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Fundamental and Clinical Medicine

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Vol 6, No 2 (2021)
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ORIGINAL RESEARCH

8-15 558
Abstract

Aim. To substantiate the need for coordinating measures to prevent rabies in adjacent territories with similar conditions for the spread of this infection.

Materials and Methods. We retrospectively analyzed spatiotemporal trends in rabies spread during 1950-2020 by studying available statistics from nine Siberian territories (Altai Republic, Altai Region, Tyva Republic, Khakassia, Buryatia, Krasnoyarsk Region, Transbaikal Region, Irkutsk Region and Kemerovo Region). Mapping of rabies cases in humans (n = 124) and animals (n = 1648) was carried out using QGIS 3.16.3, ArcMap 10.8.1 and ArcScene 10.8.1 software and open electronic landscape maps Natural Earth and OpenStreetMap.

Results. We revealed two periods of intensive rabies spread in southern Siberia: 1) from 1950 to 1983; 2) from 2002 to the present time. However, human rabies was recorded only during the first period. In all studied territories, inter-epizootic periods lasted from 10 to > 40 years. Geographical analysis identified a mosaic localization pattern and a relative isolation of the affected areas. After 2002, there has been a connection between location of animal rabies cases with agricultural lands and a consistent advance of epizootics from west to east and north-east in all territories, excepting Irkutsk Region. The identified regional features of the spatial distribution of rabies were due to a mountainous terrain and a connection of some forest-steppe areas with similar landscapes of neighboring countries.

Conclusions. Southern Siberia is characterized by long rabies-free periods and by the infection foci isolated from other areas as a result of periodic viral invasions from adjacent territories. These features determine the common approaches to the organization of preventive measures across the territories, suggesting their increased efficiency due to the numerous natural barriers and the possibility to concentrate the resources within the small areas. Our results indicate the feasibility of a regional approach to rabies control. 

16-23 573
Abstract

Aim. To identify clustering areas of COVID-19 cases during the first 3 months of pandemic in a million city.

Materials and Methods. We collected the data on polymerase chain reaction verified cases of novel coronavirus infection (COVID-19) in Omsk for the period from April, 15 until July 1, 2020. We have drawn heat maps using Epanechnikov kernel and calculated Getis-Ord general G statistic (Gi*). Analysis of geographic information was carried out in QGIS 3.14 Pi (qgis.org) software using the Visualist plugin.

Results. Having inspected spatial distribution of COVID-19 cases, we identified certain clustering areas. The spread of COVID-19 involved Sovietskiy, Central and Kirovskiy districts, and also Leninskiy and Oktyabrskiy districts a short time later. We found uneven spatiotemporal distribution of COVID-19 cases infection across Omsk, as 13 separate clusters were documented in all administrative districts of the city.

Conclusions. Rapid assessment of spatial distribution of the infection employing geographic information systems enables design of kernel density maps and harbors a considerable potential for real-time planning of preventive measures. 

24-30 566
Abstract

Aim. To evaluate the role of intestinal dysbiosis in the development of urinary tract infections in children admitted to a multidisciplinary hospital.

Materials and Methods. We performed a bacteriological analysis of 2,694 urine samples collected from ≤ 3-years-old children who have been admitted to a multidisciplinary hospital (Kemerovo, Russian Federation). Urine specimens were inoculated by the 4-sector technique. Concurrently, we quantified the intestinal microbiota and its antimicrobial resistance in 100 children with urinary tract infections.

Results. Titers of pathogenic microbes significantly differed in patients from distinct units (p = 0.02). The highest number of positive samples was detected in the neonatal pathology and neonatal intensive care units (43.8% each) as well as urology unit (37.9%). The most frequent pathogens belonged to Enterobacteriaceae family, in particular Escherichia coli, Klebsiella spp., Enterobacter spp., and Proteus spp. All studied children (100/100) suffered from intestinal dysbiosis. Titers of Bifidobacterium spp. and Lactobacillus spp. were reduced to 6 (5.0; 8.0) and 5 (4.0; 6.0) lg CFU/g, respectively. In 89.2% children, Escherichia coli lac+ levels were elevated to 9-10 lg CFU/g. Of note, 18.9% children had high Escherichia coli lac- titers [8 (6.0; 9.0) lg] and 24.3% had high Escherichia coli hly+ titers [5 (4.5; 6.0) lg] in the intestine. We have also found a high frequency (44.6%) and density [8.1 (7.0; 8.5) lg] of Klebsiella spp., in the intestinal mucosa of such patients. Notably, Enterobacter spp. and Proteus spp. were abundant [7 (5.0; 8.0) CFU/g] in the intestinal microbiota of 10.8% children. The prevalence of resistance strains in the studied setting reached 63%.

