Search results for: Natalya Sergeeva

Authors: Marina Nosik, Irina Rymanova, Sergei Sevostyanihin, Natalya Sergeeva, Alexander Sobkin

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This paper presents results of the survey regarding the awareness about HIV/AIDS among HIV-infected individuals. A questionnaire covering various aspects of HIV-infection was conducted among 110 HIV-infected individuals who attended the G.A. Zaharyan Moscow Tuberculosis Clinic, Department for the treatment of TB patients with HIV. The questionnaire included questions about modes of HIV transmission and preventive measures against HIV/AIDS, as well as questions about age, gender, education, and employment status. The survey revealed that the respondents in the whole had a good knowledge regarding modes of HIV transmission and preventive measures against HIV/AIDS: about 83,6% male respondents and 85,7% female respondents gave accurate answers regarding the HIV-infection. However, the overwhelming majority of the study participants, that is, 88,5% men and 98% women, was quite ignorant about the risk of acquiring HIV through saliva and toothbrush of HIV-infected individual. Though that risk is rather insignificant, it is still biologically possible. And this gap in knowledge needs to be filled. As the study showed another point of concern was the fact, that despite the knowledge of HIV transmission risk through unprotected sex about 40% percent of HIV-positive men and 25% of HIV-positive women did not insist on using condoms with their sexual partners. These findings indicate that there are still some aspects about HIV-infection which needed to be clarified and explained through more detailed and specific educational programmes.

Keywords: AIDS, HIV transmission risks, HIV misconceptions, risk behavior

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Authors: Igor Astrov, Natalya Berezovski

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This paper focuses on a critical component of the situational awareness (SA), the control of autonomous vertical flight for vectored thrust aerial vehicle (VTAV). With the SA strategy, we proposed a neural network motion control procedure to address the dynamics variation and performance requirement difference of flight trajectory for a VTAV. This control strategy with using of NARMA-L2 neurocontroller for chosen model of VTAV has been verified by simulation of take-off and forward maneuvers using software package Simulink and demonstrated good performance for fast stabilization of motors, consequently, fast SA with economy in energy can be asserted during search-and-rescue operations.

Keywords: NARMA-L2 neurocontroller, situational awareness, vectored thrust aerial vehicle, aviation

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Authors: M. Nosik, I. Rymanova, N. Adamovich, S. Sevostyanihin, K. Ryzhov, Y. Kuimova, A. Kravtchenko, N. Sergeeva, A. Sobkin

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HIV and Tuberculosis (TB) infections each speed the other's progress. HIV-infection increases the risk of TB disease. At the same time, TB infection is associated with clinical progression of HIV-infection. HIV+TB co-infected patients are also at higher risk of acquiring new opportunistic infections. An important feature of disease progression and clinical outcome is the innate and acquired immune responses. HIV and TB, however, have a spectrum of dysfunctions of the immune response. As cytokines play a crucial role in the immunopathology of both infections, it is important to study immune interactions in patients with dual infection HIV+TB. Plasma levels of proinflammatory cytokines IL-2, IFN-γ and immunoregulating cytokines IL-4, IL-10 were evaluated in 75 patients with dual infection HIV+TB, 58 patients with HIV monoinfection and 50 patients with TB monoinfection who were previously naïve for HAART. The decreased levels of IL-2, IFN-γ, IL-4 and IL-10 were observed in patients with dual infection HIV+TB in comparison with patients who had only HIV or TB which means the profound suppression of Th1 and Th2 cytokine secretion. Thus, those cytokines could possibly serve as immunological markers of progression of HIV-infection in patients with TB.

Keywords: HIV, tuberculosis (TB), HIV associated with TB, Th1/ Th2 cytokine expression

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Authors: Natalya G. Filimonova, Mariya G. Ozerova, Irina N. Ermakova

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The long-term strategy of the economic development of Russia up to 2030 is based on the concept of sustainable growth. The determining factor of such development is complex changes in the economic system which may be achieved by making progressive changes in its structure. The structural changes determine the character and the direction of economic development, as well as they include all elements of this system without exception, and their regulated character ensures the most rapid aim achievement. This article has discussed the industrial structure of the agriculture in Russia. With the use of the system of indexes, the article has determined the directions, intensity, and speed of structural shifts. The influence of structural changes on agricultural production development has been found out. It is noticed that the changes in the industrial structure are synchronized with the changes in the organisation and economic structure. Efficiency assessment of structural changes allowed to trace the efficiency of structural changes and elaborate the main directions for agricultural policy improvement.

