Browse publications by year: 2016

  1. Chow LS, Rajagopal H, Paramesran R, Alzheimer's Disease Neuroimaging Initiative
    Magn Reson Imaging, 2016 07;34(6):820-831.
    PMID: 26969762 DOI: 10.1016/j.mri.2016.03.006
    Medical Image Quality Assessment (IQA) plays an important role in assisting and evaluating the development of any new hardware, imaging sequences, pre-processing or post-processing algorithms. We have performed a quantitative analysis of the correlation between subjective and objective Full Reference - IQA (FR-IQA) on Magnetic Resonance (MR) images of the human brain, spine, knee and abdomen. We have created a MR image database that consists of 25 original reference images and 750 distorted images. The reference images were distorted with six types of distortions: Rician Noise, Gaussian White Noise, Gaussian Blur, DCT compression, JPEG compression and JPEG2000 compression, at various levels of distortion. Twenty eight subjects were chosen to evaluate the images resulting in a total of 21,700 human evaluations. The raw scores were then converted to Difference Mean Opinion Score (DMOS). Thirteen objective FR-IQA metrics were used to determine the validity of the subjective DMOS. The results indicate a high correlation between the subjective and objective assessment of the MR images. The Noise Quality Measurement (NQM) has the highest correlation with DMOS, where the mean Pearson Linear Correlation Coefficient (PLCC) and Spearman Rank Order Correlation Coefficient (SROCC) are 0.936 and 0.938 respectively. The Universal Quality Index (UQI) has the lowest correlation with DMOS, where the mean PLCC and SROCC are 0.807 and 0.815 respectively. Student's T-test was used to find the difference in performance of FR-IQA across different types of distortion. The superior IQAs tested statistically are UQI for Rician noise images, Visual Information Fidelity (VIF) for Gaussian blur images, NQM for both DCT and JPEG compressed images, Peak Signal-to-Noise Ratio (PSNR) for JPEG2000 compressed images.
    MeSH terms: Adult; Algorithms; Female; Humans; Image Processing, Computer-Assisted/methods*; Magnetic Resonance Imaging/methods*; Magnetic Resonance Imaging/statistics & numerical data; Male; Normal Distribution; Databases, Factual/statistics & numerical data; Artifacts; Young Adult; Signal-To-Noise Ratio
  2. Ng YY, Wah W, Liu N, Zhou SA, Ho AF, Pek PP, et al.
    Resuscitation, 2016 May;102:116-21.
    PMID: 26970031 DOI: 10.1016/j.resuscitation.2016.03.002
    BACKGROUND: The incidence of out-of-hospital cardiac arrest (OHCA) in women is thought to be lower than that of men, with better outcomes in some Western studies.
    OBJECTIVES: This study aimed to investigate the effect of gender on OHCA outcomes in the Pan-Asian population.
    METHODOLOGY: This was a retrospective, secondary analysis of the Pan Asian Resuscitation Outcomes Study (PAROS) data between 2009 and 2012. We included OHCA cases which were presumed cardiac etiology, aged 18 years and above and resuscitation attempted by emergency medical services (EMS) systems. We used multi-level mixed-effects logistic regression models to account for the clustering effect of individuals within the country. Primary outcome was survival to hospital discharge.
    RESULTS: We included a total of 40,159 OHCA cases, 40% of which were women. We found that women were more likely to be older and have an initial non-shockable arrest rhythm; they were more likely to receive bystander cardio-pulmonary resuscitation (CPR). The univariate analysis showed that women were significantly less likely to have return of spontaneous circulation (ROSC) at scene or in the emergency department (ED), and had lower rates of survival-to-admission and discharge, and poorer overall and cerebral performance outcomes. There was however, no significant gender difference on outcomes after adjustment of other confounders. Women in the reproductive age group (age 18-44 years) were significantly more likely to have ROSC at scene or in the ED, higher rates of survival-to-admission and discharge, and have better overall and cerebral performance outcomes after adjustment for differences in baseline and pre-hospital factors. Menopausal women (age 55 years and above) were less likely to survive to admission after adjusting for other pre-hospital characteristics but not after age adjustment.
