Pusat Pengajian Sains Perubatan - Tesis

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A randomized control trial: insertion of peripherally inserted central catheter (picc) in neonates; mathematical formula versus direct measurement
(2023-02)
Jusili, Syamila Huda
Introduction Peripherally inserted central catheters (PICC) is commonly used in preterm infants. However, many studies have shown a high need for adjustment of their position after insertion. The aim of this study was to test a new method to estimate the ideal catheter depth for cubital PICC insertion in preterm infants. Methods A multi-center randomized, controlled trial was conducted, comparing direct measurement from insertion site to sternal notch (control group) versus a formula based on the length of the infant (intervention group) to estimate the ideal depth of cubital PICC in preterm infants with a birth of less than 1.5kg. The primary outcome was the rate of correctly placed PICCs. Catheter related complications were also monitored. Results There was no difference in baseline characteristics between the intervention group and the control group except for a significant lower birth weight in the intervention group. There was no significant difference in correct placement between the intervention and the control groups (6 out of 25 or 24% vs 10 out of 27 or 37% respectively, p=0.309). There was also no significant difference in complication rates between the two groups. Discussion and conclusion This study did not show benefits of using an alternative formula for estimation of catheter depth for cubital PICC insertion in preterm infants. As in previous studies the rate of correct initial placement was low and there is definitely a need for studies to identify better ways to estimate the depth of PICC insertion for preterm infants.
A study of antibiotic agents prescribed, guideline compliance and associated factor of antibiotic failure among the hospitalised paediatric and adult general medical patients in Hospital Universiti Sains Malaysia
(2023)
Ramli, Nurshahira
Background: Antibiotic is the commonest drugs used in hospitals. Inappropriate use of antibiotics has been shown to contribute to the occurrence of multidrug-resistant organisms (MROs). Understanding antibiotic prescription patterns is essential for combatting limited access and excessive use of antibiotics and controlling resistance. Thus, we evaluated antibiotic agents prescribed and the associated factor of antibiotic failure among hospitalized adult and pediatric patients in Hospital USM. Methodology: This was a retrospective study of antibiotic patterns among the adult general and pediatric general medical wards. A total of 227 patients were identified after had fulfilled the inclusion and exclusion criteria. This study used descriptive and inferential analysis to find out the objectives. The descriptive analysis includes the frequencies, percentage, mean and standard deviation, carried out to determine the patient’s demographic, patient’s clinical diagnosis, and patients comorbid. The inferential statistics involving simple logistic and multiple logistic regression are conducted to identify the factors associated with antibiotics failure. Results: Respiratory tract infections were found to be the highest infection sites and treated with antibiotics among all age groups with a total of 163 patients. Among these, 57.7% (94 patients) have been prescribed with penicillin with β-lactamase inhibitor group, followed by 28.8% (47 patients) with macrolide and a balance of 13.5% with other groups. Amoxicillin and clavulanic acid were reported to be the commonest among the penicillin with β-lactamase inhibitor group prescribed which was 65.2%. A total of 160 (70.5%) patients' prescription was noted as a single prescription while only 67 (29.5%) were of 2 antibiotics combination prescription. Most of them were given parenterally(75.3%). As of notes, more than half of prescriptions 60.8% (138) were deemed compliance to the guidelines. The rate of antibiotic failure was 12.8% (29) which was quite similar to a few other studies. 3 factors that been identified as the significant associated factor of antibiotic failure in this study were female sex (OR, 3.459; 95% CI, 1.075,11.130), the presence of acute kidney injury (OR, 3.084; 95% CI, 1.021, 9.311) and resistant organisms (OR, 2.961; 95% CI, 3.813,97.916). Conclusion: Most of the antibiotics prescribed in this study were penicillin with β-lactamase inhibitors. Despite this, there was only 12.8% (29) antibiotic failure and only 3 significant associated factors of failure were reported. Further larger scale and longer study needed to look for more antibiotic prescriptions not limited to the medical ward but including all disciplines such as surgical, orthopaedic, obstetrics, and gynaecology to conclude more realistic rate of antibiotic failure and associated factors.