Keywords: Russian agricultural sectors, sectoral structure, organizational and economic structure, structural changes

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Authors: A. H. Tadevosyan, S. K. Mayrapetyan, N. B. Tavakalyan, K. I. Pyuskyulyan, A. H. Hovsepyan, S. N. Sergeeva

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Soil contamination with radiocesium has a long-term radiological impact due to its long physical half-life (30.1 years for 137Cs and 2 years for 134Cs) and its high biological availability. 137Cs causes the largest concerns because of its deleterious effect on agriculture and stock farming, and, thus, human life for decades. One of the important aspects of the problem of contaminated soils remediation is understand of protective actions aimed at the reduction of biological migration of radionuclides in soil-plant system. The most effective way to bind radionuclides is the use of selective sorbents. The proposed research mainly aims to achieve control on transfer of 137Cs in a system growing media–plant due to counter ions variation in the polymeric sorbents. As the research object, Japanese basil-Perilla frutescens was chosen. Productivity of plants depending on the presence (control-without presence of polymer) and type of polymer material, as well as content of 137Cs in plant material has been determined. The character of different polymers influences on the 137Cs migration in growing media–plant system as well as accumulation in the plants has been cleared up.

Keywords: radioceaseum, Japanese basil, polymer, soil-plant system

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Authors: Khon Natalya, Kim Alla, Mukhitdinova Tansulu

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The aim of the research was to reveal the link between mental variables, such as spatial abilities, memory, intellect and professional experience of drivers. Participants were allocated within 4 groups: no experience, inexperienced, skilled and professionals (total 85 participants). Level of ability for spatial navigation and indicator of nonverbal memory grow along the process of accumulation of driving experience. At high levels of driving experience this tendency is especially noticeable. The professionals having personal achievements in driving (racing) differ from skilled drivers in better feeling of direction which is specific for them not just in a short-term situation of an experimental task, but in life-size perspective. The level of ability of mental rotation does not grow with growth of driving experience which confirms the multiple intelligence theory according to which spatial abilities represent specific, other than logical intelligence type of intellect. The link between spatial abilities, memory, intellect, and professional experience of drivers seems to be different relating spatial navigation or mental rotation as different kinds of spatial abilities.

Keywords: memory, spatial ability, intellect, drivers

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Authors: Jennifer Natalya Fink

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Since the racial reckoning of 2020, almost every major educational institution has incorporated diversity, equity, and inclusion (DEI) principles into its administrative, hiring, and pedagogical practices. Yet these DEI principles rarely incorporate explicit language or critical thinking about disability. Despite the fact that according to the World Health Organization, one in five people worldwide is disabled, making disabled people the larger minority group in the world, disability remains the neglected stepchild of DEI. Drawing on disability studies and crip theory frameworks, the underlying causes of this exclusion of disability from DEI, such as stigma, shame, invisible disabilities, institutionalization/segregation/delineation from family, and competing models and definitions of disability are examined. This paper explores both the ideological and practical shifts necessary to include disability in university DEI initiatives. It offers positive examples as well as conceptual frameworks such as 'divers ability' for so doing. Using Georgetown University’s 2020-2022 DEI initiatives as a case study, this paper describes how curricular infusion, accessibility, identity, community, and diversity administration infused one university’s DEI initiatives with concrete disability-inclusive measures. It concludes with a consideration of how the very framework of DEI itself might be challenged and transformed if disability were to be included.

