Displaying publications 21 - 35 of 35 in total

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  1. Fong CY, Khine MM, Peter AB, Lim WK, Rozalli FI, Rahmat K
    J Clin Neurosci, 2017 Feb;36:73-75.
    PMID: 27887978 DOI: 10.1016/j.jocn.2016.10.050
    A 14-year-old girl presented with encephalopathy, delirium and ophthalmoplegia following a 3day history of high-grade fever. Brain MRI on day 6 of illness showed diffusion restricted ovoid lesion in the splenium of corpus callosum. Dengue virus encephalitis was diagnosed with positive PCR for dengue virus type-2 in both serum and cerebrospinal fluid. She made a complete recovery from day 10 of illness. Repeat brain MRI on day 12 of illness showed resolution of the splenial lesion. Serial diffusion tensor imaging (DTI) showed normal fractional anisotropy values on resolution of splenial lesion indicating that MERS was likely due to transient interstitial oedema with preservation of white matter tracts. This is the first reported case of MERS following dengue virus infection. It highlights the usefulness of performing serial DTI in understanding the underlying pathogenesis of MERS. Our case report widens the neurological manifestations associated with dengue infection and reiterates that patients with MERS should be managed supportively as the splenial white matter tracts are reversibly involved in MERS.
  2. Fong CY, Hong SY, Ong LC, Lim WK, Lua PL
    Epilepsy Behav, 2019 May;94:52-58.
    PMID: 30884408 DOI: 10.1016/j.yebeh.2019.02.008
    BACKGROUND: An information technology (IT)-based epilepsy educational program, the Interactive Animated Epilepsy Education Programme (IAEEP), can potentially help improve awareness, knowledge, and attitude (AKA) of parents of children with epilepsy (CWE) enabling CWE to lead a normal life. Our study aimed to assess the following: i) baseline level of epilepsy AKA of Malaysian parents of CWE and explore potential characteristics associated with low levels of AKA; ii) effectiveness of the IAEEP in improving parental AKA, and whether these effects remained stable over time; and iii) effects of the IAEEP on parental mental state and perception of their child's quality of life.

    METHODS: This prospective study includes parents of CWE aged 8-18 years old with no comorbidities. Epilepsy education was delivered using the IAEEP. Parents completed an AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), and 4-6 months (TP3) after the provision of IAEEP. Parent proxy report of Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL)-25 questionnaire and Depression, Anxiety, and Stress Scale (DASS)-21 questionnaire was completed at TP1 and TP3.

    RESULTS: A total of 78 parents participated in the study. At baseline (TP1), parental responses were rated as "moderate" for awareness domain, "high" for knowledge domain, "very positive" for attitude domain, and "good" for total AKA score domain. No epilepsy or parental characteristics were associated with the low baseline parental AKA levels. After IAEEP intervention, there was a significant increase in all AKA subdomain scores. Post-IAEEP, the AKA of parents were rated as "very high" for awareness domain, "very high" for knowledge domain, "very positive" for attitude domain, and "excellent" for total AKA domain at both TP2 and TP3. Parent proxy CHEQOL-25 report showed significant increments in interpersonal/social and secrecy scale scores between TP1 and TP3. There were no significant differences in the DASS-21 scores between TP1 and TP3.

    CONCLUSION: The IAEEP is an effective epilepsy educational tool to increase the levels of AKA among parents of CWE. Following the use of the IAEEP, parents of CWE also reported an improvement of their child's quality of life in the interpersonal/social and epilepsy secrecy CHEQOL-25 domains. There was no impact on parental mental health following exposure to the IAEEP.

  3. Fong CY, Saw MT, Li L, Lim WK, Ong LC, Gan CS
    Brain Dev, 2021 Apr;43(4):538-547.
    PMID: 33358123 DOI: 10.1016/j.braindev.2020.12.003
    OBJECTIVE: Describe the outcome of a Malaysian cohort of children with acute necrotising encephalopathy (ANE).

