Browse publications by year: 2017

  1. Shakya R, Tarulli GA, Sheng L, Lokman NA, Ricciardelli C, Pishas KI, et al.
    Oncogene, 2017 08;36(31):4469-4480.
    PMID: 28368395 DOI: 10.1038/onc.2017.66
    Missense mutations in the TP53 tumor-suppressor gene inactivate its antitumorigenic properties and endow the incipient cells with newly acquired oncogenic properties that drive invasion and metastasis. Although the oncogenic effect of mutant p53 transcriptome has been widely acknowledged, the global influence of mutant p53 on cancer cell proteome remains to be fully elucidated. Here, we show that mutant p53 drives the release of invasive extracellular factors (the 'secretome') that facilitates the invasion of lung cancer cell lines. Proteomic characterization of the secretome from mutant p53-inducible H1299 human non-small cell lung cancer cell line discovered that the mutant p53 drives its oncogenic pathways through modulating the gene expression of numerous targets that are subsequently secreted from the cells. Of these genes, alpha-1 antitrypsin (A1AT) was identified as a critical effector of mutant p53 that drives invasion in vitro and in vivo, together with induction of epithelial-mesenchymal transition markers expression. Mutant p53 upregulated A1AT transcriptionally through the involvement with its family member p63. Conditioned medium containing secreted A1AT enhanced cell invasion, while an A1AT-blocking antibody attenuated the mutant p53-driven migration and invasion. Importantly, high A1AT expression correlated with increased tumor stage, elevated p53 staining and shorter overall survival in lung adenocarcinoma patients. Collectively, these findings suggest that A1AT is an indispensable target of mutant p53 with prognostic and therapeutic potential in mutant p53-expressing tumors.
    MeSH terms: alpha 1-Antitrypsin/genetics*; Cell Cycle; Cell Movement; Humans; Lung Neoplasms/pathology*; Mutation; Neoplasm Invasiveness; Up-Regulation; Tumor Suppressor Protein p53/genetics*; Tumor Suppressor Protein p53/physiology; Proteomics; Cell Line, Tumor; Epithelial-Mesenchymal Transition
  2. Tan YF, Teng CL, Chua KB, Voon K
    J Infect Dev Ctries, 2017 Mar 31;11(3):215-219.
    PMID: 28368854 DOI: 10.3855/jidc.9112
    INTRODUCTION: Pteropine orthoreovirus (PRV) is an emerging zoonotic respiratory virus that has spilled over from bats to humans. Though initially found only in bats, further case studies have found viable virus in ill patients.

    METHODOLOGY: PubMed was queried with the keywords of Nelson Bay orthoreovirus OR Pteropine orthoreovirus OR Melaka orthoreovirus OR Kampar orthoreovirus, and returned 17 hits.

    RESULTS: Based on prevalence studies, the presence of PRV has been reported in Malaysia and Vietnam, both developing countries. Other case reports also provide further evidence of the presence of PRV in the Southeast Asian region. Despite the absence of PRV in their home countries, travellers from Hong Kong and Japan to Indonesia have returned to their countries ill with this virus, indicating that local communities in Indonesia might be affected by this virus.

    CONCLUSIONS: This work aims to bring to light this emerging zoonotic respiratory virus circulating among developing countries in Southeast Asia. To improve the understanding of PRV of the medical and scientific community in the Southeast Asian region, this work introduces the general features of PRV, reports of imported PRV, prevalence, and clinical features of PRV. Gaps in knowledge about PRV have also been identified in this work, and we hope that future studies can be undertaken to improve our understanding of this virus.

