Displaying publications 41 - 54 of 54 in total

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  1. Ho WS, Balan G, Puthucheary S, Kong BH, Lim KT, Tan LK, et al.
    Microb Drug Resist, 2012 Aug;18(4):408-16.
    PMID: 22394084 DOI: 10.1089/mdr.2011.0222
    The emergence of Escherichia coli resistant to extended-spectrum cephalosporins (ESCs) is of concern as ESC is often used to treat infections by Gram-negative bacteria. One-hundred and ten E. coli strains isolated in 2009-2010 from children warded in a Malaysian tertiary hospital were analyzed for their antibiograms, carriage of extended-spectrum beta-lactamase (ESBL) and AmpC genes, possible inclusion of the beta-lactamase genes on an integron platform, and their genetic relatedness. All E. coli strains were sensitive to carbapenems. About 46% of strains were multidrug resistant (MDR; i.e., resistant to ≥3 antibiotic classes) and almost half (45%) were nonsusceptible to ESCs. Among the MDR strains, high resistance rates were observed for ampicillin (98%), tetracycline (75%), and trimethoprim/sulfamethoxazole (73%). Out of 110 strains, bla(TEM-1) (49.1%), bla(CTX-M) (11.8%), and bla(CMY-2) (6.4%) were detected. Twenty-one strains were ESBL producers. CTX-M-15 was the predominant CTX-M variant found and this is the first report of a CTX-M-27-producing E. coli strain from Malaysia. Majority (3.1%) of the strains harbored class 1 integron-encoded integrases with a predominance of aadA and dfr genes within the integron variable region. No gene cassette encoding ESBL genes was found and integrons were not significantly associated with ESBL or non-ESBL producers. Possible clonal expansion was observed for few CTX-M-15-positive strains but the O25-ST131 E. coli clone known to harbor CTX-M-15 was not detected while CMY-2-positive strains were genetically diverse.
  2. Ho WS, Tan LK, Ooi PT, Yeo CC, Thong KL
    BMC Vet Res, 2013;9:109.
    PMID: 23731465 DOI: 10.1186/1746-6148-9-109
    Postweaning diarrhea caused by pathogenic Escherichia coli, in particular verotoxigenic E. coli (VTEC), has caused significant economic losses in the pig farming industry worldwide. However, there is limited information on VTEC in Malaysia. The objective of this study was to characterize pathogenic E. coli isolated from post-weaning piglets and growers with respect to their antibiograms, carriage of extended-spectrum beta-lactamases, pathotypes, production of hemolysins and fimbrial adhesins, serotypes, and genotypes.
  3. Loh KB, Ramli N, Tan LK, Roziah M, Rahmat K, Ariffin H
    Eur Radiol, 2012 Jul;22(7):1413-26.
    PMID: 22434420 DOI: 10.1007/s00330-012-2396-3
    OBJECTIVES: The degree and status of white matter myelination can be sensitively monitored using diffusion tensor imaging (DTI). This study looks at the measurement of fractional anistropy (FA) and mean diffusivity (MD) using an automated ROI with an existing DTI atlas.

    METHODS: Anatomical MRI and structural DTI were performed cross-sectionally on 26 normal children (newborn to 48 months old), using 1.5-T MRI. The automated processing pipeline was implemented to convert diffusion-weighted images into the NIfTI format. DTI-TK software was used to register the processed images to the ICBM DTI-81 atlas, while AFNI software was used for automated atlas-based volumes of interest (VOIs) and statistical value extraction.

    RESULTS: DTI exhibited consistent grey-white matter contrast. Triphasic temporal variation of the FA and MD values was noted, with FA increasing and MD decreasing rapidly early in the first 12 months. The second phase lasted 12-24 months during which the rate of FA and MD changes was reduced. After 24 months, the FA and MD values plateaued.

    CONCLUSION: DTI is a superior technique to conventional MR imaging in depicting WM maturation. The use of the automated processing pipeline provides a reliable environment for quantitative analysis of high-throughput DTI data.

    KEY POINTS: Diffusion tensor imaging outperforms conventional MRI in depicting white matter maturation. • DTI will become an important clinical tool for diagnosing paediatric neurological diseases. • DTI appears especially helpful for developmental abnormalities, tumours and white matter disease. • An automated processing pipeline assists quantitative analysis of high throughput DTI data.

  4. Hamzah N, Narayanan V, Ramli N, Mustapha NA, Mohammad Tahir NA, Tan LK, et al.
    BMJ Open, 2019 09 18;9(9):e028711.
    PMID: 31537559 DOI: 10.1136/bmjopen-2018-028711
    OBJECTIVES: To measure the clinical, structural and functional changes of an individualised structured cognitive rehabilitation in mild traumatic brain injury (mTBI) population.

