Displaying publications 21 - 40 of 75 in total

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  1. Heat shock response and metabolic stress in the tropical estuarine copepod Pseudodiaptomus annandalei converge at its upper thermal optimum
    Low JSY, Chew LL, Ng CC, Goh HC, Lehette P, Chong VC
    J Therm Biol, 2018 May;74:14-22.
    PMID: 29801619 DOI: 10.1016/j.jtherbio.2018.02.012
    Heat shock response (HSR), in terms of transcription regulation of two heat shock proteins genes hsp70 and hsp90), was analysed in a widespread tropical copepod Pseudodiaptomus annandalei. The mRNA transcripts of both genes were quantified after copepods at a salinity of 20 underwent an acclimation process involving an initial acclimation temperature of 29 °C, followed by gradual thermal ramping to the target exposure temperature range of 24-36 °C. The respective cellular HSR and organismal metabolism, measured by respiratory activity at exposure temperatures, were compared. The fold change in mRNA expression for both hsp70 and hsp90 (8-9 fold) peaks at 32 °C, which is very close to 32.4 °C, the upper thermal optimum for respiration in the species. Unexpectedly, the modelled HSR curves peak at only 3 °C (hsp90) and 3.5 °C (hsp70) above the mean water temperature (29.32 °C) of the copepod in the field. We propose that copepods in tropical waters adopt a preparative HSR strategy, early at the upper limit of its thermal optimum, due to the narrow thermal range of its habitat thus precluding substantial energy demand at higher temperatures. However, the model suggests that the species could survive to at least 36 °C with short acclimation time. Nevertheless, the significant overlap between its thermal range of hsp synthesis and the narrow temperature range of its habitat also suggests that any unprecedented rise in sea temperature would have a detrimental effect on the species.
  2. Slow carbamazepine clearance in a nonadherent Malay woman with epilepsy and thyrotoxicosis
    Yeap LL, Lim KS, Ng CC, Hui-Ping Khor A, Lo YL
    Ther Drug Monit, 2014 Feb;36(1):3-9.
    PMID: 24342894 DOI: 10.1097/FTD.0000000000000024
    The authors describe a case of a 37-year-old Malay lady with an unusually slow carbamazepine clearance, which may be related to genetic polymorphisms of drug metabolizing enzymes and transporters. When given a small daily dose of 200 mg immediate-release carbamazepine, this patient experienced drowsiness. Subsequently, she reduced her carbamazepine dose to 200 mg twice a week (on Mondays and Fridays), resulting in poor seizure control. At the same time, the patient was diagnosed with hyperthyroidism and was given carbimazole and propranolol. Hyperthyroidism and the concurrent use of these antihyperthyroid agents may have further slowed down the metabolism of carbamazepine. Therapeutic drug monitoring of carbamazepine was carried out, and a slow carbamazepine clearance of 1.45 L·h⁻¹ per 70 kg was observed. Genotyping of selected genetic variants in CYP3A4, CYP3A5, EPHX1, ABCB1, and ABCC2 revealed that she has CYP3A5*3/*3 and ABCB1 3435-CC genotypes. Both genotypes have been shown to be associated with higher adjusted mean serum carbamazepine concentration in Chinese and Korean patients with epilepsy. Physicians should be vigilant about the risk of adverse effects among patients with a slow carbamazepine clearance, especially in Malays. Simulations of carbamazepine dosing regimen based on the pharmacokinetic parameters of this patient were performed to allow individualization of drug therapy.
  3. Investigating the decay rates of Escherichia coli relative to Vibrio parahemolyticus and Salmonella Typhi in tropical coastal waters
    Lee CW, Ng AY, Bong CW, Narayanan K, Sim EU, Ng CC
    Water Res, 2011 Feb;45(4):1561-70.
    PMID: 21146847 DOI: 10.1016/j.watres.2010.11.025
    Using the size fractionation method, we measured the decay rates of Escherichia coli, Salmonella Typhi and Vibrio parahaemolyticus in the coastal waters of Peninsular Malaysia. The size fractions were total or unfiltered, <250 μm, <20 μm, <2 μm, <0.7 μm, <0.2 μm and <0.02 μm. We also carried out abiotic (inorganic nutrients) and biotic (bacterial abundance, production and protistan bacterivory) measurements at Port Dickson, Klang and Kuantan. Klang had highest nutrient concentrations whereas both bacterial production and protistan bacterivory rates were highest at Kuantan. We observed signs of protist-bacteria coupling via the following correlations: Protistan bacterivory-Bacterial Production: r = 0.773, df = 11, p < 0.01; Protist-Bacteria: r = 0.586, df = 12, p < 0.05. However none of the bacterial decay rates were correlated with the biotic variables measured. E. coli and Salmonella decay rates were generally higher in the larger fraction (>0.7 μm) than in the smaller fraction (<0.7 μm) suggesting the more important role played by protists. E. coli and Salmonella also decreased in the <0.02 μm fraction and suggested that these non-halophilic bacteria did not survive well in seawater. In contrast, Vibrio grew well in seawater. There was usually an increase in Vibrio after one day incubation. Our results confirmed that decay or loss rates of E. coli did not match that of Vibrio, and also did not correlate with Salmonella decay rates. However E. coli showed persistence where its decay rates were generally lower than Salmonella.
  4. Ethnic variation of genetic (idiopathic) generalized epilepsy in Malaysia
    Lim KS, Ng CC, Chan CK, Foo WS, Low JS, Tan CT
    Seizure, 2017 Feb;45:24-27.
    PMID: 27912112 DOI: 10.1016/j.seizure.2016.11.011
    PURPOSE: Ethnic variation in epilepsy classification was reported in the Epilepsy Phenome/Genome Project. This study aimed to determine the ethnic variation in the prevalence of genetic (idiopathic) generalized epilepsy (GGE) and GGE with family history in a multi-ethnic Asian population in Malaysia.

