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  1. Phua VC, Wong WQ, Tan PL, Bustam AZ, Saad M, Alip A, et al.
    Asian Pac J Cancer Prev, 2015;16(4):1449-53.
    PMID: 25743814
    BACKGROUND: Oral capecitabine is increasingly replacing intravenous 5-fluorouracil in many chemotherapy regimens. However, data on the risk of febrile neutropaenia (FN) and treatment related death (TRD) with the drug remain sparse outside of clinical trial settings despite its widespread usage. This study aimed to determine these rates in a large cohort of patients treated in the University of Malaya Medical Centre (UMMC).

    MATERIALS AND METHODS: We reviewed the clinical notes of all patients prescribed with oral capecitabine chemotherapy for any tumour sites in University Malaya Medical Centre (UMMC) from 1st January 2009 till 31st June 2010. Information collected included patient demographics, histopathological features, treatment received including the different chemotherapy regimens and intent of treatment whether the chemotherapy was given for neoadjuvant, concurrent with radiation, adjuvant or palliative intent. The aim of this study is to establish the pattern of usage, FN and TRD rates with capecitabine in clinical practice outside of clinical trial setting. FN is defined as an oral temperature >38.5°or two consecutive readings of >38.0° for 2 hours and an absolute neutrophil count <0.5 x 109/L, or expected to fall below 0.5 x 109/L (de Naurois et al., 2010). Treatment related death was defined as death occurring during or within 30 days of last chemotherapy treatment.

    RESULTS: Between 1st January 2009 and 30th June 2010, 274 patients were treated with capecitabine chemotherapy in UMMC. The mean age was 58 years (range 22 to 82 years). Capecitabine was used in 14 different tumour sites with the colorectal site predominating with a total of 128 cases (46.7%), followed by breast cancer (35.8%). Capecitabine was most commonly used in the palliative setting accounting for 63.9% of the cases, followed by the adjuvant setting (19.7%). The most common regimen was single agent capecitabine with 129 cases (47.1%). The other common regimens were XELOX (21.5%) and ECX (10.2%). The main result of this study showed an overall FN rate of 2.2% (6/274). The overall TRD rate was 5.1% (14/274). The FN rate for the single agent capecitabine regimen was 1.6% (2/129) and the TRD rate was 5.4% (7/129). All the TRDs were with single agent capecitabine regimen were used for palliative intent.

    CONCLUSIONS: Oral capecitabine is used widely in clinical practice in a myriad of tumour sites and bears a low risk of febrile neutropaenia. However, capecitabine like any other intravenous chemotherapeutic agent carries a significant risk of treatment related death.