Conclusions. More than 75% children with urinary tract infections suffer from intestinal dysbiosis. The microbiome of these patients was predominantly composed of Enterobacteriaceae and was characterized by high titers of Escherichia coli lac+, Klebsiella spp., Enterobacte spp., and Proteus spp. Similar profile of antimicrobial resistance in urinary and intestinal isolates of enterobacteria suggests intestinal microbiome as the main source of pathogens causing urinary tract infections in children. 

31-40 507
Abstract

Aim. To find reliable ultrasound markers of efficient non-pharmacological correction of hypofibrinolysis at preconception period in patients with recurrent pregnancy loss.

Materials and Methods. We conducted a single-center, prospective, non-randomized study in patients with recurrent pregnancy loss and hypofibrinolysis (n = 120), who received intermittent pneumatic compression during preconception care. During the pregnancy, we performed a comprehensive 3D ultrasound examination of the endometrium and corpus luteum in the VOCAL mode. Then, we compared patients with (n = 97) and without (n = 23) favorable outcome. Predictive power of the ultrasound parameters was evaluated by a calculation of the area under the receiver operating characteristic (ROC) curve (AUC) and ROC curve comparison.

Results. Vascularization flow index of endometrial perfusion (AUC = 0.566) and corpus luteum (AUC = 0.639) was identified as a potential marker of efficient intermittent pneumatic compression at preconception period.

Conclusions. Adequate perfusion of endometrium and corpus luteum, reflected by vascularization flow index, may indirectly indicate successful trophoblast invasion and minimize the risk of recurrent pregnancy loss. 

41-50 410
Abstract

Aim. To study the features of gestation in women with a combination of antiphospholipid and TORCH syndromes in relation to preconception care.

Materials and Methods. We analyzed 137 medical records of women with a past medical history of pregnancy loss and antiphospholipid syndrome (APS), focusing on the presence or absence of plasmapheresis in the preconception period, and further ranking the patients into 2 subgroups (with and without TORCH syndrome). As a control group, we included 28 pregnant women without both syndromes.

Results. Gestation in women with combined APS and TORCH syndromes was accompanied by a 10-fold higher risk of threatened abortion in the first trimester and 3-fold higher risk of placental insufficiency as compared to those without both syndromes. Notably, the combination of the syndromes doubled the risk of placental insufficiency in comparison with APS alone. The lack of plasmapheresis in patients with APS and TORCH syndrome was associated with > 2-fold higher risk of threatened abortion. Further, in patients with APS and TORCH syndrome, lack of plasmapheresis increased the likelihood of developing fetal hypoxia by a factor of 2 and 3 in comparison with those diagnosed with APS alone or control patients.

Conclusions. TORCH syndrome is a major risk factor of adverse outcome in pregnant women with APS. Inclusion of plasmapheresis into the preconception care in women with APS and TORCH syndrome significantly reduced the development of pregnancy complications. 

51-58 474
Abstract

Aim. To find the predictors of severe pre-eclampsia in women without any established risk factors.

Materials and Methods. We consecutively recruited 200 pregnant women (100 with severe pre-eclampsia and 100 with uncomplicated pregnancy and successful delivery). Criteria of inclusion were age from 18 to 35 years, absence of significant comorbid conditions (cardiovascular diseases, autoimmune diseases, metabolic disorders, and kidney diseases), absence of family history and past medical history of pre-eclampsia and thromboembolism, singleton pregnancy, and body mass index in the first trimester < 35 kg/m2 . We assessed allele and genotype distribution across several gene polymorphisms (ADD1-1378G>T, AGT704T>C, AGT-521C>T, AGTR1-1166A>C, AGTR2-1675G>A, NO3-894G>C, and NO3-786T>C) potentially associated with severe pre-eclampsia.

Results. We found that the combination of AGTR2-1675АA and eNOS3-786СC polymorphisms (p = 0.04), bacteriuria (p < 0.001), acute respiratory infections (p = 0.011) and acute vulvovaginitis in second and third trimesters (p = 0.013), smoking (p < 0.001), and past medical history of abortions (p = 0.017) were risk factors of severe pre-eclampsia.

Conclusions. Predictors of severe pre-eclampsia revealed in this study can be used in the development of personalised prognostication during pregnancy in patients without conventional risk factors of pre-eclampsia. 

59-65 1031
Abstract

Aim. To identify risk factors for abnormal uterine activity.

Materials and Methods. We recruited 200 pregnant women who delivered in the Maternity Hospital of the Podgorbunskiy Regional Clinical Emergency Hospital from 2018 to 2019, evaluating course of pregnancy and labor activity. Patients were further stratified into those who delivered at term (n = 100) but had abnormal uterine activity and those with urgent delivery (n = 100).

