USE OF MICRONUCLEUS EXPERIMENTS FOR THE DETECTION OF HUMAN CANCER RISKS: A BRIEF OVERVIEW

Introduction. Micronuclei (MN) are small extranuclear DNA-containing structures that are formed as a consequence of structural and numerical chromosomal aberrations. The advantage of MN experiments compared to conventional chromosomal analyses in metaphase cells is that the scoring is by far less time consuming and laborious. MN experiments are currently widely used for the routine screening of chemicals in vitro and in vivo but also for environmental control and human biomonitoring Objectives. The purpose of this review was to collect data on the use of MN experiments for the detection of increased cancer risks as a consequence of environmental, lifestyle and occupational exposures and the detection/diagnosis of different forms of cancer. Methods. Analysis of the literature on methods for MN experiments with humans; as well as the use of this technique in different areas of research. Results. To date, a wide range of protocols for human biomonitoring studies has been developed for the measurement of MN formation in peripheral blood cells and in epithelial from different organs (buccal and nasal cavity, cervix and bladder). In addition to MN, other nuclear anomalies can be scored which reflect genetic instability as well as acute toxicity and the division of target cells. Conclusions. The evidence is accumulating that MN can be used as a diagnostic tool for the detection of increased cancer risks as well as for the early diagnosis of cervical and bladder cancer

CANCER AND COVID-19. A COMBAT STRATEGY

Strict quarantine measures and the unpreparedness of the medical industry have exacerbated public health problems on all continents. The number of patients with advanced stages of cancer has increased at the end of the year. Several approaches could mitigate the negative effects of Covid-19 on screening programs. International oncology organization «European Society of Medical Oncology» (ESMO) has launched a section COVID 19 on its website. We believe that some aspects of the ESMO recommendations should be widely presented. The feasibility of vaccinating cancer patients against COVID-19 is undeniable

APPRECIATION TO THE EDITORIAL BOARD, AUTHORS, REVIEWERS, AND THE EDITORIAL STAFF FOR THEIR CONTRIBUTIONS TO THE "PROCEEDINGS OF THE SHEVCHENKO SCIENTIFIC SOCIETY" FOR THE YEARS 2020-2021

Dear Reader! We express our sincere appreciation to all the authors, reviewers, members of the editorial board, and the editorial staff for their tireless contributions during these difficult years 2020-2021. The preparation of each issue of "The Proceedings of the Shevchenko Scientific Society: Medical Sciences” ensures its continuing development. The Journal is accepted by the Content Selection & Advisory Board of Scopus to the international indexing Scopus; to the international catalog of journals Ulrichsweb & Ulrichs; and to the Norsk Center for Forsknings data. As an open-access journal that undergoes peer review, the Editors have received multiple manuscripts from multiple countries. Information from the website shows that we had readers in 134 countries.

