Predictors of Unfavorable Prognosis in Patients with Heart Failure After Cardioverter-Defibrillator Implantation According to the Prospective Part of the Kuzbass Registry.

AIM: Identification of clinical and instrumental predictors for non-arrhythmic death in patients with heart failure (HF) and implantable cardioverter-defibrillator (ICD). MATERIAL AND METHODS: Through a telephone survey and examination of medical records from hospital and polyclinic databases, data were obtained on the alive/dead status and causes of death for 260 patients with heart failure (HF) and ICD included in the Kuzbass Registry of Patients with ICD. The follow-up period was 1.5 years. Clinical and instrumental parameters entered into the registry before the ICD implantation were included in a univariate and multivariate step-by-step analysis using the logistic (for qualitative variables) and linear (for quantitative variables) regression with calculation of regression coefficients and construction of a prognostic regression model. The quality of the created model was assessed using a ROC analysis. RESULTS: During the observation period, 54 (20.8%) patients died. In 21 (38.8%) patients, death occurred in the hospital and was caused by acute decompensated heart failure in 15 (71.4%) patients, myocardial infarction in 3 (14.3%) patients, stroke in 1 (4.7%) patient, and pneumonia in 2 (9.5%) patients. 33 (61.2%) patients died outside the hospital; the cause of death was stated as the underlying disease associated with acute decompensated heart failure: in 9 (27.2%) patients, dilated cardiomyopathy; in 1 (3.0%) patient, rheumatic mitral disease; and in 23 (69.7%) patients, ischemic cardiomyopathy. According to the univariate regression model, the risk of death in the long-term period was increased by the QT interval prolongation (U 2.41, p = 0.0161); elevated pulmonary artery systolic pressure (U 4.30, p=0.0000) and increased left atrial size according to echocardiography (U 2.98, p=0.0029); stage IIB HF (OR 2.41; 95% CI: 1.26-4.6), NYHA III-IV (OR 3.03; 95% CI: 1.58-5.81); chronic obstructive pulmonary disease (OR 5.24; 95% CI: 2.04-13.45); and lack of optimal drug therapy (ODT) for HF before ICD implantation (OR 2.41; 95% CI: 1.29-4.49). The multivariate analysis identified the most significant factors included in the prognostic regression model: pulmonary artery systolic pressure above 45 mm Hg, social status, chronic obstructive pulmonary disease, and lack of ODT for HF. CONCLUSION: To ensure a maximum benefit from ICD, the factors that increase the likelihood of non-arrhythmic death should be considered before making a decision on ICD implantation. Particular attention should be paid to mandatory ODT for HF as the main modifiable risk factor for unfavorable prognosis.

Complexation ability of tetrasulfosubstituted cobalt(II) phthalocyanine toward ORF3a protein of SARS-CoV-2 virus.

Complex formation processes of tetrasulfosubstituted cobalt(II) phthalocyanine with ORF3a accessory protein of SARS-CoV-2 coronavirus were studied. The interaction of ORF3a protein with SARS-CoV-2 virus with tetrasulfosubstituted cobalt(II) phthalocyanine affords a stable complex in which metallophthalocyanine exists in the monomeric form. The complex formation induces slight changes in the secondary structure of the protein by increasing the fraction of disordered fragments of the polypeptide chain. The photoirradiation of the complex of ORF3a protein of SARS-CoV-2 virus with tetrasulfosubstituted cobalt(II) phthalocyanine leads to the photooxidation of amino acid residues of the protein.

Synthesis of water-soluble porphyrin with tyrosine fragments and study of its interaction with S-protein of SARS-CoV-2.