    SETTING: A single centre study, Malaysia.

    PARTICIPANTS: Adults aged between 18 and 60 years with mTBI as a result of road traffic accident, with no previous history of head trauma, minimum of 9 years education and abnormal cognition at 3 months will be included. The exclusion criteria include pre-existing chronic illness or neurological/psychiatric condition, long-term medication that affects cognitive/psychological status, clinical evidence of substance intoxication at the time of injury and major polytrauma. Based on multiple estimated calculations, the minimum intended sample size is 50 participants (Cohen's d effect size=0.35; alpha level of 0.05; 85% power to detect statistical significance; 40% attrition rate).

    INTERVENTIONS: Intervention group will receive individualised structured cognitive rehabilitation. Control group will receive the best patient-centred care for attention disorders. Therapy frequency for both groups will be 1 hour per week for 12 weeks.

    OUTCOME MEASURES: Primary: Neuropsychological Assessment Battery-Screening Module (S-NAB) scores. Secondary: Diffusion Tensor Imaging (DTI) parameters and Goal Attainment Scaling score (GAS).

    RESULTS: Results will include descriptive statistics of population demographics, CogniPlus cognitive program and metacognitive strategies. The effect of intervention will be the effect size of S-NAB scores and mean GAS T scores. DTI parameters will be compared between groups via repeated measure analysis. Correlation analysis of outcome measures will be calculated using Pearson's correlation coefficient.

    CONCLUSION: This is a complex clinical intervention with multiple outcome measures to provide a comprehensive evidence-based treatment model.

    ETHICS AND DISSEMINATION: The study protocol was approved by the Medical Research Ethics Committee UMMC (MREC ID NO: 2016928-4293). The findings of the trial will be disseminated through peer-reviewed journals and scientific conferences.

    TRIAL REGISTRATION NUMBER: NCT03237676.

  5. Hapuarachchi HC, Bandara KB, Sumanadasa SD, Hapugoda MD, Lai YL, Lee KS, et al.
    J Gen Virol, 2010 Apr;91(Pt 4):1067-76.
    PMID: 19955565 DOI: 10.1099/vir.0.015743-0
    Chikungunya fever swept across many South and South-east Asian countries, following extensive outbreaks in the Indian Ocean Islands in 2005. However, molecular epidemiological data to explain the recent spread and evolution of Chikungunya virus (CHIKV) in the Asian region are still limited. This study describes the genetic Characteristics and evolutionary relationships of CHIKV strains that emerged in Sri Lanka and Singapore during 2006-2008. The viruses isolated in Singapore also included those imported from the Maldives (n=1), India (n=2) and Malaysia (n=31). All analysed strains belonged to the East, Central and South African (ECSA) lineage and were evolutionarily more related to Indian than to Indian Ocean Islands strains. Unique genetic characteristics revealed five genetically distinct subpopulations of CHIKV in Sri Lanka and Singapore, which were likely to have emerged through multiple, independent introductions. The evolutionary network based on E1 gene sequences indicated the acquisition of an alanine to valine 226 substitution (E1-A226V) by virus strains of the Indian sublineage as a key evolutionary event that contributed to the transmission and spatial distribution of CHIKV in the region. The E1-A226V substitution was found in 95.7 % (133/139) of analysed isolates in 2008, highlighting the widespread establishment of mutated CHIKV strains in Sri Lanka, Singapore and Malaysia. As the E1-A226V substitution is known to enhance the transmissibility of CHIKV by Aedes albopictus mosquitoes, this observation has important implications for the design of vector control strategies to fight the virus in regions at risk of chikungunya fever.
  6. Ng CG, Tan LK, Gill JS, Koh OH, Jambunathan S, Pillai SK, et al.
    Asia Pac Psychiatry, 2013 Apr;5 Suppl 1:118-22.
    PMID: 23857847 DOI: 10.1111/appy.12056
    INTRODUCTION: This study aims to examine the validity and reliability of the Malay version of Attitudes toward Lesbians and Gay Men (MVATL/MVATG) among a group of medical students in Malaysia.
    METHODS: It is a cross-sectional study of 173 medical students in the Faculty of Medicine, University of Kuala Lumpur, Malaysia. The participants were given the MVATL/MVATG, Index of Attitudes toward Homosexuals (IATH), Homosexuality Attitude Scale (HAS) and the English version of Attitude toward Lesbians and Gay Men. Two weeks later, these students were given the MVATLG again.
    RESULTS: Significant correlation was found between the individual scores of MVATL and MVATG with IATH and HAS in the results. The scale was able to differentiate Muslim and Non-Muslim subjects. The internal consistency (Cronbach's alpha) of both the MVATL and MVATG were good, at 0.76 and 0.82, respectively. The parallel form reliability (Pearson's correlation) of MVATL was 0.0.73 and 0.74 for MVATG. The test-retest reliability of MVATL/MVATG was good (Intraclass correlation coefficient, ICC = 0.67 for MVATL and 0.60 for MVATG).
    DISCUSSION: The MVATLG demonstrated good psychometric properties in measuring attitudes toward homosexuality among a group of medical students in Malaysia and it could be used as a simple instrument on young educated Malaysian adults.
    KEYWORDS: Malaysia; attitude; gay men; homosexuality; lesbians; validation
  7. Chuah SH, Tan LK, Md Sari NA, Chan BT, Hasikin K, Lim E, et al.
    J Magn Reson Imaging, 2023 Jul 15.
    PMID: 37452574 DOI: 10.1002/jmri.28915
    BACKGROUND: Increased afterload in aortic stenosis (AS) induces left ventricle (LV) remodeling to preserve a normal ejection fraction. This compensatory response can become maladaptive and manifest with motion abnormality. It is a clinical challenge to identify contractile and relaxation dysfunction during early subclinical stage to prevent irreversible deterioration.

