Nonspecific Reactions Research Articles

Psychological stress and cardiovascular diseases: clinical case

In the modern world, stress occupies a leading place among significant problems for humanity, being an etiological factor of about 80% of diseases. Social, physical and psychological factors can act as stressors that influence and determine the non-specific response of the body. In most cases, the nonspecific stress-induced reaction of the body is manifested by the picture of psychovegetative syndrome, an important component of which is the activation of the sympathetic nervous system. In a prolonged stress situation, psychovegetative syndrome can be a manifestation of stress-induced anxiety. Anxiety is detected in more than 25% of patients with a general somatic profile. Stress-induced reactions and anxiety can subsequently contribute to the development of psychogenic somatic pathology, including the cardiovascular pathology. Acute or chronic stress situation increases the risks of developing arterial hypertension, coronary heart disease, heart rhythm disorders. In the presence of background cardiac pathology, stress-induced reactions contribute to the deterioration of its course and reduce the effectiveness of treatment. The above indicates the need for a comprehensive assessment of the condition of patients with a general somatic profile. The active use in practical medicine of psychometric and psychodiagnostic scales for anxiety and depression is shown to assess the mental status of patients. When detecting stress-induced reactions or comorbid psychopathology, inclusion of psychotropic drugs, including antipsychotics (alimemazine), is indicated in the complex therapy. Timely administration of alimemazine in patients with a general somatic profile stops psychovegetative manifestations, has positive somatotropic effects due to the multimodal mechanism of action of the drug. In this clinical case, the use of alimemazine in a patient with hypertension, rhythm disorders and comorbid anxiety is presented.

Target-Catalyzed Self-Assembly of DNA-Streptavidin Nanogel for Enzyme-Free miRNA Assay.

Rapid, sensitive, specific, and user-friendly microRNA (miRNA) assays are in high demand for point-of-care diagnosis. Target-catalyzed toehold-mediated strand displacement (TMSD) has received increasing attention as an enzyme-free molecular tool for DNA detection. However, the application of TMSD to miRNA targets is challenging because relatively weak DNA/RNA hybridization leads to failure in the subtle kinetic control of multiple hybridization steps. Here, a simple method is presented for miRNA assay based on the one-pot self-assembly of Y-shaped DNAs with streptavidin via an miRNA-catalyzed TMSD cascade reaction. A single miRNA catalyzes the opening cycle of DNA hairpin loops to generate multiple Y-shaped DNAs carrying biotin and a quencher at the end of their arms. Introducing a single base-pair mismatch near the toehold facilitates RNA-triggered strand displacement while barely disturbing nonspecific reactions. The Y-shaped DNAs are self-assembled with fluorescently labeled streptavidin (sAv), which produces nanoscale DNA-sAv nanogel particles mediating efficient Förster resonance energy transfer in their 3D network. The enhancing effect dramatically reduces the detection limit from the nanomolar level to the picomolar level. This work proves that TMSD-based DNA nanogel with a base-pair mismatch incorporated to a hairpin structure is a promising approach towards sensitive and accurate miRNA assay.

Pathophysiology of Inflammatory Bowel Disease: Innate Immune System.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is a heterogeneous state of chronic intestinal inflammation with no exact known cause. Intestinal innate immunity is enacted by neutrophils, monocytes, macrophages, and dendritic cells (DCs), and innate lymphoid cells and NK cells, characterized by their capacity to produce a rapid and nonspecific reaction as a first-line response. Innate immune cells (IIC) defend against pathogens and excessive entry of intestinal microorganisms, while preserving immune tolerance to resident intestinal microbiota. Changes to this equilibrium are linked to intestinal inflammation in the gut and IBD. IICs mediate host defense responses, inflammation, and tissue healing by producing cytokines and chemokines, activating the complement cascade and phagocytosis, or presenting antigens to activate the adaptive immune response. IICs exert important functions that promote or ameliorate the cellular and molecular mechanisms that underlie and sustain IBD. A comprehensive understanding of the mechanisms underlying these clinical manifestations will be important for developing therapies targeting the innate immune system in IBD patients. This review examines the complex roles of and interactions among IICs, and their interactions with other immune and non-immune cells in homeostasis and pathological conditions.