    METHOD: In this cross-sectional study, 392 patients with a clinical diagnosis of GGE were recruited in the neurology outpatient clinic, University of Malaya Medical Centre (UMMC), from January 2011 till April 2016.

    RESULTS: In our epilepsy cohort (n=2100), 18.7% were diagnosed to have GGE. Of those, 28.6% >(N=112) had family history of epilepsy with a mean age of seizure onset of 16.5 years old, and 42.0% had myoclonic seizures (N=47). The lifetime prevalence of epilepsy among first-degree relative of those with GGE and positive family history was 15.0%. Analysis according to ethnicity showed that Malaysian Chinese had the lowest percentage of GGE among those with epilepsy (12.3%), as compared with Indian and Malay (25.3% and 21.3%, p<0.001). In addition, 32.1% of these Indian patients with GGE had positive family history, which is more than the Malay (26.4%) and Chinese (27.5%) ethnic groups. Consanguineous marriage was noted in 5 Indian families with positive family history (9.6%).

    CONCLUSION: There was ethnic variation in the prevalence of GGE, whereby the Malaysian Chinese had the lowest percentage of GGE as compared with Indian and Malay. A substantial proportion of GGE had positive family history among the three ethnics groups.

    Study site: neurology outpatient clinic, University of Malaya Medical Centre (UMMC)
  5. Fulltext Small interfering RNA-mediated silencing of nicotinamide phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) induce growth inhibition and apoptosis in human multiple myeloma cells: A preliminary study
    Bong IP, Ng CC, Fakiruddin SK, Lim MN, Zakaria Z
    Bosn J Basic Med Sci, 2016 Nov 10;16(4):268-275.
    PMID: 27754828 DOI: 10.17305/bjbms.2016.1568
    Multiple myeloma (MM) is a malignancy of B lymphocytes or plasma cells. Our array-based comparative genomic hybridization findings revealed chromosomal gains at 7q22.3 and 1q42.3, where nicotinamide (NAM) phosphoribosyltransferase (NAMPT) and lysosomal trafficking regulator (LYST) genes are localized, respectively. This led us to further study the functions of these genes in myeloma cells. NAMPT is a key enzyme involved in nicotinamide adenine dinucleotide salvage pathway, and it is frequently overexpressed in human cancers. In contrast, little is known about the function of LYST in cancer. The expression of LYST is shown to affect lysosomal size, granule size, and autophagy in human cells. In this study, the effects of small interfering RNA (siRNA)-mediated silencing of NAMPT and LYST on cell proliferation and apoptosis were evaluated in RPMI 8226 myeloma cells. Transfection efficiencies were determined by quantitative real time reverse transcriptase PCR. Cell proliferation was determined using MTT assay, while apoptosis was analyzed with flow cytometry using Annexin V-fluorescein isothiocyanate/propidium iodide assay. The NAMPT protein expression in siRNA-treated cells was estimated by enzyme-linked immunosorbent assay. Our results showed that NAMPT and LYST were successfully knockdown by siRNA transfection (p < 0.05). NAMPT or LYST gene silencing significantly inhibited cell proliferation and induced apoptosis in RPMI 8226 cells (p < 0.05). Silencing of NAMPT gene also decreased NAMPT protein levels (p < 0.01). Our study demonstrated that NAMPT and LYST play pivotal roles in the molecular pathogenesis of MM. This is the first report describing the possible functions of LYST in myelomagenesis and its potential role as a therapeutic target in MM.
  6. An Overview of Culinary and Medicinal Mushrooms in Neurodegeneration and Neurotrauma Research
    Wong KH, Ng CC, Kanagasabapathy G, Yow YY, Sabaratnam V
    Int J Med Mushrooms, 2017;19(3):191-202.
    PMID: 28605334 DOI: 10.1615/IntJMedMushrooms.v19.i3.10
