02. Master's Thesis
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Item Unknown ANALYSIS OF IMMUNIZATION COVERAGE AND INSIGHTS INTO VACCINE ACCEPTANCE IN PARENTS OF CHILDREN AFFECTED WITH CHRONIC DISEASES (FOCUS ON ONCOLOGICAL AND NEUROLOGICAL PATIENTS)(Nazarbayev University School of Medicine, 2024) Khalimzhanova, ShakhnozaObjectives: Although vaccination can be considered as one of the most successful public health interventions to prevent infectious diseases, there are many people who remain vaccine hesitant. Children affected with chronic diseases have increased risk of infectious disease complications compared to healthy children, therefore their vaccine coverage should be optimal. Our aim was to measure vaccination coverage among children with chronic diseases admitted to NRCMCH pediatric Neurology and Oncology departments. Also, we aimed to study parental beliefs and determinants of vaccine hesitancy among parents. Methods: This prospective cross-sectional paper-based study was conducted between April 2022 to July 2023. Results: Overall, 59 participants were recruited to participate in our study to answer the paper-based questionnaire about their demographic information, their child’s vaccine coverage and their attitude towards vaccination. All the participants were 100% were female participants and the highest percentage of parents (45.8%) were between the ages 30-39. We found out that vaccination coverage in two departments was similar with a mean score of 0.81 and 0.77 in Neurology and Oncology, respectively. However, parents in neurology department were more vaccine hesitant compared to parents in oncology department with a mean score of 2.9 and 3.35 in Neurology and Oncology respectively.Item Unknown THE EFFECTS OF EARLY AND LATE INTERMITTENT FASTING ON THE INFLAMMATION IN MEN AND WOMEN(Nazarbayev University School of Medicine, 2024) Zhorabek, IliyasAlthough studies show the effectiveness of time-restricted feeding (TRF) regimen for weight loss, there is limited data to suggest if an early or late eating window is more effective. The objective of this case-crossover study was to compare the effects of early TRF and late TRF on body parameters, lipid profile, and inflammatory markers. Young, healthy individuals with body mass index (BMI) no more than 29.9 were recruited. They were randomly assigned into two groups, which practiced TRF for 4 weeks starting with either an early or late eating window. After 4 weeks, the participants returned to their regular eating time for two weeks, after which they switched their eating time. Body measurements and blood tests for lipid profile and inflammatory markers were conducted before and after each fasting period. 44 participants were recruited and divided in a 1:1 ratio into two groups. Early TRF regimen was shown to be more effective in lowering BMI compared to late TRF, with mean difference in change of 0.484±0.60 kg/m2 (p-value < 0.05). There was no statistically significant difference in changes in total cholesterol, LDL, HDL, triglycerides, CRP, and homocysteine. The results of this study suggest that early TRF regimen is more effective for weight-loss than late TRF, while the lipid profile and inflammatory markers are not significantly affected.Item Restricted SYMPTOMS CLASSIFICATION OF PATIENTS RECEIVING END-OF-LIFE CARE IN KAZAKHSTAN(Nazarbayev University School of Medicine, 2024) Bekish, LyazzatPalliative care is a developing medical field that focuses on the provision of emotional, social support along with professional medical help from a group of professionals. Currently, palliative care plays a key role in improving the quality of life of the population in end of life care. In Kazakhstan the end of life care still needs recognition among the general population along with its lack of hospices, staff and proper educational programs. Therefore, the proper analysis of palliative care in Kazakhstan will provide a clear picture of the end of life care in Kazakhstan. The most essential aspect of development of palliative care is assessment of the patients who are eligible for it. The study identifies the categories of the patients who receive the following help in Kazakhstan. The paper will analyze the symptoms (physical and mental state) and pathologies and their stage of progression of the palliative care patients in Kazakhstan. The study will be a crucial step to design better palliative care services in KazakhstanItem Restricted EXPRESSION