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Performance of the rural health improvement scheme in reducing the incidence of waterborne diseases in rural Sarawak, Malaysia

Liew KB, Lepesteur M

Trans R Soc Trop Med Hyg, 2006 Oct;100(10):949-55.
PMID: 16730364 DOI: 10.1016/j.trstmh.2005.11.018

This study evaluates and discusses the impact of the rural health improvement scheme in reducing the incidence of dysentery, enteric fever, cholera and viral hepatitis in Sarawak, Malaysia, using data compiled from state and federal health department reports. This study suggests that from 1963 to 2002, water supply intervention contributed to a more than 200-fold decrease in dysentery and a 60-fold decrease in enteric fever. Variations in reporting of viral hepatitis during that period make it difficult to detect a trend. Cholera was still endemic in 2002. Cholera and dysentery outbreaks, occurring when rural populations relied on contaminated rivers for their water supply, suggested that sanitation intervention was not as effective in reducing waterborne diseases. Recommendations are made for successive one-component interventions focusing on catchment management to ensure protection of current and alternative water supplies.
Fulltext Clinical impact of implementation of a dengue outbreak preparedness and contingency plan in a tertiary hospital

Suraya Hanim Abdullah Hashim, Liew K. Y., Sahadevan M., Shoib M. S., Zainal Abidin H., Abidin N. N., et al.

Malaysian Journal of Medicine and Health Sciences, 2019;15(106):67-67.
MyJurnal

Introduction:Increasing number and the complexity of dengue cases pose a great challenge. The dengue outbreak preparedness and contingency plan is a series of collective intervention or polices put into place via collective agreement between administrative, Medical, Emergency Department and Intensive Care Unit (ICU). The aim of this paper is to evaluate the impact implementation of a dengue contingency plan on the clinical outcome of dengue cases. Methods: Implementation of the dengue outbreak preparedness and contingency plan was commenced in 2017. A pre-intervention (2017) and post-intervention (2018) retrospective review of mortality cases and referral to ICU were undertaken. The interventions included mandatory fast review by Emergency Physician, Medical Physi-cian and Anaesthesist in Emergency Department for ill patients (Dengue Care Pathway), cohorting dengue patient to one ward with mandatory monitoring and review system, clinical management adhering to the Clinical Practice Guideline of Management of Dengue Infection in Adults (2015), referring ill patients to ICU, deployment of nurses and experienced doctors to the dengue ward based on ratio of staff to patients, increasing number of doctors on-call at the dengue ward and a dengue bed manager system led by the Matron and Sisters. The plan was activated by mutual agreement between the Head of Medical Department and the Hospital Director. Results: There was a marked increment of admission of dengue cases into intensive care unit by 59% either directly from emergency department or the dengue wards in 2018 compared to 2017. The mortality rates reduced significantly from 5.4 deaths for every 1000 admission in 2017 to 3.3 in 2018. This is a reduction 2.1 death for every 1000 dengue admission. Conclusion:The implementation of the dengue outbreak preparedness and contingency plan aided the team to provide best care and practice in dengue management especially in the severely ill.
Malignant phyllodes tumors of the breast: A single institution experience