    MeSH terms: Animals; Asia, Southeastern/epidemiology; Humans; Reoviridae Infections/epidemiology*; Reoviridae Infections/pathology; Reoviridae Infections/virology*; Respiratory Tract Infections/epidemiology*; Respiratory Tract Infections/pathology; Respiratory Tract Infections/virology*; Tropical Climate; Zoonoses/epidemiology*; Zoonoses/pathology; Zoonoses/virology*; Prevalence; Orthoreovirus/isolation & purification*; Communicable Diseases, Emerging/epidemiology; Communicable Diseases, Emerging/pathology; Communicable Diseases, Emerging/virology
  3. Lai LL, Chan WK, Sthaneshwar P, Nik Mustapha NR, Goh KL, Mahadeva S
    PLoS One, 2017;12(4):e0174982.
    PMID: 28369100 DOI: 10.1371/journal.pone.0174982
    Wisteria floribunda agglutinin-positive Mac-2 binding protein (WFA+-M2BP) has been suggested to be useful for the assessment of disease severity in non-alcoholic fatty liver disease (NAFLD). Consecutive adult NAFLD patients who had a liver biopsy were included. Serum WFA+-M2BP level was measured using a lectin-antibody sandwich immunoassay using a chemiluminescence enzyme immunoassay machine (HISCL-5000, Sysmex, Kobe, Japan). The measured levels were indexed using the following equation: Cut-off index (COI) = ([WFA+-M2BP]sample-[WFA+-M2BP]NC) / ([WFA+-M2BP]PC-[WFA+-M2BP]NC), where PC = positive control and NC = negative control. Histopathological examination of liver biopsy specimen was reported according to Non-Alcoholic Steatohepatitis (NASH) Clinical Research Network Scoring System. Data for 220 cases were analyzed. The AUROC of the COI for the diagnosis of NASH was 0.65. The AUROC of the COI for the diagnosis of steatosis grade ≥2 and 3 was 0.64 and 0.53, respectively. The AUROC of the COI for the diagnosis of lobular inflammation grade ≥1, ≥2 and 3 was 0.57, 0.68 and 0.59, respectively. The AUROC of the COI for the diagnosis of hepatocyte ballooning grade ≥1 and 2 was 0.64 and 0.65, respectively. The AUROC of the COI for the diagnosis of fibrosis stage ≥1, ≥2, ≥3 and 4 was 0.61, 0.71, 0.74 and 0.84, respectively. Out of the 220 cases, 152 cases were the same 76 patients who had a repeat liver biopsy after 48 weeks of intervention. The AUROC of the change in the COI to detect improvement in steatosis, lobular inflammation, hepatocyte ballooning and fibrosis was 0.57, 0.54, 0.59 and 0.52, respectively. In conclusion, serum WFA+-M2BP was most useful for the diagnosis of significant fibrosis, advanced fibrosis and cirrhosis in NAFLD patients. However, it was less useful for differentiating NASH from non-NASH, and for diagnosis and follow-up of the individual histopathological components of NASH.
    MeSH terms: Antigens, Neoplasm/blood*; Diagnosis, Differential; Female; Humans; Immunoassay; Inflammation/diagnosis; Liver Cirrhosis/blood; Liver Cirrhosis/pathology*; Male; Membrane Glycoproteins/blood*; Middle Aged; Obesity/pathology; Hepatocytes/pathology; Wisteria/metabolism*; Receptors, N-Acetylglucosamine/metabolism*; Plant Lectins/metabolism*; Luminescence; Non-alcoholic Fatty Liver Disease/blood; Non-alcoholic Fatty Liver Disease/diagnosis*; Non-alcoholic Fatty Liver Disease/pathology
  4. Swarna Nantha Y, Puri A, Mohamad Ali SZ, Suppiah P, Che Ali SA, Ramasamy B, et al.
    Fam Pract, 2017 09 01;34(5):532-538.
    PMID: 28369346 DOI: 10.1093/fampra/cmx017
    Background: Individuals with type 2 diabetes mellitus (DM) are at a greater risk of tuberculosis (TB) reactivation. There is a paucity of information about the risk factors associated with latent tuberculosis infection (LTBI) in patients with diabetes.

    Objective: We conducted an observational study to compare the prevalence and risk factors associated with LTBI factors in Malaysian adults with and without DM.

    Methods: Four hundred and four patients with DM and 359 patients with non-DM at a regional primary care clinic were recruited as participants in this case-control study. The tuberculin sensitivity test (TST) was performed. The presence of LTBI was defined by a TST value of 10 mm in DM patients and 10 mm in the non-DM group. A logistic regression model was used to identify variables associated with LTBI.

    Results: There was no statistical significant difference in the prevalence rates seen between the DM and non-DM group of the study. LTBI prevalence among patients with DM was 28.5%. The proportion of patients in the non-DM group with LTBI was 29.2%. When a critical cut-off of 8 mm was used, the adjusted odds ratio of LTBI in DM patients was 1.88 (95% confidence interval: 1.22-2.82). Smoking was an independent risk factor for LTBI regardless of DM status. HbA1c levels or anthropometric measurements were not associated with LTBI in diabetic patients.

    Conclusions: There is no significant risk of contracting LTBI in DM patients using the standard 10-mm TST cut-off. Nonetheless, using lower cut-offs in a DM population appear valid. Smoking is an important predictor of LTBI.
    MeSH terms: Ambulatory Care Facilities; Diabetes Mellitus, Type 2/complications*; Female; Humans; Malaysia/epidemiology; Male; Middle Aged; Risk Factors; Tuberculin Test; Prevalence; Case-Control Studies; Latent Tuberculosis/epidemiology*
  5. Jeong W, Snell GI, Levvey BJ, Westall GP, Morrissey CO, Ivulich S, et al.
    J Antimicrob Chemother, 2017 Jul 01;72(7):2089-2092.
    PMID: 28369489 DOI: 10.1093/jac/dkx085
    Objectives: This study describes the clinical outcomes and therapeutic drug monitoring (TDM) following posaconazole suspension pre-emptive therapy in lung transplant (LTx) recipients.

    Methods: This was a single-centre, retrospective cohort study evaluating posaconazole suspension pre-emptive therapy in LTx recipients between January 2009 and December 2015.

