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  1. Tan QY, Zomer E, Owen AJ, Chin KL, Liew D
    Tob Control, 2020 01;29(1):111-117.
    PMID: 30610080 DOI: 10.1136/tobaccocontrol-2018-054677
    BACKGROUND: The loss of productivity arising from tobacco use in low/middle-income countries has not been well described. We sought to examine the impact of cigarette smoking on population health and work productivity in Malaysia using a recently published measure, the productivity-adjusted life year (PALY).

    METHODS: A life table model was constructed using published Malaysian demographic and mortality data. Our analysis was limited to male smokers due to the low smoking prevalence in females (1.1%). Male smokers aged 15-64 years were followed up until 65 years or until death. The population attributable risk, health-related quality of life decrements and relative reduction in productivity due to smoking were sourced from published data. The analysis was repeated assuming the cohorts were never smokers, and the differences in outcomes represented the health and productivity burden conferred by smoking. The cost of productivity loss was estimated based on the gross domestic product per equivalent full-time worker in Malaysia.

    RESULTS: Tobacco use is highly prevalent among working-age males in Malaysia, with 4.2 million (37.5%) daily smokers among men aged between 15 and 64 years. Overall, our model estimated that smoking resulted in the loss of over 2.1 million life years (2.9%), 5.5 million (8.2%) quality-adjusted life years (QALYs) and 3.0 million (4.8%) PALYs. Smoking was estimated to incur RM275.3 billion (US$69.4 billion) in loss of productivity.

    CONCLUSION: Tobacco use imposes a significant public health and economic burden among working-age males in Malaysia. This study highlights the need of effective public health interventions to reduce tobacco use.

  2. Lo TS, Chua S, Tan YL, Patrimonio MC, Pue LB
    PLoS One, 2018;13(12):e0207375.
    PMID: 30513097 DOI: 10.1371/journal.pone.0207375
    OBJECTIVE: To compare the ultrasonographic positional changes of mid-urethral sling(MUS) tape in relation to symphysis pubis, and the different clinical outcomes among women who underwent MUS insertion with MiniArcTM or MonarcTM for the treatment of stress urinary incontinence 3 years after.

    MATERIALS AND METHODS: A retrospective follow-up study on patients with clinically confirmed stress urodynamic incontinence and urodynamic stress incontinence who had undergone MiniArc or Monarc surgery. Data regarding preoperative evaluation, intraoperative complications and post-operative follow-ups were collated. Main outcome is to determine the change in position of the sling through measurement of the x- and y-axis at rest and during Valsalva maneuver using the 3D introital ultrasound.

    RESULTS: A total of 138 patients were evaluated, 82 belonged to Monarc and 56 to MiniArc. At 3years, objective and subjective cure rates for MiniArc and Monarc were comparable (88%, 91%; p>0.05; 83%, 89%, p>0.05 respectively). Ultrasonographic changes between MiniArc and Monarc from 6 months to 3 years, showed MiniArc to exhibit significant movement in both x- [3.0 ±0.4 mm vs. 2.2 ±0.3 mm (p = 0.02) at rest; 2.6 ±0.3 mm vs. 1.6 ±0.3 mm (p<0.001) during valsalva] and y-axis [3.5 ±0.5 mm vs. 2.0 ±0.3 mm (p<0.001) at rest; 3.3 ±0.5 mm vs. 2.9 ±0.3 mm (p = 0.037) during Valsalva]. The mobility of MiniArc was significantly more than Monarc from rest to Valsalva (1.1 ±0.4 mm vs. 0.3 ±0.3 mm, p = 0.001). Tightness of the sling assessed from the major and minor axis of the urethral core had no significant difference in both groups at rest and during Valsalva. Urethral kinking percentage and the location of the sling did not yield statistical difference.

    CONCLUSION: Maintenance of continence rates of mid-urethral slings depends on the compressive effect of the sling on the urethra, urethral kinking, and sling fixation. From 6months to 3 years, MiniArc changed its position in both x- and y-axis over time, which the authors attribute to loosening of the anchoring mechanism since no clinical relevance could be sought.