Keywords: diversity, equity, inclusion, disability, crip theory, accessibility

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives. The age of the disease onset could have an impact on the effect of therapy in systemic sclerosis(SSc). Late-age onset in SSc could have a more severe course of the disease and worse clinical effects on therapy. The aim of our study was to evaluate changes in skin fibrosis on rituximab(RTX) therapy in patients with SSc and different ages of the disease onset. Methods. 151 patients with SSc were included in this study. Patients were divided into groups depending on the age of the disease onset: group 1 - younger than 30 years (40 patients(26%), group 2 - 31-59 years (90 patients(60%) and group 3 – more than 60 years (21 patients(14%). The mean follow-up period was 13±2.3month. The mean age was 48±13years, female-83% of patients, and the diffuse cutaneous subset of the disease had 52% of patients. The mean disease duration was 6.4±5years. The cumulative mean dose of RTX was 1.5±0.6grams. Patients received RTX as a therapy for interstitial lung disease. All patients received prednisone at a dose of 11.6±4.8mg/day, immunosuppressants received 48% of them. The results at baseline and at the end of the follow-up are presented in the form of mean values. Results. There was a significant decrease of modified Rodnan skin score(mRss) in all groups: in group 1 - from 10.2±8 to 7.7±6.5(p=0.01); in group 2 - from 9±7.2 to 6.2±4.7(p=0.0001); in group 3 - from 20.5±14.1 to 10.8±9.4(p=0.001). There was a significant decrease of the activity index (EScSG-AI): in group 1 from 2.5±1.8 to 1.3±1.1; in group 2 – from 3.2±1.6 to 1.5±1.2; in group 3 – from 4.2±2.1 to 1.3±1. Conclusion. There was a significant improvement in skin fibrosis in a year after initiation of RTX therapy regardless of the age of the disease onset. The improvement was more pronounced in the group with late-age onset of the disease, but these data require further investigations.

Keywords: skin fibrosis, systemic sclerosis, rituximab, disease onset

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Authors: Vladimir Mantsevich, Natalya Maslova, Petr Arseyev

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We investigated the tunneling current peculiarities in the system of two coupled by means of the external field quantum dots (QDs) weakly connected to the electrodes in the presence of Coulomb correlations between localized electrons by means of Heisenberg equations for pseudo operators with constraint. Special role of multi-electronic states was demonstrated. Various single-electron levels location relative to the sample Fermi level and to the applied bias value in symmetric tunneling contact were investigated. Rabi frequency tuning results in the single-electron energy levels spacing. We revealed the appearance of negative tunneling conductivity and demonstrated multiple switching "on" and "off" of the tunneling current depending on the Coulomb correlations value, Rabi frequency amplitude and energy levels spacing. We proved that Coulomb correlations strongly influence the system behavior. We demonstrated the presence of multi-stability in the coupled QDs with Coulomb correlations when single value of the tunneling current amplitude corresponds to the two values of Rabi frequency in the case when both single-electron energy levels are located slightly above eV and are close to each other. This effect disappears when the single-electron energy levels spacing increases.

Keywords: Coulomb correlations, negative tunneling conductivity, quantum dots, rabi frequency

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives. C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are associated with severe course, increased morbidity and mortality in systemic sclerosis (SSc). The aim of our study was to assess changes in CRP and ESR in SSc patients during long-term RTX therapy. Methods. This study included 113 patients with SSc. Mean age was 48.1±13 years, female-85%. The mean disease duration was 6±5 years. The diffuse cutaneous subset of the disease had 55% of patients. All pts had interstitial lung disease (ILD). All patients received prednisolone at a mean dose of 11.6±4.8 mg/day, and 53 of them - were immunosuppressants at inclusion. Patients received RTX due to the ineffectiveness of previous therapy for ILD. The parameters were evaluated over the periods: at baseline (point 0), 13±2.3 month (point 1, n=113), 42±14 month (point 2, n=80) and 79±6.5 month (point 3, n=25) after initiation of RTX therapy. Cumulative mean dose of RTX at point 1 = 1.7±0.6g, at point 2 = 3±1.5g, and at point 3 = 3.8±2.4g. The results are presented in the form of mean values, delta(Δ)-difference between the baseline parameter and follow-up point. Results. There was an improvement in studied parameters on RTX therapy. There was a significant decrease of ESR, CRP and activity index (EScSG-AI) at all observation points (p=0.001). In point 1: ΔCRP was 6.7 mg/l, ΔESR = 7.4 mm/h, ΔActivity index (EScSG-AI) = 1.7. In point 2: ΔCRP was 8.7 mg/l, ΔESR = 7.5 mm/h, ΔActivity index (EScSG-AI) = 1.9. In point 3: ΔCRP was 16.1 mg/l, ΔESR = 11 mm/h, ΔActivity index (EScSG-AI) = 2.1. Conclusion. There was a significant decrease in CRP and ESR during long-term RTX therapy, which correlated with a decrease in the disease activity index. RTX is an effective treatment option for SSc with an elevation of acute-phase reactants.

