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  1. Tee PYE, Chu SYC, Kok CCY, Foo M, Tan CZJ, Foo JB, et al.
    Curr Pharm Biotechnol, 2024 Jul 12.
    PMID: 39005116 DOI: 10.2174/0113892010316710240626042205
    Clustered Regions of Interspersed Palindromic Repeat (CRISPR)-based techniques have been utilized in various research areas, including agriculture, biotechnology, and medicine. With the use of a short sequence guide RNA and CRISPR-associated (Cas) protein, this technique allows for robust, site-specific manipulation of the genome, aiding researchers in making important biomedical discoveries and scientific advancements. In this review, we explored the applications of CRISPR/Cas systems in the field of parasitology for the identification and validation of novel functional genes, diagnosis of parasitic infections, reduction of parasite virulence, and the disruption of disease transmission. We also discussed how CRISPR can be used for the development of therapeutics, vaccines, and drug discovery. Furthermore, the challenges and future perspectives of this technology are also highlighted.
  2. Mohd Faiz MN, Abd Rahman MSH, Nurazfalina AAA, Jennifer T, Nabil S, Tan JK, et al.
    Med J Malaysia, 2024 Jul;79(4):443-451.
    PMID: 39086342
    INTRODUCTION: Oral health problems are frequently overlooked in patients with epilepsy. We evaluate the oral health status of epilepsy patients from a tertiary teaching hospital.

    MATERIALS AND METHODS: We conducted a cross-sectional study of epilepsy patients from the neurology clinic, Hospital Canselor Tuanku Muhriz, Kuala Lumpur. The dental assessment included the decayed, missing and filled teeth (DMFT) criteria, as well as the plaque and periodontal status by dentists.

    RESULTS: A total of 151 patients were recruited. The median age of onset of epilepsy was 16 (IQR 7-30) years, with generalised seizures at 59.6% and focal seizures in 40.4% of patients. Fair or poor oral health was present in 59 (39.1%) and gingivitis was seen in 65 (43%). The median DMFT decayed (D), missing (M) and filled teeth (FT) was 3 (IQR 1- 7). The median age of patients with fair or poor oral health was older (40 years, IQR 31-51) than the patients with excellent or good oral health (33 years, IQR 26-45), (p=0.014). Multivariate logistic regression analysis showed that carbamazepine (Odds Ratios, OR: 3.694; 95% Confidence Intervals, 95%CI: 1.314, 10.384) and hypertension (OR 6.484; 95%CI: 1.011, 41.594) are the risk factors for fair or poor oral health. Phenytoin use is 4.271 times more likely to develop gingivitis (OR 4.271; 95% CI: 1.252, 14.573).

    CONCLUSION: Factors that contribute to fair or poor oral health include age, antiseizure medications like phenytoin and carbamazepine, and hypertension. Effective preventive strategies should be implemented to maintain oral health in epilepsy patients.