    CONCLUSION: Differences in survival outcomes between reproductive and menopausal women highlight a need for further investigations into the plausible social, pathologic or hormonal basis.
    KEYWORDS: Gender; Out-of-hospital cardiac arrest; Registry
    MeSH terms: Emergency Medical Services; Emergency Service, Hospital; Female; Humans; Male; Patient Discharge; Registries; Retrospective Studies; Incidence; Logistic Models; Cardiopulmonary Resuscitation; Out-of-Hospital Cardiac Arrest
  3. Shilpi JA, Saha S, Chong SL, Nahar L, Sarker SD, Awang K
    Chem Biodivers, 2016 May;13(5):483-503.
    PMID: 26970405 DOI: 10.1002/cbdv.201400373
    Chisocheton is one of the genera of the family Meliaceae and consists of ca. 53 species; the distribution of most of those are confined to the Indo-Malay region. Species of broader geographic distribution have undergone extensive phytochemical investigations. Previous phytochemical investigations of this genus resulted in the isolation of mainly limonoids, apotirucallane, tirucallane, and dammarane triterpenes. Reported bioactivities of the isolated compounds include cytotoxic, anti-inflammatory, antifungal, antimalarial, antimycobacterial, antifeedant, and lipid droplet inhibitory activities. Aside from chemistry and biological activities, this review also deals briefly with botany, distribution, and uses of various species of this genus.
  4. Jahan MS, Nozulaidi M, Khairi M, Mat N
    J Plant Physiol, 2016 May 20;195:1-8.
    PMID: 26970687 DOI: 10.1016/j.jplph.2016.03.002
    Light-harvesting complexes (LHCs) in photosystem II (PSII) regulate glutathione (GSH) functions in plants. To investigate whether LHCs control GSH biosynthesis that modifies guard cell abscisic acid (ABA) sensitivity, we evaluated GSH content, stomatal aperture, reactive oxygen species (ROS), weight loss and plant growth using a ch1-1 mutant that was defective of LHCs and compared this with wild-type (WT) Arabidopsis thaliana plants. Glutathione monoethyl ester (GSHmee) increased but 1-chloro-2,4 dinitrobenzene (CDNB) decreased the GSH content in the guard cells. The guard cells of the ch1-1 mutants accumulated significantly less GSH than the WT plants. The guard cells of the ch1-1 mutants also showed higher sensitivity to ABA than the WT plants. The CDNB treatment increased but the GSHmee treatment decreased the ABA sensitivity of the guard cells without affecting ABA-induced ROS production. Dark and light treatments altered the GSH content and stomatal aperture of the guard cells of ch1-1 and WT plants, irrespective of CDNB and GSHmee. The ch1-1 mutant contained fewer guard cells and displayed poor growth, late flowering and stumpy weight loss compared with the WT plants. This study suggests that defective LHCs reduced the GSH content in the guard cells and increased sensitivity to ABA, resulting in stomatal closure.
    MeSH terms: Abscisic Acid/pharmacology*; Darkness; Diazonium Compounds/pharmacology; Glutathione/analogs & derivatives; Glutathione/metabolism; Glutathione/pharmacology; Light; Mutation; Plant Growth Regulators/pharmacology*; Arabidopsis/drug effects; Arabidopsis/genetics; Arabidopsis/physiology*; Arabidopsis/radiation effects; Reactive Oxygen Species/metabolism; Plant Leaves/drug effects; Plant Leaves/genetics; Plant Leaves/physiology; Plant Leaves/radiation effects; Arabidopsis Proteins/genetics; Arabidopsis Proteins/metabolism; Photosystem II Protein Complex/genetics; Photosystem II Protein Complex/metabolism*; Light-Harvesting Protein Complexes/genetics; Light-Harvesting Protein Complexes/metabolism*; Plant Stomata/drug effects; Plant Stomata/genetics; Plant Stomata/physiology; Plant Stomata/radiation effects
  5. Young G, Collins PW, Colberg T, Chuansumrit A, Hanabusa H, Lentz SR, et al.
    Thromb Res, 2016 May;141:69-76.
    PMID: 26970716 DOI: 10.1016/j.thromres.2016.02.030
    INTRODUCTION: Paradigm™4 was an international extension trial investigating the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in haemophilia B patients (FIX activity ≤2%; aged 13-70years) who had previously participated in phase III pivotal (paradigm™2) or surgery (paradigm™3) trials.