    Results: Forty-two LTx recipients were prescribed posaconazole suspension pre-emptively. Aspergillus fumigatus was the most commonly isolated fungal organism. Of the patients receiving posaconazole suspension as the initial antifungal post-LTx, 93% had eradication of colonization at 6 months after commencing therapy. In contrast, only 61% had eradication of fungal colonization when posaconazole suspension was administered following initial therapy with voriconazole. Posaconazole suspension appeared to be well tolerated, although one case was curtailed following concern about abnormal liver function and another due to nausea/vomiting. TDM was performed in 37 patients. The initial median (IQR) trough plasma concentration ( C min ) following 400 mg twice-daily posaconazole suspension was 0.78 (0.46-1.19) mg/L. Doses beyond 800 mg daily did not appear to result in a higher median C min.

    Conclusions: Early initiation of posaconazole suspension pre-emptive therapy in LTx recipients appears to be well tolerated and may potentially afford favourable clinical outcomes.

    MeSH terms: Adult; Antifungal Agents/administration & dosage; Antifungal Agents/adverse effects; Antifungal Agents/blood*; Antifungal Agents/therapeutic use; Aspergillosis/drug therapy*; Aspergillosis/microbiology; Aspergillus fumigatus/drug effects*; Aspergillus fumigatus/isolation & purification; Female; Humans; Male; Middle Aged; Retrospective Studies; Suspensions; Triazoles/administration & dosage*; Triazoles/adverse effects; Triazoles/blood*; Triazoles/therapeutic use; Cohort Studies; Lung Transplantation*; Treatment Outcome; Drug Monitoring; Voriconazole/therapeutic use; Transplant Recipients*
  6. Gnanasegaran N, Govindasamy V, Simon C, Gan QF, Vincent-Chong VK, Mani V, et al.
    Eur J Clin Invest, 2017 Mar 30.
    PMID: 28369799 DOI: 10.1111/eci.12753
    BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic (DA-ergic) neurons in the substantia nigra (SN) and represented as a huge threat to the geriatric population. Cell replacement therapies (CRTs) have been proposed as a promising strategy to slow down or replace neuronal loss. Among the widely available cell sources, dental pulp stem cells (DPSCs) portray as an attractive source primarily due to their neural crest origin, ease of tissue procurement and less ethical hurdles.

    MATERIALS AND METHODS: We first demonstrated the in vitro differentiation ability of DPSCs towards DA-ergic-like cells before evaluating their neuro-protection/neuro-restoration capacities in MPTP-induced mice. Transplantation via intrathecal was performed with behavioural assessments being evaluated every fortnight. Subsequent analysis investigating their immuno-modulatory behaviour was conducted using neuronal and microglial cell lines.

    RESULTS: It was apparent that the behavioural parameters began to improve corresponding to tyrosine hydroxylase (TH), dopamine transporter (DAT) and dopamine decarboxylase (AADC) immunostaining in SN and striatum as early as 8-week post-transplantation (P < 0·05). About 60% restoration of DA-ergic neurons was observed at SN in MPTP-treated mice after 12-week post-transplantation. Similarly, their ability to reduce toxic effects of MPTP (DNA damages, reactive oxygen species and nitric oxide release) and regulate cytokine levels was distinctly noted (P < 0·05) upon exposure in in vitro model.

    CONCLUSIONS: Our results suggest that DPSCs may provide a therapeutic benefit in the old-aged PD mice model and may be explored in stem cell-based CRTs especially in geriatric population as an attempt towards 'personalized medicine'.

  7. Tan TS, Syed Hassan S, Yap WB
    Lett Appl Microbiol, 2017 Jun;64(6):446-451.
    PMID: 28370088 DOI: 10.1111/lam.12738
    The study aimed to construct a recombinant Lactobacillus casei expressing the nonstructural (NS) 1 protein of influenza A virus H5N1 on its cell wall. The NS1 gene was first amplified and fused to the pSGANC332 expression plasmid. The NS1 protein expression was carried out by Lact. casei strain C1. PCR screening and DNA sequencing confirmed the presence of recombinant pSG-NS1-ANC332 plasmid in Lact. casei. The plasmid was stably maintained (98·94 ± 1·65%) by the bacterium within the first 20 generations without selective pressure. The NS1 was expressed as a 49-kDa protein in association with the anchoring peptide. The yield was 1·325 ± 0·065 μg mg(-1) of bacterial cells. Lactobacillus casei expressing the NS1 on its cell wall was red-fluorescently stained, but the staining was not observed on Lact. casei carrying the empty pSGANC332. The results implied that Lact. casei strain C1 is a promising host for the expression of surface-bound NS1 protein using the pSGANC332 expression plasmid.

    SIGNIFICANCE AND IMPACT OF THE STUDY: The study has demonstrated, for the first time, the expression of nonstructural 1 (NS1) protein of influenza A virus H5N1 on the cell wall of Lactobacillus casei using the pSGANC332 expression plasmid. Display of NS1 protein on the bacterial cell wall was evident under an immunofluorescence microscopic observation. Lactobacillus casei carrying the NS1 protein could be developed into a universal oral influenza vaccine since the NS1 is highly conserved among influenza viruses.

