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Fulltext Recent developments in antiviral agents against enterovirus 71 infection

Tan CW, Lai JK, Sam IC, Chan YF

J Biomed Sci, 2014;21:14.
PMID: 24521134 DOI: 10.1186/1423-0127-21-14

Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.
Fulltext Enterovirus 71 uses cell surface heparan sulfate glycosaminoglycan as an attachment receptor

Tan CW, Poh CL, Sam IC, Chan YF

J Virol, 2013 Jan;87(1):611-20.
PMID: 23097443 DOI: 10.1128/JVI.02226-12

Enterovirus 71 (EV-71) infections are usually associated with mild hand, foot, and mouth disease in young children but have been reported to cause severe neurological complications with high mortality rates. To date, four EV-71 receptors have been identified, but inhibition of these receptors by antagonists did not completely abolish EV-71 infection, implying that there is an as yet undiscovered receptor(s). Since EV-71 has a wide range of tissue tropisms, we hypothesize that EV-71 infections may be facilitated by using receptors that are widely expressed in all cell types, such as heparan sulfate. In this study, heparin, polysulfated dextran sulfate, and suramin were found to significantly prevent EV-71 infection. Heparin inhibited infection by all the EV-71 strains tested, including those with a single-passage history. Neutralization of the cell surface anionic charge by polycationic poly-d-lysine and blockage of heparan sulfate by an anti-heparan sulfate peptide also inhibited EV-71 infection. Interference with heparan sulfate biosynthesis either by sodium chlorate treatment or through transient knockdown of N-deacetylase/N-sulfotransferase-1 and exostosin-1 expression reduced EV-71 infection in RD cells. Enzymatic removal of cell surface heparan sulfate by heparinase I/II/III inhibited EV-71 infection. Furthermore, the level of EV-71 attachment to CHO cell lines that are variably deficient in cell surface glycosaminoglycans was significantly lower than that to wild-type CHO cells. Direct binding of EV-71 particles to heparin-Sepharose columns under physiological salt conditions was demonstrated. We conclude that EV-71 infection requires initial binding to heparan sulfate as an attachment receptor.
Fulltext Inhibition of enterovirus 71 infection by antisense octaguanidinium dendrimer-conjugated morpholino oligomers

Tan CW, Chan YF, Quah YW, Poh CL

Antiviral Res, 2014 Jul;107:35-41.
PMID: 24769243 DOI: 10.1016/j.antiviral.2014.04.004

Enterovirus 71 (EV-71) infections are generally manifested as mild hand, foot and mouth disease, but have been reported to cause severe neurological complications with high mortality rates. Treatment options remain limited due to the lack of antivirals. Octaguanidinium-conjugated morpholino oligomers (vivo-MOs) are single-stranded DNA-like antisense agents that can readily penetrate cells and reduce gene expression by steric blocking of complementary RNA sequences. In this study, inhibitory effects of three vivo-MOs that are complementary to the EV-71 internal ribosome entry site (IRES) and the RNA-dependent RNA polymerase (RdRP) were tested in RD cells. Vivo-MO-1 and vivo-MO-2 targeting the EV-71 IRES showed significant viral plaque reductions of 2.5 and 3.5 log10PFU/ml, respectively. Both vivo-MOs reduced viral RNA copies and viral capsid expression in RD cells in a dose-dependent manner. In contrast, vivo-MO-3 targeting the EV-71 RdRP exhibited less antiviral activity. Both vivo-MO-1 and 2 remained active when administered either 4h before or within 6h after EV-71 infection. Vivo-MO-2 exhibited antiviral activities against poliovirus (PV) and coxsackievirus A16 but vivo-MO-1 showed no antiviral activities against PV. Both the IRES-targeting vivo-MO-1 and vivo-MO-2 inhibit EV-71 RNA translation. Resistant mutants arose after serial passages in the presence of vivo-MO-1, but none were isolated against vivo-MO-2. A single T to C substitution at nucleotide position 533 was sufficient to confer resistance to vivo-MO-1. Our findings suggest that IRES-targeting vivo-MOs are good antiviral candidates for treating early EV-71 infection, and vivo-MO-2 is a more favorable candidate with broader antiviral spectrum against enteroviruses and are refractory to antiviral resistance.
Fulltext Low postpandemic wave SARS-CoV-2 seroprevalence in Kuala Lumpur and Selangor, Malaysia

