07. School of Medicine
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Item 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 Analysis of factors associated with profitability of Kazakhstani state hospitals and polyclinics.(Nazarbayev University School of Medicine, 2018-05) Shayakhmetov, YerassylThe following study analyzed factors affecting profitability of medical state enterprises. The primary interest of the study was the effect of corporate governance on financial performance of oblast level hospitals and primary care clinics. It was found that the presence of a supervisory board for the hospital or clinic is associated with decreased probability of producing net positive income (37% less chance) in these organizations. Also it was found that characteristics of supervisory boards like number of people in the board and meetings held by supervisory boards are not associated with profitability of state medical enterprises. The profitability of state medical organizations also differed between regions of the country and between organizations located in cities and rural regions.Item Embargo ANALYSIS OF GCIP FUNCTION IN RHEUMATOID ARTHRITIS(Nazarbayev University School of Medicine, 2024) Sabyrbekova, AzizaRheumatoid arthritis is a condition that affects people globally, with a prevalence that varies between 0.1% to 2%, and unfortunately, current treatments are ineffective for about 30% of patients. To find new targets for treatment, the causes of RA have to be further examined. The primary objective of this research study is to examine the role of Grap2 cyclin-D interacting protein (GCIP) in the development of RA. According to recent studies, GCIP can inhibit cell proliferation, and downregulation of GCIP may contribute to fibroblast-like synoviocytes (FLS) overgrowth in RA patients. However, most research has been conducted only in vitro, and information about the mechanism of GCIP function in FLS is still limited. Based on the research findings of an in vivo mouse model, it was observed that the expression of GCIP is downregulated in mice induced with RA compared to untreated mice. Further research is needed to fully comprehend the role of GCIP in RA and its potential therapeutic implicationsItem Restricted Analysis of GCIP Function in Rheumatoid Arthritis(Nazarbayev University School of Medicine, 2024-04-29) Nessipbekova, AssemThe global burden of rheumatoid arthritis (RA) is increasing for the ageing population. The disease is characterized by progressive joint inflammation and tissue destruction. One of the key players in the pathogenesis of RA is synovial fibroblasts (SF), which invade and destroy the cartilage in the joints. However, the exact molecular mechanism which explains their abnormal outgrowth is yet to be elucidated. Grap2 cyclin D interacting protein (GCIP), a protein related to Id proteins, plays a role in cell cycle progression and gene expression by blocking interactions between (CREB) binding protein (CBP) and RNA polymerase II complexes. A recent study has shown that Grap2 cyclin D interacting protein (GCIP) has been downregulated in the synovial fibroblasts in rheumatoid arthritis patients, suggesting its involvement in disease progression. The knockdown of the GCIP protein resulted in the increased growth of synovial fibroblasts, consequently leading to the upregulation of Cyclin D1, a crucial cell cycle and cell proliferation player regulated by the CREB. This thesis aimed to explore the role of GCIP in the pathogenesis of rheumatoid arthritis by establishing a mouse model of rheumatoid arthritis and testing how GCIP knockout affects the proliferation of synovial fibroblast during RA. Two cohorts of WT and GCIP KO C57BL/6 mice were utilized to induce RA with 2 different protocols. The protocol 2 resulted in a more pronounced disease phenotype in males. Female mice from both showed no visible signs of RA. The role of GCIP on the proliferation of the synovial fibroblasts was not established necessitating a larger cohort size and choosing male mice as a subject.Item Open Access Antibiotic/antimicrobial resistance patterns of bacterial pathogens isolates from national research center for mother and child health in Astana, Kazakhstan(Nazarbayev University School of Medicine, 2018-05) Iskhakova, DinaraThe rapid emergence of drug resistant bacteria is occurring worldwide, endangering the efficacy of antibiotics, which have transformed medicine and saved millions of lives (1-6). Many decades after the first patients were treated with antibiotics, bacterial infections have again become a threat (7). The antibiotic resistance crisis has been attributed to the overuse and misuse of these medications, as well as a lack of new drug development by the pharmaceutical industry due to reduced economic incentives and challenging regulatory requirements.Item Restricted Assessing the role of EBV in modulation of gene expression profile of H4 neuroglioma and U118 glioblastoma cell lines consistent with Alzheimer's disease(Nazarbayev University School of Medicine, 2024-04-26) Omarova, ZhannurEpstein-Barr virus (EBV), a ubiquitous