Browse publications by year: 2018

  1. Saiman MZ, Mustafa NR, Verpoorte R
    Methods Mol Biol, 2018;1815:437-455.
    PMID: 29981141 DOI: 10.1007/978-1-4939-8594-4_31
    The plant Catharanthus roseus is a rich source of terpenoid indole alkaloids (TIA). Some of the TIA are important as antihypertensive (ajmalicine) and anticancer (vinblastine and vincristine) drugs. However, production of the latter is very low in the plant. Therefore, in vitro plant cell cultures have been considered as a potential supply of these chemicals or their precursors. Some monomeric alkaloids can be produced by plant cell cultures, but not on a level feasible for commercialization, despite extensive studies on this plant that deepened the understanding of the TIA biosynthesis and its regulation. In order to analyze the metabolites in C. roseus cell cultures, this chapter presents the method of TIA, carotenoids, and phytosterols analyses. Furthermore, an NMR-based metabolomics approach to study C. roseus cell culture is described.
    MeSH terms: Carotenoids/analysis*; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy/methods*; Phytosterols/analysis*; Reference Standards; Spectrophotometry, Ultraviolet; Suspensions; Cell Culture Techniques/methods*; Catharanthus/metabolism*; Secologanin Tryptamine Alkaloids/analysis*; Metabolomics/methods*; Plant Cells/metabolism*
  2. Rasouli E, Shahnavaz Z, Basirun WJ, Rezayi M, Avan A, Ghayour-Mobarhan M, et al.
    Anal Biochem, 2018 09 01;556:136-144.
    PMID: 29981317 DOI: 10.1016/j.ab.2018.07.002
    Human papillomavirus (HPV) is one of the most common sexually transmitted disease, transmitted through intimate skin contact or mucosal membrane. The HPV virus consists of a double-stranded circular DNA and the role of HPV virus in cervical cancer has been studied extensively. Thus it is critical to develop rapid identification method for early detection of the virus. A portable biosensing device could give rapid and reliable results for the identification and quantitative determination of the virus. The fabrication of electrochemical biosensors is one of the current techniques utilized to achieve this aim. In such electrochemical biosensors, a single-strand DNA is immobilized onto an electrically conducting surface and the changes in electrical parameters due to the hybridization on the electrode surface are measured. This review covers the recent developments in electrochemical DNA biosensors for the detection of HPV virus. Due to the several advantages of electrochemical DNA biosensors, their applications have witnessed an increased interest and research focus nowadays.
    MeSH terms: DNA, Single-Stranded/analysis*; DNA, Viral/analysis*; Humans; Biosensing Techniques/methods*; Papillomaviridae*; Papillomavirus Infections/diagnosis; Electrochemical Techniques/methods*; Limit of Detection
  3. Hamezah HS, Durani LW, Yanagisawa D, Ibrahim NF, Aizat WM, Bellier JP, et al.
    Exp Gerontol, 2018 Oct 01;111:53-64.
    PMID: 29981398 DOI: 10.1016/j.exger.2018.07.002
    Decrease in multiple functions occurs in the brain with aging, all of which can contribute to age-related cognitive and locomotor impairments. Brain atrophy specifically in hippocampus, medial prefrontal cortex (mPFC), and striatum, can contribute to this age-associated decline in function. Our recent metabolomics analysis showed age-related changes in these brain regions. To further understand the aging processes, analysis using a proteomics approach was carried out. This study was conducted to identify proteome profiles in the hippocampus, mPFC, and striatum of 14-, 18-, 23-, and 27-month-old rats. Proteomics analysis using ultrahigh performance liquid chromatography coupled with Q Exactive HF Orbitrap mass spectrometry identified 1074 proteins in the hippocampus, 871 proteins in the mPFC, and 241 proteins in the striatum. Of these proteins, 97 in the hippocampus, 25 in mPFC, and 5 in striatum were differentially expressed with age. The altered proteins were classified into three ontologies (cellular component, molecular function, and biological process) containing 44, 38, and 35 functional groups in the hippocampus, mPFC, and striatum, respectively. Most of these altered proteins participate in oxidative phosphorylation (e.g. cytochrome c oxidase and ATP synthase), glutathione metabolism (e.g. peroxiredoxins), or calcium signaling pathway (e.g. protein S100B and calmodulin). The most prominent changes were observed in the oldest animals. These results suggest that alterations in oxidative phosphorylation, glutathione metabolism, and calcium signaling pathway are involved in cognitive and locomotor impairments in aging.
    MeSH terms: Adenosine Triphosphate; Animals; Atrophy; Biological Phenomena; Calmodulin; Chromatography, Liquid; Cognition; Corpus Striatum; Electron Transport Complex IV; Glutathione; Hippocampus; Oxidative Phosphorylation; Mass Spectrometry; Neostriatum; Prefrontal Cortex; Calcium Signaling; Proteome; Proteomics; Rats; Peroxiredoxins; Metabolomics
  4. Bartlett AW, Truong KH, Songtaweesin WN, Chokephaibulkit K, Hansudewechakul R, Ly PS, et al.
    AIDS, 2018 07 31;32(12):1689-1697.
    PMID: 29794827 DOI: 10.1097/QAD.0000000000001883
    OBJECTIVES: The aim of this study was to describe characteristics of perinatally HIV-infected adolescents (PHIVAs), factors associated with mortality, and outcomes at transition.