    Culinary and medicinal mushrooms have been appreciated since prehistoric times as valuable resources for food and medicine. Edible mushrooms represent an untapped source of nutraceuticals and valuable palatable food. Long considered tonics, they are now treasured as functional foods that can improve human health and quality of life. Numerous studies have provided insights into the neuroprotective effects of edible mushrooms, which are attributed to their antioxidant, antineuroinflammatory, and cholinesterase inhibitory properties, and their ability to prevent neuronal death. Here we review the recent literature on the role of culinary and medicinal mushrooms in the management of neurodegenerative diseases and neurotrauma. We highlight some of the molecular mechanisms for how these alternative medicines provide health benefits that could help us to harness their neuroprotective effects.
  7. Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes
    Chan CK, Low JS, Lim KS, Low SK, Tan CT, Ng CC
    Neurol Sci, 2020 Mar;41(3):591-598.
    PMID: 31720899 DOI: 10.1007/s10072-019-04122-9
    INTRODUCTION: Genetic (idiopathic) generalized epilepsy (GGE) is a common form of epilepsy characterized by unknown aetiology and a presence of genetic component in its predisposition.

    METHODS: To understand the genetic factor in a family with GGE, we performed whole exome sequencing (WES) on a trio of a juvenile myoclonic epilepsy/febrile seizure (JME/FS) proband with JME/FS mother and healthy father. Sanger sequencing was carried out for validation of WES results and variant detection in other family members.

    RESULTS: Predictably damaging variant found in affected proband and mother but absent in healthy father in SCN1A gene was found to be associated with generalized epilepsy and febrile seizure. The novel non-synonymous substitution (c.5753C>T, p.S1918F) in SCN1A was found in all family members with GGE, of which 4/8 were JME subtypes, and/or febrile seizure, while 3 healthy family member controls did not have the mutation. This mutation was also absent in 41 GGE patients and 414 healthy Malaysian Chinese controls.

    CONCLUSION: The mutation is likely to affect interaction between the sodium channel and calmodulin and subsequently interrupt calmodulin-dependent modulation of the channel.

  8. Genetic polymorphisms of ATG16L1 and IRGM genes in Malaysian patients with Crohn's disease
    Kee BP, Ng JG, Ng CC, Hilmi I, Goh KL, Chua KH
    J Dig Dis, 2020 Jan;21(1):29-37.
    PMID: 31654602 DOI: 10.1111/1751-2980.12829
    OBJECTIVE: To investigate the association between genetic polymorphisms in ATG16L1 and IRGM genes and the development of Crohn's disease (CD) in Malaysian patients.

    METHODS: Altogether 335 participants were recruited, including 85 patients with CD and 250 unrelated healthy controls, and their informed consent was obtained. Genomic DNA was extracted via a conventional phenol-chloroform extraction method. Six single nucleotide polymorphisms (SNPs) in ATG16L1 and IRGM genes were genotyped using TaqMan SNP genotyping assays. Associations between SNP and CD were determined using Fisher's exact test, odds ratio, and 95% confidence interval. Statistical power and the Hardy-Weinberg equilibrium were also calculated.

    RESULTS: Two SNPs (rs2241880 and rs6754677) in the ATG16L1 gene were significantly associated with the onset of CD in the Malaysian population. The A allele and homozygous A/A genotype of the rs2241880 A/G polymorphism were protective against CD in the overall Malaysian and Malay population. The G allele and homozygous G/G genotype of the rs6754677 G/A polymorphism were protective in the Indian population, whereas the homozygous A/A genotype showed a risk of developing CD. The homozygous G/G genotype of IRGM rs11747270 was significantly present in the controls. However, this significance was not observed in a race-stratified analysis. All three ATG16L1 SNPs were associated with inflamed terminal ileum. IRGM rs4958847 and rs11747270 increased the risk of developing arthritis in patients with CD.