Sam IC, Chong YM, Tan CW, Chan YF

J Med Virol, 2021 02;93(2):647-648.
PMID: 32790206 DOI: 10.1002/jmv.26426
Fulltext Inhibition of enterovirus 71 (EV-71) infections by a novel antiviral peptide derived from EV-71 capsid protein VP1

Tan CW, Chan YF, Sim KM, Tan EL, Poh CL

PLoS One, 2012;7(5):e34589.
PMID: 22563456 DOI: 10.1371/journal.pone.0034589

Enterovirus 71 (EV-71) is the main causative agent of hand, foot and mouth disease (HFMD). In recent years, EV-71 infections were reported to cause high fatalities and severe neurological complications in Asia. Currently, no effective antiviral or vaccine is available to treat or prevent EV-71 infection. In this study, we have discovered a synthetic peptide which could be developed as a potential antiviral for inhibition of EV-71. Ninety five synthetic peptides (15-mers) overlapping the entire EV-71 capsid protein, VP1, were chemically synthesized and tested for antiviral properties against EV-71 in human Rhabdomyosarcoma (RD) cells. One peptide, SP40, was found to significantly reduce cytopathic effects of all representative EV-71 strains from genotypes A, B and C tested, with IC(50) values ranging from 6-9.3 µM in RD cells. The in vitro inhibitory effect of SP40 exhibited a dose dependent concentration corresponding to a decrease in infectious viral particles, total viral RNA and the levels of VP1 protein. The antiviral activity of SP40 peptide was not restricted to a specific cell line as inhibition of EV-71 was observed in RD, HeLa, HT-29 and Vero cells. Besides inhibition of EV-71, it also had antiviral activities against CV-A16 and poliovirus type 1 in cell culture. Mechanism of action studies suggested that the SP40 peptide was not virucidal but was able to block viral attachment to the RD cells. Substitutions of arginine and lysine residues with alanine in the SP40 peptide at positions R3A, R4A, K5A and R13A were found to significantly decrease antiviral activities, implying the importance of positively charged amino acids for the antiviral activities. The data demonstrated the potential and feasibility of SP40 as a broad spectrum antiviral agent against EV-71.
Fulltext High prevalence of methicillin-resistant Staphylococcus aureus (MRSA) on doctors' neckties

Koh KC, Husni S, Tan JE, Tan CW, Kunaseelan S, Nuriah S, et al.

Med J Malaysia, 2009 Sep;64(3):233-5.
PMID: 20527275 MyJurnal

We set out to investigate whether neckties worn by doctors are more likely to be contaminated with Methicillin resistant Staphylococcus aureus (MRSA) compared to neckties worn by preclinical medical undergraduates who have never been exposed to a hospital environment. We discovered that more than half (52%) of neckties worn by doctors were contaminated with Staphylococcus and out of these, 62% of them were identified as MRSA. In contrast, none of the student's ties were contaminated with MRSA. Due to the high prevalence of staphylococcus detected on doctors' neckties, we recommend that health care workers do not wear neckties.
Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF

Rev Med Virol, 2019 09;29(5):e2073.
PMID: 31369184 DOI: 10.1002/rmv.2073

Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.
Fulltext A rule-based energy management scheme for long-term optimal capacity planning of grid-independent microgrid optimized by multi-objective grasshopper optimization algorithm

Bukar AL, Tan CW, Yiew LK, Ayop R, Tan WS

Energy Convers Manag, 2020 Oct 01;221:113161.
PMID: 32834297 DOI: 10.1016/j.enconman.2020.113161