    METHOD: Retrospective study of children with ANE seen at University of Malaya Medical Centre from 2014 to 2019. All clinical details including ANE-severity score (ANE-SS), immunomodulation treatment and neurodevelopmental long-term outcome were collected.

    RESULTS: Thirteen patients had ANE and brainstem death occurred in 5. In 10 patients (77%) viruses were isolated contributing to ANE: 8 influenza virus, 1 acute dengue infection, and 1 acute varicella zoster infection. The ANE-SS ranged 2-7: 9 were high risk and 4 were medium risk. Among the 8 survivors; 1 was lost to follow-up. Follow-up duration was 1-6 years (median 2.2). At follow-up among the 4 high-risk ANE-SS: 2 who were in a vegetative state, 1 remained unchanged and 1 improved to severe disability; the other 2 with severe disability improved to moderate and mild disability respectively. At follow-up all 3 medium-risk ANE-SS improved: 2 with severe disability improved to moderate and mild disability respectively, while 1 in a vegetative state improved to severe disability. Early treatment with immunomodulation did not affect outcome.

    CONCLUSION: Our ANE series reiterates that ANE is a serious cause of encephalopathy with mortality of 38.5%. All survivors were in a vegetative state or had severe disability at discharge. Most of the survivors made a degree of recovery but good recovery was seen in 2. Follow-up of at least 12 months is recommended for accurate prognostication. Dengue virus infection needs to be considered in dengue endemic areas.

  4. Fong CY, Lim WK, Kong AN, Lua PL, Ong LC
    Epilepsy Behav, 2017 10;75:6-12.
    PMID: 28806633 DOI: 10.1016/j.yebeh.2017.06.037
    Sudden unexpected death in epilepsy (SUDEP) is an important cause of mortality in epilepsy. To date, there is only one published UK study evaluating information provision of SUDEP among parents of children with epilepsy (CWE), and there are no studies published from Asia. Although SUDEP information provision is recommended among parents of CWE, it is uncertain if these recommendations are applicable to Asian countries due to the different cultural attitude towards epilepsy. Our prospective cohort study consisted of multiethnic parents of children with epilepsy (CWE) seen in a tertiary hospital in Malaysia. Information on SUDEP was delivered to parents using an epilepsy educational software program. Participants completed a set of standardized questionnaire and Depression Anxiety Stress Scales-Short Form (DASS-21) immediately after and retested 3-6months after the SUDEP information provision. A total of 127 parents (84 mothers) participated in the study. The CWE consisted of 3 ethnic groups (38% Malay, 30% Chinese, 32% Indian) with a mean age of 9.6years. Majority (70.9%) felt positive after SUDEP information provision, 90.6% wanted SUDEP discussion for themselves with 70.1% wanted SUDEP discussion with their child, and a lower proportion (58.3%) would discuss SUDEP with their child. None of the participants reported increased symptoms of depression, stress or anxiety attributed to SUDEP information provision. Most parents took steps to reduce SUDEP risk, and most parents did not report an impact on their own functioning. However, there was an increase in parental report over time of impact on their child's functioning following SUDEP information (P<0.05). In conclusion, most Malaysian parents of CWE wanted SUDEP information. Following SUDEP information disclosure, majority did not report negative emotions; however, an increase in parents over time reported an impact on their child. Our findings reiterate that provision of SUDEP information should form part of care of CWE and parents should receive ongoing support as they undergo a period of parenting adjustment when dealing with the information provided.
  5. Lizazman MA, Jong VYM, Chua P, Lim WK, Karunakaran T
    Nat Prod Res, 2023 Jun;37(12):2043-2048.
    PMID: 35997666 DOI: 10.1080/14786419.2022.2116021
    Previous phytochemical investigations reported that Calophyllum spp have biosynthesized a wide range of bioactive phenolics such as xanthones and coumarins. The phytochemical study conducted on the stem bark of C. canum has led to the isolation of eight trioxygenated xanthones namely: 5-methoxytrapezifolixanthone (1), 5-methoxyananixanthone (2), caloxanthone C (3), 1,5-dihydroxy-3-methoxy-4-isoprenylxanthone (4), 6-deoxyisojacareubin (5), euxanthone (6), trapezifolixanthone (7), ananixanthone (8), together with three common triterpenoids, β-sitosterol (9), friedelin (10), and stigmasterol (11). Furthermore, xanthones 1 and 2 were isolated for the first time as naturally occurring xanthones from the plant extract. The structures of these compounds were identified and elucidated using advanced spectroscopic techniques such as 1 D & 2 D NMR, MS, and FTIR. The neuroprotective property of selected compounds was tested through in vitro stroke model. Among all tested compounds, 1 µm of compounds 8, 9, and 10 showed significant neuroprotective activity via reduction of apoptosis by ∼ 50%.
  6. Rajiah K, Lim WK, Madeline Teoh PL, Binti Mas'od MA, Lim WY, Poh Chou LL, et al.
    Int J Clin Pract, 2021 Sep;75(9):e14096.
    PMID: 33619786 DOI: 10.1111/ijcp.14096
    BACKGROUND: Community pharmacists play a significant part in providing oral healthcare advice as there are significant connections between oral healthcare and body system healthcare.