    CONCLUSION: We found a significant association between SNP, which are located in autophagy-related genes, and CD in a Malaysian population.

  9. Ultrasound-guided central venous vascular access-novel needle navigation technology compared with conventional method: A randomized study
    Chew SC, Beh ZY, Hakumat Rai VR, Jamaluddin MF, Ng CC, Chinna K, et al.
    J Vasc Access, 2020 Jan;21(1):26-32.
    PMID: 31148509 DOI: 10.1177/1129729819852057
    PURPOSE: Central venous catheter insertion is a common procedure in the intensive care setting. However, complications persist despite real-time ultrasound guidance. Recent innovation in needle navigation technology using guided positioning system enables the clinician to visualize the needle's real-time position and trajectory as it approaches the target. We hypothesized that the guided positioning system would improve performance time in central venous catheter insertion.

    METHODS: A prospective randomized study was conducted in a single-center adult intensive care unit. In total, 100 patients were randomized into two groups. These patients underwent internal jugular vein central venous catheter cannulation with ultrasound guidance (short-axis scan, out-of-plane needling approach) in which one group adopted conventional method, while the other group was aided with the guided positioning system. Outcomes were measured by procedural efficacy (success rate, number of attempts, time to successful cannulation), complications, level of operators' experience, and their satisfaction.

    RESULTS: All patients had successful cannulation on the first attempt except for one case in the conventional group. The median performance time for the guided positioning system method was longer (25.5 vs 15.5 s; p = 0.01). And 86% of the operators had more than 3-year experience in anesthesia. One post-insertion hematoma occurred in the conventional group. Only 88% of the operators using the guided positioning system method were satisfied compared to 100% in the conventional group.

    CONCLUSION: Ultrasound-guided central venous catheter insertion via internal jugular vein was a safe procedure in both conventional and guided positioning system methods. The guided positioning system did not confer additional benefit but was associated with slower performance time and lower satisfaction level among the experienced operators.