  3. Arip M, Selvaraja M, R M, Tan LF, Leong MY, Tan PL, et al.
    Front Pharmacol, 2022;13:879495.
    PMID: 36249774 DOI: 10.3389/fphar.2022.879495
    Antimicrobial resistance (AMR) occurs when microbes no longer respond to any pharmacological agents, rendering the conventional antimicrobial agents ineffective. AMR has been classified as one of the top 10 life-threatening global health problems needed multilevel attention and global cooperation to attain the Sustainable Development Goals (SDGs) according to the World Health Organization (WHO), making the discovery of a new and effective antimicrobial agent a priority. The recommended treatments for drug-resistant microbes are available but limited. Furthermore, the transformation of microbes over time increases the risk of developing drug resistance. Hence, plant metabolites such as terpenes, phenolic compounds and alkaloids are widely studied due to their antibacterial, antiviral, antifungal and antiparasitic effects. Plant-derived antimicrobials are preferred due to their desirable efficacy and safety profile. Plant metabolites work by targeting microbial cell membranes, interfering with the synthesis of microbial DNA/RNA/enzymes and disrupting quorum sensing and efflux pump expression. They also work synergistically with conventional antibiotics to enhance antimicrobial effects. Accordingly, this review aims to identify currently available pharmacological therapies against microbes and AMR, as well as to discuss the importance of plant and secondary metabolites as a possible solution for AMR together with their mechanisms of action. All the information was obtained from government databases, WHO websites, PubMed, Springer, Google Scholar and Science Direct. Based on the information obtained, AMR is regarded as a significant warning to global healthcare. Plant derivatives such as secondary metabolites may be considered as potential therapeutic targets to mitigate the non-ending AMR.
  4. M H Subari IAA, Mutthumanickam G, Hj Jikal M, Shah MD, Tan JK, Tan YS, et al.
    Toxicon, 2024 Nov 28;251:108133.
    PMID: 39426425 DOI: 10.1016/j.toxicon.2024.108133
    In Malaysia, mushroom poisoning poses a significant public health concern, particularly as local communities frequently consume wild mushrooms without fully recognizing the potential dangers they present. Ingestion of wild mushrooms, which resemble edible species but contain deadly chemicals, is the main cause of poisoning risk. The genus Entoloma (Fr.) P. Kumm is dispersed worldwide, with over 1500 species recorded. Entoloma mastoideum, a poisonous mushroom, was recorded for the first time at Kota Marudu district, Sabah, Malaysia, where ten cases of mushroom poisoning outbreaks were recorded during the rainy season of October 2019. The morphological characters of the specimens were documented and their microscopic features were analyzed using compound microscope and scanning electron microscope. A phylogenetic tree was constructed using Maximum likelihood and Bayesian analysis. Chemical profiling of the poisonous mushroom specimen was done via liquid chromatograph mass spectrometry (LC-MS/MS) to identify toxic metabolites. The phylogenetic analysis showed that the Bornean E. mastoideum is closely related to the Chinese isolates (100% BS/1.0 PP). LC-MS/MS profiling detected a total of 162 metabolites that were classified into ten general groups, where several toxic compounds were detected amongst the aromatics, essential amino acids, and fatty acid derivatives. The toxic compounds identified in the mushroom extract, including amino acid derivatives such as 3,4,5,6-tetrahydroxyynorleucine, valpromide, and betaine, have been reported to cause neurotoxicity, cardiotoxicity, liver damage, and gastrointestinal harm. The presence of these toxic compounds underscores the need for caution when consuming wild mushrooms. Further research on poisonous Entoloma species is vital for developing accurate identification methods and understanding their toxic potential. This knowledge is essential for enhancing public awareness, preventing mushroom poisoning incidents and safeguarding public health.
  5. Tan KE, Her ZP, Zhang C, Yeo KS, Weiskittel T, Howe C, et al.
    iScience, 2026 Mar 20;29(3):115144.
    PMID: 41858882 DOI: 10.1016/j.isci.2026.115144
    Neuroblastoma (NB) accounts for 10% of pediatric cancer-related deaths, is often highly metastatic at diagnosis, and has a 5-year-survival rate of <50% for patients with high-risk disease. We previously showed that the transcriptional coactivator LMO1 cooperates with the MYCN oncogene to enhance NB tumorigenesis and metastasis. To better understand this synergy, we performed single-cell RNA sequencing analysis on primary tumors from transgenic zebrafish overexpressing MYCN alone or with LMO1. Interestingly, we found that the macrophage populations from the two tumor types were transcriptionally distinct, and LMO1 increased cancer-cell secretion of cytokines associated with metastasis and angiogenesis. Conditioned media from LMO1-expressing NB cells activated PI3K-Akt signaling and MMP expression in human macrophages, enhancing matrix degradation and promoting NB cell migration in vivo. Our data suggest that LMO1 overexpression in MYCN-amplified NB cells increases the pro-metastatic properties of macrophages in the tumor-cell microenvironment, which is important for driving NB metastasis.
  6. Kok SHW, Chong WK, Khor J, Liu R, Tan LS, Low J, et al.
    Small, 2025 Mar 12.
    PMID: 40072339 DOI: 10.1002/smll.202501119
    The design of highly efficient photocatalysts to photoreduce nitrogen (N2) to ammonia (NH3) under mild conditions is extremely challenging. In this work, various molar ratio of molybdenum (Mo) is incorporated into Bi12O17Cl2 via a hydrothermal process. The resulting Mo-doped Bi12O17Cl2 exhibits remarkable solar-driven activity for N2 photo fixation without any scavengers or sacrificial agents. The optimal sample with 5% Mo dopants displays an NH3 yield of 39.83 µmol g-1 h-1, a 1.6-fold improvement over undoped pristine Bi12O17Cl2. The impressive performance is attributed to the synergistic effects of oxygen vacancies (OVs) and Mo-loading, enhancing light absorption and extending photo-response through band gap reduction. Additional contributions arise from the enriched active sites, facilitating N2 adsorption and electron transport to the reactants. Density functional theory calculations reveal that Mo integration induces significant charge redistribution around the active sites, thereby reducing the energy barrier associated with N2 activation and protonation. In-depth investigation into the reaction pathway unravels the step-by-step reaction process which further elucidates the beneficial role of Mo loading in the overall N2 photoconversion process. As a whole, this work promotes a simple and effective engineering approach based on heteroatom doping as an efficacious strategy to design highly active photocatalysts toward N2 photo fixation.
  7. Figueras MM, Okada N, Tan CK, Aquino MC, Tan MCJ, Lun KW, et al.
    J Glaucoma, 2025 Mar 13.
    PMID: 40071977 DOI: 10.1097/IJG.0000000000002564
    PRCIS: In this retrospective cohort study, the 1-year cumulative probability of failure was comparable, achieving 52.20% in the phacoemulsification-iStent inject W (phaco/iStent) group and 47.80% in the phacoemulsification-micropulse transscleral laser therapy (phaco/MPTLT) group (P=0.994).

