Browse publications by year: 2017

  1. Soon G, Pingguan-Murphy B, Akbar SA
    J Mech Behav Biomed Mater, 2017 04;68:26-31.
    PMID: 28135639 DOI: 10.1016/j.jmbbm.2017.01.028
    This study utilizes the technique of self-assembly to fabricate arrays of nanoislands on (001)-oriented yttria-stabilized zirconia single crystal substrates with miscut of 10° toward <110> direction. These self-assembled nanostructures were annealed at 1100°C for 5h upon doping with 10mol% gadolinium-doped ceria (GDC) by powder-suspension based method. X-Ray diffraction result showed that the miscut substrate after doping GDC was in the cubic phase. Energy dispersive X-ray (EDX) illustrates that the nanopatterned material contains all the elements from the GDC source and yttria-stabilized zirconia (YSZ) substrate. It also demonstrates a higher surface roughness and a more hydrophilic surface. The nanostructured materials were subsequently used for an in vitro study using a human fetal osteoblastic cell line (hFOB). An improved spreading, enhanced cell proliferation and up-regulated alkaline phosphatase activity (ALP) were observed on the nanopatterned substrates compared to the control substrates. Calcium deposits, which were stained positively by Alizarin Red S, appeared to be more abundant on the nanopatterned surfaces on day 7. The overall findings suggest that post fabrication treatment with surface modification such as creating a nanostructure (e.g. nanopatterns) can improve biocompatibility.
    MeSH terms: Biocompatible Materials; Cell Line; Humans; Osteoblasts/cytology*; Yttrium/chemistry*; Zirconium/chemistry*; Nanostructures/chemistry*
  2. Mbous YP, Hayyan M, Hayyan A, Wong WF, Hashim MA, Looi CY
    Biotechnol Adv, 2017 Mar-Apr;35(2):105-134.
    PMID: 27923764 DOI: 10.1016/j.biotechadv.2016.11.006
    Deep eutectic solvents (DESs) have been touted recently as potential alternatives to ionic liquids (ILs). Although they possess core characteristics that are similar to those of ILs (e.g., low volatility, non-flammability, low melting points, low vapor pressure, dipolar nature, chemical and thermal stability, high solubility, and tuneability), DESs are superior in terms of the availability of raw materials, the ease of storage and synthesis, and the low cost of their starting materials. As such, they have become the subject of intensive research in various sectors, notably the chemical, electrochemical, and biological sectors. To date, the applications of DESs have shown great promise, especially in the medical and biotechnological fields. In spite of these various achievements, the safety concern for these mixtures must be sufficiently addressed. Indeed, in order to exploit the vast array of opportunities that DESs offer to the biological industry, first, they must be established as safe mixtures. Hence, the biotechnological applications of DESs only can be implemented if they are proven to have negligible or low toxicity profiles. This review is the first of its kind, and it discusses two current aspects of DES-based research. First, it describes the properties of these mixtures with ample focus on their toxicity profiles. Second, it provides an overview of the breakthroughs that have occurred and the foreseeable prospects of the use of DESs in various biotechnological and biological applications.
    MeSH terms: Biotechnology*; Solvents*; Ionic Liquids*; Bioengineering*
  3. Sambasevam Y, Omar Farouk AA, Tengku Mohamad TA, Sulaiman MR, Bharatham BH, Perimal EK
    Eur J Pharmacol, 2017 Feb 05;796:32-38.
    PMID: 27988285 DOI: 10.1016/j.ejphar.2016.12.020
    Neuropathic pain arises from the injury of nervous system. The condition is extremely difficult to be treated due to the ineffectiveness and presence of various adverse effects of the currently available drugs. In the present study, we investigated the antiallodynic and antihyperlagesic properties of cardamonin, a naturally occurring chalcone in chronic constriction injury (CCI)-induced neuropathic pain mice model. Our findings showed that single and repeated dose of intra-peritoneal administration of cardamonin (3, 10, 30mg/kg) significantly inhibited (P<0.001) the chronic constriction injury-induced neuropathic pain using the Hargreaves plantar test, Randall-Selitto analgesiometer test, dynamic plantar anesthesiometer test and the cold plate test in comparison with the positive control drug used (amitriptyline hydrochloride, 20mg/kg, i.p.). Pre-treatment with naloxone hydrochloride (1mg/kg, i.p.) and naloxone methiodide (1mg/kg, s.c) significantly reversed the antiallodynic and antihyperalgesic effects of cardamonin in dynamic plantar anesthesiometer test and Hargreaves plantar test, respectively. In conclusion, the current findings demonstrated novel antiallodynic and antihyperalgesic effects of cardamonin through the activation of the opioidergic system both peripherally and centrally and may prove to be a potent lead compound for the development of neuropathic pain drugs in the future.