Liew KW, Siti Zubaidah S, Doreen L

Med J Malaysia, 2018 10;73(5):297-300.
PMID: 30350808 MyJurnal

BACKGROUND: Malignant phyllodes tumors of the breast are uncommon fibroepithelial breast tumors with diverse biological behavior. Our study aim is to share our experience in treating patients with malignant phyllodes presenting to our center.
PATIENTS AND METHODS: A total of 11 cases of malignant phyllodes were retrospectively reviewed between Nov 2014 and Oct 2017.
RESULTS: The median age was 45 years old (31- 61 years). The median pathological tumor size was 10.5cm (2-28cm). 6 patients (55%) were premenopausal. 7 patients (64%) were treated eventually with mastectomy and 4 (36%) were treated with breast conserving surgery. 4 (36%) patients had Axillary Clearance done while axillary sampling was done in 2 patient. The remainder 5 (45%) required axillary clearance at a later op. 6 (55%) patients received postoperative radiotherapy. After a median follow up period of 11 months (range 4-33 months), 8 developed local recurrence. The overall 2 year survival rate was 18%.
CONCLUSION: Malignant Phyllodes tumors are rare tumors that occur in fairly young women, when compared with the adenocarcinoma of the breast. They tend to grow to reach large with absence of nodal metastasis. Ultimately surgery is the mainstay of management but with postoperative radiotherapy it can decrease the local recurrence rates in certain presentations however recurrence rate is high and overall survival rates are poor.
Lignin biodegradation and ligninolytic enzyme studies during biopulping of Acacia mangium wood chips by tropical white rot fungi

Liew CY, Husaini A, Hussain H, Muid S, Liew KC, Roslan HA

World J Microbiol Biotechnol, 2011 Jun;27(6):1457-68.
PMID: 25187145 DOI: 10.1007/s11274-010-0598-x

White rot fungi are good lignin degraders and have the potential to be used in industry. In the present work, Phellinus sp., Daedalea sp., Trametes versicolor and Pycnoporus coccineus were selected due to their relatively high ligninolytic enzyme activity, and grown on Acacia mangium wood chips under solid state fermentation. Results obtained showed that manganese peroxidase produced is far more compared to lignin peroxidase, suggesting that MnP might be the predominating enzymes causing lignin degradation in Acacia mangium wood chips. Cellulase enzyme assays showed that no significant cellulase activity was detected in the enzyme preparation of T. versicolor and Phellinus sp. This low cellulolytic activity further suggests that these two white rot strains are of more interest in lignin degradation. The results on lignin losses showed 20-30% of lignin breakdown at 60 days of biodegradation. The highest lignin loss was found in Acacia mangium biotreated with T. versicolor after 60 days and recorded 26.9%, corresponding to the percentage of their wood weight loss recorded followed by P. coccineus. In general, lignin degradation was only significant from 20 days onwards. The overall percentage of lignin weight loss was within the range of 1.02-26.90% over the biodegradation periods. Microscopic observations conducted using scanning electron microscope showed that T. versicolor, P. coccineus, Daedalea sp. and Phellinus sp. had caused lignin degradation in Acacia mangium wood chips.
Fulltext Pathogenic Role of Exosomes in Epstein-Barr Virus (EBV)-Associated Cancers

Teow SY, Liew K, Khoo AS, Peh SC

Int J Biol Sci, 2017;13(10):1276-1286.
PMID: 29104494 DOI: 10.7150/ijbs.19531

Exosomes are 40- to 100-nm membrane-bound small vesicles that carry a great variety of cellular cargoes including proteins, DNA, messenger RNAs (mRNAs), and microRNAs (miRNAs). These nanovesicles are detected in various biological fluids such as serum, urine, saliva, and seminal fluids. Exosomes serve as key mediators in intercellular communication by facilitating the transfer and exchange of cellular components from cells to cells. They contain various pathogenic factors whereby their adverse effects have been implicated in multiple viral infections and cancers. Interestingly, accumulating evidences showed that exosomes derived from tumour viruses or oncoviruses, exacerbate virus-associated cancers by remodelling the tumour microenvironment. In this review, we summarize the contributing factors of Epstein-Barr virus (EBV) products-containing exosomes in viral pathogenesis and their potential implications in EBV-driven malignancies. Understanding the biological role of these exosomes in the disease would undoubtedly boost the development of a more comprehensive strategy to combat EBV-associated cancers and to better predict the therapeutic outcomes. Furthermore, we also highlight the potentials and challenges of EBV products-containing exosomes being employed as diagnostic markers and therapeutic targets for EBV-related cancers. Since these aspects are rather underexplored, we attempt to underline interesting areas that warrant further investigations in the future.
2-Methoxy-1,4-Naphthoquinone (MNQ) suppresses the invasion and migration of a human metastatic breast cancer cell line (MDA-MB-231)