  10. Phytoassessment of Vetiver grass enhanced with EDTA soil amendment grown in single and mixed heavy metal-contaminted soil
    Ng CC, Boyce AN, Abas MR, Mahmood NZ, Han F
    Environ Monit Assess, 2019 Jun 14;191(7):434.
    PMID: 31201562 DOI: 10.1007/s10661-019-7573-2
    Over the years, ethylene-diamine-tetra-acetate (EDTA) has been widely used for many purposes. However, there are inadequate phytoassessment studies conducted using EDTA in Vetiver grass. Hence, this study evaluates the phytoassessment (growth performance, accumulation trends, and proficiency of metal uptake) of Vetiver grass, Vetiveria zizanioides (Linn.) Nash in both single and mixed heavy metal (Cd, Pb, Cu, and Zn)-disodium EDTA-enhanced contaminated soil. The plant growth, metal accumulation, and overall efficiency of metal uptake by different plant parts (lower root, upper root, lower tiller, and upper tiller) were thoroughly examined. The relative growth performance, metal tolerance, and phytoassessment of heavy metal in roots and tillers of Vetiver grass were examined. Metals in plants were measured using the flame atomic absorption spectrometry (F-AAS) after acid digestion. The root-tiller (R/T) ratio, biological concentration factor (BCF), biological accumulation coefficient (BAC), tolerance index (TI), translocation factor (TF), and metal uptake efficacy were used to estimate the potential of metal accumulation and translocation in Vetiver grass. All accumulation of heavy metals were significantly higher (p < 0.05) in both lower and upper roots and tillers of Vetiver grass for Cd + Pb + Cu + Zn + EDTA treatments as compared with the control. The single Zn + EDTA treatment accumulated the highest overall total amount of Zn (8068 ± 407 mg/kg) while the highest accumulation for Cu (1977 ± 293 mg/kg) and Pb (1096 ± 75 mg/kg) were recorded in the mixed Cd + Pb + Cu + Zn + EDTA treatment, respectively. Generally, the overall heavy metal accumulation trends of Vetiver grass were in the order of Zn > Cu > Pb > Cd for all treatments. Furthermore, both upper roots and tillers of Vetiver grass recorded high tendency of accumulation for appreciably greater amounts of all heavy metals, regardless of single and/or mixed metal treatments. Thus, Vetiver grass can be recommended as a potential phytoextractor for all types of heavy metals, whereby its tillers will act as the sink for heavy metal accumulation in the presence of EDTA for all treatments.
  11. Fulltext Using DNA Barcodes to Aid the Identification of Larval Fishes in Tropical Estuarine Waters (Malacca Straits, Malaysia)
    Chu C, Loh KH, Ng CC, Ooi AL, Konishi Y, Huang SP, et al.
    Zool Stud, 2019;58:e30.
    PMID: 31966331 DOI: 10.6620/ZS.2019.58-30
    Larval descriptions of tropical marine and coastal fishes are very few, and this taxonomic problem is further exacerbated by the high diversity of fish species in these waters. Nonetheless, accurate larval identification in ecological and early life history studies of larval fishes is crucial for fishery management and habitat protection. The present study aimed to evaluate the usefulness of DNA barcodes to support larval fish identification since conventional dichotomous keys based on morphological traits are not efficient due to the lack of larval traits and the rapid morphological changes during ontogeny. Our molecular analysis uncovered a total of 48 taxa (21 families) from the larval samples collected from the Klang Strait waters encompassing both spawning and nursery grounds of marine and estuarine fishes. Thirty-two (67%) of the larval taxa were identified at the species level, two taxa (4%) at the genus level, and 14 taxa (29%) at family level. The relatively low rate of species-level identification is not necessarily due to the DNA barcoding method per se, but a general lack of reference sequences for speciose and non- commercial fish families such as Gobiidae, Blenniidae, and Callionymidae. Larval morphology remains important in species diagnoses when molecular matches are ambiguous. A lower ethanol percentage (50%) for larva preservation is also useful to keep the body of larvae intact for morphological identification, and to preserve DNA for subsequent molecular analyses. The 10% Chelex resin used to extract DNA is also cost- effective for long term monitoring of larval fishes. Hence, the DNA barcoding method is an effective and easy way to aid the identification of estuarine larval fishes at the species level.
  12. Prostaglandin-endoperoxide synthase (PTGS2) and Defensin beta 1 (DEFB1) gene polymorphisms are not associated with periodontitis in Malays
    Jagender Singh JK, Vaithilingam RD, Ng CC, Baharuddin NA, Hasnur Safii S, Rahman MT
    Malays J Pathol, 2021 Dec;43(3):425-434.
    PMID: 34958064
    INTRODUCTION: In line with the association of prostaglandin-endoperoxide synthase 2 (PTGS2) and defensin beta 1 (DEFB1) single nucleotide polymorphisms (SNPs) with periodontitis among the Chinese and European populations, the current study was aimed to assess the same association among the Malays in Malaysia.

    METHODS: Blood samples of individuals with periodontitis (PD) (n=72) and periodontally healthy (PH) (n=62) donors were obtained from Malaysian Periodontal Database and Biobanking system (MPDBS). Genomic DNA samples were analyzed for three PTGS2 SNPs (rs5275, rs20417, rs689466,) and one DEFB1 SNP (rs1047031) using Taqman SNP genotyping assays. Notably, rs20417 and rs689466 were located in the promoter region while rs5275 and rs1047031 were located in the 3' untranslated region of the transcript. Association between the SNPs and PD were then analyzed using genotypic association analysis (additive, dominant and recessive models).

    RESULTS: The allelic frequency for the rs689466-G was higher in PD group (35.2%) compared that in PH group (29.0%). However, the association of rs689466-G and other SNPs with PD was not statistically significant (at 95% CI). No associations were observed for genotypic associations between the PTGS2 and DEFB1 SNPs with PD susceptibility.

    CONCLUSIONS: PTGS2 (rs5275, rs20417, and rs689466) and DEFB1 (rs1047031) polymorphism was not associated with PD in Malays, unlike the Chinese, Taiwanese & European population. This suggests that other causal variants might be involved in the development and progression of PD among Malays.

  13. Determinants of low bone mineral density in children with epilepsy
    Fong CY, Kong AN, Noordin M, Poh BK, Ong LC, Ng CC
    Eur. J. Paediatr. Neurol., 2018 Jan;22(1):155-163.
    PMID: 29122496 DOI: 10.1016/j.ejpn.2017.10.007
    INTRODUCTION: Children with epilepsy on long-term antiepileptic drugs (AEDs) are at risk of low bone mineral density (BMD). The aims of our study were to evaluate the prevalence and determinants of low BMD among Malaysian children with epilepsy.

