[Particularities of arterial stiffness dynamics on the background of breast cancer chemotherapy].

BACKGROUND: Modern breast cancer chemotherapy regimens (BC) consider individual patient parameters and ranges of cardiotoxic doses. However, clinicians often record clinical and laboratory-instrumental signs of cardio- and vasculotoxicity in patients, which emphasizes the high importance of searching for markers of early toxic response. AIM: To study the characteristics of the response of arterial stiffness on the background of anthracycline-containing chemotherapy to determine potential markers of vasculotoxicity in BC patients. MATERIALS AND METHODS: 20 women with a BC were included. The patients received 4 cycles of chemotherapy in the doxorubicin + cyclophosphane (AC) regimen with an interval of 2-3 weeks, then they were injected with paclitaxel weekly for 12 injections, or docetaxel once every 3 weeks. All patients underwent TTE, arterial stiffness determination by the "gold standard" method and using volumetric sphygmography before the start of treatment, after the completion of the anthracycline component and after the end of taxanes. RESULTS: The average age of the patients was 45.5±5.31 years. After completing the course of anthracyclines, there was a significant increase in heart rate (from 65.6±9.3 to 73.3±10.1 beats/min.), a decrease in SBP (from 122.6±9.9 to 116.5±12.3 mmHg) and DBP (from 78.9±8.5 to 76.2±8.6 mmHg), a decrease in carotid femoral pulse wave velocity (cfPWV) (from 9.32±1.41 to 7.85±1.57 m/s), CAVI index on the left (from 6.78±0.81 to 6.5±0.88), the velocity of the cardio-ankle pulse wave on the right and left (from 6.7±0.6 to 6.5±0.7 m/s; from 7.0±0.6 to 6.3±0.8 m/sc, respectively). After the completion of the taxane, there was a tendency to increase these indicators, however, they remained significantly lower compared to the values before the start of treatment. CONCLUSION: A comparative analysis of arterial stiffness indicators at different stages of chemotherapy showed a more pronounced reaction of cfPWV, CAVI, cardio-ankle pulse wave to the administration of anthracyclines, which presumably may be associated with concomitant hemodynamic restructuring.

[The Case of Fulminant Myocarditis].

Fulminant myocarditis (FM) is a severe form of inflammatory myocardial injury rapidly developing as acute heart failure, cardiogenic shock, or life-threatening disturbances of cardiac rhythm. FM requires intensive treatment including drug therapy, mechanical circulatory support, and in some cases - heart transplantation. Echocardiography can be used as a screening method of diagnostics. Magnetic resonance imaging of the heart often cannot be performed because of hemodynamic instability of a patient, therefore endomyocardial biopsy with histological and immunohistochemical studies as well as molecular-genetic analysis of obtained samples is required for final diagnosis. Prognosis of the disease is determined by histological picture. In most cases, after cessation of acute stage of the inflammatory process, FM has a favorable long-term prognosis. In this article we present a clinical case of FM and review of current literature on diagnosis and treatment of this disease.

Blood-Derived RNA- and microRNA-Hydrolyzing IgG Antibodies in Schizophrenia Patients.

Abzymes with various catalytic activities are the earliest statistically significant markers of existing and developing autoimmune diseases (AIDs). Currently, schizophrenia (SCZD) is not considered to be a typical AID. It was demonstrated recently that antibodies from SCZD patients efficiently hydrolyze DNA and myelin basic protein. Here, we showed for the first time that autoantibodies from 35 SCZD patients efficiently hydrolyze RNA (cCMP > poly(C) > poly(A) > yeast RNA) and analyzed site-specific hydrolysis of microRNAs involved in the regulation of several genes in SCZD (miR-137, miR-9-5p, miR-219-2-3p, and miR-219a-5p). All four microRNAs were cleaved by IgG preparations (n = 21) from SCZD patients in a site-specific manner. The RNase activity of the abzymes correlated with SCZD clinical parameters. The data obtained showed that SCZD patients might display signs of typical autoimmune processes associated with impaired functioning of microRNAs resulting from their hydrolysis by the abzymes.