Liew K, Yong PV, Lim YM, Navaratnam V, Ho AS

Toxicol In Vitro, 2014 Apr;28(3):335-9.
PMID: 24291160 DOI: 10.1016/j.tiv.2013.11.008

Metastasis contributes to the escalating mortality rate among cancer patients worldwide. The search for novel and more effective anti-metastatic agent is crucial owing to the lack of anticancer drugs that can successfully combat metastasis. Hence, this study aims to examine the effects of 2-Methoxy-1,4-Naphthoquinone (MNQ) towards the metastasis of MDA-MB-231 cells. In invasion assays, the number of cells permeating across a Matrigel barrier was found to be decreased in a dose-dependent manner upon treatment with MNQ (0-7.5 μM). In wound-healing migration assays, MNQ exhibited dose-dependent inhibition of cell migration in which significant reduction in the zone of closure was observed as compared to untreated controls. Furthermore, the proteolytic activity of a pivotal metastatic mediator, matrix metalloproteinase-9 (MMP-9) was also downregulated by MNQ as determined by gelatin zymography. This study reports for the first time, the ability of MNQ to inhibit the invasion and migration characteristics of a highly metastatic MDA-MB-231 cancer cell line.
Differential proteomic analysis on the effects of 2-methoxy-1,4-naphthoquinone towards MDA-MB-231 cell line

Liew K, Yong PV, Navaratnam V, Lim YM, Ho AS

Phytomedicine, 2015 May 15;22(5):517-27.
PMID: 25981917 DOI: 10.1016/j.phymed.2015.03.007

We have previously reported the anti-metastatic effects of 2-methoxy-1,4-naphthoquinone (MNQ) against MDA-MB-231 cell line.
Antibacterial Action of Curcumin against Staphylococcus aureus: A Brief Review

Teow SY, Liew K, Ali SA, Khoo AS, Peh SC

J Trop Med, 2016;2016:2853045.
PMID: 27956904

Curcumin, the major constituent of Curcuma longa L. (Zingiberaceae family) or turmeric, commonly used for cooking in Asian cuisine, is known to possess a broad range of pharmacological properties at relatively nontoxic doses. Curcumin is found to be effective against Staphylococcus aureus (S. aureus). As demonstrated by in vitro experiment, curcumin exerts even more potent effects when used in combination with various other antibacterial agents. Hence, curcumin which is a natural product derived from plant is believed to have profound medicinal benefits and could be potentially developed into a naturally derived antibiotic in the future. However, there are several noteworthy challenges in the development of curcumin as a medicine. S. aureus infections, particularly those caused by the multidrug-resistant strains, have emerged as a global health issue and urgent action is needed. This review focuses on the antibacterial activities of curcumin against both methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA). We also attempt to highlight the potential challenges in the effort of developing curcumin into a therapeutic antibacterial agent.
Fulltext Development of a luciferase/luciferin cell proliferation (XenoLuc) assay for real-time measurements of Gfp-Luc2-modified cells in a co-culture system

Teow SY, Liew K, Che Mat MF, Marzuki M, Abdul Aziz N, Chu TL, et al.

BMC Biotechnol, 2019 06 14;19(1):34.
PMID: 31200673 DOI: 10.1186/s12896-019-0528-4

BACKGROUND: In vitro modelling of cancer cells is becoming more complex due to prevailing evidence of intimate interactions between cancer cells and their surrounding stroma. A co-culture system which consists of more than one cell type is physiologically more relevant and thus, could serve as a useful model for various biological studies. An assay that specifically detects the phenotypic changes of cancer cells in a multi-cellular system is lacking for nasopharyngeal carcinoma (NPC).
RESULTS: Here, we describe a luciferase/luciferin (XenoLuc) assay that could specifically measure changes in the proliferation of cancer cells in the co-culture system using two modified NPC patient-derived tumour xenograft (PDTXs) cells: Xeno284-gfp-luc2 and XenoB110-gfp-luc2. Through this assay, we are able to show that the growth of NPC xenograft cells in both two-dimensional (2D) and three-dimensional (3D) models was enhanced when co-cultured with normal human dermal fibroblasts (NHDFs). In addition, potential applications of this assay in in vitro drug or inhibitor screening experiments are also illustrated.
CONCLUSIONS: XenoLuc assay is specific, sensitive, rapid and cost-effective for measuring the growth of luciferase-expressing cells in a co- or multiple-culture system. This assay may also be adapted for tumour microenvironment studies as well as drug screening experiments in more complex 3D co-culture systems.
Fulltext CD24, CD44 and EpCAM enrich for tumour-initiating cells in a newly established patient-derived xenograft of nasopharyngeal carcinoma