Keywords: C-reactive protein, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Balgaisha Mukanova, Natalya Glazyrina, Sergey Glazyrin

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The formulated problem of optimization of the technological process of water treatment for thermal power plants is considered in this article. The problem is of multiparametric nature. To optimize the process, namely, reduce the amount of waste water, a new technology was developed to reuse such water. A mathematical model of the technology of wastewater reuse was developed. Optimization parameters were determined. The model consists of a material balance equation, an equation describing the kinetics of ion exchange for the non-equilibrium case and an equation for the ion exchange isotherm. The material balance equation includes a nonlinear term that depends on the kinetics of ion exchange. A direct problem of calculating the impurity concentration at the outlet of the water treatment plant was numerically solved. The direct problem was approximated by an implicit point-to-point computation difference scheme. The inverse problem was formulated as relates to determination of the parameters of the mathematical model of the water treatment plant operating in non-equilibrium conditions. The formulated inverse problem was solved. Following the results of calculation the time of start of the filter regeneration process was determined, as well as the period of regeneration process and the amount of regeneration and wash water. Multi-parameter optimization of water treatment process for thermal power plants allowed decreasing the amount of wastewater by 15%.

Keywords: direct problem, multiparametric optimization, optimization parameters, water treatment

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives. There is very few data on changes of the musculoskeletal manifestations (artritis, arthralgia, muscle weakness, etc.) in systemic sclerosis (SSc) on rituximab (RTX) therapy. The aim of our study was to assess the severity of the musculoskeletal involvement in SSc patients (pts) and its changes during RTX therapy. Methods. Our study included 103 pts with SSc. The mean followup period was 12.6±10.7 months. The mean age was 47±12.9 years, female-87 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. All pts had interstitial lung disease (ILD) and were positive for ANA, 67% of them were positive for antitopoisomerase-1. All patients received prednisolone at a dose of 11.3±4.5 mg/day, immunosuppressants at inclusion received 47% of them. Pts received RTX due to the ineffectiveness of previous therapy for ILD. The cumulative mean dose of RTX was 1.7±0.6 grams. Arthritis was observed in 22 pts (21%), arthralgias in 47 pts (46%). Muscle weakness was observed in 17 pts (17%). Tendon friction rubs was established in 7 pts (7%). The results at baseline and at the end of the follow up are presented in the form of mean values. Results. There was an improvement of all outcome parameters and musculoskeletal manifestations on RTX therapy. There was a decrease in the number of pts with arthritis from 22 (21%) to 10 (9%), a decrease in the number of pts with arthralgias from 47 (46%) to 31 (30%). The number of pts with muscle weakness decreased from 17 (17%) to 7 (7%). The number of pts with tendon friction rubs decreased from 7 (7%) to 3 (3%). The creatine phosphokinase decreased from 365.5±186 to 70.8±50.4 (p=0.00006). The C-reactive protein (CRP) decreased from 23.2±31.3 to 8.62±7.4 (p=0.001). The dose of prednisolone was reduced from 11.3±4.5 to 9.8±3.5 mg/day (p=0.0004). Conclusion. In our study, musculoskeletal involvement was detected in almost half of the patients with SSc-ILD. There was an improvement of musculoskeletal manifestations despite a small cumulative dose of RTX. We also managed to reduce the dose of glucocorticosteroids. The improvement of musculoskeletal manifestations was accompanied by a decrease in laboratory parameters - creatine phosphokinase and CRP. RTX is effective option for treatment of musculoskeletal manifestations in SSc.