Off-grid electrification of remote communities using sustainable energy systems (SESs) is a requisite for realizing sustainable development goals. Nonetheless, the capacity planning of the SESs is challenging as it needs to fulfil the fluctuating demand from a long-term perspective, in addition to the intermittency and unpredictable nature of renewable energy sources (RESs). Owing to the nonlinear and non-convex nature of the capacity planning problem, an efficient technique must be employed to achieve a cost-effective system. Existing techniques are, subject to some constraints on the derivability and continuity of the objective function, prone to premature convergence, computationally demanding, follows rigorous procedures to fine-tune the algorithm parameters in different applications, and often do not offer a fair balance during the exploitation and exploration phase of the optimization process. Furthermore, the literature review indicates that researchers often do not implement and examine the energy management scheme (EMS) of a microgrid while computing for the capacity planning problem of microgrids. This paper proposes a rule-based EMS (REMS) optimized by a nature-inspired grasshopper optimization algorithm (GOA) for long-term capacity planning of a grid-independent microgrid incorporating a wind turbine, a photovoltaic, a battery (BT) bank and a diesel generator (

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). In which, a rule-based algorithm is used to implement an EMS to prioritize the usage of RES and coordinate the power flow of the proposed microgrid components. Subsequently, an attempt is made to explore and confirm the efficiency of the proposed REMS incorporated with GOA. The ultimate goal of the objective function is to minimize the cost of energy (COE) and the deficiency of power supply probability (DPSP). The performance of the REMS is examined via a long-term simulation study to ascertain the REMS resiliency and to ensure the operating limit of the BT storage is not violated. The result of the GOA is compared with particle swarm optimization (PSO) and a cuckoo search algorithm (CSA). The simulation results indicate that the proposed technique's superiority is confirmed in terms of convergence to the optimal solution. The simulation results confirm that the proposed REMS has contributed to better adoption of a cleaner energy production system, as the scheme significantly reduces fuel consumption,

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2

emission and COE by 92.4%, 92.3% and 79.8%, respectively as compared to the conventional

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n

. The comparative evaluation of the algorithms shows that REMS-GOA yields a better result as it offers the least COE (objective function), at $0.3656/kW h, as compared to the REMS-CSA at $0.3662/kW h and REMS-PSO at $0.3674/kW h, for the desired DPSP of 0%. Finally, sensitivity analysis is performed to highlight the effect of uncertainties on the system inputs that may arise in the future.
Vaccine candidates generated by codon and codon pair deoptimization of enterovirus A71 protect against lethal challenge in mice

Lee MHP, Tan CW, Tee HK, Ong KC, Sam IC, Chan YF

Vaccine, 2021 03 19;39(12):1708-1720.
PMID: 33640144 DOI: 10.1016/j.vaccine.2021.02.024

Enterovirus A71 (EV-A71) causes hand, foot and mouth disease (HFMD) in young children. It is associated with severe neurological complications and death. This study aims to develop a live-attenuated vaccine by codon deoptimization (CD) and codon-pair deoptimization (CPD) of EV-A71. CD is generated by introducing the least preferred codons for amino acids while CPD increases the presence of underrepresented codon pairs in the specific genes. CD and CPD chimeras were generated by synonymous mutations at the VP2, VP3, VP1 and 2A gene regions, designated as XYZ. All twelve deoptimized viruses were viable with similar replication kinetics, but the plaque sizes were inversely proportional to the level of deoptimization. All the deoptimized viruses showed attenuated growth in vitro with reduced viral protein expression at 48 h and lower viral RNA at 39 °C. Six-week-old ICR mice were immunized intraperitoneally with selected CD and CPD X and XY vaccine candidates covering the VP2-VP3 and VP2-VP3-VP1 genes, respectively. All vaccine candidates elicited high anti-EV-A71 IgG levels similar to wild-type (WT) EV-A71. The CD X and CPD X vaccines produced robust neutralizing antibodies but not the CD XY and CPD XY. On lethal challenge, offspring of mice immunized with WT, CD X and CPD X were fully protected, but the CD XY- and CPD XY-vaccinated mice had delayed symptoms and eventually died. Similarly, active immunization of 1-day-old suckling mice with CD X, CPD X and CD XY vaccine candidates provided complete immune protection but CPD XY only protected 40% of the challenged mice. Histology of the muscles from CD X- and CPD X-vaccinated mice showed minimal pathology compared to extensive inflammation in the post-challenged mock-vaccinated mice. Overall, we demonstrated that the CD X and CPD X elicited good neutralizing antibodies, conferred immune protection and are promising live-attenuated vaccine candidates for EV-A71.
Fulltext Enterovirus A71 DNA-Launched Infectious Clone as a Robust Reverse Genetic Tool