    DESIGN: Ongoing observational database collating clinical data on HIV-infected children and adolescents in Asia.

    METHODS: Data from 2001 to 2016 relating to adolescents (10-19 years) with perinatal HIV infection were analysed to describe characteristics at adolescent entry and transition and combination antiretroviral therapy (cART) regimens across adolescence. A competing risk regression analysis was used to determine characteristics at adolescent entry associated with mortality. Outcomes at transition were compared on the basis of age at cART initiation.

    RESULTS: Of 3448 PHIVA, 644 had reached transition. Median age at HIV diagnosis was 5.5 years, cART initiation 7.2 years and transition 17.9 years. At adolescent entry, 35.0% had CD4+ cell count less than 500 cells/μl and 51.1% had experienced a WHO stage III/IV clinical event. At transition, 38.9% had CD4+ cell count less than 500 copies/ml, and 53.4% had experienced a WHO stage III/IV clinical event. Mortality rate was 0.71 per 100 person-years, with HIV RNA ≥1000 copies/ml, CD4+ cell count less than 500 cells/μl, height-for-age or weight-for-age z-score less than -2, history of a WHO stage III/IV clinical event or hospitalization and at least second cART associated with mortality. For transitioning PHIVA, those who commenced cART age less than 5 years had better virologic and immunologic outcomes, though were more likely to be on at least second cART.

    CONCLUSION: Delayed HIV diagnosis and cART initiation resulted in considerable morbidity and poor immune status by adolescent entry. Durable first-line cART regimens to optimize disease control are key to minimizing mortality. Early cART initiation provides the best virologic and immunologic outcomes at transition.

    MeSH terms: Adolescent; Asia; Child; Child, Preschool; Hospitalization; Humans; Longitudinal Studies; Regression Analysis; RNA; HIV Infections; CD4 Lymphocyte Count; Anti-Retroviral Agents
  5. Tu Y, Ahmad N, Briscoe J, Zhang DW, Krause S
    Anal Chem, 2018 07 17;90(14):8708-8715.
    PMID: 29932632 DOI: 10.1021/acs.analchem.8b02244
    Light-addressable potentiometric sensors (LAPS) are of great interest in bioimaging applications such as the monitoring of concentrations in microfluidic channels or the investigation of metabolic and signaling events in living cells. By measuring the photocurrents at electrolyte-insulator-semiconductor (EIS) and electrolyte-semiconductor structures, LAPS can produce spatiotemporal images of chemical or biological analytes, electrical potentials and impedance. However, its commercial applications are often restricted by their limited AC photocurrents and resolution of LAPS images. Herein, for the first time, the use of 1D semiconducting oxides in the form of ZnO nanorods for LAPS imaging is explored to solve this issue. A significantly increased AC photocurrent with enhanced image resolution has been achieved based on ZnO nanorods, with a photocurrent of 45.7 ± 0.1 nA at a light intensity of 0.05 mW, a lateral resolution as low as 3.0 μm as demonstrated by images of a PMMA dot on ZnO nanorods and a pH sensitivity of 53 mV/pH. The suitability of the device for bioanalysis and bioimaging was demonstrated by monitoring the degradation of a thin poly(ester amide) film with the enzyme α-chymotrypsin using LAPS. This simple and robust route to fabricate LAPS substrates with excellent performance would provide tremendous opportunities for bioimaging.
    MeSH terms: Animals; Cattle; Chymotrypsin/metabolism*; Equipment Design; Lasers; Light; Polyesters/metabolism*; Potentiometry/instrumentation*; Semiconductors; Zinc Oxide/chemistry*; Biosensing Techniques/instrumentation*; Nanotubes/ultrastructure; Nanotubes/chemistry*
  6. Law LS, Norhasmah S, Gan WY, Mohd Nasir MT
    Public Health Nutr, 2018 Oct;21(15):2819-2830.
    PMID: 29976262 DOI: 10.1017/S136898001800160X
    OBJECTIVE: To examine the types of coping strategies practised by Indigenous women or Orang Asli (OA) in Peninsular Malaysia during times of food shortage and to determine the level of severity for food insecurity that will trigger each specific coping strategy.

