03. Bachelor's Thesis
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Item Embargo PROFILING UNDIAGNOSED DIABETES IN A WORKING AGE KAZAKH POPULATION(Nazarbayev University School of Medicine, 2022-04-25) Zhailkhan, AkbotaUndiagnosed diabetes (UDM) is a major public health concern. Almost half of all diabetic patients are unaware of their condition, which puts them at higher risk of mortality and serious comorbidities. Timely detection of UDM should decrease the social and economic costs associated with diabetes worldwide and can be achieved through establishing its risk profile, which differs for each country. Diabetes also shows varying degrees of insulin resistance (IR) and β-cell function possibly affecting the disease progression. UDM has been understudied in Kazakhstan, and this research aims to update the current understanding of its prevalence, cardiovascular risks and glucose metabolism profile in the local population. Total of 476 people were included in the analysis. The prevalence of UDM was 11.97% (95% CI, 9.20-15.24%), and it was represented by a significantly older population and worse cardiovascular risk profile. Stepwise-forward logistic regression identified systolic blood pressure, older age and total cholesterol as significant predictors of UDM. Using HOMA-IR and HOMA-β scores, k-means clustering defined three distinct UDM phenotypes. Phenotypes with β-cell dysfunction were more prevalent and showed higher risk for cardiovascular disease, which has possible implications for personalized treatment in diabetes care.Item Restricted HOW DO CTHRC1 AND MATRIX METALLOPROTEINASES AFFECT PATHOLOGIC ACTIVITIES OF FIBROBLAST-LIKE SYNOVIOCYTES IN RHEUMATOID ARTHRITIS?(Nazarbayev University School of Medicine, 2023) Kozhdan, KamilyaRheumatoid arthritis (RA) is an intricate autoimmune condition impacting approximately 1% of the global adult population. One of the key characteristics of this disease is the tendency of activated fibroblast-like synoviocytes (FLS) to invade and damage joint tissues. Recently, there has been a significant focus on discovering biomarkers that can precisely forecast the development of RA. One potential set of biomarkers includes collagen triple helix repeat-containing protein 1 (CTHRC1) and metalloproteinases (MMPs) proteins associated with migration and invasiveness of fibroblast-like synoviocytes, which are responsible for instigating inflammation and joint destruction in RA. The objective of this work is to investigate how CTHRC1 and MMPs are associated with the movement and invasive properties of FLS in the progression of RA. The study aims to assess whether the expression of these proteins can be used to anticipate the development of RA. The research will entail evaluating how CTHRC1 and MMP levels affect FLS pathogenesis. The conventional diagnostic markers for RA were used to show the correlation between potential biomarkers expression and disease activity. The results of this study could be significant for developing new targets for treatment and therapies for RA.Item Restricted PERIOSTIN IN INFLAMMATORY BOWEL DISEASE (IBD)(Nazarbayev University School of Medicine, 2023) Maratov, MadiThe review summarizes current research findings on the link between inflammatory bowel disease (IBD) and periostin. IBD includes Crohn's disease (CD) and ulcerative colitis (UC). IBD can be caused by four established factors, namely genetic changes, environmental factors, microbiome changes, and immune dysfunction. It has been shown that during IBD, the concentration of serum periostin increases. This is because periostin level rises during tissue damage and allergic reactions. In fact, periostin exhibits six functions: cell recruitment, fibrosis, cell proliferation and apoptosis, activation of various cytokines, angiogenesis, and cancer development. Current studies show that periostin contributes to IBD's fibrogenesis, cell migration, and cell proliferation. Additionally, studies show that during IBD predominant location of periostin is around intestinal crypts, the expression of periostin increases in cell response to IL-6, IL-13, and TGF-β and periostin is associated with NF-kB and YAP/TAZ signaling pathways. Furthermore, the review discusses how periostin is involved in colitis-associated cancer and periostin’s predictive and therapeutic roles in IBD.Item Restricted DEMOGRAPHIC AND CLINICAL PORTRAIT OF WOMEN WITH RECURRENT PREGNANCY LOSS IN KAZAKHSTAN(Nazarbayev University School of Medicine, 2023) Turmagambet, LuizaBackground. Recurrent pregnancy loss (RPL) is a