Anti-diabetic and anti-lethargic effects of stichopus horrens extract in type 2 diabetes-induced sprague dawley male rats
(2025-01)
Vixuan, Eng
Diabetes mellitus is a chronic metabolic disorder, that is attributed to either insufficient insulin production by the pancreas or impaired response of body cells to insulin. Present medication like metformin has brought significant therapeutic effects in treating this disease but the side effects prompt the researchers to explore other alternative treatments especially natural products. This study aimed to investigate the potential of different sea cucumber samples of Stichopus horrens, differentiated by extraction methods, in reducing fasting blood glucose level, minimising fatigue condition, and restoring structure and function in organs of diabetic type 2-induced rats. Two extraction methods were utilised in this study, which are hydrolysis and high-pressure processing (HPP). The first extract of sea cucumber was subjected to hydrolysis only, while the second extract was exposed to HPP only. The last extract of sea cucumber was subjected to both hydrolysis and HPP. In the in-vitro assay, human umbilical vein endothelial cells (HUVECs) were exposed to three Stichopus horrens body wall samples, and a positive control, metformin with concentrations ranging from 6.25 to 4000 µg/mL in MTT assay to obtain starting dosage of treatments for animal study. The in-vivo study involved Sprague Dawley (SD) rats, which included the induction of high fat diet for five weeks, 110 mg/kg of nicotinamide injection, followed by 55 mg/kg of streptozotocin (STZ) into creating Type 2 diabetes mellitus (T2DM) rat model. Rats were randomly grouped into six groups; normal control (n=3), diabetic control (n=3), metformin-treated group (n=3), sea cucumber extract (hydrolysis only) (n=3), sea cucumber extract (HPP only) (n=3), and sea cucumber extract (HPP and hydrolysis) (n=4). The findings displayed a decreasing trend in cell viability with increasing sea cucumber concentration with ICS0 values of 3.771 ± 0.152 µg/mL in sea cucumber extract (hydrolysis only), 3.783 ± 0.063 µg/mL in sea cucumber extract (HPP only), and 4.006 ± 0.054 µg/mL in sea cucumber extract (HPP and hydrolysis) while metformin depicted an increasing trend of cell viability with ECS0 value of 4.931 ± 4.044 µg/mL. As a result, the starting dosage for animal study pertaining to different treatments is 150 mg/kg each. The findings depicted decreasing trend of blood glucose level after four weeks of treatments with 150 mg/kg sea cucumber samples and increased exercise tolerance in sea cucumber extract (HPP and hydrolysis) group with 150 mg/kg. Apart from that, sea cucumbers exhibited mild restoration in histological changes of liver, kidney, and pancreas. The short treatment duration of sea cucumber on diabetic rats might prove that sea cucumber is a promising candidate for the development of novel product in the future.
Anticancer effects of apis cerana and heterotrigona itama honeys on temozolomide-resistant glioblastoma cells
(2025-01)
Hui, You Ying
Glioblastoma is characterized by high aggressiveness and poor prognosis with median survival rate of less than 15 months. Due to the complexity of surgery to remove whole tumour and rapid development of chemoresistance towards temozolomide (TMZ), apitherapy using honey emerges as potential alternative treatment for glioblastoma due to its rich phenolic compounds with high antioxidant properties. However, the difference between Apis cerana honey and Heterotrigona itama honey for anti-glioblastoma effects has not been extensively studied. In this study, the phytochemical composition of A. cerana and H. itama honey were compared using phytochemical screening test and fourier transform infrared spectroscopy (FTIR) analysis. Their antioxidant capabilities were also compared using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Then, the half-maximal inhibitory concentration (IC50) values of both honeys on TMZ-resistant glioblastoma cell line (DBTRG-05MG cells) were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, while the analysis of cancer invasiveness and recurrence were determined through scratch assay and clonogenic assay respectively. After that, gene expressions between both honey-treated DBTRG-05MG cells were compared using quantitative reverse transcription polymerase chain reaction (qRT-PCR) to elucidate their effects towards apoptosis (MDM2 gene), metastasis (WNT5A gene) and chemoresistance (YTHDF2 gene). The analysis revealed that A. cerana honey contained higher levels of alkaloid and saponin as compared to H. itama honey, which contributed to its higher antioxidant activity as evidenced via the DPPH assay. This data was also supported by its lower IC50 value (130.5 ± 33.1 mg/mL) than H. itama honey (185.8 ± 27.6 mg/mL) in 72-hour treatment on DBTRG-05MG cells. In contrast, H. itama honey contained higher levels of flavonoid than A. cerana honey. Both honeys shared similar functional groups as indicated in FTIR analysis. A. cerana honey exerted strong inhibitory effect towards invasiveness and migration of DBTRG-05MG cells with its lowest closure percentage up to 72 hours while H. itama honey exerted strong prophylactic effect towards recurrence of DBTRG-05MG cells with its lowest colony number formed. However, there was no significant difference in MDM2, WNT5A and YTHDF2 expressions between honey-treated DBTRG-05MG cells. These findings suggest that A. cerana honey could be more effective in killing TMZ-resistant glioblastoma cells while H. itama honey could be more effective in preventing glioblastoma recurrence. The anticancer effect of each phytochemical in both honeys should be further investigated in future for better elucidation towards apoptotic, metastasis and chemoresistance mechanisms
Assesment of monocyte phagocytosis in the presence of synovial-fluid-derived exosomes from osteoarthritis patients
(2025-01)
Ruhani, Muhammad Akid
Osteoarthritis (OA) is a degenerative joint disease characterised by cartilage degradation, inflammation, and joint dysfunction, and monocytes play an important role in its pathogenesis via phagocytosis and inflammatory regulation. This study investigated the effect of synovial fluid-derived exosomes from OA patients on monocyte phagocytic activity. Synovial fluid (SF) was harvested from OA patients undergoing total knee arthroplasty, and exosomes were isolated by ultracentrifugation. Monocytes from healthy donor were cultured for 24 and 48 hours at different exosome concentrations (1:10, 1:20, and 1:40). Then, pHrodo™ Green E. coli conjugates were used to measure monocyte phagocytosis, which was quantified by flow cytometry. The findings demonstrated a significant increase in monocyte phagocytic activity upon exosome treatment, indicating a modulatory effect. These findings provide insight into the interaction between exosomes and monocyte in OA pathogenesis, underlining the possibility of exosome-based treatments to manage this degenerative illness