PATTERNS OF DIFFERENT ISOFORMS OF PERIOSTIN IN CANCER DEVELOPMENT AND PROGRESSION(Nazarbayev University School of Medicine, 2024) Bimurat, BikadishaExtracellular matrix-associated proteins have a key role in modulation of intercellular communication, which is an important mechanism in cancer development and progression. Periostin, a small matricellular protein interacting with different ECM molecules, originally isolated in murine osteoblasts, is involved in both physiologic and pathological processes such as tissue repair, bone growth, epithelial-mesenchymal transition, inflammation, allergies, tumor development and progression. The expression of periostin is markedly elevated in different cancer types (lung, breast, pancreatic, ovarian, colorectal, gastric and other). Even though the contribution of periostin in cellular processes and their underlying mechanisms are still the subject of research, it has widely been reported that periostin drives the process of cell survival, proliferation, and migration. This potential is especially crucial in the context of cancers where periostin contributes to adhesion, invasion, and tumor metastasis. There exist different isoforms of periostin produced by alternative splicing. These different isoforms could have different functions in tumor development and progression. The present study intends to shed light on functions of different periostin isoforms with specific emphasis on periostin isoforms in different cancers.Item Restricted AN EVALUATION OF SKIN AND EYE CONDITIONS ASSOCIATED WITH SOLAR ULTRAVIOLET RADIATION EXPOSURE IN THE CENTRAL ASIAN COUNTRIES: A SYSTEMATIC REVIEW OF THE LITERATURE.(Nazarbayev University School of Medicine, 2024) Assylbek, NurkaliCentral Asian nations consist of Azerbaijan, Tajikistan, Kyrgyzstan, Kazakhstan, Uzbekistan, and Turkmenistan which are located from western China throughout Central Asia to the Caucasian mountains. Central Asia does not have open access to seas and oceans, which make the climate distinctively continental with predominant cloudless, hot, and dry weather conditions. In summer, the temperature usually rises to 50 °C [2,19]. UV Radiation reaching Earth's surface area in these locations is impacted by things including ozone layer thickness, solar geometry, cloud covers and atmospheric aerosols. UV light strength is expressed as watts per square centimeter (mW/cm2). In Figure 1, Central Asian nations are exhibited with Moderate-High UV indexes according to the global solar UV indexes because of their geographical location...Item Restricted RETROSPECTIVE ANALYSIS OF MATERNAL, NEONATAL AND EARLY-LIFE RISK FACTORS IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE.(Nazarbayev University School of Medicine, 2024) Yegembayeva, NurgulBackground: IBD is believed to arise from genetic, environmental and geological aspects. Possibly related environmental factors extend from a child delivery mode and exposures in first year such as breastfeeding, antibiotic administration to late adulthood exposures as smoking, lifestyle, infections and diet. Methods: We have recruited 50 patients in each group: cases and controls.Cases consisted of children with IBD, while the control group included children who didn’t have a history of IBD or any autoimmune disease. The data is analyzed by logistic regression. Risk factors that could promote the IBD are the objective of this study. Results: Logistic analysis revealed that risk of developing of IBD is significantly associated height at birth (adjusted OR 1.79;95% CI:1.17 – 2.74,p<0.007), inversely associated with birth week (adjusted OR 0.33;95% CI:0.2 – 0.56,p<0.001) and formula feeding (adjusted OR 0.1; 95% CI:0.018 – 0.63, p=0.014). Conclusion: Our study revealed that the odds of developing IBD increases by 79% with an increase of height at birth by 1 cm, however the odds decrease by 69% as birth week increases by 1 week. Children which were fed with formula have substantially lower odds of developing IBD.Item Restricted EARLY VERSUS LATE TIME-RESTRICTED EATING AS A NEW APPROACH FOR PREVENTION OF CARDIOVASCULAR DISEASES.