PSYCHO-EMOTIONAL ASPECTS IN THE FORMATION OF PAIN SYNDROME CHARACTERISTICS IN PATIENTS WITH MULTIPLE SCLEROSIS

Introduction: Pain syndromes, anxiety, and depression are common syndromes in multiple sclerosis (MS). Comorbidity of pain and depression or pain and anxiety exists in up to one-third of MS patients. Based on the biopsychosocial model of pain, given the high prevalence of these symptoms and their frequent combination in MS, which is significantly higher than in the general population, we can hypothesize the relationship between the characteristics of pain and anxiety and depression in patients with MS. Objectives: To assess the prevalence of anxiety and depression among MS patients with pain syndromes and analyze the relationship between anxiety and depression with pain syndromes' characteristics in patients with MS. Methods: Data were collected prospectively at Lviv Regional Multiple Sclerosis Center. 120 randomly selected patients with a confirmed diagnosis of multiple sclerosis were examined. 104 of them had pain syndromes during the last month. Complaints and medical history, analysis of medical records, neurological and general medical examination of the patients were collected. Depressive symptoms and anxiety were assessed in all patients using the Hospital Anxiety and Depression Scale (HADS) questionnaire. In patients with pain syndromes, the Visual analogue scale (VAS), Short-form McGill Pain Questionnaire 2 (SF-MPQ-2), Pain Detect were used to assess pain characteristics. Results: The levels of anxiety and depression were higher in the group of MS patients with pain. The level of anxiety was 9.0 [6,0; 12,75] in the group with pain and 7.0 [4,0; 9,25] in the group without pain (p=0.04). The level of depression was 7.0 [4,0; 10,0] in the group with pain and 4.0 [1,75; 6,0] in the group without pain (p<0,01). It was found that part of MS patients with pain syndromes with anxiety was 36.5%, and 29.8% had a subclinical level of anxiety; part of MS patients with pain syndromes with depression was 19.23%. The proportion of patients with anxiety was highest in patients with neuropathic pain: 56.3% ± 8.8% vs. 22.4% ± 6.0% with nociceptive, p<0.01. A similar situation is observed in patients with depression. The share of patients with depression was higher in the group with neuropathic pain 37.5% ± 8.6%, compared to 14.3% ± 5.0% with nociceptive, p=0.02. The proportion of patients with MS without signs of anxiety and depression is significantly higher among patients with nociceptive pain (p<0,05). Also, the correlational relationship between the level of anxiety and depression with the level of the neuropathic type of pain manifestation was found (r=0,40; p<0,01 and r=0,30; p<0,01). Levels of anxiety and depression correlated with the average pain intensity per month (r = 0,21; p=0,03) and did not have a statistically significant relationship with pain intensity at the time of examination and the strongest pain for the last month. The anxiety and depression had correlations with all components of the structure of pain syndromes (according to sfMPQ-2), but the most pronounced direct correlation was found between anxiety and the affective component of pain (r=0,57; p<0,01). It was also found that the level of anxiety was proved to be higher in patients who have 2-3 pain syndromes, than in patients with one pain syndrome: 12.0 [8,0; 14,0] points against 8.0 [5,0; 11,0] points, p<0.01. Besides, this localization of pain in the arms, shoulders and back was related to higher levels of anxiety (r=0.22; p=0.03). Conclusion: Pain syndromes, anxiety, and depression are widespread among patients with MS and there is a relationship between them. MS patients with pain have higher levels of anxiety and depression than MS patients without pain. It is also noteworthy that among MS patients with pain syndromes, high levels of anxiety are detected. Anxiety and depression also have a pronounced relationship with a neuropathic component of pain in patients with MS. Besides this, the presence of more than one pain syndrome, high average pain intensity per month is associated with higher levels of anxiety and depression. The localization of pain in the arms, shoulders and back is related to higher anxiety levels. These discoveries, combined with modern neuroimaging technologies used in the next step of our study, will provide a better understanding of both pain and its structure, as well as anxiety and depression

ADVANCES IN SCIENCE EDITING AND COMMUNICATION (PART 3)

In the second half of 2021, 2 webinars and a meeting of the editorial team of the journal “Proceedings of the Shevchenko Scientific Society. Medical Sciences ” took place online. These events took place as a continuation of a specially designed program of lectures and masterclasses in English to improve the writing skills of modern high-quality scientific publications. These events were held with the support of Danylo Halytsky Lviv National Medical University, the Shevchenko Scientific Society, the Western Scientific Centre of the National Academy of Sciences of Ukraine, the Ministry of Education and Science of Ukraine, and the Council of Scientific Editors of Ukraine. Registered participants had the opportunity to view online broadcasts and recordings of the events at “Рroceedings of the Shevchenko Scientific Society. Medical Sciences” journal Facebook page and Youtube channel (https://www.youtube.com/channel/UC40L7KlZ5UU4hrMj_--yqHw). Each registered participant received a certificate with a certain number of points of continuous professional development