Investigation of Apparent Solid Phase-Only Red Cell Serologic Reactivity: Clinical and Laboratory Correlations.

Solid phase red cell adherence is a sensitive platform for blood group antibody detection, but non-specific reactions may occur. The aim of this study was to define the clinical characteristics of patients with these reactions and their associated laboratory findings. An 8-month retrospective review of a regional blood bank database was performed. One hundred and seventy-three patients were identified with apparent nonspecific solid phase (NSP) reactivity. Serologic findings were recorded, and each patient's electronic health record was interrogated. NSP reactivity was the most common positive finding in the laboratory. Of 173 patients with NSP, 167 had documented concurrent tube testing. Of these, 165 were negative, one demonstrated nonspecific reactivity, and one anti-Lea was identified. Most positive solid phase antibody screens had negative panel testing, with fewer cases of pan-reactivity or sporadic reactivity. Follow-up testing was either negative (85.5%) or demonstrated NSP reactivity (14.5%). No new blood group antibodies were identified. Most patients were female (72.8%), with pregnancy being the leading diagnosis (35.8%); however, this mirrored the distribution of cases received in the laboratory. When pregnant patients were excluded, female and male patients had the same average age, and the gender distribution and the primary diagnoses of NSP patients mirrored those of all patients evaluated. Solid phase antibody detection is known to be sensitive, but nonspecific reactions are relatively common. Compared to other studies, the evolution of NSP to clinically significant antibodies was not seen, female patients did not have a predilection for NSP reactivity, and NSP was not associated with certain diagnoses.

False positives in infectious serology : a rare issue that should not be ignored

Although rare, false-positive results from infectious serology tests can mislead the practitioner and have harmful consequences for the patient. The causes are not always clear, but there are certain principles that are important to be aware of, and that help to interpret these diagnostic puzzles correctly. Similarities between different families of pathogens, the technical characteristics of the tests used, the use of therapeutic human immunoglobulins, the detection of vaccine-induced antibodies or even the detection of vaccine antigens themselves can cause non-specific reactions. This article uses examples from routine laboratory practice to illustrate the problem and draw the attention of the treating physician to this issue.

FEATURES OF CHANGES IN INTEGRATIVE INDICATORS OF ENDOGENOUS INTOXICATION, REACTIVITY, INFLAMMATION ACTIVITY IN PATIENTS WITH CHRONIC VIRAL HEPATITIS AND CHRONIC RENAL FAILURE

The aim: to study the peculiarities of changes in integrative indicators of endogenous intoxication, reactivity and activity of inflammation in patients with chronic viral hepatitis B and C, and with chronic renal failure undergoing hemodialysis. Materials and methods. 19 patients with chronic viral hepatitis B (HBV) and chronic viral hepatitis C (HCV) with chronic renal failure and patients with chronic kidney disease (KD) were examined. Comparison group included 40 healthy blood donors. Epidemiological, clinical and laboratory examination was performed. Indicators of endogenous intoxication, nonspecific reactivity and inflammatory activity were calculated and analyzed using statistical criteria (M±m, Student's test and Mann–Whitney test). Results: an increase in the integrative indicators of endogenous intoxication in patients with the combined pathology of chronic KD and chronic viral hepatitis (VH) is a consequence of the activation of tissue disintegration, cytolysis of hepatocytes and a significant impairment of liver function. A change in the indices of non-specific inflammation indicate expressed activity of the inflammatory process and immunological disorder of reactivity. These changes also suggest decompensated endotoxicosis, as a possible consequence of a chronic infectious process and decompensated endogenous intoxication. Indicators of leukocyte intoxication index (LII), leukocyte shift index (ISL), hematological intoxication index (HII), intoxication index severity (IIS), immunoreactivity index (IR), neutrophil-monocyte ratio (NMR) are increased in all patients with chronic KD, which may be related to the actual cause of development – glomerulonephritis, chronic pyelonephritis, concomitant pathology. More pronounced deviations were found in men of both groups than in women, which may be related to greater adherence to diet, water load between hemodialysis procedures in the latter. Conclusions. Patients receiving invasive manipulations, including hemodialysis, belong to the risk group and are more susceptible, taking into account immunodeficiency, to infection with hepatitis viruses than the general population. CVH is one of the most common types of lesions in them. The obtained changes, namely, a more pronounced increase in the integrative indicators of endogenous intoxication, in patients with the combined pathology of CKD and CVH indicate the activation of the processes of tissue decay, cytolysis of hepatocytes and significant liver function impairment. At the same time, a change in indices of non-specific inflammation indicates a pronounced activity of the inflammatory process and an immunological disorder of reactivity. A clear systemic reaction to inflammatory processes in the body of patients is determined, the probable development of decompensated endogenous intoxication, which is possible consequence of a chronic infectious process. A simultaneous increase in ISL and a decrease in ILG was established, which is associated with the development of endogenous intoxication and a violation of immunological reactivity due to autointoxication of the body. A decrease in Ilymph indicates an active adaptive reaction of white blood cells and a cell-type immunodeficiency, in particular, a decrease in non-specific anti-infective protection. Indicators of LII, ISL, HII, IIS, IR, NMR are increased in all patients with CKD, which may be related to the actual cause of development – glomerulonephritis, chronic pyelonephritis, etc. The difference of integrative indicators between men and women was established, more pronounced deviations from normal were found in men of both groups than in women, which may be associated with greater adherence to diet, water load between hemodialysis procedures in the latter.