    MeSH terms: Amitriptyline; Quaternary Ammonium Compounds; Animals; Chalcone; Constriction; Pharmaceutical Preparations; Lead; Naloxone; Neuralgia; Chalcones; Mice
  4. Sakai N, Shirasaka J, Matsui Y, Ramli MR, Yoshida K, Ali Mohd M, et al.
    Chemosphere, 2017 Apr;172:234-241.
    PMID: 28081507 DOI: 10.1016/j.chemosphere.2016.12.139
    Five homologs (C10-C14) of linear alkylbenzene sulfonate (LAS) were quantitated in surface water collected in the Langat and Selangor River basins using liquid chromatography-tandem mass spectrometry (LC-MS/MS). A geographic information system (GIS) was used to spatially analyze the occurrence of LAS in both river basins, and the LAS contamination associated with the population was elucidated by spatial analysis at a sub-basin level. The LAS concentrations in the dissolved phase (<0.45 μm) and 4 fractions separated by particle size (<0.1 μm, 0.1-1 μm, 1-11 μm and >11 μm) were analyzed to elucidate the environmental fate of LAS in the study area. The environmental risks of the observed LAS concentration were assessed based on predicted no effect concentration (PNEC) normalized by a quantitative structure-activity relationship model. The LAS contamination mainly occurred from a few populated sub-basins, and it was correlated with the population density and ammonia nitrogen. The dissolved phase was less than 20% in high contamination sites (>1000 μg/L), whereas it was more than 60% in less contaminated sites (<100 μg/L). The environmental fate of LAS in the study area was primarily subject to the adsorption to suspended solids rather than biodegradation because the LAS homologs, particularly in longer alkyl chain lengths, were considerably absorbed to the large size fraction (>11 μm) that settled in a few hours. The observed LAS concentrations exceeded the normalized PNEC at 3 sites, and environmental risk areas and susceptible areas to the LAS contamination were spatially identified based on their catchment areas.
    MeSH terms: Chromatography, Liquid; Environmental Monitoring/methods*; Malaysia; Surface-Active Agents/analysis; Surface-Active Agents/toxicity; Water Pollutants, Chemical/analysis*; Water Pollutants, Chemical/toxicity; Alkanesulfonic Acids/analysis*; Alkanesulfonic Acids/toxicity; Risk Assessment; Quantitative Structure-Activity Relationship; Geographic Information Systems; Rivers; Tandem Mass Spectrometry; Spatial Analysis
  5. Zhu W, Zheng W, Hu X, Xu X, Zhang L, Tian J
    Biochim Biophys Acta Proteins Proteom, 2017 Apr;1865(4):404-413.
    PMID: 28087425 DOI: 10.1016/j.bbapap.2017.01.004
    Lonicera japonica Thunb., also known as Jin Yin Hua and Japanese honeysuckle, is used as a herbal medicine in Asian countries. Its flowers have been used in folk medicine in the clinic and in making food or healthy beverages for over 1500years in China. To investigate the molecular processes involved in L. japonica development from buds to flowers exposed to UV radiation, a comparative proteomics analysis was performed. Fifty-four proteins were identified as differentially expressed, including 42 that had increased expression and 12 that had decreased expression. The levels of the proteins related to glycolysis, TCA/organic acid transformation, major carbohydrate metabolism, oxidative pentose phosphate, stress, secondary metabolism, hormone, and mitochondrial electron transport were increased during flower opening process after exposure to UV radiation. Six metabolites in L. japonica buds and flowers were identified and relatively quantified using LC-MS/MS. The antioxidant activity was performed using a 1,1-diphenyl-2-picrylhydrazyl assay, which revealed that L. japonica buds had more activity than the UV irradiated flowers. This suggests that UV-B radiation induces production of endogenous ethylene in L. japonica buds, thus facilitating blossoming of the buds and activating the antioxidant system. Additionally, the higher metabolite contents and antioxidant properties of L. japonica buds indicate that the L. japonica bud stage may be a more optimal time to harvest than the flower stage when using for medicinal properties.
    MeSH terms: Citric Acid Cycle/radiation effects; Glycolysis/radiation effects; Ultraviolet Rays*; Proteome/biosynthesis*; Lonicera/metabolism*; Flowers/metabolism*; Metabolome/radiation effects*
  6. Lee M, Mariapun S, Rajaram N, Teo SH, Yip CH
    BMC Public Health, 2017 01 28;17(1):127.