    METHODS: Patients chose to continue treatment with nonacog beta pegol in either one of two once-weekly prophylaxis arms (10IU/kg or 40IU/kg), or an on-demand arm (40IU/kg for mild/moderate bleeds; 80IU/kg for severe bleeds). The primary objective was to evaluate immunogenicity; key secondary objectives included assessing safety and haemostatic efficacy in the treatment and prevention of bleeds.

    RESULTS: Seventy-one patients received prophylaxis or on-demand treatment. No patient developed an inhibitor and no safety concerns were identified. The success rate for the treatment of reported bleeds was 94.6%; most (87.9%) resolved with one injection. The median annualised bleeding rate for patients on prophylaxis was 1.36 (interquartile range [IQR] 0.00-2.23) and 1.00 (IQR 0.00-2.03) for the 10 and 40IU/kg treatment arms, respectively. The mean FIX activity trough achieved for 10 and 40IU once weekly was 9.8% and 21.3%, respectively. Fourteen patients on prophylaxis underwent 23 minor surgical procedures; haemostatic perioperative outcomes for all of those evaluated were 'excellent' or 'good'.

    CONCLUSIONS: Nonacog beta pegol showed a favourable tolerability profile (with no safety issues identified) with good prophylactic protection and control of bleeding in previously treated adult and adolescent haemophilia B patients.

    MeSH terms: Adolescent; Adult; Aged; Hemophilia B/complications; Hemophilia B/drug therapy*; Hemophilia B/prevention & control; Factor IX/administration & dosage; Factor IX/adverse effects; Factor IX/therapeutic use*; Hemorrhage/complications; Hemorrhage/drug therapy*; Hemorrhage/prevention & control; Hemostatics/administration & dosage; Hemostatics/adverse effects; Hemostatics/therapeutic use*; Humans; Middle Aged; Polyethylene Glycols/administration & dosage; Polyethylene Glycols/adverse effects; Polyethylene Glycols/therapeutic use*; Recombinant Proteins/administration & dosage; Recombinant Proteins/adverse effects; Recombinant Proteins/therapeutic use; Young Adult
  6. Abu Hassan MR, Ismail I, Mohd Suan MA, Ahmad F, Wan Khazim WK, Othman Z, et al.
    Epidemiol Health, 2016;38:e2016007.
    PMID: 26971697 DOI: 10.4178/epih.e2016007
    OBJECTIVES: This is the first study that estimates the incidence and mortality rate for colorectal cancer (CRC) patients in Malaysia by sex and ethnicity.

    METHODS: The 4,501 patients were selected from National Cancer Patient Registry-Colorectal Cancer data. Patient survival status was cross-checked with the National Registration Department. The age-standardised rate (ASR) was calculated as the proportion of CRC cases (incidence) and deaths (mortality) from 2008 to 2013, weighted by the age structure of the population, as determined by the Department of Statistics Malaysia and the World Health Organization world standard population distribution.

    RESULTS: The overall incidence rate for CRC was 21.32 cases per 100,000. Those of Chinese ethnicity had the highest CRC incidence (27.35), followed by the Malay (18.95), and Indian (17.55) ethnicities. The ASR incidence rate of CRC was 1.33 times higher among males than females (24.16 and 18.14 per 100,000, respectively). The 2011 (44.7%) CRC deaths were recorded. The overall ASR of mortality was 9.79 cases, with 11.85 among the Chinese, followed by 9.56 among the Malays and 7.08 among the Indians. The ASR of mortality was 1.42 times higher among males (11.46) than females (8.05).

    CONCLUSIONS: CRC incidence and mortality is higher in males than females. Individuals of Chinese ethnicity have the highest incidence of CRC, followed by the Malay and Indian ethnicities. The same trends were observed for the age-standardised mortality rate.

    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Ethnic Groups/statistics & numerical data; Female; Health Surveys; Humans; Malaysia/epidemiology; Male; Middle Aged; Mortality; Sex Factors; Colorectal Neoplasms/ethnology; Colorectal Neoplasms/mortality; Colorectal Neoplasms/epidemiology*; Incidence; Age Distribution; Young Adult
  7. Melaku T, Srikanth A, Getaye Y, Admasu S, Alkalmi R
    PMID: 26971864 DOI: 10.3352/jeehp.2016.13.9
    This study aimed to compare the perceptions of pharmacy clerkship students and clinical preceptors of preceptors' teaching behaviors at Gondar University. A cross-sectional study was conducted among pharmacy clerkship students and preceptors during June 2014 and December 2015. A 52-item structured questionnaire was self-administered to 126 students and 23 preceptors. The responses are presented using descriptive statistics. The Mann-Whitney U test was applied to test the significance of differences between students and preceptors. The response rate was 89.4% for students and 95.6% for preceptors. Statistically significant differences were observed in the responses regarding two of the five communication skills that were examined, six of the 26 clinical skills, and five of the 21 parameters involving feedback. The mean scores of preceptors (2.6/3) and students (1.9/3) regarding instructors' ability to answer questions were found to be significantly different (P= 0.01). Students and preceptors gave mean scores of 1.9 and 2.8, respectively, to a question regarding preceptors' application of appropriate up-to-date knowledge to individual patients (P= 0.00). Significant differences were also noted between students and instructors regarding the degree to which preceptors encouraged students to evaluate their own performance (P= 0.01). Discrepancies were noted between students and preceptors regarding preceptors' teaching behaviors. Preceptors rated their teaching behaviors more highly than students did. Short-term training is warranted for preceptors to improve some aspects of their teaching skills.
  8. Norhayati MN, Nik Hazlina NH, Aniza AA
    Women Birth, 2016 Oct;29(5):443-449.
    PMID: 26972285 DOI: 10.1016/j.wombi.2016.02.002
    Little is known regarding the impact on maternal functional status in women who have survived severe obstetric complications.
  9. Suppiah J, Saraswathy TS, Amry K, Yusof A, Saat Z
    Asian Pac J Trop Med, 2016 Mar;9(3):252-5.
    PMID: 26972396 DOI: 10.1016/j.apjtm.2016.01.037
    OBJECTIVE: To identify the circulating serotypes of human echovirus in Malaysia from 2002 to 2013.