A covalent inhibitor targeting the papain-like protease from SARS-CoV-2 inhibits viral replication.

Covalent inhibitors of the papain-like protease (PLpro) from SARS-CoV-2 have great potential as antivirals, but their non-specific reactivity with thiols has limited their development. In this report, we performed an 8000 molecule electrophile screen against PLpro and identified an α-chloro amide fragment, termed compound 1, which inhibited SARS-CoV-2 replication in cells, and also had low non-specific reactivity with thiols. Compound 1 covalently reacts with the active site cysteine of PLpro, and had an IC50 of 18 μM for PLpro inhibition. Compound 1 also had low non-specific reactivity with thiols and reacted with glutathione 1-2 orders of magnitude slower than other commonly used electrophilic warheads. Finally, compound 1 had low toxicity in cells and mice and has a molecular weight of only 247 daltons and consequently has great potential for further optimization. Collectively, these results demonstrate that compound 1 is a promising lead fragment for future PLpro drug discovery campaigns.

Subacute Thyroiditis Developing Within 2 Days of Vaccination Against COVID-19 with BNT162b2 mRNA.

Cases of subacute thyroiditis after vaccination, including against COVID-19, have been increasingly reported.Subacute thyroiditis should be considered in patients with anterior cervical pain with no significant abnormal pharyngeal findings and/or severe palpitations after COVID-19 vaccination because these can be diagnostic clues.It is important to note that this condition can occur as early as a few days after vaccination, in order to avoid diagnostic pitfalls.

MORPHOLOGICAL CHANGES OF THE BLADDER WALL AS A RESULT OF THE ACTION OF EPIRUBICIN

Summary. Intravesical administration of chemopreparations is widely used in clinical practice and in experiments. However, there are practically no data on morphological changes during the action of chemotherapy drugs on the mucous membrane of the urinary bladder. Aim: to establish the patterns of morphological changes in the layers of the bladder wall during intravesical administration of epirubicin. Object and methods: the studies use white outbred rats (females, weight 200-250 g). Epirubicin was administered intravesically. Morphological changes of the bladder wall were assessed by light microscopy of fixed preparations of cells stained with hematoxylin and eosin after 2 hours; 3, 7 and 21 days after administration of the epirubicin. The obtained results were analyzed by the method of variational statistics. Results: the obtained data indicate significant disorders on the side of the bladder wall, namely atrophic changes and fibrosis of the submucosal base. Morphological changes indicated circulatory disorders in the vessels of the bladdemucous membrane and the submucosal base, which was accompanied by a significant nonspecific inflammatory reaction. Conclusions: obtained morphological and morphometric data indicate significant changes in the bladder wall of rats under the action of the chemotherapy drug epirubicin.