  2. Tan SH, Mun KS, Chandran PA, Manuel AM, Prepageran N, Waran V, et al.
    Childs Nerv Syst, 2015 Jul;31(7):1165-9.
    PMID: 25712744 DOI: 10.1007/s00381-015-2667-9
    This paper reports an unusual case of a transsphenoidal encephalocele and discusses our experience with a minimally invasive management. To the best of our knowledge, we present the first case of a combined endoscopic transnasal and transoral approach to a transsphenoidal encephalocele in an infant.
  3. Gan HY, Gan HM, Tan MH, Lee YP, Austin CM
    Mitochondrial DNA A DNA Mapp Seq Anal, 2016 11;27(6):4099-4100.
    PMID: 25629489
    The complete mitochondrial genome of the hermit crab Clibanarius infraspinatus was recovered by genome skimming using Next-Gen sequencing. The Clibanarius infraspinatus mitogenome has 16,504 base pairs (67.94% A + T content) made up of 13 protein-coding genes, 2 ribosomal subunit genes, 22 transfer RNAs and a putative 1500 bp non-coding AT-rich region. The Clibanarius infraspinatus mitogenome sequence is the first for the family Diogenidae and the second for the superfamily Paguroidea and exhibits a translocation of the ND3 gene not previously reported for the Decapoda.
  4. Tan JL, Ngeow YF, Wee WY, Wong GJ, Ng HF, Choo SW
    Sci Rep, 2014;4:7169.
    PMID: 25417557 DOI: 10.1038/srep07169
    Mycobacterium iranicum is a newly reported mycobacterial species. We present the first comparative study of M. iranicum UM_TJL and other mycobacteria. We found M. iranicum to have a close genetic association with environmental mycobacteria infrequently associated with human infections. Nonetheless, UM_TJL is also equipped with many virulence genes (some of which appear to be the consequence of transduction-related gene transfer) that have been identified in established human pathogens. Taken all together, our data suggest that M. iranicum is an environmental bacterium adapted for pathogenicity in the human host. This comparative study provides important clues and forms the basis for future functional studies on this mycobacterium.
  5. Tan CE, Jaffar A, Tong SF, Hamzah MS, Mohamad N
    Med Educ Online, 2014 Jan;19(1):25605.
    PMID: 28440130 DOI: 10.3402/meo.v19.25605
    Introduction The Comprehensive Healthcare (CHC) module was developed to introduce pre-clinical medical and pharmacy students to the concept of comprehensive healthcare. This study aims to explore their shared learning experiences within this module. Methodology During this module, medical and pharmacy students conducted visits to patients' homes and to related community-based organisations in small groups. They were required to write a reflective journal on their experiences regarding working with other professions as part of their module assessment. Highly scored reflective journals written by students from the 2011/2012 academic session were selected for analysis. Their shared learning experiences were identified via thematic analysis. We also analysed students' feedback regarding the module. Results Analysis of 25 selected reflective journals revealed several important themes: 'Understanding of impact of illness and its relation to holistic care', 'Awareness of the role of various healthcare professions' and 'Generic or soft skills for inter-professional collaboration'. Although the primary objective of the module was to expose students to comprehensive healthcare, the students learnt skills required for future collaborative practice from their experiences. Discussion The CHC module provided early clinical exposure to community-based health issues and incorporated some elements of inter-professional education. The students learnt about the roles of other healthcare professions and acquired soft skills required for future collaborative practice during this module.
  6. Roohani K, Tan SW, Yeap SK, Ideris A, Bejo MH, Omar AR
    J Vet Sci, 2015;16(4):447-57.
    PMID: 25643805 DOI: 10.4142/jvs.2015.16.4.447