    PMID: 28129762 DOI: 10.1186/s12889-017-4015-3
    BACKGROUND: The incidence of breast cancer in Asia is increasing because of urbanization and lifestyle changes. In the developing countries in Asia, women present at late stages, and mortality is high. Mammographic screening is the only evidence-based screening modality that reduces breast cancer mortality. To date, only opportunistic screening is offered in the majority of Asian countries because of the lack of justification and funding. Nevertheless, there have been few reports on the effectiveness of such programmes. In this study, we describe the cancer detection rate and challenges experienced in an opportunistic mammographic screening programme in Malaysia.

    METHODS: From October 2011 to June 2015, 1,778 asymptomatic women, aged 40-74 years, underwent subsidised mammographic screening. All patients had a clinical breast examination before mammographic screening, and women with mammographic abnormalities were referred to a surgeon. The cancer detection rate and variables associated with a recommendation for adjunct ultrasonography were determined.

    RESULTS: The mean age for screening was 50.8 years and seven cancers (0.39%) were detected. The detection rate was 0.64% in women aged 50 years and above, and 0.12% in women below 50 years old. Adjunct ultrasonography was recommended in 30.7% of women, and was significantly associated with age, menopausal status, mammographic density and radiologist's experience. The main reasons cited for recommendation of an adjunct ultrasound was dense breasts and mammographic abnormalities.

    DISCUSSION: The cancer detection rate is similar to population-based screening mammography programmes in high-income Asian countries. Unlike population-based screening programmes in Caucasian populations where the adjunct ultrasonography rate is 2-4%, we report that 3 out of 10 women attending screening mammography were recommended for adjunct ultrasonography. This could be because Asian women attending screening are likely premenopausal and hence have denser breasts. Radiologists who reported more than 360 mammograms were more confident in reporting a mammogram as normal without adjunct ultrasonography compared to those who reported less than 180 mammograms.

    CONCLUSION: Our subsidised opportunistic mammographic screening programme is able to provide equivalent cancer detection rates but the high recall for adjunct ultrasonography would make screening less cost-effective.

    MeSH terms: Adult; Aged; Breast Neoplasms/diagnosis*; Breast Neoplasms/economics; Breast Neoplasms/prevention & control; Cost-Benefit Analysis; Female; Humans; Income; Malaysia; Mammography/economics; Mammography/statistics & numerical data*; Mass Screening/economics; Mass Screening/statistics & numerical data*; Middle Aged; Incidence; Early Detection of Cancer/economics; Early Detection of Cancer/statistics & numerical data*
  7. Gunasekaran R, Shaker MR, Mohd-Zin SW, Abdullah A, Ahmad-Annuar A, Abdul-Aziz NM
    BMC Complement Altern Med, 2017 Jan 28;17(1):79.
    PMID: 28129764 DOI: 10.1186/s12906-017-1600-z
    Coconut oil is commonly used as herbal medicine worldwide. There is limited information regarding its effects on the developing embryo and infant growth.
    MeSH terms: Animals; Body Weight/drug effects; Cocos/chemistry*; Diet*; Dietary Fats, Unsaturated/adverse effects; Dietary Fats, Unsaturated/blood; Fatty Acids/analysis; Fatty Acids, Essential/blood*; Feeding Behavior; Female; Hair/drug effects*; Mice, Inbred Strains; Nuts/chemistry; Plant Oils/adverse effects*; Plant Oils/chemistry; Pregnancy; Weight Gain/drug effects*; Maternal Nutritional Physiological Phenomena*
  8. Karami A, Groman DB, Wilson SP, Ismail P, Neela VK
    Environ Pollut, 2017 Apr;223:466-475.
    PMID: 28129952 DOI: 10.1016/j.envpol.2017.01.047
    There are serious concerns over the adverse impacts of microplastics (MPs) on living organisms. The main objective of this study was to test the effects of MPs on the total length, weight, condition factor (CF), transcriptional level of antioxidant, anti and pro-apoptotic, and neurotransmitter genes, and the histopathology of the gill, liver, brain, kidney, and intestine in the larvae of zebrafish (Danio rerio). Fish were exposed to one of three levels of pristine low-density polyethylene (LDPE) fragments (5, 50, or 500 μg/L) for 10 or 20 days. No significant changes were observed in any of the selected biomarkers across MP concentrations at days 10 or 20. The expression of casp9 (caspase 9, apoptosis-related cysteine protease), casp3a (caspase 3, apoptosis-related cysteine protease a) and cat (catalase), however, were significantly lower in the larvae sampled at day 20 than day 10. We provide evidence that virgin short-term exposure to LDPE fragments has minimal impact on biomarker responses in D. rerio larvae.
