Pusat Pengajian Sains Perubatan - Tesis
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- PublicationA comparison between goat milk and cow milk supplementation on nutritional status among paediatrics with cerebral palsy in Kelantan(2024-04)Shamsudin, JulianaGoat milk (GM) can be used as an alternative if cerebral palsy (CP) children are unable to tolerate cow milk. The purpose of this study was to compare the anthropometric, biochemical, clinical, and dietary intake of powdered GM versus CM among CP children in Kelantan, Malaysia. The study consists of two phases: Phase 1 focuses on determining and analysing the proximate and fatty acids profile of GM and CM, while Phase 2 involves the intervention study. In Phase 1, a grand total of 20 GM samples were analysed, along with 1 GM sample (reference) and 1 CM sample. The study’s criteria for references on GM and CM involved the use of powdered full cream milk as a primary ingredient or the most popular brand among consumers. Meanwhile, during Phase 2 of the study (quasi-experimental design, single blind), a total of 87 children with CP were randomly assigned to either goat milk (GM, n=43) or cow milk (CM, n=44). The research achieved an 82.1% response rate. The study included children between the ages of 4 and 12, but excluded those with severe cases of CP who needed special nutritional requirements such as inborn error metabolism, tube feedings, and cow milk protein allergy (CMPA). In the intervention group, the mean age was 9.05 ± 2.30 years, while in the control group, it was 8.27 ± 2.55 years. The gender distribution was as follows: in the GM group, 53.5% were male and 46.5% were female, while in the CM group, 70.5% were male and 29.5% were female. Milk powder in the form of a sachet (21-23 grams, twice a day) was provided from the start of the study until the end of the 4 months (3 meetings; baseline, 2-months, and 4-months). Anthropometric data (weight, height, BMI, MUAC, triceps and subscapular skinfold measurements, body fat percentage), biochemical data (hemoglobin and hematocrit), clinical data (systolic and diastolic blood pressure and heart rate), and dietary intake were gathered from baseline to 4-months. The Phase 1 study found that only nine GM samples out of 20 contained pure GM (based on the ingredient label), and sample G17 was chosen as goat milk for Phase 2 because it contained the highest medium-chain fatty acid (MCFA) content of 2803.9 mg (12.97%) compared to CM, 765 mg (7.19%), and the other goat milk samples. Phase 2 results show that GM showed greater improvements. There were significant differences in triceps skinfold measurement (0.33 mm vs -0.20 mm, p=0.024) and vitamin B1 (p=0.043), while other parameters did not show significant differences between GM and CM after the intervention (p>0.05). Furthermore, there was a reduction in calcium (p=0.040) and vitamin B12 (p=0.022) levels between GM and CM. In conclusion, laboratory analysis shows that GM has a higher MCFA content than CM. Meanwhile, for the intervention study, GM can be used as a tolerable supplement for CP children based solely on significant differences in triceps skinfold measurement and vitamin B1 levels. Moreover, calcium and vitamin B12 intake decreased in the daily diet of GM in comparison to CM. Further research is needed to confirm and explore this matter over a longer duration, with the necessity of conducting blood tests to assess the decrease in calcium and vitamins from the daily diet.
- PublicationAntimetastatic and immunomodulatory potential of strobilanthes crispus subfraction and its specific major components in experimental breast cancer model(2018-02)Baraya, Yusha'u Shu'aibuStrobilanthes crispus (S. crispus), is a Malaysian herb locally known as ‗Pecah kaca‘ or ‗Jin batu‘ which have demonstrated potent anticancer effects in both in vitro and in vivo models. However, there is paucity of information on the inhibition of metastasis and immune activation potentials of S. crispus as part of its anticancer mechanism. Thus in this study, the antimetastatic and immunomodulatory activities of S. crispus subfraction (SCS) and its specific major constituents, lutein and β-sitosterol were investigated, particularly to unravel the underlying mechanisms involved, using in vitro and in vivo models of breast cancer. In the in vitro study, murine and human breast cancer cell (BCC) lines, 4T1 and MDA-MB-231, respectively, were treated with SCS and investigated for antimetastatic activity using cell proliferation, wound-healing and invasion assays. The results showed that SCS induced moderate cell growth arrest after 24h (100 μg/ml) and 48h (75 μg/ml) treatment of 4T1 and MDA-MB-231 BCC lines compared to the untreated control cells. SCS moderately inhibited metastasis independent of its cytotoxic effects due to inhibition of migration and invasion of cancer cells below the half maximal inhibitory concentration compared to the untreated control cells. In addition, flow cytometry was carried out to evaluate the expression of cell surface immune markers (CIITA, MHC I and MHC II) in 4T1 cells treated with SCS (50 μg/ml) for 24h, and the results showed considerable expression of all the tested proteins compared to the isotype control. The in vivo study evaluated the antimetastatic and immunomodulatory activities of SCS, lutein and β-sitosterol in 4T1-induced mouse mammary carcinoma model. Beginning from 2 mm tumor size, five each (n = 5) from tumor bearing mice (TM) were administered SCS (TM-S group), lutein (TM-L group) and β-sitosterol (TM-β group) by oral gavage daily for 30 days, and the response to treatment was assessed based on the outcome of the tumor growth parameters, as well as hematological and histomorphological analyses. The results demonstrated a few complete regression of primary tumor (20%) in TM-S (100 mg/kg/day) and partial tumor regression in the rest of TM-S, TM-L and TM-β (50 mg/kg/day), and without secondary tumor formation or tumor-associated lesions in the major organs of treated groups compared to the TM group. The tumor regression was linked to blockage of tumor evasion of the immune system and activation of T cell-mediated tumor destruction, as indicated by significant increase in CD4, CD8, CD45RO, CIITA, IL2, MHCI and MHCII expression with concomitant decrease in CD68 expression compared to the TM group. In addition, SCS relatively modulated tumor cell migration, invasion and angiogenesis, through downregulation of MMP9, MUC1 and VEGF in comparison with the TM group. Additionally, TM-S showed significant increase in E-cadherin expression with resultant decrease in N-cadherin, vimentin and Twist expression SCS. In general, these results demonstrate for the first time that SCS induced antimetastasis and immune system activation effects as part of its anticancer mechanism in 4T1-induced mouse mammary tumor model, and SCS-related bioactive constituents, especially lutein could perhaps contribute significantly to the anticancer potential of SCS.