    PURPOSE: To compare the 1-year efficacy and safety of phacoemulsification combined with iStent Inject W (phaco/iStent) and phacoemulsification combined with micropulse transscleral laser therapy (phaco/MPTLT).

    METHODS: Retrospective cohort study that included patients with mild-moderate open angle glaucoma (OAG) and cataract who underwent either phaco/iStent or phaco/MPTLT in a tertiary hospital in Singapore between August 1, 2016 and December 31, 2022. The primary outcome measures were cumulative probabilities of failure between the two groups with failure defined as disease progression by Ocular Coherence Tomography (OCT-RNFL) or Visual Field Test (VFT), repeat glaucoma surgery, and inability to maintain intraocular pressure (IOP) lower than pre-operative baseline or the use of glaucoma medications for 2 consecutive visits after 1 month post-operatively. Additionally, post-operative mean IOP, average number of IOP lowering medications, visual acuity, and complications were analyzed.

    RESULTS: Forty-six patients were included. 23 eyes underwent phaco/iStent and 23 had phaco/MPTLT. The two groups had comparable cumulative probabilities of failure (52.20% phaco/iStent, 47.80% phaco/MPTLT; P=0.994) and mean IOP (15.57+2.95 mmHg phaco /iStent, 14.39+2.25 mmHg phaco/MPTLT; P=0.136) after 1 year. The change in IOP before surgery to 12 months is -1.04+3.07 mmHg in the phaco/iStent group (P=0.593) and -2.43+4.12 mmHg in the phaco/MPTLT group (P=0.022). Both achieved significant medication reduction burden (P<0.05). Intra-operative and post-operative complication rates were similar.

    CONCLUSION: Both groups showed comparable surgical efficacy and safety after 1 year. The phaco/MPTLT group demonstrated sustained IOP reduction 1 year post-operatively.