(Nazarbayev University School of Medicine, 2024) Ibraimova, IlviraWorldwide, cardiovascular diseases (CVD) are a common problem, which can be avoided by changing eating habits. Time restricting eating (TRE), which is the subtype of intermittent fasting (IF), is based on the idea of eating within defined time intervals daily. Evidence shows that TRE results in CVDs risk reduction by improving lipid composition, decreasing inflammation, and reducing blood pressure levels. Also, the combination of TRE diet with our bodies’ inner biological clock, meaning circadian rhythm increases the success of reduction of weight and CVD risk factors. The main goal of this pilot study is to compare the effectiveness of early TRE with late TRE in weight reduction and improving CVDs risk factors. This study was conducted among general population of Astana and included 34 healthy participants. This is a randomized cross-over study and participants were randomly divided into the early TRE group (eating window by 5 pm) and late TRE group (eating window from 12 pm) with an eating window of 6-8 hours. The participants went through 2 weeks preparation phase, 4 weeks of the TRE phase, 2 weeks of the washout period, and 4 weeks of switched TRE phase. The results showed that early TRE resulted in greater decrese in BMI and LDL levels in comparison with the late TREItem Restricted DEXMEDETOMIDINE FOR REGIONAL ANESTHESIA: AN UMBRELLA REVIEW(Nazarbayev University School of Medicine, 2024) Dossymbek, DayanaObjective: To determine the perioperative effect of dexmedetomidine as a pharmacological adjunct to the regional anesthesia in adult surgical patients. Introduction: Dexmedetomidine is an α-sympathomimetic drug, which has a high selectivity and specificity for α2-adrenoceptor of noradrenergic neurons and affects the modulation of pain perception. Multiple systematic reviews and meta-analyses are associated with advantages of administering dexmedetomidine as an adjuvant drug for adult surgical patients with regional anesthesia. Inclusion criteria: In this umbrella analysis, relevant systematic reviews and meta-analyses involving adult patients (older than 18 years) undergoing surgery and receiving preoperative regional anesthesia with dexmedetomidine as an adjuvant drug and published before January 2024 are eligible for inclusion. Methods: 22 relevant articles were screened and 14 of them were excluded after full-text assessment due to failing to meet all inclusion criteria or/and meeting one of the exclusion criteria. The remaining eight studies were critically appraised and primary and secondary outcomes of the articles were assessed. Results: Perineural administration of dexmedetomidine in brachial plexus block for upper limb surgery prolongs the duration of analgesia compared to local anesthetics alone. Discussion: Further investigations on the topic would help make umbrella review more comprehensive and result in recommendations of a high statistical value and credibility.Item Restricted ANALYSIS OF IMMUNIZATION COVERAGE AND INSIGHTS INTO VACCINE ACCEPTANCE IN PARENTS OF CHILDREN AFFECTED WITH CHRONIC DISEASES (FOCUS ON RHEUMATOLOGICAL AND NEPHROLOGICAL PATIENTS)(Nazarbayev University School of Medicine, 2024) Sardarbek, DanaIntroduction: Patients with chronic conditions are at increased risk of severe complications following infectious diseases due to their immunocompromised state. The rate of vaccine preventable diseases and its complications has declined significantly with high vaccine coverage among certain populations. Although children with chronic diseases have higher susceptibility for severe course of infection, vaccine hesitancy among their legal representatives is still high. Methods: This cross-sectional study was conducted from April 2022 to September 2023. The study analyses the data from a paper-based survey of 63 parents of chronically ill children. Results: 36 responses from nephrology department and 27 responses from rheumatology department were collected. Majority of the respondents were married female parents at the age between 30-39 and having university degree. Overall, the survey participants predominantly agree with the statements that claim the importance (61.1% and 74.1%), effectiveness (58.3% and 55.5%) and safety of the vaccination (41.7% and 59.3%) among both nephrology and rheumatology departments, respectively. Conclusion: Parents are concerned about safety of vaccines for children with chronic diseases who receive specialized therapy. The vaccine coverage is inadequate, with the higher immunization rate among rheumatological patients compared to nephrological patients. While parents of nephrological patients are more vaccine hesitant.Item Restricted THE INFLUENCE OF ADVANCED MATERNAL AGE ON PREGNANCY COURSE AND OUTCOME IN PATIENTS WITH GLUCOSE METABOLISM DISORDERS IN