THE ROLE AND PLACE OF DAMAGE CONTROL SURGERY IN MILITARY MEDICAL EVACUATION DOCTRINE DURING HOSTILITIES IN MODERN WAR

Introduction: The severity of the combined injury, traumatic shock, blood loss and traumatic prolonged primary surgery are the cause of high mortality injured patients. In civilian medicine, damage control technology is widely used to treat patients with severe polytrauma, which has improved the survival of this group of patients. Objective: Analyze the effectiveness of using "damage control" technology in wounded with polytrauma at the second level of medical care during war conflict in Eastern Ukraine and organization of combat casualty care. Methods: Medical and statistical analysis of the effectiveness medical treatment for patients combat-ralated injuried and polytrauma performed on the basis of a mobile military hospital during 2015-2019 period. Results: In 660 patients with combat multiple and combined injuries and in 1027 - with severe military combined trauma, medical tratment was provide by "damage control" technology. The main task of the first stage of surgery intervention was to stop the bleeding and stabilize the patient condition. 130 patients with intra-abdominal bleeding underwent laparotomy, temporary stop of bleeding, blood sampling for autotransfusion and temporary closure of the abdominal cavity. For the purpose of temporary hemostasis in 15 patients abdominal tamponade was performed, in 26 - liver tamponade, in 24 - splenectomy, in 6 - nephrectomy and in 6 - put the clamps were applied to bleeding vessels. In 14% injured patients definitive stage of surgical procedures were performed at the second level of medical care on the background of abdominal compartment syndrome in 10, visceral edema in 14 and peritonitis in 40 patients. Conclusions: Providing emergency medical treatment, surgical procedures and intensive care at the second level of medical tretment using the technology of "damage control" and timely patients evacuation are the key to reducing mortality and complications of military surgical trauma

ARTIFICIAL INTELLIGENCE AND NEXT GENERATION PATHOLOGY: TOWARDS PERSONALIZED MEDICINE

Introduction. Over the past few decades, thanks to advances in algorithm development, the introduction of available computing power, and the management of large data sets, machine learning methods have become active in various fields of life. Among them, deep learning possesses a special place, which is used in many spheres of health care and is an integral part and prerequisite for the development of digital pathology. Objectives. The purpose of the review was to gather the data on existing image analysis technologies and machine learning tools developed for the whole-slide digital images in pathology. Methods: Analysis of the literature on machine learning methods used in pathology, staps of automated image analysis, types of neural networks, their application and capabilities in digital pathology was performed. Results. To date, a wide range of deep learning strategies have been developed, which are actively used in digital pathology, and demonstrated excellent diagnostic accuracy. In addition to diagnostic solutions, the integration of artificial intelligence into the practice of pathomorphological laboratory provides new tools for assessing the prognosis and prediction of sensitivity to different treatments. Conclusions: The synergy of artificial intelligence and digital pathology is a key tool to improve the accuracy of diagnostics, prognostication and personalized medicine facilitation

ENDOTHELIAL DYSFUNCTION UNDER EXPERIMENTAL SUBARACHNOID HEMORRHAGE. POSSIBLE WAYS OF PHARMACOCORRECTION

Purpose of the article: to study the effect of acelysine and nimodipine on certain endothelial dysfunction indicators and to evaluate their therapeutic efficacy after subarachnoid hemorrhage in rats. Materials and Methods: an experimental study was carried out using 50 Wistar rats of both sexes. Spontaneous subarachnoid hemorrhage was modeled in animals. Three groups of animals were identified: a control group, a group of animals received a standard therapeutic dose of acelysine, and a group received a standard therapeutic dose of nimotop. Each group included 15 animals. There were also 5 intact animals. The animals were withdrawn from the experiment on days 4 and 7 after the motor and exploratory activity determination. Motor and exploratory activity determination was carried out following SAH with the “Open Field” technique. Determination of biochemical markers of endothelial dysfunction was performed in a rat brain homogenate. Results and discussion. It was found that modeling of subarachnoid hemorrhage (SAH) led to the oxidative stress development development and the product of oxidative modification of proteins (nitrotyrosine (Ntz) on the 4th and especially on the 7th day of the experiment) increase in the brain tissues. Starting from the 4th day, we registered a compensatory increase in the activity of NO-synthase (NOS) - by 56%, followed by a decrease in its activity on the 7th day, by more than 33% against the intact group of animals. It was registered a compensatory increase in VEGF-A in rats with SAH modeling on the 4th day of the experiment and its further decrease on the 7th day. The established pathobiochemical changes in the brain tissue were accompanied by the cognitive deficit development in experimental animals, especially on the 7th day of the SAH. SAH led to a significant decrease in the total activity of animals by 2.63 times, a decrease in the distance traveled by animals by 1.89 times, the number of freezes increased by 1.86 times and the immobility of animals increased when moving from the periphery to the center and immobility in the center of the arena (anxiety, fear, disorientation), as well as a decrease in the distance traveled and the speed of movement in illuminated center of the arena 2 and 2.6 times, respectively. Experimental therapy with acelysine 15 mg/kg led to the normalization of biochemical indicators of endothelial dysfunction: concentration of nitrotyrosine, starting from the 4th day of the experiment, increased eNOS activity and VEGF-A concentration (by 75% and 64% on 7th day). The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. Administration of namidopine resulted in only a slight increase in VEGF-A concentration. Acelysine and nimotope significantly increased the total activity of rats on the 7th day after SAH by 76.3% and 48.8%, respectively. In animals treated with acelysine, anxiety and fear decreased. The animals were less aggressive and more empathic - long-term grooming increased 3 times. The administration of nimotop in rats survived SAH had a less pronounced positive effect on behavior. Nimotop did not effect on indicators of general activity and did not increase the total distance traveled. Animals received nimtop were inactive by the 7th day of treatment. Conclusions: Experimental therapy with acelysine led to the normalization of biochemical parameters of endothelial dysfunction, namely nitrotyrosine concentration, starting from the 4th day of the experiment and increased eNOS activity and VEGF-A concentration. It should be noted that, in contrast to the rats of the control group, under prescription of acelysine, there was an increase in the concentration of eNOS and VEGF-A both on the 4th and 7th days of the experiment. The administration of namidopine led to less pronounced effects, statistically significant changes occurred only in relation to the VEGF-A concentration. The administration of acelysin to animals after SAH had a beneficial effect on the emotional status and behavior of animals, and also led to the normalization of their general activity and orientation-exploratory activity. The mechanism of edotheliotropic effect of acelysine, in our opinion, is associated with its antioxidant effects, modulating impact on endothelial NOS, as well as its property, indirectly, to influence on increase VEGF content. Nimotope therapy had no effect on the emotional status and behavior of the animals. The use of calcium channel blockers revealed such side effects as depression, drowsiness, diplopia, and disorientation