  8. Koh HP, Ab Jalal H, Koo YP, Chen MSY, Selvaratanam M, Bhuvanendran Pillai A, et al.
    J Pharm Policy Pract, 2025;18(1):2457410.
    PMID: 39877033 DOI: 10.1080/20523211.2025.2457410
    BACKGROUND: The emergency medicine (EM) pharmacist is an integrated part of the Emergency Department (ED) interdisciplinary team in many countries, including Malaysia. The presence of EM pharmacists in the ED has positively impacted patient outcomes. Data on EM pharmacists' interventions is scarce in the Asian region. In Malaysia, data on interventions done by EM pharmacists in the EDs was unavailable. This study aimed to assess the type of interventions done by EM pharmacists in the ED of tertiary public hospitals in Malaysia.

    METHODS: This cross-sectional, multicenter study involved EM pharmacists from 14 tertiary hospitals in Malaysia. All accepted interventions done by EM pharmacists in the ED for patients admitted to the Red (critical) and Yellow (semi-critical) zones from January to June 2022 were extracted from the Clinical Pharmacy Report Form. All data were analyzed descriptively.

    RESULTS: The EM pharmacists documented 1659 accepted interventions on 1584 patients during the study period. Inappropriate regimens (n = 1117, 67.3%) and incomplete prescriptions (n = 339, 20.4%) were the main categories of accepted interventions in ED. Inappropriate drug (n = 574, 34.6%), dose (n = 292, 17.6%), and frequency (n = 176, 10.6%) were the top three subcategory interventions documented under inappropriate regimens. Antimicrobials, antihypertensives, and proton pump inhibitors were the commonest drug intervened under the categories of inappropriate drug intervention. There were 272 (16.4%) accepted interventions on high-alert medications (HAMs). Insulin, enoxaparin, and noradrenaline were the most intervened HAMs.

    CONCLUSION: Inappropriate treatment regimens were the most common intervention category done by EM pharmacists in Malaysia. The significant number of interventions done by EM pharmacists demonstrated the importance of EM pharmacists as integral members of the EM team. This data can help improve the quality of clinical pharmacy services in the ED and is important for the future expansion of clinical pharmacy services in all EDs across Malaysia, neighbouring countries, and other developing countries.

  9. Gan GG, Wong LLL, Abdul Rahman MHF, Boo YL, Chew LP, Ho KW, et al.
    Malays J Med Sci, 2026 Aug;33(4):7-36.
    PMID: 42936371 DOI: 10.21315/mjms-03-2026-153
    The rising incidence of multiple myeloma (MM) in Malaysia, combined with limited access to newer therapies, highlights the need for locally adapted clinical guidance. This consensus aimed at establishing expert recommendations for the management of MM within Malaysia's resource-variable healthcare system. A modified Delphi process was conducted with 11 haematologists. To inform evidence-based recommendations, a targeted literature review was performed from January 2012 to June 2025. These recommendations were then evaluated using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria. A total of 58 consensus statements were developed across various areas, including diagnosis, staging, treatment of newly diagnosed and relapsed/refractory disease, renal impairment, infection prevention, high-risk smouldering myeloma, and supportive care. Agreement was assessed using a three-point Likert scale, with all statements achieving ≥ 80% consensus. Consensus recommendations highlighted that triplet induction remains the minimum standard for transplant-eligible patients in Malaysia. Quadruplet regimens deliver deeper responses and improved survival but are limited by regulatory and cost barriers across Asian health systems. In transplant-ineligible patients, treatment should be individualised based on age, frailty, cytogenetic risk, comorbidities, and financial considerations. Novel cellular and immune-based therapies, including CAR-T cells and bispecific antibodies, offer meaningful benefit in heavily pretreated disease, though availability remains restricted. Infection prophylaxis, immunoglobulin support, vaccination, and proactive management of myeloma-related bone disease are essential components of comprehensive care. Continued efforts to improve access to advanced diagnostics, novel therapies, and clinical trial participation will be critical to further enhance outcomes. This consensus provides a standardised, evidence-based framework to optimise MM care and improve patient outcomes nationally.
  10. Gopalai AA, Lim JL, Li HH, Zhao Y, Lim TT, Eow GB, et al.
    Mol Genet Genomic Med, 2019 Nov;7(11):e604.
    PMID: 31487119 DOI: 10.1002/mgg3.604
    BACKGROUND: The LRRK2 gene is associated with Parkinson's disease (PD) as a number of mutations within the gene have been shown to be susceptibility factors. Studies on various global populations have determined that mutations such as G2019S, G2385R, and R1628P in LRRK2 increase the risk of developing PD while the N551K-R1398H haplotype is associated with conferring protection against developing PD. Here we report a study looking at the N551K and R1398H variants for the first time in the Malaysian population.