PREGNANCY(Nazarbayev University School of Medicine, 2024) Khusain, ArailymThe prevalence of pregnancies in women of advanced age, which is defined to be over 35 years, has increased globally, raising concerns about associated risks such as hypertension, gestational diabetes (GD), preeclampsia, miscarriage and preterm birth. Even though these risks are widely recognized, the impact of advanced age on the course and outcome of pregnancy among women with glucose metabolism disorders (GMDs) is still underexplored. This study aims to examine the specific impact of advanced maternal age on pregnancy courses and outcomes in women with GMDs. The clinical records of women with GMDs who gave birth between 2013 and 2017 where retrospectively analyzed. 281 women were divided into three groups by age: <35, 35- 40 and >40 years old. According to the study results, there is a significant association between advanced maternal age and higher body mass index (BMI), blood pressure (BP) and pre-pregnancy hypertension in patients with GMDs. Interestingly, fasting glucose levels were lower with gestational diabetes diagnosed at earlier gestational ages as maternal age increased. Among the neonatal outcomes, the analysis showed significantly higher incidence of neonatal hypoglycemia with advancing maternal age, and the frequency of macrosomia was also higher among these patients. Therefore, early screening and targeted monitoring of women of advanced age with GMDs is highly recommended to mitigate these risks. Further research is needed to develop comprehensive management strategies for this high-risk population and to develop a pre-pregnancy program focused on dietary and lifestyle modifications to improve the pregnancy outcomes in advanced age pregnancies with GMDs.Item Restricted SOLUBLE TAM RECEPTORS ARE POTENTIAL REGULATORS OF BLADDER CANCER PROGRESSION(Nazarbayev University School of Medicine, 2024) Kuantayeva, AkmaralBladder cancer cells such as RT112 and T24 cells contain TAM receptors called Axl, Tyro3 and Mer. These TAM receptors are cleaved and form soluble forms that can have impacts on signaling pathways. The hypothesis of this dissertation is that soluble TAMs initiate downstream signals that can be correlated with progression of bladder cancer. Therefore, RT112 and T24 bladder cancer cell lines were analyzed using cell culture, western blotting, and wound healing assay. These cells illustrate morphological changes and increased migration after addition of recombinant - TAM receptors. Moreover, the soluble TAM receptors are found in RT112 and T24 that are biologically active.Item Restricted KNOWLEDGE OF PERINATAL DEPRESSION AND ATTITUDES TOWARDS ITS SCREENING AMONG RESIDENTS OF MEDICAL UNIVERSITIES IN KAZAKHSTAN: A CROSS-SECTIONAL STUDY(Nazarbayev University School of Medicine, 2024) Togzhan, YerlankyzyBackground: Perinatal depression (PD), a non-psychotic depressive condition, can begin during pregnancy (antenatal depression) and last for up to a year after birth (postnatal depression). Antenatal depression is 26.3% and postnatal depression is 27.6% prevalent worldwide. This study aims to assess the level of knowledge and awareness regarding PD as well as the attitudes of residents in Kazakhstani medical universities on its screening. Our study also aimed to explore how participants' demographics, knowledge, and attitudes about PD relate to their intention to screen for PD in the future. Methods: A cross-sectional online questionnaire covering 87 residents was conducted among residents from medical universities and centers in Kazakhstan. Knowledge questions were developed based on previous studies (Jones et al., 2011; Chrzan-Dętkoś & Walczak-Kozłowska, 2020). Data was analyzed using the Stata software version 17. We assessed the relationships between dependent and independent variables using the Fisher exact test, chi-square, t-test, and bivariate analyses. Results: Results revealed a moderate level of knowledge about antenatal and postnatal depression, highlighting significant gaps in understanding risk factors and treatment modalities. Despite this, attitudes toward screening were generally positive, with a notable intention among residents to screen for PD in their future practice. Significant factors influencing the intention to screen were the residency program, personal acquaintance with PD-affected individuals, postnatal knowledge scores, attitudes, and interest in training, barriers included Ministry of Health