    OBJECTIVE: To systematically review the literature regarding the knowledge, attitudes and practice of community pharmacists in managing oral healthcare problems.

    METHODS: A systematic review was conducted through Scopus, PubMed and Google Scholar databases. Studies regarding knowledge, attitudes and practice of management of dental care by community pharmacists between 1990 and 2019 were included.

    RESULTS: Forest plot was performed to access knowledge, attitudes and practice of community pharmacist on oral healthcare. The results showed there were 44% of community pharmacists have a lack of knowledge on oral healthcare to provide an appropriate recommendation to patients with dental problems. Eighty-eight per cent of community pharmacists were willing to improve their knowledge of oral healthcare. There were 86% of them recognised that their role was significant in oral health. However, there were 59% of community pharmacists who had poor attitude in providing oral health information.

    CONCLUSIONS: Community pharmacists were lacking knowledge on oral health mainly because of paucity in providing appropriate training courses. This has led to poor practices towards oral healthcare as they were unable to provide suitable products recommendations to the patients. This has led the community pharmacists into lack of attitudes in providing oral health information. However, most of the community pharmacists were conscious of their role in the oral healthcare system and were willing to improve their knowledge of oral healthcare.

  7. Wong MNL, Tang IP, Chor YK, Lau KS, John AR, Hii KC, et al.
    BMC Pediatr, 2020 09 24;20(1):448.
    PMID: 32972390 DOI: 10.1186/s12887-020-02348-7
    BACKGROUND: Haemoptysis is an uncommon presenting symptom in children and is usually caused by acute lower respiratory tract infection or foreign body aspiration. We report a rare case of right unilateral pulmonary vein atresia (PVA) as the underlying aetiology of recurrent haemoptysis in a child.

    CASE PRESENTATION: A 4 years old girl presented with history of recurrent haemoptysis. Bronchoscopic evaluation excluded a foreign body aspiration but revealed right bronchial mucosal hyperaemia and varices. Diagnosis of right unilateral PVA was suspected on transthoracic echocardiography which demonstrated hypoplastic right pulmonary artery and non-visualization of right pulmonary veins. Final diagnosis was confirmed on cardiac CT angiography. A conservative treatment approach was opted with consideration for pneumonectomy in future when she is older.

    CONCLUSION: Rarer causes should be considered when investigating for recurrent haemoptysis in children. Bronchoscopy and cardiac imaging are useful tools to establish the diagnosis of unilateral PVA in our case.