The multistage purposeful synthesis of 5,15-bis(4'-l-N-tyrosinylamidophenyl)-10,20-bis(N-methylpyridin-3'-yl)porphine diiodide was carried out, and the optimum synthesis conditions were determined. 5,15-Bis(4'-nitrophenyl)-10,20-bis(pyridin-3'-yl)porphine served as the starting porphyrin. The structure, individual character, and purity of the target compound were proved by electron spectroscopy, 1H NMR spectroscopy, mass spectrometry (MALDI TOF), and TLC. Specific features of the interaction of the synthesized porphyrin with S-protein of SARS-CoV-2 were studied using spectral and thermochemical methods, including conditions of photoirradiation. The photoirradiation of the synthesized porphyrin in a complex with the SARS-CoV-2 S-protein can result in the partial oxidation of amino acid residues of the protein and distort its primary and secondary structures. The photoirradiation of the S-protein complex with the porphyrin decreases its thermal resistance to melting by 15 °C compared to the free S-protein and causes porphyrin release.

Interaction of 5-[4'-(N-Methyl-1,3-benzimidazol-2-yl)phenyl]-10,15,20-tri-(N-methyl-3'-pyridyl)porphyrin Triiodide with SARS-CoV-2 Spike Protein.

The results of experimental studies of the interaction of the S-protein with a monohetaryl-substituted porphyrin containing a benzimidazole residue are presented. It has been revealed that the S-protein forms high-affinity complexes with the specified porphyrin. The porphyrin binding by the SARS-CoV-2 S-protein has proceeded stepwise; at the first stage, the driving force of the complexation is electrostatic interaction between the surface negatively charged regions of the protein and cationic substituents of the porphyrin. At the second stage, the target complex of the S-protein with the porphyrin is formed. It has been established that the introduction of 5-[4'-(N-methyl-1,3-benzimidazol-2-yl)phenyl]-10,15,20-tri-(N-methyl-3'-pyridyl)porphyrin triiodide into a solution of the S-protein complex with the angiotensin-converting enzyme leads to the replacement of the latter with the porphyrin. Displacement of the angiotensin-converting enzyme from the complex with the S-protein under the action of 5-[4'-(N-methyl-1,3-benzimidazol-2-yl)phenyl]-10,15,20-tri-(N-methyl-3'-pyridyl)porphyrin triiodide is the experimental evidence for the porphyrin binding at the receptor-binding domain of the S-protein.

Spectral and theoretical study of SARS-CoV-2 ORF10 protein interaction with endogenous and exogenous macroheterocyclic compounds.

The coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 coronavirus has spread rapidly around the world in a matter of weeks. Most of the current recommendations developed for the use of antivirals in COVID-19 were developed during the initial waves of the pandemic, when resources were limited and administrative or pragmatic criteria took precedence. The choice of drugs for the treatment of COVID-19 was carried out from drugs approved for medical use. COVID-19 is a serious public health problem and the search for drugs that can relieve the disease in infected patients at various stages is still necessary. Therefore, the search for effective drugs with inhibitory and/or virucidal activity is a paramount task. Accessory proteins of the virus play a significant role in the pathogenesis of the disease, as they modulate the host's immune response. This paper studied the interaction of one of the SARS-CoV-2 accessory proteins ORF10 with macroheterocyclic compounds - protoporphyrin IX d.m.e., Fe(III)protoporphyrin d.m.e. and 5,10,15,20-tetrakis(3'-pyridyl)chlorin tetraiodide, which are potential inhibitors and virucidal agents. The SARS-CoV-2 ORF10 protein shows the highest affinity for Chlorin, which binds hydrophobically to the alpha structured region of the protein. Protoporphyrin is able to form several complexes with ORF10 close in energy, with alpha- and beta-molecular recognition features, while Fe(III)protoporphyrin forms complexes with the orientation of the porphyrin macrocycle parallel to the ORF10 alpha-helix. Taking into account the nature of the interaction with ORF10, it has been suggested that Chlorin may have virucidal activity upon photoexposure. The SARS-CoV-2 ORF10 protein was expressed in Escherichia coli cells, macroheterocyclic compounds were synthesized, and the structure was confirmed. The interaction between macrocycles with ORF10 was studied by spectral methods. The results of in silico studies were confirmed by experimental data.