    METHOD: Cross-sectional study of ambulant children with epilepsy on long-term AEDs for >1 year seen in a tertiary hospital in Malaysia from 2014 to 2015. Detailed assessment of anthropometric measurements; environmental lifestyle risk factors; serum vitamin D, calcium and parathyroid hormone levels; genotyping of single nucleotide polymorphisms of genes in vitamin D and calcium metabolism; and lumbar spine BMD were obtained. Low BMD was defined as BMD Z-score ≤ -2.0 SD.

    RESULTS: Eighty-seven children with mean age of 11.9 years (56 males) participated in the study. The prevalence of low lumbar BMD was 21.8% (19 patients). Multivariate logistic regression analysis identified polytherapy >2 AEDs (OR: 7.86; 95% CI 1.03-59.96), small frame size with wrist breadth of <15th centile (OR 14.73; 95% CI 2.21-98.40), and body mass index Z-score 2 AEDs, underweight or with small frame size as they are at higher risk of having low BMD.

  14. Inclusion bodies of recombinant Epstein-Barr virus capsid antigen p18 as potential immobilized antigens in enzyme immunoassays for detection of nasopharyngeal carcinoma
    Lim CS, Goh SL, Kariapper L, Krishnan G, Lim YY, Ng CC
    Clin Chim Acta, 2015 Aug 25;448:206-10.
    PMID: 26164385 DOI: 10.1016/j.cca.2015.07.008
    Development of indirect enzyme-linked immunosorbent assays (ELISAs) often utilizes synthetic peptides or recombinant proteins from Escherichia coli as immobilized antigens. Because inclusion bodies (IBs) formed during recombinant protein expression in E. coli are commonly thought as misfolded aggregates, only refolded proteins from IBs are used to develop new or in-house diagnostic assays. However, the promising utilities of IBs as nanomaterials and immobilized enzymes as shown in recent studies have led us to explore the potential use of IBs of recombinant Epstein-Barr virus viral capsid antigen p18 (VCA p18) as immobilized antigens in ELISAs for serologic detection of nasopharyngeal carcinoma (NPC).
  15. Genetic interaction between GABRA1 and ERBB4 variants in the pathogenesis of genetic generalized epilepsy
    Chan CK, Lim KS, Low SK, Tan CT, Ng CC
    Epilepsy Res, 2023 Jan;189:107070.
    PMID: 36584483 DOI: 10.1016/j.eplepsyres.2022.107070
    Epilepsy is a complex neurological disease that can be caused by both genetic and environmental factors. Many studies have been conducted to investigate the genetic risk variants and molecular mechanisms of epilepsy. Disruption of excitation-inhibition balance (E/I balance) is one of the widely accepted disease mechanisms of epilepsy. The maintenance of E/I balance is an intricate process that is governed by multiple proteins. Using whole exome sequencing (WES), we identified a novel GABRA1 c.448G>A (p.E150K) variant and ERBB4 c.1972A>T (p.I658F, rs190654033) variant in a Malaysian Chinese family with genetic generalized epilepsy (GGE). The GGE may be triggered by dysregulation of E/I balance mechanism. Segregation of the variants in the family was verified by Sanger sequencing. All family members with GGE inherited both variants. However, family members who carried only one of the variants did not show any symptoms of GGE. Both the GABRA1 and ERBB4 variants were predicted damaging by MutationTaster and CADD, and protein structure analysis showed that the variants had resulted in the formation of additional hydrogen bonds in the mutant proteins. GABRA1 variant could reduce the efficiency of GABAA receptors, and constitutively active ERBB4 receptors caused by the ERBB4 variant promote internalization of GABAA receptors. The interaction between the two variants may cause a greater disruption in E/I balance, which is more likely to induce a seizure. Nevertheless, this disease model was derived from a single small family, further studies are still needed to confirm the verifiability of the purported disease model.
  16. Tranexamic Acid in Pediatric Scoliosis Surgery: A Prospective Randomized Trial Comparing High-dose and Low-dose Tranexamic Acid in Adolescent Idiopathic Scoliosis Undergoing Posterior Spinal Fusion Surgery
    Hasan MS, Yunus SN, Ng CC, Chan CYW, Chiu CK, Kwan MK
    Spine (Phila Pa 1976), 2021 Nov 15;46(22):E1170-E1177.
    PMID: 33882541 DOI: 10.1097/BRS.0000000000004076
    STUDY DESIGN: Prospective randomized double-blinded trial.