Results. The most significant risk factors for abnormal uterine activity were smoking (OR = 26.9, 95% CI = 9.1-79.6), lack of prenatal care visits (OR=16,882, 95% CI = 7.3-39.2), common-law marriage (OR = 5.4, 95% CI = 2.3-12.5), low socioeconomic status (OR = 2.5, 95% CI = 1.3-4.6), higher education (OR = 4.5, 95% CI = 2.5-8.2), and age > 30 years (OR = 3.6, 95% CI = 1.0-13.5). Patients with abnormal uterine activity more frequently suffered from dysmenorrhea, cervical pathology (OR = 1.8, 95% CI = 0.9-3.7), anemia (OR = 1.7, 95% CI = 0.9-3.1), and obesity (OR=2.6, 95% CI = 1.2-5.5). The leading factors associated with abnormal uterine activity are normal birth canal and fetoplacental unit as well as proper cervical ripening.

Conclusions. Psychophysiological alterations represent a major risk factor for abnormal uterine activity, contributing to placental insufficiency, fetal growth restriction, and premature rupture of membranes. Procedures aimed at cervical ripening may reduce the incidence of abnormal uterine activity and improve both maternal and newborn outcomes. 

66-74 441
Abstract

Aim. To estimate psychophysiological changes during workspace virtualization.

Materials and Methods. We evaluated the psychophysiological profile of 10 healthy right-handed males aged 25 to 45 years before, during and after the working in a virtual reality (VR) headset. All participants had higher education, normal or corrected to normal vision, and were experienced computer users. Psychometric testing included a neurological examination, assessment of functional and feedback-related brain activity (reaction time, errors, and missed signals) and attention span, quantification of processed symbols in the 1st and 4th minutes of Bourdon test, analysis of short-term memory (10 words, 10 numbers and 10 meaningless syllables memorization) and spatial perception, and multi-channel electroencephalography recording in rest.

Results. Deterioration of psychometric indicators after a cognitive load in a VR headset was documented only in the most difficult tasks: the number of errors increased by 93% in the brain performance test and by 65% in the attention distribution test. The analysis of electroencephalography data showed that the delta rhythm and theta1 rhythm activity decreased by 28 and 13%, respectively, after working in a VR headset as compared to baseline values, while alpha1 rhythm activity increased by 96%. Probably, the observed electroencephalography changes corresponded to the patterns of brain activation associated with cognitive load and the resulting fatigue.

Conclusions. We developed a suitable approach for the psychometric testing before and after working in VR headset, which demonstrated general tolerance and acceptable subjective difficulties to VR load. 

75-81 401
Abstract

Aim. To analyze age and gender distribution in patients with Gilbert's syndrome.

Materials and Methods. We consecutively recruited 115 patients with Gilbert's syndrome. All patients underwent genotyping of the rs8175347 polymorphism within the UGT1A1 gene using allele-specific polymerase chain reaction to confirm the diagnosis.

Results. The age of initial diagnosis ranged from 3 years to 71 years, with the majority (44.3%) of cases detected ≤ 20 years of age. Mean ± standard error and median age of the diagnosis were 30.03 ± 1.72 years and 23 years. Despite the proportion of females and males among patients was similar, age distribution at primary diagnosis was significantly different across the genders. In women, Gilbert's syndrome was most frequently detected between 11 and 20 years (23.1%) and between 51 and 60 years (19.2%). In contrast, male adolescents were more prone to the development of Gilbert's syndrome, as 47.6% of male patients belonged to this age category.

Conclusions. Variable age of Gilbert's syndrome diagnosis is probably determined by an individual combination of genetic causes (e.g., mutation of the UGT1A1 gene) and additional risk factors. Adolescents compose a significant proportion of patients. Because of relatively mild disease in many patients and unpredictability of the provoking factors, primary detection of Gilbert's syndrome can be delayed. Differences in age of Gilbert's syndrome diagnosis across the genders can be partially explained by organizational reasons associated with the current screening programs. 