ПРИМЕНЕНИЕ ГИПЕРБАРИЧЕСКОЙ ОКСИГЕНОТЕРАПИИ В КОМПЛЕКСНОМ ЛЕЧЕНИИ ЖЕЛЕЗОДЕФИЦИТНОЙ ПОСЛЕРОДОВОЙ АНЕМИИ

Iron deficiency is the most common cause of postpartum anemia due to food habits, insufficient maternal iron reserves at the beginning of pregnancy, in-creased iron requirements associated with pregnancy, and blood loss during childbirth. As a non-drug treatment the use of hyperbaric oxygen therapy (HBO) is proposed. The main essence of the action of HBO is reduced to a rapid in-crease in oxygen tension in tissues due to an increase in the amount of dissolved oxygen in the blood, an increase in its diffusion rate between the blood and the hypoxic tissue site. Non-specific adaptive reactions developing during the use of HBO provide a wide range of therapeutic effects. At the same time, along with the beneficial effect, hyperoxia can also have a toxic effect, the clinic of which de-pends on the duration of exposure, individual sensitivity to oxygen, on the influ-ence of concomitant factors: temperature environment, physical activity, density of the gas mixture. The implementation of the compensatory capabilities of HBO is promising only with timely optimal use of the method.

RELATIONSHIPS BETWEEN LIPID PROFILE AND COMPLETE BLOOD CELL COUNT PARAMETERS

Aim. Given that blood cells play an important role in both atherogenesis and lipid metabolism, the research aimed to assess the specifics of the relationship between the parameters of the blood lipid spectrum and the complete blood count (CBC).
 Materials and Methods. A total of 475 individuals (245 female and 230 male) were included in the study, who simultaneously underwent CBC and determination of lipid profile, namely: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), very low-density lipoprotein cholesterol (VLDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG). Statistical processing of the obtained data was carried out using the "Statistica for Windows 6.0" software package (Statsoft, USA).
 Results. An increase in levels of TC and LDL-C was associated with an increase in the count of lymphocytes and erythrocytes. A rise in VLDL-C and, accordingly, TG levels, as well as a decrease in the level of HDL-C, were associated with an increase in the total leukocyte count in the blood without a significant change in the ratio of their different types, and an increase in erythrocyte sedimentation rate. The count of platelets was directly related to the level of LDL-C and increased in the case of a combination of elevated levels of LDL-C and TG.
 Discussion. The obtained results indicate that the disposal of excess lipoproteins is based on various types of immune reactions. An increase in the levels of VLDL-C and TG is associated with the development of a nonspecific leukocyte reaction, and an increase in LDL-C levels is associated with a more specific platelet-lymphocytic response. A simultaneous increase in LDL-C and TG levels can be associated with the development of both specific and non-specific immune reactions. An increase in the level of HDL-C leads to a decrease in the intensity of innate and adaptive immune responses. Therefore, the lipid profile of patients should be evaluated by taking into account the blood cell counts, especially in the process of hypolipidemic treatment.
 Conclusions. An atherogenic lipid profile is associated with increased counts of all blood cells, reflecting specific and nonspecific immune reactions in response to elevated levels of various lipid groups. Platelets play an important role in lipid metabolism.
 Connection of the research with scientific programs, plans, and topics. The study is a fragment of the planned scientific research of the Department of Internal Medicine No. 2 of the Danylo Halytsky Lviv National Medical University: "Peculiarities and markers of the course of internal diseases under conditions of combination with metabolic syndrome and metabolically associated fatty liver disease", state registration number: 0122U000165.

RESULTS OF CYTOLOGICAL STUDY IN EXPERIMENTAL ANIMALS WITH AND WITHOUT TREATMENT OF ULCERATIVE NECROTIC GINGIVITIS WITH A COMPLEX OF DRUGS WITH ANTIOXIDANT PROPERTIES