  3. Tan TL, Tang YJ, Ching LJ, Abdullah N, Neoh HM
    Sci Rep, 2018 Nov 12;8(1):16698.
    PMID: 30420768 DOI: 10.1038/s41598-018-35144-6
    The purpose of this meta-analysis was to compare the ability of the qSOFA in predicting short- (≤30 days or in-hospital mortality) and long-term (>30 days) mortality among patients outside the intensive care unit setting. Studies reporting on the qSOFA and mortality were searched using MEDLINE and SCOPUS. Studies were included if they involved patients presenting to the ED with suspected infection and usage of qSOFA score for mortality prognostication. Data on qSOFA scores and mortality rates were extracted from 36 studies. The overall pooled sensitivity and specificity for the qSOFA were 48% and 86% for short-term mortality and 32% and 92% for long-term mortality, respectively. Studies reporting on short-term mortality were heterogeneous (Odd ratio, OR = 5.6; 95% CI = 4.6-6.8; Higgins's I2 = 94%), while long-term mortality studies were homogenous (OR = 4.7; 95% CI = 3.5-6.1; Higgins's I2 = 0%). There was no publication bias for short-term mortality analysis. The qSOFA score showed poor sensitivity but moderate specificity for both short and long-term mortality, with similar performance in predicting both short- and long- term mortality. Geographical region was shown to have nominal significant (p = 0.05) influence on qSOFA short-term mortality prediction.
  4. Takaoka H, Low VL, Tan TK, Sofian-Azirun M, Chen CD, Lau KW, et al.
    Acta Trop, 2019 Feb;190:320-328.
    PMID: 30496721 DOI: 10.1016/j.actatropica.2018.11.025
    Simulium pumatense sp. nov. is described from Vietnam, and is placed in the Simulium feuerborni species-group of the subgenus Simulium (Nevermannia) Enderlein. Its morphological characteristics include the relatively smaller numbers of the following three numerical features: inner teeth of the female mandible (15-18), minute conical processes (16) on the female cibarium, and male upper-eye facets (in 15 vertical columns and 16 horizontal rows). Keys are constructed to distinguish this species from four species of the same group in Vietnam. Our molecular analysis of the DNA barcoding COI gene shows that this species is most closely related to cytoform A of the S. feuerborni complex from Thailand.
  5. Sim SM, Lai PSM, Tan KM, Lee HG, Sulaiman CZ
    Asia Pac J Public Health, 2018 11;30(8):737-749.
    PMID: 30486652 DOI: 10.1177/1010539518811161
    The aim of our study was to develop and validate the return and disposal of unused medications (ReDiUM), as there are currently no validated tools available (worldwide) to assess this. The ReDiUM was developed by an expert panel. It was then administered to community-dwelling adults, who could understand English, at baseline and 2 weeks later. A total of 338/354 participants agreed to participate (response rate = 95.4%). Flesch reading ease was 60. The overall Cronbach's α was 0.703 (range = 0.609-0.762). At test-retest, κ values ranged from 0.244 to 0.523. Median total knowledge score was 60% (interquartile range = 40% to 70%). The majority of participants (94.4%) knew that improper drug disposal has harmful effects on the environment. However, their knowledge was low (11.2%) regarding the disposal of pressurized metered-dose inhalers in the garbage. The ReDiUM was found to be a valid and reliable instrument to assess the knowledge, attitude, and practice on the ReDiUM in Malaysia.
  6. Oslan SNH, Tan JS, Saad MZ, Halim M, Mohamed MS, Ariff AB
    Bioprocess Biosyst Eng, 2019 Mar;42(3):355-365.
    PMID: 30483888 DOI: 10.1007/s00449-018-2040-y
    Pasteurella multocida serotype B:2 is the causative agent of haemorrhagic septicaemia, a fatal disease in cattle and buffaloes. For use as a vaccine in the treatment of HS disease, an efficient cultivation of attenuated gdhA derivative P. multocida B:2 (mutant) for mass production of viable cells is required. In this study, the role of amino acids and vitamins on the growth of this particular bacterium was investigated. Initially, three basal media (Brain-heart infusion, Terrific broth, and defined medium YDB) were assessed in terms of growth performance of P. multocida B:2. YDB medium was selected and redesigned to take into account the effects of amino acids (glutamic acid, cysteine, glycine, methionine, lysine, tyrosine, and histidine) and vitamins (vitamin B1, nicotinic acid, riboflavin, pyridoxine, pantothenic acid, and biotin). High viable cell number was largely affected by the availability of micronutrient components and macronutrients. Histidine was essential for the growth whereby a traceable amount (20 mM) was found to greatly enhance the growth of gdhA derivative P. multocida B:2 mutant (6.6 × 109 cfu/mL) by about 19 times as compared to control culture (3.5 × 108 cfu/mL). In addition, amongst the vitamins added, riboflavin exhibited the highest impact on the viability of gdhA derivative P. multocida B:2 mutant (5.3 × 109 cfu/mL). Though the combined histidine and riboflavin in the culture eventually did not promote the stacking impact on cell growth and cell viability, nonetheless, they were still essential and important in either growth medium or production medium.
  7. Chong LC, Ganesan H, Yong CY, Tan WS, Ho KL
    PLoS One, 2019;14(2):e0211740.
    PMID: 30707739 DOI: 10.1371/journal.pone.0211740