Assessment of the impact of computed tomography (CT) slice thickness on image noise and noise power spectrum (NPS)
(2025-07)
Nadzim, Akma Fatiny Mohammad
Slice thickness in computed tomography (CT) plays a critical role in image quality and diagnostic accuracy. This study aims to assess the impact of CT slice thickness on image noise and the Noise Power Spectrum (NPS) using the IndoQCT software. CT images were acquired using a water phantom at various slice thicknesses, and the resulting data were analyzed using the image analysis module in IndoQCT. Image noise was evaluated by calculating the standard deviation within a uniform region of interest, while the NPS was computed to examine the frequency distribution of the noise. The findings indicate that varying slice thickness significantly affects the level of image noise and its frequency characteristics. Thinner slices tend to produce images with higher noise but better spatial resolution, whereas thicker slices reduce noise at the expense of image detail. In this project, a water phantom was scanned using varying slice thicknesses ranging from 0.6 mm to 10 mm. The resulting images were analysed using IndoQCT software to quantify image noise and evaluate the NPS across the different slice thicknesses. Image noise was measured in terms of standard deviation within a uniform region of interest, while the NPS was used to characterise the spatial frequency distribution of the noise. These results are essential for determining the optimal slice thickness for quality control and clinical scanning purpose.
Cardioprotective effects of bunga kantan (etlingera elatior) in hypercholesterolaemic myocardial infarction sprague dawley rats
(2025-01)
Selvapaandian, Sharran
Cardiovascular diseases (CVDs), especially myocardial infarction (MI), remain a global health challenge with high mortality rates. Despite advancements in surgical and pharmacological interventions, the prevalence of MI continues to rise, often linked to risk factors such as hypercholesterolaemia. Alternative therapies utilising natural compounds with cardioprotective properties offer a promising alternative for addressing these limitations. This study investigates the potential of Etlingera elatior aqueous extract (EEAE) as a preventive treatment against hypercholesterolaemia-induced MI. The research employed a high-cholesterol diet (HCD) to induce hypercholesterolaemia in male Sprague-Dawley rats, followed by isoprenaline administration to induce MI. Rats treated with EEAE at 1000 mg/kg were evaluated over 12 weeks. Parameters, including blood pressure and cholesterol levels, were taken. Histopathological analyses were conducted to observe structural improvements in the myocardium. Results demonstrated that EEAE had no significant effect in lowering cholesterol levels and blood pressure but showed capability in preserving cardiac integrity. EEAE-treated groups exhibited enhanced histological recovery compared to untreated controls. These findings suggest that EEAE holds potential as a natural therapeutic agent for preventing MI in hypercholesterolemic conditions. Further research is needed to explore its mechanisms and applicability in clinical settings
Clinical utility of extended red blood cell parameters in the diagnosis of latent iron deficiency and thalassaemia trait in Hospital Universiti Sains Malaysia
(2023)
Sockalingam, Sivanesan
Introduction: Recognition of latent iron deficiency (LID) and thalassemia trait (TT) are challenging with the use of standard red blood cell (RBC) parameters. Accurate diagnosis is vital as the management of iron deficiency and haemoglobinopathy are different. The use of extended RBC parameters - reticulocyte haemoglobin equivalent (RET-He), percentage of microcytic RBC <60fL (MicroR), and percentage of hypochromic RBC <17pg (HYPO-He) may aid in the detection of LID and TT. The study aims to determine the diagnostic ability of these extended RBC parameters to distinguish LID and TT. Methodology: This was a prospective, case-control study conducted in Hospital USM from August 2021 to June 2022. 162 out of 212 blood donors who fulfilled the inclusion criteria were classified into the control group, LID group and TT group based on RBC parameters, serum ferritin and thalassaemia status. Between-group comparisons, receiver operating characteristic (ROC) curve analysis and comparison of area under the curve (AUC) for the RBC parameters were determined. The optimal cut-off was determined using the best Youden index. Result: There were 17 (10.5%) subjects with LID, 26 (16.0%) subjects with TT and 119 (73.5%) subjects in the control group. Standard RBC parameters were within the reference interval for all groups except for RBC (in females), MCV and MCH in the TT group. In LID and TT, RET-He and MicroR were lower and higher than the reference interval respectively, while HYPO-He was within the reference interval in all the groups. Taking into consideration the reference interval, RET-He was the best parameter to distinguish LID (AUC 0.723, 95% CI 0.608-0.839; 76.47% sensitivity and 73.95% specificity at 30.1pg cut-off) and TT (AUC 0.832, 95% CI 0.749-0.914; 84.62% sensitivity and 73.11% specificity at 30.2pg cut-off) from control. MicroR was the best parameter to distinguish TT from LID (AUC 0.742, 95% CI 0.591-0.893; 65.38% sensitivity and 76.47% specificity at 6.5% cut-off). Although the AUC of RET-He and MicroR were not significantly different in all the case comparisons, only MicroR was significantly higher in TT (median 9.1%, IQR 17.5) than LID (median 4.0%, IQR 6.1). Conclusion: Among the extended RBC parameters, RET-He was the best parameter for the detection of LID and TT, while MicroR performed well in differentiating TT from LID. These accessible parameters through modern automated haematology analyzers are low cost, with high throughput and rapid turn-around time can optimize the management of iron deficiency and thalassemia screening in the population.
