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  1. The Will Rogers phenomenon in the staging of breast cancer - does it matter?
    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.
  2. Valproate-induced reversible sensorineural hearing loss: a case report with serial audiometry and pharmacokinetic modelling during a valproate rechallenge
    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.
  3. Fulltext Ultra-low-voltage CMOS-based current bleeding mixer with high LO-RF isolation
    Tan GH, Sidek RM, Ramiah H, Chong WK, Lioe de X
    ScientificWorldJournal, 2014;2014:163414.
    PMID: 25197694 DOI: 10.1155/2014/163414
    This journal presents an ultra-low-voltage current bleeding mixer with high LO-RF port-to-port isolation, implemented on 0.13 μm standard CMOS technology for ZigBee application. The architecture compliments a modified current bleeding topology, consisting of NMOS-based current bleeding transistor, PMOS-based switching stage, and integrated inductors achieving low-voltage operation and high LO-RF isolation. The mixer exhibits a conversion gain of 7.5 dB at the radio frequency (RF) of 2.4 GHz, an input third-order intercept point (IIP3) of 1 dBm, and a LO-RF isolation measured to 60 dB. The DC power consumption is 572 µW at supply voltage of 0.45 V, while consuming a chip area of 0.97 × 0.88 mm(2).
  4. Prenylated xanthones from mangosteen as promising cholinesterase inhibitors and their molecular docking studies
    Khaw KY, Choi SB, Tan SC, Wahab HA, Chan KL, Murugaiyah V
    Phytomedicine, 2014 Sep 25;21(11):1303-9.
    PMID: 25172794 DOI: 10.1016/j.phymed.2014.06.017
    Garcinia mangostana is a well-known tropical plant found mostly in South East Asia. The present study investigated acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitory activities of G. mangostana extract and its chemical constituents using Ellman's colorimetric method. Cholinesterase inhibitory-guided approach led to identification of six bioactive prenylated xanthones showing moderate to potent cholinesterases inhibition with IC50 values of lower than 20.5 μM. The most potent inhibitor of AChE was garcinone C while γ-mangostin was the most potent inhibitor of BChE with IC50 values of 1.24 and 1.78 μM, respectively. Among the xanthones, mangostanol, 3-isomangostin, garcinone C and α-mangostin are AChE selective inhibitors, 8-deoxygartanin is a BChE selective inhibitor while γ-mangostin is a dual inhibitor. Preliminary structure-activity relationship suggests the importance of the C-8 prenyl and C-7 hydroxy groups for good AChE and BChE inhibitory activities. The enzyme kinetic studies indicate that both α-mangostin and garcinone C are mixed-mode inhibitors, while γ-mangostin is a non-competitive inhibitor of AChE. In contrast, both γ-mangostin and garcinone C are uncompetitive inhibitors, while α-mangostin is a mixed-mode inhibitor of BChE. Molecular docking studies revealed that α-mangostin, γ-mangostin and garcinone C interacts differently with the five important regions of AChE and BChE. The nature of protein-ligand interactions is mainly hydrophobic and hydrogen bonding. These bioactive prenylated xanthones are worthy for further investigations.
  5. Variability and repeatability of quantitative, Fourier-domain optical coherence tomography Doppler blood flow in young and elderly healthy subjects
    Tayyari F, Yusof F, Vymyslicky M, Tan O, Huang D, Flanagan JG, et al.
    Invest Ophthalmol Vis Sci, 2014 Dec;55(12):7716-25.
    PMID: 25335983 DOI: 10.1167/iovs.14-14430
    The purpose of this study was to determine the within-session variability and between-session repeatability of spectral Fourier-domain optical coherence tomography (Doppler FD-OCT) Doppler retinal blood flow measurements in young and elderly subjects.
  6. Fulltext Comprehensive Healthcare module: medical and pharmacy students' shared learning experiences
    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.
  7. Intervention to improve intensive care nurses' knowledge of sedation assessment and management
    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.

  8. Fulltext HLA-B*15:02 association with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis in an Indian population: a pooled-data analysis and meta-analysis
    Khor AH, Lim KS, Tan CT, Wong SM, Ng CC
    Epilepsia, 2014 Nov;55(11):e120-4.