REVIEW ARTICLES

82-102 736
Abstract

A growing incidence, prevalence, morbidity and mortality from cardiovascular disease dictate an urgent need in identification of its risk factors and their pathogenetic links with coronary artery disease and stroke. Aging of the population is inevitably associated with an increasing prevalence of comorbid conditions. Among them are disorders of mineral homeostasis which, often being neglected, are clearly associated with major adverse cardiovascular events and cardiovascular death. Maintenance of mineral homeostasis in the human body is largely dependent on the formation of calciprotein particles (CPPs) which arise in the blood upon the binding of a mineral chaperone fetuin-A to nascent calcium phosphate crystals, thereby aggregating excessive calcium (Ca2+) and phosphate (PO4 3-), removing them from the bloodstream and preventing extraskeletal calcification. During the circulation, CPPs are internalised by arterial endothelial cells and provoke endothelial dysfunction through endothelial activation, endothelialto-mesenchymal transition and impairment of endothelial mechanotransduction. Animal studies demonstrated that regular intravenous injections of CPPs lead to intimal hyperplasia and adventitial/perivascular inflammation in the absence of any other cardiovascular risk factors, indicating pathophysiological importance of CPPs for cardiovascular disease. Further, a number of clinical studies suggested an association of an augmented serum calcification propensity or elevated CPP count with arterial hypertension, myocardial infarction, chronic brain ischemia, ischemic stroke and cardiovascular death in patients with chronic kidney disease (including those with end-stage renal disease as well as kidney transplant recipients) and individuals with a preserved renal function. Here, we critically discuss the pathophysiological consequences of CPP formation, mechanisms of their pathogenic effects, and potential therapeutic interventions. 

103-115 750
Abstract

Currently, around 34 million people worldwide suffer from atrial fibrillation (AF), with the number projected to double by 2060. Despite the treatment of AF has been significantly improved during the recent years, AF is still associated with an increased risk of severe complications such as systemic thromboembolism, progression of heart failure, stroke, and myocardial infarction. Due to a high risk of disability and mortality, AF represent a major socioeconomic problem for the healthcare in most countries, also because of related financial costs. Obesity, most often represented by metabolic syndrome, is widely recognized as an epidemic of the XXI century. Here we review the features of AF development in patients with metabolic syndrome, suggesting novel avenues for the primary prevention of AF. 

116-123 504
Abstract

Albeit endometriosis is one of the most common gynecological diseases, its diagnosis and treatment remain controversial. The reasons behind this include: 1) multifactorial pathogenesis and insufficiently studied mechanisms of endometriosis; 2) relatively low diagnostic value of minimally invasive examination in relation to this disease; 3) inefficiency of current therapeutic approaches in many patient settings. In our opinion, uncovering the causes of endometriosis and factors promoting its progression is the cornerstone of its successful management. Here we review the lessons from genome-wide and candidate gene association studies, discuss the expression of regulatory miRNAs and describe the role of heat shock protein 90, annexin A2, and peroxiredoxin 2 in controlling DNA integrity in the eutopic endometrium. Further, we highlight the role of cytokeratin-19 in urine as a feasible diagnostic marker of endometriosis. Clinicians and basic researchers concur that the molecular basis of endometriosis is still in its infancy and current understanding of its pathophysiology remains poor. Recent progress in -omics approaches and bioinformatics paved the way for complex investigations of regulated cell death, proliferation, cell invasion and angiogenesis, opening the avenue for the novel approaches to treat endometriosis. Yet, the diversity of symptoms and an absence of sensitive and specific biomarkers frequently delay and complicate the diagnosis. In addition, surgery represents the only appropriate option to reliably confirm the diagnosis and to establish the disease extent, reducing patient adherence and postponing the start of the treatment. In this review, we discuss challenges in the diagnosis of endometriosis as well as relevant and potentially informative biomarkers. 

124-135 767
Abstract

Male infertility is an urgent medical and demographic threat worldwide, in particular in industrial regions suffering from environmental pollution. Here we performed an analysis of epidemiological studies and meta-analyses of prevalence, causes, and risk factors of male reproductive disorders. Among the well-defined risk factors determining male infertility are hormonal imbalance, sexually transmitted infections, other inflammatory diseases, hereditary mutations, and congenital malformations. Less studied causes of male infertility are acquired mutations and gene polymorphisms, immune disorders, oxidative stress, and chronic conditions. To date, there is no consensus on the contribution of lifestyle, bad habits, working environment, and climatic factors to male infertility. As such, 40-50% male infertility cases are characterized as idiopathic. 

CASE REPORTS

136-141 460
Abstract

Here we present a clinical case of microstomia with the focus on the oral rehabilitation of the patient. Microstomia, an abnormal contracture of the mouth, occurred in this case as a result of alveolar resection due to cancer, and scarring impeded mouth opening. The patient needed a partial removable laminar denture for the upper jaw. Prosthetics became possible upon normalization of oral mucosa. We describe the imprint preparation features in conditions of lacking right alveolar appendix and crossover fold after surgery. The formation of the wax board in combination with molding allowed demarcation of denture border. The laminar denture successfully replaced jaw and teeth defects, restored proper mastication, improved mouth moistening and speech, as well as facial aesthetics and quality of life. 



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ISSN 2500-0764 (Print)
ISSN 2542-0941 (Online)