    DESIGN: A qualitative case study was conducted. Pertinent information about each type of coping strategy was gathered by in-depth interviews. To gauge the level of severity for each of the coping strategies, focus group discussions (FGD) were held. Thematic analysis was used for data analysis.

    SETTING: OA villages in the states of Kelantan, Pahang, Perak and Selangor, Malaysia.

    SUBJECTS: Sixty-one OA women from three ethnic groups (Senoi, Proto-Malay and Negrito) for in-depth interviews and nineteen OA women from the Proto-Malay ethnic group for three FGD.

    RESULTS: The findings identified twenty-nine different coping strategies and these were divided into two main themes: food consumption (sub-themes of food consumption included dietary changes, diversification of food sources, decreasing the number of people and rationing) and financial management (sub-themes of financial management included increasing household income, reducing expenses for schooling children and reducing expenses on daily necessities). Three levels of severity were derived: less severe, severe and very severe.

    CONCLUSIONS: This information would enable local authorities or non-governmental organisations to more precisely target and plan interventions to better aid the OA communities needing assistance in the areas of food sources and financial management.

    MeSH terms: Adaptation, Psychological*; Adult; Feeding Behavior/ethnology*; Feeding Behavior/psychology*; Female; Food Supply*; Humans; Malaysia/ethnology; Qualitative Research; Asian Continental Ancestry Group/psychology*; Young Adult
  7. McColl H, Racimo F, Vinner L, Demeter F, Gakuhari T, Moreno-Mayar JV, et al.
    Science, 2018 07 06;361(6397):88-92.
    PMID: 29976827 DOI: 10.1126/science.aat3628
    The human occupation history of Southeast Asia (SEA) remains heavily debated. Current evidence suggests that SEA was occupied by Hòabìnhian hunter-gatherers until ~4000 years ago, when farming economies developed and expanded, restricting foraging groups to remote habitats. Some argue that agricultural development was indigenous; others favor the "two-layer" hypothesis that posits a southward expansion of farmers giving rise to present-day Southeast Asian genetic diversity. By sequencing 26 ancient human genomes (25 from SEA, 1 Japanese Jōmon), we show that neither interpretation fits the complexity of Southeast Asian history: Both Hòabìnhian hunter-gatherers and East Asian farmers contributed to current Southeast Asian diversity, with further migrations affecting island SEA and Vietnam. Our results help resolve one of the long-standing controversies in Southeast Asian prehistory.
    MeSH terms: Asia, Southeastern; Humans; Population/genetics; Genetic Variation; Genome, Human*; Sequence Analysis, DNA; Asian Continental Ancestry Group/genetics; History, Ancient; Human Migration/history*; DNA, Ancient
  8. Ghasemzadeh A, Jaafar HZE, Baghdadi A, Tayebi-Meigooni A
    Molecules, 2018 07 05;23(7).
    PMID: 29976903 DOI: 10.3390/molecules23071646
    Gingerols and shogaols are compounds found in ginger (Zingiber officinale Roscoe); shogaols are found in lower concentration than gingerols but exhibit higher biological activities. This work studied the effects of different drying methods including open sun drying (OSD) solar tunnel drying (STD) and hot air drying (HAD) with various temperature on the formation of six main active compounds in ginger rhizomes, namely 6-, 8-, and 10-gingerols and 6-, 8-, and 10-shogaols, as well as essential oil content. Antioxidant and antimicrobial activity of dried ginger was also evaluated. High performance liquid chromatography (HPLC) analysis showed that after HAD with variable temperature (120, 150 and 180 °C), contents of 6-, 8-, and 10-gingerols decreased, while contents of 6-, 8-, and 10-shogaol increased. High formation of 6-, 8-, and 10-shogaol contents were observed in HAD (at 150 °C for 6 h) followed by STD and OSD, respectively. OSD exhibited high content of essential oil followed by STD and HAD method. Ginger-treated with HAD exhibited the highest DPPH (IC50 of 57.8 mg/g DW) and FRAP (493.8 µM of Fe(II)/g DM) activity, compared to STD and OSD method. HAD ginger exhibited potent antimicrobial activity with lower minimum inhibition concentration (MIC) value against bacteria strains followed by STD and OSD, respectively. Ginger extracts showed more potent antimicrobial activity against Gram positive bacteria than Gram negative bacteria strains. Result of this study confirmed that conversion of gingerols to shogaols was significantly affected by different drying temperature and time. HAD at 150 °C for 6 h, provides a method for enhancing shogaols content in ginger rhizomes with improving antioxidant and antimicrobial activities.
    MeSH terms: Anti-Infective Agents/analysis*; Anti-Infective Agents/pharmacology; Antioxidants/analysis*; Antioxidants/pharmacology; Catechols/analysis*; Catechols/pharmacology; Chromatography, High Pressure Liquid; Desiccation/methods*; Fatty Alcohols/analysis*; Fatty Alcohols/pharmacology; Gram-Negative Bacteria/drug effects; Gram-Positive Bacteria/drug effects; Guaiacol/analogs & derivatives; Guaiacol/analysis; Guaiacol/pharmacology; Microbial Sensitivity Tests; Oils, Volatile/analysis; Oils, Volatile/pharmacology; Plant Extracts/chemistry; Plant Oils/analysis; Plant Oils/pharmacology; Ginger/chemistry*
  9. Tan BL, Norhaizan ME, Chan LC
    PMID: 29977314 DOI: 10.1155/2018/6578648
    Manilkara zapota (L.) P. Royen (family: Sapotaceae) is commonly called sapodilla, or locally known as ciku. The detailed mechanisms underlying Manilkara zapota leaf methanol extract against HeLa human cervical cancer cells have yet to be investigated. Therefore, our present study is designed to investigate the ability to induce apoptosis and the underlying mechanisms of Manilkara zapota leaf methanol extract inducing cytotoxicity in HeLa cells. The apoptotic cell death was assessed using Annexin V-propidium iodide staining. Intracellular reactive oxygen species (ROS) and mitochondrial membrane potential activities were measured using dichlorodihydrofluorescein diacetate and MitoLite Orange, respectively, by NovoCyte Flow Cytometer. Bax and Bcl-2 expression were evaluated using Enzyme-Linked Immunosorbent Assay. Caspase-3 activity was determined using a colorimetric assay. The associated biological interaction pathways were evaluated using quantitative real-time PCR. Our data showed that HeLa cells were relatively more sensitive to Manilkara zapota leaf methanol extract than other cancer cell lines studied. Overall analyses revealed that Manilkara zapota leaf methanol extract can inhibit the viability of HeLa cells, induce mitochondrial ROS generation, and inhibit nuclear factor-kappa B (NF-κB) and epidermal growth factor receptor (EGFR) transcriptional activities. Our results suggested that Manilkara zapota leaf methanol extract might represent a potential anticervical cancer agent.
    MeSH terms: Methanol; Uterine Cervical Neoplasms; Colorimetry; Female; HeLa Cells; Humans; Propidium; NF-kappa B; Annexin A5; Reactive Oxygen Species; Sapotaceae; Citrus sinensis; Manilkara; bcl-2-Associated X Protein; Membrane Potential, Mitochondrial; Caspase 3; Real-Time Polymerase Chain Reaction
  10. Lim CH, Tseng CW, Lin CT, Huang WN, Chen YH, Chen YM, et al.
    SAGE Open Med, 2018;6:2050312118781895.
    PMID: 29977547 DOI: 10.1177/2050312118781895
    Objective: To examine the clinical utility of tumor markers in dermatomyositis/polymyositis patients in Taiwan.