Comparison study of different activity for image quality of nm/ct 670 pro system using lehr and megp collimators
(2025-06)
Zamri, Ainin Zahraa
Single Photon Emission Computed Tomography (SPECT) remains a cornerstone in nuclear medicine for evaluating functional processes within the body. This study aims to compare the image quality of the GE Discovery NM/CT 670 Pro system using two types of collimators consist of Low Energy High Resolution (LEHR) and Medium Energy General Purpose (MEGP) which performs across different activity levels of technetium-99m (Tc-99m), specifically 7 mCi and 12 mCi point source. A NEMA 2012/IEC 2008 Image Quality Phantom was used to simulate clinical conditions. Parameters evaluated included sensitivity, spatial resolution (FWHM), signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR), with image reconstruction performed using the OSEM algorithm. The GE Discovery NM/CT 670 Pro Gamma Camera was employed for this study. Results demonstrated that MEGP collimators produced higher sensitivity at lower activity (7 mCi), while LEHR collimators consistently outperformed in terms of spatial resolution, SNR, and CNR, especially at higher activity (12 mCi). The findings highlight the trade-off between resolution and sensitivity based on collimator type and radiopharmaceutical activity. At higher activities, MEGP benefited from greater count collection but suffered from reduced image clarity due to scatter, whereas LEHR maintained superior image contrast and noise suppression. This study supports the importance of optimizing collimator choice and activity level based on clinical imaging goals. The results provide valuable insight for improving image quality, dose management, and diagnostic accuracy in SPECT imaging protocols.
Detection of synovial fluid-derived exosomes internalization by thp-1 cells
(2025-01)
Faizal, Hanina Sofea
Exosomes are small vesicles involved in intercellular communication, carrying bioactive molecules that influence immune responses and inflammation. Synovial fluid-derived exosomes have garnered attention for their potential roles in joint diseases like osteoarthritis and rheumatoid arthritis. Despite the growing interest in synovial fluidderived exosomes and their potential role in immune modulation and joint diseases, there is limited understanding of how these exosomes are internalized by immune cells, particularly monocytes, which this study aims to address by examining the internalization process in a human monocytic cell line (THP-1 cells). This study explores the internalization of these exosomes by THP-1 cells to understand their impact on immune modulation. DAPI-labelled THP-1 cells were cultured with PKH67-labelled synovial fluid-derived exosomes, and their interactions were observed using fluorescence microscopy. The uptake was analysed at two incubation times (24 and 48 hours) and cellto- exosome ratios (1:10, 1:20, and 1:40) using ImageJ software. Flow cytometry confirmed CD14 expression on THP-1 cells. Results showed significant exosome internalization, with the cell-to-exosome ratio being the key factor affecting uptake, while no significant difference was observed between the two incubation periods. This study emphasizes the role of exosome-to-cell ratio in the internalization process, contributing to the understanding of understanding of how these exosomes interact with immune cells
Determination of humoral immune response in mice immunised with milk expressing three-tb epitopes
(2025-01)
Martin, Patricia Jane Wilfred
Tuberculosis (TB) continues to pose significant global health challenges despite the widespread use of the Bacillus Calmette-Guérin (BCG) vaccine. However, its limitations in inducing robust mucosal immunity, especially in adults, necessitate alternative approaches. This study explores the potential of a novel oral vaccine utilizing milk containing multi-epitope TB antigens. This study investigates the humoral immune response elicited in Balb/c mice immunized with milk containing multi-epitope tuberculosis antigens. These antigens which are Ag85B, Acr, and RpfE were expressed in goat milk with a secretory IgA fusion construct designed to produce milk containing multi-epitope TB:IgA to enhance mucosal immunity. The mices were immunized with five treatment groups which are Milk Daily (MD), Normal Milk (NM), BCG only (BCG-O), BCG + Milk Daily (BCG-MD), and BCG + Normal Milk (BCG-NM) to assess immune responses against three Mycobacterium tuberculosis epitopes. Two weeks post-immunization, serum, saliva, and BAL fluid samples were collected for analysis. ELISA plates were coated with the respective antigens to measure antigen-specific IgA and IgG levels. Optical density (OD) readings were used to quantify immune responses, and statistical analysis was conducted to determine significant differences between treatment groups. The immunized mice groups, including BCG and milk combinations, demonstrated varying levels of systemic IgG and mucosal IgA antibodies in serum, saliva, and bronchoalveolar lavage samples. Among the treatment groups, the milk-based vaccine candidate elicited robust antigen-specific IgG and IgA responses, indicating its potential for providing targeted immunity. These findings indicate the vaccine's potential to address key challenges of TB prevention, particularly in targeting mucosal surfaces which is the primary site of Mycobacterium tuberculosis infection. This study highlights the promise of oral mucosal vaccines as a complementary or alternative strategy to intradermal BCG vaccination, aiming to enhance protection and control TB more effectively. Future research and clinical trials are needed to validate these findings and further optimize this innovative vaccine approach