    MeSH terms: Animals; Cell Wall/genetics; Cell Wall/metabolism; Humans; Influenza, Human/prevention & control*; Influenza, Human/virology; Influenza Vaccines/genetics*; Lactobacillus casei/genetics; Lactobacillus casei/metabolism*; Viral Nonstructural Proteins/genetics; Viral Nonstructural Proteins/metabolism*; Influenza A Virus, H5N1 Subtype/genetics; Influenza A Virus, H5N1 Subtype/immunology*
  8. Liu J, Tan CSY, Yu Z, Li N, Abell C, Scherman OA
    Adv Mater, 2017 Jun;29(22).
    PMID: 28370560 DOI: 10.1002/adma.201605325
    Recent progress on highly tough and stretchable polymer networks has highlighted the potential of wearable electronic devices and structural biomaterials such as cartilage. For some given applications, a combination of desirable mechanical properties including stiffness, strength, toughness, damping, fatigue resistance, and self-healing ability is required. However, integrating such a rigorous set of requirements imposes substantial complexity and difficulty in the design and fabrication of these polymer networks, and has rarely been realized. Here, we describe the construction of supramolecular polymer networks through an in situ copolymerization of acrylamide and functional monomers, which are dynamically complexed with the host molecule cucurbit[8]uril (CB[8]). High molecular weight, thus sufficient chain entanglement, combined with a small-amount dynamic CB[8]-mediated non-covalent crosslinking (2.5 mol%), yields extremely stretchable and tough supramolecular polymer networks, exhibiting remarkable self-healing capability at room temperature. These supramolecular polymer networks can be stretched more than 100× their original length and are able to lift objects 2000× their weight. The reversible association/dissociation of the host-guest complexes bestows the networks with remarkable energy dissipation capability, but also facile complete self-healing at room temperature. In addition to their outstanding mechanical properties, the networks are ionically conductive and transparent. The CB[8]-based supramolecular networks are synthetically accessible in large scale and exhibit outstanding mechanical properties. They could readily lead to the promising use as wearable and self-healable electronic devices, sensors and structural biomaterials.
    MeSH terms: Biocompatible Materials; Cartilage; Electric Conductivity; Imidazoles; Molecular Weight; Polymers; Temperature; Acrylamide; Polymerization
  9. Yeap WC, Lee FC, Shabari Shan DK, Musa H, Appleton DR, Kulaveerasingam H
    Plant J, 2017 Jul;91(1):97-113.
    PMID: 28370622 DOI: 10.1111/tpj.13549
    The oil biosynthesis pathway must be tightly controlled to maximize oil yield. Oil palm accumulates exceptionally high oil content in its mesocarp, suggesting the existence of a unique fruit-specific fatty acid metabolism transcriptional network. We report the complex fruit-specific network of transcription factors responsible for modulation of oil biosynthesis genes in oil palm mesocarp. Transcriptional activation of EgWRI1-1 encoding a key master regulator that activates expression of oil biosynthesis genes, is activated by three ABA-responsive transcription factors, EgNF-YA3, EgNF-YC2 and EgABI5. Overexpression of EgWRI1-1 and its activators in Arabidopsis accelerated flowering, increased seed size and oil content, and altered expression levels of oil biosynthesis genes. Protein-protein interaction experiments demonstrated that EgNF-YA3 interacts directly with EgWRI1-1, forming a transcription complex with EgNF-YC2 and EgABI5 to modulate transcription of oil biosynthesis pathway genes. Furthermore, EgABI5 acts downstream of EgWRKY40, a repressor that interacts with EgWRKY2 to inhibit the transcription of oil biosynthesis genes. We showed that expression of these activators and repressors in oil biosynthesis can be induced by phytohormones coordinating fruit development in oil palm. We propose a model highlighting a hormone signaling network coordinating fruit development and fatty acid biosynthesis.
    MeSH terms: Fruit/genetics; Fruit/metabolism*; Plant Growth Regulators/metabolism; Plant Oils/metabolism; Plant Proteins/genetics; Plant Proteins/metabolism; Transcription Factors/genetics; Transcription Factors/metabolism; Gene Expression Regulation, Plant/genetics; Gene Expression Regulation, Plant/physiology; Arecaceae/genetics; Arecaceae/metabolism*
  10. Shafie H, Syed Zakaria SZ, Adli A, Shareena I, Rohana J
    Pediatr Int, 2017 Jul;59(7):776-780.
    PMID: 28370991 DOI: 10.1111/ped.13285
    BACKGROUND: Occlusive body wrap using polyethylene plastic applied immediately after birth had been shown to reduce hypothermia among preterm infants. Various adjunct methods have been studied in an attempt to further reduce the incidence of hypothermia. This study was conducted to determine whether polyethylene cap is more effective than cotton cap as an adjunct to polyethylene occlusive body wrap in reducing hypothermia in preterm infants.