    METHODS: A total of 31 retrospective samples from non-polio acute flacid paralysis, hand-food-and-mouth disease, viral meningitis and enterovirus cases were subjected to amplification of partial VP1 gene by RT-PCR.

    RESULTS: Sequencing and phylogenetic analysis of the partial sequences identified presence of human echovirus and human coxsackie viruses. It was found that echovirus 11 was the commonly circulating serotype followed by echovirus 6, echovirus 7, echovirus 3, echovirus 9, echovirus 30 and echovirus 1 in decreasing order. Additionally two types of human coxsackie virus isolates were detected which were coxsackie A24 and B3.

    CONCLUSIONS: From the findings, there is a possibility that echovirus 11 is the predominant serotype among Malaysian patients with echovirus infection. However, a larger sample size will yield a more confident result to support this evidence.

  10. Tan KY, Tan CH, Sim SM, Fung SY, Tan NH
    Comp Biochem Physiol C Toxicol Pharmacol, 2016 Jul-Aug;185-186:77-86.
    PMID: 26972756 DOI: 10.1016/j.cbpc.2016.03.005
    The Southeast Asian monocled cobras (Naja kaouthia) exhibit geographical variations in their venom proteomes, especially on the composition of neurotoxins. This study compared the neuromuscular depressant activity of the venoms of N. kaouthia from Malaysia (NK-M), Thailand (NK-T) and Vietnam (NK-V), and the neutralization of neurotoxicity by a monospecific antivenom. On chick biventer cervicis nerve-muscle preparation, all venoms abolished the indirect twitches, with NK-T venom being the most potent (shortest t90, time to 90% twitch inhibition), followed by NK-V and NK-M. Acetylcholine and carbachol failed to reverse the blockade, indicating irreversible/pseudo-irreversible post-synaptic neuromuscular blockade. KCl restored the twitches variably (NK-M preparation being the least responsive), consistent with different degree of muscle damage. The findings support that NK-T venom has the most abundant curarimimetic alpha-neurotoxins, while NK-M venom contains more tissue-damaging cytotoxins. Pre-incubation of tissue with N. kaouthia monovalent antivenom (NKMAV) prevented venom-induced twitch depression, with the NK-T preparation needing the largest antivenom dose. NKMAV added after the onset of neuromuscular depression could only halt the inhibitory progression but failed to restore full contraction. The findings highlight the urgency of early antivenom administration to sequester as much circulating neurotoxins as possible, thereby hastening toxin elimination from the circulation. In envenomed mice, NKMAV administered upon the first neurological sign neutralized the neurotoxic effect, with the slowest full recovery noticed in the NK-T group. This is consistent with the high abundance of neurotoxins in the NK-T venom, implying that a larger amount or repeated dosing of NKMAV may be required in NK-T envenomation.
    MeSH terms: Animals; Animals, Newborn; Antivenins/pharmacology*; Chickens; Cobra Neurotoxin Proteins/metabolism; Cobra Neurotoxin Proteins/toxicity*; Disease Models, Animal; Dose-Response Relationship, Drug; Elapid Venoms/metabolism; Elapid Venoms/toxicity*; Malaysia; Male; Mice, Inbred ICR; Muscle Contraction/drug effects*; Neuromuscular Junction/drug effects*; Neuromuscular Junction/metabolism; Neuromuscular Junction/pathology; Neuromuscular Junction/physiopathology; Snake Bites/drug therapy*; Snake Bites/metabolism; Snake Bites/pathology; Snake Bites/physiopathology; Thailand; Time Factors; Vietnam; Elapidae/metabolism*; Cholinergic Agonists/pharmacology; Recovery of Function
  11. Marsden PA, Satia I, Ibrahim B, Woodcock A, Yates L, Donnelly I, et al.
    Chest, 2016 06;149(6):1460-6.
    PMID: 26973014 DOI: 10.1016/j.chest.2016.02.676
    BACKGROUND: Cough is recognized as an important troublesome symptom in the diagnosis and monitoring of asthma. Asthma control is thought to be determined by the degree of airway inflammation and hyperresponsiveness but how these factors relate to cough frequency is unclear. The goal of this study was to investigate the relationships between objective cough frequency, disease control, airflow obstruction, and airway inflammation in asthma.