Determination of total immunoglobulin g and immunoglobulin g subclass response against sars-cov-2 omicron variant in pfizer and sinovac vaccinated serum samples
(2025-01)
Ravi, Syamalan
The COVID-19 pandemic, caused by the highly transmissible SARS-CoV-2 virus, continues to pose significant global health challenges. The emergence of variants such as Omicron has raised concerns regarding immune escape, waning immunity, and the long-term effectiveness of COVID-19 vaccines. While vaccination remains the most effective strategy in mitigating severe disease and transmission, differences in immune responses elicited by various vaccine platforms necessitate further investigation. This study aimed to evaluate the humoral immune response, focusing on total Immunoglobulin G (IgG) levels and IgG subclasses (IgG1 and IgG4), in individuals vaccinated with Pfizer-BioNTech (BNT162b2) and Sinovac (CoronaVac) vaccines. A total of 14 participants were recruited, with seven receiving Pfizer and seven receiving Sinovac. Serum samples were collected at six critical time points: pre-vaccination, post-first dose, two weeks after the second dose, and post-booster doses at two, 26, and 52 weeks. An indirect enzyme-linked immunosorbent assay (ELISA) was employed to quantify spike-specific IgG responses. The results demonstrated a significant increase in total IgG levels over time in both vaccine groups (p < 0.0001). Sinovac recipients exhibited higher total IgG levels (predicted mean: 1.984) compared to Pfizer recipients (predicted mean: 1.442). IgG1 levels remained comparable between both groups across all time points (p > 0.05), with Sinovac showing a transiently higher IgG1 response at two- and 26-weeks post-booster. In contrast, IgG4 levels significantly increased in Pfizer recipients at later booster time points (26 and 52 weeks, p < 0.05), whereas Sinovac elicited a less pronounced IgG4 response. These findings suggest that Sinovac induces a stronger early total IgG response, while Pfizer leads to a more pronounced IgG4 response after booster doses. The distinct patterns of IgG subclass distribution may influence long-term immunity and immune regulation following vaccination. Understanding these differential immune responses is essential for optimizing booster strategies, refining vaccine policies, and ensuring prolonged protection against emerging SARS-CoV-2 variants
Dosimetry comparison of aapm tg-43 and monte carlo calculations in 192ir hdr brachytherapy for patients with tongue cancer using egs_brachy source code
(2025-07)
Rosli, Fatin Hanis Mohd
High-dose-rate (HDR) brachytherapy employing Iridium-192 is a recognized technique for the treatment of tongue cancer, providing the benefit of delivering highly conformal doses while protecting adjacent critical structures. The American Association of Physicists in Medicine Task Group 43 (AAPM TG 43) formalism serves as the prevailing clinical standard for dose calculations; however, it operates under the assumption of a uniform water environment, thereby overlooking patient-specific anatomical differences. This study examines the variances between the AAPM TG 43 formalism and Monte Carlo (MC) simulations utilizing the egs_brachy application, which facilitates more precise patientspecific dose calculations by incorporating heterogeneities. CT datasets from three patients with tongue cancer who underwent HDR brachytherapy were examined. Treatment plans based on AAPM TG-43 were created using the Oncentra Brachy Treatment Planning System (TPS). Subsequently, these plans were transferred into the egs_brachy MC simulation framework through the eb_gui interface, enabling voxel-based modeling of patient anatomy and the simulation of dose distributions with detailed tissue assignment schemes. Dose Volume Histograms (DVHs) and statistical metrics such as D90, D100 for the Planning Target Volume (PTV), and D0.1cc, D1.0cc, and D2.0cc for organs at risk (OARs) were evaluated across both methodologies. The results indicated significant differences in the dosimetric parameters between the AAPM TG-43 and MC simulations. The AAPM TG-43 approach typically overestimated doses to the GTV while underestimating doses to specific OARs, highlighting its limitations in addressing patientspecific anatomical complexities. These findings emphasize the potential of MC simulations using egs_brachy as a more precise and reliable alternative for dose calculation in HDR brachytherapy, especially in anatomically intricate regions such as the oral cavity.