    OBJECTIVE: The objective of this study is to determine the efficacy of high-dose versus low-dose tranexamic acid (TXA) in adolescent idiopathic scoliosis (AIS) corrective surgery.

    SUMMARY OF BACKGROUND DATA: Corrective surgery for AIS is associated with significant blood loss. Evidence on the optimum TXA dose to reduce bleeding in pediatric population is scarce.

    METHODS: A total of 166 AIS patients aged between 10 and 21 years, of American Society of Anesthesiologists (ASA) physical status I and II, preoperative hemoglobin >10 g/dL, platelet count >150,000 cells/L and Cobb angle of >45° scheduled for elective single-stage posterior spinal fusion (PSF) surgery by two attending surgeons were included between March 2017 and November 2018. Patients were randomized into Group A (High Dose, 30 mg/kg TXA loading dose followed by 10 mg/kg/h infusion) and Group B (Low Dose, 10 mg/kg TXA loading dose followed by 1 mg/kg/h infusion). The primary outcome was total surgical blood loss between both groups. Secondary outcomes were transfusion requirement, perioperative changes in hemoglobin and coagulation profiles, adverse events, and factors that influence total blood loss.

    RESULTS: The mean total surgical blood loss between the two groups was not significant (Group A: 928.8 ± 406.1 mL [range: 348-1857 mL]; Group B: 918.1 ± 406.2 mL [range: 271-2000 mL], P = 0.865). The median duration of surgery was 120 minutes. One patient in each group received allogenic blood transfusion during the perioperative period. There were no significant changes in hemoglobin and coagulation profile at pre-operation, post-operation 0 hour and 48 hours. Sex, number of vertebral levels fused, and duration of surgery were independently associated with total surgical blood loss. No adverse events were observed perioperatively.

    CONCLUSION: Low-dose TXA was as efficacious as high-dose TXA in reducing blood loss and allogenic blood transfusion for AIS patients undergoing PSF surgery.Level of Evidence: 1.

  17. Fulltext A Developing Nation's Experience in Using Simulation-Based Training as a Preparation Tool for the Coronavirus Disease 2019 Outbreak
    Loh PS, Chaw SH, Shariffuddin II, Ng CC, Yim CC, Hashim NHM
    Anesth Analg, 2021 Jan;132(1):15-24.
    PMID: 33002931 DOI: 10.1213/ANE.0000000000005264
    BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic affected and overwhelmed many health care systems around the world at an unprecedented speed and magnitude with devastating effects. In developing nations, smaller hospitals were unprepared to face this outbreak nor had strategies in place to do so at the beginning. Here, we describe the preparation in an anesthetic department using simulation-based training over 2 weeks, as the number of cases rose rapidly.

    METHODS: Three areas of priority were identified as follows: staff safety, patient movement, and possible clinical scenarios based on simulation principles in health care education. Staff was rostered and rotated through stations for rapid-cycle deliberate practice to learn donning and doffing of personal protective equipment (PPE) and powered air-purifying respirator (PAPR). For difficult airway management, Peyton's 4 steps for skills training and Harden's Three Circle model formed the structure in teaching the core skills. Several clinical scenarios used system probing to elicit inadequacies followed by formal debriefing to facilitate reflection. Finally, evaluation was both immediate and delayed with an online survey after 1 month to examine 4 levels of reaction, learning, behavior, and impact based on the Kirkpatrick Model. Frequency and thematic analysis were then conducted on the quantitative and qualitative data, respectively.

    RESULTS: A total of 15 of 16 (93%) consultants, 16 (100%) specialists, and 81 (100%) medical officers in the department completed training within 2 consecutive weeks. Reaction and part of the learning were relayed immediately to trainers during training. In total, 42 (39%) trained staff responded to the survey. All were satisfied and agreed on the relevance of training. A total of 41 respondents (98%; 95% confidence interval [CI], 87-99) answered 16 of 20 questions correctly on identifying aerosol-generating procedures (AGP), indications for PPE, planning and preparation for airway management to achieve adequate learning. About 43% (95% CI, 27-59) and 52% (95% CI, 36-68) recalled donning and doffing steps correctly. A total of 92 responses from 33 respondents were analyzed in the thematic analysis. All respondents reported at least 1 behavioral change in intended outcomes for hand hygiene practice (20%), appropriate use of PPE (27%), and airway management (10%). The emerging outcomes were vigilance, physical distancing, planning, and team communication. Finally, the impact of training led to the establishment of institutional guidelines followed by all personnel.