- PublicationAssessment of the protective role of green tea Extract against the ciprofloxacin induced toxicity on Mandibular condylar cartilage of wistar rats(2022-07)Alsocoty, Ameera Kamal KhaleelThe head of the mandibular condyle is covered with mandibular condylar cartilage which acts as the center of growth in the craniofacial complex. Ciprofloxacin is a fluoroquinolone which is important for treating a life-threatening bacterial infection. It has a chondrotoxic effect in growing condylar cartilage. Green tea has attracted a significant attention for its multiple health benefits, and the previous researches uncover the importance of dietary choices for prevention of the chondrotoxic effect of ciprofloxacin. The objective of the present study was to investigate the preventive potential of green tea extract on the mandibular chondrotoxicity induced by ciprofloxacin in juvenile male Wistar Albino rats. In the present study, twenty-five rats were used. Five rats were used for the pilot study, and the other twenty were divided into four equal groups. On day 32 of age, all the animals in Ciprofloxacin/Water and Ciprofloxacin / Green tea treated groups were subcutaneously injected by ciprofloxacin as two subcutaneous injections of 600 mg/kg of body weight, eight hours apart, while the Saline/Water and Saline/Green tea groups were subcutaneously injected by saline. The Saline/Green tea and Ciprofloxacin / Green tea groups were intragastically gavaged by green tea extract in an oral dose of 300 mg/kg/day, eight days before the subcutaneously injection of saline or ciprofloxacin. On day 34, all the animals were anaesthetized, blood collection by cardiac puncture was taken, and the mandibular condyle samples were taken immediately and processed. The results showed that the intragastric gavage of green tea extract can cause a non-significant change in the magnesium, calcium, and vitamin E serum levels in all the groups studied (p>0.05), but the zinc serum level in the Saline/Green tea and Ciprofloxacin / Green tea groups showed a significant increase in comparison with the others two groups (p<0.05). The Ciprofloxacin/Water group showed a significant decrease in the mandibular condylar cartilage thickness, cartilage cells number, and proteoglycans content in comparison with the other three groups (p<0.05). Statistical analysis also showed a significant decrease in Mankin score in the Ciprofloxacin / Green tea group in comparison with the Ciprofloxacin/Water group (p<0.05). The Ciprofloxacin / Green tea group showed a significant increase in the Bcl-2 immune expression (p<0.05) and a non-significant increase (p>0.05) in collagen II immune expression in comparison with the Ciprofloxacin/Water group. This study provides the first evidence that green tea extract can decrease the chondrotoxic effects of ciprofloxacin in a rat model.
- PublicationCoping in medical professionalism and mental wellbeing among Universiti Sains Malaysia medical students(2024-05)Sattar, KamranThe main aim of medical education is to cultivate students with good mental wellbeing and professional competence, equipping them to serve the community effectively. However, the journey of medical students is not without psychological challenges. Concerns about the mental wellbeing (MWB) of students and its impact on medical professionalism (MP) are widespread. Research indicates that adopting effective coping strategies (CSs) can help students navigate through adversity and maintain their professionalism. This study explores how CSs influence both MWB and MP among undergraduate medical students, employing an exploratory sequential mixed-method approach. In the phase one, qualitative data was gathered through scoping reviews (ScRs) and focus group discussions (FGDs), focusing on three key components - CSs, MWB, and MP. Phase two involved constructing a hypothetical model illustrating the interplay between CSs, MWB, and MP, guided by insights from phase one. Six medical education experts validated the model's core concepts, theories, and framework. In the subsequent phase, quantitative data from a cross-sectional survey involving 234 students were collected using five inventories - Dundee inventory, DASS-9, Brief COPE, CBI, and TEQ. Structural equation modelling (SEM) was performed to assess the causal relationships between CSs, MWB, and MP. The findings from phase one underscored the significance of 'respect' in nurturing MP, while attributes like altruism, accountability, duty excellence, honour, integrity, and respect for others were central in assessing MP. Psychological distress, including stress, anxiety, and depression, along with burnout, emerged as common manifestations of MWB issues. Notably, students experiencing MWB issues identified support as a primary coping strategy. Additionally, burnout was found to be inversely associated with empathy. During phase two, the hypothetical model revealed how CSs, MWB, and MP are interconnected, drawing upon evidence synthesis from ScRs, FGDs and the expert panel. Subsequent SEM analysis revealed that professional behaviour showed an inverse correlation with burnout, with negative coping worsening the situation, while positive coping strategies protected empathy. The study highlighted the importance of self-compassion and empathy in alleviating burnout and enhancing professional satisfaction. Moreover, it highlighted the detrimental impact of MWB issues on MP. Although creating a comprehensive program for medical professionalism is a challenging task, it is important for medical faculties to start with foundational activities that emphasize teaching the fundamental aspects of professionalism, including defining relevant definitions and attribute
- PublicationCytotoxic and molecular effects of betel quid and areca nut extracts on selected oral epithelial cell lines(2022-08)Al-Tayar, Badr Abdullah SaeedThe habit of betel quid chewing is widely prevalent in many parts of Asia. Betel quid comprises areca nut, betel leaf, lime, and other potential constituents such as tobacco and essences. The main ingredient of betel quid is areca nut. Many epidemiological studies link betel quid and areca nut chewing to oral cancer. Therefore, this study aimed to investigate the effect of areca nut and betel quid on mouth-ordinary-epithelium1 (MOE1) and human oral squamous carcinoma (HSC-2). Phytochemical compounds were identified using GC–MS. MOE1 and HSC-2 cells were treated with high concentrations (25–100%) and low concentrations (0.0122– 25%) and subjected to MTT assay. The cell and nuclei morphological changes were observed under inverted phase contrast and fluorescence microscopes. Following microarray analysis, the gene expression data was subjected to bioinformatic analysis. Microarray data was validated by analysing the expression of six selected genes through real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Arecoline was identified as the major chemical compound in areca nut alkaloids, while phenol, 2 methoxy4 (1propenyl) was the major chemical compound in betel quid phenolics. MOE1 treated with areca nut decreased in viability starting from 0.0244% until 1.56%. However, at concentrations 6.25% and above, the cells viability increased. With betel quid treatment, MOE1, cell viability started to decrease at extract concentration of 0.78% (24 hours) and 3.125% (48 and 72 hours). However, at concentration 50% and 100%, the cell viability increased significantly. Areca nut treatment on HSC-2 decreased the cell viability tremendously at all concentrations and treatment time. Betel quid concentration from 6.25% to 25% decreased HSC-2 viability significantly at all treatment duration. Based on the cytotoxicity data, two concentrations were selected, which were 0.0976% for areca nut and 6.25% for betel quid for the subsequent experiments. Microscopy findings indicated that the extracts caused noticeable morphological changes such as cell shrinkage and ballooning, nuclei condensation, and fragmentation. The microarray gene expression analysis revealed that the total number of DEGs in MOE1 treated with areca nut and betel quid compared to controls was 3,038 and 1,985, respectively, while in HSC-2, it was 4,413 and 1,110, respectively. The shared upregulated DEGs of areca nut treatment were CLDN4, PIM1, and HBEGF. KEGG analysis suggested the genes are associated with few main pathways, including the ErbB signalling pathway. The shared upregulated DEGs for betel quid treatment are HMOX-1, GCLM, and EGLN3. Its KEGG analysis suggested an association with a few pathways, mainly ferroptosis. RT-qPCR results of selected genes validated the microarray gene expression. In conclusion, areca and betel quid showed different effects on normal and malignant epithelial cells, whereby cell survival mechanism might play an important role in cells treated with betel quid compared to the areca nut treatment.