    Macrobrachium rosenbergii nodavirus (MrNV) is the causative agent of white tail disease (WTD) which seriously impedes the production of the giant freshwater prawn and has a major economic impact. MrNV contains two segmented RNA molecules, which encode the RNA dependent RNA polymerase (RdRp) and the capsid protein (MrNV-CP) containing 371 amino acid residues. MrNV-CP comprises of the Shell (S) and the Protruding (P) domains, ranging from amino acid residues 1-252 and 253-371, respectively. The P-domain assembles into dimeric protruding spikes, and it is believed to be involved in host cell attachment and internalization. In this study, the recombinant P-domain of MrNV-CP was successfully cloned and expressed in Escherichia coli, purified with an immobilized metal affinity chromatography (IMAC) and size exclusion chromatography (SEC) up to ~90% purity. Characterization of the purified recombinant P-domain with SEC revealed that it formed dimers, and dynamic light scattering (DLS) analysis demonstrated that the hydrodynamic diameter of the dimers was ~6 nm. Circular dichroism (CD) analysis showed that the P-domain contained 67.9% of beta-sheets, but without alpha-helical structures. This is in good agreement with the cryo-electron microscopic analysis of MrNV which demonstrated that the P-domain contains only beta-stranded structures. Our findings of this study provide essential information for the production of the P-domain of MrNV-CP that will aid future studies particularly studies that will shed light on anti-viral drug discovery and provide an understanding of virus-host interactions and the viral pathogenicity.
  8. Acquah C, Agyei D, Obeng EM, Pan S, Tan KX, Danquah MK
    Crit Rev Food Sci Nutr, 2020;60(7):1195-1206.
    PMID: 30714390 DOI: 10.1080/10408398.2018.1564234
    The food and health applications of bioactive peptides have grown remarkably in the past few decades. Current elucidations have shown that bioactive peptides have unique structural arrangement of amino acids, conferring distinct functionalities, and molecular affinity characteristics. However, whereas interest in the biological potency of bioactive peptides has grown, cost-effective techniques for monitoring the structural changes in these peptides and how these changes affect the biological properties have not grown at the same rate. Due to the high binding affinity of aptamers for other biomolecules, they have a huge potential for use in tracking the structural, conformational, and compositional changes in bioactive peptides. This review provides an overview of bioactive peptides and their essential structure-activity relationship. The review further highlights on the types and methods of synthesis of aptamers before the discussion of the prospects, merits, and challenges in the use of aptamers for bioaffinity interactions with bioactive peptides.
  9. Nur Husna SM, Tan HT, Mohamud R, Dyhl-Polk A, Wong KK
    Ther Adv Med Oncol, 2018;10:1758835918808509.
    PMID: 30542378 DOI: 10.1177/1758835918808509
    Breast cancer is the global leading cause of cancer-related death in women and it represents a major health burden worldwide. One of the promising breast cancer therapeutic avenues is through small molecule inhibitors (SMIs) which have undergone rapid progress with successful clinical trials. Recently, three emerging and vital groups of proteins are targeted by SMIs for breast cancer treatment, namely cyclin-dependent kinase 4 and 6 (CDK4/6), poly (adenosine diphosphate-ribose) polymerase (PARP) and phosphoinositide 3-kinase (PI3K). Several of these inhibitors have been approved for the treatment of breast cancer patients or progressed into late-stage clinical trials. Thus, modeling from these successful clinical trials, as well as their limitations, is pivotal for future development and trials of other inhibitors or therapeutic regimens targeting breast cancer patients. In this review, we discuss eight recently approved or novel SMIs against CDK4/6 (palbociclib, ribociclib and abemaciclib), PARP (olaparib, veliparib and talazoparib), and PI3K (buparlisib and alpelisib). The mechanisms of action, series of clinical trials and limitations are described for each inhibitor.
  10. Saeed N, Khoo CS, Remli R, Law ZK, Periyasamy P, Osman SS, et al.
    Front Neurol, 2018;9:966.
    PMID: 30564184 DOI: 10.3389/fneur.2018.00966
    Leptospirosis is a spirochetal zoonotic disease with a wide clinical spectrum, often underdiagnosed especially when presented as an acute neurological manifestation. We report a case of a 24-year-old man with serologically positive leptospirosis, who presented with altered sensorium, seizures and subsequently developed cortical blindness. His brain MRI revealed bilateral occipital and later parietal lobe cerebritis.
  11. Abduraman MA, Hariono M, Yusof R, Rahman NA, Wahab HA, Tan ML
    Heliyon, 2018 Dec;4(12):e01023.
    PMID: 30560214 DOI: 10.1016/j.heliyon.2018.e01023
    Background: Dengue infection is an endemic infectious disease and it can lead to dengue fever, dengue hemorrhagic fever, and/or dengue shock syndromes. Dengue NS2B/NS3 protease complex is essential for viral replication and is a primary target for anti-dengue drug development. In this study, a NS2B/NS3 protease inhibition assay was developed using AlphaScreen® beads and was used to screen compounds for their protease inhibition activities.