    METHODS: Participants with asthma underwent 24-h ambulatory cough monitoring and assessment of exhaled nitric oxide, spirometry, methacholine challenge, and sputum induction (cell counts and inflammatory mediator levels). Asthma control was assessed by using the Global Initiative for Asthma (GINA) classification and the Asthma Control Questionnaire (ACQ). The number of cough sounds was manually counted and expressed as coughs per hour (c/h).

    RESULTS: Eighty-nine subjects with asthma (mean ± SD age, 57 ± 12 years; 57% female) were recruited. According to GINA criteria, 18 (20.2%) patients were classified as controlled, 39 (43.8%) partly controlled, and 32 (36%) uncontrolled; the median ACQ score was 1 (range, 0.0-4.4). The 6-item ACQ correlated with 24-h cough frequency (r = 0.40; P < .001), and patients with uncontrolled asthma (per GINA criteria) had higher median 24-h cough frequency (4.2 c/h; range, 0.3-27.6) compared with partially controlled asthma (1.8 c/h; range, 0.2-25.3; P = .01) and controlled asthma (1.7 c/h; range, 0.3-6.7; P = .002). Measures of airway inflammation were not significantly different between GINA categories and were not correlated with ACQ. In multivariate analyses, increasing cough frequency and worsening FEV1 independently predicted measures of asthma control.