    A Newcastle disease virus (NDV) isolate designated IBS002 was isolated from a commercial broiler farm in Malaysia. The virus was characterised as a virulent strain based on the multiple basic amino acid motif of the fusion (F) cleavage site (112)RRRKGF(117) and length of the C-terminus extension of the hemagglutinin-neuraminidase (HN) gene. Furthermore, IBS002 was classified as a velogenic NDV with mean death time (MDT) of 51.2 h and intracerebral pathogenicity index (ICPI) of 1.76. A genetic distance analysis based on the full-length F and HN genes showed that both velogenic viruses used in this study, genotype VII NDV isolate IBS002 and genotype VIII NDV isolate AF2240-I, had high genetic variations with genotype II LaSota vaccine. In this study, the protection efficacy of the recombinant genotype VII NDV inactivated vaccine was also evaluated when added to an existing commercial vaccination program against challenge with velogenic NDV IBS002 and NDV AF2240-I in commercial broilers. The results indicated that both LaSota and recombinant genotype VII vaccines offered full protection against challenge with AF2240-I. However, the LaSota vaccine only conferred partial protection against IBS002. In addition, significantly reduced viral shedding was observed in the recombinant genotype VII-vaccinated chickens compared to LaSota-vaccinated chickens.
  7. Tan NC, Ng CJ, Rosemary M, Wahid K, Goh LG
    Asia Pac Fam Med, 2014;13(1):17.
    PMID: 25606021 DOI: 10.1186/s12930-014-0017-9
    Primary care research is at a crossroad in South Pacific. A steering committee comprising a member of WONCA Asia Pacific Regional (APR) council and the President of Fiji College of General Practitioners garnered sponsorship from Fiji Ministry of Health, WONCA APR and pharmaceutical agencies to organize the event in October 2013. This paper describes the processes needed to set up a national primary research agenda through the collaborative efforts of local stakeholders and external facilitators using a test case in South Pacific.
  8. Chan KG, Tan WS, Chang CY, Yin WF, Mumahad Yunos NY
    Genome Announc, 2015;3(2).
    PMID: 25767237 DOI: 10.1128/genomeA.00100-15
    Aeromonas hydrophila has emerged worldwide as a human pathogen. Here, we report the draft whole-genome sequence of a freshwater isolate from Malaysia, A. hydrophila strain M062, and its N-acylhomoserine lactone genes are also reported here.
  9. Gan HM, Tan MH, Lee YP, Hammer MP, Austin CM
    Mitochondrial DNA A DNA Mapp Seq Anal, 2016 11;27(6):4187-4188.
    PMID: 25600740
    The mitogenome of an Australian sample of the mudskipper, Periophthalmus minutus, was recovered from partial sequencing using the MiSeq sequencer. This mudskipper has a mitogenome of 16,506 base pairs (55% A + T content) made up of two ribosomal subunit genes, 13 protein-coding genes, 22 transfer RNAs, and a 838 bp non-coding AT-rich region. This is the first sequenced mitogenome for the genus Periophthalmus and the fifth for the subfamily Oxudercinae.
  10. McGonigle R, Yap WB, Ong ST, Gatherer D, Bakker SE, Tan WS, et al.
    J Struct Biol, 2015 Feb;189(2):73-80.
    PMID: 25557498 DOI: 10.1016/j.jsb.2014.12.006
    Virus-like particles composed of the core antigen of hepatitis B virus (HBcAg) have been shown to be an effective platform for the display of foreign epitopes in vaccine development. Heterologous sequences have been successfully inserted at both amino and carboxy termini as well as internally at the major immunodominant epitope. We used cryogenic electron microscopy (CryoEM) and three-dimensional image reconstruction to investigate the structure of VLPs assembled from an N-terminal extended HBcAg that contained a polyhistidine tag. The insert was seen to form a trimeric spike on the capsid surface that was poorly resolved, most likely owing to it being flexible. We hypothesise that the capacity of N-terminal inserts to form trimers may have application in the development of multivalent vaccines to trimeric antigens. Our analysis also highlights the value of tools for local resolution assessment in studies of partially disordered macromolecular assemblies by cryoEM.
  11. Lu J, Wei H, Wu J, Jamil MF, Tan ML, Adenan MI, et al.
    PLoS One, 2014;9(12):e115648.
    PMID: 25535742 DOI: 10.1371/journal.pone.0115648
    INTRODUCTION: Mitragynine is a major bioactive compound of Kratom, which is derived from the leave extracts of Mitragyna speciosa Korth or Mitragyna speciosa (M. speciosa), a medicinal plant from South East Asia used legally in many countries as stimulant with opioid-like effects for the treatment of chronic pain and opioid-withdrawal symptoms. Fatal incidents with Mitragynine have been associated with cardiac arrest. In this study, we determined the cardiotoxicity of Mitragynine and other chemical constituents isolated using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

