Displaying publications 41 - 60 of 72 in total

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  1. Ker-Woon C, Abd Ghafar N, Hui CK, Mohd Yusof YA, Wan Ngah WZ
    BMC Cell Biol., 2015;16:2.
    PMID: 25887200 DOI: 10.1186/s12860-015-0053-9
    Acacia honey (AH) has been proven to improve skin wound healing, but its therapeutic effects on corneal epithelium has not been elucidated to date. This study aimed to investigate the effects of AH on cultured corneal epithelial cells (CEC) on in vitro corneal abrasion wound healing model. Six New Zealand white rabbits' CEC were isolated and cultured until passage 1. Circular wound area was created onto a confluent monolayer CEC using a corneal trephine which mimicked corneal abrasion and treated with 0.025% AH supplemented in basal medium (BM) and complete cornea medium (CCM). Wound healing was measured as the percentage of wound closure by the migration of CEC on day 0, day 3 and day 6, post wound creation. The morphological changes of CEC were assessed via phase contrast microscopy. Gene and protein expressions of cytokeratin (CK3), fibronectin and cluster of differentiation 44 (CD44) in AH treated groups and control groups were determined by real-time PCR and immunocytochemistry, respectively.
  2. Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Mohd Ramli ES, Aminuddin A, et al.
    PMID: 25789255 DOI: 10.1186/s40200-015-0136-3
    BACKGROUND: Previous studies on the relationship between bone health and metabolic syndrome (MS) have revealed heterogeneous results. There are limited studies employing bone quantitative ultrasonometry in evaluating this relationship. This study aimed to determine the relationship between MS and bone health in a group of Malaysian middle-aged and elderly men using bone quantitative ultrasonometry.

    METHODS: This cross-sectional study recruited 309 free living Chinese and Malay men aged 40 years and above residing in Klang Valley, Malaysia. Their demographic and anthropometric data were collected. Their calcaneal speed of sound (SOS) was measured using a CM-200 bone ultrasonometer. Their blood was collected for the evaluation of lipid profile, total testosterone and sex hormone-binding globulin. The joint interim MS definition was used for the classification of subjects. Multiple linear regression analysis was used to assess the association between SOS and indicators of MS and the presence of MS, with suitable adjustment for confounders.

    RESULTS: There was no significant difference in SOS value between MS and non-MS subjects (p > 0.05). The SOS values among subjects with different MS scores did not differ significantly (p > 0.05). There were no significant associations between SOS values and indicators of MS or the presence of MS (p > 0.05).

    CONCLUSIONS: The relationship between bone health and MS is not significant in Malaysian middle-aged and elderly men. A longitudinal study should be conducted to evaluate the association between bone loss and MS to confirm this finding.