  8. Fong CY, Low P, Ng KH, Heng HS, Chong ASL, Ong LC, et al.
    Epilepsy Behav, 2023 Dec;149:109536.
    PMID: 38008017 DOI: 10.1016/j.yebeh.2023.109536
    BACKGROUND: A computer game-based epilepsy educational programme (Epigame) can potentially improve the awareness, knowledge and attitude (AKA) and quality of life (QOL) of children with epilepsy (CWE). Our study among Malaysian CWE aimed to assess the: i) baseline level of epilepsy AKA and potential characteristics associated with poor levels of AKA, ii) effectiveness of Epigame in improving AKA and QOL of CWE.

    METHOD: Prospective cohort study on CWE age 7-18 years old with no comorbidities. Epilepsy education was delivered using Epigame. CWE completed AKA questionnaire before (time point 1 [TP1]), immediately after (TP2), 3 months (TP3) after provision of Epigame. Child self-report Health-Related Quality of Life Measurement for Children with Epilepsy (CHEQOL-25) questionnaire was completed at TP1 and TP3.

    RESULTS: Total of 106 CWE participated in this study (mean age of 13.3 years). Baseline (TP1) AKA was rated "very low to moderate" for awareness domain in 95.3 %, "very low to moderate" for knowledge domain in 67 %, "negative to indifferent" for attitude domain in 54.7 %, and "very poor to moderate' for total AKA score domain in 84 %. "Positive to very positive" for child attitude domain was significantly associated with parents with "positive to very positive" for attitude domain (OR 10.6, 95 % CI 3.23-34.66). "Good to excellent" for total child AKA domain was significantly associated with parents with "Good to excellent" for total AKA domain (OR 5.2, 95 % CI 1.16-15.02) and with 

  9. Shafiee MN, Lim WK, Poh Shwen Shi C, Mohamed Yasin IA, Azemi AF, Zakaria ML, et al.
    Horm Mol Biol Clin Investig, 2021 Aug 09;42(4):403-410.
    PMID: 34364315 DOI: 10.1515/hmbci-2021-0017
    OBJECTIVES: To determine the significance of tumour PTEN protein expression in endometrioid endometrial carcinoma (EEC) and it is correlation with tumour characteristics.

    METHODS: A total of 30 eligible archived paraffin-embedded tissue blocks from 61 EEC cases (January 2015-December 2017) were retrieved from the Histopathology Laboratory in Universiti Kebangsaan Malaysia Medical Centre (UKMMC) following institutional ethic approval. For PTEN protein detection, immunohistochemistry (IHC) staining was performed and the data was correlated with clinicopathologic parameters.

    RESULTS: Fourteen samples (46.7%) showed positive PTEN protein expression, while 16 (53.3%) were negative. The mean age was 62.00 ± 9.51 years old, while the mean Body Mass Index (BMI) was 27.28 ± 7.16 kg/m2. There was no significant difference between age (p=0.27, 95% CI: -10.98 to 3.21) and BMI (p=0.67, 95% CI: -4.30 to 6.58) with PTEN protein expression. There were significant correlation between PTEN protein expression with myometrial invasion (p=0.010), but not with lymphovascular space invasion (p=0.743), grade (p=0.532), stage (p=0.733) and CA-125 level (p=0.47). The higher stage correlates with the presence of LVSI (p=0.002). PTEN positive associated with longer disease-free-interval (p=0.025), but not improving the overall survival (p=0.38).

    CONCLUSIONS: Positive PTEN protein expression correlates with less myometrial invasion.