    METHODS AND RESULTS: The rapid delayed rectifier potassium current (IKr), L-type Ca2+ current (ICa,L) and action potential duration (APD) were measured by whole cell patch-clamp. The expression of KCNH2 and cytotoxicity was determined by real-time PCR and Caspase activity measurements. After significant IKr suppression by Mitragynine (10 µM) was confirmed in hERG-HEK cells, we systematically examined the effects of Mitragynine and other chemical constituents in hiPSC-CMs. Mitragynine, Paynantheine, Speciogynine and Speciociliatine, dosage-dependently (0.1∼100 µM) suppressed IKr in hiPSC-CMs by 67%∼84% with IC50 ranged from 0.91 to 2.47 µM. Moreover, Mitragynine (10 µM) significantly prolonged APD at 50 and 90% repolarization (APD50 and APD90) (439.0±11.6 vs. 585.2±45.5 ms and 536.0±22.6 vs. 705.9±46.1 ms, respectively) and induced arrhythmia, without altering the L-type Ca2+ current. Neither the expression, and intracellular distribution of KCNH2/Kv11.1, nor the Caspase 3 activity were significantly affected by Mitragynine.

    CONCLUSIONS: Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.

  12. Tan MP, Kamaruzzaman SB, Zakaria MI, Chin AV, Poi PJ
    Geriatr Gerontol Int, 2015 Jan 22.
    PMID: 25613422 DOI: 10.1111/ggi.12446
    METHODS: Information on sociodemographics, dependency using the Barthel index and fall characteristics were collected from consecutive patients attending the ED over a 6-month period. Barthel score was reassessed at 12 months. Ten-year mortality data were obtained through the National Registry Department.
    RESULTS: A total of 198 participants, with a mean age (standard deviation) of 76.2 years (6.3 years) and 74% women, were recruited. Of these, 70% sustained falls indoors, while 49% of falls occurred between 06.00 to 12.00 hours. Total Barthel scores were significantly lower at 1-year follow up compared with baseline (median [interquartile range], 20 [2] vs 18 [5], P 
  13. Tan GH, Bhoo-Pathy N, Taib NA, See MH, Jamaris S, Yip CH
    Cancer Epidemiol, 2015 Feb;39(1):115-7.
    PMID: 25475062 DOI: 10.1016/j.canep.2014.11.005
    Changes in the American Joint Commission on Cancer staging for breast cancer occurred when the 5th Edition was updated to the 6th Edition.
  14. Tan AW, Tay L, Chua KH, Ahmad R, Akbar SA, Pingguan-Murphy B
    Int J Nanomedicine, 2014;9:5389-401.
    PMID: 25473278 DOI: 10.2147/IJN.S72659
    Two important criteria of an ideal biomaterial in the field of stem cells research are to regulate the cell proliferation without the loss of its pluripotency and to direct the differentiation into a specific cell lineage when desired. The present study describes the influence of TiO2 nanofibrous surface structures on the regulation of proliferation and stemness preservation of adipose-derived stem cells (ADSCs). TiO2 nanofiber arrays were produced in situ onto Ti-6Al-4V substrate via a thermal oxidation process and the successful fabrication of these nanostructures was confirmed by field emission scanning electron microscopy (FESEM), energy dispersive spectrometer (EDS), X-ray diffractometer (XRD), and contact angle measurement. ADSCs were seeded on two types of Ti-6Al-4V surfaces (TiO2 nanofibers and flat control), and their morphology, proliferation, and stemness expression were analyzed using FESEM, AlamarBlue assay, flow cytometry, and quantitative real-time polymerase chain reaction (qRT-PCR) after 2 weeks of incubation, respectively. The results show that ADSCs exhibit better adhesion and significantly enhanced proliferation on the TiO2 nanofibrous surfaces compared to the flat control surfaces. The greater proliferation ability of TiO2 nanofibrous surfaces was further confirmed by the results of cell cycle assay. More importantly, TiO2 nanofibrous surfaces significantly upregulate the expressions of stemness markers Sox-2, Nanog3, Rex-1, and Nestin. These results demonstrate that TiO2 nanofibrous surfaces can be used to enhance cell adhesion and proliferation while simultaneously maintaining the stemness of ADSCs, thereby representing a promising approach for their potential application in the field of bone tissue engineering as well as regenerative therapies.
  15. Koe XF, Tengku Muhammad TS, Chong AS, Wahab HA, Tan ML
    Food Sci Nutr, 2014 Sep;2(5):500-20.
    PMID: 25473508 DOI: 10.1002/fsn3.122
    A multiplex RT-qPCR was developed to examine CYP1A2, CYP2D6, and CYP3A4 induction properties of compounds from food and herbal sources. The induction of drug metabolizing enzymes is an important pharmacokinetic interaction with unique features in comparison with inhibition of metabolizing enzymes. Cytochrome induction can lead to serious drug-drug or drug-food interactions, especially if the coadministered drug plasma level is critical as it can reduce therapeutic effects and cause complications. Using this optimized multiplex RT-qPCR, cytochrome induction properties of andrographolide, curcumin, lycopene, bergamottin, and resveratrol were determined. Andrographolide, curcumin, and lycopene produced no significant induction effects on CYP1A2, CYP2D6, and CYP3A4. However, bergamottin appeared to be a significant in vitro CYP1A2 inducer starting from 5 to 50 μmol/L with induction ranging from 60 to 100-fold changes. On the other hand, resveratrol is a weak in vitro CYP1A2 inducer. Examining the cytochrome induction properties of food and herbal compounds help complement CYP inhibition studies and provide labeling and safety caution for such products.
  16. Ullah S, Bustam MA, Nadeem M, Naz MY, Tan WL, Shariff AM
    ScientificWorldJournal, 2014;2014:940502.
    PMID: 25436237 DOI: 10.1155/2014/940502
    Melamine formaldehyde (MF) resins have been synthesized at different reaction temperature and pH values. Different molar ratios of melamine and formaldehyde were used to synthesize the corresponding resins. The prepared resin samples were characterized by using molecular weight determination viscometry and thermogravimetric analysis (TGA). The maximum percentage of solid content (69.7%) was obtained at pH 8.5 and 75°C temperature. The molecular weight of MF resin was increased with an increase of melamine monomer concentration. The highest residual weight 14.125 wt.% was obtained with sample 10.
  17. Ramoo V, Abdullah KL, Tan PS, Wong LP, Chua PY
    Nurs Crit Care, 2016 Sep;21(5):287-94.
    PMID: 25271143 DOI: 10.1111/nicc.12105
    BACKGROUND: Sedation management is an integral component of critical care practice. It requires the greatest attention of critical care practitioners because it carries significant risks to patients. Therefore, it is imperative that nurses are aware of potential adverse consequences of sedation therapy and current sedation practice recommendations.