- PublicationDevelopment and effectiveness of educational module on pre-pregnancy care among women of reproductive age with diabetes in Terengganu(2024-03)Fauzi, Tengku Muhammad Fakhruddin Tengku MdBackground: Diabetes Mellitus (DM) stands as one of the major global health challenges of the twenty-first century. When DM is not well-managed, marked by maternal hyperglycaemia before and during the early stages of pregnancy, it significantly increases the risk of severe complications for both the mother and the developing foetus. Pre-Pregnancy Care (PPC) is particularly crucial for mothers with diabetes, as it provides substantial benefits to both the mother and the developing foetus. Objective: To develop and assess the effectiveness of the Educational Module on Pre-Pregnancy Care Among women of reproductive age with diabetes in Terengganu. Methodology: This study was structured in two primary phases: The first phase involved conducting a needs assessment, developing the educational module, and validating it. The second phase was a quasi-experimental study aimed at evaluating the module's effectiveness. The module's development followed the ADDIE model and included five stages: 1) Needs Assessment (A) 2) Consulting Experts for Module Design (D) 3) Post-Development Validation of the Educational Module for Pre-Pregnancy Care in women of reproductive age with diabetes (D), and 4) Implementing PPC Health Education. The quasi-experimental phase involved 90 diabetic women of reproductive age, with 45 in the intervention group from Dungun and 45 in the control group from Kuala Nerus, selected via simple random sampling. The intervention group utilized the newly developed module (I). The effectiveness of the module is determined through data analysis, encompassing improvements in knowledge and attitudes regarding PPC using Repeated Measures Analysis of Variance (RM-ANOVA) (E). Result: Focus Group Discussions (FGDs) was employed to assess needs and found four main themes: knowledge-related needs, attitude-related needs, health service-related needs, and perception-related needs. The module, divided into five units, covers the impact of diabetes on mothers and babies, the importance of PPC for diabetic mothers, PPC components, benefits of contraception, and maintaining controlled diabetes for the safety of both mother and baby. Experts assessed its content validity (S-CVI) as 1.0 and face validity as 0.99. There were significant changes in knowledge scores over time (F (1,88) = 76.87, p < 0.001), with a notable difference between the intervention and control groups in mean knowledge scores (F (1,88) = 5.71, p < 0.019) and a significant interaction effect (F (1,88) = 210.32, p < 0.001). Attitude scores also showed significant overall changes within groups over time (F (1,88) = 71.31, p < 0.001), with a significant mean score difference between groups regardless of time (F (1,88) = 67.47, p < 0.001) and a notable group-time interaction (F (1,88) = 127.81, p = 0.042). Conclusion: The study in Terengganu identified a significant need for a Pre-Pregnancy Care (PPC) educational module tailored for diabetic women of reproductive age, motivated by their desire for a healthy pregnancy. The developed module, validated for both reliability and relevance, effectively improved knowledge and attitudes towards PPC among the intervention group, as demonstrated by the quasi-experimental study's results.
- PublicationDevelopment and validation of a questionnaire assessing expectations of the characteristics of friendly primary health services from men's perspective(2023-03)Aziz, Muhammad Zikri AbBackground: Underutilization of healthcare services may contribute to poor health status among men. This study aimed to explore men’s experiences with primary health services and their expectations regarding the characteristics of friendly primary health services in Kelantan, Malaysia, and develop a questionnaire assessing those expectations. Methodology: The study was conducted in two phases using a mixed-method approach. Phase One involved the development of a questionnaire based on an extensive literature review, in-depth interviews with adult males in Kelantan, content validation, face validation, and pilot testing. Face-to-face interviews were conducted with 15 adult males purposefully selected using a maximum variation sampling method from six governmentbased primary health facilities in Kelantan. Data were transcribed and analyzed using the thematic analysis method. The qualitative study findings were used as the basis for item generation. The procedure was followed by content validation by seven experts and face validation by ten adult males in Kelantan. Phase two involves exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) to measure the questionnaire’s internal structure validity and reliability. A cross-sectional study was conducted for EFA with 280 conveniently selected participants and followed by another 280 for CFA in eight government primary health clinics in Kelantan. Results: The interview findings showed that the theme of men’s experience with existing primary health services was derived from four subthemes: provision of health services, health promotion delivery, attributes of healthcare providers, and the physical environment of the health facilities. Four other subthemes formed the theme of men’s expectations of the characteristics of friendly primary health services: meeting men’s needs in primary health services, approaching men through effective health promotion strategies, standards of a healthcare provider from a men’s viewpoint, and a comfortable physical environment for men. A new questionnaire was developed with 69 items and four domains. Following the content validation phases, items were reduced to 65, with several items with low I-CVI maintained for testing in the following process. Two items were deleted during face validation, with the remaining 63 items tested for EFA, yielding a new hypothesized model with 44 items and eight domains. The model was revised during CFA, and the best model of five domains and 39 items that met the model fitness analysis was chosen as the final questionnaire. Conclusion: The newly developed questionnaire with 39 items in five respective domains, which are the provision of health services, service time extension, health promotion and education, characteristics of healthcare providers, and physical environment of health facilities, is a valid and reliable instrument for assessing expectations of the characteristics of friendly primary health services from men’s perspective in Kelantan.