Keywords: arthritis, musculoskeletal involvement, systemic sclerosis, rituximab

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Objectives: The duration of the disease could be one of the leading factors in the effectiveness of therapy in systemic sclerosis (SSc). The aim of the study was to assess how the duration of the disease affects the changes of lung function in patients(pts) with interstitial lung disease (ILD) associated with SSc during long-term RTX therapy. Methods: We prospectively included 113pts with SSc in this study. 85% of pts were female. Mean age was 48.1±13years. The diffuse cutaneous subset of the disease had 62pts, limited–40, overlap–11. The mean disease duration was 6.1±5.4years. Pts were divided into 2 groups depending on the disease duration - group 1 (less than 5 years-63pts) and group 2 (more than 5 years-50 pts). All pts received prednisolone at mean dose of 11.5±4.6 mg/day and 53 of them - immunosuppressants at inclusion. The parameters were evaluated over the periods: at baseline (point 0), 13±2.3mo (point 1), 42±14mo (point 2) and 79±6.5mo (point 3) after initiation of RTX therapy. Cumulative mean dose of RTX in group 1 at point 1 was 1.7±0.6 g, at point 2 = 3.3±1.5g, at point 3 = 3.9±2.3g; in group 2 at point 1 = 1.6±0.6g, at point 2 = 2.7±1.5 g, at point 3 = 3.7±2.6 g. The results are presented in the form of mean values, delta(Δ), median(me), upper and lower quartile. Results. There was a significant increase of forced vital capacity % predicted (FVC) in both groups, but at points 1 and 2 the improvement was more significant in group 1. In group 2, an improvement of FVC was noted with a longer follow-up. Diffusion capacity for carbon monoxide % predicted (DLCO) remained stable at point 1, and then significantly improved by the 3rd year of RTX therapy in both groups. In group 1 at point 1: ΔFVC was 4.7 (me=4; [-1.8;12.3])%, ΔDLCO = -1.2 (me=-0.3; [-5.3;3.6])%, at point 2: ΔFVC = 9.4 (me=7.1; [1;16])%, ΔDLCO =3.7 (me=4.6; [-4.8;10])%, at point 3: ΔFVC = 13 (me=13.4; [2.3;25.8])%, ΔDLCO = 2.3 (me=1.6; [-5.6;11.5])%. In group 2 at point 1: ΔFVC = 3.4 (me=2.3; [-0.8;7.9])%, ΔDLCO = 1.5 (me=1.5; [-1.9;4.9])%; at point 2: ΔFVC = 7.6 (me=8.2; [0;12.6])%, ΔDLCO = 3.5 (me=0.7; [-1.6;10.7]) %; at point 3: ΔFVC = 13.2 (me=10.4; [2.8;15.4])%, ΔDLCO = 3.6 (me=1.7; [-2.4;9.2])%. Conclusion: Patients with an early SSc have more quick response to RTX therapy already in 1 year of follow-up. Patients with a disease duration more than 5 years also have response to therapy, but with longer treatment. RTX is effective option for the treatment of ILD-SSc, regardless of the duration of the disease.

Keywords: interstitial lung disease, systemic sclerosis, rituximab, disease duration

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Authors: Irina S. Kolesnikova, Alexander A. Dolskiy, Natalya A. Lemskaya, Yulia V. Maksimova, Asia R. Shorina, Alena S. Telepova, Alexander S. Graphodatsky, Dmitry V. Yudkin

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A cytogenetic and molecular genetic study of the family with a male child who had mental retardation and autistic features revealed an abnormal chromosome 13 bearing an enlarged p-arm with amplified ribosomal DNA (rDNA) in a boy and his father. Cytogenetic analysis using standard G-banding and FISH with labeled rDNA probes revealed an abnormal chromosome 13 with an enlarged p-arms due to rDNA amplification in a male child, who had clinically confirmed mental retardation and an autistic behavior. This chromosome is evidently inherited from the father, who has morphologically the same chromosome, but is healthy. The karyotype of the mother was normal. Ag-NOR staining showed brightly stained large whole-p-arm nucleolus organizer regions (NORs) in a child and normal-sized NORs in his father with 13p+-NOR-amount mosaicism. qRT-PCR with specific primers showed highly increased levels of 18S, 28S and 5,8 S ribosomal RNA (rRNA) in the patient’s blood samples compared to a normal healthy control donor. Both patient’s father and mother had no elevated levels of rRNAs expression. Thus, in this case, rRNA level seems to correlate with mental retardation in familial individuals with 13p+. Our findings of rRNA overexpression in a patient with mental retardation and his parents may show a possible link between the karyotype (p-arm enlargement due to rDNA amplification), rDNA functionality (rRNA overexpression), functional changes in the brain and mental retardation. The study is supported by Russian Science Foundation Grant 15-15-10001.

Keywords: mental retardation, ribosomal DNA–rDNA, ribosomal RNA–rRNA, nucleolus organizer region–NOR, chromosome 13

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Authors: Dmitriy Syssoyev, Aslan Seitkamzin, Natalya Lim, Kamilla Mussina, Abduzhappar Gaipov, Dimitri Poddighe, Dinara Galiyeva