    PURPOSE: To evaluate the changes of regional wall dynamics in 3D + time domain as remodeling progresses in AS.

    STUDY TYPE: Retrospective.

    POPULATION: A total of 31 AS patients with reduced and preserved ejection fraction (14 AS_rEF: 7 male, 66.5 [7.8] years old; 17 AS_pEF: 12 male, 67.0 [6.0] years old) and 15 healthy (6 male, 61.0 [7.0] years old).

    FIELD STRENGTH/SEQUENCE: 1.5 T Magnetic resonance imaging/steady state free precession and late-gadolinium enhancement sequences.

    ASSESSMENT: Individual LV models were reconstructed in 3D + time domain and motion metrics including wall thickening (TI), dyssynchrony index (DI), contraction rate (CR), and relaxation rate (RR) were automatically extracted and associated with the presence of scarring and remodeling.

    STATISTICAL TESTS: Shapiro-Wilk: data normality; Kruskal-Wallis: significant difference (P 

  8. Goh CH, Tan LK, Lovell NH, Ng SC, Tan MP, Lim E
    Comput Methods Programs Biomed, 2020 Nov;196:105596.
    PMID: 32580054 DOI: 10.1016/j.cmpb.2020.105596
    BACKGROUND AND OBJECTIVES: Continuous monitoring of physiological parameters such as photoplethysmography (PPG) has attracted increased interest due to advances in wearable sensors. However, PPG recordings are susceptible to various artifacts, and thus reducing the reliability of PPG-driven parameters, such as oxygen saturation, heart rate, blood pressure and respiration. This paper proposes a one-dimensional convolution neural network (1-D-CNN) to classify five-second PPG segments into clean or artifact-affected segments, avoiding data-dependent pulse segmentation techniques and heavy manual feature engineering.

    METHODS: Continuous raw PPG waveforms were blindly allocated into segments with an equal length (5s) without leveraging any pulse location information and were normalized with Z-score normalization methods. A 1-D-CNN was designed to automatically learn the intrinsic features of the PPG waveform, and perform the required classification. Several training hyperparameters (initial learning rate and gradient threshold) were varied to investigate the effect of these parameters on the performance of the network. Subsequently, this proposed network was trained and validated with 30 subjects, and then tested with eight subjects, with our local dataset. Moreover, two independent datasets downloaded from the PhysioNet MIMIC II database were used to evaluate the robustness of the proposed network.

    RESULTS: A 13 layer 1-D-CNN model was designed. Within our local study dataset evaluation, the proposed network achieved a testing accuracy of 94.9%. The classification accuracy of two independent datasets also achieved satisfactory accuracy of 93.8% and 86.7% respectively. Our model achieved a comparable performance with most reported works, with the potential to show good generalization as the proposed network was evaluated with multiple cohorts (overall accuracy of 94.5%).

    CONCLUSION: This paper demonstrated the feasibility and effectiveness of applying blind signal processing and deep learning techniques to PPG motion artifact detection, whereby manual feature thresholding was avoided and yet a high generalization ability was achieved.