complex health challenge with multiple risk factors. No conclusive study describes demographical and clinical risk factors associated with RPL in Kazakhstan. This study aims to identify demographic and clinical risk factors that influence or contribute to RPL in Kazakhstan. Methods. This cross-sectional study was conducted among women with RPL attending outpatient clinics in Astana, Kazakhstan. The primary study instrument was a 23-item clinical questionnaire. Nonparametric statistical tests and correlation analysis examined differences and associations between variables. Results. Ninety-five study subjects with two or more spontaneous miscarriages participated in this study. The median number of pregnancies (gravidity) and live births (parity) were 3.5 and 0, respectively. The number of pregnancies and deliveries was statistically discernible from the number of spontaneous miscarriages. Spearman's correlation analysis showed positive correlations between gravidity and parity with RPL (r-value = 0.86 and 0.30). Conclusion. There is a direct association between gravidity and parity with RPL. However, no statistical discerning was found concerning identified risk factors such as maternal age and BMI. Further research is needed to verify the magnitude of the current study’s findings and to identify additional risk factors that predispose Kazakhstani women to RPL.Item Restricted DEVELOPING A SYSTEM FOR ANALYZING THE DOWNSTREAM EFFECTS OF CCL5 DERIVATIVES ON THE CCR5 PATHWAY(Nazarbayev University School of Medicine, 2023) Mustafa, KamshatBackground: Various types of diseases are known to be influenced by the ССL5/ССR5 pathway, including cancers and HIV. Inhibiting the attachment of CCL5 to CCR5 has shown promise in preclinical studies as a way to suppress the growth of the tumor and improve outcomes in cancer patients. In this study, we want to observe how p21, p53, and Mdm2 protein expressions that play important roles in cell growth will change with different modifications of CCL5. We aim to check the level of expression of these proteins in the cell line derived from brеаst саnсеr - МСF-7. Маtеrіаls & Меtһоds: МСF-7, МDА-МВ-231, СНО/CCR5, and СНО/WT cell lines were cultured for further RNA isolation, RT-PCR, and qPCR experiments. RNA isolation and RT-PCR were performed in order to check whether the expected genes exist. In order to check the expression levels of three target proteins quantitative PCR was done. Results: RT-PCR interpretation on a gel showed that cell lines express p21, Mdm2, and GAPDH genes, but failed to show p53. Only MDA-MB-231 cells were positive for CCR5 on a gel. qPCR analysis failed to determine Ct values for GAPDH and p53. That is why we were unable to calculate gene expression values for target genes and the experiment should be repeated.Item Restricted REGIONAL ANESTHESIA FOR PAIN CONTROL IN PEDIATRIC ONCOLOGY PATIENTS(Nazarbayev University School of Medicine, 2023-04) Baizhanova, AliyaAround 70% of all childhood cancer patients suffer from severe pain. This pain originates either from metastasizing tumor cells or as the outcome of therapy meant to deal with tumor. If managed inadequately, such pain can lead to many hazardous sequelae. However, there are extreme cases when pain does not respond to any treatment. For such cases, regional anaesthesia or nerve blocks are utilized as the utmost pain control measure. Blocks are used to treat pain in patients who no longer respond to conventional opioid-based treatment or whose worsened condition makes it impossible to receive any other therapy. The data on the use of nerve blocks for such cases in children population is limited. This review discusses the regional anesthesia techniques used in pediatric oncology patients. It was concluded that nerve blocks, although rarely performed, are a safe and efficient way of pain control in pediatric oncology patients. The major settings for block performance are postoperative pain control and palliative care. We observed that block indication and its outcomes depend on unique health circumstances in which they should be performed. Patients with similar diagnoses had differing outcomes while receiving the same block treatment.Item Open Access ASSOCIATIONS OF INSULIN RESISTANCE, Β-CELL FUNCTIONING, AND CARDIOVASCULAR RISK FACTORS WITH PREDIABETES IN A WORKING AGE POPULATION FROM TURKISTAN(Nazarbayev University School of Medicine, 2023-04-20) Li, Mariya; Sarria-Santamera, AntonioThe incidence of T2DМ will increase each year since the prevalence of people with prediabetes is even higher. This