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Background: Data on the epidemiology of congenital heart defects (CHD) in Kazakhstan is scarce. Therefore, the aim of this study was to describe the incidence, prevalence and all-cause mortality of patients with CHD in Kazakhstan, using national large-scale registry data from the Unified National Electronic Healthcare System (UNEHS) for the period of 2014-2020. Methods: In this retrospective cohort study, the included data pertained to all patients diagnosed with CHD in Kazakhstan and registered in UNEHS between January 2014 and December 2020. CHD was defined based on International Classification of Diseases 10th Revision (ICD-10) codes Q20-Q26. Incidence, prevalence, and all-cause mortality rates were calculated per 100,000 population. Survival analysis was performed using Cox proportional hazards regression modeling and the Kaplan-Meier method. Results: In total, 66,512 patients were identified. Among them, 59,534 (89.5%) were diagnosed with a single CHD, while 6,978 (10.5%) had more than two CHDs. The median age at diagnosis was 0.08 years (interquartile range (IQR) 0.01 – 0.66) for people with multiple CHD types and 0.39 years (IQR 0.04 – 8.38) for those with a single CHD type. The most common CHD types were atrial septal defect (ASD) and ventricular septal defect (VSD), accounting for 25.8% and 21.2% of single CHD cases, respectively. The most common multiple types of CHD were ASD with VSD (23.4%), ASD with patent ductus arteriosus (PDA) (19.5%), and VSD with PDA (17.7%). The incidence rate of CHD decreased from 64.6 to 47.1 cases per 100,000 population among men and from 68.7 to 42.4 among women. The prevalence rose from 66.1 to 334.1 cases per 100,000 population among men and from 70.8 to 328.7 among women. Mortality rates showed a slight increase from 3.5 to 4.7 deaths per 100,000 in men and from 2.9 to 3.7 in women. Median follow-up was 5.21 years (IQR 2.47 – 11.69). Male sex (HR 1.60, 95% CI 1.45 - 1.77), having multiple CHDs (HR 2.45, 95% CI 2.01 - 2.97), and living in a rural area (HR 1.32, 95% CI 1.19 - 1.47) were associated with a higher risk of all-cause mortality. Conclusion: The incidence of CHD in Kazakhstan has shown a moderate decrease between 2014 and 2020, while prevalence and mortality have increased. Male sex, multiple CHD types, and rural residence were significantly associated with a higher risk of all-cause mortality.

Keywords: congenital heart defects (CHD), epidemiology, incidence, Kazakhstan, mortality, prevalence

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Authors: Liudmila Garzanova, Lidia Ananyeva, Olga Koneva, Olga Ovsyannikova, Oxana Desinova, Mayya Starovoytova, Rushana Shayahmetova, Anna Khelkovskaya-Sergeeva

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Abstract Objectives. Rituximab (RTX) shown a positive effect in the treatment of systemic sclerosis (SSc). But there is still not enough data on comparing the effectiveness of RTX with immunosuppressants (IS). The aim of our study was to compare changes of lung function and skin score in SSc between two groups of patients (pts) - on RXT therapy (prescribed after ineffectiveness of previous therapy with IS) and on therapy with IS only. Methods. This study included 103 pts received RTX as an addition to previous therapy (group 1) and 65 pts received therapy with IS and prednisolone (group 2). The mean follow-up period was 12.6±10.7months. In group 1 the mean age was 47±12.9 years, female – 88 pts (84%), the diffuse cutaneous subset of the disease had 55 pts (53%). The mean disease duration was 6.2±5.5 years. 82% pts had interstitial lung disease (ILD) and 92% were positive for ANA, 67% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 11.3±4.5 mg/day, IS at inclusion received 47% of them. The cumulative mean dose of RTX was 1.7±0.6 g. In group 2 the mean age was 50.8±13.8 years, female-53 pts (82%), the diffuse cutaneous subset of the disease had 44 pts (68%). The mean disease duration was 8.8±7.7 years. 81% pts had ILD and 88% were positive for ANA, 58% of them were positive for antitopoisomerase-1. All pts received prednisolone at a dose of 8.69±4.28 mg/day, IS received 57% of them. Cyclophosphamide (CP) received 45% of pts. The cumulative mean dose of CP was 10.2±15.1g. D-penicillamine received 30% of pts. Other pts was on mycophenolate mofetil or methotrexate therapy in single cases. The pts of the compared groups did not differ in the main demographic and clinical parameters. The results are presented as delta (Δ) - difference between the baseline parameter and follow up point. Results. In group 1 there was an improvement of all outcome parameters: increased of forced vital capacity, % predicted - ΔFVC=4% (p=0.0004); Diffusing capacity for carbon monoxide, % predicted remained stable (ΔDLCO=0.1%); improvement of the Rodnan skin score-ΔmRss=3.4 (p=0.001); decrease of Activity index (EScSG-AI) - ΔActivity index=1.7 (p=0.001). In group 2 the changes was insignificant: ΔFVC=-2.3%, ΔmRss=0.87, ΔActivity index=0.3. But there was a significant decrease of DLCO: ΔDLCO=-5.1% (p=0.001). Conclusion. The results of our study confirm the data on the positive effect of RTX in complex therapy in pts with SSc (decrease of skin induration, increase of FVC, stabilization of DLCO). Meantime, pts on IS and prednisolone therapy shown the worsening of lung function and insignificant changes of other clinical parameters. RTX could be considered as a more effective option in complex treatment of SSc in comparison with IS therapy