    AIMS AND OBJECTIVES: To evaluate the impact of an educational intervention on nurses' knowledge of sedation assessment and management.

    DESIGNS AND METHODS: A quasi-experimental design with a pre- and post-test method was used. The educational intervention included theoretical sessions on assessing and managing sedation and hands-on sedation assessment practice using the Richmond Agitation Sedation Scale. Its effect was measured using self-administered questionnaire, completed at the baseline level and 3 months following the intervention.

    RESULTS: Participants were 68 registered nurses from an intensive care unit of a teaching hospital in Malaysia. Significant increases in overall mean knowledge scores were observed from pre- to post-intervention phases (mean of 79·00 versus 102·00, p < 0·001). Nurses with fewer than 5 years of work experience, less than 26 years old, and with a only basic nursing education had significantly greater level of knowledge improvement at the post-intervention phase compared to other colleagues, with mean differences of 24·64 (p = 0·001), 23·81 (p = 0·027) and 27·25 (p = 0·0001), respectively. A repeated-measures analysis of variance revealed a statistically significant effect of educational intervention on knowledge score after controlling for age, years of work and level of nursing education (p = 0·0001, ηp (2) = 0·431).

    CONCLUSION: An educational intervention consisting of theoretical sessions and hands-on sedation assessment practice was found effective in improving nurses' knowledge and understanding of sedation management.