study is aimed to describe the clinical, biochemical, and metabolic characteristics of people with prediabetes, analyse the effect of insulin resistance (IR) and impaired β-cell function identified by the homeostasis model assessment values on prediabetes, and identify the risk factors for prediabetes, IR and impaired function of β-cell. The data for the study was obtained from workers of the Khoja Akhmet Yassawi International Kazakh-Turkish University (Turkistan, Kazakhstan). The final sample contained 419 participants aged between 27-69, including 237 healthy and 182 prediabetic individuals. Multivariable logistic regression models were computed. This study demonstrated prediabetes population has older age, a high median BMI and systolic blood pressure, high obesity prevalence, and dyslipidemia characteristics. IR and impaired β-cell function are positively correlated with prediabetes. Waist circumference, age, systolic blood pressure, IR, and poor β-cell are risk factors for prediabetes. Prediabetes is positively associated with IR and poor β-cell function. No model was found to describe IR risk factors in the population. Still, it revealed that age and total cholesterol levels could be used to predict poor β-cell function in prediabetic individuals.Item Embargo ELECTROPORATION AS A TRANSFECTION METHOD FOR MB49 UROTHELIAL CARCINOMA CELL LINE(Nazarbayev University School of Medicine, 2023-04-25) Orazaliyeva, MadinaIn recent years, periostin has gained research interest as a possible prognostic biomarker tool for many cancer types due to its strong correlation with poor prognosis and metastasis. However, in the case of bladder cancer, the physiological role of periostin in its development and progression remains poorly understood. To explore this further, transfection, a research strategy commonly used to examine certain gene functions, was performed. In this study, the MB49 cells, a murine urothelial carcinoma cell line, were transiently transfected with periostin DNA in vitro via electroporation. The study aimed to determine whether electroporation is more effective for transfecting MB49 cells with periostin plasmid than chemical reagents. The results showed that electroporation efficiency was low relative to transfection efficiency obtained using chemical reagents, with a transfection efficiency rate of only 4.22%. This finding suggests that electroporation is not an effective method for transient transfection of MB49 cells with periostin plasmid in vitro compared to transfection using cationic lipid reagents, highlighting the limitations of this transfection method. In future studies, alternative physical and non-physical transfection techniques should be explored to improve the transfection efficiency of MB49 cells.Item Open Access SOLUBLE TAM RECEPTOR AXL TRIGGERS CHANGES IN CELL BEHAVIOR AND SIGNALING OF BLADDER CANCER CELLS(Nazarbayev University School of Medicine, 2023-04-25) Kaliyeva, AlmiraAXL, a member of the TAM family, has emerged as a potential target for treating bladder cancer due to its role in cellular activities and tumorigenesis. This receptor was found to be overexpressed in cancer. Here, the soluble form of AXL (sAXL) is studied. sAXL has been proposed to act as a decoy receptor, which sequesters growth arrest-specific 6 (Gas6) ligand and shuts down Gas6/AXL axis. This hypothesis has been supported by several studies that demonstrated a high-affinity binding between sAXL and Gas6. Nevertheless, the role of sAXL in cellular signaling in bladder cancer has not been studied. This study investigated if sAXL affects cell behavior and signaling of bladder cancer cells and if it can act as a decoy. The recombinant AXL and Gas6 were used for the analysis, and cells were cultured with further incubation with these proteins. Western blotting was used to investigate the expression of AXL downstream targets. The findings revealed that sAXL has a similar effect on cells as Gas6, proposing that sAXL may participate in homophilic and heterophilic binding with TAM receptors. Moreover, sAXL sequestered Gas6 in pAkt-308 activation. As a future perspective, a broader analysis of the interactions between soluble AXL and TAM receptors is needed.Item Restricted SYNTHESIS AND CHARACTERIZATION OF COMPOSITE CHITOSAN-BASED DRUG DELIVERY SYSTEM LOADED WITH A CYTOKINE(Nazarbayev University School of Medicine, 2023-04-25) Tabyldiyeva, LauraСhitosan is a naturally occurring biomaterial with great potential in tissue engineering, wound healing, and drug delivery. Its various properties such as