    PMID: 25266342 DOI: 10.1111/epi.12802
    This study aimed to investigate the prevalence and association of HLA-B*15:02 with carbamazepine-induced Stevens-Johnson syndrome and toxic epidermal necrolysis (CBZ-SJS/TEN) in the Indian population in Malaysia, which mostly originated from Southern India. HLA-B alleles in five Indian case patients with CBZ-SJS/TEN and 52 CBZ-tolerant controls, and followed by a pooled sample of seven cases from two centers in Malaysia were analyzed. Positive association for HLA-B*15:02 with CBZ-SJS/TEN was detected in Indians (40% [2/5] vs. 3.8% [2/52], odds ratio [OR] 16.7, p = 0.0349), of which 80% (4/5) of the Indian patients originated from Southern India. A pooled sample of seven cases showed stronger association between HLA-B*15:02 and CBZ-SJS/TEN (57.1% [4/7] vs. 3.8% [2/52], OR 33.3, 95% confidence interval [CI] 4.25-162.21, p = 1.05 × 10(-3)). Subsequent meta-analysis on Indians from Malaysia and India further demonstrated a significant and strong association between HLA-B*15:02 and CBZ-SJS/TEN (OR 38.54; 95% CI 6.83-217.34, p < 1.0 × 10(-4)). Our study is the first on Indians predominantly from Southern India that demonstrated HLA-B*15:02 as a strong risk factor for CBZ-SJS/TEN despite a low population allele frequency. This stressed the importance of testing for HLA-B*15:02, irrespective of the ancestral background, including populations with low allele frequency.
  9. Novel lipase purification methods - a review of the latest developments
    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.
  10. Ultrasonography and clinical outcomes following surgical anti-incontinence procedures (Monarc vs Miniarc)
    Lo TS, Tan YL, Wu PY, Cortes EF, Pue LB, Al-Kharabsheh A
    Eur J Obstet Gynecol Reprod Biol, 2014 Nov;182:91-7.
    PMID: 25265496 DOI: 10.1016/j.ejogrb.2014.09.015
    To evaluate the ultrasound morphology and its clinical outcome among women who had undergone Miniarc™ vs Monarc™ in the treatment of stress urinary incontinence (SUI).
  11. Application of chitosan and its derivatives as adsorbents for dye removal from water and wastewater: a review
    Vakili M, Rafatullah M, Salamatinia B, Abdullah AZ, Ibrahim MH, Tan KB, et al.
    Carbohydr Polym, 2014 Nov 26;113:115-30.
    PMID: 25256466 DOI: 10.1016/j.carbpol.2014.07.007
    Chitosan based adsorbents have received a lot of attention for adsorption of dyes. Various modifications of this polysaccharide have been investigated to improve the adsorption properties as well as mechanical and physical characteristics of chitosan. This review paper discusses major research topics related to chitosan and its derivatives for application in the removal of dyes from water. Modification of chitosan changes the original properties of this material so that it can be more suitable for adsorption of different types of dye. Many chitosan derivatives have been obtained through chemical and physical modifications of raw chitosan that include cross-linking, grafting and impregnation of the chitosan backbone. Better understanding of these varieties and their affinity toward different types of dye can help future research to be properly oriented to address knowledge gaps in this area. This review provides better opportunity for researchers to better explore the potential of chitosan-derived adsorbents for removal of a great variety of dyes.
  12. Efficacy of electromagnetic therapy for urinary incontinence: A systematic review
    Lim R, Lee SW, Tan PY, Liong ML, Yuen KH
    Neurourol Urodyn, 2015 Nov;34(8):713-22.
    PMID: 25251335 DOI: 10.1002/nau.22672
    To review whether patients with urinary incontinence (UI) treated with magnetic stimulation (MS) have a higher continence rate compared to sham.
  13. Fulltext A review of feature extraction software for microarray gene expression data
    Tan CS, Ting WS, Mohamad MS, Chan WH, Deris S, Shah ZA
    Biomed Res Int, 2014;2014:213656.