Long-term outcomes in patients with an implanted cardioverter-defibrillator according to the Kuzbass registry.

Aim    To analyze long-term outcomes by results of the prospective part of the Kuban registry of patients with an implantable cardioverter defibrillator (ICD).Material and methods    A prospective analysis of the incidence of hard endpoints and changes in the condition was performed for 260 patients with ICD successively added to the Registry of Patients with Implantable Cardioverter Defibrillator" from 2015 through 2019.Results    At the time of ICD implantation, all patients had chronic heart failure (CHF), mostly of ischemic etiology with a low left ventricular ejection fraction (LVEF); median LVEF was 30 (25; 36.5) %. 54 of 266 (21.9 %) patients died by 2021; 17 of them (31.5 %) died in the hospital; in 76.5 % of cases, death was caused by acute decompensated heart failure (HF). 139 (53.5%) patients were readmitted; 66 (25.4 %) hospitalizations were related with ICDs (lead revision or reimplantation); acute cardiovascular events developed in 38 (14.6 %) patients; 12 (4.6%) patients underwent percutaneous coronary interventions; orthotopic heart transplantation was performed for 4 patients. ICD shocks were recorded in 27 (10.4 %) patients. After the ICD implantation, median LVEF remained unchanged, 31 (25; 42) vs. 30 (25; 36.5) % (р>0.05). However, both objective and subjective HF symptoms worsened. Thus, the number of patients with IIB stage CHF increased from 29.6  to 88.8 % (р<0.01) and with NYHA III CHF from 24.2  to 34.5 % (p<0.05). 80 (30.8%) patients visited cardiologists on a regular basis. Only 7.3% of patients received an optimal drug therapy. During the observation period, the rate of beta-blocker treatment considerably decreased, from 90.6  to 64.3 % (р<0.01), and the rate of the mineralocorticoid receptor antagonist treatment decreased from 50.8  to 17.4 % (р<0.01). The rate of the diuretic treatment was inconsistent with the severity of patients' condition.Conclusion    Most of the problems the patients encountered after the ICD implantation were related with an inadequate treatment of the underlying disease. Since the majority of patients with ICD have a low LVEF, it is essential to focus on prescribing an optimal drug therapy and maintaining compliance with this therapy.

[Clinical and anamnestic characteristics of patients with an implanted cardioverter-defibrillator in real clinical practice (data from the Kuzbass register)].

Aim      To study the consistency of the practice of management, selection and routing of patients at high risk of sudden cardiac death (SCD) selected for cardioverter-defibrillator implantation (CDI) with current clinical guidelines and to evaluate the quality of subsequent outpatient follow-up and treatment based on a retrospective analysis of clinical amnestic data from the Kuzbass Registry of Patients with CDI.Material and methods  The study was based on the Registry of Patients with Implanted Cardioverter Defibrillator and included successive data of 28 patients hospitalized to the Kizbass Cardiological Center from 2015 through 2019. Social and clinical amnestic characteristics, indications for CVI, and concomitant drug therapy were analyzed retrospectively. Statistical analyses were performed with the Statistica 10.0 software (Statsoft, USA).Results Median age of patients was 59 (53; 66) years; 239 (83.6 %) men were included; 29 (10.1%) people were employed, CHI was performed in 182 (63.6 %) patients for prevention of SCC, and for secondary prevention in 104 (36.4 %) patients. 208 (72.7 %) patients were diagnosed with ischemic heart disease (IHD), and 145 (67.9 %) of them underwent myocardial revascularization. Noncoronarogenic diseases were found in 78 (27.3 %) patients, and most of them were diagnosed with dilated cardiomyopathy. All patients had chronic heart failure (CHF); half of them had stage IIA CHF. Median left ventricular ejection fraction was 30 (25; 36,5) % according to echocardiography using the Simpson method. Comorbidity was found in 151 (52.8 %) patients. 128 (44.8%) patients received a triple neurohormonal blockade for CHF treatment; titration to target doses was not performed in any of them. Antiarrhythmics were administered to 150 (52.4 %) patients.Conclusion      According to the data from the Kuzbass Registry of CVI, the main patient cohort consisted of men of pension age with IHD and CHF. Before CVI, more than a half of them had not received an optimum drug therapy and not all of them had received target lesion revascularization. Creating and analysis of Registries of CHI patients is an effective method for identifying existing problems in patient management before CVI and for optimizing their subsequent follow-up and treatment.