    Methods: The assay system utilized a known NS2B/NS3 peptide substrate, a recombinant of NS2B/NS3 protease with proprietary StrepTactin® donor and nickel chelate acceptor beads in 384-well format.

    Results: The optimized assay to screen for NS2B/NS3 protease inhibitors was demonstrated to be potentially useful with reasonable z' factor, coefficient variance and signal to background ratio. However, screening of synthesized thioguanine derivatives using the optimized AlphaScreen® assay revealed weak NS2B/NS3 inhibition activities.

    Conclusion: The AlphaScreen® assay to screen for NS2B/NS3 protease inhibitors is potentially applicable for high throughput screening.

  12. Tan JM, Karthivashan G, Gani SA, Fakurazi S, Hussein MZ
    Chem Cent J, 2016;10:81.
    PMID: 28028386 DOI: 10.1186/s13065-016-0228-2
    In this paper, we demonstrate the preparation of silibinin-loaded carbon nanotubes (SWSB) with surface coating agents via non-covalent approach as an effective drug delivery system. The resulting surface-coated SWSB nanocomposites are extensively characterized by Fourier transform infrared (FTIR) and Raman spectroscopies, ultraviolet-visible (UV-Vis) spectrometry and field emission scanning electron microscopy (FESEM). The FTIR and Raman studies show that an additional layer is formed by these coating agents in the prepared nanocomposites during the coating treatment and these results are confirmed by FESEM. Drug loading and release profiles of the coated SWSB nanocomposites in phosphate buffered saline solution at pH 7.4 is evaluated by UV-Vis spectrometry. The in vitro results indicate that the surface-modified nanocomposites, with SB loading of 45 wt%, altered the initial burst and thus, resulted in a more prolonged and sustained release of SB. In addition, these nanocomposites exhibit a pseudo-second-order release kinetic which was driven by the ion exchange between the ionized SWSB and the anions in the release medium. The cytotoxicity effect of the resulting nanocomposites on normal mouse fibroblast cells is evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. It is observed that the surfactant and polymer coating improved the biocompatibility of the SWSB nanocomposites significantly, which deem further exploitation for their application as potential anticancer drug delivery system.
  13. Low LE, Tan LT, Goh BH, Tey BT, Ong BH, Tang SY
    Int J Biol Macromol, 2019 Apr 15;127:76-84.
    PMID: 30639596 DOI: 10.1016/j.ijbiomac.2019.01.037
    Stimuli-responsive drug release and controlled delivery play crucial roles in enhancing the therapeutic efficacy and lowering over-dosage induced side effects. In this paper, we report magnetically-triggered drug release and in-vitro anti-colon cancer efficacy of Fe3O4@cellulose nanocrystal (MCNC)-stabilized Pickering emulsions containing curcumin (CUR). The loading efficiency of CUR in the micron-sized (≈7 μm) MCNC-stabilized Pickering emulsions (MCNC-PE) template was found to be 99.35%. The drug release profiles showed that the exposure of MCNC-PE to external magnetic field (EMF) (0.7 T) stimulated the release of bioactive from MCNC-PE achieving 53.30 ± 5.08% of the initial loading over a 4-day period. The MTT assay demonstrated that the CUR-loaded MCNC-PE can effectively inhibits the human colon cancer cells growth down to 18% in the presence of EMF. The formulation also resulted in 2-fold reduction on the volume of the 3-D multicellular spheroids of HCT116 as compared to the control sample. The MCNC particle was found to be non-toxic to brine shrimp up to a concentration of 100 μg/mL. Our findings suggested that the palm-based MCNC-PE could be a promising yet effective colloidal drug delivery system for magnetic-triggered release of bioactive and therapeutics.
  14. Wan SA, Teh CL, Jobli AT, Cheong YK, Chin WV, Tan BB
    J Med Case Rep, 2019 Jan 08;13(1):8.
    PMID: 30626451 DOI: 10.1186/s13256-018-1940-4
    BACKGROUND: Gout is a monosodium urate deposition disease which is prevalent worldwide. The usual manifestations are crystal arthropathy and tophi deposition in the soft tissues. Spinal tophi may also occur and are rarely reported, resulting in various clinical manifestations such as back pain, spinal cord compression, radiculopathy, and even mimicking epidural abscess and spondylodiscitis.