  3. Wee LH, Morad NA, Aan GJ, Makpol S, Wan Ngah WZ, Mohd Yusof YA
    Asian Pac J Cancer Prev, 2015;16(15):6549-56.
    PMID: 26434873
    The PI3K-Akt-mTOR, Wnt/β-catenin and apoptosis signaling pathways have been shown to be involved in genesis of colorectal cancer (CRC). The aim of this study was to elucidate whether combination of Gelam honey and ginger might have chemopreventive properties in HT29 colon cancer cells by modulating the mTOR, Wnt/β-catenin and apoptosis signaling pathways. Treatment with Gelam honey and ginger reduced the viability of the HT29 cells dose dependently with IC50 values of 88 mg/ml and 2.15 mg/ml respectively, their while the combined treatment of 2 mg/ml of ginger with 31 mg/ml of Gelam honey inhibited growth of most HT29 cells. Gelam honey, ginger and combination induced apoptosis in a dose dependent manner with the combined treatment exhibiting the highest apoptosis rate. The combined treatment downregulated the gene expressions of Akt, mTOR, Raptor, Rictor, β-catenin, Gsk3β, Tcf4 and cyclin D1 while cytochrome C and caspase 3 genes were shown to be upregulated. In conclusion, the combination of Gelam honey and ginger may serve as a potential therapy in the treatment of colorectal cancer through inhibiton of mTOR, Wnt/β catenin signaling pathways and induction of apoptosis pathway.
  4. Chin KY, Ima-Nirwana S, Ibrahim S, Mohamed IN, Wan Ngah WZ
    Nutrients, 2014 Nov 26;6(12):5419-33.
    PMID: 25431881 DOI: 10.3390/nu6125419
    Vitamin D insufficiency is a global health problem. The data on vitamin D status in Malaysian men is insufficient. This study aimed to investigate vitamin D status among Chinese and Malay men in Malaysia and its associating factors. A cross-sectional study was conducted on 383 men aged 20 years and above, residing in Klang Valley, Malaysia. Their age, ethnicity, body anthropometry and calcaneal speed of sound (SOS) were recorded. Their fasting blood was collected for serum 25-hydroxyvitamin D (25(OH)D), intact parathyroid (PTH), total calcium and inorganic phosphate assays. Vitamin D deficiency was defined as a serum 25(OH)D level <30 nmol/L and insufficiency as a serum 25(OH)D level between 30 and 50 nmol/L. The overall prevalence of vitamin D deficiency was 0.5%, and insufficiency was 22.7%. Vitamin D deficiency and insufficiency were more prevalent in the Malays compared to the Chinese. Being Chinese, older in age, having lower body mass index (BMI) and a high physical activity status were associated significantly with a higher serum 25(OH)D level (p < 0.05). The serum PTH level was inversely associated with the serum 25(OH)D level (p < 0.05). As a conclusion, a significant proportion of Malaysian men have vitamin D insufficiency, although deficiency is uncommon. Steps should be taken to correct the vitamin D status of these men.
  5. Ng PL, Rajab NF, Then SM, Mohd Yusof YA, Wan Ngah WZ, Pin KY, et al.
    J Zhejiang Univ Sci B, 2014 Aug;15(8):692-700.
    PMID: 25091987 DOI: 10.1631/jzus.B1300303
    OBJECTIVE: The combination effect of Piper betle (PB) and 5-fluorouracil (5-FU) in enhancing the cytotoxic potential of 5-FU in inhibiting the growth of colon cancer cells was investigated.
    METHODS: HT29 and HCT116 cells were subjected to 5-FU or PB treatment. 5-FU and PB were then combined and their effects on both cell lines were observed after 24 h of treatment. PB-5-FU interaction was elucidated by isobologram analysis. Apoptosis features of the treated cells were revealed by annexin V/PI stain. High-performance liquid chromatography (HPLC) was performed to exclude any possible chemical interaction between the compounds.
    RESULTS: In the presence of PB extract, the cytotoxicity of 5-FU was observed at a lower dose (IC50 12.5 µmol/L) and a shorter time (24 h) in both cell lines. Both cell lines treated with 5-FU or PB alone induced a greater apoptosis effect compared with the combination treatment. Isobologram analysis indicated that PB and 5-FU interacted synergistically and antagonistically in inhibiting the growth of HT29 and HCT116 cells, respectively.
    CONCLUSIONS: In the presence of PB, a lower dosage of 5-FU is required to achieve the maximum drug effect in inhibiting the growth of HT29 cells. However, PB did not significantly reduce 5-FU dosage in HCT116 cells. Our result showed that this interaction may not solely contribute to the apoptosis pathway.