Changes in the quantitative indicators of non-specific resistance systems of the body indicate a damage to homeostasis in the body and the development of a pathological process. The state of defense systems largely determines the course and provides a predictive characteristic of the intensity and effectiveness of treatment measures. In patients with inflammatory processes of periapical tissues, there is an imbalance of factors that characterize the state of local resistance of the oral cavity and the mucous membrane of the gums. Also, quantitative and qualitative changes in indicators of phagocytosis, chemotaxis of leukocytes, secretion of cytokines, immunoglobulins, and bactericidal activity of humoral factors of the body's defense were observed.
 Laboratory animals with experimental model of ulcerative-necrotic gingivitis by chemical burn were divided into three groups: intact, control, and experimental. Animals of the control group were not treated; in the experimental group, complex of drugs was applied to the ulcer surface, which included Thiotriazoline ointment, Zinc oxide, and 0.05% Chlorhexidine solution. In the selected periods of observation (3rd, 5th, 7th, and 10th days), cytological examination of smears was used to determine the adsorption reaction of microorganisms (ARM) by counting the number of bacteria adsorbed on the surface of each epithelial cell (based on 100 cells).
 At the beginning of the observation, sharp decrease in the number of highly differentiated cells was noted in the smears of animals of the control group, cells of the III stage of differentiation prevailed, and the IDC decreased to 67.52% of the level of intact animals. In all subsequent periods, animals of the control group showed a gradual increase in the IDC index due to an increase in cells in the V stage of differentiation on the surface of the ulcer. The CDI value was significantly different from the norm on the 5th day, with a value of 75.15% of the physiological level, and on the 7th day, with a value of 87.54%. Only on the 10th day was an unreliable difference from the average indicator with 99.13% to its value.
 In the experimental group, on the 3rd day, sharp and reliable decrease in the number of highly differentiated pools of epitheliocytes and the dominance of cells in the III stage of differentiation was observed, the number of which reached the value of 44.0±1.5%. As a result, at this time, the CDI value decreased relative to the indicator of intact animals to 69.85% of its level. At the end of the observation, the CDI value reliably exceeded the level of intact animals by 4.12%.
 The most significant decrease in the value of ARM in animals of the control group was detected on the 3rd day, which in percentage value was 76% of the value of intact animals. On the 5th day, the value of "ARM +" increased slightly (only by 4%) to 80% of the physiological norm, and on the 7th day by another 5.5% to 85.5%. Even at the end of the experiment, the "RAM +" indicator in the animals of the control group was significantly lower than that of the intact animals. It was equal to 90% of it.
 In the experimental group, unlike the control group, satisfactory state of local non-specific resistance in the area of the damaged mucosa was observed only on the 3rd and 5th days. The value of "ARM+" in these terms was only 79.46% and 83.6% of the value of intact animals, respectively. Due to the local effect of the developed complex of drugs, the state of non-specific resistance on the 7th day of observation reached a value corresponding to the "good" level. The "ARM +" percentage value increased to 93.6% of intact animals. At the end of the observation, it reached 97.87% of the physiological norm.
 Therefore, the cytological study's data coincided with the results of a visual examination of the course of healing of local gingivitis of chemical origin. Due to the additional local anti-inflammatory effect of the developed complex of drugs, it became possible to achieve the normalization of the damaged local non-specific reactivity of the oral mucosa faster (on average, for 3-4 days), and the stimulating regenerative effect promotes more rapid differentiation of epitheliocytes and complete restoration of the damaged area of the gums in a shorter time (on average, 2 -3 days) treatment terms.

The risk of modification of the immune response of the body in agricultural workers from the effects of a biological factor

The issues of timely identification of workers in need of in-depth examination remain relevant and priority; substantiation of criteria for the formation of risk groups, taking into account the assessment of early nonspecific reactions of the body in order to timely ensure rational schemes for the organization of therapeutic and recreational activities. The analysis of the available literature data on determining the role of the immune system in the development of pathology in workers under conditions of industrial microbiological risk seems relevant. We have carried out a systematic search and analysis of modern domestic and foreign literature on the designated topic. Hygienic studies indicate that respiratory dusts, chemicals, conditionally pathogenic saprophytic microorganisms prevail as part of the complex of working environment factors. As a result of adsorption on dust particles, microorganisms are able to trigger the development of pathological processes, followed by the release of inflammatory mediators. Other interrelated and interdependent molecular mechanisms also take part in the processes of formation of inflammation of the respiratory tract. Maintaining the balance of the levels of pro- and anti-inflammatory regulatory proteins - cytokines is the basis for maintaining an adequate balance and the formation of anti-infectious immunity. Epithelial cells are the main organ capable of performing the functions of a barrier to prevent the spread of an infectious agent to the lower respiratory tract. The analysis of scientific literature indicates a significant contribution of microbial contamination of the air of the working area by saprophytic microorganisms to the development of immuno-mediated general somatic, production-related and occupational morbidity. There is not enough work on a clear disclosure of the patterns of immune response, the stage-by-stage indicators of endogenous protection mechanisms, which make it possible to justify timely diagnostic measures and high-quality medical supervision of employees.