[The Risk Zone As A Factor Of Professional Burn-Out Of Medical Workers].

The article presents the results of study of risk zones and factors of professional burn-out of medical workers. The theoretical foundation of syndrome of emotional burn-out, features of professional activity and individual characteristics of public health professionals are revealed. The original study used the Maslach-Jackson technique adapted by N.E. Vodopyanova to determine levels of burn-out depending on age and career pattern. The risk zones of everyday professional activity include such external factors as unregulated duration of working time and high load per single specialist due to deficiency of physicians, inadequate level of social support and legal safety, absence of market mechanisms of compensation of health damage, absence of national patient-oriented system within the framework of health care modernization, unpredictability of behavior of patients. The given priorities and difficulties are studied on the example of the Republic of Mari-El. The Republic takes measures concerning training of physicians (a special faculty is organized) social support and stimulation of medical workers in rural area is developed. However, there is deficiency of physicians, load per single physician increases, level of salary did not fit requirements of the May decrees of the President of the Russian Federation. The reduction of risk zones of professional burn-out will favor development of national patient-oriented health care system, introduction of automated work places for physicians and increasing of their qualification, development of comfortable environment and atmosphere of friendliness in medical organizations.

[The microbiological monitoring as a basis of epidemiological control and anti-microbial therapy in conditions of multi-type hospital.]

The study was carried out to investigate features of microbiota and resistance to antibiotics of agents isolated from bio-material of patients in the conditions of multi-type hospital. The microbiological analysis was applied to 6148 samples using optimal set of corresponding techniques (classical tests, chromogenic mediums, immune serological, Maldi-Tof mass spectrometry). The resistance to antibiotics was established by using disk diffusion test (EUCAST 2016, Adagio analyzer). The leading role in etiology of pyoinflammatory processes belongs to E. coli, coagulase-negative staphylococci, enterococci, C. albicans. In the department of contaminated surgery among leaders are S. aureus, opportunistic enterobacteria, hemolytic streptococci, non-fermentative gram-negative microorganisms. In the department of traumatology and orthopedics first place was for representatives of enterobacteria family headed by E. coli, then follows S. aureus and after that other types of microorganisms. The main representatives of microorganisms, isolated from patients of the department of anesthesiology and reanimation, occurred blue pus bacillus, S.aureus, Klebsiella. In the department of therapy first place was for pneumoccocus and yeast-like fungi genus Candida. The resistance to antibiotics of main microflora differs depending on perspective of profile departments. It is extremely important to examine accurately for detection of agent of disease and to establish sensitivity to antibiotics of various groups.

Combined use of EPR and 23Na MAS NMR spectroscopy for assessing the properties of the mixed cobalt-nickel-manganese layers of P3-NayCo1-2xNixMnxO2.

Knowledge on the formation of mixed transition metal layers on lithium and sodium transition metal oxides, Li/Na(Co,Ni,Mn,)O2, determines the ability to control their electrochemical properties as electrode materials in alkaline ion batteries. Taking this into account, herein we combine the EPR and 23Na MAS NMR spectroscopic techniques to gain insights into the structural peculiarities of the mixed cobalt-nickel-manganese layers of NayCo1-2xNixMnxO2 with a three-layer stacking (P3-type) structure. Two types of compositions are examined where diamagnetic Co3+ and paramagnetic Ni3+ and Mn4+ are stabilized: Na2/3Co1/3Ni1/3Mn1/3O2 and Na1/2Ni1/2Mn1/2O2. EPR spectroscopy operating in the X- and Q-band region is applied with an aim to improve the spectra resolution and, on the other hand, to provide straightforward information on the coordination of the transition metal ions inside the layers. The analysis of EPR spectra is based on the reference for the Mn4+ and Ni2+ ions occurring simultaneously in oxides with two layer stacking, P2-Na2/3Ni1/3Mn2/3O2. Complementary to EPR, 23Na MAS NMR spectroscopy at high spinning rates is undertaken to assess the local structure of the Na nucleus in the layered P3-NayCo1-2xNixMnxO2 oxides. All results are discussed taking into account the EPR and NMR data for the well-known lithium analogues O3-LiCo1/3Ni1/3Mn1/3O2 and O3-LiNi1/2Mn1/2O2. Finally, the structure peculiarities of the transition metal layers extracted from the EPR and NMR methods are demonstrated by electrochemical intercalation of Li+ ions into P3-NayCo1-2xNixMnxO2.