directives and insufficient training. Conclusion: Recommendations include the development of educational resources and integrating mental health education into medical curricula to equip future physicians to manage PD effectively.Item Embargo INVESTIGATING APOPTOSIS AS A POTENTIAL PATHWAY FOR ANTICANCER MECHANISM OF PHENFORMIN(Nazarbayev University School of Medicine, 2024) Amangelsin, YernarApoptosis is an essential cellular process that maintains cellular homeostasis. Dysregulation of apoptosis can lead to uncontrolled cell proliferation, which may result in the development of cancer. Targeting apoptosis has emerged as a promising strategy for cancer treatment. Biguanides, including metformin and phenformin, are known to activate AMP-activated protein kinase (AMPK) and have been identified as potential drugs for cancer prevention. It has been highlighted that phenformin has a greater antitumor activity compared to metformin. Because phenformin is more lipophilic and hence can easily enter the cells. Studies have proposed that phenformin's antiproliferative activity is attributed to its ability to induce cellular apoptosis. However, the anticancer activity and mechanism of apoptosis induction of phenformin can vary depending on the type of cancer. In light of this, we sought to evaluate the antiproliferative activity of phenformin on various cancer cell lines and to explore the role of apoptosis in phenformin's anticancer activity...Item Open Access UNDERSTANDING THE IMPACT OF COVID-19 PANDEMIC ON THE MENTAL HEALTH OF THE FRONTLINE MEDICAL WORKERS IN A POST-PANDEMIC PERIOD: A SCOPING REVIEW(Nazarbayev University School of Medicine, 2024-05-02) Danbayeva, SamalThe COVID-19 pandemic has brought unprecedented challenges to global healthcare systems, with frontline medical workers facing immense pressure and strain. This scoping review examines the impact of the pandemic on the mental health of healthcare workers in the post-pandemic period, focusing on studies published from 2021 onwards. Through a systematic literature search, utilizing the Arksey and O'Malley framework, relevant articles were identified from databases including PubMed, Embase, Nazarbayev University Library, and Google Scholar. A total of 20 articles were analyzed, comprising cross-sectional studies, qualitative research, and systematic reviews. The findings reveal a significant prevalence of mental health conditions among healthcare workers post-pandemic, with post-traumatic stress disorder (PTSD), burnout, anxiety, and depression emerging as primary concerns. Factors contributing to mental health challenges include high stress levels, moral dilemmas, and inadequate support systems. The review highlights the importance of implementing interventions to support healthcare workers' mental health, such as regular screening, access to counseling services, and resilience training. Organizational support and policy changes are also crucial to mitigate workplace stressors and foster a supportive environment. Despite the importance of this topic, the available literature on post-pandemic mental health remains limited, emphasizing the need for further research and comprehensive meta-analyses. Addressing the mental health needs of healthcare workers is essential not only for their well-being but also for ensuring the provision of quality patient care.Item Restricted DIFFERENTIAL GENE EXPRESSION ANALYSIS BETWEEN ELITE ATHLETES AND SEDENTARY INDIVIDUALS(Nazarbayev University School of Medicine, 2024-04-03) Babatola,Toluwanimi AyoadeThis study examined gene expression differences between elite athletes and sedentary individuals, exploring the genetic basis of physical activity. Utilizing "transcriptomic analysis and physical activity" among other keywords, 35 datasets were analyzed with the GEO2R tool, identifying 7,314 exercise-related genes. The most frequent nine genes (ATF3, NR4A2, NR4A3, NFIL3, SOCS3, SIK1, SLC2A3, MYC, MAFF) were further studied using the STRING database and qPCR analysis, with HBB as the qPCR normalization reference. Ethical approval was obtained, and the study involved 10 participants (5 triathletes, 5 sedentary) with no chronic health issues. Blood samples were collected, and RNA was extracted for qPCR analysis. The results showed that the mean Ct values did not differ significantly between the groups; however, variances were observed in the expression of the NR4A3 and NR4A2 genes. Additionally, fold change (log2fc) calculations revealed a four-fold decrease in NR4A2 and a two-fold decrease in the SLC2A3 gene in athletes compared to sedentary individuals.