    METHODS: Cases (523) which conformed to the United Kingdom PD Brain Bank Criteria for PD were recruited through trained neurologists and age- and ethnically matched controls (491) were individuals free of any neurological disorder. The N551K and R1398H mutations were genotyped using the Taqman SNP genotyping assay.

    RESULTS: A significant protective association for N551K was found in those of Malay ancestry, with a protective trend seen for R1398H. A meta-analysis of Chinese individuals in this cohort with other published cohorts of Chinese ancestry indicated a significant protective role for N551K and R1398H.

    CONCLUSION: This study reports that the N551K-R1398H haplotype is also relevant to the Malaysian population, with a significant protective effect found in those of Malay and Chinese ancestries.

  11. Tan AH, Chong CW, Lim SY, Yap IKS, Teh CSJ, Loke MF, et al.
    Ann Neurol, 2021 03;89(3):546-559.
    PMID: 33274480 DOI: 10.1002/ana.25982
    OBJECTIVE: Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a functional readout of microbial activity, have scarcely been investigated. We investigated fecal microbiome and metabolome alterations in PD, and their clinical relevance.

    METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.

    RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.

    INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.

  12. Woo KT, Chan CM, Mooi CY, -L-Choong H, Tan HK, Foo M, et al.
    Clin. Nephrol., 2010 Nov;74(5):372-83.
    PMID: 20979946
    This review of 2,586 renal biopsies over the past 3 decades in Singapore documents the changing pattern of glomerulonephritis (GN) from that of a third world country to that of a developed nation. In the 1st decade, mesangial proliferative glomerulonephritis was the most common form of primary GN, just as it was in the surrounding Asian countries. In the 2nd decade, the prevalence of mesangial proliferative GN decreased with a rise in membranous, GN which is also seen in China and Thailand. In the 3rd decade, there was a dramatic increase in focal sclerosing glomerulosclerosis. This increase reflects aging and obesity in keeping with more developed countries like Australia, India, Thailand and the United States of America. IgA nephritis remains the most common GN. Apart from the geographical influence, other socioeconomic factors play a significant role in the evolution of the renal biopsy pattern. Mesangial proliferative GN remains prevalent in many Asian countries, but in Singapore the prevalence is decreasing just as it is in Japan, Korea and Malaysia. Worldwide, the prevalence of focal sclerosing glomerulosclerosis continues to increase in many countries.
  13. Chun-Ern Ng D, Liew CH, Tan KK, Lim HY, Zailanalhuddin NEB, Tan SF, et al.
    Pediatr Int, 2023;65(1):e15690.
    PMID: 38037505 DOI: 10.1111/ped.15690
    BACKGROUND: We describe the epidemiology, clinical characteristics, and outcomes of multisystem inflammatory syndrome in children (MIS-C) among children from Negeri Sembilan, Malaysia.

    METHODS: A retrospective, multicentre, observational study was performed among children ≤15 years old who were hospitalized for MIS-C between January 18, 2021 and June 30, 2023. The incidence of MIS-C was estimated using reported SARS-CoV-2 cases and census population data. Descriptive analyses were used to summarize the clinical presentation and outcomes.