    Method: Data were collected retrospectively from the database of Taichung Veterans General Hospital in Taiwan from 1998 to 2014. Patients who fulfilled Bohan and Peter criteria of dermatomyositis/polymyositis were recruited. Serum level of tumor markers including carcinoembryonic antigen, alpha-fetoprotein, carbohydrate antigen 125, carbohydrate antigen 19-9 and carbohydrate antigen 15-3 were measured. The occurrence of malignancies and interstitial lung disease was identified. The association of tumor markers with malignancies and interstitial lung disease was examined using Chi-square test or Fisher's exact test.

    Results: Among the enrolled 151 patients, 98 (64.9%) dermatomyositis and 53 (35.1%) polymyositis, a total of 15 malignancies were detected: breast ductal carcinoma (n = 4), bladder transitional cell carcinoma (n = 2), lung adenocarcinoma (n = 2), cervical intraepithelial neoplasia 3 and papillary squamous cell carcinoma (n = 2), colorectal (colon and rectal adenocarcinoma) (n = 2), uterine adenocarcinoma (n = 1), nasopharyngeal carcinoma (n = 1) and hematological malignancy (myelodysplastic with excess blast cells) (n = 1). Among the patients with malignancies, 13 (86.7%) had dermatomyositis, 2 (13.3%) polymyositis and 3 (20%) interstitial lung disease. The mean duration from dermatomyositis/polymyositis diagnosis to the occurrence of malignancies was 6.05 ± 5.69 years. There was no significant association of raised tumor markers with the occurrence of malignancies (p > 0.085), while a significant association was observed between the elevated levels of carbohydrate antigen 15-3 and the presence of interstitial lung disease (p = 0.006).