double-stranded DNA virus, also known as human herpesvirus 4, is implicated in a variety of neurological disorders. It is recognized as a major risk factor for multiple sclerosis. Recent studies have revealed a potential role for EBV infection in the pathogenesis of Alzheimer's disease (AD). EBV is known to influence host gene expression through its proteins and non-coding RNAs, including latent genes such as EBNA1 and LMP, as well as lytic genes such as BZLF1. Extensive research has examined the influence of EBV on cellular gene expression during tumorigenesis, however, little research has been conducted to understand how EBV influences gene expression associated with AD. This study aimed to explore the association between EBV and AD by testing the hypothesis that EBV elements, such as EBNA-1, cause changes in host gene expression consistent with the AD gene expression profile in the nervous tissue. To test this hypothesis, bioinformatics analysis of three GEO AD brain cell type-specific gene expression datasets was performed and the expression changes of the three identified genes – EBF1, EGR1, and GFAP – were examined in EBV-infected and uninfected H4 neuroglioma and U118 glioblastoma cell lines. EBV infection was carried out using cell-free viral supernatant. Changes in gene expression were assessed using qPCR. This study is the first to explore experimental methods for EBV infection of H4 and U118 cells. Although latent EBV infection was not detected in infected cells using primers for EBNA1, EBER1, and EBER2, the levels of EBF1, EGR1, and GFAP in infected cells changed at different days post-infection compared with control cells. Similar to AD brain cell types, EBF1 and GFAP were increased in infected U118 cells compared to uninfected cells. An increase in EGR1 was first observed in both cell lines after infection, followed by a downward trend, consistent with the results of the bioinformatics analysis. Further analysis is needed to assess whether these changes were specifically related to EBV infection. In conclusion, the thesis work highlights the need and importance of more research on the link between EBV infection and AD, as certain cellular changes after EBV infection were similar with brain cell types affected by AD.Item Restricted ASSESSING THE ROLE OF EBV PROTEINS IN AMYLOID-BETA AGGREGATION ASSOCIATED WITH INDUCTION OF ALZHEIMER'S DISEASE(Nazarbayev University School of Medicine, 2024-04-26) Berikkara, AsselBackground: Alzheimer’s disease represents the most prevalent form of neurocognitive decline. The key distinguishing pathological markers within the central nervous system involve the aggregation of senile plaques resulting from a two-step cleavage of the amyloid precursor protein by beta- and gamma-secretase enzymes sequentially. Previous studies have demonstrated a positive correlation between individuals who have mononucleosis due to EBV infection and their increased vulnerability to Alzheimer's disease. Hence, a new outlook on the disease etiology known as the "infectious hypothesis" has directed attention toward the Epstein-Barr virus (EBV), a double-stranded DNA virus, in terms of its potential contribution to plaque formation and inflammation associated with Alzheimer's disease. Methods: H4 neuroglioma and U118 glioblastoma cell lines were directly infected with EBV containing supernatant. The expression of APP and Tau mRNA was detected by qPCR. Protein levels were measured using ELISA with anti-APP antibodies, both before and after viral infection. Virus-free H4 and U118 cell lines were used as controls for comparative statistical analysis of mRNA and protein levels of the APP gene. Results: Infected U118 cell growth was maintained for more than 20 days, while H4 cells died out after the 7th day post-infection. qPCR results showed a consistent decrease in wild-type APP, APP-KPI, and APP-770 mRNA levels throughout the infection period, while Tau protein exhibited a statistically significant decrease in its expression level. In H4 cells, there was a decrease in WT APP and APP-KPI, while tau protein showed an enhanced mRNA level compared to the control. Conclusion: Direct EBV infection of glial cells resulted in alterations in the expression of Alzheimer's disease hallmark genes (WT APP, APP-770, APP-751, and Tau) in both H4 and U118 cell lines in a time-dependent manner.Item Restricted Association between tap water quality and self-reported gastrointestinal and kidney diseases among residents of Astana(Nazarbayev University School of Medicine, 2019) Yessimkulova, FarizaAccess and supply of safe water are vital for human well-being. Previous studies show that the quality of drinking water may affect human health outcomes. This study is aimed to examine perception regarding tap water quality among Astana city residents and its association with gastrointestinal (GI) tract and kidneys associated diseases. A self-reported questionnaire was used for data collection. The survey was distributed via social media groups and hard copies were given in hands. In total, 371 responses were included in the analysis....Item