- PublicationDevelopment of a new hybrid regression model: an application of fuzzy regression and multilayer feedforward neural network(2023-08)Tabnjh, Abedelmlek Kalefh SleemanHerbal extracts have been utilized in oral health to treat various ailments, including inflammation, as antimicrobial plaque agents, antiseptics, antioxidants, histamine release prevention, and as antibacterial, antifungal, antiviral, and antimicrobial analgesics. Herbal medication also functions in healing, plaque reduction in the oral cavity, and immune enhancement. There is minimal research that has used regression to link knowledge with practice and other sociodemographic variables in HMOH. To develop a hybrid model by considering bootstrap, neural network, and fuzzy regression for HMOH KP, to measure the efficacy and efficiency of the developed hybrid model for HMOH KP, and to validate the newly developed hybrid model. This study aims to develop the best strategy for handling data analysis, especially in HMOH KP, which combines fuzzy regression and Multi-layer Feedforward Neural Network (MLFFNN). R-programming software is used to write the developed syntax. All the essential steps are summarized in the R syntax. The new hybrid regression model incorporating bootstrapping, MLFFNN, and fuzzy regression increases the precision of the estimated parameters and compensates for the ambiguous relationship between the dependent and independent variables. The MLFFNN method has successfully measured the effectiveness, efficiency, and accuracy of the new hybrid model. The R2 value and the predicted value obtained are used to validate the derived model. Conclusion: This thesis presents a new methodology for creating precise and validated regression models through the utilization of the HMOH KP dataset. Moreover, this approach can be extended to any other dataset that aligns with the provided assumptions.
- PublicationDevelopment of Malaysia breast cancer survival prognostic tool (myBeST) for prediction of survival probability among women with breast cancer in Malaysia(2023-03)Mohd Nasrullah Nik Ab., KadirBackground: Breast cancer accounts for a sizeable portion of newly diagnosed cancer. Prognostic tools were developed to inform patients regarding their outcomes. Performance of Western-centric tools found to be less accurate when applied in our setting with PREDICT breast cancer (PREDICT) had an acceptable accuracy. Objective: The study aimed to develop predictive models for survival among women with breast cancer in Malaysia, to compare its performance with PREDICT and the model’s algorithm was incorporated to develop a web-based Malaysian Breast Cancer Survival Prognostic Tool (myBeST). Methodology: This study consists of two phases. Phase 1 is a retrospective cohort study using data abstracted from seven regional breast cancer referral centres in Malaysia. We collected 13 predictors and survival outcomes. Time-to-event Cox proportional hazard (PH) analysis and two supervised machine learning classifiers (decision tree (DT) and artificial neural networks (ANN)) were employed to model and predict five-year survival probability. The model with the best performance indices was compared with the PREDICT tool. Subsequently, in Phase 2, the model was deployed in a web-based format with accompanying content to describe the tool. The website underwent several user-centred iterative development stages, including content (n = 8) and face validity (n = 20) assessments by medical specialists and medical officers. Results: There were 1,006 patients included for model derivation and validation. They were mostly Malay, with ductal carcinoma, hormone-sensitive, HER2-negative, at T2, N1-stage, without metastasis, received surgery and chemotherapy. The five-year survival was 60.5% (95% CI: 57.6, 63.6). By the Cox PH model, Indians had a higher hazard of death compared to Malay (Adjusted HR (Adj. HR): 1.77, 95% CI: 1.19, 2.63). Histological type, cancer grade, tumour, node, and metastasis stage at diagnosis significantly associated with death. Those who received surgery (Adj. HR: 0.49, 95% CI: 0.28, 0.87), chemotherapy (Adj. HR: 0.59, 95% CI: 0.44, 0.79), and radiotherapy (Adj. HR: 0.70, 95% CI: 0.51, 0.96) had a lower risk of death. Cox PH model outperformed the DT and ANN model in terms of accuracy (Cox PH: 0.841, DT: 0.811, ANN: 0.821), F1-score (Cox PH: 0.879, DT: 0.859, ANN: 0.870) and the area under the receiver operating characteristic curve (AUC; Cox PH: 0.891, DT: 0.39, ANN: 0.877). The Cox PH was more accurate in predicting five-year survival probability with a higher AUC (0.78, 95% CI: 0.73, 0.82) than PREDICT (AUC: 0.75, 95% CI 0.70, 0.80). Thus, the model was deployed as the main feature of our webbased prognostic tool. The website was developed and improved at every iterative stage. The content validity indices were ≥0.88 and face validity indices were >0.90, resulting in a functioning and user-centred prognostic tool. Conclusion: The web-based tool derived from robust Cox PH model showed promising results. Further validation, usability, and feasibility studies are necessary as the tool could potentially be used by care providers to convey individualised survival prediction for newly diagnosed breast cancer patients.
- PublicationDifferential gene expression analyses in HBE/Beta thalassaemia patients and their relationship to disease severity(2022-08)Alsaleh, Heba A. A.Haemoglobin E-beta thalassaemia (Hb E/β-thalassaemia) is a common inherited genetic disorder. It is responsible for approximately half of all severe betathalassaemia cases globally. In the state of Kelantan, 50.93% of thalassaemic patients have Hb E/β-thalassaemia, and most of the cases are commonly seen in Malay compared to Chinese and Indian. Clinical heterogeneity is the most outstanding criteria among these patients ranging from mild to severe clinical courses that need a regular blood transfusion. There are many modifiers found to affect the disease presentation. However, the exact reasons behind this heterogeneity are not fully understood. This research aimed to study the differential gene expression and their possible role in the disease presentation and complications development in both transfusion-dependent (TDT) and non-transfusion dependent (NTDT) HbE/β-thalassaemia patients. It was conducted with the aid of RT2 profiler PCR array and microarray that were used in gene expressional study in reticulocytes and erythroid progenitors, respectively. Three normal controls and a total of 20 patients were enrolled in this study; 10 (50%) were TDT, and 10 (50%) NTDT. The reticulocytes study showed the up-regulation of BAX and BAD genes in TDT patients, which have a role in apoptosis induction through the mitochondrial apoptotic pathway. Their up-regulation in TDT may play a role in the reticulocytes’ apoptosis, mature RBCs' short life span and eryptosis. Flow cytometry study showed higher apoptosis in the erythroid progenitors of TDT patients. The increased apoptosis in erythroid progenitors and the up-regulation of BAD and BAX of reticulocytes in TDT may be linked to the down-regulation of the genes involved in the PI3k/AKT pathway in the same patients’ group genes. Pathway and ontology analysis showed the involvement of osteoporosis and bone regulating factors related to the VDR pathway and the negative regulation of osteoclast differentiation in the TDT group. The genes involved can be therapeutic targets like SPP1 and MAFB. Their activation act to reduce the disease burden by reducing anaemia and alleviating bone marrow complications. In summary, our study showed the expression of interesting genes and pathways that may potentially modify the disease presentation and the development of the complications.