    Conclusion: Tumor markers were not useful in malignancy screening or dermatomyositis/polymyositis patients in this tertiary center. The evaluation of the occurrence of malignancy in dermatomyositis/polymyositis patient should include a multidimensional approach. A raised level of carbohydrate antigen 15-3 may be a potential indicator of the presence of interstitial lung disease in dermatomyositis/polymyositis patients.
    MeSH terms: Dermatomyositis*; Humans; Neoplasms; Retrospective Studies; Taiwan
  11. Ahadzadeh AS, Rafik-Galea S, Alavi M, Amini M
    Health Psychol Open, 2018 06 10;5(1):2055102918774251.
    PMID: 29977587 DOI: 10.1177/2055102918774251
    This study examined the correlation between body mass index as independent variable, and body image and fear of negative evaluation as dependent variables, as well as the moderating role of self-esteem in these correlations. A total of 318 Malaysian young adults were conveniently recruited to do the self-administered survey on the demographic characteristics body image, fear of negative evaluation, and self-esteem. Partial least squares structural equation modeling was used to test the research hypotheses. The results revealed that body mass index was negatively associated with body image, while no such correlation was found with fear of negative evaluation. Meanwhile, the negative correlation of body mass index with body image was stronger among those with lower self-esteem, while a positive association of body mass index with fear of negative evaluation was significant only among individuals with low self-esteem.
    MeSH terms: Adult; Body Image; Demography; Fear; Humans; Personality Disorders; Surveys and Questionnaires; Self Concept; Effect Modifier, Epidemiologic; Body Mass Index; Least-Squares Analysis; Young Adult
  12. Sockalingam SNMP, Awang Talip MSAA, Zakaria ASI
    Case Rep Dent, 2018;2018:6535480.
    PMID: 29977625 DOI: 10.1155/2018/6535480
    Dens evaginatus is a dental developmental anomaly that arises due to the folding of the inner dental epithelium that leads to the formation of an additional cusp or tubercle on the occlusal surface of the affected tooth. This accessory tissue projection may carry with it a narrow and constricted pulp horn extension. Occasionally, the tubercle easily fractures, thus leading to microexposure of the pulp horn and eventual pulp necrosis. Often, the pulp necrosis occurs at a time the root development of the affected tooth is incomplete. Apexification with calcium hydroxide and mineral trioxide aggregates has been the mainstay of treatment options before root canal obturation in immature nonvital permanent teeth. Lately, regenerative endodontics (maturogenesis) is becoming one of the preferred treatment modalities to manage such teeth. The current case highlights the possibility of a bioceramic material (EndoSequence Root Repair Material, BC RRM-Fast Set Putty™, Brasseler, USA) which supposed to provide apical root closure (apexification) and could also induce continuation of root growth (maturogenesis).
  13. Mohd R, Nesam T, Kamaruzaman L, Cader RA, Mustafar R, Kong WY
    Respir Med Case Rep, 2018;24:147-149.
    PMID: 29977783 DOI: 10.1016/j.rmcr.2018.05.019
    Acinetobacter baumannii is an aerobic Gram-negative coccobacillus that is associated with hospital acquired pneumonia. There is increased reporting of emergent cases of community acquired multidrug resistance (MDR) acinetobacter associated with a higher mortality due to antibiotic resistance. Community acquired MDR acinetobacter pneumonia has not been reported in Malaysia. Here we report a case of a 19-year-old army officer who presented with fever and respiratory symptoms for 5 days. He had no known medical illness before and no history of hospitalization. Upon arrival, he was in septicaemic shock, requiring invasive ventilator support and renal replacement therapy in intensive care unit. Chest radiograph showed bilateral lung consolidations and bronchoscopy revealed haemoserous and greenish bronchiole secretion. He was treated with broad spectrum antibiotics and oseltamivir. Unfortunately he died on day 3 of hospital admission. His bronchial lavage culture came back positive for MDR Acinetobacter baumannii. This case illustrates that clinicians need to be aware that MDR Acinetobacter baumannii can cause severe community acquired pneumonia. We may need to consider this diagnosis in patients who do not respond to standard therapy.
    MeSH terms: Anti-Bacterial Agents; Bronchoscopy; Drug Resistance, Microbial; Hospitalization; Humans; Intensive Care Units; Malaysia; Male; Pneumonia; Renal Replacement Therapy; Community-Acquired Infections; Drug Resistance, Multiple; Bronchoalveolar Lavage; Acinetobacter baumannii; Oseltamivir; Bronchioles
  14. Binns C, Lee MK, Low WY
    Asia Pac J Public Health, 2018 05;30(4):315-320.
    PMID: 29978722 DOI: 10.1177/1010539518783808
    The widespread availability and use of e-cigarettes in many countries has established the need for an assessment of their effect on children. By the end of 2017 the number published annually on e-cigarettes had increased to 2976 and included 171 papers on e-cigarettes and children. The objective of this commentary is to provide a review and public health perspective on the effects of e-cigarettes on children. There are four public health questions to be answered: 1. Are e-cigarettes and replenishing fluids toxic on accidental ingestion? 2. If children smoke e-cigarettes is this harmful? 3. Does exposure to second hand vapour from e-cigarettes cause harm to children? 4. Are children (adolescents) who use e-cigarettes more likely to begin smoking conventional cigarettes? There were 2229 reported exposures to e-cigarette fluids and liquid nicotine in the USA in 2017 causing cardiovascular symptoms of varying severity. No deaths were reported although the potential is always there. Exposure to e-cigarette vapor is less dangerous than cigarette smoke. However it does damage pulmonary endothelium in experimental models. No long term studies are yet available on chronic diseases although vapor does contain carcinogens. Adolescents who use e-cigarettes are more likely to become tobacco smokers. Because of the accumulating evidence of harm to children great caution should be exercised in widening the public promotion and usage of e-cigarettes. Children should avoid any contact with E-cigarettes or their vapour.
    MeSH terms: Child Health*; Adolescent; Child; Humans; Risk Factors; Electronic Cigarettes*; Vaping*
  15. Ow LL, Subramaniam N, Kamisan Atan I, Friedman T, Martin A, Dietz HP
    Female Pelvic Med Reconstr Surg, 2018 7 7;25(6):415-418.
    PMID: 29979358 DOI: 10.1097/SPV.0000000000000608
    OBJECTIVE: Genital hiatus (Gh) and perineal body (Pb) are part of the Pelvic Organ Prolapse Quantification assessment system, but it is unclear whether measurements should be taken at rest or on Valsalva. This study was designed to assess the predictive value of Gh and Pb measurements obtained at rest and on Valsalva for signs and symptoms of pelvic organ prolapse (POP).