Restricted Association of a body mass index with an in vitro fertilization outcomes(Nazarbayev University School of Medicine, 2019) Rakhimova, MakhabbatThere is evidence about the association between body mass index (BMI) and reproductive system disorders; however the impact of BMI on in vitro fertilization (IVF) treatment outcomes is still controversial in the literature. Therefore, the aim of our study was to investigate the influence of the full spectrum of body mass index (BMI) on IVF treatment and pregnancy outcomes...Item Restricted Association of climate and weather components with incidence of gastric cancer(Nazarbayev University School of Medicine, 2019) Aubakirova, MinaToday, climate change and cancer are concurrent epidemics, and while each is under scrutiny in its own field, little research concentrates on the interaction of the two. Among other oncological diseases, stomach cancer is the second most common in males and fourth most common in females in Kazakhstan. The country itself takes the twelfth place in the world for age-standardized gastric cancer incidence rates. Therefore, the purpose of the current study is to examine the association of climate and annual weather with incidence of stomach cancer. Hospital admissions for 2014-2017 were obtained from the Ministry of Health of Kazakhstan, whereas climate and weather data were extracted from publicly available online sources. Kruskal-Wallis test, Pearson’s correlation tests, and multiple linear regression with generalized estimating equation were performed in STATA-12. The analyses were done on town levels. Thus, all 87 towns of Kazakhstan were assessed in climate analysis, and 40 towns were analyzed in terms of annual weather....Item Restricted Association of nutrition related knowledge and self-efficacy with unhealthy eating behavior among university students of Astana city(Nazarbayev University School of Medicine, 2019) Ainabekova, AsselPoor diet is associated with risk for obesity, cardiovascular diseases and other noncommunicable diseases, which nowadays are the main causes of death worldwide. The aim of this study was to examine the association of unhealthy-eating behavior with nutrition-knowledge and self-efficacy to resist unhealthy eating among university students. The additional objective of our study was to determine the stages of change towards healthier eating behavior and to identify factors associated with each of the stages.Item Restricted Association of Phase II Drug Metabolizing Enzyme and Hormonal Balance Single Nucleotide Polymorphisms (SNPs) with Autism: A Case Control Study(Nazarbayev University School of Medicine, 2019) Izimov, AidarkhanAutism is a neurodevelopmental, chronic disease that is classified under Autism Spectrum Disorder (ASD) group. Considering high prevalence of 14.6 per 1000 children, all of these symptoms and conditions place both physical, emotional and economic burden on patients with autism and their relatives. One of the genetic determinants that affects ASD development is increased oxidative stress as a result of improper phase II drug metabolism enzyme function. Additionally, considering the higher prevalence of autism in males than females with a ratio of 3:1, it is important to understand genetic factors and pathways that play role in the sex difference. Therefore, the aim of this study was to analyze the association between phase II drug metabolism-related and hormonal balance related SNPs with autism. Based on the case control data among 1737 participants from Melbourne, Australia, among 6 statistically significant SNPs based on simple logistic regression, only 3 phase II metabolism related SNPs were statistically significant in final, age and gender adjusted model – GSTP1, QR1 and HO-1. None of the hormonal balance related SNPs were statistically significant at the final model. Considering high power of this study, based on the finding several possible implications can be applied in the future, including early diagnosis and the diet based on genetic profiling.Item Restricted ASSOCIATION OF POSITIVE MENTAL HEALTH LITERACY WITH MENTAL WELL-BEING AMONG UNDERGRADUATE STUDENTS OF NAZARBAYEV UNIVERSITY(Nazarbayev University School of Medicine, 2022) Akisheva, GuldanaBackground The increase in the prevalence of mental disorders in young adults requires more attention on improving mental health and mental health literacy (MHL). Although majority of previous studies focused on recognition and prevention of mental illnesses, very few studies were focused on positive mental health literacy (PMeHL), part of MHL which defines knowledge about how to obtain and maintain good mental health. Therefore, the aim of this study was to examine the relationship between positive mental health literacy and mental well-being of undergraduate students in Kazakhstan. Methods The data was obtained from a cross-sectional study based on a survey of 122 undergraduate students aged 18–22 years at Nazarbayev University in Nur-Sultan city. WHO-5 Well-Being Index was utilized to evaluate mental well-being, and Mental Health Promoting Knowledge-10 item scale (MHPK-10) was used to assess PMeHL. The relationship was evaluated using a multiple linear regression model adjusting for possible covariates, including socio-demographic and lifestyle characteristics of students. Statistical threshold was determined at p<0.05. Results The sample included 35% of males and 65% of females, with the mean age of 19.5 years. PMeHL had a positive impact on mental wellbeing, where every increase in the score of PMeHL was significantly associated with increase in the score of mental well-being by 0.23, while adjusting for gender, age, family’s support, father’s education level, and physical exercising behaviour. Additionally, gender differences were observed in mental well-being, where mean of mental well-being was equal to 2.80 for males and 2.27 for females. Gender, physical exercising behaviour, father’s degree of education, family’s support were found to be sufficient in predicting mental wellbeing of undergraduate students. Conclusion Current study determined the positive impact of PMeHL on undergraduate students’ well-being. Additionally, family’s support and physical exercising behaviour have shown an advantageous effect on establishing better mental wellness. The results of the study can be used by stakeholders of Kazakhstan in public health campaigns that are focused on the improvement of adolescents’ mental health. Keywords: mental well-being, positive mental health literacy, undergraduate students, Kazakhstan, surveyItem Open Access Association of problem gambling with psychosocial characteristics among undergraduate students in Astana, Kazakhstan(Nazarbayev University School of Medicine, 2018-04-27) Janabel, GulziraBackground. The prevalence of probable pathological gamblers among college students worldwide doubled in 15 years. While gambling addiction causes financial and social losses, there is lack of studies on gambling involvement in Kazakhstan. Aims. The current research aims to find the prevalence of gambling, explore the link with sociodemographic and psychological variables among college and university students is Astana, Kazakhstan. The study also aims to evaluate the association between gambling and school satisfaction, which was not reported before. Methods. The analysis included questionnaires of 399 students from three universities and three colleges in Astana, using random sampling. The survey consisted of demographic questions, and scales on anxiety and depression, alcohol use, school satisfaction, family cohesion and suicide ideation. Results. From 399 questionnaires analyzed, 5.76% were classified as pathological gamblers according to the gambling scale used. The most popular gambling type was betting on sport events with bookmakers. 12.4% reported placing a bet through bookmakers at present time, and of them 91.5% were male, around half (46.8%) were categorized as some-problem gamblers, and one-third (36.1%) as pathological gamblers. Two-third of them (66%) did not reach legal age for gambling. Pathological gamblers in comparison with non-gamblers/non-problem gamblers are more likely to be male, aged older than 21, have alcohol use disorders, have lower family cohesion, more frequent suicide ideation, and their fathers have no after school education. Some-problem gamblers in comparison with non-gamblers/non-problem gamblers are more likely to be male, have lower school satisfaction, show symptoms of depression, and do not combine work and study. Conclusions. The study gives the first overview for gambling problem and associated problems among undergraduate students in Astana. Associates of problem gambling is consistent with the literature. Since every fourth male in the study places a bet with bookmakers, and majority had a gambling problem, there is need for developing interventions to increase awareness and prevent problem gambling and associated psychosocial problems.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 Restricted Athletes of Astana: characteristics and associations of sports related injuries and psychological disorders(Nazarbayev University School of Medicine, 2019) Bex, TorekhanIn addition to the positive effects of sport on the general health of a person, it is also accompanied by a high risk of injury. According to SRITO in 2010 about 10500 athletes sustained sports related injury. Additionally athletes face psychological disorders, like insomnia, depression and anger episodes. Sports related injuries and a psychological disorder affects each other, increasing the risk of developing psychological and physical traumas. The aim of this study is to identify the prevalence and possible risk factors of injuries and mental disorders among athletes of Astana....Item Open Access Awareness, Knowledge and Attitudes about human papillomavirus infection and vaccination among university students in Astana(Nazarbayev University School of Medicine, 2018-05) Shokanbayeva, TorgynHuman Papilloma virus is one of the most common infections caused by a virus. Most importantly is the fact that this infection can lead to cervical cancer, which represents a great burden for