Dysregulation of transcriptomic profiles of mm1.s and u266 multiple myeloma cell lines treated with epigenetic inhibitors
(2024-09)
Ismail, Nor Hayati
Multiple myeloma (MM) is a hematological malignancy characterized by the uncontrolled proliferation of plasma cells in the bone marrow. Epigenetic dysregulation plays a pivotal role in MM pathogenesis, making epigenetic inhibitors promising therapeutic targets. This study examines the effects of three epigenetic inhibitors—Trichostatin A (TSA), Panobinostat (PAN), and 5-azacytidine (5-AZA) on MM1.S and U266 cell lines, focusing on transcriptomic dysregulation and the identification of core genes associated with survival outcomes. Dose-response curves revealed that all three inhibitors inhibited cell proliferation in a dose-dependent manner, with PAN showing the most potent anti-proliferative effect at the half maximal inhibitory concentration (IC50) dose. Flow cytometry analysis indicated significant changes in cell cycle distribution upon treatment. TSA, PAN, and 5-AZA induced G0/G1 phase arrest, suppression in S phase and no changes observed in G2/M phase in MM1.S cells and U266 cells. Apoptosis assays demonstrated that MM1.S cell lines experienced late apoptosis with the highest impact induced by PAN. Meanwhile, U266 cell lines demonstrated early apoptosis event after treatment with epigenetic inhibitors and the most profound impact induced by 5-AZA. KEGG enrichment analysis of both MM cell lines treated with these epigenetic inhibitors identified significant pathways involving cell adhesion molecules, microRNAs in cancer, and viral protein interactions with cytokines and receptors. Notably, this study also demonstrated that PAN and 5-AZA treatments upregulated certain core histone genes (H2A, H2B, H3, H4), co-impacting chromatin structure and gene regulation, thus influencing cellular processes and therapeutic responses. Furthermore, Kaplan-Meier plot analysis revealed that core genes linked to transcriptomic dysregulation were significantly associated with improved overall survival (OS) outcomes. The highest number of survival-associated core genes was found in 5-AZA-treated cell lines. Specifically, 5-AZA treatment increased the expression of similar core genes in both MM1.S and U266 cells, downregulating KIF20A, KIF4A, and PLK1, which correlated significantly with improved OS rate (log-rank P: 1.4e-16). In PAN-treated MM cell lines, ORC1, MCM2, MCM5, and CXCL1 were identified as core genes with therapeutic potential. TSA-treated U266 cell lines revealed more significant core genes than MM1.S cell lines, with APOE emerging as a key gene linked to improved survival outcomes (log-rank P < 1e-16). Overall, this study provides comprehensive insights into the transcriptomic alterations induced by epigenetic inhibitors in MM cell lines. These findings enhance the understanding of MM pathogenesis and offer potential therapeutic targets for treating this challenging disease.
Early predictive value of procalcitonin to albumin ratio for intensive care unit mortality in severe sepsis patients
(2023)
Manas, Siti Afifah Abd
Objective: High procalcitonin (PCT) and low albumin (ALB) concentrations have been associated with mortality in sepsis. The present study aimed to investigate the prognostic value of PCT to ALB ratio (PCT: ALB) for ICU mortality in septic patients. Methods: This was a registry based retrospective observational study conducted in the Intensive Care Unit (ICU) of Hospital Universiti Sains Malaysia over a 3-year period. Consecutive adult patients admitted to the ICU who underwent simultaneous measurement of PCT and ALB who fulfilled the Sepsis-3 criteria were recruited. Serum PCT was measured with a point-of-care analyzer available in the ICU (Finecare™ PCT Rapid Test). Predictive performance of PCT: ALB was assessed by analysis of the receiver-operating characteristic (ROC) curve. Results: A total of 185 sepsis patients were recruited. The primary outcome of all-cause ICU mortality was 35.1%. Baseline PCT was significantly higher while baseline ALB was significantly lower in the non-survivors compared to the survivors [9.8 (IQR 2.64 - 40.65) vs 2.07 (IQR 0.55 – 9.08) ng/mL and 26 (SD = 5) vs 30 (SD = 6) g/L, respectively, P <0.001]. The computed PCT: ALB was significantly higher in the non-survivors compared to the survivors [0.40 (IQR 0.11 – 1.63) vs 0.06 (IQR 0.02 – 0.31), P <0.001]. The area under the ROC curve of PCT: ALB for discrimination of ICU-mortality was 0.731 (95% CI 0.615-0.840) which was higher than PCT alone (AUC 0.721, 95% CI 0.651-0.785). The ideal cut-off value for PCT: ALB was 0.12 with sensitivity of 73.85% and specificity of 60.83%. Conclusion: PCT: ALB is a potentially reliable tool to aid in the mortality prediction of sepsis although this requires further validation in a prospective multi-center study.