Data on bulk rock compositions, geochemical and textural contrasts between central and marginal parts of dykes, and MELTS modeling of lamprophyre dykes in the Kola Alkaline Carbonatite Province (N Europe).

This publication is a series of datasets that accompany a manuscript on petrology of lamprophyre dykes in the Kola Alkaline Carbonatite Province (N Europe) [1]. The datasets served as the basis for interpretation of melt crystallization for lamprophyric and carbonatitic dykes in the crust, to supplement many papers devoted to mantle sources and melting parameters of these rocks based on radiogenic isotopes and trace elements. The first dataset contains bulk major and trace element compositions of the dykes in three areas, Kandalaksha, Kandaguba and Turiy Mys, along with supplementary information on sampling locations and dyke characteristics. The second dataset represents photos, major and trace element plots illustrating extreme mineralogical and textural heterogeneity and layering observed in some dykes. The photographs include field photographs, optical and electron microscopy shots for thin sections in central and marginal parts of the dykes. They should be viewed together with Harker and REE diagrams illustrating the changes from dyke margins to dyke cores. The third and fourth datasets are output tables from Ryolite-MELTS software used to model crystal fractionation of the dykes from the parental melts and various P, T, fO2, XCO2, XH2O parameters. One table shows compositions of evolved melts, while the other lists crystallizing phases.

Synthesis of Hetaryl-Substituted Asymmetric Porphyrins and Their Affinity to SARS-CoV-2 Helicase.

Novel porphyrin compounds containing benzothiazole, benzoxazole, and benzimidazole moieties have been prepared and their structures have been confirmed. Molecular docking of non-symmetric hetaryl-substituted porphyrins and chlorin e6 with SARS-CoV-2 helicase has been carried out. The affinity of hetaryl-substituted porphyrins to this protein has been found significantly higher than that of the drugs approved by the FDA and chlorin e6. The structure of the complexes of SARS-CoV-2 helicase with the considered macroheterocyclic compounds has been analyzed. Possible ways to inhibit and photoinactivate SARS-CoV helicase have been suggested basing on the localization of porphyrins and chlorin e6 in the helicase domains.

[Current understanding of the role of age-related hypogonadism in the development of cardiovascular diseases].

The literature review presents novel data on the prevalence of age-related hypogonadism and its relationship with aging, its impact on the circulatory system and cardiovascular diseases. This review summarizes the methods for diagnosing age-related hypogonadism, its association with traditional cardiovascular risk factors such as dyslipidemia, insulin resistance and diabetes mellitus, obesity, arterial hypertension. The mechanisms of the possible direct effect of testosterone on endothelium and vascular tone, the role of hormone replacement therapy as a way of preventing cardiovascular diseases are discussed.

Carcinogenesis Associated with Human Papillomavirus Infection. Mechanisms and Potential for Immunotherapy.