Tan CW, Tee HK, Lee MH, Sam IC, Chan YF

PLoS One, 2016;11(9):e0162771.
PMID: 27617744 DOI: 10.1371/journal.pone.0162771

Enterovirus A71 (EV-A71) causes major outbreaks of hand, foot and mouth disease, and is occasionally associated with neurological complications and death in children. Reverse genetics is widely used in the field of virology for functional study of viral genes. For EV-A71, such tools are limited to clones that are transcriptionally controlled by T7/SP6 bacteriophage promoter. This is often time-consuming and expensive. Here, we describe the development of infectious plasmid DNA-based EV-A71 clones, for which EV-A71 genome expression is under transcriptional control by the CMV-intermediate early promoter and SV40 transcriptional-termination signal. Transfection of this EV-A71 infectious DNA produces good virus yield similar to in vitro-transcribed EV-A71 infectious RNA, 6.4 and 5.8 log10PFU/ml, respectively. Infectious plasmid with enhanced green fluorescence protein and Nano luciferase reporter genes also produced good virus titers, with 4.3 and 5.0 log10 PFU/ml, respectively. Another infectious plasmid with both CMV and T7 promoters was also developed for easy manipulation of in vitro transcription or direct plasmid transfection. Transfection with either dual-promoter infectious plasmid DNA or infectious RNA derived from this dual-promoter clone produced infectious viral particles. Incorporation of hepatitis delta virus ribozyme, which yields precise 3' ends of the DNA-launched EV-A71 genomic transcripts, increased infectious viral production. In contrast, the incorporation of hammerhead ribozyme in the DNA-launched EV-A71 resulted in lower virus yield, but improved the virus titers for T7 promoter-derived infectious RNA. This study describes rapid and robust reverse genetic tools for EV-A71.
Polysulfonate suramin inhibits Zika virus infection

Tan CW, Sam IC, Chong WL, Lee VS, Chan YF

Antiviral Res, 2017 07;143:186-194.
PMID: 28457855 DOI: 10.1016/j.antiviral.2017.04.017

Zika virus (ZIKV) is an arthropod-borne flavivirus that causes newborn microcephaly and Guillian-Barré syndrome in adults. No therapeutics are available to treat ZIKV infection or other flaviviruses. In this study, we explored the inhibitory effect of glycosaminoglycans and analogues against ZIKV infection. Highly sulfated heparin, dextran sulfate and suramin significantly inhibited ZIKV infection in Vero cells. De-sulfated heparin analogues lose inhibitory effect, implying that sulfonate groups are critical for viral inhibition. Suramin, an FDA-approved anti-parasitic drug, inhibits ZIKV infection with 3-5 log10 PFU viral reduction with IC50value of ∼2.5-5 μg/ml (1.93 μM-3.85 μM). A time-of-drug-addition study revealed that suramin remains potent even when administrated at 1-24 hpi. Suramin inhibits ZIKV infection by preventing viral adsorption, entry and replication. Molecular dynamics simulation revealed stronger interaction of suramin with ZIKV NS3 helicase than with the envelope protein. Suramin warrants further investigation as a potential antiviral candidate for ZIKV infection. Heparan sulfate (HS) is a cellular attachment receptor for multiple flaviviruses. However, no direct ZIKV-heparin interaction was observed in heparin-binding analysis, and downregulate or removal of cellular HS with sodium chlorate or heparinase I/III did not inhibit ZIKV infection. This indicates that cell surface HS is not utilized by ZIKV as an attachment receptor.
VP1 residues around the five-fold axis of enterovirus A71 mediate heparan sulfate interaction