Enhancing in-house plasmid dna extraction using customized glass fiber membrane
(2025)
Jamel, Jazmi Aiman
Plasmid DNA extraction and purification from bacterial cells are the foundations of many biotechnological processes. The extracted plasmid can be used for a variety of purposes, including genetic research, forensic analysis, and medical diagnosis. In-house extraction kits that are more cost effective and can produce comparable results to the commercial ones are still being pursue by many researchers. In this study we aimed to develop an in-house glass fiber membrane based plasmid extraction kit and compare its yield and purity with commercial kit. The commercial reference kits used in this study will be the Qiagen plasmid extraction kit. The in-house columns with different pore sizes (0.22 μm, 0.45 μm, and 0.80 μm) and number of membrane layers (1, 2 and 6 layers) were self-assembled. The membrane pore size of 0.80 μm yield the highest DNA concentration. the column assembled with 2 layers of GF-0.80 membrane produced highest DNA yield during DNA extraction. The final optimized in-house glass fiber membrane method showed comparable yield and purity (P>0.05) results to the commercial Qiagen plamid DNA extraction kits
Evaluating interfraction motion thresholds in image-guided radiotherapy (IGRT) for lung and spine stereotactic body radiotherapy (SBRT)
(2025-07)
Xin, Lau En
Stereotactic body radiotherapy (SBRT) is an advanced technique for small tumour volumes that requires precise dose delivery due to its hypofractionated nature and steep dose gradients. However, tumour motion, particularly respiratory-induced displacement, poses a challenge to treatment accuracy. This study aimed to evaluate interfraction motion thresholds using kilovoltage cone-beam computed tomography (kV-CBCT) in image-guided radiotherapy (IGRT) for lung and spine SBRT at Hospital Pakar Universiti Sains Malaysia (HPUSM). Methods: For seven lung SBRT cases, tumour motion was measured in Eclipse treatment planning system (TPS) by measuring the distance between contours of average gross tumour volume (GTV) and GTV from maximum and minimum respiratory phases using 4D-gated slow CT simulation images. Interfraction motion was quantified using kV-CBCT across 18 lung and spine SBRT patients, evaluating translational and rotational displacements over 3 to 5 treatment fractions. The mean interfraction displacements were evaluated against the AAPM TG-142 recommended thresholds (≤ 1 mm/°). Results: Tumour motion was highest in the superior-inferior (Y) direction during both maximum (mean = 0.3371 ± 0.4043 cm) and minimum (mean = 0.1205 ± 0.1677 cm) phases. A strong correlation (ρ ≥ 0.7) was observed between tumour motion and average GTV volume in most axes but the relationships were not statistically significant (p > 0.05). Interfraction displacement was highest in the lateral axis for lung SBRT (mean = 22.89 ± 33.75 mm) while spine SBRT showed more stable displacements, with the highest in vertical axis (mean = 22.38 ± 27.36 mm). No significant differences in displacement were observed across fractions and between simulation techniques (p > 0.05). The ratio of AAPM TG-142 threshold to actual displacement was approximately 1:20 for translational displacement and nearly 1:1 for rotational displacement. Conclusion: Interfraction motion displacements exceeded AAPM TG-142 translational threshold, highlighting the need of further study for motion management to optimise SBRT delivery.