    RELEVANCE TO CLINICAL PRACTICE: This study highlighted the importance of continuing education to increase nurses' understanding of intensive care practices, which is vital for improving the quality of patient care.

  18. Tan CH, Show PL, Ooi CW, Ng EP, Lan JC, Ling TC
    Biotechnol J, 2015 Jan;10(1):31-44.
    PMID: 25273633 DOI: 10.1002/biot.201400301
    Microbial lipases are popular biocatalysts due to their ability to catalyse diverse reactions such as hydrolysis, esterification, and acidolysis. Lipases function efficiently on various substrates in aqueous and non-aqueous media. Lipases are chemo-, regio-, and enantio-specific, and are useful in various industries, including those manufacturing food, detergents, and pharmaceuticals. A large number of lipases from fungal and bacterial sources have been isolated and purified to homogeneity. This success is attributed to the development of both conventional and novel purification techniques. This review highlights the use of these techniques in lipase purification, including conventional techniques such as: (i) ammonium sulphate fractionation; (ii) ion-exchange; (iii) gel filtration and affinity chromatography; as well as novel techniques such as (iv) reverse micellar system; (v) membrane processes; (vi) immunopurification; (vi) aqueous two-phase system; and (vii) aqueous two-phase floatation. A summary of the purification schemes for various bacterial and fungal lipases are also provided.
  19. Yeap LL, Lim KS, Lo YL, Bakar MZ, Tan CT
    Epileptic Disord, 2014 Sep;16(3):375-9.
    PMID: 25167568 DOI: 10.1684/epd.2014.0671
    Hearing loss has been reported with valproic acid (VPA) use. However, this is the first case of VPA-induced hearing loss that was tested and confirmed with a VPA rechallenge, supported by serial audiometry and pharmacokinetic modelling. A 39-year-old truck driver with temporal lobe epilepsy was treated with VPA at 400 mg, twice daily, and developed hearing loss after each dose, but recovered within three hours. Hearing loss fully resolved after VPA discontinuation. Audiometry performed five hours after VPA rechallenge showed significant improvement in hearing thresholds. Pharmacokinetic modelling during the VPA rechallenge showed that hearing loss occurred at a level below the therapeutic range. Brainstem auditory evoked potential at three months after VPA discontinuation showed bilateral conduction defect between the cochlear and superior olivary nucleus, supporting a pre-existing auditory deficit. VPA may cause temporary hearing threshold shift. Pre-existing auditory defect may be a risk factor for VPA-induced hearing loss. Caution should be taken while prescribing VPA to patients with pre-existing auditory deficit.
  20. Tan CE, Fok MW, Luk KD, Cheung KM
    J Orthop Surg (Hong Kong), 2014 Aug;22(2):224-7.
    PMID: 25163961
    PURPOSE. To evaluate the insertion torque and pullout strength of pedicle screws with or without repositioning. METHODS. 20 fresh porcine lumbar vertebrae of similar size were used. The entry point was at the site just lateral and distal to the superior facet joint of the vertebra, and to a depth of 35 mm. A 6.2-mm-diameter, 35-mm-long pedicle screw was inserted parallel to the superior end plate on one side as control. On the other side, an identical screw was first inserted 10º caudal to the superior end plate, and then repositioned parallel to the superior end plate. The insertional torque and pullout strength were measured. RESULTS. Three of the specimens were excluded owing to pedicle fractures during the pullout test. Repositioned pedicle screws were significantly weaker than controls in terms of the maximum insertional torque (3.20 ± 0.28 vs. 2.04 ± 0.28 Nm, 36% difference, p<0.01) and pullout strength (1664 ± 378 vs.1391 ± 295 N, p<0.01). CONCLUSION. Repositioning pedicle screws should be avoided, especially when the pedicle wall is breached. If repositioning is deemed necessary, augmentation with polymethyl methacrylate or a screw with a larger diameter should be considered.
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