    MeSH terms: Animals; Body Weight/drug effects; Female; Gene Expression Regulation/drug effects; Genetic Markers/genetics*; Intestines/drug effects; Intestines/metabolism; Larva/anatomy & histology; Larva/cytology; Larva/drug effects*; Larva/genetics*; Male; Zebrafish/anatomy & histology; Zebrafish/genetics*; Zebrafish/growth & development; Oxidative Stress/drug effects; Polyethylene/toxicity*; Polyethylene/chemistry*; Body Size/drug effects
  9. Makita Y, Ng KK, Veera Singham G, Kawashima M, Hirakawa H, Sato S, et al.
    DNA Res, 2017 Apr 01;24(2):159-167.
    PMID: 28431015 DOI: 10.1093/dnares/dsw056
    Natural rubber has unique physical properties that cannot be replaced by products from other latex-producing plants or petrochemically produced synthetic rubbers. Rubber from Hevea brasiliensis is the main commercial source for this natural rubber that has a cis-polyisoprene configuration. For sustainable production of enough rubber to meet demand elucidation of the molecular mechanisms involved in the production of latex is vital. To this end, we firstly constructed rubber full-length cDNA libraries of RRIM 600 cultivar and sequenced around 20,000 clones by the Sanger method and over 15,000 contigs by Illumina sequencer. With these data, we updated around 5,500 gene structures and newly annotated around 9,500 transcription start sites. Second, to elucidate the rubber biosynthetic pathways and their transcriptional regulation, we carried out tissue- and cultivar-specific RNA-Seq analysis. By using our recently published genome sequence, we confirmed the expression patterns of the rubber biosynthetic genes. Our data suggest that the cytoplasmic mevalonate (MVA) pathway is the main route for isoprenoid biosynthesis in latex production. In addition to the well-studied polymerization factors, we suggest that rubber elongation factor 8 (REF8) is a candidate factor in cis-polyisoprene biosynthesis. We have also identified 39 transcription factors that may be key regulators in latex production. Expression profile analysis using two additional cultivars, RRIM 901 and PB 350, via an RNA-Seq approach revealed possible expression differences between a high latex-yielding cultivar and a disease-resistant cultivar.
    MeSH terms: Latex/biosynthesis*; Plant Proteins/genetics; RNA, Messenger; Rubber/metabolism*; Transcription Factors; Sequence Analysis, RNA; RNA, Plant; Hevea/genetics*; Hevea/metabolism; Biosynthetic Pathways/genetics*; Transcriptome*
  10. Ahmad A, Razali MH, Mamat M, Mehamod FS, Anuar Mat Amin K
    Chemosphere, 2017 Feb;168:474-482.
    PMID: 27855344 DOI: 10.1016/j.chemosphere.2016.11.028
    This study aims to develop a highly efficient adsorbent material. CNTs are prepared using a chemical vapor deposition method with acetylene and synthesized mesoporous Ni-MCM41 as the carbon source and catalyst, respectively, and are then functionalized using 3-aminopropyltriethoxysilane (APTES) through the co-condensation method and loaded with commercial TiO2. Results of X-ray powder diffraction (XRD), Raman spectra, and Fourier transform infrared spectroscopy (FTIR) confirm that the synthesized CNTs grown are multi-walled carbon nanotubes (MWNTs). Transmission electron microscopy shows good dispersion of TiO2 nanoparticles onto functionalized-CNTs loaded TiO2, with the diameter of a hair-like structure measuring between 3 and 8 nm. The functionalized-CNTs loaded TiO2 are tested as an adsorbent for removal of methyl orange (MO) in aqueous solution, and results show that 94% of MO is removed after 10 min of reaction, and 100% after 30 min. The adsorption kinetic model of functionalized-CNTs loaded TiO2 follows a pseudo-second order with a maximum adsorption capacity of 42.85 mg/g. This study shows that functionalized-CNTs loaded TiO2 has considerable potential as an adsorbent material due to the short adsorption time required to achieve equilibrium.