    METHODS: This is a retrospective study involving 416 women who presented to a tertiary urogynecology unit with symptoms of pelvic floor dysfunction. Genital hiatus and Pb were measured at rest and on maximal Valsalva. The strength of association between binary markers of POP and measurements of Gh/Pb was estimated using logistic regression analysis. Receiver operator characteristic statistics were used to compare predictive values of Gh and Pb measurements obtained at rest and on Valsalva.

    RESULTS: A total of 451 women were seen during the study period. Thirty-five were excluded owing to missing data, leaving 416. Fifty-four percent (n = 223) complained of POP symptoms. On examination, 80% (n = 332) had significant POP (stage 2+ in anterior or posterior compartments or stage 1+ in the central compartment). On imaging, significant POP was diagnosed in 66% (n = 275). Mean hiatal area was 22 cm (SD, 7; range, 5-49 cm) at rest and 30 cm (SD, 10; range, 11-69 cm) on Valsalva. Genital hiatus and Pb measured on Valsalva were consistently stronger predictors of prolapse symptoms and objective prolapse (by clinician examination and by ultrasound) than at Gh and Pb measured at rest. The corresponding area under the curve values were significantly larger for Gh/Pb measures on Valsalva after adjusting for multiple confounders.

    CONCLUSIONS: Genital hiatus/Pb measured on maximal Valsalva is a superior predictor of symptoms and signs of POP compared with Gh/Pb at rest.