- PublicationDifferential tractography pipelines study in asymptomatic individuals with cerebral small vessel disease(2022-02)Safri, Amanina AhmadIntroduction: Cerebral small vessel disease (CSVD) is frequently discovered as an asymptomatic (‘silent’) finding during magnetic resonance imaging (MRI) brain scanning. Diffusion-based MRI, such as diffusion tensor imaging (DTI), is an emerging neuroimaging technique to detect and evaluate the CSVD manifestations, such as white matter hyperintensities (WMHs). DTI has been used progressively, but there is no gold standard for optimising the DTI pipeline processing, especially in the CSVD study. Therefore, to make the best use of DTI, several technical and methodological considerations must be made. Objective: The goal of this study is to establish a series of DTI pipeline processing either in a single or a combination of multiple well-established software packages in order to study their compatibility, reproducibility, and reliability in the assessment of white matter ischaemic integrity in asymptomatic CSVD. Methods: Sixty (n = 60) asymptomatic people (mean age, 39.82 years old ± 11.32) were recruited and had their brains scanned with a 3T MRI scanner. Twenty (n = 20) of the participants had WMHs. Four pipeline processing were established: P1(MedINRIA), P2 (DSI Studio), P3 (DTI Toolkit and TrackVis), and P4 (3Dslicer). Results: Each established DTI pipeline processing profile and user interface differences were discussed, including the programming language used, estimated total processing times, and their strengths and weaknesses. The comparison between each of the DTI pipelines processing was determined to be P2 as the best among the other pipelines processing used in this study based on the highest relative score of user interface differences. P2 also has a good reliability score (α = 0.86).
- PublicationDiscovering neural signatures of alpha brainwave indicative of attentional effect during melodic and rhythmic quranic recitation: a study of Universiti Sains Malaysia Health Campus community(2024-01)Shab, Mas SyazwaneeAttention is an established cognitive feature of alpha brainwaves (8-13 Hz). The Holy Quran has long been established to contribute to many psychological benefits, among others, the attentional effect. While research on the neuroscientific correlates of Quranic recitation is increasing over the past two decades, findings that project it to attention-inducing effect is scarce. In the present study, thirty (N=30) healthy participants (n Muslim=15, non-Muslim=15) were recruited and subjected to passive listening of five auditory stimuli, for three minutes each, consisting of Quranic and non-Quranic stimuli. To visualize the neural sources and the spectra of alpha power, the neuroimaging technique of complementary electroencephalography-magnetoencephalography (EEG-MEG) recording is used. The raw brain signals were processed and analysed using Brainstorm software. During the presentation of auditory stimuli, brain regions such as the precuneus, cuneus, calcarine, parietal and occipital showed significantly less neural activation, which reciprocated to higher alpha power. The increment in alpha power reflected attentional effect. The data underlines the idea that attention effect induced by Quranic recitation can plausibly be used to enhance attention level.
- PublicationEffect of autologous platelet rich plasma on non-surgical periodontal therapy for periodontitis in selected pakistani patients with uncontrolled type-ii diabetes mellitus(2023-12)Athar, YousafThe susceptibility to periodontal disease is often cited as the “sixth complication of diabetes mellitus” making it the most common oral complication of diabetes. Treatment for periodontal disease includes various non-surgical and surgical approaches. The metabolic disturbances in diabetic patients may lower their resistance to infections and may help in both initiation and progression of developing inflammatory periodontal disease. The use of autologous platelet concentrates has exhibited considerable promise as a conservative therapy towards periodontal treatment. The objective of the study was to evaluate the effects of platelet rich plasma placement in deep periodontal pockets, following non-surgical periodontal therapy (NSPT) in patients with standardized uncontrolled type II diabetes. The study groups comprised two patient groups receiving non-surgical periodontal therapy and platelet rich plasma in two different concentrations and a control group receiving NSPT only. An inter and Intra group comparison of Periodontal parameters including periodontal pocket depth, alveolar bone loss and gingival index along with pro-inflammatory cytokine, Tumour Necrosis Factor Alpha (TNF-α), interleukin 1β (IL-1 β) levels and C-reactive protein levels was conducted at 45- and 90-day interval. Overall average age was 50.17 with SD = 7.13. Both interventional groups exhibited statistically significant gain in bone height. PRP 1 group showed maximum gain in alveolar bone levels. A trend towards lower HbA1c levels was shown after NSPT and adjunctive PRP placement. The PRP groups exhibited lower the levels of circulating C- reactive protein. This reduction in levels of pro-inflammatory cytokines in plasma and improved periodontal parameters indicated a conducive environment towards periodontal tissue healing and improved diabetic control.