ОСОБЕННОСТИ АДАПТАЦИИ МОЛОДЫХ ЛЮДЕЙ К НОВЫМ УСЛОВИЯМ ОКРУЖАЮЩЕЙ СРЕДЫ ПРИ СМЕНЕ МЕСТА ЖИТЕЛЬСТВА

The purpose of the work was to identify patterns of adaptation of young people to new environmental conditions when changing their place of residence. The study was carried out from September 2021 to June 2022, with the participation of134 people, 32 men and 102 women aged 18–20, first-year students of state universities in Volgograd. The gender, age, place of birth and place of residence of the respondents before entering the university were taken into account. To assess the level of systemic maladjustment, in terms of psychological, psychophysiological and psychosomatic symptoms of extreme tension of the body, a blank test by I.N. Gurvich, developed at the Psychoneurological Research Institute. V.M. Ankylosing spondylitis in1992. Manifestations of a stress reaction (Giessen questionnaire of somatic complaints) and anxiety-depressive disorders (HADS scale) were taken into account, and the presence of suicidal ideation was determined –modulo suicidal ideas of the Columbian Suicidal Seriousness Scale (C-SSRS). The functional status, in relation to the stress resistance of the subjects, was assessed by the level of the general nonspecific reactivity of the organism. As a result of the studies performed, it was determined that the maximum development of systemic maladjustment, at the time of passing the second examination session, is characteristic of male students who arrived to study in Volgograd from other regions of Russia. Throughout the spectrum of the studied symptoms of disa-daptation, both in the somatic (headaches, pains in the stomach, heart, abdomen) and in the mental (insomnia, physical fatigue, depression, suicidal ideation) sphere, their prevalence in groups of non-indigenous students is characteristic. residents of the Volgograd region, which is especially pronounced in men. In addition, male students, representatives of other regionsofRussia are characterized by a high level of general non-specific reactivity, indicating their low stress resistance, and men –the natives of the Volgograd region, in general, are characterized by an averagelevel of general non-specific reactivity of the organism.Women –participants in the study, both indigenous and non-indigenous residents of the Volgograd region, are characterized by a high level of non-specific reactivity, which implies an increasedstress reactivity of the body, and, accordingly,a risk of systemic maladaptation.

Development and study of the performance of a reagent kit for the identification of <i>Vibrio cholerae</i> and <i>Vibrio parahaemolyticus</i> by multilocus allele-specific polymerase chain reaction in clinical trials

BACKGROUND: Cholera belongs to the group of infections, and the fight against it is regulated by the WHO International Health Regulations (2005). To date, several test systems have been developed for the polymerase chain reaction (PCR) detection of Vibrio cholerae strains. However, no PCR test systems have been registered for detecting V. parahaemolyticus DNA in clinical material in Russia.
 AIM: To conduct clinical trials and evaluate the performance of the Reagent kit for identification of V. cholerae and V. parahaemolyticus by multilocus allele-specific PCR (kit of reagents Vibrio-screen FL) for the state registration of the specified medical device.
 MATERIALS AND METHODS: The study presents the results of the clinical trials for the reagent kit Vibrio-screen FL that has been developed to optimize the means and methods of identification and differentiation of pathogens of dangerous infections based on data on the diversity of genomes. Clinical trials were conducted at the Head Center of Hygiene and Epidemiology of the FMBA of Russia (license from 02.12.2013 No. ФС-99-01-008342; permission of the Ministry of Health from 16.05.2013 No. 300n) in accordance with the program of clinical trials No. 20.ПМКИ-042/10.20 from 23.09.2020 (Clinical Trial Certificate No. 01.AK-042/10.20 dated 12.10.2020). The clinical trials of the developed reagent kit Vibrio-screen FL used clinical strains of microorganisms of the genus Vibrio and other microorganism species as target analytes. Bacteriological method and multilocus PCR with hybridization-fluorescence detection were used.
 RESULTS: The reagent kit Vibrio-screen FL is a medical device for professional use in clinical laboratory diagnostics. The analytical sensitivity of the reagent kit Vibrio-screen FL was at least 106 copies of the SecY gene when determining belonging to the genus Vibrio; to the species V. cholerae, at least 106 copies of the hlyA gene; and to the species V. parahaemolyticus, at least 106 copies of the vppC gene. When determining the analytical specificity, no non-specific reactions with DNA samples of other microorganism species were found. A medical device for in vitro diagnostics A reagent kit for the identification of V. cholerae and V. parahaemolyticus by multilocus allele-specific PCR (Vibrio-screen FL) meets the requirements of the intended use, which allows it to be used for the differentiation of V. cholerae and V. parahaemolyticus strains isolated from a cultured clinical samples by multilocus allele-specific polymerase chain reaction with hybridization-fluorescent detection. The registration certificate No. РЗН 2021/13360 from 08.02.2021 was received. By the order of Roszdravnadzordated 08.02.2021 No. 1041, a reagent kit Vibrio-screen FL by the Rostov-on-Don Anti-Plague Institute of Rospotrebnadzor was admitted to distribution on the territory of the Russian Federation.
 CONCLUSIONS: The reagent kit Vibrio-screen FL is a high-quality, effective, and safe diagnostic medical device for in vitro diagnostics with sufficient diagnostic sensitivity and specificity to identify specific fragments of Vibrio spp., V. cholerae, and V. parahaemolyticus nucleic acids. These allows it to be used in clinical laboratory diagnostics for epidemiological analysis and registration of diseases caused by pathogenic vibrions.