Tan CW, Sam IC, Lee VS, Wong HV, Chan YF

Virology, 2017 01 15;501:79-87.
PMID: 27875780 DOI: 10.1016/j.virol.2016.11.009

Enterovirus A71 (EV-A71) is a neurotropic enterovirus that uses heparan sulfate as an attachment receptor. The molecular determinants of EV-A71-heparan sulfate interaction are unknown. With In silico heparin docking and mutagenesis of all possible lysine residues in VP1, we identified that K162, K242 and K244 are responsible for heparin interaction and inhibition. EV-A71 mutants with K242A and K244A rapidly acquired compensatory mutations, T100K or E98A, and Q145R-T237N respectively, which restored the heparin-binding phenotype. Both VP1-98 and VP1-145 modulates heparin binding. Heparin-binding phenotype was completely abolished with VP1-E98-E145, but was restored by an E98K or E145Q substitution. During cell culture adaptation, EV-A71 rapidly acquired K98 or Q/G145 to restore the heparin-binding phenotype. Together with next-generation sequencing analysis, our results implied that EV-A71 has high genetic plasticity by modulating positively-charged residues at the five-fold axis during in vitro heparin adaptation. Our finding has impact on EV-A71 vaccine production, evolutionary studies and pathogenesis.
Fulltext Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans

Tan CW, Wittwer K, Lim XF, Uehara A, Mani S, Wang LF, et al.

Emerg Microbes Infect, 2019;8(1):787-795.
PMID: 31132935 DOI: 10.1080/22221751.2019.1621668

Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sources of human infection. In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay. To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys. Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted. Additionally, one of the uninfected animals seroconverted, implying active shedding and transmission of PRV3M. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.
Fulltext A comprehensive review of demand side management in distributed grids based on real estate perspectives

Dahiru AT, Daud D, Tan CW, Jagun ZT, Samsudin S, Dobi AM

Environ Sci Pollut Res Int, 2023 Jul;30(34):81984-82013.
PMID: 36652076 DOI: 10.1007/s11356-023-25146-x

A major challenge in renewable energy planning and integration with existing systems is the management of intermittence of the resources and customer demand uncertainties that are attributed to climates. In emerging distributed grids, state-of-the-art optimization techniques were used for cost and reliability objectives. In the existing literature, power dispatch and demand side management schemes were implemented for various techno-economic objectives. In renewable energy-based distributed grids, power dispatch is strategic to system operations. However, demand side management is preferred, as it allows more options for customer participation and active management of energy in buildings. Moreover, the demand side management can simply follow supplies. This paper investigates the implications of demand side management as it affects planning and operations in renewable energy-based distributed grids. Integration of demand side management in customer-oriented plans such as the time-of-use and real-time-pricing on residential and commercial demands is conceptualised to ensure effective customer participation which maintains the valued comforts. Moreover, the optimised tariff integrated demand side management implementations based on the utility-initiated demand response programmes are envisaged to offset conflicting objectives of the economy and customer comforts within residential and commercial demands and are also viewed as a step towards efficient management of energy in buildings.
Identification and characterization of neutralization epitopes at VP2 and VP1 of enterovirus A71

NikNadia N, Tan CW, Ong KC, Sam IC, Chan YF

J Med Virol, 2018 06;90(6):1164-1167.
PMID: 29457642 DOI: 10.1002/jmv.25061

Enterovirus A71 (EV-A71) neutralization escape mutants were generated with monoclonal antibody MAB979 (Millipore). The VP2-T141I and VP1-D14N substitutions were identified. Using reverse genetics, infectious clones with these substitutions were constructed and tested by neutralization assay with immune sera from mice and humans. The N-terminus VP1-14 is more important than EF loop VP2-141 in acute human infection, mainly because it recognised IgM present in acute infection. The N-terminus VP1 could be a useful target for diagnostics and therapeutic antibodies in acute infection.
Occupational rehabilitation in Singapore and Malaysia

Chan KF, Tan CW, Yeo DS, Tan HS, Tan FL, Tan EW, et al.

