Gales in 1733, and its assessment in clinical conditions became possible at the end of the 19th – beginning of the 20th century, after the invention of the sphygmomanometer and the introduction of non-invasive blood pressure measurement using the Riva-Rocci and Korotkov methods. Historically, blood pressure variability has been viewed as a random factor caused by measurement error, which prevents accurate blood pressure measurement. Вlood pressure variability was considered the so-called «background noise», which was not given any importance and tried to overcome with the help of improving monitoring. However, already at the end of the last century, the discussion of the clinical significance of this indicator in patients with hypertension began. The clinical significance and prognostic implications of blood pressure variability have been demonstrated by a series of clinical and population-based studies conducted in recent years, in which elevated blood pressure variability was associated with a higher risk of target organ damage, cardiovascular events, cardiovascular and total mortality independently of blood pressure level. The review presents modern concepts of blood pressure variability, its classification, and assessment methods. The pathogenetic significance of short-term BP variability in patients with arterial hypertension is reviewed, with a discussion of the available evidence regarding the significance of short-term blood pressure variability in cardiovascular risk stratification.