    KEYWORDS: 5-Fluorouracil; Herb-drug interaction; Isobologram analysis; Piper betle L.; Piperaceae
  6. Abd Ghafar N, Chua KH, Wan Ngah WZ, Che Hamzah J, Othman F, Abd Rahman R, et al.
    Cell Tissue Bank, 2014 Mar;15(1):25-34.
    PMID: 23292197 DOI: 10.1007/s10561-012-9360-y
    The in vivo quiescent corneal stroma keratocytes need to be transformed to activated state in order to obtain sufficient number of cells either for monolayer evaluation or corneal stroma reconstruction. This study aimed to investigate the phenotypic characterization of corneal stromal cells during culture expansion from the limbal region of the cornea. Isolated corneal keratocytes from limbal tissue of New Zealand White Strain rabbits' corneas (n = 6) were culture expanded until three passages. Keratocytes morphology was examined daily with viability, growth rate, number of cell doubling and population doubling time were recorded at each passage. The expression of collagen type 1, aldehyde dehydrogenase (ALDH), lumican and alpha smooth muscle actin (α-SMA) were detected by RT-PCR. Immunocytochemistry was also used to detect ALDH, α-SMA, collagen type I and Cytokeratin-3 (CK3). Growth kinetic study revealed that the growth rate was low at the initial passage but increase to about two folds with concomitant reduction in population doubling time in later passages. Freshly isolated and cultured keratocytes expressed collagen type 1, ALDH and lumican but α-SMA expression was absent. However, α-SMA was expressed along with the other genes during culture expansion. Keratocytes at P1 expressed all the proteins except CK3. These results suggest that cultured keratocytes maintained most of the gene expression profile of native keratocytes while the emergence of α-SMA in serial passages showed a mix population of various phenotypes. The phenotypic characterization of monolayer keratocytes provides useful information before reconstruction of bioengineered tissue or in vitro pharmaceutical applications.
  7. Abdul Rahman A, Jamal AR, Harun R, Mohd Mokhtar N, Wan Ngah WZ
    PMID: 24980711 DOI: 10.1186/1472-6882-14-213
    Gamma-tocotrienol (GTT), an isomer of vitamin E and hydroxy-chavicol (HC), a major bioactive compound in Piper betle, has been reported to possess anti-carcinogenic properties by modulating different cellular signaling events. One possible strategy to overcome multi-drug resistance and high toxic doses of treatment is by applying combinational therapy especially using natural bioactives in cancer treatment.
  8. Makpol S, Jam FA, Rahim NA, Khor SC, Ismail Z, Yusof YA, et al.
    Clin Ter, 2014;165(1):e39-45.
    PMID: 24589959
    Antioxidant has been recognized to inhibit UV-induced melanogenesis. This study aimed to elucidate the molecular mechanism of tyrostat, tocopherol and tocotrienol-rich fraction in inhibiting melanogenesis in human skin melanocytes.
  9. Wan Hasan WN, Kwak MK, Makpol S, Wan Ngah WZ, Mohd Yusof YA
    PMID: 24559113 DOI: 10.1186/1472-6882-14-72
    Nuclear factor-erythroid 2 p45 related factor 2 (Nrf2) is a primary transcription factor, protecting cells from oxidative stress by regulating a number of antioxidants and phase II detoxifying enzymes. Dietary components such as sulforaphane in broccoli and quercetin in onions have been shown to be inducers of Nrf2. Piper betle (PB) grows well in tropical climate and the leaves are used in a number of traditional remedies for the treatment of stomach ailments and infections among Asians. The aim of this study was to elucidate the effect of Piper betle (PB) leaves extract in Nrf2 signaling pathway by using 2 types of cells; mouse embryonic fibroblasts (MEFs) derived from wild-type (WT) and Nrf2 knockout (N0) mice.
  10. Heng EC, Karsani SA, Abdul Rahman M, Abdul Hamid NA, Hamid Z, Wan Ngah WZ
    Eur J Nutr, 2013 Oct;52(7):1811-20.
    PMID: 23287846 DOI: 10.1007/s00394-012-0485-3
    PURPOSE: Tocotrienol possess beneficial effects not exhibited by tocopherol. In vitro studies using animal models have suggested that these effects are caused via modulation of gene and protein expression. However, human supplementation studies using tocotrienol-rich isomers are limited. This study aims to identify plasma proteins that changed in expression following tocotrienol-rich fraction (TRF) supplementation within two different age groups.