    MeSH terms: Female; Humans; Retrospective Studies; ROC Curve; Ultrasonography; Vulva; Logistic Models; Pelvic Floor; Pelvic Organ Prolapse
  16. Earp M, Tyrer JP, Winham SJ, Lin HY, Chornokur G, Dennis J, et al.
    PLoS One, 2018;13(7):e0197561.
    PMID: 29979793 DOI: 10.1371/journal.pone.0197561
    Epithelial ovarian cancer (EOC) is the fifth leading cause of cancer mortality in American women. Normal ovarian physiology is intricately connected to small GTP binding proteins of the Ras superfamily (Ras, Rho, Rab, Arf, and Ran) which govern processes such as signal transduction, cell proliferation, cell motility, and vesicle transport. We hypothesized that common germline variation in genes encoding small GTPases is associated with EOC risk. We investigated 322 variants in 88 small GTPase genes in germline DNA of 18,736 EOC patients and 26,138 controls of European ancestry using a custom genotype array and logistic regression fitting log-additive models. Functional annotation was used to identify biofeatures and expression quantitative trait loci that intersect with risk variants. One variant, ARHGEF10L (Rho guanine nucleotide exchange factor 10 like) rs2256787, was associated with increased endometrioid EOC risk (OR = 1.33, p = 4.46 x 10-6). Other variants of interest included another in ARHGEF10L, rs10788679, which was associated with invasive serous EOC risk (OR = 1.07, p = 0.00026) and two variants in AKAP6 (A-kinase anchoring protein 6) which were associated with risk of invasive EOC (rs1955513, OR = 0.90, p = 0.00033; rs927062, OR = 0.94, p = 0.00059). Functional annotation revealed that the two ARHGEF10L variants were located in super-enhancer regions and that AKAP6 rs927062 was associated with expression of GTPase gene ARHGAP5 (Rho GTPase activating protein 5). Inherited variants in ARHGEF10L and AKAP6, with potential transcriptional regulatory function and association with EOC risk, warrant investigation in independent EOC study populations.
    MeSH terms: Female; Genotype; Humans; Risk Factors; Genetic Predisposition to Disease; Monomeric GTP-Binding Proteins/genetics*; Polymorphism, Single Nucleotide/genetics; Quantitative Trait Loci/genetics; A Kinase Anchor Proteins/genetics*; Genetic Association Studies; Rho Guanine Nucleotide Exchange Factors/genetics*
  17. Yee A, Loh HS, Ong TA, Ng CG, Sulaiman AH
    Am J Mens Health, 2018 Sep;12(5):1705-1718.
    PMID: 29973132 DOI: 10.1177/1557988318784152
    Methadone is largely recognized as an effective treatment for opiate-dependent patients; however, it causes reduced brain dopaminergic action resulting in significant sexual dysfunction. Bupropion is a dopamine reuptake inhibitor which can potentially improve erectile function among male patients on methadone (MMT). This is a phase II, randomized, double-blind, parallel-group, placebo-controlled trial, involving 80 MMT male patients (73.4%) with mean age of 42.83 years ±9.68. These MMT male patients were randomly assigned into two groups to receive bupropion and placebo, respectively. The primary efficacy outcome measure was the difference between the two groups in end-point mean improvement scores using the measurement of Clinical Global Impression Scale adapted for Sexual Function (CGI-SF) at baseline (week 0) and at weeks 2, 4, and 6. Malay version of the sexual desire inventory-2 (SDI-2-BM) and Malay version of International Index of Erectile Function 15 (Mal-IIEF-15) domain scores were evaluated as secondary parameters. Improvement of the end-point mean from baseline were seen across the scores of SDI-2-BM (mean difference = 11.77 ± 2.90, 95% confidence interval (CI) [3.89, 19.54], p < .001) and Mal-IIEF-15 (mean difference = 8.37 ± 2.71, 95% CI [15.75, 0.99], p = .02), and the total plasma testosterone level (mean difference = 4.03, 95% CI [0.90, 7.15], p = .01). A categorical improvement of "much/very much improved" (CGI-SF score = 2) was reported by 58.3% ( n = 21/36) of bupropion SR-assigned versus 27.7% ( n = 10/36) placebo-assigned patient. Bupropion was well tolerated with no serious adverse events reported other than insomnia (17.7%). Six weeks of bupropion SR treatment reported significant improvement in key aspects of sexual function among male opiate-dependent patients on methadone maintenance treatment with emergent sexual dysfunction.
    MeSH terms: Adult; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Humans; Erectile Dysfunction/chemically induced; Erectile Dysfunction/drug therapy*; Male; Methadone/administration & dosage; Methadone/adverse effects*; Middle Aged; Prognosis; Sexual Dysfunction, Physiological/chemically induced*; Sexual Dysfunction, Physiological/drug therapy*; Bupropion/adverse effects; Bupropion/therapeutic use*; Treatment Outcome; Risk Assessment
  18. Jan S, Lee SW, Sawhney JPS, Ong TK, Chin CT, Kim HS, et al.
    BMC Cardiovasc Disord, 2018 07 04;18(1):139.
    PMID: 29973147 DOI: 10.1186/s12872-018-0859-4
    BACKGROUND: The EPICOR Asia (long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients in Asia) study (NCT01361386) was an observational study of patients hospitalized for acute coronary syndromes (ACS) enrolled in 218 hospitals in eight countries/regions in Asia. This study examined costs, length of stay and the predictors of high costs during an ACS hospitalization.

    METHODS AND RESULTS: Data for patients hospitalized for an ACS (n = 12,922) were collected on demographics, medical history, event characteristics, socioeconomic and insurance status at discharge. Patients were followed up at 6 weeks' post-hospitalization for an ACS event to assess associated treatment costs from a health sector perspective. Primary outcome was the incurring of costs in the highest quintile by country and index event diagnosis, and identification of associated predictors. Cost data were available for 10,819 patients. Mean length of stay was 10.1 days. The highest-cost countries were China, Singapore, and South Korea. Significant predictors of high-cost care were age, male sex, income, country, prior disease history, hospitalization in 3 months before index event, no dependency before index event, having an invasive procedure, hospital type and length of stay.

    CONCLUSIONS: Substantial variability exists in healthcare costs for hospitalized ACS patients across Asia. Of concern is the observation that the highest costs were reported in China, given the rapidly increasing numbers of procedures in recent years.