    RESULTS: The study included 53 patients with a median age of 5.7 years (IQR 1.8-8.7 years); 75.5% were males. The overall incidence of MIS-C was approximately 5.9 cases per 1,000,000 person-months. Pediatric intensive care unit (PICU) admission was required for 22 (41.5%) patients. No mortalities were recorded. Children aged 6-12 years were more likely to present with cardiac dysfunction/shock (odds ratio [OR] 5.43, 95% confidence interval [CI] 1.67-17.66), whereas children below 6 years were more likely to present with a Kawasaki disease phenotype (OR 5.50, 95% CI 1.33-22.75). Twenty patients (37.7%) presented with involvement of at least four organ systems, but four patients (7.5%) demonstrated single-organ system involvement.

    CONCLUSION: An age-based variation in the clinical presentation of MIS-C was demonstrated. Our findings suggest MIS-C could manifest in a spectrum, including single-organ involvement. Despite the high requirement for PICU admission, the prognosis of MIS-C was favorable, with no recorded mortalities.

  14. Lim PC, Tan HH, Mohd Noor NA, Chang CT, Wong TY, Tan EL, et al.
    J Pharm Policy Pract, 2023 Jul 05;16(1):83.
    PMID: 37408067 DOI: 10.1186/s40545-023-00583-8
    BACKGROUND: Pharmacist's involvement in optimizing medication adherence among diabetic patients has been implemented for over a decade. Diabetes Medication Therapy Adherence Clinic (DMTAC) was set up to educate diabetic patients, monitor treatment outcomes, and manage drug-related problems. While evidence shows that pharmacist-led DMTAC was effective in reducing HbA1c, there was limited data regarding the impact of different intervention types and default to follow-up on glycemic control.

    AIM: To assess the impact DMTAC on glycemic control and the difference in glycemic control between hospital and health clinic settings as well as defaulter and non-defaulter. In addition, the impact of pharmacist's interventions, DMTAC follow-up frequencies, and duration of diabetes on glycemic control were also determined.

    METHODS: A retrospective study was conducted among diabetes patients under DMTAC care between January 2019 and June 2020 in five hospitals and 23 primary health clinics. Patients' demographics data, treatment regimens, frequencies of DMTAC visits, defaulter (absent from DMTAC visits) and types of pharmacists' intervention were retrieved from patients' medical records and electronic database. HbA1c was collected at baseline, 4-6 months (post-1), and 8-12 months (post-2).

    RESULTS: We included 956 patients, of which 60% were females with a median age of 58.0 (IQR: 5.0) years. Overall, the HbA1c reduced significantly from baseline (median: 10.2, IQR: 3.0) to post-1 (median: 8.8, IQR: 2.7) and post-2 (median: 8.3, IQR: 2.6%) (p 

  15. Lim WH, Ng CH, Tan DJH, Xiao J, Fu CE, Ong C, et al.
    Transplantation, 2024 Feb 01;108(2):473-482.
    PMID: 37439778 DOI: 10.1097/TP.0000000000004718
    BACKGROUND: Liver transplantation (LT) offers patients with decompensated cirrhosis the best chance at long-term survival. With the rising prevalence of diabetes, further clarity is needed on the impact of receiving a liver allograft from a donor with diabetes on post-LT outcomes. This study aims to evaluate the impact of donor diabetes on clinical outcomes after LT.

    METHODS: This is a retrospective analysis of the United Network for Organ Sharing registry data of LT recipients from January 1, 2000, to December 31, 2021. Outcomes analysis was performed using Cox proportional model for all-cause mortality and graft failure. Confounding was reduced by coarsened exact matching causal inference analysis.

    RESULTS: Of 66 960 donors identified, 7178 (10.7%) had diabetes. Trend analysis revealed a longitudinal increase in the prevalence of donor diabetes ( P  

  16. Gopalai AA, Lim SY, Aziz ZA, Lim SK, Tan LP, Chong YB, et al.
    Ann Acad Med Singap, 2013 May;42(5):237-40.
    PMID: 23771111
    INTRODUCTION: The G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects.