Fluorometric kinetic determination of aflatoxin B1 by combining Cd-free ternary quantum dots induced photocatalysis and chemometrics

Upon exposure to Reactive Oxygen Species (ROS), Aflatoxin B1 undergone the formation of a highly fluorescent derivative, which was exploited to develop a straightforward methodology for the determination of AFB1 in food samples. Cd-free AgInS2 ternary quantum dots were used as ROS generators, upon visible light irradiation, and kinetic photoluminescence data (PL) collected throughout AFB1 photocatalysis was used to build-up a second-order dataset seeking to overcome selectivity issues related to QDs non-specific reactivity. The use of a flexible multivariate calibration model, as is the case of U-PLS/RBL, allowed to extract useful information from the PL dataset and enabled to achieve the second-order advantage making possible to accurately determine AFB1 even in the presence of unknown interfering species not included in the calibration set. The developed approach allowed the accurate quantification of AFB1 in rice samples at concentration levels in conformity with the EU regulation.

DISCOVERY OF ADAPTATIONAL REACTIONS: A NEW MILESTONE IN THE DEVELOPMENT OF ONCOLOGY

The celebration of the 90th anniversary of the National Medical Research Centre for Oncology at the Ministry of Health of the Russian Federation in the past 2021 expanded its time frame due to other anniversaries that are inextricably linked with the scientific activities of the Rostov Cancer Centre. First of all, this is the 115th anniversary of the birth of M.A. Ukolova, the founder of fundamental research at the Centre for Oncology, the 65th anniversary of the establishment of the experimental department, and the 45th anniversary of the discovery of "Pattern of development of qualitatively differing general nonspecific adaptational reactions of the organism” made by Garkavi L.Kh., Ukolova E. B. and Kvakina E.B.

IMPLEMENTATION OF THE PRINCIPLES OF ACTIVATION ELECTROMAGNETOTHERAPY IN EXPERIMENTAL ONCOLOGY

Identification of an important mechanism of homeostasis associated with the existence of a periodic system of general nonspecific adaptational reactions of the body (AR) [1-3] as well as the study of the conditions for the development of the anti-stress AR of high levels of reactivity as the most favorable AR for an organism, allowed determining the requirements for the parameters of external regulatory actions, acting factors and regimes of their application.

ACCOMPANYING TRANSCRANIAL MAGNETOTHERAPY IN COMBINATION TREATMENT OF HIGH-GRADE GLIAL BRAIN TUMORS

Low survival and poor quality of life in patients with high-grade brain gliomas (HGG) dictate the need to develop and promote new approaches, including accompanying transcranial magnetic therapy (TMT) with pulse-type magnetic field (PT MF) and ultra-low-frequency magnetic fields (ULF MF), characterized by their non-invasiveness and safety in applied procedures. The key point of these original wave technologies is the construction of algorithms of the actions based on the principles of activation therapy, which was developed as a result of the discovery “Pattern of development of qualitatively differing general nonspecific adaptational reactions of the organism” (Scientific Discovery Registration Certificate No. 158 issued by the Committee on Inventions and Discoveries at the Council of Ministers of the USSR, 1975).