    CONCLUSIONS: Simulation-based training was a useful preparation tool for small institutions with limited time, resources, and manpower in developing nations. These recommendations represent the training experience to address issues of "when" and "how" to initiate urgent "medical education" during an outbreak.

  18. Association of HLA-B*15:13 and HLA-B*15:02 with phenytoin-induced severe cutaneous adverse reactions in a Malay population
    Chang CC, Ng CC, Too CL, Choon SE, Lee CK, Chung WH, et al.
    Pharmacogenomics J, 2017 03;17(2):170-173.
    PMID: 26927288 DOI: 10.1038/tpj.2016.10
    Phenytoin (PHT) is a common cause of severe cutaneous adverse reactions (SCARs), including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS). Although HLA-B*15:02 is associated with PHT-induced SJS/TEN (PHT-SJS/TEN) in Han Chinese and Thais, the genetic basis for susceptibility to PHT-induced SCARs (PHT-SCAR) in other populations remains unclear. We performed a case-control association study by genotyping the human leukocyte antigen (HLA)-B alleles of 16 Malay PHT-SCAR patients (13 SJS/TEN and 3 DRESS), 32 PHT-tolerant controls and 300 healthy ethnicity-matched controls. A novel genetic biomarker, HLA-B*15:13, showed significant association with PHT-SJS/TEN (53.8%, 7/13 cases) (odds ratio (OR) 11.28, P=0.003) and PHT-DRESS (100%, 3/3 cases) (OR 59.00, P=0.003) when compared with PHT-tolerant controls (9.4%, 3/32 controls). We also confirmed HLA-B*15:02 association with PHT-SJS/TEN (61.5%, 8/13 cases vs 21.9%, 7/32 controls; OR 5.71, P=0.016) when compared with PHT-tolerant controls. These alleles may serve as markers to predict PHT-SCAR in Malays.
  19. Analysis of interleukin-10 promoter single nucleotide polymorphisms and risk of non-Hodgkin lymphoma in a Malaysian population
    Lim YY, Chin YM, Tai MC, Fani S, Chang KM, Ong TC, et al.
    Leuk Lymphoma, 2015 Jan;56(1):163-8.
    PMID: 24684230 DOI: 10.3109/10428194.2014.907895
    We evaluated the association of two IL10 single nucleotide polymorphisms (SNPs) (rs1800896 and rs1800871) with non-Hodgkin lymphoma (NHL) risk in the three major races of the Malaysian population (Malay, Chinese and Indian; 317 cases and 330 controls). Our initial screening demonstrated that rs1800871 but not rs1800896 was significantly associated with increased NHL risk in Malays (pMalay-Rec = 0.007) and Chinese only (pChinese-Rec = 0.039). Subsequent combined analysis of the Malay and Chinese revealed significant association of rs1800871 with all (ALL) NHL subtypes (pMeta-ALL-NHL-Rec = 0.001), ALL B-cell subtypes (pMeta-ALL-B-cell-Rec = 0.003), diffuse large B-cell lymphoma (DLBCL) subtype (pMeta-DLBCL-Rec = 0.002) and ALL T-cell subtypes (pMeta-ALL-T-cell-Rec = 0.031). SNP rs1800896 showed increased risk only in follicular lymphoma (FL) (pMeta-FL-Dom = 0.0004). We also detected a male-specific association of rs1800871 with increased NHL risk (pMeta-Male-ALL-NHL-Rec = 0.006) in the combined analysis. To our knowledge, this is the first report on the association of IL10 promoter SNPs with NHL susceptibility in the three major races of Malaysia.
  20. Association of common genetic variants with vitamin D status in Malaysian children with epilepsy
    Kong AN, Fong CY, Ng CC, Mohamed AR, Khoo TB, Ng RL, et al.
    Seizure, 2020 Jul;79:103-111.
    PMID: 32464532 DOI: 10.1016/j.seizure.2020.05.009
    PURPOSE: Children with epilepsy (CWE) are at risk of vitamin D deficiency. Single nucleotide polymorphisms (SNPs) affecting the vitamin D pathway are potentially important risk factors for serum 25-hydroxyvitamin D [25(OH)D] concentration. The aims of our study were to evaluate the association of vitamin d-related SNPs to serum 25(OH)D concentrations in Malaysian CWE.

    METHODS: Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children.

    RESULTS: 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P < 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR: 0.16; 95% CI: 0.06-0.49; P = 0.001) and this association was not found in the healthy children group.

    CONCLUSIONS: Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.

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