Human papillomavirus (HPV) infection is responsible for approximately 5% of all cancers and is associated with 30% of all pathogen-related cancers. Cervical cancer is the third most common cancer in women worldwide; about 70% of cervical cancer cases are caused by the high-risk HPVs (HR HPVs) of genotypes 16 and 18. HPV infection occurs mainly through sexual contact; however, viral transmission via horizontal and vertical pathways is also possible. After HPV infection of basal keratinocytes or ecto-endocervical transition zone cells, viral DNA persists in the episomal form. In most cases, infected cells are eliminated by the immune system. Occasionally, elimination fails, and HPV infection becomes chronic. Replication of HPVs in dividing epithelial cells is accompanied by increased expression of the E6 and E7 oncoproteins. These oncoproteins are responsible for genomic instability, disruption of the cell cycle, cell proliferation, immortalization, and malignant transformation of HPV-infected cells. Besides, E6 and E7 oncoproteins induce immunosuppression, preventing the detection of HPV-infected and transformed cells by the immune system. HPV integration into the genome of the host cell leads to the upregulation of E6 and E7 expression and contributes to HPV-associated malignization. Prophylactic HPV vaccines can prevent over 80% of HPV-associated anogenital cancers. The vaccine elicits immune response that prevents initial infection with a given HPV type but does not eliminate persistent virus once infection has occurred and does not prevent development of the HPV-associated neoplasias, which necessitates the development of therapeutic vaccines to treat chronic HPV infections and HPV-associated malignancies.

Low voltage control of exchange coupling in a ferromagnet-semiconductor quantum well hybrid structure.

Voltage control of ferromagnetism on the nanometer scale is highly appealing for the development of novel electronic devices with low power consumption, high operation speed, reliable reversibility and compatibility with semiconductor technology. Hybrid structures based on the assembly of ferromagnetic and semiconducting building blocks are expected to show magnetic order as a ferromagnet and to be electrically tunable as a semiconductor. Here, we demonstrate the electrical control of the exchange coupling in a hybrid consisting of a ferromagnetic Co layer and a semiconductor CdTe quantum well, separated by a thin non-magnetic (Cd,Mg)Te barrier. The electric field controls the phononic ac Stark effect-the indirect exchange mechanism that is mediated by elliptically polarized phonons emitted from the ferromagnet. The effective magnetic field of the exchange interaction reaches up to 2.5 Tesla and can be turned on and off by application of 1V bias across the heterostructure.

[Neurophysiological peculiarities of cognitive activity in patients anxiety-depressive and hypochondriacal disorders]. / Neirofiziologicheskie osobennosti kognitivnoi deiatel'nosti u patsientov s trevozhno-depressivnymi i ipokhondricheskimi rasstroistvami.

AIM: To study neurophysiological features of the cognitive activity in patients with anxiety-depressive and hypochondriacal disorders. MATERIAL AND METHODS: The study included 65 people: 16 with hypochondriacal disorder, 23 with mixed anxiety and depressive disorder, and 26 control subjects. Heart rate variability method and electroencephalography were used. RESULTS AND CONCLUSION: There was a decrease in the beta-1 frequency range in EEG after performing cognitive test in patients with mixed anxiety and depressive disorder. Patients with hypochondriacal disorder had the reduced duration of RR intervals; increased beta-1 frequency range in the resting state; the increase in the dominant beta-2 frequency during the cognitive test, and in the standard deviation of theta-wave frequencies after the cognitive test.

[Patterns of brain functional connectivity in frontal and temporal lobe epilepsies]. / Patterny funktsional'noi konnektivnosti mozga pri visochnoi i lobnoi épilepsii.

AIM: To examine alterations of functional connectivity (FC) of the brain in patients with frontal and temporal lobe epilepsies. MATERIAL AND METHODS: Forty-three patients, aged 18-55 years, including 32 with temporal lobe epilepsy (TLE) and 11 with frontal lobe epilepsy (FLE), and 32 age/gender-matched healthy controls (HC) underwent structural and functional MRI on 1,5 T scanner. Imaging data were further analysed for functional connectivity characteristics by seed-based and ICA analyses. RESULTS: Most prominent in the TLE group, was a decrease in FC of insula and peri-insular cortical regions compared to HC. These alterations of FC in left-side TLE were significant on the left. An increase of FC between dorsal part of attention resting network and regions of temporal and parietal cortices characterized right-side TLE. In addition, TLE group had decreased FC between anterior cingulate and basal ganglia. All the significant alterations of FC in FLE related to increased FC in patients compared to HC. FC of temporal regions was altered to a greater extent. CONCLUSION: Localization and lateralization of seizure focus determines the alterations of brain FC in patients with focal epilepsy.