    MeSH terms: Adsorption; Azo Compounds/chemistry*; Coloring Agents/analysis; Industrial Waste/analysis; Propylamines/chemistry*; Silanes/chemistry*; Titanium/chemistry*; Waste Disposal, Fluid/methods*; Water Pollutants, Chemical/chemistry*; Nanotubes, Carbon/chemistry*; Nanocomposites/chemistry
  11. Matejcic M, de Batlle J, Ricci C, Biessy C, Perrier F, Huybrechts I, et al.
    Int J Cancer, 2017 Mar 15;140(6):1246-1259.
    PMID: 27905104 DOI: 10.1002/ijc.30536
    Epidemiological studies have reported inconsistent findings for the association between B vitamins and breast cancer (BC) risk. We investigated the relationship between biomarkers of folate and vitamin B12 and the risk of BC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Plasma concentrations of folate and vitamin B12 were determined in 2,491 BC cases individually matched to 2,521 controls among women who provided baseline blood samples. Multivariable logistic regression models were used to estimate odds ratios by quartiles of either plasma B vitamin. Subgroup analyses by menopausal status, hormone receptor status of breast tumors (estrogen receptor [ER], progesterone receptor [PR] and human epidermal growth factor receptor 2 [HER2]), alcohol intake and MTHFR polymorphisms (677C > T and 1298A > C) were also performed. Plasma levels of folate and vitamin B12 were not significantly associated with the overall risk of BC or by hormone receptor status. A marginally positive association was found between vitamin B12 status and BC risk in women consuming above the median level of alcohol (ORQ4-Q1  = 1.26; 95% CI 1.00-1.58; Ptrend  = 0.05). Vitamin B12 status was also positively associated with BC risk in women with plasma folate levels below the median value (ORQ4-Q1  = 1.29; 95% CI 1.02-1.62; Ptrend  = 0.03). Overall, folate and vitamin B12 status was not clearly associated with BC risk in this prospective cohort study. However, potential interactions between vitamin B12 and alcohol or folate on the risk of BC deserve further investigation.
    MeSH terms: Adult; Aged; Alcohol Drinking/adverse effects; Alcohol Drinking/epidemiology; Breast Neoplasms/blood; Breast Neoplasms/genetics; Breast Neoplasms/epidemiology*; Breast Neoplasms/chemistry; Diet; Estrogens; Europe/epidemiology; Female; Folic Acid/blood*; Folic Acid Deficiency/blood; Folic Acid Deficiency/epidemiology*; Follow-Up Studies; Humans; Life Style; Middle Aged; Neoplasms, Hormone-Dependent/blood; Neoplasms, Hormone-Dependent/epidemiology; Progesterone; Risk Factors; Vitamin B 12/blood*; Vitamin B 12 Deficiency/blood; Vitamin B 12 Deficiency/epidemiology*; Biomarkers/blood; Case-Control Studies; Genes, erbB-2; Polymorphism, Single Nucleotide; Methylenetetrahydrofolate Reductase (NADPH2)/genetics*
  12. Durier N, Yunihastuti E, Ruxrungtham K, Kinh NV, Kamarulzaman A, Boettiger D, et al.
    J Viral Hepat, 2017 03;24(3):187-196.
    PMID: 27917597 DOI: 10.1111/jvh.12630
    Data on markers of hepatitis C virus (HCV) disease in HIV-HCV-coinfected patients in resource-limited settings are scarce. We assessed HCV RNA, HCV genotype (GT), IL28B GT and liver fibrosis (FibroScan® ) in 480 HIV-infected patients with positive HCV antibody in four HIV treatment centres in South-East Asia. We enrolled 165 (34.4%) patients in Jakarta, 158 (32.9%) in Bangkok, 110 (22.9%) in Hanoi and 47 (9.8%) in Kuala Lumpur. Overall, 426 (88.8%) were male, the median (IQR) age was 38.1 (34.7-42.5) years, 365 (76.0%) reported HCV exposure through injecting drug use, and 453 (94.4%) were on combination antiretroviral therapy. The median (IQR) CD4 count was 446 (325-614) cells/mm3 and 208 (94.1%) of 221 patients tested had HIV-1 RNA <400 copies/mL. A total of 412 (85.8%) had detectable HCV RNA, at a median (IQR) of 6.2 (5.4-6.6) log10 IU/mL. Among 380 patients with HCV GT, 223 (58.7%) had GT1, 97 (25.5%) had GT3, 43 (11.3%) had GT6, eight (2.1%) had GT4, two (0.5%) had GT2, and seven (1.8%) had indeterminate GT. Of 222 patients with IL28B testing, 189 (85.1%) had rs12979860 CC genotype, and 199 (89.6%) had rs8099917 TT genotype. Of 380 patients with FibroScan® , 143 (37.6%) had no/mild liver fibrosis (F0-F1), 83 (21.8%) had moderate fibrosis (F2), 74 (19.5%) had severe fibrosis (F3), and 79 (20.8%) had cirrhosis (F4). One patient (0.3%) had FibroScan® failure. In conclusion, a high proportion of HIV-HCV-coinfected patients had chronic HCV infection. HCV GT1 was predominant, and 62% of patients had liver disease warranting prompt treatment (≥F2).