Keywords: immunosuppressants, interstitial lung disease, systemic sclerosis, rituximab

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Authors: Knol Hester, Müller Swantje, Danchenko Natalya

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Objective: Falls in older people cause an autonomy loss and result in an economic burden. LCare is an AI-based application to manage fall risks. The study's aim was to assess the effect of LCare use on patient outcomes in nursing homes in Germany. Methods: LCare identifies and monitors fall risks through a 3D-gait analysis and a digital questionnaire, resulting in tailored recommendations on fall prevention. A study was conducted with AOK Baden-Württemberg (01.09.2019- 31.05.2021) in 16 care facilities. Assessments at baseline and follow-up included: a fall risk score; falls (baseline: fall history in the past 12 months; follow-up: a fall record since the last analysis); fall-related injuries and hospitalizations; gait speed; fear of falling; psychological stress; nurses experience on app use. Results: 94 seniors were aged 65-99 years at the initial analysis (average 84±7 years); 566 mobility analyses were carried out in total. On average, the fall risk was reduced by 17.8 % as compared to the baseline (p<0.05). The risk of falling decreased across all subgroups, including a trend in dementia patients (p=0.06), constituting 43% of analyzed patients, and patients with walking aids (p<0.05), constituting 76% of analyzed patients. There was a trend (p<0.1) towards fewer falls and fall-related injuries and hospitalizations (baseline: 23 seniors who fell, 13 injury consequences, 9 hospitalizations; follow-up: 14 seniors who fell, 2 injury consequences, 0 hospitalizations). There was a 16% improvement in gait speed (p<0.05). Residents reported less fear of falling and psychological stress by 38% in both outcomes (p<0.05). 81% of nurses found LCare effective. Conclusions: In the presented study, the use of LCare app was associated with a reduction of fall risk among nursing home residents, improvement of health-related outcomes, and a trend toward reduction in injuries and hospitalizations. LCare may help to improve senior resident care and save healthcare costs.

Keywords: falls, digital healthcare, falls prevention, nursing homes, seniors, AI, digital assessment

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Authors: Mohamad Ammar Ayass, Natalya Griko, Victor Pashkov, Wanying Cao, Kevin Zhu, Jin Zhang, Lina Abi Mosleh

Abstract:

Respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent for coronavirus disease 2019 (COVID-19). Early evidence pointed at the angiotensin-converting enzyme 2 (ACE-2) expressed on the epithelial cells of the lung as the main entry point of SARS-CoV-2 into the cells. The viral entry is mediated by the binding of the Receptor Binding Domain (RBD) of the spike protein that is expressed on the surface of the virus to the ACE-2 receptor. As the number of SARS-CoV-2 variants continues to increase, mutations arising in the RBD of SARS-CoV-2 may lead to the ineffectiveness of RBD targeted neutralizing antibodies. To address this limitation, the objective of this study is to develop a combination of aptamers that target different regions of the RBD, preventing the binding of the spike protein to ACE-2 receptor and subsequent viral entry and replication. A safe and innovative biomedical tool was developed to inhibit viral infection and reduce the harms of COVID-19. In the present study, DNA aptamers were developed against a recombinant trimer S protein using the Systematic Evolution of Ligands by Exponential enrichment (SELEX). Negative selection was introduced at round number 7 to select for aptamers that bind specifically to the RBD domain. A series of 9 aptamers (ADI2010, ADI2011, ADI201L, ADI203L, ADI205L, ADIR68, ADIR74, ADIR80, ADIR83) were selected and characterized with high binding affinity and specificity to the RBD of the spike protein. Aptamers (ADI25, ADI2009, ADI203L) were able to bind and pull down endogenous spike protein expressed on the surface of SARS-CoV-2 virus in COVID-19 positive patient samples and determined by liquid chromatography- tandem mass spectrometry analysis (LC-MS/MS). LC-MS/MS data confirmed that aptamers can bind to the RBD of the spike protein. Furthermore, results indicated that the combination of the 9 best aptamers inhibited the binding of the purified trimer spike protein to the ACE-2 receptor found on the surface of Vero E6 cells. In the same experiment, the combined aptamers displayed a better neutralizing effect than antibodies. The data suggests that the selected aptamers could be used in therapy to neutralize the effect of the SARS-CoV-2 virus by inhibiting the interaction between the RBD and ACE-2 receptor, preventing viral entry into target cells and therefore blocking viral replication.