    METHODS: Subjects were divided into two age groups-32 ± 2 (young) and 52 ± 2 (old) years old. Four subjects from each group were assigned with TRF (78% tocotrienol and 22% tocopherol, 150 mg/day) or placebo capsules for 6 months. Fasting plasma were obtained at 0, 3, and 6 months. Plasma tocopherol and tocotrienol levels were determined. Plasma proteome was resolved by 2DE, and differentially expressed proteins identified by MS. The expressions of three proteins were validated by Western blotting.

    RESULTS: Six months of TRF supplementation significantly increased plasma levels of tocopherols and tocotrienols. Proteins identified as being differentially expressed were related to cholesterol homeostasis, acute-phase response, protease inhibitor, and immune response. The expressions of Apolipoprotein A-I precursor, Apolipoprotein E precursor, and C-reactive protein precursor were validated. The old groups showed more proteins changing in expression.

    CONCLUSIONS: TRF appears to not only affect plasma levels of tocopherols and tocotrienols, but also the levels of plasma proteins. The identity of these proteins may provide insights into how TRF exerts its beneficial effects. They may also be potentially developed into biomarkers for the study of the effects and effectiveness of TRF supplementation.

  11. Chin KY, Soelaiman IN, Mohamed IN, Mohamed N, Shuid AN, Muhammad N, et al.
    J Clin Densitom, 2013 Apr-Jun;16(2):189-95.
    PMID: 22572528 DOI: 10.1016/j.jocd.2012.03.004
    The local normative value in quantitative ultrasound (QUS) equipment needs to be established for wider application and accurate classification of patients into respective fracture risk groups. The present study aimed to establish the calcaneal speed of sound (SOS) value for Chinese and Malay men in Malaysia and determine the difference between calcaneal SOS of the local population and the reference values provided by the manufacturer for each age group. This study will also determine the effect of using the manufacturer's young adult (20-29yr) reference or the local young adult reference to classify the subjects into the respective risk groups. Eight hundred forty Malay and Chinese men residing in central peninsular Malaysia were recruited and their calcaneal QUS value was determined using the CM-200 machine (Furuno Electric, Nishinomiya City, Japan). The results showed that the differences in SOS values between Chinese and Malay men were not significant across all the age groups studied (p>0.05). The age-dependent reduction of SOS value assumed a biphasic form, which was evident at 30-39yr and older than 60yr. The calcaneal SOS of the subject under study was significantly higher as compared with the manufacturer's reference (based on Japanese population) in all groups aged 40yr and older (p<0.05). A significant proportion of the subjects in the osteoporosis group was misclassified using the manufacturer's young adult reference as compared with using the local young adult reference (p<0.05). In conclusion, the overall normative value of SOS obtained was suitable for Chinese and Malay men in Malaysia, and a local reference value should be applied to avoid misclassification of subjects into the respective risk groups.
  12. Huri HZ, Makmor-Bakry M, Hashim R, Mustafa N, Wan Ngah WZ
    Int J Clin Pharm, 2012 Dec;34(6):863-70.
    PMID: 22869200 DOI: 10.1007/s11096-012-9682-7
    BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are frequently admitted to the hospital with severe or acute hyperglycaemia secondary to an acute illness or disease. Uncontrolled glycaemia is a significant problem during severe or acute hyperglycaemia.

    OBJECTIVE: This study sought to identify demographic, clinical, and genetic factors that may contribute to increased insulin resistance or worsening of glycaemic control in patients with T2DM.

    SETTING: This prospective cohort study included 156 patients with T2DM and severe or acute hyperglycaemia who were treated with insulin at any medical ward of the National University of Malaysia Medical Centre.

    METHOD: Insulin resistance was determined using the homeostatic model assessment-insulin resistance index. Glycaemic control during the episode of hyperglycaemia was assessed as the degree to which the patient achieved the target glucose levels. The polymerase chain reaction-restriction fragment length polymorphism method was used to identify polymorphisms in insulin receptor substrate (IRS) genes.

    MAIN OUTCOME MEASURE: Identification of possible predictors (demographic, clinical, or genetic) for insulin resistance and glycaemic control during severe/acute hyperglycaemia.