  10. Teh BT, Lim K, Yong CH, Ng CCY, Rao SR, Rajasegaran V, et al.
    Nat Genet, 2017 Nov;49(11):1633-1641.
    PMID: 28991254 DOI: 10.1038/ng.3972
    Durian (Durio zibethinus) is a Southeast Asian tropical plant known for its hefty, spine-covered fruit and sulfury and onion-like odor. Here we present a draft genome assembly of D. zibethinus, representing the third plant genus in the Malvales order and first in the Helicteroideae subfamily to be sequenced. Single-molecule sequencing and chromosome contact maps enabled assembly of the highly heterozygous durian genome at chromosome-scale resolution. Transcriptomic analysis showed upregulation of sulfur-, ethylene-, and lipid-related pathways in durian fruits. We observed paleopolyploidization events shared by durian and cotton and durian-specific gene expansions in MGL (methionine γ-lyase), associated with production of volatile sulfur compounds (VSCs). MGL and the ethylene-related gene ACS (aminocyclopropane-1-carboxylic acid synthase) were upregulated in fruits concomitantly with their downstream metabolites (VSCs and ethylene), suggesting a potential association between ethylene biosynthesis and methionine regeneration via the Yang cycle. The durian genome provides a resource for tropical fruit biology and agronomy.
  11. Lim SY, Dy Closas AMF, Tan AH, Lim JL, Tan YJ, Vijayanathan Y, et al.
    Parkinsonism Relat Disord, 2023 Mar;108:105296.
    PMID: 36682278 DOI: 10.1016/j.parkreldis.2023.105296
    BACKGROUND: Progressive supranuclear palsy (PSP) is a rare, disabling, neurodegenerative disease, with few studies done in Asian populations.

    METHODS: We prospectively characterized the clinical features and disease burden in a consecutively-recruited multi-ethnic Asian PSP cohort. Patients were extensively phenotyped using the Movement Disorder Society (MDS-PSP) clinical diagnostic criteria and the PSP-Clinical Deficits Scale (PSP-CDS). Caregiver burden was measured using the modified Zarit Burden Interview (ZBI). Investigations (neuroimaging and genetic tests) were reviewed.

    RESULTS: There were 104 patients (64.4% male; 67.3% Chinese, 21.2% Indians, 9.6% Malays), consisting of 48.1% Richardson syndrome (PSP-RS), 37.5% parkinsonian phenotype (PSP-P), and 10.6% progressive gait freezing phenotype (PSP-PGF). Mean age at motor onset was 66.3 ± 7.7 years, with no significant differences between the PSP phenotypes. Interestingly, REM-sleep behaviour disorder (RBD) symptoms and visual hallucinations (considered rare in PSP) were reported in 23.5% and 22.8% of patients, respectively, and a family history of possible neurodegenerative or movement disorder in 20.4%. PSP-CDS scores were highest (worst) in PSP-RS; and correlated moderately with disease duration (rs = 0.45, P 

  12. Ng ASL, Tan AH, Tan YJ, Lim JL, Lian MM, Dy Closas AM, et al.
    Mov Disord, 2024 Aug 16.
    PMID: 39149795 DOI: 10.1002/mds.29932
    BACKGROUND: Progressive supranuclear palsy (PSP) is largely a sporadic disease with few reported familial cases. Genome-wide association studies (GWAS) in sporadic PSP in Caucasian populations have identified MAPT as the most commonly associated genetic risk locus with the strongest effect size. At present there are limited data on genetic factors associated with PSP in Asian populations.

    OBJECTIVES: Our goal was to investigate the genetic factors associated with PSP in Southeast Asian PSP patients.

    METHODS: Next-generation sequencing (whole-exome, whole-genome and targeted sequencing) was performed in two Asian cohorts, comprising 177 PSP patients.

    RESULTS: We identified 17 pathogenic or likely pathogenic variants in 16 PSP patients (9%), eight of which were novel. The most common relevant genetic variants identified were in MAPT, GBA1, OPTN, SYNJ1, and SQSTM1. Other variants detected were in TBK1, PRNP, and ABCA7-genes that have been implicated in other neurodegenerative diseases. Eighteen patients had a positive family history, of whom two carried pathogenic MAPT variants, and one carried a likely pathogenic GBA1 variant. None of the patients had expanded repeats in C9orf72. Furthermore, we found 16 different variants of uncertain significance in 21 PSP patients in PSEN2, ABCA7, SMPD1, MAPT, ATP13A2, OPTN, SQSTM1, CYLD, and BSN.