    MeSH terms: Adult; Alleles; Asia, Southeastern/epidemiology; Female; Genotype; Humans; Interleukins/genetics; Liver Cirrhosis/pathology*; Male; Middle Aged; RNA, Viral/blood; HIV Infections/complications*; HIV Infections/epidemiology; Hepacivirus/classification; Hepacivirus/genetics; Hepacivirus/isolation & purification; CD4 Lymphocyte Count; Hepatitis C Antibodies/blood; Viral Load; Hepatitis C, Chronic/complications*; Hepatitis C, Chronic/epidemiology; Hepatitis C, Chronic/pathology*; Hepatitis C, Chronic/virology; Coinfection/complications*; Coinfection/epidemiology; Coinfection/pathology*; Coinfection/virology
  13. Fortner RT, Hüsing A, Kühn T, Konar M, Overvad K, Tjønneland A, et al.
    Int J Cancer, 2017 Mar 15;140(6):1317-1323.
    PMID: 27935083 DOI: 10.1002/ijc.30560
    Endometrial cancer risk prediction models including lifestyle, anthropometric and reproductive factors have limited discrimination. Adding biomarker data to these models may improve predictive capacity; to our knowledge, this has not been investigated for endometrial cancer. Using a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, we investigated the improvement in discrimination gained by adding serum biomarker concentrations to risk estimates derived from an existing risk prediction model based on epidemiologic factors. Serum concentrations of sex steroid hormones, metabolic markers, growth factors, adipokines and cytokines were evaluated in a step-wise backward selection process; biomarkers were retained at p 
    MeSH terms: Adult; Aged; Blood Glucose/analysis; Blood Proteins/analysis; Europe/epidemiology; Female; Follow-Up Studies; Hormones/blood; Humans; Inflammation/blood; Inflammation/epidemiology; Lipids/blood; Middle Aged; Surveys and Questionnaires; Risk; Biomarkers, Tumor/blood*; Comorbidity; Incidence; Case-Control Studies; Single-Blind Method; Cytokines/blood; Endometrial Neoplasms/blood; Endometrial Neoplasms/epidemiology*; Risk Assessment; Metabolic Syndrome X/blood
  14. Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.
    Cancer Med, 2017 Jan;6(1):173-185.
    PMID: 28000426 DOI: 10.1002/cam4.985
    We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.
    MeSH terms: Adult; Aged; Antineoplastic Agents/administration & dosage*; Antineoplastic Agents/therapeutic use; Breast Neoplasms/drug therapy*; Breast Neoplasms/pathology; Female; Humans; Malaysia; Middle Aged; Prognosis; Singapore; Survival Analysis; Treatment Outcome; Chemotherapy, Adjuvant; Carcinoma, Ductal, Breast/drug therapy*; Carcinoma, Ductal, Breast/pathology; Disease-Free Survival; Neoadjuvant Therapy; Taxoids/administration & dosage*; Taxoids/therapeutic use; Neoplasm Grading
  15. Vadivelu J, Vellasamy KM, Thimma J, Mariappan V, Kang WT, Choh LC, et al.
    PLoS Negl Trop Dis, 2017 01;11(1):e0005241.
    PMID: 28045926 DOI: 10.1371/journal.pntd.0005241
    BACKGROUND: During infection, successful bacterial clearance is achieved via the host immune system acting in conjunction with appropriate antibiotic therapy. However, it still remains a tip of the iceberg as to where persistent pathogens namely, Burkholderia pseudomallei (B. pseudomallei) reside/hide to escape from host immune sensors and antimicrobial pressure.

    METHODS: We used transmission electron microscopy (TEM) to investigate post-mortem tissue sections of patients with clinical melioidosis to identify the localisation of a recently identified gut microbiome, B. pseudomallei within host cells. The intranuclear presence of B. pseudomallei was confirmed using transmission electron microscopy (TEM) of experimentally infected guinea pig spleen tissues and Live Z-stack, and ImageJ analysis of fluorescence microscopy analysis of in vitro infection of A549 human lung epithelial cells.