    CASE PRESENTATION: We report a case of a 42-year-old Chinese man with underlying gout who presented with back pain and radiculopathy. The diagnosis of spinal tophi was unsuspected and he was initially treated for epidural abscess and spondylodiscitis. He underwent a laminectomy and posterolateral fusion during which tophus material was discovered. He recovered and medications for gout were started.

    CONCLUSION: Spinal tophi are rare. The diagnosis is difficult and spinal tophi may be mistaken for epidural abscess, spondylodiscitis, or neoplasm.
  15. Win ST, Tan PC, Balchin I, Khong SY, Si Lay K, Omar SZ
    Am J Obstet Gynecol, 2019 04;220(4):387.e1-387.e12.
    PMID: 30633917 DOI: 10.1016/j.ajog.2019.01.004
    BACKGROUND: Labor is induced in 20-30% of maternities, with an increasing trend of use. Labor induction with oral misoprostol is associated with reduced risk of cesarean deliveries and has a safety and effectiveness profile comparable to those of mechanical methods such as Foley catheter use. Labor induction in nulliparous women continues to be challenging, with the process often quite protracted. The eventual cesarean delivery rate is high, particularly when the cervix is unfavorable and ripening is required. Vaginal examination can cause discomfort and emotional distress particularly to nulliparous women, and plausibly can affect patient satisfaction with the induction and birth process.

    OBJECTIVE: The aim of this study was to evaluate regular (4-hourly prior to each oral misoprostol dose with amniotomy when feasible) compared with restricted (only if indicated) vaginal assessments during labor induction with oral misoprostol in term nulliparous women MATERIALS AND METHODS: We performed a randomized trial between November 2016 and September 2017 in a university hospital in Malaysia. Our oral misoprostol labor induction regimen comprised 50 μg of misoprostol administered 4 hourly for up to 3 doses in the first 24 hours. Participants assigned to regular assessment had vaginal examinations before each 4-hourly misoprostol dose with a view to amniotomy as soon as it was feasible. Participants in the restricted arm had vaginal examinations only if indicated. Primary outcomes were patient satisfaction with the birth process (using an 11-point visual numerical rating scale), induction to vaginal delivery interval, and vaginal delivery rate at 24 hours.