SRSF2 or TET2 Mutations in Patients with MDS Predict Increased Red Blood Cell Alloimmunization

INTRODUCTION: Chronic inflammation is associated with increased red blood cell (RBC) alloimmunization. Patients with sickle cell disease (SCD), systemic lupus erythematosus and inflammatory bowel disease, all conditions with increased levels of inflammation, have been shown to be more alloimmunized when compared to the general population. High prevalence rates of RBC alloimmunization have also been observed in patients with myelodysplastic syndrome (MDS). It has recently been shown that an inflammatory microenvironment may be a key driver of MDS pathogenesis. There are a few specific genes recurrently mutated in MDS that have been found to be associated with activation of the innate immune system and formation of the inflammasome, including some involved in epigenetic modification - ASXL1, DNMT3A, EZH2 and TET2 - and spliceosome formation - SF3B1, SRSF2 and U2AF1. The aim of this study was to determine if the genetic mutations driving the inflammatory milieu in MDS could simultaneously be creating an environment that promotes alloimmunization. PATIENTS AND METHODS: We identified patients diagnosed with a myeloid neoplasm, including patients with MDS and acute myeloid leukemia (AML), between 2015 and 2020 on whom a type and screen had been ordered. We recorded the patients’ primary diagnosis, sex, race/ethnicity, age at first sequencing, somatic mutations identified by next generation sequencing (NGS), blood type, antibody screen results, specific alloantibodies and autoantibodies identified, and number of RBC and platelet units transfused. Patients with an autoantibody, a clinically significant alloantibody, or non-specific reactivity with a potential antibody under investigation on their screen were put in the positive antibody screen category, and those with reactivity solely due to Rh immune globulin or monoclonal antibody therapy were put in the negative antibody screen category. Univariate logistic regression was run separately for patients initially diagnosed with AML and those initially diagnosed with a non-AML myeloid neoplasm (MN), using sex, age, race/ethnicity, number of RBC units transfused, and somatic mutation, to determine if any of these variables had a significant association with a positive antibody screen. If quasi-complete separation issues existed, Firth's method for separation was applied to the logistic regression model. All analyses were conducted using a 95% confidence level. RESULTS: Seventy-six patients met inclusion criteria; 44 were male and 32 were female, and ranged in age from 14 to 89 years. The majority of patients were Caucasian (n = 64). Thirty-three patients had an initial diagnosis of AML; 43 were initially diagnosed with a MN, including MDS (n = 36), myeloproliferative neoplasm (n = 2), chronic myelomonocytic leukemia (n = 4) and chronic myeloid leukemia (n = 1). Number of RBC units transfused ranged from 3 - 112 in patients with AML and 0 - 131 in patients with a MN. Thirteen patients with AML had a positive antibody screen (39.4%), compared to 21 patients with a MN (48.8%). Patients with AML most often developed an alloantibody without an accompanying autoantibody (58.3%), while patients with a MN most often developed alloantibodies in addition to autoantibodies (52.4%). Patients with a MN and a SRSF2 mutation had a significantly increased rate of allo- or auto-immunization as compared to patients with AML and a SRSF2 mutation (p-value = 0.035). Similarly, patients with a MN and a TET2 mutation had a significantly increased rate of allo- or auto-immunization as compared to patients with AML and a TET2 mutation (p-value = 0.021). CONCLUSIONS: In patients with a MN, the presence of a SRSF2 or TET2 mutation predicted the presence of at least one allo- or autoantibody. Our data support the hypothesis that genetic mutations involved in formation of the inflammasome may be involved in the increased alloimmunization seen in patients with MDS. Our study of alloimmunization in MDS, and further studies like it, may enable us to predict based on genetic mutations which patients with MDS may be at increased risk for becoming alloimmunized. Similar to prophylactic C, E and K antigen matching that some blood banks employ in patients with SCD to minimize formation of alloantibodies, extended phenotype matching for the most immunogenic antigens could also be considered in patients with MDS and SRSF2 or TET2 mutations to decrease alloimmunization in this patient population.