Hoe SLL, Tan LP, Abdul Aziz N, Liew K, Teow SY, Abdul Razak FR, et al.

Sci Rep, 2017 09 28;7(1):12372.
PMID: 28959019 DOI: 10.1038/s41598-017-12045-8

Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.
Parallel genome-wide RNAi screens identify lymphocyte-specific protein tyrosine kinase (LCK) as a targetable vulnerability of cell proliferation and chemoresistance in nasopharyngeal carcinoma

Liew K, Yu GQS, Wei Pua LJ, Wong LZ, Tham SY, Hii LW, et al.

Cancer Lett, 2021 Apr 28;504:81-90.
PMID: 33587980 DOI: 10.1016/j.canlet.2021.02.006

Despite recent in advances in the management of nasopharyngeal carcinoma (NPC), development of targeted therapy remains challenging particularly in patients with recurrent or metastatic disease. To search for clinically relevant targets for the treatment of NPC, we carried out parallel genome-wide functional screens to identified essential genes that are required for NPC cells proliferation and cisplatin resistance. We identified lymphocyte-specific protein tyrosine kinase (LCK) as a key vulnerability of both proliferation and cisplatin resistance. Depletion of endogenous LCK or treatment of cells with LCK inhibitor induced tumor-specific cell death and synergized cisplatin sensitivity in EBV-positive C666-1 and EBV-negative SUNE1 cells. Further analyses demonstrated that LCK is regulating the proliferation and cisplatin resistance through activation of signal transducer and activator of transcription 5 (STAT5). Taken together, our study provides a molecular basis for targeting LCK and STAT5 signaling as potential druggable targets for the management of NPC.
Fulltext Happiness Maximization Is a WEIRD Way of Living

Krys K, Kostoula O, van Tilburg WAP, Mosca O, Lee JH, Maricchiolo F, et al.

Perspect Psychol Sci, 2024 Feb 13.
PMID: 38350096 DOI: 10.1177/17456916231208367

Psychological science tends to treat subjective well-being and happiness synonymously. We start from the assumption that subjective well-being is more than being happy to ask the fundamental question: What is the ideal level of happiness? From a cross-cultural perspective, we propose that the idealization of attaining maximum levels of happiness may be especially characteristic of Western, educated, industrial, rich, and democratic (WEIRD) societies but less so for others. Searching for an explanation for why "happiness maximization" might have emerged in these societies, we turn to studies linking cultures to their eco-environmental habitat. We discuss the premise that WEIRD cultures emerged in an exceptionally benign ecological habitat (i.e., faced relatively light existential pressures compared with other regions). We review the influence of the Gulf Stream on the Northwestern European climate as a source of these comparatively benign geographical conditions. We propose that the ecological conditions in which WEIRD societies emerged afforded them a basis to endorse happiness as a value and to idealize attaining its maximum level. To provide a nomological network for happiness maximization, we also studied some of its potential side effects, namely alcohol and drug consumption and abuse and the prevalence of mania. To evaluate our hypothesis, we reanalyze data from two large-scale studies on ideal levels of personal life satisfaction-the most common operationalization of happiness in psychology-involving respondents from 61 countries. We conclude that societies whose members seek to maximize happiness tend to be characterized as WEIRD, and generalizing this across societies can prove problematic if adopted at the ideological and policy level.

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