biocompatibility, biodegradability, and antimicrobial activity make it an attractive candidate for biomedical applications. In addition, chitosan can be synthesized into various conformations, including nanoparticles, scaffolds, hydrogel, and cryogel. Among them, cryogel is considered one of the practical conformations due to its macroporous structure and enhanced mechanical strength. In this study, macroporous cryogel composed of chitosan (CHI), hydroxyapatite (HA), heparin (Hep), and polyvinyl alcohol (PVA) cross-linked with glutaraldehyde (GA) was synthesized to design a drug-delivery system. The compounds mentioned above were chosen to create a cryogel with enhanced mechanical strength, biocompatibility, lower degradation rate, and bioavailability. The study's main purpose was to examine a controlled release of a drug from composite cryogel. In order to observe the sustained release of a drug from the designed drug-delivery system, cytokine interleukin-10 (IL-10) was incorporated into composite chitosan cryogel. As a result, CHI-PVA-HA-Hep-GA proved to be an effective drug-delivery system as it was able to release IL-10 in a controlled manner. Designed composite cryogel might have a high potential as a therapeutic agent in tissue engineering and the treatment of various diseases.Item Restricted RETROSPECTIVE ANALYSIS OF DELAYED GRAFT FUNCTION INCIDENCE IN KIDNEY TRANSPLANT IN KAZAKHSTAN(Nazarbayev University School of Medicine, 2023-04-25) Mailina, DariyaThe incidence of delayed graft function (DGF) poses a considerable challenge, impacting both graft and patient survival. The objective of this paper was to investigate the incidence of DGF and factors that contribute to its manifestation in a group of 115 kidney transplant recipients in Kazakhstan. A multivariate logistic regression showed that the overall incidence of DGF was found to be 13.91%, with deceased donor kidney recipients exhibiting a higher rate (41.17%) as opposed to living donor recipients (9.28%). Moreover, analysis disclosed a marginally significant relationship between the age of the recipient and DGF risk (OR: 1.08, 95% CI: 0.99-1.19, p = 0.090). Additionally, a statistically significant correlation between obtaining an organ from a deceased donor and an elevated risk of DGF (OR:69.28301, 95% CI: 4.48-1071.76 a p = 0.002), was established. The relationship between HLA mismatch and DGF risk was found to be of borderline statistical significance (OR: 0.96, 95% CI: 0.92-1.00, p = 0.052). No meaningful association between gender and DGF risk was detected. The findings underscore the significance of donor type concerning DGF risk and propose potential links between recipient age and HLA mismatch.Item Restricted RETROSPECTIVE ANALYSIS OF GRAFT SURVIVAL INCIDENCE AFTER KIDNEY TRANSPLANTATION IN KAZAKHSTAN(Nazarbayev University School of Medicine, 2023-04-25) Alpysbayeva, YerkegulNowadays, graft survival after kidney transplantation has become a heated issue. The incidence of graft loss remained high for years. This is also true for Kazakhstan, where according to the latest data (2018) the graft loss was 90% in a 10-year time period. The aim of this retrospective study is to evaluate the rate of graft survival in Kazakhstan using the latest available data and identify the factors affecting the graft loss. The significance of this study is that the results obtained show more recent epidemiological situation in Kazakhstan and update the existing data on graft survival. The materials and methods included the collection of raw data from the Unified National Electronic Health System and statistical analysis such as Cox Proportional Hazards Survival Regression test. The results obtained are the following: the rate of the graft survival is 64% while the incidence rate of graft loss is 36%. The analysis of factors that affect the graft survival showed no statistical significance due to the small sample size (77), hence not included in the final results. Overall, the study demonstrated the importance of collecting large database to evaluate the rate of graft survival after kidney transplantation.Item Restricted MESENCHYMAL STEM CELLS: ISOLATION FROM MOUSE BONE MARROW AND DIFFERENTIATION TOWARDS MYOCARDIAL CELLS USING SPECIFIC GROWTH FACTORS(Nazarbayev University School of Medicine, 2023-04-25) Zhumagul, DiasThe study investigated the effect of epidermal growth factor, vascular endothelial growth factor, bone morphogenic protein, fibroblast growth factor, activin, and insulin-like growth factor family proteins on the mesenchymal stem cell differentiation