Kazakhstani women. There is a vaccine to prevent cervical cancer. Kazakhstan has introduced human papilloma virus vaccination program. However, there are no published public health studies about behavioral perception towards HPV and HPV vaccination that could support and encourage such a vaccination program.Item Open Access Awareness, perceptions and understanding of postpartum women and healthcare providers about the postpartum depression: a qualitative study(Nazarbayev University School of Medicine, 2018-05) Kanderzhanova, Akbota;Postpartum depression is a major public health problem and linked to mothers’ reduced ability of sensitive parenting and increased risk of developmental delays of children. Its prevalence was estimated as 13% in Western countries and 19.8% in lower and middle-income countries. No previous studies have explored the perspectives of postpartum women and healthcare providers regarding postpartum depression in Kazakhstan. The aim of this research is to explore postpartum women’s and healthcare providers’ awareness, understanding and perceptions of postpartum depression, acceptability of the Edinburgh Postnatal Depression Scale (EPDS), and postpartum mental healthcare practices in Kazakhstani context.Item Open Access THE AXL INHIBITOR TP-0903 AND ARTESUNATE SYNERGISE TO INDUCE REACTIVE OXYGEN SPECIES, DNA DAMAGE AND APOPTOSIS IN TRIPLE NEGATIVE BREAST CANCER CELLS(Nazarbayev University School of Medicine, 2024-01) Terragno, MirkoTriple Negative Breast Cancer (TNBC) is an aggressive, often rapidly growing form of breast cancer. TNBC usually displays a basal molecular phenotype that associates with epithelial mesenchymal transition (EMT), a cellular program that confers chemoresistance and metastasis. Approximately 56% of TNBC cases show a basal-like gene expression profile and roughly 46% of TNBC patients have distant metastasis. In general, the absence of molecular targets in TNBC is the main obstacle for the development of an effective therapy. For example, TNBC does not respond to endocrine and anti-human epidermal receptor (HER2) treatments as it does not express estrogen and progesterone receptors (ESR/PgR) and human epidermal receptor 2 (HER2). In addition, though initially TNBC is more responsive to cytotoxic drugs compared to other subtypes, TNBC presents a higher relapse rate. Therefore, new anti-TNBC treatment strategies are urgently needed. Drug combination therapy for TNBC could rely on protocols whereby EMT reversal sensitizes TNBC to anti-cancer compounds that are effective against epithelial tumors. Recently, the anti-malaria compound Artesunate (ART) has been shown to exert cytotoxicity in breast cancer by generating reactive oxygen species (ROS) and DNA double strand breaks (DSBs). However, the effect was more pronounced in tumors of epithelial than mesenchymal origin. In this project, the hypothesis was to verify whether EMT inhibition could sensitize TNBC cell lines to ART cytotoxicity. To address this, two aims were pursued. Aim 1 verified whether receptor tyrosine kinase (RTK) AXL inhibitors TP-0903/R428 and AXL/ZEB1 knockdown sensitised TNBC cell lines to ART-generated ROS, DNA damage and apoptosis. Aim 2 was to test whether TP-0903 and AXL/ZEB1 knockout in TNBC cell lines suppressed expression of superoxide dismutase 1/2 (SOD1/2), glutathione peroxidase 8 (GPX8) and catalase (CAT)...Item Embargo BARRIERS AND FACILITATORS OF MARATHON TRAINING IN KAZAKHSTAN(School of Medicine, 2023) Mirali, AltynayPurpose: To examine the barriers and facilitators of marathon training among non-elite athletes in Kazakhstan. Methods: A cross-sectional survey was conducted using a validated questionnaire on a purposely selected sample of 93 marathon runners who had marathon training in Kazakhstan. Data were analyzed using the R program, R studio. Descriptive statistics and bivariate analysis were done. Results: Of a total of 93 participants, 46% of them were female runners and 53% were males. The mean age of participants is 29.85 and the standard deviation of 8.26. The vast majority of participants were Kazak and Muslim, 84%. Almost 91% of respondents live in urban areas. Prominent barriers to marathon training were Lack of time, Fear of getting injured, Bad weather conditions, Current health conditions, and no suitable facilities. Facilitators included enjoying and having fun, learning new skills and experiences, gaining more self-confidence, and making new friends and support from the family. A significant association was determined between occupation and health barriers, and personal beliefs/motivation(p<0.05). There was a statistically significant association between encouragement and residence, occupation, working with a coach, and support from the workplace(p<0.05). Conclusion: The results indicated that marathon runners may benefit from a supportive and sport-friendly environment. Therefore, marathon organizers and health promotion organizations should do enjoined work to develop new health promotion programs and create physical activity supportive groups to increase physical activity and marathon participation.