J Occup Rehabil, 2011 Mar;21 Suppl 1:S69-76.
PMID: 21328063 DOI: 10.1007/s10926-011-9289-1

INTRODUCTION: Asia is the new and favored magnet of economic attention and foreign investments after it made an almost uneventful rebound from the depths of financial crisis of 2008/2009. Not many Western observers fully understand the diversity that is Asia other than perhaps its 2 growing economic giants of China and India. Indeed many smaller countries like Singapore and Malaysia in South East Asia along with Australia and Hong Kong (a Special Administrative Region within China) look to symbiotic relationships with these two economic giants. The purpose of this discussion paper is to examine the current issues related to the development and provision of occupational rehabilitation services in Singapore and Malaysia with a forward-looking view of how Asia's different developing societies could potentially benefit from better alignment of occupational rehabilitation practices and sharing of expertise through international collaboration and dialogue platforms.
METHODS: Seven therapists and one physician who are frequently involved in occupational rehabilitation services in their home countries critically reviewed the current issues in Singapore and Malaysia which included analysis of the prevalence and cost of occupational injury; overview of workers' compensation system; current practices, obstacles, and challenges in providing occupational rehabilitation and return to work practices. They also offered opinions about how to improve the occupational rehabilitation programs of their two home countries.
CONCLUSION: Even though Malaysia and Singapore are two different countries, in many ways their current provision of occupational rehabilitation services and the problems they face with are very similar. There is a lot of room for systemic improvements that require government support and action. Most prominently, the training of more healthcare professionals in the assessment and rehabilitation of the injured worker should be encouraged. There could be better liaison between the many stakeholders and more funding made available to develop resources and to jump start strategic programs. As these two countries are witnessing rapid economic growth, more resources should be allocated to establish holistic care of the injured workers emphasizing early interventions and prevention of chronic disabilities.
Fulltext Audit of hypertension in general practice

Chan SC, Chandramani T, Chen TY, Chong KN, Harbaksh S, Lee TW, et al.

Med J Malaysia, 2005 Oct;60(4):475-82.
PMID: 16570710

An audit of hypertension management was done in October 2004 in nine general practice (GP) clinics. Two structure, ten process and two outcome indicators were assessed. Results showed that targets were achieved in only four indicators, i.e., weight recording (89%), BP monitoring (85.8%), follow-up interval not exceeding 6 months (87.9%) and mean diastolic BP (73.9%). The other indicators (hypertension registry, reminder mechanisms for defaulters, recording of smoking, height, fundoscopy, monitoring of lipid profile, blood sugar, ECG, renal function and achievement of target mean systolic pressure) showed adequacy percentages varying from 22.1 to 68.7. Out of the 1260 patients assessed, 743 (59%) achieved a mean BP < or = 140/90 (or < or = 130/80 mmHg with diabetes mellitus / renal insufficiency) in the last 3 recorded readings. There was a vast difference between individual clinics. Reasons for not achieving targets were discussed and remedial measures for implementation were recommended.
Fulltext Sciatic nerve repair with tissue engineered nerve: Olfactory ensheathing cells seeded poly(lactic-co-glygolic acid) conduit in an animal model

Tan CW, Ng MH, Ohnmar H, Lokanathan Y, Nur-Hidayah H, Roohi SA, et al.

Indian J Orthop, 2013 Nov;47(6):547-52.
PMID: 24379458 DOI: 10.4103/0019-5413.121572

BACKGROUND AND AIM: Synthetic nerve conduits have been sought for repair of nerve defects as the autologous nerve grafts causes donor site morbidity and possess other drawbacks. Many strategies have been investigated to improve nerve regeneration through synthetic nerve guided conduits. Olfactory ensheathing cells (OECs) that share both Schwann cell and astrocytic characteristics have been shown to promote axonal regeneration after transplantation. The present study was driven by the hypothesis that tissue-engineered poly(lactic-co-glycolic acid) (PLGA) seeded with OECs would improve peripheral nerve regeneration in a long sciatic nerve defect.
MATERIALS AND METHODS: Sciatic nerve gap of 15 mm was created in six adult female Sprague-Dawley rats and implanted with PLGA seeded with OECs. The nerve regeneration was assessed electrophysiologically at 2, 4 and 6 weeks following implantation. Histopathological examination, scanning electron microscopic (SEM) examination and immunohistochemical analysis were performed at the end of the study.
RESULTS: Nerve conduction studies revealed a significant improvement of nerve conduction velocities whereby the mean nerve conduction velocity increases from 4.2 ΁ 0.4 m/s at week 2 to 27.3 ΁ 5.7 m/s at week 6 post-implantation (P < 0.0001). Histological analysis revealed presence of spindle-shaped cells. Immunohistochemical analysis further demonstrated the expression of S100 protein in both cell nucleus and the cytoplasm in these cells, hence confirming their Schwann-cell-like property. Under SEM, these cells were found to be actively secreting extracellular matrix.
CONCLUSION: Tissue-engineered PLGA conduit seeded with OECs provided a permissive environment to facilitate nerve regeneration in a small animal model.
Fulltext Isolation and Characterization of Six Vibrio parahaemolyticus Lytic Bacteriophages From Seafood Samples