    TRIAL REGISTRATION: NCT01361386 .

    MeSH terms: Aged; Asia/epidemiology; Female; Hospitalization/economics*; Humans; Length of Stay/economics; Male; Middle Aged; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome; Process Assessment (Health Care)/economics*; Hospital Costs*; Acute Coronary Syndrome/diagnosis; Acute Coronary Syndrome/economics*; Acute Coronary Syndrome/epidemiology; Acute Coronary Syndrome/therapy*; Healthcare Disparities/economics*
  19. Win KN, Trivedi A, Lai AS
    Ind Health, 2018 Nov 21;56(6):566-571.
    PMID: 29973468 DOI: 10.2486/indhealth.2018-0053
    In 2012, there were about 2.3 million deaths worldwide attributed to work. The highest workplace fatality rate (WFR) was reported on construction sites due to high risk activities. Globally, fall from height is the leading cause of fatal injuries for construction workers. The objectives are to determine Brunei Darussalam's demographic distribution of occupational fatality; identify causal agents and industry where occupational fatalities commonly occur; and determine WFR by year. This cross-sectional study retrospectively reviewed records of occupational fatality which were notified to the Occupational Health Division, Ministry of Health, from January 2012 until December 2016. Notified occupational fatalities in Brunei over a five-year period was 50. Most of the cases were in 31-40 age group. 38% of fatality cases occurred in Indonesian workers. 60% were from the Construction industry. 38% were due to fall from height. WFR averaged 5.28 and the highest industry-specific fatality rate was seen in the Construction industry, ranging from 27.94 to 56.45 per 100,000 workers. WFR for Brunei Darussalam from 2012 to 2016 was similar to that of Malaysia, but higher than Singapore and the UK. Industry-specific fatality rate for the Construction and Manufacturing industries were higher than those of Singapore and the UK.
    MeSH terms: Accidental Falls/mortality; Accidents, Occupational/mortality*; Adolescent; Adult; Brunei/epidemiology; Cross-Sectional Studies; Female; Humans; Male; Middle Aged; Retrospective Studies; Socioeconomic Factors; Global Health; Occupational Health; Workplace/statistics & numerical data*; Age Distribution; Young Adult; Construction Industry/statistics & numerical data
  20. Alsalahi A, Alshawsh MA, Chik Z, Mohamed Z
    Exp Anim, 2018 Nov 01;67(4):517-526.
    PMID: 29973470 DOI: 10.1538/expanim.18-0057
    People consume Catha edulis (khat) for its euphoric effect, and type 1 diabetics have claimed that khat could reduce elevated levels of blood sugar. However, khat has been suggested to provoke diabetes mellitus through destruction of pancreatic β-cells. This study investigated the effect of an ethanolic khat extract on pancreatic functions in type 1 diabetes (T1DM)-induced male Sprague-Dawley rats and to assess its in vitro cytotoxicity in rat pancreatic β-cells (RIN-14B). T1DM was induced in a total of 20 rats with a single intraperitoneal injection of 75 mg/kg of streptozotocin. The rats were distributed into four groups (n=5): the diabetic control, 8 IU insulin-treated, 200 mg/kg khat-treated, and 400 mg/kg khat-treated groups. Another 5 rats were included as a nondiabetic control. Body weight, fasting blood sugar, and caloric intake were recorded weekly. Four weeks after treatment, the rats were sacrificed, and blood was collected for insulin, lipid profile, total protein, amylase, and lipase analysis, while pancreases were harvested for histopathology. In vitro, khat exerted moderate cytotoxicity against RIN-14B cells after 24 and 48 h but demonstrated greater inhibition against RIN-14B cells after 72 h. Neither 200 mg/kg nor 400 mg/kg of khat produced any significant reduction in blood sugar; however, 200 mg/kg khat extract provoked more destruction of pancreatic β-cells as compared with the diabetic control. Ultimately, neither 200 mg/kg nor 400 mg/kg of khat extract could produce a hypoglycemic effect in T1DM-induced rats. However, 200 mg/kg of khat caused greater destruction of pancreatic β-cells, implying that khat may cause a direct cytotoxic effect on pancreatic β-cells in vitro.
    MeSH terms: Animals; Blood Glucose/metabolism; Cell Line; Diabetes Mellitus, Experimental/metabolism*; Diabetes Mellitus, Experimental/physiopathology*; Dose-Response Relationship, Drug; Humans; Male; Pancreas/physiopathology*; Plant Extracts/pharmacology; Plant Extracts/toxicity*; Streptozocin; Time Factors; Tumor Cells, Cultured; Rats, Sprague-Dawley; Catha/chemistry*; Insulin-Secreting Cells/drug effects*
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