[Association study of genetic markers of schizophrenia and its cognitive endophenotypes].

A replicative analysis of associations of 15 SNPs located in the regions of 11 genes (TCF4, VRK2, NOTCH4, ZNF804A, AGBL1, RELN, ZFP64P1, KCNB2, CSMD1, CPVL, NRIP1) and three intergenic regions (SLCO6A1/LINCOO491, LOC105376248/LOC105376249, SPA17/NRGN) with schizophrenia was conducted in the Russian population of the Siberian region. These SNPs were previously identified in genome-wide association studies (GWAS) of schizophrenia and cognitive abnormalities. The present study confirmed associations of KCNB2 rs2247572, CSMD1 rs2616984, and intergenic rs12807809 located in SPA17/NRGN with schizophrenia. It was established that the frequency of the CSMD1 rs2616984 G/G genotype was higher in patients compared to the control group (OR = 1.73; CI: 1.14­2.62; р = 0.0337). The frequencies of the KCNB2 rs2247572 TT genotype (OR = 0.41; CI: 0.20­0.87; р = 0.0485) and intergenic rs12807809 CT genotype located in SPA17/NRGN (OR = 0.70; CI: 0.53­0.94; р = 0.0464) were significantly decreased in patients compared to the control group.

[The patterns of alteration of content of growth-stimulating and growth-inhibiting factors in blood serum under ß-cell chronic lymphatic leukemia and their diagnostic value.]

The article evaluates balance of growth-stimulating and growth-inhibiting factors in blood serum of patients with different stages of B-cell chronic lymphatic leukemia residing on examination and hospital treatment in Saratov clinic of occupational pathology and hematology in 2007-2016. The indices of content of VEGF165, PDGF-AB, pRb, p53 and p73 in blood serum was detected using solid-phase enzyme-linked immunosorbent assay. The specific characteristic of B-cell chronic lymphatic leukemia became stably higher content of growth-stimulating cytokines of development of disease that permitted to conclude about (VEGF165, PDGF-AB) in dynamics of development of disease that permitted to conclude about their important role in mechanisms of oncogene transformation and stimulation of proliferation activity of neoplastic cells at various stages of pathology. At the same time, disturbance of anti-proliferation signals under B-cell chronic lymphatic leukemia was characterized by singleat-once decreasing of controlling cell cycle of several mechanisms of regulation of changing G1-phase to S-phase conditioned by low level of inhibitors of cyclin-dependent kinases (p53 and p73) and inadequate expression of regulator of cellular cycle of protein pRb.

CYP1A2 and CYP2D6 Gene Polymorphisms in Schizophrenic Patients with Neuroleptic Drug-Induced Side Effects.

Polymorphic variants of CYP1A2 and CYP2D6 genes of the cytochrome P450 system were studied in patients with schizophrenia with drug-induced motor disorders and hyperprolactinemia against the background of long-term neuroleptic therapy. We revealed an association of polymorphic variant C-163A CYP1A2*1F of CYP1A2 gene with tardive dyskinesia and association of polymorphic variant 1846G>A CY2D6*4 and genotype A/A of CYP2D6 gene (responsible for debrisoquin-4-hydroxylase synthesis) with limbotruncal tardive dyskinesia in patients with schizophrenia receiving neuroleptics for a long time.

[Creation of a statistical model for prediction of Hodgkin's lymphoma in young adults].