    METHODS: The subjects consisted of preterm infants 24-34 weeks' gestation born at Universiti Kebangsaan Malaysia Medical Centre. Infants were randomly assigned to NeoCap or control groups. Infants in both groups were wrapped in polyethylene sheets from the neck downwards immediately after birth without prior drying. Infants in the control group had their heads dried and subsequently covered with cotton caps while infants in the NeoCap group had polyethylene caps put on without drying. Axillary temperature was measured on admission to the neonatal intensive care unit (NICU), and after having been stabilized in the incubator.

    RESULTS: Among the 80 infants recruited, admission hypothermia (axillary temperature <36.5°C) was present in 37 (92.5%) and in 40 (100%) in the NeoCap and control groups, respectively. There was no significant difference in mean temperature on NICU admission between the two groups (35.3 vs 35.1°C, P = 0.36). Mean post-stabilization temperature, however, was significantly higher in the NeoCap group (36.0 vs 35.5°C, P = 0.01).

    CONCLUSION: Combined use of polyethylene body wrap and polyethylene cap was associated with a significantly higher mean post-stabilization temperature compared with polyethylene body wrap and cotton cap.

    MeSH terms: Bandages*; Clothing*; Female; Humans; Hypothermia/prevention & control*; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases/prevention & control*; Male; Intensive Care, Neonatal/methods*; Treatment Outcome; Polyethylene*; Cotton Fiber*
  11. Jackson KMP, Rathinasabapathy T, Esposito D, Komarnytsky S
    Mol Nutr Food Res, 2017 Sep;61(9).
    PMID: 28371117 DOI: 10.1002/mnfr.201601118
    SCOPE: Chicory (Cichorium intybus L.) is a perennial herb often consumed as a vegetable, whereas the ground and roasted roots are blended as a coffee substitute. Caffeoylquinic or chlorogenic acids (CQA), the abundant intermediates of lignin biosynthesis in chicory, have been reported to improve glucose metabolism in humans, but the functional group in their structure responsible for this effect has not been yet characterized.

    METHODS AND RESULTS: Here, we showed that three di-O-caffeoylquinic acids suppressed hepatic glucose production in H4IIE rat hepatoma cells by reducing expression of glucose-6-phosphatase (G6Pase) and phosphoenolpyruvate carboxykinase (PEPCK), two key enzymes that regulate hepatic gluconeogenesis. Direct comparisons between CQAs and their metabolites (3-caffeoylquinic, caffeic, and quinic acids) revealed the caffeic acid moiety alone was responsible for the observed effects. Further analysis suggested the activation of PI3K and MAPK pathways as a method of controlling gene expression was shared between caffeoylquinic and caffeic acids. These compounds promoted increased mitochondrial respiration and cellular metabolism, in part by inducing oxidative phosphorylation and proton leak.

    CONCLUSION: We concluded that the caffeic acid moiety was important for suppression of hepatic gluconeogenesis and hyperglycemia, ultimately strengthening the link between dietary interventions based on caffeic acid-containing plant foods and healthy glucose metabolism.

    MeSH terms: Animals; Gluconeogenesis/drug effects; Hypoglycemic Agents/pharmacology*; Pharmacogenetics; Quinic Acid/analogs & derivatives*; Quinic Acid/pharmacology; Structure-Activity Relationship; Plant Roots/chemistry; Chicory/chemistry*; Phosphatidylinositol 3-Kinases/physiology; MAP Kinase Signaling System; Cell Line, Tumor; Rats
  12. Hossain MZ, Daud S, Nambiar P, Razak FA, Ab-Murat N, Saub R, et al.
    Arch Oral Biol, 2017 Aug;80:51-55.
    PMID: 28371626 DOI: 10.1016/j.archoralbio.2017.03.018
    OBJECTIVE: The aim of this study was to investigate correlations between dental pulp cell count of odontoblasts, subodontoblasts and fibroblasts and age, within different age groups. Formulation of regression equations using the dental pulp cell count for predicting age was attempted.

    DESIGN: Eighty-one extracted teeth were grouped into two age groups (6-25 years, 26-80 years). The teeth were demineralized and histological sections were prepared for cell count. Regression equations were generated from regression analysis of cell count and tested for age estimation.

    RESULTS: The number of dental pulp cells were found to increase until around the third decade of life and following this, the odontoblasts and subodontoblasts cell numbers began to decline while the fibroblasts seemed to remain almost stationary. The Pearson correlation test revealed a significant positive correlation between the cell number for all type of cells and age in the 6-25 years group (r=+0.791 for odontoblasts, r=+0.600 for subodontoblasts and r=+0.680 for fibroblasts). In the 26-80 years age group, a significant negative correlation of the odontoblasts (r=-0.777) and subodontoblasts (r=-0.715) with age was observed but for fibroblasts, the correlation value was negligible (r=-0.165). Regression equations generated using odontoblasts and subodontoblasts cell number were applicable for age estimation. The standard error of estimates (SEEs) were around±5years for 6-25 years and±8years for 26-80 years age groups. The mean values of the estimated and chronological ages were not significantly different.

    CONCLUSIONS: A significant correlation between the cell count of odontoblasts and subodontoblasts with age was demonstrated. Regression equations using odontoblasts and subodontoblasts cell number can be used to predict age with some limitations.