[Functioning features of the mirror neuron system in patients with affective disorders]. / Osobennosti funktsionirovaniia sistemy zerkal'nykh neironov u bol'nykh s affektivnymi rasstroistvami.

AIM: To reveal EEG patterns and activation of neural network changes during perception and realization of a simple motor act in healthy subjects and patients with affective disorders. MATERIAL AND METHODS: The patient group consisted of 15 people with affective disorders, the control group included 11 normals. As task subjects were asked to observe the movement of the experimenter hand (clenching of the hand), then submit this motion and then repeat it by themselves. EEG recording and EEG analysis were conducted. To identify activation areas, sLORETA method was used for solving the inverse problem of EEG. RESULTS AND CONCLUSION: In patients with affective disorders, the activation of the brain mirror system occurred in the left temporal region, while in healthy people such activation was observed in the temporal lobes of the two hemispheres and in the frontal upper, middle and lower convolutions.

Host and symbiont intraspecific variability: The case of Paramecium calkinsi and "Candidatus Trichorickettsia mobilis".

Newly isolated strains of the ciliate Paramecium calkinsi and their cytoplasmic bacterial endosymbionts were characterized by a multidisciplinary approach, including live observation, ultrastructural investigation, and molecular analysis. Despite morphological resemblance, the characterized P. calkinsi strains showed a significant molecular divergence compared to conspecifics, possibly hinting for a cryptic speciation. The endosymbionts were clearly found to be affiliated to the species "Candidatus Trichorickettsia mobilis" (Rickettsiales, Rickettsiaceae), currently encompassing only bacteria retrieved in an obligate intracellular association with other ciliates. However, a relatively high degree of intraspecific divergence was observed as well, thus it was possible to split "Candidatus Trichorickettsia" into three subspecies, one of which represented so far only by the newly characterized endosymbionts of P. calkinsi. Other features distinguished the members of each different subspecies. In particular, the endosymbionts of P. calkinsi resided in the cytoplasm and possessed numerous peritrichous flagella, although no motility was evidenced, whereas their conspecifics in other hosts were either cytoplasmic and devoid of flagella, or macronuclear, displaying flagellar-driven motility. Moreover, contrarily to previously analyzed "Candidatus Trichorickettsia" hosts, infected P. calkinsi cells frequently became amicronucleate and demonstrated abnormal cell division, eventually leading to decline of the laboratory culture.

[Excision of Carbohydrate-Modified dNMP Analogues from DNA 3' end by Human Apurinic/Apyrimidinic Endonuclease 1 (APE1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1)].

We have studied the excision efficiency of human apurinic/apyrimidinic endonuclease 1 (APE1) and tyrosyl-DNA phosphodiesterase 1 (TDP1) on matched or mismatched bases located at the 3' end of DNA primers. We have used model DNA duplexes, which mimic DNA structures that occur during either replication (DNA with a 3' recessed end) or repair (DNA with a single-strand break). Both APE1 and TDP1 are more efficient in removing ribose-modified dNMP residues from mismatched pairs rather than canonical pairs. Thus, both of these enzymes may act as proofreading factors during the repair synthesis catalyzed by DNA polymerases including DNA polymerase ß (Polß). The design of new DNA polymerase inhibitors, which act as DNA or RNA chain terminators, is one of the main strategies in the development of antiviral agents. The excision efficacy of APE1 and TDP1 has also been studied for 3'-modified DNA duplexes that contain ddNMP or phosphorylated morpholino nucleosides (MorB) commonly used as terminators in the DNA synthesis. We have also investigated the insertion of ddNTP and morpholino nucleotides catalyzed by Polß and human immunodeficiency virus reverse transcriptase. This experiment has pointed to MorCyt, cytosine-containing morpholino nucleoside, as a potential antiviral agent.