    RESULTS: TEM investigations revealed intranuclear localization of B. pseudomallei in cells of infected human lung and guinea pig spleen tissues. We also found that B. pseudomallei induced actin polymerization following infection of A549 human lung epithelial cells. Infected A549 lung epithelial cells using 3D-Laser scanning confocal microscopy (LSCM) and immunofluorescence microscopy confirmed the intranuclear localization of B. pseudomallei.

    CONCLUSION: B. pseudomallei was found within the nuclear compartment of host cells. The nucleus may play a role as an occult or transient niche for persistence of intracellular pathogens, potentially leading to recurrrent episodes or recrudescence of infection.

    MeSH terms: Actins/metabolism; Animals; Cell Nucleus/microbiology*; Guinea Pigs; Humans; Liver/metabolism; Liver/microbiology; Lung/metabolism; Lung/microbiology; Melioidosis/metabolism; Melioidosis/microbiology*; Spleen/metabolism; Spleen/microbiology; Burkholderia pseudomallei/growth & development; Burkholderia pseudomallei/physiology*; Microbial Viability
  16. Joseph CJ, Khoo TB, Lee KY
    BMJ Case Rep, 2017 Jan 06;2017.
    PMID: 28062435 DOI: 10.1136/bcr-2016-218044
    An infant, who was born preterm at 36 weeks, presented with fever and ulcer at umbilical region which progressed to necrotising fasciitis of anterior abdominal wall. He was treated with intravenous penicillin, intravenous cloxacillin and local application of medicated honey. Subsequently, he required wound debridement. Postoperatively, he required prolonged invasive ventilation due to poor respiratory effort which was associated with hypotonia and areflexia. Nerve conduction study revealed absent responses. The diagnosis of infant botulism was made based on the clinical presentation, nerve conduction study and his clinical progress. Botulinum immunoglobulin was not available. He was treated with intravenous immunoglobulin and oral pyridostigmine. He was successfully extubated after 37 days, and currently the patient is doing well.
    MeSH terms: Botulism/diagnosis; Botulism/drug therapy*; Cholinesterase Inhibitors/therapeutic use*; Debridement/methods; Honey*; Humans; Infant; Male; Paralysis/microbiology; Pyridostigmine Bromide/therapeutic use*; Ulcer/microbiology; Ulcer/therapy; Umbilicus; Wound Infection/therapy; Immunoglobulins, Intravenous/therapeutic use*; Treatment Outcome; Fasciitis, Necrotizing/microbiology; Fasciitis, Necrotizing/therapy*
  17. Lam CW, AbuBakar S, Chang LY
    J Virol Methods, 2017 05;243:1-9.
    PMID: 28082163 DOI: 10.1016/j.jviromet.2017.01.004
    Nipah virus (NiV) is a highly pathogenic zoonotic paramyxovirus with unusual broad host tropism and is designated as a Category C pathogen by the U.S. National Institute of Allergy and Infectious Diseases. NiV infection is initiated after binding of the viral G glycoprotein to the host cell receptor. The aim of this study was to map the NiV G glycoprotein cell binding domain using a phage display system. The NiV G extracellular domain was truncated and displayed as attachment proteins on M13 phage g3p minor coat protein. The binding efficiency of recombinant phages displaying different regions of NiV G to mammalian cells was evaluated. Results showed that regions of NiV G consisting of amino acids 396-602 (recombinant phage G4) and 498-602 (recombinant phage G5) demonstrated the highest binding to both Vero (5.5×103 cfu/ml and 5.6×103 cfu/ml) and THP-1 cells (3.5×103 cfu/ml and 2.9×103 cfu/ml). However, the binding of both of these recombinant phages to THP-1 cells was significantly lower than to Vero cells, and this could be due to the lack of primary host cell receptor expression on THP-1 cells. Furthermore, the binding between these two recombinant phages was competitive suggesting that there was a common host cell attachment site. This study employed an approach that is suitable for use in a biosafety level 2 containment laboratory without the need to use live virus to show that NiV G amino acids 498-602 play an important role for attachment to host cells.
    MeSH terms: Animals; Binding Sites; Cell Line; Cercopithecus aethiops; Glycoproteins/metabolism*; Humans; Protein Binding; Viral Structural Proteins/metabolism*; Bacteriophage M13/genetics; Peptide Library; Nipah Virus/physiology*; Virus Attachment*; Protein Domains
  18. Wan Hassan WN, Yusof ZY, Shahidan SS, Mohd Ali SF, Makhbul MZ
    Health Qual Life Outcomes, 2017 Jan 26;15(1):23.