in three lineages, including endothelial cells, smooth muscle cells, and cardiomyocytes. Established protocols for isolating mesenchymal stem cells and their differentiation were used during the experiment with some procedures and recommendations adjustment. The study analyzed growth factors’ effect on stem cell differentiation by observing cells’ morphological changes and immunofluorescent imaging analysis of specific cell markers. The results demonstrated that induction with growth factors was sufficient to differentiate the cells into all three lineages, which was evidenced by the morphological changes and expression of lineage-specific markers CD31, alpha-SMA, and cardiac troponin, and downregulation of stem cells specific marker CD105 for endothelial cells, smooth muscle cells, and cardiomyocytes, respectively. The findings demonstrate that mesenchymal stem cells derived from mice bone marrow can differentiate in a multilinear fashion when induced with growth factors, giving rise to three major types of heart cells, meaning its great potential in regenerative medicine, more specifically, the treatment of heart failure after ischemic heart diseases by compensating for the cell loss after myocardial infarction.Item Restricted GENERAL ATTITUDES TOWARDS AND READINESS FOR MEDICAL ARTIFICIAL INTELLIGENCE AMONG STUDENTS AT NAZARBAYEV UNIVERSITY SCHOOL OF MEDICINE.(Nazarbayev University School of Medicine, 2023-04-25) Sembekova, AnaraIntroduction: Artificial intelligence is taking over the leading positions in medical technologies. AI in healthcare not only performs basic computational tasks, but also exceeds human performance in many areas of healthcare. Aim: This study aims to analyze the attitudes and readiness of students at Nazarbayev University School of Medicine (NUSOM) to the upcoming AI integration. Methods: 91 students were asked to fill out an online survey that collected data of respondents’ characteristics and AI familiarity, general attitudes, and general readiness assessment scales. The General Attitudes towards Artificial Intelligence Scale (GAAIS) developed by Schepman and Rodway (2020) and the Medical Artificial Intelligence Readiness Scale for Medical Students (MAIRS-MS; Karaca et al., 2021) were used in the study. Results: Most of the students had a low knowledge of AI with a mean = 45.56. Majority of the participants did not have any educational experience both in (95.6%) and outside (85.7%) the institution. Positive attitudes section: mean = 2.75 (SD = 0.64), while negative attitudes: mean = 3.01 (SD = 0.81). The readiness mean = 2.42 (SD = 0.60) out of 5.00. Conclusion: The research determined that most of the students had negative to neutral attitudes and poor readiness to medical AI. However, knowledge about AI and positive attitudes had a significant correlation with preparedness. The findings can be used to inform educational policymakers and educational institutions to develop curriculums involving AI, and ensure its ethical and optimized application in medicine. Keywords: artificial intelligence, machine learning, healthcare, medicine, attitudes, readiness, medical studentsItem Restricted THE ANALYSIS OF A PATIENT SURVIVAL RATE AFTER KIDNEY TRANSPLANTATION IN KAZAKHSTANT(Nazarbayev University School of Medicine, 2023-04-25) Kuspanov, AbualiKidney transplantation has become a broadly used practice in Kazakhstan. However, it is vital to ensure the high survival rates of patients after this procedure. Therefore, this paper is trying to evaluate the extent to which factors such as age, donor type, HLA mismatch, and maintenance therapy affect survival. To perform this, the discharge reports of 77 patients were analyzed, and a database with the variables was created. Then, the Cox and logistic regression models were used to analyze the effect of variables on patient survival. Overall, ten or 13% of death cases were reported among this group, so the patient survival rate is 87%. However, the unadjusted Cox and logistic regression models showed no significant statistical effect of age, gender, donor type, HLA mismatch, and type of drugs used. Although the literature justifies their odds and hazard ratios, the small sample size might be the reason for their insignificant statistical effect. It is recommended to further analyze the patient survival rate with a much larger sample size and other potential risk factors.Item Open Access INTER- AND INTRA-OBSERVER VARIABILITY OF LEFT VENTRICULAR HEMODYNAMIC FORCES DERIVED FROM FEATURE-TRACKING CARDIAC MAGNETIC RESONANCE.