    MATERIALS AND METHODS: Eight hundred and twenty-eight subjects (404 PD patients, and 424 age and gender-matched control subjects without neurological disorders) were recruited. Genotyping was done by Taqman® allelic discrimination assay on an Applied Biosystems 7500 Fast Real-Time PCR machine.

    RESULTS: The heterozygous A419V genotype was found in only 1 patient with PD, compared to 3 in the control group (0.4% vs 1.3%), giving an odds ratio of 0.35 (95% confidence interval (CI), 0.01 to 3.79; P = 0.624).

    CONCLUSION: A419V is not an important LRRK2 risk variant in our Asian cohort of patients with PD. Our data are further supported by a literature review which showed that 4 out of 6 published studies reported a negative association of this variant in PD.

  17. Tiong KH, Tan BS, Choo HL, Chung FF, Hii LW, Tan SH, et al.
    Oncotarget, 2016 Sep 06;7(36):57633-57650.
    PMID: 27192118 DOI: 10.18632/oncotarget.9328
    Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.
  18. Gopalai AA, Ahmad-Annuar A, Li HH, Zhao Y, Lim SY, Tan AH, et al.
    PMID: 27174169 DOI: 10.1002/ajmg.b.32454
    PARK16 was identified as a risk factor for Parkinson's disease in a Japanese cohort; however, subsequent studies in the other populations including the Chinese, European, Caucasian, and Chilean have shown a protective role instead. To investigate this locus in our Malaysian cohort, 1,144 individuals were screened for five SNPs in the PARK16 locus and logistic regression analysis showed that the A allele of the rs947211 SNP reduced the risk of developing PD via a recessive model (Odds ratio 0.57, P-value 0.0003). Pooled analysis with other Asian studies showed that A allele of the rs947211 SNP decreased the risk of developing PD via a recessive model (Odds ratio 0.71, P-value 0.0001). In addition, when meta-analysis was performed with other Asian population, three SNPs (rs823128, rs823156, and rs11240572) reduced risk of developing PD via a dominant model. © 2016 Wiley Periodicals, Inc.
  19. Khor HM, Tan MP, Kumar CS, Singh S, Tan KM, Saedon NB, et al.
    Arch Osteoporos, 2022 Nov 30;17(1):151.
    PMID: 36447075 DOI: 10.1007/s11657-022-01183-w
    The challenges of hip fracture care in Malaysia is scarcely discussed. This study evaluated the outcomes of older patients with hip fracture admitted to a teaching hospital in Malaysia. We found that one in five individuals was no longer alive at one year after surgery. Three out of five patients did not recover to their pre-fracture mobility status 6 months following hip fracture surgery.

    PURPOSE: With the rising number of older people in Malaysia, it is envisaged that the number of fragility hip fractures would also increase. The objective of this study was to determine patient characteristics and long-term outcomes of hip fracture in older individuals at a teaching hospital in Malaysia.

    METHODS: This was a prospective observational study which included consecutive patients aged  ≥ 65 years old admitted to the orthopedic ward with acute hip fractures between March 2016 and August 2018. Patient socio-demographic details, comorbidities, pre-fracture mobility status, fracture type, operation and anesthesia procedure, and length of stay were recorded. Post-fracture mobility status was identified at 6 months. Cox proportional hazard analysis was used to assess the risk of death in all patients.

    RESULTS: 310 patients (70% women) with the mean age of 79.89 years (SD 7.24) were recruited during the study period. Of these, 284 patients (91.6%) underwent surgical intervention with a median time to surgery of 5 days (IQR 3-8) days. 60.4% of patients who underwent hip fracture surgery did not recover to their pre-fracture mobility status. One year mortality rate was 20.1% post hip fracture surgery. The independent predictor of mortality included advanced age (hazard ratio, HR = 1.05, 95% CI = 1.01-1.08; p = 0.01), dependency on activities of daily living (HR = 2.08, 95% CI = 1.26-3.45; p = 0.01), and longer length of hospitalization (HR = 1.02, 95% CI = 1.01-1.04; p 

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