[Neuronet restructuring in focal and generalized epilepsy according to resting state fMRI]. / Neirosetevye perestroiki pri fokal'noi i generalizovannoi épilepsii po dannym fMRT pokoia.

AIM: To compare neuronet restructuring in focal and generalized epilepsy. MATERIAL AND METHODS: Seventy-seven patients, aged from 18 to 65 years, with the diagnosis of epilepsy, including 63 patients with focal epilepsy and 14 with generalized epilepsy, were examined. A control group included 23 healthy people. Neuronet restructuring was studied using fMRI. RESULTS AND CONCLUSION: According to resting state fMRI, there were between-group differences in spatial organization (activity map) of the brain structures as well as in the results of cross-correlation analysis of interaction maps of resting-state networks. It has been concluded that functional restructuring in connectomes in focal and generalized epilepsy have the opposite patterns of disorganization (toward increase or decrease) in most structures studied though there are structures with the same direction of connectivity changes.

[Diagnosis and treatment of benign paroxysmal positional vertigo in common clinical practice]. / Diagnostika i lechenie bol'nykh s dobrokachestvennym paroksizmal'nym pozitsionnym golovokruzheniem v povsednevnoi klinicheskoi praktike.

AIM: To analyze typical medical practice in managing patients with benign paroxysmal positional vertigo (BPPV). SUBJECTS AND METHODS: 33 patients (5 men and 28 women; mean age, 58 years) with BPPV who had been referred for consultation to the Medical Diagnostic Department, Clinic of Nervous Diseases, I.M. Sechenov First Moscow State Medical University, regarding for vertigo, were examined. Information about the disease before visiting the clinic, such as the duration of vertigo, its pattern, and triggers, previously established diagnoses, prescribed treatment and its efficacy, concomitant diseases, was analyzed. RESULTS: BPPV was not timely diagnosed in 93.9% of cases. The cause of vertigo was most commonly mistakenly assumed to be cerebrovascular disease (66.6%) and cervical spine pathology (15.1%). During a primary examination, none of the patients underwent positional tests (otoneurological examination) that formed the basis for the diagnosis of BPPV. Alternatively, 90.3% of cases underwent instrumental examination: magnetic resonance imaging of the brain, X-ray of the cervical spine, and ultrasonic duplex scanning of the brachiocephalic arteries. Ineffective diagnosis led to the choice of nonoptimal treatment tactics: instead of therapeutic repositioning maneuvers (RM), the patients received therapy with drugs, such as various vasoactive agents (84.8%), nootropic and chondroprotective drugs (12%), or muscle relaxants (9.1%). After BPPV was detected, all patients underwent curative RM, which resulted in regression of the disease. One-year follow-up of the patients showed that the therapeutic effect of RM persisted. CONCLUSION: Lack of effective and timely diagnosis of BPPV reflects physicians' poor awareness that this condition is the most common cause of vestibular vertigo. The role of vascular and cervicogenic factors in the development of vertigo is overestimated. Most patients with BPPV undergo unreasonable examinations and receive ineffective treatment. It is necessary to raise awareness of BPPV among of physicians and to set up specialized centers for the management of patients with dizziness.

AP Endonuclease 1 as a Key Enzyme in Repair of Apurinic/Apyrimidinic Sites.

Human apurinic/apyrimidinic endonuclease 1 (APE1) is one of the key participants in the DNA base excision repair system. APE1 hydrolyzes DNA adjacent to the 5'-end of an apurinic/apyrimidinic (AP) site to produce a nick with a 3'-hydroxyl group and a 5'-deoxyribose phosphate moiety. APE1 exhibits 3'-phosphodiesterase, 3'-5'-exonuclease, and 3'-phosphatase activities. APE1 was also identified as a redox factor (Ref-1). In this review, data on the role of APE1 in the DNA repair process and in other metabolic processes occurring in cells are analyzed as well as the interaction of this enzyme with DNA and other proteins participating in the repair system.