    RESULTS: A polymorphism in IRS1, r.2963 G>A (p.Gly972Arg), was a significant predictor of both insulin resistance [odds ratios (OR) 4.48; 95 % confidence interval (CI) 1.2-16.7; P = 0.03) and worsening of glycaemic control (OR 6.04; 95 % CI 0.6-64.6; P = 0.02). The use of loop diuretics (P < 0.05) and antibiotics (P < 0.05) may indirectly predict worsening of insulin resistance or glycaemic control in patients with severe/acute hyperglycaemia.

    CONCLUSION: Clinical and genetic factors contribute to worsening of insulin resistance and glycaemic control during severe/acute hyperglycaemia in patients with T2DM. Early identification of factors that may influence insulin resistance and glycaemic control may help to achieve optimal glycaemic control during severe/acute hyperglycaemia.

  13. Abdul Murad NA, Othman Z, Khalid M, Abdul Razak Z, Hussain R, Nadesan S, et al.
    Dig Dis Sci, 2012 Nov;57(11):2863-72.
    PMID: 22669205 DOI: 10.1007/s10620-012-2240-2
    BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown.

    AIMS: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes.

    METHODS: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations.

    RESULTS: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC).

    CONCLUSIONS: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.

  14. Then SM, Sanfeliu C, Top GM, Wan Ngah WZ, Mazlan M
    PMID: 22217149 DOI: 10.1186/1743-7075-9-1
    Down syndrome (DS) neurons are more susceptible to oxidative stress and previous studies have shown that vitamin E was able to reduce oxidative stress and improve DS neurons' viability. Therefore, this study was done to investigate the protective role of γ-tocotrienol (γT3) in DS neurons from hydrogen peroxide (H2O2) -induced oxidative stress. The pro-apoptosis tendency of γT3 was compared to α-tocopherol (αT) in non-stress condition as well.
  15. Chin KY, Soelaiman IN, Mohamed IN, Ibrahim S, Wan Ngah WZ
    Arch Osteoporos, 2012;7:135-45.
    PMID: 23225291 DOI: 10.1007/s11657-012-0091-2
    The influences of age, physical activity, and body anthropometry on calcaneal speed of sound are different among young adults, middle-aged, and elderly men.
  16. Lin TS, Abd Latiff A, Abd Hamid NA, Wan Ngah WZ, Mazlan M
    PMID: 23097676 DOI: 10.1155/2012/491027
    Diabetes is a common cause of delayed wound healing. The aim of the study was to determine the effect of topical administration of tocopherol cream on the wound healing process in diabetic rats. The study was conducted using 18 male Sprague Dawley rats which were divided into three groups: (I) diabetic rats receiving control cream (n = 6), (II) diabetic rats receiving 0.06% tocopherol cream (n = 6), and (III) diabetic rats receiving 0.29% tocopherol cream (n = 6). Four cutaneous wounds were created at the dorsal region of the rats. Wound healing was assessed by total protein content, rate of wound closure estimation, and histological studies on the tenth day after wounding. Tocopherol treatment enhanced the wound healing process by increasing rate of wound closure and total protein content significantly (P < 0.05) compared to the control group. Histological observation also showed better organized epithelium and more collagen fibers in the tocopherol treated groups. Application of tocopherol cream enhances wound healing process in diabetic condition which is known to cause delay in wound healing.
  17. Chin SF, Ibahim J, Makpol S, Abdul Hamid NA, Abdul Latiff A, Zakaria Z, et al.
    Nutr Metab (Lond), 2011;8(1):42.
    PMID: 21702918 DOI: 10.1186/1743-7075-8-42
    Vitamin E supplements containing tocotrienols are now being recommended for optimum health but its effects are scarcely known. The objective was to determine the effects of Tocotrienol Rich Fraction (TRF) supplementation on lipid profile and oxidative status in healthy older individuals at a dose of 160 mg/day for 6 months.