    CONCLUSIONS: Ambulatory cough frequency monitoring provides an objective assessment of asthma symptoms that correlates with standard measures of asthma control but not airflow obstruction or airway inflammation. Moreover, cough frequency and airflow obstruction represent independent dimensions of asthma control.
    MeSH terms: Adult; Aged; Asthma; Breath Tests/methods; Bronchial Provocation Tests/methods; Cough; Female; Forced Expiratory Volume; Great Britain; Humans; Inflammation/diagnosis; Longitudinal Studies; Male; Middle Aged; Nitric Oxide/analysis; Spirometry/methods; Statistics as Topic; Time Factors; Disease Management; Symptom Assessment/methods
  12. Reed Z, Cardosa MJ
    Vaccine, 2016 06 03;34(26):2967-2970.
    PMID: 26973065 DOI: 10.1016/j.vaccine.2016.02.077
    Although outbreaks of Hand, Foot, and Mouth Disease (HFMD) in young children have long been recognized worldwide, the occurrence of rare and life-threatening neurological, respiratory, and cardiac complications has propelled this common condition into the spotlight as a major public health problem in the affected countries. Various enteroviruses cause HFMD, but the severe complications have been mostly associated with enterovirus 71 (EV71). Medical treatment is supportive and measures to interrupt transmission have been challenging to implement. Preventive vaccines could have an important clinical impact, especially among children younger than 3 years old who are most susceptible to the neurological complications. Several groups in the highly affected Asia-Pacific region are working towards vaccines against EV71 and some candidates have progressed to late-stage clinical trials with two vaccines recently reported to have been approved by the regulatory authorities in China. This report summarizes current issues and progress in the development of vaccines against EV71.
    MeSH terms: Child, Preschool; Clinical Trials as Topic; Hand, Foot and Mouth Disease/prevention & control*; Humans; Viral Vaccines/therapeutic use*; Enterovirus A, Human*; Biomedical Research/trends
  13. Satterfield BA, Dawes BE, Milligan GN
    Vaccine, 2016 06 03;34(26):2971-2975.
    PMID: 26973068 DOI: 10.1016/j.vaccine.2015.12.075
    Nipah virus (NiV) is a highly pathogenic, recently emerged paramyxovirus that has been responsible for sporadic outbreaks of respiratory and encephalitic disease in Southeast Asia. High case fatality rates have also been associated with recent outbreaks in Malaysia and Bangladesh. Although over two billion people currently live in regions in which NiV is endemic or in which the Pteropus fruit bat reservoir is commonly found, there is no approved vaccine to protect against NiV disease. This report examines the feasibility and current efforts to develop a NiV vaccine including potential hurdles for technical and regulatory assessment of candidate vaccines and the likelihood for financing.
    MeSH terms: Animals; Asia, Southeastern; Chiroptera/virology; Drug Evaluation, Preclinical; Humans; Viral Vaccines/therapeutic use*; Biomedical Research/trends; Nipah Virus*; Henipavirus Infections/prevention & control*
  14. Mamidi MK, Das AK, Zakaria Z, Bhonde R
    Osteoarthritis Cartilage, 2016 Aug;24(8):1307-16.
    PMID: 26973328 DOI: 10.1016/j.joca.2016.03.003
    Treatment for articular cartilage damage is quite challenging as it shows limited repair and regeneration following injury. Non-operative and classical surgical techniques are inefficient in restoring normal anatomy and function of cartilage in osteoarthritis (OA). Thus, investigating new and effective strategies for OA are necessary to establish feasible therapeutic solutions. The emergence of the new discipline of regenerative medicine, having cell-based therapy as its primary focus, may enable us to achieve repair and restore the damaged articular cartilage. This review describes progress and development of employing mesenchymal stromal cell (MSC)-based therapy as a promising alternative for OA treatment. The objective of this review is to first, discuss how in vitro MSC chondrogenic differentiation mimics in vivo embryonic cartilage development, secondly, to describe various chondrogenic differentiation strategies followed by pre-clinical and clinical studies demonstrating their feasibility and efficacy. However, several challenges need to be tackled before this research can be translated to the clinics. In particular, better understanding of the post-transplanted cell behaviour and learning to enhance their potency in the disease microenvironment is essential. Final objective is to underscore the importance of isolation, storage, cell shipment, route of administration, optimum dosage and control batch to batch variations to realise the full potential of MSCs in OA clinical trials.
    MeSH terms: Cartilage, Articular; Cell Differentiation; Humans; Osteoarthritis; Chondrogenesis; Mesenchymal Stromal Cells*
  15. Soga T, Lim WL, Khoo AS, Parhar IS
    PMID: 26973595 DOI: 10.3389/fendo.2016.00015