  9. Leong CO, Lim E, Tan LK, Abdul Aziz YF, Sridhar GS, Socrates D, et al.
    Magn Reson Med, 2019 02;81(2):1385-1398.
    PMID: 30230606 DOI: 10.1002/mrm.27486
    PURPOSE: To evaluate a 2D-4D registration-cum-segmentation framework for the delineation of left ventricle (LV) in late gadolinium enhanced (LGE) MRI and for the localization of infarcts in patient-specific 3D LV models.

    METHODS: A 3-step framework was proposed, consisting of: (1) 3D LV model reconstruction from motion-corrected 4D cine-MRI; (2) Registration of 2D LGE-MRI with 4D cine-MRI; (3) LV contour extraction from the intersection of LGE slices with the LV model. The framework was evaluated against cardiac MRI data from 27 patients scanned within 6 months after acute myocardial infarction. We compared the use of local Pearson's correlation (LPC) and normalized mutual information (NMI) as similarity measures for the registration. The use of 2 and 6 long-axis (LA) cine-MRI scans was also compared. The accuracy of the framework was evaluated using manual segmentation, and the interobserver variability of the scar volume derived from the segmented LV was determined using Bland-Altman analysis.

    RESULTS: LPC outperformed NMI as a similarity measure for the proposed framework using 6 LA scans, with Hausdorrf distance (HD) of 1.19 ± 0.53 mm versus 1.51 ± 2.01 mm (endocardial) and 1.21 ± 0.48 mm versus 1.46 ± 1.78 mm (epicardial), respectively. Segmentation using 2 LA scans was comparable to 6 LA scans with a HD of 1.23 ± 0.70 mm (endocardial) and 1.25 ± 0.74 mm (epicardial). The framework yielded a lower interobserver variability in scar volumes compared with manual segmentation.

    CONCLUSION: The framework showed high accuracy and robustness in delineating LV in LGE-MRI and allowed for bidirectional mapping of information between LGE- and cine-MRI scans, crucial in personalized model studies for treatment planning.

  10. Radhakrishnan AK, Raj VL, Tan LK, Liam CK
    Biomed Res Int, 2013;2013:981012.
    PMID: 23865080 DOI: 10.1155/2013/981012
    Asthma susceptibility genes are mapped to a region on human chromosome 5q31-q33, which contains a cluster of proinflammatory cytokine genes such as interleukin-13 (IL-13), which is associated with asthma. This study investigated the allele frequencies of two single nucleotide polymorphisms (SNPs) (-1111C>T and 4257C>A) in the IL-13 gene between asthmatics and healthy volunteers as well as the relationship between these SNPs and IL-13 production. DNA extracted from buffy coat of asthmatic and control subjects was genotyped using the PCR-RFLP method. Amount of IL-13 produced by mitogen-stimulated peripheral blood leucocytes PBLs (PBLs) was determined by ELISA. The frequencies of the -1111C and 4257G wild-type alleles were 0.52 and 0.55 in asthmatics and were 0.67 and 0.56 in controls. A significant (P < 0.05) association was found between genotype and allele frequencies of SNP at position -1111C>T between asthmatic and control groups (OR, 1.810; 95% CI = 1.184 to 2.767; P < 0.05). The mitogen-stimulated PBLs from asthmatics produced higher amounts of IL-13 production (P < 0.001). The 4257GA heterozygous and 4257AA homozygous mutant alleles were associated with higher IL-13 production in asthmatics (P < 0.05). Our results show that the -1111T mutant allele are associated with asthma and the 4257A mutant alleles are associated with elevated IL-13 production.
  11. Azlan CA, Wong JHD, Tan LK, A D Huri MSN, Ung NM, Pallath V, et al.
    Phys Med, 2020 Dec;80:10-16.
    PMID: 33070007 DOI: 10.1016/j.ejmp.2020.10.002
    PURPOSE: We present the implementation of e-learning in the Master of Medical Physics programme at the University of Malaya during a partial lockdown from March to June 2020 due to the COVID-19 pandemic.

    METHODS: Teaching and Learning (T&L) activities were conducted virtually on e-learning platforms. The students' experience and feedback were evaluated after 15 weeks.

    RESULTS: We found that while students preferred face-to-face, physical teaching, they were able to adapt to the new norm of e-learning. More than 60% of the students agreed that pre-recorded lectures and viewing videos of practical sessions, plus answering short questions, were beneficial. Certain aspects, such as hands-on practical and clinical experience, could never be replaced. The e-learning and study-from-home environment accorded a lot of flexibility. However, students also found it challenging to focus because of distractions, lack of engagement and mental stress. Technical problems, such as poor Internet connectivity and limited data plans, also compounded the problem.