  18. Saif-Ali R, Harun R, Al-Jassabi S, Wan Ngah WZ
    Acta Biochim. Pol., 2011;58(2):179-86.
    PMID: 21633728
    This study aimed to investigate the associations of hepatocyte nuclear factor 4 (HNF4) alpha single nucleotide polymorphisms (SNPs) and haplotype with insulin resistance and metabolic syndrome parameters. Nine SNPs spanning the HNF4 alpha P2 promoter (rs4810424, rs1884613 and rs1884614) and coding region (rs2144908, rs6031551, rs6031552, rs1885088, rs1028583 and rs3818247) were genotyped in 160 subjects without diabetes or metabolic syndrome. The HNF4 alpha P2 promoter SNPs rs4810424, rs1884613 and rs1884614 were associated with insulin resistance (p = 0.017; 0.037; 0.024) and body mass index (BMI) (p = 0.03; 0.035; 0.039). The intron 1D SNP rs2144908 was associated with high-density lipoprotein cholesterol (HDLc) (p = 0.020) and the intron 9 SNP rs3818247 showed association with systolic (p = 0.02) and diastolic (p = 0.034) blood pressure. HNF4 alpha common haplotype CCCGTC associated with higher insulin resistance (p = 0.022), fasting blood glucose (FBG) (p = 0.035) and lower HDLc (p = 0.001). In conclusion, subjects with HNF4 alpha P2 variants and haplotypes have been shown to have a higher insulin resistance and are therefore at a higher risk for developing type 2 diabetes mellitus.
  19. Zailan N, Abdul Rashid AH, Das S, Abdul Mokti NA, Hassan Basri J, Teoh SL, et al.
    Clin Ter, 2010;161(6):515-21.
    PMID: 21181079
    Chlorella vulgaris (CV) is a green microalgae enriched with nutrients, vitamins, minerals and chlorophyll. The aim of our study was to evaluate the potential wound healing effects of CV as a dressing while comparing it to sodium alginate dressing.
  20. Then SM, Mazlan M, Mat Top G, Wan Ngah WZ
    Cell Mol Neurobiol, 2009 Jun;29(4):485-96.
    PMID: 19172392 DOI: 10.1007/s10571-008-9340-8
    Besides acting as potent free radical scavengers, tocopherols and tocotrienols have been known to have non-antioxidant properties such as the involvement of alpha-tocopherol (alphaT) in PKC pathway and the anti-cancer properties of gamma-tocotrienol (gammaT3). This study aims to elucidate whether protective effects shown by alphaT and gammaT3 in H(2)O(2)-induced neuron cultures have anti-apoptotic or pro-apoptotic tendency toward the initiation of neuronal apoptosis. H(2)O(2) is used to induce apoptosis in primary cerebellar neuron cultures which is attenuated by pretreatment of alphaT or gammaT3 at concentrations < or =10 microM. Similar to our previous work, gammaT3 was found to be neurotoxic at concentrations > or =100 microM, whereas alphaT showed no neurotoxicity. Cellular uptake of gammaT3 was higher than that of alphaT. Treating cells simultaneously with either gammaT3 or alphaT and with then H(2)O(2) led to higher expression of Bax and Bcl-2 than in neurons exposed to H(2)O(2) alone. Analysis of Bcl-2/Bax ratio as 'survival index' showed that both pretreatment of gammaT3 and alphaT followed by H(2)O(2) increase the 'survival index' of Bcl-2/Bax ratio compared to H(2)O(2)-treated cells, while treatment of gammaT3 alone decrease the ratio compared to unchanged Bcl2/Bax ratio of similar treatment with alphaT alone. Similar treatment of gammaT3 decreased p53 expression and activates p38 MAPK phosphorylation, whereas alphaT did not alter its expression compared to H(2)O(2)-treated cells. Treating neurons with only gammaT3 or alphaT increased the expression of Bax, Bcl-2, p53, and p38 MAPK compared to control with gammaT3 exerting stronger expression for proteins involved than alphaT. In conclusion, low doses of gammaT3 and alphaT confer neuroprotection to H(2)O(2)-treated neurons via their antioxidant mechanism but gammaT3 has stronger pro-apoptosis tendency than alphaT by activating molecules involved in the neuronal apoptotic pathway in the absence of H(2)O(2).
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