    PMID: 25250315 DOI: 10.1155/2014/213656
    When gene expression data are too large to be processed, they are transformed into a reduced representation set of genes. Transforming large-scale gene expression data into a set of genes is called feature extraction. If the genes extracted are carefully chosen, this gene set can extract the relevant information from the large-scale gene expression data, allowing further analysis by using this reduced representation instead of the full size data. In this paper, we review numerous software applications that can be used for feature extraction. The software reviewed is mainly for Principal Component Analysis (PCA), Independent Component Analysis (ICA), Partial Least Squares (PLS), and Local Linear Embedding (LLE). A summary and sources of the software are provided in the last section for each feature extraction method.
  14. Fulltext Neglected tropical diseases among two indigenous subtribes in peninsular Malaysia: highlighting differences and co-infection of helminthiasis and sarcocystosis
    Lee SC, Ngui R, Tan TK, Muhammad Aidil R, Lim YA
    PLoS One, 2014;9(9):e107980.
    PMID: 25248116 DOI: 10.1371/journal.pone.0107980
    Soil-transmitted helminth (STH) infections have been documented among these minority groups since 1938. However the prevalence of STH is still high among these communities. Most studies tend to consider the Orang Asli (indigenous) as a homogenous group. In contrary, different subtribes have their own cultural practices. To understand this variation better, we studied the prevalence and associated factors of STH and other gut parasitic infections among two common subtribes (i.e. Temuan and Temiar). Results showed that the prevalence of the overall STH infections was higher in the Temuan subtribe (53.2% of 171) compared to the Temiar subtribe (52.7% of 98). Trichuris trichiura (46.2%) was the most prevalent parasite in the Temuan subtribe, followed by Ascaris spp. (25.7%) and hookworm (4.1%). In contrast, Ascaris spp. (39.8%) was more prevalent among the Temiar subtribe, preceded by T. trichiura (35.7%) and finally hookworm (8.3%). There were also co-infections of helminthiasis and intestinal protozoa among both Temuan and Temiar subtribes with rates being three times higher among the Temiar compared to Temuan. The most common co-infection was with Entamoeba histolytica/dispar/moshkovskii (n = 24; 24.5%, 16.0-33.0), followed by Giardia spp. (n = 3; 3.1%, -0.3-6.5). In Temuan, STH infection individuals were also infected with Entamoeba histolytica/dispar/moshkovskii (n = 11; 6.4%, 5.0-13.8), Cryptosporidium spp. (n = 3, 1.8%, -0.2-3.8) and Giardia spp. (n = 2, 1.2%, -0.4-2.8). In comparison, there was no Cryptosporidium spp. detected among the Temiar. However, it was interesting to note that there was an occurrence of co-infection of intestinal helminthiasis and sarcocystosis (intestinal) in a Temiar individual. The last report of sarcocystosis (muscular) among the Orang Asli was in 1978. The present study highlighted the importance of understanding the variation of infections amongst the different Orang Asli subtribes. It is vital to note these differences and use this knowledge to customise effective control measures for the various subtribes.
  15. Acne prevalence, severity and risk factors among medical students in Malaysia
    Muthupalaniappen L, Tan HC, Puah JW, Apipi M, Sohaimi AE, Mahat NF, et al.
    Clin Ter, 2014;165(4):187-92.
    PMID: 25203331 DOI: 10.7417/CT.2014.1731
    BACKGROUND AND AIMS: Acne is a common skin disorder which can cause physical scaring and impact the quality of life. The aim of this study is to determine the prevalence, severity and the risk factors for developing acne among medical students in Universiti Kebangsaan Malaysia (UKM).
    MATERIALS AND METHODS: A cross sectional study among UKM medical students from academic year 1 to 5 was conducted from July 2011 to May 2012. A total of 361 students were selected by stratified cluster sampling method. Baseline data of the students, risk factors, height and weight were recorded. Acne severity was graded using the Comprehensive Acne Severity Scale (CASS).
    RESULTS: The prevalence of acne among medical students is 68.1% (n=246). Males and females were almost equally affected (1:1.1). Majority students with acne were graded as almost clear (55.7%, n=137), mild (35.0%, n=86), moderate (7.7%, n=19), and severe (1.6%, n=4). More than half of them had developed acne scars (59.0%, n= 213). Males were found to be at higher risk of developing acne compared to females (p<0.05, OR=4.734; 95%CL=2.726-8.222). They are also at higher risk of developing moderate and severe grades of acne compared to females (p=0.001). The odds for developing acne was higher when mother (p=0.029; OR=1.752; 95%CL=1.058-2.902) or father (p=0.027; OR=1.852; 95%CL=1.072-3.201) had acne. When both parents were affected by acne the odds of developing acne was 3 times. (p=0.025; OR=3.056; 95%CL=1.153-8.094).