The aim of this study was to create a multi-dimensional correlation matrix of determinants giving information on the degree of influence on survival of young adults with Hodgkin's lymphoma each variable as well as the effect of the interaction of these variables with each other. 87 patients with Hodgkin's lymphoma at the age of 19 to 29 years (mean age 24 ± 4 years) were included in the study. Multiple matrix containing the coefficients of correlation of survival and correlation coefficients of 35 analyzed factors was of 5 significant determinants (volume of tumor lesion, stage IV of disease, E-damage, accelerated erythrocyte sedimentation rate, leukocytosis). Construction of the correlation matrix in order to select factors to be included in the equation, which contained the pair correlation coefficients of overall survival and each of factors, showed that only the volume of tumor lesion (correlation coefficient 0.2570, p = 0.026) influences on sign-result. Multiple regression equation is represented as follows ȳ=0,166667-0,227273x[volume]; R2=0,0643674507. This equation allows for given values of the factor «volume of tumor lesion" to have theoretical values of resultant sign (survival), substituting the actual values of the factor in it.

[POLYHEXAMETHYLENE BIGUANID HYDROCHLORIDE (BIGUANELLE) THERAPY OF BACTERIAL VAGINOSIS].

UNLABELLED: The aim of our study was to determine the efficacy and tolerability of local therapy with polyhexamethylene biguanid hydrochloride (BIGUANELLE) in women with anaerobic vaginal infection. MATERIAL AND METHODS: We include in our study 23 women (18-50) with established by AMSEL criteria bacterial vaginosis. In all of the women at the beginning and at the end of the survey was performed gynecological examination and microbiological research (AMSEL). The therapeutic scheme at all women is with a single vaginal application of gynecological solution BIGUANELLE. Effectiveness of the treatment was evaluated according to clinical complaints and microbiological research (Amsel criteria: Ph 4.5 >; KOH (+); "clue cells"; specific vaginal fluorine). Tolerability of patients to treatment was assessed by questionnaire. RESULTS: Clinical complaints of patients after the therapy decreased as follows: vaginal fluorine with 73.9%; odor--75%; pruritus--50%; discomfort--90%. Microbiological research and their evaluation by AMSEL, showed the therapeutic efficacy of the therapy in 16 (69.6%) of all (n-23) patients. At 7 (30.4%) women, the treatment remained without effect. At questionnaire answers, 73.9% patients were satisfied with the application of BIGUANELLE, 95.6% of them have implemented it easily, 95.6% of women believe that BIGUANELLE is more convenient to use in comparison with similar products which have a daily application, and none of the patients (100%) have any complaints in applying this gynecological solution. CONCLUSIONS: BIGUANELLE showed good clinical efficacy in the treatment of bacterial vaginosis. It is easily applied and well tolerated by the patients.

[Obesity in metabolic syndrome, as well as kidney dysfunction]. / Ozhirenie pri metabolicheskom sindrome i pochechnaia disfunktsiia.

The presence of metabolic syndrome (MS) in a patient allows him to be assigned to a group at high risk for atherosclerosis, cardiovascular events, coronary heart disease, and type 2 diabetes mellitus. In addition, MS negatively affects not only the heart and vessels, but also kidney function, which leads to chronic kidney disease (CKD). MS is pathogenetically associated with CKD and is an independent prognostic factor of the development of the latter, namely, the involvement of the kidney frequently determines prognosis and quality of life in these patients. The paper gives a modern view on the concept of MS and CKD and considers its main diagnostic criteria, etiology, and pathogenesis. The study of the relationships between MS and CKD may suggest that the high prevalence of kidney dysfunction in the general population is largely determined by metabolic nephropathies, including obesity-related nephropathy. The identification of risk factors and poor prognostic markers in this category of patients seems to be extremely important for the early diagnosis of the disease and their timely elimination is one of the main approaches to the comprehensive prevention of CKD in these patients.

[The results of monitoring of antigen types of rotaviruses of group A on the territory of the Russian Federation in 2011-2015.]