    MeSH terms: Dental Pulp; Fibroblasts; Odontoblasts; Regression Analysis; Tooth; Tooth Extraction
  13. Chander S, Tang CR, Al-Maqtari HM, Jamalis J, Penta A, Hadda TB, et al.
    Bioorg Chem, 2017 06;72:74-79.
    PMID: 28371664 DOI: 10.1016/j.bioorg.2017.03.013
    In the present study, a series of fourteen 5-benzoyl-4-methyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-2-one derivatives were designed, synthesized and characterized by appropriate spectral analysis. Further, titled compounds were in-vitro screened against wild HIV-1 RT enzyme using ELISA based colorimetric assay, in which four compounds significantly inhibited the RT activity with IC50≤25µM. Moreover, two significantly active compounds of the series, A10 and A11 exhibited IC50 values 8.62 and 6.87µM respectively, during the in-vitro assay. Structure Activity Relationship (SAR) studies were performed for the synthesized compounds in order to estimate the effect of substitution pattern on the RT inhibitory potency. The cytotoxicity of the synthesized compounds was evaluated against T lymphocytes. Further, putative binding modes of the significantly active (A11) and the least active (A4) compounds with wild HIV-1 RT were also investigated using docking studies.
    MeSH terms: Benzodiazepines/chemical synthesis; Benzodiazepines/pharmacology*; Benzodiazepines/chemistry; Dose-Response Relationship, Drug; Structure-Activity Relationship; Molecular Structure; CD4-Positive T-Lymphocytes; Reverse Transcriptase Inhibitors/chemical synthesis; Reverse Transcriptase Inhibitors/pharmacology*; Reverse Transcriptase Inhibitors/chemistry; HIV Reverse Transcriptase/antagonists & inhibitors*; HIV Reverse Transcriptase/metabolism; Molecular Docking Simulation
  14. Bhoo-Pathy NT, Inaida S, Tanaka S, Taib NA, Yip CH, Saad M, et al.
    Cancer Epidemiol, 2017 06;48:56-61.
    PMID: 28371729 DOI: 10.1016/j.canep.2017.03.007
    BACKGROUND: The benefit of adjuvant chemotherapy in women with T1N0M0 breast cancers is unclear. While gene expression-based prognostic assays may aid management of women with early estrogen receptor (ER) positive tumors, therapeutic decision-making in women with early stage ER negative tumors remains fraught with difficulties. We investigated the association between adjuvant chemotherapy and overall survival in women with T1N0M0, hormone receptor negative breast cancers.

    METHOD: All newly diagnosed breast cancer patients with node-negative and hormone receptor negative tumors measuring≤2cm at the University Malaya Medical Centre (Malaysia) from 1993 to 2013 were included. Mortality of patients with and without adjuvant chemotherapy were compared and adjusted for possible confounders using propensity score.

    RESULTS: Of 6732 breast cancer patients, 341 (5.1%) had small (≤2cm), node-negative and hormone receptor negative tumors at diagnosis. Among them, only 214 (62.8%) received adjuvant chemotherapy. Five-year overall survival was 88.1% (95% confidence interval (CI): 82.0%-94.2%) for patients receiving chemotherapy and 89.6% (95% CI: 85.1%-94.1%) for patients without chemotherapy. Chemotherapy was not associated with survival following adjustment for age, ethnicity, tumor size, tumor grade, HER2 status, lympho-vascular invasion, type of surgery and radiotherapy administration. However, chemotherapy was associated with a significant survival advantage (adjusted hazard ratio: 0.35, 95%CI: 0.14-0.91) in a subgroup of women with high-grade tumors.

    CONCLUSION: Adjuvant chemotherapy does not appear to be associated with a survival benefit in women with T1N0M0, hormone receptor negative breast cancer except in those with high-grade tumors.