    Kisspeptin, a newly discovered neuropeptide, regulates gonadotropin-releasing hormone (GnRH). Kisspeptins are a large RF-amide family of peptides. The kisspeptin coded by KiSS-1 gene is a 145-amino acid protein that is cleaved to C-terminal peptide kisspeptin-10. G-protein-coupled receptor 54 (GPR54) has been identified as a kisspeptin receptor, and it is expressed in GnRH neurons and in a variety of cancer cells. In this study, enhanced green fluorescent protein (EGFP) labeled GnRH cells with migratory properties, which express GPR54, served as a model to study the effects of kisspeptin on cell migration. We monitored EGFP-GnRH neuronal migration in brain slide culture of embryonic day 14 transgenic rat by live cell imaging system and studied the effects of kisspeptin-10 (1 nM) treatment for 36 h on GnRH migration. Furthermore, to determine kisspeptin-induced molecular pathways related with apoptosis and cytoskeletal changes during neuronal migration, we studied the expression levels of candidate genes in laser-captured EGFP-GnRH neurons by real-time PCR. We found that there was no change in the expression level of genes related to cell proliferation and apoptosis. The expression of ankyrin repeat domain-containing protein (ankrd) 26 in EGFP-GnRH neurons was upregulated by the exposure to kisspeptin. These studies suggest that ankrd 26 gene plays an unidentified role in regulating neuronal movement mediated by kisspeptin-GPR54 signaling, which could be a potential pathway to suppress cell migration.
    MeSH terms: Animals; Cell Movement; Gonadotropin-Releasing Hormone; Neurons; Ankyrin Repeat; Apoptosis; Cell Proliferation; Green Fluorescent Proteins; Rats; Rats, Transgenic; Kisspeptins; Real-Time Polymerase Chain Reaction
  16. Aw YK, Ong KS, Lee LH, Cheow YL, Yule CM, Lee SM
    Front Microbiol, 2016;7:219.
    PMID: 26973605 DOI: 10.3389/fmicb.2016.00219
    Emergence of antimicrobial resistance coupled with the slowdown in discovery of new antimicrobial compounds points to serious consequences for human health. Therefore, scientists are looking for new antimicrobial compounds from unique and understudied ecosystems such as tropical peat swamp forests. Over the course of isolating antimicrobial producing bacteria from North Selangor tropical peat swamp forest, Malaysia, a Gram variable, rod shaped, endospore forming, facultative anaerobic novel strain MSt1(T) that exerts potent and broad spectrum antimicrobial activity was isolated. Phylogenetic analysis using 16S rRNA gene sequences showed that strain MSt1(T) belonged to the genus Paenibacillus with the highest similarity to Paenibacillus elgii SD17(T) (99.5%). Whole genome comparison between strain MSt1(T) with its closely related species using average nucleotide identity (ANI) revealed that similarity between strain MSt1(T) with P. elgii B69 (93.45%) and Paenibacillus ehimensis A2 (90.42%) was below the recommended threshold of 95%. Further analysis using in silico pairwise DDH also showed that similarity between strain MSt1(T) with P. elgii B69 (55.4%) and P. ehimensis A2 (43.7%) was below the recommended threshold of 70%. Strain MSt1(T) contained meso-diaminopilemic acid in the cell wall and MK-7 as the major menaquinone. The major fatty acids of strain MSt1(T) were anteiso-C15:0 (48.2%) and C16:0 (29.0%) whereas the polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, one unknown lipid, two unknown glycolipids, and one unknown phospholipid. Total DNA G+C content of strain MSt1(T) was 51.5 mol%. The extract from strain MSt1(T) exerted strong antimicrobial activity against Escherichia coli ATCC 25922 (MIC = 1.5 μg/mL), MRSA ATCC 700699 (MIC = 25 μg/mL) and Candida albicans IMR (MIC = 12.5 μg/mL). Partially purified active fraction exerted a strong effect against E. coli ATCC 25922 resulting in cell rupture when viewed with SEM. Based on distinctive taxonomic differences between strain MSt1(T) when compared to its closely related type species, we propose that strain MSt1(T) represents a novel species within the genus of Paenibacillus, for which the name Paenibacillus tyrfis sp. nov. (= DSM 100708(T) = MCCC 1K01247(T)) is proposed.
    MeSH terms: Anti-Bacterial Agents; Base Composition; Candida albicans; Cardiolipins; Escherichia coli; Fatty Acids; Glycolipids; Humans; Phosphatidylethanolamines; RNA, Ribosomal, 16S; Soil; Vitamin K 2; Wetlands; Methicillin-Resistant Staphylococcus aureus; Paenibacillus
  17. Yap KP, Ho WS, Gan HM, Chai LC, Thong KL
    Front Microbiol, 2016;7:270.
    PMID: 26973639 DOI: 10.3389/fmicb.2016.00270
    Typhoid fever, caused by Salmonella enterica serovar Typhi, remains an important public health burden in Southeast Asia and other endemic countries. Various genotyping methods have been applied to study the genetic variations of this human-restricted pathogen. Multilocus sequence typing (MLST) is one of the widely accepted methods, and recently, there is a growing interest in the re-application of MLST in the post-genomic era. In this study, we provide the global MLST distribution of S. Typhi utilizing both publicly available 1,826 S. Typhi genome sequences in addition to performing conventional MLST on S. Typhi strains isolated from various endemic regions spanning over a century. Our global MLST analysis confirms the predominance of two sequence types (ST1 and ST2) co-existing in the endemic regions. Interestingly, S. Typhi strains with ST8 are currently confined within the African continent. Comparative genomic analyses of ST8 and other rare STs with genomes of ST1/ST2 revealed unique mutations in important virulence genes such as flhB, sipC, and tviD that may explain the variations that differentiate between seemingly successful (widespread) and unsuccessful (poor dissemination) S. Typhi populations. Large scale whole-genome phylogeny demonstrated evidence of phylogeographical structuring and showed that ST8 may have diverged from the earlier ancestral population of ST1 and ST2, which later lost some of its fitness advantages, leading to poor worldwide dissemination. In response to the unprecedented increase in genomic data, this study demonstrates and highlights the utility of large-scale genome-based MLST as a quick and effective approach to narrow the scope of in-depth comparative genomic analysis and consequently provide new insights into the fine scale of pathogen evolution and population structure.