The data of seasonal monitoring are presented concerning antigen types of rotaviruses group A circulating on the territory of the Russian Federation in the periods of seasonal uprising of morbidity in 2011-2015. Annually, the study included from 10 to 12 subjects of the Russian Federation with annual testing from 444 to 728 samples from children aged younger than 5 years with acute infection diarrhea. In the seasons of 2011-2012, 2012-2013, 2013-2014, 2014-2015 the most prevalent [P] G types of rotaviruses correspondingly made up to: G4[P]8 -50.2%-36.5%-43.8%-1.6%; G1[P]8 - 26.6%-14.3%-27.3%-22.5%; G3[P]8 - 4.4%-23.7%-4.2%-2.0%; G9[P]8 - 4.3%-5.3%-10.1%-7.1%; G2[P]4 - 7.7%-7.9%-9.0%-3.1%. The expressed territorial irregularity of prevalence of antigen types of retroviruses was observed.

Serum Glutathione in Patients with Schizophrenia in Dynamics of Antipsychotic Therapy.

Serum concentrations of oxidized and reduced glutathione were measured in 73 patients with schizophrenia at admission and in dynamics of therapy with traditional and atypical antipsychotic drugs. The level of reduced glutathione in patients with schizophrenia with manifest clinical symptoms was lower than in normal subjects. Atypical neuroleptics produced virtually no effects on the glutathione system, while therapy with typical antipsychotics led to further decrease in the levels of reduced glutathione, thus aggravating the imbalance of metabolic processes typical of schizophrenia.

Serum levels of neurosteroids in patients with affective disorders.

According modern biological hypotheses of the pathogenesis of affective disorders, hypothalamic-pituitary-adrenal axis dysfunction play a special role in the pathogenesis of this condition. Our study shows that the range of neuroprotective neurosteroids is gender- and nosology-dependent. Patients with affective disorders have reduced levels of dehydroepiandrosterone and dehydroepiandrosterone sulfate; the most pronounced deficiency of neuroprotective neurosteroids is typical of patients with a single depressive episode. Reduced levels of neurosteroids producing an anabolic effect probably indicate depletion of adaptive capacities of the hypothalamic-pituitary-adrenal system in affective disorders.

[Characteristics of Membrane-Bound Pool of Leukocyte Lactate Dehydrogenase in Healthy Men of Different Age].

The study of isoenzymes of leucocyte lactate dehydrogenase (LDH) in healthy men of different age showed a decrease in the membrane-bound pool of LDH-1 and LDH-4 in 40-year-old males as compared with 20-year-old males. The results indicate an age-related reduction of the reserve membrane-bound pool of several LDH isoforms.

[Changes in gingival blood circulation in patients with provisional fixed acrylic dentures].

The adhesion of oral microorganisms to the surface of teeth and dental restorative materials is often the starting point in the developments of caries and periodontal disease. Formation of biofilm on the surface provisional acrylic bridge is especially quickly and can potentially generate decay or periodontal disease on the teeth. Occlusion trauma and occlusion disorders effects on increasing of injure regional periodontal tissues. Using ultrasonic doppler diagnostics oral mucosal blood flow was measured in 79 patients with periodontitis of medium severity with different hygiene conditions before and during orthopedic treatment by provisional fixed dentures was model by different methods. According to the results of this study was stated optimization of oral mucosal blood flow after pre-prosthetic treatments and the supportive hygiene periodontal care during the treatment. Results was used for reduce of functional stress in the in periodontal tissues during the orthopedic alignment by the use of fixed dentures. Specific prosthodontic hygiene protocol and model by individual articulator must be used to treat patients with widespread chronic periodontitis by interim prostheses.

[Associations of serum neuromarkers with clinical features of Parkinson's disease]. / Assotsiatsii syvorotochnykh neiromarkerov s klinicheskimi osobennostyami bolezni Parkinsona.