    MeSH terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/mortality; Breast Neoplasms/pathology; Female; Humans; Middle Aged; Prognosis; Survival Analysis; Chemotherapy, Adjuvant/methods*
  15. Yu CY, Ang GY, Chong TM, Chin PS, Ngeow YF, Yin WF, et al.
    J Antimicrob Chemother, 2017 04 01;72(4):1253-1255.
    PMID: 28031273 DOI: 10.1093/jac/dkw541
    MeSH terms: Escherichia coli/genetics*; Genome, Bacterial/genetics*; Escherichia coli Proteins/genetics*
  16. Fisher D, Michaels J, Hase R, Zhang J, Kataria S, Sim B, et al.
    J Antimicrob Chemother, 2017 04 01;72(4):1221-1226.
    PMID: 28077673 DOI: 10.1093/jac/dkw551
    Objectives: Healthcare facilities internationally have grown outpatient parenteral antibiotic administration services for the last few decades. The literature contains publications from dozens of countries describing systematized processes with specialist oversight and their levels of service provision and outcomes. Such descriptions are absent in the majority of Asian countries. We sought to elucidate the extent and nature of outpatient parenteral antibiotic therapy (OPAT) in Asia and to consider the ramifications and opportunities for improvement.
    Methods: Utilizing colleagues and their personal networks, we surveyed healthcare facilities across 17 countries in Asia to ascertain the current means (if any) of providing OPAT. In that survey we also sought to explore the capacity and interest of these facilities in developing systematized OPAT services.
    Results: Responses were received from 171 different healthcare facilities from 17 countries. Most (97/171, 57%) stated that they administer outpatient parenteral antibiotics, but only 5 of 162 facilities (3%) outside of Singapore described comprehensive services with specialist oversight.
    Conclusions: There is very likely a large unrecognized problem of unchecked outpatient parenteral antibiotic administration in Asia. Developing comprehensive and systematized OPAT in Asia is needed as a priority in an environment in which the infectious diseases community is demanding broad stewardship approaches. There are nonetheless challenges in establishing and sustaining OPAT programmes. Local champions and leverage off identified local incentives and needs are key to regional advancement.
    Study site: unclear (convenient sample from contacts of investigators)
    Note: Questionnaire available here:
    https://academic.oup.com/jac/article/72/4/1221/2888431#supplementary-data
    MeSH terms: Ambulatory Care; Anti-Bacterial Agents/administration & dosage*; Anti-Bacterial Agents/therapeutic use; Asia/epidemiology; Communicable Diseases/drug therapy*; Communicable Diseases/epidemiology; Humans; Infusions, Parenteral*; Outpatients*; Singapore/epidemiology
  17. Hafiza MN, Isa MI
    Carbohydr Polym, 2017 Jun 01;165:123-131.
    PMID: 28363531 DOI: 10.1016/j.carbpol.2017.02.033
    Addition of doping materials can possibly enhance the ionic conduction of solid polymer electrolyte (SPE). In this work, a new SPE using 2-hydroxyethyl cellulose (2-HEC) incorporated with different ammonium nitrate (NH4NO3) composition was prepared via solution casting method. Studies of structural properties were conducted to correlate the ionic conductivity of 2-HECNH4NO3SPE using X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. Encouraging result was obtained as the ionic conductivity increased about two orders of magnitude upon addition of 12wt% of NH4NO3. XRD analysis shows the most amorphous SPE was obtained at 12-NH4NO3. From FTIR spectra, the interactions between 2-HEC and NH4NO3were observed by the shifts of COH peak from 1355cm-1to 1330cm-1and the presence of new NH peak in the OH region. The spectrum has been validated theoretically using Gaussian software. The results obtained from this study corroborate that the complexes of 2-HEC and NH4NO3responsible to promote the ionic conductivity to the higher value.
  18. Ab Malik N, Mohamad Yatim S, Lam OL, Jin L, McGrath CP
    J Med Internet Res, 2017 03 31;19(3):e87.
    PMID: 28363880 DOI: 10.2196/jmir.7024
    BACKGROUND: Oral hygiene care is of key importance among stroke patients to prevent complications that may compromise rehabilitation or potentially give rise to life-threatening infections such as aspiration pneumonia.

    OBJECTIVE: The aim of this study was to evaluate the effectiveness of a Web-based continuing professional development (CPD) program on "general intention" of the health carers to perform daily mouth cleaning for stroke patients using the theory of planned behavior (TPB).

    METHODS: A double-blind cluster randomized controlled trial was conducted among 547 stroke care providers across 10 hospitals in Malaysia. The centers were block randomized to receive either (1) test intervention (a Web-based CPD program on providing oral hygiene care to stroke patients using TPB) or (2) control intervention (a Web-based CPD program not specific to oral hygiene). Domains of TPB: "attitude," "subjective norm" (SN), "perceived behavior control" (PBC), "general intention" (GI), and "knowledge" related to providing oral hygiene care were assessed preintervention and at 1 month and 6 months postintervention.

    RESULTS: The overall response rate was 68.2% (373/547). At 1 month, between the test and control groups, there was a significant difference in changes in scores of attitude (P=.004) and subjective norm (P=.01), but not in other TPB domains (GI, P=.11; PBC, P=.51; or knowledge, P=.08). At 6 months, there were significant differences in changes in scores of GI (P=.003), attitude (P=.009), SN (P

    MeSH terms: Data Collection; Double-Blind Method; Education, Nursing/methods; Female; Health Education/methods*; Humans; Male; Oral Hygiene/education*; Surveys and Questionnaires; Survivors; Internet/utilization*; Stroke/therapy*
  19. Ambrose KK, Ishak T, Lian LH, Goh KJ, Wong KT, Ahmad-Annuar A, et al.
    BMJ Open, 2017 03 31;7(3):e010711.
    PMID: 28363916 DOI: 10.1136/bmjopen-2015-010711
    OBJECTIVE: The lack of epidemiological data and molecular diagnostic services in Malaysia has hampered the setting-up of a comprehensive management plan for patients with myotonic dystrophy type 1 (DM1), leading to delayed diagnosis, treatment and support for patients and families. The aim of this study was to estimate the prevalence of DM1 in the 3 major ethnic groups in Malaysia and evaluate the feasibility of a single tube triplet-primed PCR (TP-PCR) method for diagnosis of DM1 in Malaysia.