    RESULTS: Data from 204 participants (101 regular, 103 restricted) were analyzed. The patient satisfaction score with the birth process was as follows (median [interquartile range]): 7 [6-9] vs 8 [6-10], P = .15. The interval of induction to vaginal delivery (mean ± standard deviation) was 24.3 ± 12.8 vs 31.1 ± 15.0 hours (P = .013). The vaginal delivery rate at 24 hours was 27.7% vs 20.4%; (relative risk [RR], 1.4; 95% confidence interval [CI], 0.8-2.3; P = .14) for the regular vs restricted arms, respectively. The cesarean delivery rate was 50% vs 43% (RR, 1.1; 95% CI, 0.9-1.5; P = .36). When assessed after delivery, participants' fidelity to their assigned vaginal examination schedule in a future labor induction was 45% vs 88% (RR, 0.5; 95% CI, 0.4-0.7; P < .001), and they would recommend their assigned schedule to a friend (47% vs 87%; RR, 0.6; 95% CI, 0.5-0.7; P < .001) in the regular compared with the restricted arms, respectively.

    CONCLUSION: Despite a shorter induction to vaginal delivery interval with regular vaginal examination and a similar vaginal delivery rate at 24 hours and birth process satisfaction score, women expressed a higher preference for the restricted examination schedule and were more likely to recommend such a schedule to a friend.

  16. A/L B Vasanth Rao VR, Tan SH, Candasamy M, Bhattamisra SK
    Diabetes Metab Syndr, 2018 11 30;13(1):754-762.
    PMID: 30641802 DOI: 10.1016/j.dsx.2018.11.054
    Diabetic nephropathy (DN) is a major cause of end-stage renal disease and affects a large number of individuals with diabetes. However, the development of specific treatments for DN has not yet been identified. Hence, this review is concisely designed to understand the molecular pathways leading to DN in order to develop suitable therapeutic strategies. Extensive literature search have been carried in regard with the pathogenesis and pathophysiology of DN, drug targets and updates on clinical trials, the consequences associated with DN and the potential biomarkers for diagnosis and prediction of DN are discussed in this review. DN is characterised by microalbuminuria and macroalbuminuria, and morphological changes such as glomerular thickening, interstitial fibrosis, formation of nodular glomerulosclerosis and decreased endothelial cell fenestration. Besides, the involvement of renin-angiotensin-aldosterone system, inflammation and genetic factors are the key pathways in the progression of DN. In regard with drug development drugs targeted to epidermal growth factor, inflammatory cytokines, ACTH receptor and TGFβ1 receptors are in pipeline for clinical trials whereas, several drugs have also failed in phase III and phase IV of clinical trials due to lack of efficacy and severe adverse effect. The research on DN is limited with respect to its pathogenesis and drug development. Thus, a more detailed understanding of the pathogenesis of DN is very essential to progress in the drug development process.
  17. Wu YX, Kim YJ, Kwon TH, Tan CP, Son KH, Kim T
    Nat Prod Res, 2020 Jun;34(12):1786-1790.
    PMID: 30470128 DOI: 10.1080/14786419.2018.1527832
    Mulberry (Morus alba L.) root bark (MRB) was extracted using methanol and the extracts were subjected to tests of anti-inflammatory effects. The ethyl acetate fraction demonstrated the best anti-inflammatory effects. Purified compounds, sanggenon B, albanol B and sanggenon D, showed inhibitory effects on NO production in LPS-stimulated RAW264.7 cells and albanol B demonstrated the best anti-inflammatory effects. Regarding the underlying molecular mechanisms, further investigations showed that treatments with Albanol B reduced production of pro-inflammatory cytokines and decreased expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). These results would contribute to development of novel anti-inflammatory drugs from MRB.
  18. Fong W, Liew I, Tan D, Lim KH, Low A, Leung YY
    Clin Exp Rheumatol, 2018 05 24;36 Suppl 112(3):89-93.
    PMID: 29846168
    OBJECTIVES: To describe the features and treatment outcomes of IgG4-RD in multi-ethnic patients in Singapore.
    METHODS: Retrospective study was performed on IgG4-RD patients identified from patient databases in a tertiary hospital.
    RESULTS: Fourty-two patients (76% male) were included; 79% fulfilled the 2011 comprehensive diagnostic criteria for IgG4-RD for definite IgG4-RD. 81% were Chinese and 19% were Malays. Common initial manifestations included jaundice (52%), abdominal pain (36%) and swollen salivary glands (26%). Only 36% had a history of allergy. 83% had ≥ 1 organ involvement. Erythrocyte sedimentation rate, immunoglobulin E, IgG2 and IgG4 levels were elevated in 84%, 100%, 70% and 44% of patients, respectively. The most common histopathological feature was >10 IgG4+ cells per high power field (66%). 94% (34/36) of patients were treated with moderate to high doses of glucocorticoids, including 17 patients with combination immunosuppressants. Of these, all patients responded to therapy by 3 months. With a median (range) follow-up of 4.1 (0.4-13.8) years, 69% (25/36) needed low dose of glucocorticoids to maintain disease remission. Twenty-six per cent had relapse of disease, of which 82% had disease recurrence in the same organs.
    CONCLUSIONS: Pancreatitis, lymphoadenopathy and cholangitis were the commonest manifestations in Asians with IgG4-RD. All patients responded to glucocorticoid therapy by 3 months, two-thirds required maintenance therapy with glucocorticoids, and one-quarter developed relapse of disease.
  19. Tai MLS, Goh KJ, Kadir KAA, Zakaria MI, Yap JF, Tan KS
    Singapore Med J, 2019 May;60(5):236-240.
    PMID: 30488077 DOI: 10.11622/smedj.2018150
    INTRODUCTION: Intravenous (IV) thrombolysis with alteplase (rt-PA) is effective in ischaemic stroke. The primary objective was to evaluate predictors of functional outcome in acute ischaemic stroke (AIS) patients treated with IV rt-PA. The secondary objective was to assess the outcome with the modified Rankin scale (mRS). We also examined the predictive value of the Totaled Health Risks in Vascular Events (THRIVE) score.