Tan CW, Rukayadi Y, Hasan H, Abdul-Mutalib NA, Jambari NN, Hara H, et al.

Front Microbiol, 2021;12:616548.
PMID: 33776954 DOI: 10.3389/fmicb.2021.616548

Vibrio parahaemolyticus is a foodborne pathogen that is frequently isolated from a variety of seafood. To control this pathogenic Vibrio spp., the implementation of bacteriophages in aquaculture and food industries have shown a promising alternative to antibiotics. In this study, six bacteriophages isolated from the seafood samples demonstrated a narrow host range specificity that infecting only the V. parahaemolyticus strains. Morphological analysis revealed that bacteriophages Vp33, Vp22, Vp21, and Vp02 belong to the Podoviridae family, while bacteriophages Vp08 and Vp11 were categorized into the Siphoviridae family. All bacteriophages were composed of DNA genome and showed distinctive restriction fragment length polymorphism. The optimal MOI for bacteriophage propagation was determined to be 0.001 to 1. One-step growth curve revealed that the latent period ranged from 10 to 20 min, and the burst size of bacteriophage was approximately 17 to 51 PFU/cell. The influence of temperature and pH levels on the stability of bacteriophages showed that all bacteriophages were optimally stable over a wide range of temperatures and pH levels. In vitro lytic activity of all bacteriophages demonstrated to have a significant effect against V. parahaemolyticus. Besides, the application of a bacteriophage cocktail instead of a single bacteriophage suspension was observed to have a better efficiency to control the growth of V. parahaemolyticus. Results from this study provided a basic understanding of the physiological and biological properties of the isolated bacteriophages before it can be readily used as a biocontrol agent against the growth of V. parahaemolyticus.
Fulltext Prevalence and antibiotic resistance patterns of Vibrio parahaemolyticus isolated from different types of seafood in Selangor, Malaysia

Tan CW, Rukayadi Y, Hasan H, Thung TY, Lee E, Rollon WD, et al.

Saudi J Biol Sci, 2020 Jun;27(6):1602-1608.
PMID: 32489301 DOI: 10.1016/j.sjbs.2020.01.002

Vibrio parahaemolyticus is a foodborne bacterial pathogen that may cause gastroenteritis in humans through the consumption of seafood contaminated with this microorganism. The emergence of antimicrobial and multidrug-resistant bacteria is another serious public health threat worldwide. In this study, the prevalence and antibiotic susceptibility test of V. parahaemolyticus in blood clams, shrimps, surf clams, and squids were determined. The overall prevalence of V. parahaemolyticus in seafood was 85.71% (120/140), consisting of 91.43% (32/35) in blood clam, 88.57% (31/35) in shrimps, 82.86% (29/35) in surf clams, and 80% (28/35) in squids. The majority of V. parahaemolyticus isolates from the seafood samples were found to be susceptible to most antibiotics except ampicillin, cefazolin, and penicillin. The MAR indices of V. parahaemolyticus isolates ranged from 0.04 to 0.71 and about 90.83% of isolates were found resistant to more than one antibiotic. The high prevalence of V. parahaemolyticus in seafood and multidrug-resistant isolates detected in this study could pose a potential risk to human health and hence appropriate control methods should be in place to minimize the potential contamination and prevent the emergence of antibiotic resistance.

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