    MeSH terms: Genotype; Humans; Mutation; Nicotinic Acids; Phylogeny; Public Health; Salmonella typhi; Succinimides; Typhoid Fever; Genetic Variation; Virulence; Genome; Genomics; Multilocus Sequence Typing; Phylogeography
  18. Suparji NS, Chan G, Sapili H, Arshad NM, In LL, Awang K, et al.
    PLoS One, 2016;11(3):e0151472.
    PMID: 26974436 DOI: 10.1371/journal.pone.0151472
    Geranylated 4-phenylcoumarins, DMDP-1 & -2 isolated from Mesua elegans were investigated for anticancer potential against human prostate cancer cells. Treatment with DMDP-1 & -2 resulted in cell death in a time and dose dependent manner in an MTT assay on all cancer cell lines tested with the exception of lung adenocarcinoma cells. DMDP-1 showed highest cytotoxic efficacy in PC-3 cells while DMDP-2 was most potent in DU 145 cells. Flow cytometry indicated that both coumarins were successful to induce programmed cell death after 24 h treatment. Elucidation on the mode-of-action via protein arrays and western blotting demonstrated death induced without any significant expressions of caspases, Bcl-2 family proteins and cleaved PARP, thus suggesting the involvement of caspase-independent pathways. In identifying autophagy, analysis of GFP-LC3 showed increased punctate in PC-3 cells pre-treated with CQ and treated with DMDP-1. In these cells decreased expression of autophagosome protein, p62 and cathepsin B further confirmed autophagy. In contrary, the DU 145 cells pre-treated with CQ and treated with DMDP-2 has reduced GFP-LC3 punctate although the number of cells with obvious GFP-LC3 puncta was significantly increased in the inhibitor-treated cells. The increase level of p62 suggested leakage of cathepsin B into the cytosol to trigger potential downstream death mediators. This correlated with increased expression of cathepsin B and reduced expression after treatment with its inhibitor, CA074. Also auto-degradation of calpain-2 upon treatment with DMDP-1 &-2 and its inhibitor alone, calpeptin compared with the combination treatment, further confirmed involvement of calpain-2 in PC-3 and DU 145 cells. Treatment with DMDP-1 & -2 also showed up-regulation of total and phosphorylated p53 levels in a time dependent manner. Hence, DMDP-1 & -2 showed ability to activate multiple death pathways involving autophagy, lysosomal and endoplasmic reticulum death proteins which could potentially be manipulated to develop anti-cancer therapy in apoptosis resistant cells.
    MeSH terms: Antineoplastic Agents/isolation & purification; Antineoplastic Agents/pharmacology*; Antineoplastic Agents/chemistry; Autophagy/drug effects; Calpain/metabolism; Coumarins/isolation & purification; Coumarins/pharmacology*; Coumarins/chemistry; Endoplasmic Reticulum/drug effects; Endoplasmic Reticulum/metabolism; Humans; Lysosomes/drug effects; Lysosomes/metabolism; Male; Prostatic Neoplasms/enzymology*; Prostatic Neoplasms/pathology*; Blotting, Western; Reproducibility of Results; Signal Transduction/drug effects; Inhibitory Concentration 50; Caspases/metabolism; Cell Line, Tumor
  19. See JX, Samudi C, Saeidi A, Menon N, Choh LC, Vadivelu J, et al.
    PLoS Negl Trop Dis, 2016 Mar;10(3):e0004503.
    PMID: 26974441 DOI: 10.1371/journal.pntd.0004503
    Burkholderia pseudomallei (B. pseudomallei), the causative agent of melioidosis, is a deadly pathogen endemic across parts of tropical South East Asia and Northern Australia. B. pseudomallei can remain latent within the intracellular compartment of the host cell over prolonged periods of time, and cause persistent disease leading to treatment difficulties. Understanding the immunological mechanisms behind persistent infection can result in improved treatment strategies in clinical melioidosis.
  20. Looi LJ, Aris AZ, Haris H, Yusoff FM, Hashim Z
    Chemosphere, 2016 Jun;152:265-73.
    PMID: 26974481 DOI: 10.1016/j.chemosphere.2016.02.126
    The present study examined the concentrations of mercury (Hg), methylmercury (MeHg), and selenium (Se) in the multiple tissues of the Plotosus canius and Periophthalmodon schlosseri collected from the Strait of Malacca. The mean value in mg kg(-1) of Hg (P. canius: 0.34 ± 0.19; P. schlosseri: 0.32 ± 0.18) and MeHg in muscle (P. canius: 0.14 ± 0.11; P. schlosseri: 0.17 ± 0.11) were below the Codex general standard for contaminants and toxins in food and feed (CODEX STAN 193-1995), the Malaysian Food Regulation 1985 and the Japan Food Sanitation Law. For P. canius, the liver contained the highest concentrations of Hg (0.48 ± 0.07 mg kg(-1)) and MeHg (0.21 ± 0.00 mg kg(-1)), whereas for P. schlosseri, the gill contained the highest concentrations of Hg (0.36 ± 0.06 mg kg(-1)) and MeHg (0.21 ± 0.05 mg kg(-1)). The highest concentration of (80)Se (mg kg(-1)) was observed in the liver of P. canius (20.34 ± 5.68) and in the gastrointestinal tract (3.18 ± 0.42) of P. schlosseri. The selenium:mercury (Se:Hg) molar ratios were above 1 and the positive selenium health benefit value (HBVSe) suggesting the possible protective effects of Se against Hg toxicity. The estimate weekly intakes (EWIs) in μg kg(-1) body weight (bw) week(-1) of Hg (P. canius: 0.27; P. schlosseri: 0.15) and MeHg (P. canius: 0.11; P. schlosseri: 0.08) were found to be lower than the provisional tolerable weekly intake established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA). Based on the calculated EWIs, P. canius, and P. schlosseri were found to be unlikely to cause mercury toxicity in human consumption.
    MeSH terms: Animals; Body Weight; Catfishes; Food Additives; Gills; Humans; Japan; Liver; Mercury; Mercury Poisoning; Methylmercury Compounds; Muscles; Sanitation; Selenium; World Health Organization; Gastrointestinal Tract
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