    METHODS: AIS patients treated with IV rt-PA from February 2012 to August 2016 were recruited. Demographic data, National Institutes of Health Stroke Scale (NIHSS) scores, timing and neuroradiological findings were recorded. Patients received a dose of 0.9 mg/kg IV rt-PA within 4.5 hours of symptom onset. mRS score was evaluated at discharge and three months, and good and poor clinical outcomes were defined as scores of 0-2 and 3-6, respectively. Baseline THRIVE scores were assessed.

    RESULTS: 36 patients received IV rt-PA. 20 (55.6%) patients had an mRS score of 0-2 at three months. Based on THRIVE score, 86.1% had a good or moderately good prognosis. On univariate analysis, poor outcome was associated with NIHSS score before rt-PA (p = 0.03), THRIVE score (p = 0.02), stroke subtype (p = 0.049) and diabetes mellitus (DM; p = 0.06). Multiple logistic regression showed that outcome was significantly associated with NIHSS score before rt-PA (p = 0.032) and DM (p = 0.010).

    CONCLUSION: Our newly developed Malaysian IV rt-PA service is safe, with similar outcomes to the published literature. Functional outcome after thrombolysis was associated with baseline NIHSS score and DM.

  20. Loh YC, Tan CS, Ch'ng YS, Ng CH, Yeap ZQ, Yam MF
    Hypertens Res, 2019 02;42(2):182-194.
    PMID: 30464217 DOI: 10.1038/s41440-018-0139-9
    Panax notoginseng is the most valuable medicinal plant and has been used clinically for more than two thousand years to treat various diseases, including hypertension. Previous studies claimed that different isolated compounds from P. notoginseng are involved in different pathways for vasodilation. It is strongly believed that these vasodilating compounds might act synergistically in contributing vasodilatory effects via holistic signaling pathways. The present study aims to evaluate the vasodilatory effect and mechanism of action employed by the crude extract of P. notoginseng. The fingerprint of P. notoginseng was developed using tri-step FTIR and HPTLC. The contents of Rg1 and Rb1 in the active extract (PN95) were further quantified via HPTLC. The vasodilatory effect of PN95 was evaluated using an in vitro aortic ring model. The results showed that PN95 contains a high amount of Rg1 and Rb1, 25.9 and 13.6%, respectively. The vasodilatory effect of PN95 was elicited via the NO/sGC/cGMP and β2-adrenergic receptors pathways. Furthermore, PN95 could manage vascular tone by regulating action potentials via potassium and both VOCC and IP3R pathways. The results obtained fulfilled the expected outcome where the PN95 employed more signaling pathways than any of the single active compounds; hence, the holistic therapeutic effect could be achieved and would more easily translate to applications for the treatment of human diseases.
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