    DESIGN, SETTING AND PARTICIPANTS: We used PCR to determine the size of CTG repeats in 377 individuals not known to be affected by DM and 11 DM1 suspected patients, recruited from a tertiary hospital in Kuala Lumpur. TP-PCR was performed on selected samples, followed by Southern blot hybridisation of PCR amplified fragments to confirm and estimate the size of CTG expansion.

    OUTCOME MEASURES: The number of individuals not known to be affected by DM with (CTG)>18 was determined according to ethnic group and as a whole population. The χ2 test was performed to compare the distribution of (CTG)>18 with 12 other populations. Additionally, the accuracy of TP-PCR in detecting CTG expansion in 11 patients with DM1 was determined by comparing the results with that from Southern blot hybridisation.

    RESULTS: Of the 754 chromosomes studied, (CTG)>18 frequency of 3.60%, 1.57% and 4.00% in the Malay, Chinese and Indian subpopulations, respectively, was detected, showing similarities to data from Thai, Taiwanese and Kuwaiti populations. We also successfully detected CTG expansions in 9 patients using the TP-PCR method followed by the estimation of CTG expansion size via Southern blot hybridisation.

    CONCLUSIONS: The results show a low DM1 prevalence in Malaysia with the possibility of underdiagnosis and demonstrates the feasibility of using a clinical and TP-PCR-based approach for rapid and cost-effective DM1 diagnosis in developing countries.

    MeSH terms: Adult; Child, Preschool; China/ethnology; Ethnic Groups; Female; Humans; India/ethnology; Malaysia/epidemiology; Male; Middle Aged; Myotonic Dystrophy/genetics*; Myotonic Dystrophy/epidemiology; Blotting, Southern; Prevalence; Polymerase Chain Reaction; Trinucleotide Repeats/genetics*; Molecular Diagnostic Techniques; European Continental Ancestry Group/genetics; Asian Continental Ancestry Group/genetics; Myotonin-Protein Kinase/genetics*
  20. Chow CK, Corsi DJ, Gilmore AB, Kruger A, Igumbor E, Chifamba J, et al.
    BMJ Open, 2017 03 31;7(3):e013817.
    PMID: 28363924 DOI: 10.1136/bmjopen-2016-013817
    OBJECTIVES: This study examines in a cross-sectional study 'the tobacco control environment' including tobacco policy implementation and its association with quit ratio.

    SETTING: 545 communities from 17 high-income, upper-middle, low-middle and low-income countries (HIC, UMIC, LMIC, LIC) involved in the Environmental Profile of a Community's Health (EPOCH) study from 2009 to 2014.

    PARTICIPANTS: Community audits and surveys of adults (35-70 years, n=12 953).

    PRIMARY AND SECONDARY OUTCOME MEASURES: Summary scores of tobacco policy implementation (cost and availability of cigarettes, tobacco advertising, antismoking signage), social unacceptability and knowledge were associated with quit ratios (former vs ever smokers) using multilevel logistic regression models.

    RESULTS: Average tobacco control policy score was greater in communities from HIC. Overall 56.1% (306/545) of communities had >2 outlets selling cigarettes and in 28.6% (154/539) there was access to cheap cigarettes (<5cents/cigarette) (3.2% (3/93) in HIC, 0% UMIC, 52.6% (90/171) LMIC and 40.4% (61/151) in LIC). Effective bans (no tobacco advertisements) were in 63.0% (341/541) of communities (81.7% HIC, 52.8% UMIC, 65.1% LMIC and 57.6% LIC). In 70.4% (379/538) of communities, >80% of participants disapproved youth smoking (95.7% HIC, 57.6% UMIC, 76.3% LMIC and 58.9% LIC). The average knowledge score was >80% in 48.4% of communities (94.6% HIC, 53.6% UMIC, 31.8% LMIC and 35.1% LIC). Summary scores of policy implementation, social unacceptability and knowledge were positively and significantly associated with quit ratio and the associations varied by gender, for example, communities in the highest quintile of the combined scores had 5.0 times the quit ratio in men (Odds ratio (OR) 5·0, 95% CI 3.4 to 7.4) and 4.1 times the quit ratio in women (OR 4.1, 95% CI 2.4 to 7.1).

    CONCLUSIONS: This study suggests that more focus is needed on ensuring the tobacco control policy is actually implemented, particularly in LMICs. The gender-related differences in associations of policy, social unacceptability and knowledge suggest that different strategies to promoting quitting may need to be implemented in men compared to women.

    MeSH terms: Adult; Aged; Cross-Sectional Studies; Developing Countries*; Environment; Female; Health Policy*; Humans; Health Knowledge, Attitudes, Practice*; Male; Middle Aged; Patient Acceptance of Health Care*; Surveys and Questionnaires; Smoking/adverse effects; Smoking/therapy; Logistic Models; Odds Ratio; Smoking Cessation*; Developed Countries*; Tobacco Products
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