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 Open Access SOLUBLE FRAGMENT OF THE RECEPTOR TYROSINE KINASE MERTK AS A LIQUID BIOPSY BIOMARKER IN BLADDER CANCER(Nazarbayev University School of Medicine, 2024) Nazarbay, AigerimAim of the study: The main purpose of the study was to determine the effectiveness of soluble MERTK as a liquid biomarker in bladder cancer. The presence of soluble MERTK in urine samples of bladder cancer patients was analyzed using different laboratory techniques. Background: MERTK is a member of TAM receptors that are expressed in normal blood cells and cancer cells. MERTK exists in a soluble form which made by proteolytic cleavage, and it is a detectable in urine samples of patients. Currently, the available diagnostic methods for bladder cancer are mostly invasive and expensive, and they used to detect progressive forms of cancer. The main scope of many studies is the utilization of these receptors as potential biomarkers for the early detection of bladder cancer. Methodology: The small-scale preliminary study was conducted to characterize expression of MERTK in bladder cancer using the several laboratory techniques as ELISA, Western blotting, and immunohistochemistry. Study subjects were adult patients diagnosed with bladder cancer and healthy controls. Biopsy and urine samples of bladder cancer patients were used as samples. Results and Conclusion: The results of experiments showed the high expression of soluble MERTK in bladder cancer patients’ urine samples compared to samples of healthy controls. According to the results immunohistochemistry, MERTK was expressed in bladder cancer tissue of these patients. To conclude, soluble MERTK can be utilized as a liquid biomarker in bladder cancer.Item Restricted PERIOSTIN EXPRESSION IN MB49 CELL LINE(Nazarbayev University School of Medicine, 2024) Sharyktybay, AiganymPeriostin is a secreted matricellular protein known to be imbalanced in many pathological conditions, such as tissue repair, fibrosis, inflammation, tumorigenesis, and metastasis. It is often associated with advanced stages of cancer and poor outcomes. Its upregulation in different cancers and ability to develop chemoresistance in cancer tissues suggest its usage as a prognostic biomarker and curing target for prostate, breast, colorectal, pancreatic, gastric, and lung carcinoma. However, there are controversial studies regarding periostin in bladder cancers. The downrate of periostin was an indicator of high-grade bladder cancers, whereas other bladder cancer cell lines showed upregulation of periostin. The current study determined that periostin is expressed in the MB49 mouse bladder cancer cell line and suggested that further research focusing on the effect of periostin upregulation and knockdown on the tumor growth in the MB49 cell line will help cure bladder cancer by targeting periostin in the future.Item Embargo PREVALENCE AND PREDICTORS OF RESPIRATORY SYMPTOMS AMONG KAZAKHSTANI COAL MINERS(Nazarbayev University School of Medicine, 2024) Kassymova, AidaUnderground coal mining has been a crucial part of Kazakhstan’s economy for the last 30 years, yet little is known about the burden of respiratory disease and trauma among Kazakhstan miners. A cross-sectional survey among a random sample of working miners was conducted; demographic, work, and health information were collected using a standardized questionnaire.Item Open Access SCREENING FOR INHIBITORS OF DIFFERENT KRAS MUTANTS, A KEY ONCOGENE IN NONSMALL-CELL LUNG CANCER(Nazarbayev University School of Medicine, 2024) Turmagambetova, MadinaNonsmall-cell lung cancer is the most prevalent type of lung cancer accounting for 85% of all lung cancer cases. Ki-ras2 Kirsten rat sarcoma viral oncogene homolog(KRAS) belongs to the RAS family. KRAS is a common oncogenic signal transducer protein predominantly mutated in cancers at positions G12, G13, and Q61. In this study, we successfully knocked out the coding region(Exon 2) of KRAS in the H1299 cell line by CRISPR/Cas9 system. Overall 8 positive clones were detected from 128 individual colonies. The clonal subpopulations have shown various growth rates. Some clones showed higher growth rates, while others grew more slowly, due to the off-targeted effects of the CRISPR/Cas9 system. The deletion efficiency was proved by the Sanger sequencing analysis.