- PublicationEffect of epstein-barr virus (EBV) encoded latent membrane protein-1 (30 bp deletion mutant) on immune checkpoint regulation in nasopharyngeal and ebv-associated non-nasopharyngeal cancers(2024-06)Naveed, AhmedEpstein-Barr virus (EBV) is associated with several types of cancer, including nasopharyngeal, breast, gastric, and lungs. Despite previous studies showing a link between the development of Nasopharyngeal carcinoma (NPC) and the identification of EBV’s LMP1-30 bp deletion in NPC patients, several questions remain unanswered. In this research, a comparison of immune checkpoint receptor’s expression levels in 29 patients with EBV-associated NPC, 29 patients with non-NPC cancers, and 29 healthy controls (HC) was determined and evaluated for their association with EBV's LMP1-30 bp deletion mutation. The expression levels of immune checkpoint receptors (CD3, CD4, CD25, CD127, FoxP3, LAG-3, TIM-3, and TIGIT) were accessed on Tregs using flow cytometry assay. While, the detection of cytokine and chemokine concentrations (IL-10, IL-2, IFN-γ, TNF-α, IL-8, and IL-6) were performed using the simple plex assay. Furthermore, the detection of EBV’s LMP1-30 bp deletion mutation (mutant type variant) and LMP1 (wild type variant) from whole blood samples were performed using probe-based real-time PCR (qPCR). The final statistical analysis for association study was performed using different statistical tools. Most of the NPC patients were Malay (79.31%) ethnic, followed by Chinese (20.68%). WHO type III (62.06%) was the most common diagnosis for NPC patients, followed by WHO type II (27.58%) and WHO type I (10.34%). The expression of LAG-3, TIM-3 and TIGIT on Tregs was higher in NPC and non-NPC patients when compared with HC (p<0.05). As compared to non-NPC, the expression of LAG-3 and TIGIT was significantly higher in NPC patients (p<0.05). Although, the expression level of TIM-3 was slightly higher in NPC comparing to non-NPC patients but it was statistically not significant (p=0.053). There was a statistical significance observed when comparing the levels of IL-2, IFN-γ, TNFα, IL-6 and IL-8 (p<0.05) in NPC patients with HCs. However, there was no statistical difference for IL-10 (p=0.054). In case of non-NPC comparison with HCs, the significance was observed for IL-10, and IL-2 (p<0.05), while there was no statistical difference noted for IFN-γ, TNFα, IL-8 and IL-6 (p>0.05). The most dominant cytokine in NPC patients was TNF-α (10.70 ± 4.00 pg/mL); in non-NPC patients, it was IL-8 (13.36 ± 16.41 pg/mL). While IL-2 was found to be the least secreted cytokine in NPC (0.36 ± 0.25 pg/mL) and non-NPC patients (0.21 ± 0.14 pg/mL). The mutant type variant was detected in 27.58% of NPC patients, while none of sample from non-NPC and HC were found positive for the mutant type variant. The wild type variant was detected in 89.65% NPC, 65.51% non-NPC, and 3.44% of HCs. There was no association (p<0.05) found for differences in the expression of immune checkpoint biomarkers in mutant type variant cases with non-mutant type cases. These findings improve our understanding of the effects of EBV's LMP1 on immune checkpoint receptor expression levels in EBV-associated cancer patients. This could help identify potential immune checkpoint inhibitor drugs and predictive biomarkers for monitoring in EBV-associated cancer patients (NPC and non-NPC). Additionally, distinct cytokine profiles highlighted potential differences in the immune response between NPC and non-NPC individuals.
- PublicationEffect of heterotrigona itama bee bread on metabolic dysfunction-associated fatty liver disease parameters in obese male rats(2022-09)Zakaria, ZaidaAlmost 13 % of the world population suffers from obesity. Metabolic dysfunction‐associated fatty liver disease (MAFLD) is a pathological accumulation of hepatic lipid resulted from obesity and closely linked with many metabolic disorders, oxidative stress, inflammation and apoptosis. Bee bread has been reported to contain phenolic compounds and exhibits antioxidant, anti-inflammatory, and antiapoptotic properties. In addition, it significantly reduced the hepatic levels of lipogenic genes in MAFLD rat model. However, to date, it is not known whether bee bread may also improve other parameters in MAFLD. Therefore, the present study aimed to determine the phenolic composition of Heterotrigona itama bee bread and the effect of this bee bread on MAFLD parameters in obese male rats. Forty adult male Sprague Dawley rats weighing between 200-230 g were randomly divided into four groups (n=10/group): normal control (NC), high‐fat diet (HFD), bee bread (HFD+Bb, HFD+0.5 g/kg/day bee bread) and orlistat (HFD+Or, HFD+10 mg/kg/day orlistat) groups. At the end of 12th week, rats were sacrificed to obtain serum, adipose and liver tissues. Nine phenolic compounds were discovered with trans 3- hydroxycinnamic acid as the highest amount of compound to be found in the bee bread. Bee bread significantly improved liver function and histopathological changes in MAFLD rats. It also significantly down-regulated genes related to fatty acid uptake and de novo lipogenesis, up-regulated genes related to lipolysis, fatty acid β- oxidation and bile acid synthesis in the liver, hence improved hepatic lipid metabolism. Furthermore, bee bread significantly reduced liver oxidative stress markers (thiobarbituric acid reactive substance, nitric oxide, protein carbonyl), elevated antioxidant enzyme activities (superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferase, glutathione reductase) and translocation of nuclear factor erythroid 2‐related factor 2 to the nucleus, as well as mitigated proinflammatory (tumour necrosis factor-α, nuclear factor-kappa β, interleukin-1β, monocyte chemoattractant protein‐1) and pro-apoptosis (Bax, caspase-3) markers, which may be attributed to the presence of phenolic compounds in the bee bread. However, further studies are needed to elucidate other molecular mechanisms of bee bread before it is used as an alternative or complementary therapy among obese patients with MAFLD.
- PublicationElucidating the effects of sirolimus and sunitinib on nmu-induced rat breast carcinoma: in vitro and in vivo studies(2023-11)Sakri, Muhammad Shahidan MuhammadBreast cancer tissue comprises genes altered, modified or/and mutated tissue. Nowadays, there are many options available for cancer remedy which includes surgery, chemotherapy, radiotherapy as well as immune-targeted therapy. A previous study found that combining drugs helps to improve tamoxifen effects towards breast cancer. Sirolimus also known as rapamycin, is a bacterial macrolide with anti-fungal properties, immunosuppressant and anti-angiogenic agent in targeted therapy. Sunitinib is a small molecule, multi-targeted receptor tyrosine kinases (RTKs) inhibitor. In this study, the effects of sirolimus and sunitinib on the breast cancer model were elucidated. Angiogenic factors which include VEGFR-2, PDGFR-β, mTOR, HIF-1α and STAT3 were studied. In addition, the correlation study of MVD with angiogenic expression was carried out as well. For in vivo model, a total number of twenty-four (24) female Sprague Dawley’s rats were obtained from ARASC USM Kubang Kerian at day 20 of age. The experiments and procedures towards the animal were conducted strictly in accordance with approval from the Animal Ethics Committee of USM guidelines of animal care and welfare. The breast tumour was induced by NMU and grouped into 4 groups (sirolimus, sunitinib, sirolimus+sunitinib and untreated). For in vitro model, MCF-7 and MDA-MB 231 cell lines were used representing aggressive types of breast cancer. The cell lines were treated with drugs and analyzed for proteins expression as well as apoptosis. Immunohistochemistry scoring for the entire treated groups showed a significant (P<0.05) reduction of angiogenic factors expressions compared to a control group. Gene analyses of sirolimus and sunitinib treated breast tumours showed significant (P<0.05) down-regulation of angiogenic factors compared to the untreated group. This indicated anti-angiogenesis properties of sirolimus and sunitinib suppressed angiogenic pathways. MVD study by using CD31 staining showed significantly reduced number of vascular obtained from the entire treated groups compared to the untreated group. A correlation study on MVD and angiogenic factors expression showed a positive correlation between angiogenic factors (VEGFR-2, mTOR, HIF-1α and STAT3) and MVD count. On the other hand, in vitro study of MCF-7 and MDA-MD 231 cell lines revealed that treatment with sirolimus and sunitinib significantly (P<0.05) reduced cell growth as well as proliferation rates compared to untreated at the IC50 dose. The result indicated sirolimus and sunitinib as well as sirolimus+sunitinib effectively inhibited proliferation of MCF-7 and MDA-MB 231 in the time and dose-dependent manner. Apoptosis study found a significant increase of apoptotic cells obtained in the entire treated groups. In conclusion, sirolimus and sunitinib as single agents represent potential effective anti-cancer drugs for breast cancer treatment which are proven at protein and gene analysis of in vivo and in vitro models while the combination of sirolimus and sunitinib showed a synergistic effect.