Evaluation of etlingera elatior flower aqueous extract (EEAE) as treatment of colon cancer in rat model (pilot study)
(2025-01)
Shuang, Wee Lu
Colon cancer is a type of cancer that occurs in the colon or rectum. Therefore, sometimes it is also known as colorectal cancer (CRC). It is a leading cause of cancer-related deaths worldwide, even though there are available treatments for colon cancer, undesirable side effects often accompany it. Etlingera elatior, known as bunga kantan in Malaysia, is a traditional medicinal plant with high potential therapeutic effects with excellent antimicrobial, antioxidant, anticancer, antidiabetic, anti-inflammation, and anti-ageing properties. However, limited scientific research has been conducted on its antitumour effects against colon cancer. Therefore, this study investigates the in vivo antitumour effects of E. elatior flower aqueous extract (EEAE). EEAE is extracted using the sonication method. Toxicological assessment was performed using the brine shrimp lethality assay (BSLA) with a series of concentrations including concentrations of 10 mg/ml, 1 mg/ml, 3 mg/ml, 300 μg/ml, 100 μg/ml, 30 μg/ml, and 10 μg/ml. The LC50 of EEAE determined after the 24-hour incubation period was 2286 ppm (μg/ml), classifying EEAE as non-toxic based on Meyer and Clarkson toxicity standards. The antitumour efficacy of EEAE was further evaluated in an Azoxymethane-induced colon cancer model using male Sprague-Dawley rats. Histological analysis with Hematoxylin and Eosin (H&E) and Masson-Trichrome (MT) staining demonstrated substantial improvements in colon morphology upon treatment with EEAE. These findings suggest that EEAE is a promising natural product with antitumour properties against colon cancer, with no observed toxicity in vivo. Further research is warranted to explore its therapeutic potential and underlying mechanisms
Evaluation of phytochemicals, antioxidant & antimicrobial properties of cinnamomum verum extracts
(2025-01)
Sabri, Nurul Akmal
Traditional medicine has long relied on plant-based remedies to address various health issues, with cinnamon bark being widely recognized for its therapeutic properties. This study aims to investigate the phytochemical, antioxidant and antimicrobial properties of cinnamon extracts, emphasizing its potential as a natural therapeutic agent. Aqueous extract of C. verum (AECV) and ethanolic extract of C. verum (EECV) were analyzed for their bioactive compounds, revealing the presence of alkaloids, phenols, flavonoids, tannins, glycosides, and terpenoids, while saponins were detected only in AECV. Antioxidant activity was assessed using DPPH radical scavenging and total phenolic content (TPC) assays. AECV demonstrated higher antioxidant potential (IC50 = 0.233 mg/mL) than EECV (IC50 = 0.418 mg/mL), although both exhibited lower activity compared to ascorbic acid (AA) (IC50 = 0.00673 mg/mL). TPC analysis revealed that EECV (0.1001 [0.236] mg GAE/g) showed higher phenolic content than AECV (0.0227 [0.036] mg GAE/g), indicating ethanol's effectiveness in extracting phenolics. Antimicrobial activity against S. aureus and E. coli was evaluated using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays, where AECV demonstrated limited antibacterial activity against S. aureus (MIC = 20 mg/mL), while EECV exhibited no significant effects. Neither extract inhibited E. coli, likely due to insufficient extract concentrations. These findings indicate that cinnamon bark showed potential as a natural source of antioxidant, while further investigation is needed to explore its antimicrobial potential
Evaluation of source loading position in HDR brachytherapy dose calculation for patients with oral tongue cancer
(2025-06)
Britonathan, Mathilda Roshini
The dosimetric impact of six different dwell activation strategies in high-dose-rate (HDR) interstitial brachytherapy for oral tongue squamous cell carcinoma (OTSCC) was retrospectively investigated in twenty patients. Treatment plans were generated using Oncentra Treatment Planning System (TPS) with varying source loading configurations: Initial activation (uniform 0.25 cm spacing), system-optimized Autoactivation, fixed spacings of 0.50 cm, 0.75 cm, and 1.00 cm, and an alternating Zig-zag pattern. Dosimetric parameters assessed included D90, V100%, and V200% for target volume coverage, and D0.2cc and D2cc for organs at risk (OARs), specifically the mandible, pharyngeal constrictor muscles (PCM), and right and left submandibular glands (SMGs). Surface dose was also evaluated to estimate mucosal toxicity risk. All data were analyzed using SPSS version 29. Normality tests were followed by Friedman and Wilcoxon signed-rank tests, as well as repeated measures ANOVA where appropriate. The 0.50 cm dwell activation strategy demonstrated the most favorable dosimetric profile, yielding the lowest mean surface dose (0.59 Gy) and mandible D0.2cc (1.56 Gy), while maintaining adequate tumor coverage (mean D90: 5.17 Gy; V100%: 99.64%). Although the Initial plan resulted in the highest D90 (5.82 Gy), it was associated with elevated surface and OAR doses. The Zig-zag pattern achieved comparable OAR sparing to the 0.50 cm configuration but exhibited higher inter-patient variability. Wider activation intervals (0.75 cm and 1.00 cm) did not improve tumor coverage and were linked to increased dose exposure to adjacent healthy structures. Statistically significant dose reductions were observed for the mandible and PCM using tighter dwell configurations (p < 0.05). Dwell position selection significantly influenced dose distribution in HDR tongue brachytherapy. Among the strategies evaluated, the 0.50 cm dwell spacing provided the most favorable balance between target coverage and OAR sparing, supporting its consideration as an optimal source loading pattern in clinical planning.

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