    CONCLUSIONS: This study shows that the prevalence of acne among medical students is high. Hence, it is important to identify those at risk and provide optimal treatment to prevent scarring and possible low self esteem among these future doctors.
    KEYWORDS: acne vulgaris; medical; prevalence; risk factors; severity; students
  16. Oxidized derivatives of macroline, sarpagine, and pleiocarpamine alkaloids from Alstonia angustifolia
    Tan SJ, Lim JL, Low YY, Sim KS, Lim SH, Kam TS
    J Nat Prod, 2014 Sep 26;77(9):2068-80.
    PMID: 25211145 DOI: 10.1021/np500439u
    A total of 20 new indole alkaloids comprising mainly oxidized derivatives of macroline- (including alstofonidine, a macroline indole incorporating a butyrolactone ring-F), pleiocarpamine-, and sarpagine-type alkaloids were isolated from the bark and leaf extracts of Alstonia angustifolia. The structures and relative configurations of these alkaloids were determined using NMR and MS analyses and in some instances confirmed by X-ray diffraction analyses. Alkaloids 3, 7, 35, and 41 showed moderate to weak activity, while 21 showed strong activity in reversing multidrug resistance in vincristine-resistant KB cells.
  17. Fulltext Preparation of astaxanthin nanodispersions using gelatin-based stabilizer systems
    Anarjan N, Nehdi IA, Sbihi HM, Al-Resayes SI, Malmiri HJ, Tan CP
    Molecules, 2014 Sep 10;19(9):14257-65.
    PMID: 25211006 DOI: 10.3390/molecules190914257
    The incorporation of lipophilic nutrients, such as astaxanthin (a fat soluble carotenoid) in nanodispersion systems can either increase the water solubility, stability and bioavailability or widen their applications in aqueous food and pharmaceutical formulations. In this research, gelatin and its combinations with sucrose oleate as a small molecular emulsifier, sodium caseinate (SC) as a protein and gum Arabic as a polysaccharide were used as stabilizer systems in the formation of astaxanthin nanodispersions via an emulsification-evaporation process. The results indicated that the addition of SC to gelatin in the stabilizer system could increase the chemical stability of astaxanthin nanodispersions significantly, while using a mixture of gelatin and sucrose oleate as a stabilizer led to production of nanodispersions with the smallest particle size (121.4±8.6 nm). It was also shown that a combination of gelatin and gum Arabic could produce optimal astaxanthin nanodispersions in terms of physical stability (minimum polydispersity index (PDI) and maximum zeta-potential). This study demonstrated that the mixture of surface active compounds showed higher emulsifying and stabilizing functionality compared to using them individually in the preparation of astaxanthin nanodispersions.
  18. Sodium valproate-aggravated psoriasiform eruption
    Kwan Z, Che Ismail RB, Wong SM, Tan LL, Robinson S, Lim KS
    Int J Dermatol, 2014 Oct;53(10):e477-9.
    PMID: 25209632 DOI: 10.1111/ijd.12579
  19. Fulltext Emergency lung-sparing surgical repair of a complete transection of the right mainstem bronchus due to blunt chest trauma
    Sachithanandan A, Tan YS, Abdul Muis J, Rapi AR, Mohd Arif MN, Badmanaban B, et al.
    Med J Malaysia, 2014 Apr;69(2):92-4.
    PMID: 25241820 MyJurnal
    Traumatic chest injury with complete tracheo- bronchial disruption is uncommon and occurs in approximately 1% of motor vehicle accidents (MVA) (1,2). Such injuries carry a high mortality and patients rarely survive transfer to hospital. A high index of suspicion facilitates early diagnosis. Early operative intervention is vital for survival. We describe a rare case of traumatic complete disruption of the right mainstem bronchus (RMB) due to blunt chest trauma. The transected airway was reanastomosed emergently avoiding a lung resection.
  20. Fulltext Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes
    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.

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