- PublicationErgonomic risk assessment and whole-body vibration measurement in relation with work-related musculoskeletal disorders among food delivery riders in Terengganu, Malaysia(2022-12)Ahmad, ElyasBackground: Work-Related Musculoskeletal Disorders (WMSDs) were currently a subject of concern on occupational world where they were the leading cause of major disabilities and absenteeism among the workers. These phenomena affected global economic due to reduce in productivity among the workers. Pandemic Covid-19 had caused major drawback in occupational world where many people lose their job. In Malaysia, food delivery riders became the alternative and popular choice of job especially during pandemic Covid-19 as food delivery services were listed as essential service during Movement Control Orders (MCOs). However, the incidence of Road Traffic Accident (RTA) keeps increasing with high mortality rate among the riders. Many studies had reported the WMSDs were among the factors which contributed to the inappropriate riding behaviour among motorcyclist where WMSDs tend to cause psychological distress among the riders. These eventually lead to inappropriate behaviour such as speeding and violation of traffic light to chase for the trips. Meanwhile, there were many factors was revealed to be significantly associated with development of WMSDs such as working posture and exposure to the chronic vibration. Thus, this study aimed to assess the ergonomic posture using REBA Method and WBV measurement in relation with WMSDs among food delivery riders in Terengganu. Method: A cross-sectional study was conducted among 191 food delivery riders in Terengganu, Malaysia. A snowball sampling method was applied in this study where the “Captain Rider” act as the seed. This study involved answering self-administered questionnaire, REBA assessment and WBV measurement. The self-administered questionnaire contained validated Malay-Translated Standardized Nordic Musculoskeletal Questionnaire (M-SNMQ) which was designed to be completed within 30 minutes. Then, working posture was assessed using REBA method to quantify the risk of WMSDs. Meanwhile, WBV measurement was done using a calibrated Larson Davis HVM 100 Human Vibration Meter with a tri-axial accelerometer seat pad following ISO 2631-1 standards. The data was then analysed using SPSS 20.4 where descriptive analysis, simple and multiple logistic regression were performed. Result: This study revealed high prevalence of WMSDs (74.9%) among the riders which predominant by Low Back Pain (LBP) (73.3%). In addition, the mean (SD) Final REBA Score also was high which was “5”(0.88) indicating of medium risk of developing WMSDs which requires further investigation and the need of change to be done. Furthermore, the mean (SD) of Daily Vibration Exposure, A(8) was also high (0.624 (0.317) m/s2) which exceeded Exposure Action Value (EAV). Three factors were found to be the factors associated with WBV above EAV level which were average working days (aOR=1.56;95% CI=1.11,2.19;p=0.011), presence of WMSDs (aOR=2.93;95% CI=1.37,6.28;p=0.006) and suspension service (aOR=0.39;95%CI=0.19,0.82;p=0.012). This present study also proved that three factor significantly associated with WMSDs development among food delivery riders in Terengganu which were increasing average working days (aOR=2.00; 95% CI=1.34,2.98 ;p=0.001) , WBV above EAV limit (aOR=2.71;95% CI=1.13,6.53;p=0.026), and not doing stretching exercise before work (aOR=21.63; 95% CI=7.45,62.79;p<0.001). Conclusion: The high prevalence of WMSDs among food delivery riders were significantly associated with unergonomic posture which reflected by high REBA score and WBV exceeded EAV level. The result from this study should be used by health sectors as an indicator to implement change and improve the working environment of the riders. Multi-sectoral approach is vital to ensure the prevalence of WMSDs among this neglected group can be reduced which in turn can reduce the incidence of RTA and mortality among the riders.