Keywords: aptamer, ACE-2 receptor, binding inhibitor, COVID-19, spike protein, SARS-CoV-2, treatment

Procedia PDF Downloads 184

Authors: Mariia V. Efremova, Iana O. Tcareva, Anastasia D. Blokhina, Ivan S. Grebennikov, Anastasia S. Garanina, Maxim A. Abakumov, Yury I. Golovin, Alexander G. Savchenko, Alexander G. Majouga, Natalya L. Klyachko

Abstract:

During last decades magnetite nanoparticles (NPs) attract a deep interest of scientists due to their potential application in therapy and diagnostics. However, magnetite nanoparticles are toxic and non-stable in physiological conditions. To solve these problems, we decided to create two types of hybrid systems based on magnetite and gold which is inert and biocompatible: gold as a shell material (first type) and gold as separate NPs interfacially bond to magnetite NPs (second type). The synthesis of the first type hybrid nanoparticles was carried out as follows: Magnetite nanoparticles with an average diameter of 9±2 nm were obtained by co-precipitation of iron (II, III) chlorides then they were covered with gold shell by iterative reduction of hydrogen tetrachloroaurate with hydroxylamine hydrochloride. According to the TEM, ICP MS and EDX data, final nanoparticles had an average diameter of 31±4 nm and contained iron even after hydrochloric acid treatment. However, iron signals (K-line, 7,1 keV) were not localized so we can’t speak about one single magnetic core. Described nanoparticles covered with mercapto-PEG acid were non-toxic for human prostate cancer PC-3/ LNCaP cell lines (more than 90% survived cells as compared to control) and had high R2-relaxivity rates (>190 mМ-1s-1) that exceed the transverse relaxation rate of commercial MRI-contrasting agents. These nanoparticles were also used for chymotrypsin enzyme immobilization. The effect of alternating magnetic field on catalytic properties of chymotrypsin immobilized on magnetite nanoparticles, notably the slowdown of catalyzed reaction at the level of 35-40 % was found. The synthesis of the second type hybrid nanoparticles also involved two steps. Firstly, spherical gold nanoparticles with an average diameter of 9±2 nm were synthesized by the reduction of hydrogen tetrachloroaurate with oleylamine; secondly, they were used as seeds during magnetite synthesis by thermal decomposition of iron pentacarbonyl in octadecene. As a result, so-called dumbbell-like structures were obtained where magnetite (cubes with 25±6 nm diagonal) and gold nanoparticles were connected together pairwise. By HRTEM method (first time for this type of structure) an epitaxial growth of magnetite nanoparticles on gold surface with co-orientation of (111) planes was discovered. These nanoparticles were transferred into water by means of block-copolymer Pluronic F127 then loaded with anti-cancer drug doxorubicin and also PSMA-vector specific for LNCaP cell line. Obtained nanoparticles were found to have moderate toxicity for human prostate cancer cells and got into the intracellular space after 45 minutes of incubation (according to fluorescence microscopy data). These materials are also perspective from MRI point of view (R2-relaxivity rates >70 mМ-1s-1). Thereby, in this work magnetite-gold hybrid nanoparticles, which have a strong potential for biomedical application, particularly in targeted drug delivery and magnetic resonance imaging, were synthesized and characterized. That paves the way to the development of special medicine types – theranostics. The authors knowledge financial support from Ministry of Education and Science of the Russian Federation (14.607.21.0132, RFMEFI60715X0132). This work was also supported by Grant of Ministry of Education and Science of the Russian Federation К1-2014-022, Grant of Russian Scientific Foundation 14-13-00731 and MSU development program 5.13.

Keywords: drug delivery, magnetite-gold, MRI contrast agents, nanoparticles, toxicity

Procedia PDF Downloads 380