    CONCLUSIONS: The genetic findings in our PSP cohorts appear to be somewhat distinct from those in Western populations, and also suggest an overlap of the genetic architecture between PSP and other neurodegenerative diseases. Further functional studies and validation in independent Asian cohorts will be useful for improving our understanding of PSP genetics and guiding genetic screening strategies in these populations. © 2024 International Parkinson and Movement Disorder Society.

  13. Lim SY, Tan AH, Foo JN, Tan YJ, Chew EG, Annuar AA, et al.
    J Mov Disord, 2024 Apr;17(2):213-217.
    PMID: 38291878 DOI: 10.14802/jmd.24009
    Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson's disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann-Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.
  14. Nairismägi ML, Tan J, Lim JQ, Nagarajan S, Ng CC, Rajasegaran V, et al.
    Leukemia, 2016 06;30(6):1311-9.
    PMID: 26854024 DOI: 10.1038/leu.2016.13
    Epitheliotropic intestinal T-cell lymphoma (EITL, also known as type II enteropathy-associated T-cell lymphoma) is an aggressive intestinal disease with poor prognosis and its molecular alterations have not been comprehensively characterized. We aimed to identify actionable easy-to-screen alterations that would allow better diagnostics and/or treatment of this deadly disease. By performing whole-exome sequencing of four EITL tumor-normal pairs, followed by amplicon deep sequencing of 42 tumor samples, frequent alterations of the JAK-STAT and G-protein-coupled receptor (GPCR) signaling pathways were discovered in a large portion of samples. Specifically, STAT5B was mutated in a remarkable 63% of cases, JAK3 in 35% and GNAI2 in 24%, with the majority occurring at known activating hotspots in key functional domains. Moreover, STAT5B locus carried copy-neutral loss of heterozygosity resulting in the duplication of the mutant copy, suggesting the importance of mutant STAT5B dosage for the development of EITL. Dysregulation of the JAK-STAT and GPCR pathways was also supported by gene expression profiling and further verified in patient tumor samples. In vitro overexpression of GNAI2 mutants led to the upregulation of pERK1/2, a member of MEK-ERK pathway. Notably, inhibitors of both JAK-STAT and MEK-ERK pathways effectively reduced viability of patient-derived primary EITL cells, indicating potential therapeutic strategies for this neoplasm with no effective treatment currently available.
  15. Lim WK, Chew QH, He YL, Si TM, Chiu FH, Xiang YT, et al.
    Hum Psychopharmacol, 2020 11;35(6):1-7.
    PMID: 32738085 DOI: 10.1002/hup.2752
    OBJECTIVE: Studies examining coprescription and dosages of mood stabilizers (MSs) with antipsychotics for psychotic disorders are infrequent. Based on sparse extant data and clinical experience, we hypothesized that adjunctive MS use would be associated with certain demographic (e.g., younger age), clinical factors (e.g., longer illness duration), and characteristics of antipsychotic treatment (e.g., multiple or high antipsychotic doses).

    METHODS: Within an Asian research consortium focusing on pharmaco-epidemiological factors in schizophrenia, we evaluated rates of MS coprescription, including high doses (>1000 mg/day lithium-equivalents) and clinical correlates.

    RESULTS: Among 3557 subjects diagnosed with schizophrenia in 14 Asian countries, MSs were coprescribed with antipsychotics in 13.6% (n = 485) of the sample, with 10.9% (n = 53) on a high dose. Adjunctive MS treatment was associated (all p < 0.005) with demographic (female sex and younger age), setting (country and hospitalization), illness (longer duration, more hospitalizations, non-remission of illness, behavioral disorganization, aggression, affective symptoms, and social-occupational dysfunction), and treatment-related factors (higher antipsychotic dose, multiple antipsychotics, higher body mass index, and greater sedation). Patients given high doses of MSs had a less favorable illness course, more behavioral disorganization, poorer functioning, and higher antipsychotic doses.

    CONCLUSIONS: Schizophrenia patients receiving adjunctive MS treatment in Asian psychiatric centers are more severely ill and less responsive to simpler treatment regimens.

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