OBJECTIVE: To evaluate the clinical and laboratory correlation of biomarkers with anti- and pro-apoptotic activity with the severity of motor and non-motor symptoms depending on the progression rate of Parkinson's disease (PD). MATERIAL AND METHODS: A wide range of non-motor symptoms (emotional-affective, cognitive, psychotic and behavioral disorders, fatigue, sleep disorders and autonomic disorders) was evaluated using validated scales and a number of serum neuromarkers responsible for neuroplasticity and neuronal survival processes (BDNF, PDGF, cathepsin D) in 71 patients with PD (mean age 65 (55; 70) years, disease duration 7 (4; 9) years, age of onset 57 (49; 62) years). RESULTS: The concentration of biomarkers (BDNF, PDGF and cathepsin D) was the lowest in the group of patients with a rapid PD progression rate (p<0.001, p=0.001 and p=0.031, respectively), the severity of motor and most non-motor symptoms was higher (p=0.023 and p=0.001, respectively) compared to middle and slow progression rate. There were correlations between BDNF concentration and the severity of depression (r=-0.63, p<0.001), apathy (r=-0.48, p<0.001), impulsive behavioral disorders (r=0.500, p<0.001), level of cognitive functions (r=0.54, p<0.001), motor symptoms (r=-0.43, p<0.001); between PDGF level and the severity of motor manifestations of PD (r=-0.30, p=0.011), depression (r=-0.70, p<0.001), apathy (r=-0.460, p<0.001), the degree of severity of behavioral disorders (r=0.742, p<0.001). No significant correlations were observed between the level of cathepsin D and the severity of clinical manifestations of PD, which indicates the connection of cathepsin D with the general pathogenesis of PD. CONCLUSION: The possibility of using serum proteins of the neurotrophin subfamily and the protein associated with autophagy, cathepsin D, as biomarkers that determine the prognosis of PD, is considered.

[Serum neurofilament light chains in assessing the course of multiple sclerosis]. / Syvorotochnye legkie tsepi neirofilamentov v otsenke techeniya rasseyannogo skleroza.

OBJECTIVE: To study a role of serum neurofilament light chains (sNFL) in assessment of course and progression of multiple sclerosis (MS) in the population of patients with MS in the Tomsk region. MATERIAL AND METHODS: The study involved 93 patients with relapsing-remitting MS (RRMS) and secondary progressive MS (SPMS) (nRRMS=75, nSPMS=18). The study was carried out in a two-stage design: the first stage was a cross-sectional study for the entire sample; the second stage was a prospective observation with two visits for patients with relapse. sNFL concentration was determined by solid-phase ELISA. RESULTS: There was no statistically significant difference between RRMS and SPMS, and relapse and remission groups in terms of sNFL levels. Patients with a MS duration exceeding 14 years had higher rates of sNFL than those with a shorter duration (p=0.02). The subjects of the second study stage showed a decrease in sNFL from 2.05 (1.86; 2.19) pg/ml to 1.92 (1.87; 2.04) pg/ml (p=0.005), and slowdown in sNFL reduction correlated with the severity of cognitive impairment (k=0.52; p<0.05). CONCLUSION: Dynamic monitoring of sNFL allows the evaluation of the activity of the disease, as well as making an assumption about the compensatory possibilities of subsequent recovery.

[Associations between components of metabolic syndrome and cognitive impairment in patients with schizophrenia]. / Svyazi mezhdu komponentami metabolicheskogo sindroma i kognitivnymi narusheniyami u bol'nykh shizofreniei.

OBJECTIVE: To study the relationship between the individual components of the metabolic syndrome and cognitive dysfunction in patients with schizophrenia. MATERIAL AND METHODS: A total of 133 patients with schizophrenia were examined. To assess cognitive functioning, the Brief Assessment of Cognition in Schizophrenia (BACS) was used. The components of the metabolic syndrome were determined in accordance with the criteria of the International Diabetes Federation. RESULTS: Hyperglycemia in patients with schizophrenia led to a decrease in cognitive functioning in two domains: verbal fluency (ß=-10.67; p=0.019) and attention stability (ß=-9.519; p=0.043). Abdominal obesity was associated with lower indicators of executive functions (ß=-8.856; p=0.026). CONCLUSION: It is assumed that drug treatment of some components of the metabolic syndrome may affect cognitive functions in patients with schizophrenia.