- PublicationEvaluation of anti-nnav1.5 antibodies as potential therapeutic agent in suppressing breast cancer invasion and metastasis(2022-09)Sharudin, Nur AishahAdvanced-stage breast cancer has the poorest survival rates and contributes to 90% of cancer mortality, primarily due to limited molecular targets and treatment options. In this study, a novel target for metastatic breast cancer, a splice variant of Nav1.5 named ‘neonatal’ Nav1.5 (nNav1.5), a member of the family of voltage-gated sodium channels (VGSCs), was evaluated. nNav1.5 has a strong association with breast cancer metastatic potential through its role in cell migration, invasion in vitro, and metastasis in vivo. Monoclonal (mAb-nNav1.5) and polyclonal antibodies based on purified IgG (pAb-nNav1.5) or whole serum against nNav1.5 were obtained, which were evaluated as potential immunotherapeutic agents, investigating their effects on the invasion of breast cancer cells in vitro and their anti-tumoral and anti-metastatic effects in an animal model. This present study is aimed to produce monoclonal and polyclonal antibodies against a specific epitope of nNav1.5 and characterize their reactivity against nNav1.5 expressing breast cancer cells. Next, to investigate the therapeutic effects and anti-metastatic potential of these agents on the invasion of the 3D-spheroids culture of breast cancer cell lines and to evaluate the therapeutic effect of the mAb-nNav1.5 and pAb-nNav1.5 administration in a model of tumour induction with 4T1 cell line in BALB/c female mice. Findings demonstrated that the immunoreactivity of mAb-nNav1.5, pAb-nNav1.5 and serum of immunized animals against the specific nNav1.5 epitope, was confirmed in cells and lysates of nNav1.5 expressing cells, MDA-MB-231 and 4T1 cells based on ELISA, Western blotting and immunocytochemistry. Moreover, mAb-nNav1.5, pAb-nNav1.5, and nNav1.5 polyclonal serum suppressed the invasion of MDA-MB-231-3D and 4T1 3D-spheroids (30-58%, 30-50%, and 10-55%, respectively) followed by reduced nNav1.5 gene (3-5 folds) and protein expression, similar to tetrodotoxin (TTX), a potent channel blocker which was used as control drug. Finally, treatment with mAb-nNav1.5 and pAbnNav1.5 resulted in reduced tumour burden of 4T1-induced mammary tumour in BALB/c female mice, which maintained higher body weight, smaller tumour size, and absence of inflammation/macro metastatic lesions in organs (lungs, spleen, intestines, and liver) as compared to control group (PBS treated). Subsequent gene expression analysis revealed downregulation of nNav1.5 expression in the animals’ primary tumour tissues. Collectively, this study confirms the novelty of targeting nNav1.5 in suppressing breast cancer invasion and prevention of metastasis but importantly, humanized versions of mAb-nNav1.5 may represent useful passive immunotherapeutic agents to target nNav1.5 in breast cancer.
- PublicationEvaluation of gingival melanin depigmentation by using Er:YAG laser: ex-vivo and clinical studies(2018-09)Stas, Yasser TharwatGingiva hyperpigmentation is more often a non-pathological problem, but clinically it is considered unaesthetic especially in cases of excessive gingival display during smiling. Many treatment methods are available to solve the problem such as chemical peeling, surgery and laser ablation. The laser by its various wavelengths is considered a standard treatment in gingival depigmentation. Er: YAG laser is one of the most studied laser in soft tissues and hard tissues management. In this study, different power settings of the same wavelength of Er: YAG laser were compared between each other and the favorable of them were chosen for gingival depigmentation. The study was conducted in two phases beginning with ex-vivo animal tissue experiment followed by prospective human experiment phase. In the animal phase, 24 different power settings were applied in the hyperpigmented gingiva mucosa of a recently slaughtered sheep’s head. Altered zone, carbonization, speed and operator controllability parameters were examined for the purpose of choosing 4 best power settings to be applied to the human study. 2J/cm2 and 4J/cm2 fluences and SP and VLP pulse durations were chosen for the human study. In the human study, a total of 40 adult female and nonsmoker patients were recruited and were divided randomly into four groups of 10 patients each (2J/cm2VLP, 2J/cm2SP, 4J/cm2VLP and 4J/cm2SP). One power setting was applied to each group. Clinical and biological evaluation was performed. Pain, bleeding, satisfaction, carbonization, speed of removal and histological investigation parameters were tested. Ablated tissue specimen was sent for histological analysis. The four power settings proved safety, patient satisfaction and dentist controllability, and efficiency in the removal of the pigmentations. There was no statistical difference between them regarding histology, pain, satisfaction and bleeding (P>0.05). There was significant difference between groups regarding ablation time (P<0.05). Histological analysis showed a very shallow damage in the lamina propria with a depth of 10 to 60 microns. In conclusion, fluence of 2J/cm2 and 4J/cm2 with pulse duration of SP (0.3ms) and VLP (1ms) for each fluence were found to be safe, effective and efficient. Fluence <2J/cm2 might not be effective due to increase carbonization of the superficial gingiva of the lased areas, thus obscuring the vision of the operator, and fluence >5J/cm2 is uncontrollable. Peak power is less critical than the dose in aspect of ablation time. Based on ex-vivo animal study and clinical trial, examining the technical, clinical and biological aspects using Er: YAG laser in this study. The final optimum power settings obtained are: 2J/cm2 VLP which is optimum for the beginner practitioner and 4J/cm2SP which is optimum for the experienced practitioner.
- PublicationExploration of image-based stimuli to assess mental toughness among medical students of Universiti Sains Malaysia(2023-05)Nordin, Nadia IzzatiMental toughness (MT) is a psychological construct comprised of cognitive, emotional, and behavioural processes that explain an individual’s capacity to cope with stress and predicts optimal performance in adversity. Apart from psychological-based studies, researchers have been shifting to physiological and neuroscience research to advance the knowledge and understanding of mental toughness. These studies require non-invasive modulation of emotion, stress, and cognitive effort induction. This present study seeks to explore a set of image-based stimuli to assess mental toughness among medical students. The study design consisted of four phases. Phase I involved the validation of the MTQ-48 questionnaire. Phase II involved the assessment of mental toughness, depression, anxiety, and stress in medical students. Phase III involved the selection of 156 image-based stimuli from databases such as the International Affective Picture System (IAPS), the Nencki Affective Picture System (NAPS), the Emotional Picture Set (EmoPics), the Open Affective Standardized Image Set (OASIS), the Geneva Affective Picture Database (GAPED), and online licensed no copyright platforms such as Pexels and PxHere. These images were then content validated by panel of experts according to academic related and clinical related medical context. The valence and arousal of normative evaluations were obtained by medical students using self-assessment manikin (SAM). Phase IV involved the evaluation of the stress intensity of the image-based stimuli from Phase III and its relationship with mental toughness, perceived stress, and stress score. Findings from factor analyses stated that MTQ-48 is unreliable for use in medical context as the fit indices do not meet acceptable standards. Consequently, MTQ-10 resulted from the validation process in Phase I had better model fit and used throughout the study. Besides, a significant inverse relationship was found between mental toughness and depression, anxiety, and stress. Out of 156 images, only 149 images were relevant to academic and clinical related medical context and were obtained valence and arousal mean value for each image. 36 images with negative valence were used to evaluate the stress intensity of the images and its relationship with mental toughness, perceived stress, and stress questionnaire. These findings provide evidence that the stress intensity of the set of image-based stimuli was 19% significantly predicted mental toughness, 43.9 % predicted perceived stress and 19.8% predicted stress. Hence, the set of image-based stimuli possibly to be used to assess mental toughness, perceived stress, and stress along with other variables in future research to facilitate a greater understanding of the affective processes associated with mental toughness in medical students.
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