    PMID: 28126000 DOI: 10.1186/s12955-017-0600-5
    BACKGROUND: This paper describes the cross-cultural adaptation of the Psychosocial Impact of Dental Aesthetics Questionnaire (PIDAQ) into Malay version (Malay PIDAQ), an oral health-related quality of life (OHRQoL) instrument specific for orthodontics for Malaysian adolescents between 12 and 17 years old.

    METHODS: The PIDAQ was cross-culturally adapted into Malay version by forward- and backward-translation processes, followed by psychometric validations. After initial investigation of the conceptual suitability of the measure for the Malaysian population, the PIDAQ was translated into Malay, pilot tested and back translated into English. Psychometric properties were examined across two age groups (319 subjects aged 12-14 and 217 subjects aged 15-17 years old) for factor structure, internal consistency, reproducibility, discriminant and construct validity, criterion validity, and assessment of floor and ceiling effects.

    RESULTS: Fit indices by confirmatory factor analysis showed good fit statistics (comparative fit index = 0.936, root-mean-square error of approximation = 0.064) and invariance across age groups. Internal consistency and reproducibility tests were satisfactory (Cronbach's α = 0.71-0.91; intra-class correlations = 0.72-0.89). Significant differences in Malay PIDAQ mean scores were observed between subjects with severe malocclusion and those with slight malocclusion based on a self-rated and an investigator-rated malocclusion index, for all subscales and all age groups (p 

    MeSH terms: Adolescent; Child; Cross-Cultural Comparison*; Esthetics, Dental/psychology*; Female; Humans; Malaysia; Male; Psychometrics/statistics & numerical data*; Quality of Life/psychology*; Surveys and Questionnaires*; Translating*; Reproducibility of Results
  19. Bunawan H, Yen CC, Yaakop S, Noor NM
    BMC Res Notes, 2017 Jan 26;10(1):67.
    PMID: 28126013 DOI: 10.1186/s13104-017-2379-1
    The chloroplastic trnL intron and the nuclear internal transcribed spacer (ITS) region were sequenced for 11 Nepenthes species recorded in Peninsular Malaysia to examine their phylogenetic relationship and to evaluate the usage of trnL intron and ITS sequences for phylogenetic reconstruction of this genus.
    MeSH terms: Base Sequence; Cell Nucleus/genetics*; Introns/genetics*; Malaysia; Phylogeny*; Species Specificity; DNA, Chloroplast/genetics*; DNA, Ribosomal Spacer/genetics*; Sarraceniaceae/genetics*
  20. Marza AD, Jesse Abdullah FF, Ahmed IM, Teik Chung EL, Ibrahim HH, Zamri-Saad M, et al.
    Microb Pathog, 2017 Mar;104:340-347.
    PMID: 28126667 DOI: 10.1016/j.micpath.2017.01.031
    Lipopolysaccharide (LPS) of P. multocida B:2, a causative agent of haemorrhagic septicaemia (HS) in cattle and buffaloes, is considered as the main virulence factor and contribute in the pathogenesis of the disease. Recent studies provided evidences about the involvement of the nervous system in pathogenesis of HS. However, the role of P. multocida B:2 immunogens, especially the LPS is still uncovered. Therefore, this study was designed to investigate the role of P. multocida B:2 LPS to induce pathological changes in the nervous system. Nine eight-month-old, clinically healthy buffalo calves were used and distributed into three groups. Calves of Group 1 and 2 were inoculated orally and intravenously with 10 ml of LPS broth extract represent 1 × 10(12) cfu/ml of P. multocida B:2, respectively, while calves of Group 3 were inoculated orally with 10 ml of phosphate buffer saline as a control. Significant differences were found in the mean scores for clinical signs, post mortem and histopathological changes especially in Group 2, which mainly affect different anatomic regions of the nervous system, mainly the brain. On the other hand, lower scores have been recorded for clinical signs, gross and histopathological changes in Group 1. These results provide for the first time strong evidence about the ability of P. multocida B:2 LPS to cross the blood brain barrier and induce pathological changes in the nervous system of the affected buffalo calves.
    MeSH terms: Animals; Brain/pathology; Buffaloes; Hemorrhagic Septicemia/microbiology*; Hemorrhagic Septicemia/pathology; Histocytochemistry; Lipopolysaccharides/isolation & purification; Lipopolysaccharides/toxicity*; Microscopy; Nervous System/microbiology*; Nervous System/pathology; Poisoning/pathology*; Spinal Cord/pathology; Pasteurella multocida/chemistry*
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