PREDICTION OF THE DEVELOPMENT OF PERIODONTAL DISEASE

Introduction. Periodontal tissue disease is one of the most common dental pathologies, which among young people occurs with a frequency of 60% to 99%. Therefore, the problem of finding new links in the pathogenesis, the reasons for the growing prevalence of periodontal disease, as well as effective methods for its early diagnosis and prevention, is relevant. Objectives. Establish the possibility of using individual stomatological and psychophysiological features to predict the development of periodontal disease. Materials and methods. 156 students aged 18-23 years old without systemic diseases were surveyed for some features of oral hygiene and nutrition. Also the study subjects underwent a dental examination, psychological testing and the assessment of individual typological features of higher nervous activity and autonomous regulation. The model for statistical prediction were designed using neural networks. Results. Two neural networks were designed with the best predictors among dental history and examination, psychological testing, parameters of higher nervous activity and heart rate variability analysis. The diagnostic sensitivity of the first prognostic model was 83.33 % and the specificity was 92.31 %. The second model was characterized by 90.00 % sensitivity and 78.57 % specificity. Conclusion. The method of modeling using neural networks based on the index assessment of the condition of teeth hard tissues, the level of oral hygiene and the evaluation of psychophysiological features can effectively predict the risk of periodontal disease development in young people

IMMUNE CYTOPENIAS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA (PECULIARITIES, PROGNOSTIC MARKERS)

Background: Immune cytopenia (IC) is one of the major complications in chronic lymphocytic leukemia (CLL). The paper describes the peculiarities of different immune cytopenia in CLL patients and the importance of individual prognostic markers in the course of the disease. Methods: We observed 62 patients with CLL complicated by immune cytopenia. Among these patients 30 had autoimmune hemolytic anemia (AIHA), 18 experienced immune thrombocytopenia (ITP), 10 had Fisher-Evans syndrome (FES), 3 were diagnosed with partial red cell aplasia (PRCA), and immune neutropenia (IN) was revealed in 1 patient. In addition to general examination and laboratory studies, the following examinations were performed: immunophenotyping of peripheral blood lymphocytes, flow cytometry (CD5; CD19; CD20; CD23; CD38; ZAP70), Coombs test, a molecular cytogenetic study of peripheral blood lymphocytes using the FISH method with TP53 and ATM probes, the level of ß2-microglobulin. Results: It was established that the overall survival of CLL patients with IC depends on the form of the latter. The median overall survival in patients with Fisher-Evans syndrome was the shortest (75 months), slightly better survival was observed in patients with AIHA (median 80 months), the best survival was found in patients with ITP (median not reached). Among unfavorable markers of CLL with IC, there is the presence of del 11q22.3. Unfavorable prognostic markers were also the following: a positive Coombs test, high levels of ZAP 70 expression, and high levels of ß2-microglobulin