(Nazarbayev University School of Medicine, 2023-04-25) Ismailov, TemirlanHemodynamic forces (HDF) analysis represents a novel approach to quantify intraventricular pressure gradients (IVPG). Recently, a new noninvasive method for evaluating HDF based on feature tracking has been proposed, however data on the reproducibility of this method is still scanty. Thus, the aim of this study is to assess the reproducibility of HDF parameters derived from cardiac magnetic resonance (CMR). Twenty athletes' CMR studies were analyzed by two independent observers and 15 of them were re-analyzed by the same observer one week apart. Intraclass Correlation Coefficient and Bland-Altman plots were used to assess association and agreement of the Longitudinal HDF (A-B), Transverse HDF (L-S), and Impulse Angle. For two different observer measurements, there was a good association for the A-B and L-S (ICC 0.82 and 0.85, respectively; p<0.001), and quite a good association for the Impulse Angle (ICC 0.67; p<0.012). For the same observer's measurements one week apart, the ICC values for A-B, L-S, and Impulse Angle showed excellent correlation and high statistical significance (0.89, 0.93, and 0.82, respectively; p<0.001). The results of this study showed a low inter- and intra-observer variability of HDF parameters derived from CMR.Item Restricted SEMI-STRUCTURED INTERVIEW ANALYSIS OF ADULT PARTICIPANTS OF A PILOT SOCIAL PROJECT WITH THE AIM INCREASING PHYSICAL ACTIVITY FOR CHILDREN WITH AUTISM IN KAZAKHSTAN THROUGH AN ONLINE PARENT-MEDIATED INTERVENTION(Nazarbayev University School of Medicine, 2023-04-26) Akilbayev, RakhatThe objective of this research was to test the feasibility of an online-based parent-mediated intervention focused on increasing physical activity levels among children with ASD, with the focus on the qualitative analysis of post-intervention interviews. For this purpose, phenomenological methodology was applied along with semi-structured interviews and thematic analysis. The components of the intervention included: informational and physical activity promotion posts, motivational messages, goal setting, monitoring of activity and discussion with other parents. Analysis of the interviews yielded 7 themes: overall success of components, lack of time, benefits of parent communication, practical advice that can be applied right away, older children or parents participation, “we learn the needs in the course of classes”, more assistance with goal setting. Findings suggest that parents were largely satisfied with the intervention, reporting success of most of the components, for example, increased awareness, improvements of the ASD symptoms, convenience of the online format and others. Major barrier reported by parents was the lack of time, while some parents reported struggling with achieveing weekly goals.Item Restricted DIETARY PATTERNS OF ELDERLY INDIVIDUALS WITH AND WITHOUT ALZHEIMER'S DISEASE IN KAZAKHSTAN: A COMPARATIVE STUDY OF NUTRIENT INTAKE, FOOD GROUPS, AND OVERALL DIETARY QUALITY(Nazarbayev University School of Medicine, 2024) Maken, AruzhanAlzheimer's disease (AD) is the leading cause of mortality and disability in the elderly population worldwide. While various factors contribute to AD development and progression, the role of dietary patterns, particularly in under-studied regions, remains unclear. This study analyzed the dietary intake of individuals over 50, with and without AD, in Kazakhstan to determine nutritional differences and associations with AD. A cross-sectional study was conducted among AD and age-matched controls in Astana and Almaty. Dietary intake was assessed using a food frequency questionnaire. Nutrient intake was analyzed for macronutrients and micronutrients. No significant differences were observed between the nutrient intake of AD participants between cities, suggesting uniform dietary patterns among the population with AD within Kazakhstan. Furthermore, macronutrient intake revealed no differences between AD and control. Variations were observed between AD and control in micronutrients. AD participants had lower nutrient intake values in both cities, consistent with previous reports of decreased appetite and swallowing difficulties in AD patients. Our findings suggest that micronutrient intake may have neuroprotective effects in the Kazakhstani elderly population and warrants further investigation. The observed differences in micronutrient intake between AD and control groups could inform targeted nutritional interventions to prevent or mitigate AD progression in this region.