    CONCLUSION: We expect e-learning to prevail in future. Hybrid learning strategies, which includes face-to-face classes and e-learning, will become common, at least in the medical physics programme of the University of Malaya even after the pandemic.

  12. Tan LK, Too CL, Diaz-Gallo LM, Wahinuddin S, Lau IS, Heselynn H, et al.
    Arthritis Res Ther, 2021 01 30;23(1):46.
    PMID: 33514426 DOI: 10.1186/s13075-021-02431-z
    BACKGROUND: Fine-mapping of human leukocyte antigen (HLA) region for rheumatoid arthritis (RA) risk factors has identified several HLA alleles and its corresponding amino acid residues as independent signals (i.e., HLA-A, HLA-B, HLA-DPB1, and HLA-DQA1 genes), in addition to the well-established genetic factor in HLA-DRB1 gene. However, this was mainly performed in the Caucasian and East Asian populations, and data from different Asian regions is less represented. We aimed to evaluate whether there are independent RA risk variants in both anti-citrullinated protein antibody (ACPA)-positive and ACPA-negative RA patients from the multi-ethnic Malaysian population, using the fine-mapping of HLA region strategy.

    METHODS: We imputed the classical HLA alleles, amino acids, and haplotypes using the Immunochip genotyping data of 1260 RA cases (i.e., 530 Malays, 259 Chinese, 412 Indians, and 59 mixed ethnicities) and 1571 controls (i.e., 981 Malays, 205 Chinese, 297 Indians, and 87 mixed ethnicities) from the Malaysian Epidemiological Investigation of Rheumatoid Arthritis (MyEIRA) population-based case-control study. Stepwise logistic regression was performed to identify the independent genetic risk factors for RA within the HLA region.

    RESULTS: We confirmed that the HLA-DRB1 amino acid at position 11 with valine residue conferred the strongest risk effect for ACPA-positive RA (OR = 4.26, 95% CI = 3.30-5.49, PGWAS = 7.22 × 10-29) in the Malays. Our study also revealed that HLA-DRB1 amino acid at position 96 with histidine residue was negatively associated with the risk of developing ACPA-positive RA in the Indians (OR = 0.48, 95% CI = 0.37-0.62, PGWAS = 2.58 × 10-08). Interestingly, we observed that HLA-DQB1*03:02 allele was inversely related to the risk of developing ACPA-positive RA in the Malays (OR = 0.17, 95% CI = 0.09-0.30, PGWAS = 1.60 × 10-09). No association was observed between the HLA variants and risk of developing ACPA-negative RA in any of the three major ethnic groups in Malaysia.

    CONCLUSIONS: Our results demonstrate that the RA-associated genetic factors in the multi-ethnic Malaysian population are similar to those in the Caucasian population, despite significant differences in the genetic architecture of HLA region across populations. A novel and distinct independent association between the HLA-DQB1*03:02 allele and ACPA-positive RA was observed in the Malays. In common with the Caucasian population, there is little risk from HLA region for ACPA-negative RA.

  13. Kuan SW, Chua KH, Tan EW, Tan LK, Loch A, Kee BP
    PeerJ, 2022;10:e13265.
    PMID: 35441061 DOI: 10.7717/peerj.13265
    Cardiomyopathy (CMP) constitutes a diverse group of myocardium diseases affecting the pumping ability of the heart. Genetic predisposition is among the major factors affecting the development of CMP. Globally, there are over 100 genes in autosomal and mitochondrial DNA (mtDNA) that have been reported to be associated with the pathogenesis of CMP. However, most of the genetic studies have been conducted in Western countries, with limited data being available for the Asian population. Therefore, this study aims to investigate the mutation spectrum in the mitochondrial genome of 145 CMP patients in Malaysia. Long-range PCR was employed to amplify the entire mtDNA, and whole mitochondrial genome sequencing was conducted on the MiSeq platform. Raw data was quality checked, mapped, and aligned to the revised Cambridge Reference Sequence (rCRS). Variants were named, annotated, and filtered. The sequencing revealed 1,077 variants, including 18 novel and 17 CMP and/or mitochondrial disease-associated variants after filtering. In-silico predictions suggested that three of the novel variants (m.8573G>C, m.11916T>A and m.11918T>G) in this study are potentially pathogenic. Two confirmed pathogenic variants (m.1555A>G and m.11778G>A) were also found in the CMP patients. The findings of this study shed light on the distribution of mitochondrial mutations in Malaysian CMP patients. Further functional studies are required to elucidate the role of these variants in the development of CMP.
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