Browse publications by year: 2017

  1. Ooi TC, Chan KM, Sharif R
    Immunopharmacol Immunotoxicol, 2017 Oct;39(5):259-267.
    PMID: 28697633 DOI: 10.1080/08923973.2017.1344987
    CONTEXT: Zinc L-carnosine (ZnC) is a chelate of Zn and L-carnosine and is used clinically in the treatment of peptic ulcer.

    OBJECTIVE: In this study, we aim to investigate the involvement of heme oxygenase-1 (HO-1) in the anti-inflammatory effects of ZnC in lipopolysaccharide (LPS)-induced RAW 264.7 murine macrophages.

    MATERIALS AND METHODS: We used immunoblotting analysis to evaluate the involvement of HO-1 in the anti-inflammatory effects of ZnC and the signaling pathway involved was measured using Dual luciferase reporter assay.

    RESULTS: Results from immunoblotting analysis demonstrated that pretreatment of cells with ZnC enhanced the expression of HO-1 in RAW 264.7 cells. Pretreatment of cells with HO-1 inhibitor (tin protoporphyrin IX dichloride) significantly attenuated the inhibitory effects of ZnC on nitric oxide (NO) production, inducible nitric oxide synthase (iNOS) expression and NF-κB activation in LPS-induced RAW 264.7 cells, suggesting that HO-1 play an important role in the suppression of inflammatory responses induced by ZnC. Furthermore, results from co-immunoprecipitation of Nrf2 and Keap1 and dual luciferase reporter assay showed that pretreatment of ZnC was able to activate the Nrf2 signaling pathway. Treatment of cells with p38 inhibitor (SB203580), c-Jun N-terminal kinase inhibitor (SP600125), and MEK 1/2 inhibitor (U0126) did not significantly suppress the induction of HO-1 by ZnC. Moreover, our present findings suggest that the effects of ZnC on NO production, HO-1 expression, and Nrf2 activation were attributed to its Zn subcomponent, but not l-carnosine.

    CONCLUSION: Pretreatment with ZnC was able to activate Nrf2/HO-1 signaling pathway, thus suppressing the expression of inflammatory mediators, such as NO and iNOS in LPS-induced RAW 264.7 cells.

    MeSH terms: RAW 264.7 Cells; Animals; Carnosine/analogs & derivatives*; Carnosine/pharmacology; Inflammation/chemically induced; Inflammation/metabolism; Inflammation/pathology; Lipopolysaccharides/toxicity*; Macrophages/metabolism*; Macrophages/pathology; Membrane Proteins/biosynthesis*; Nitric Oxide/biosynthesis; Organometallic Compounds/pharmacology*; Zinc Compounds/pharmacology; MAP Kinase Signaling System/drug effects*; NF-E2-Related Factor 2/metabolism*; Mice; Heme Oxygenase-1/biosynthesis*; Nitric Oxide Synthase Type II/biosynthesis
  2. Mohd Noor MS, Khoo LS, Zamaliana Alias WZ, Hasmi AH, Ibrahim MA, Mahmood MS
    Forensic Sci Int, 2017 Sep;278:410.e1-410.e9.
    PMID: 28698062 DOI: 10.1016/j.forsciint.2017.05.014
    The first ever mass identification operation of skeletal remains conducted for the clandestine graves in Malaysia consisted of 165 individuals unearthed from 28 human trafficking transit camps located in Wang Kelian, along the Thai-Malaysia border. A DVI response was triggered in which expert teams comprising of pathologists, anthropologists, odontologists, radiologists and DNA experts were gathered at the identified operation centre. The Department of Forensic Medicine, Hospital Sultanah Bahiyah, Alor Star, Kedah, located approximately 75km away from Wang Kelian, was temporarily converted into a victim identification centre (VIC) as it is the nearest available forensic facility to the mass grave site. The mortuary operation was conducted over a period of 3 months from June to September 2015, and was divided into two phases; phase 1 involving the postmortem examination of the remains of 116 suspected individuals and for phase 2 the remains of 49 suspected individuals. The fact that the graves were of unknown individuals afforded the mass identification operation a sufficient duration of 2 weeks as preparatory phase enabling procedurals and daily victim identification workflow to be established, and the setting up of a temporary body storage for the designated mortuary. The temporary body storage has proven to be a significant factor in enabling the successful conclusion of the VIC operation to the final phase of temporary controlled burials. Recognition from two international observers, Mr. Andréas Patiño Umaña, from the International Committee of Red Cross (ICRC) and Prof. Noel Woodford from Victoria Institute of Forensic Medicine (VIFM) had proven the mortuary operation was in compliance to the international quality and standards. The overall victim identification and mortuary operation identified a number of significant challenges, in particular the management of commingled human remains as well as the compilation of postmortem data in the absence of antemortem data for future reconciliation. CF Index in this DVI operation is 9%, indicating the primary identifications in this operation were effective. Limitations and further improvements of the mass identification operation will be discussed. This paper details the planning, preparations and management of the mass identification operation on the exhumed human remains which was also a forensic humanitarian service for the dead with dignity and respect.
    MeSH terms: Adult; Autopsy; Burial*; Documentation; Female; Humans; Malaysia; Male; Mortuary Practice/organization & administration*; DNA Fingerprinting; Age Distribution; Sex Distribution; Crime Victims*; Continental Population Groups/statistics & numerical data; Forensic Sciences/organization & administration*; Young Adult; Human Trafficking*; Body Remains*
  3. Tan KK, Zulkifle NI, Abd-Jamil J, Sulaiman S, Yaacob CN, Azizan NS, et al.
    Infect Genet Evol, 2017 Oct;54:271-275.
    PMID: 28698156 DOI: 10.1016/j.meegid.2017.07.008
    Dengue is hyperendemic in most of Southeast Asia. In this region, all four dengue virus serotypes are persistently present. Major dengue outbreak cycle occurs in a cyclical pattern involving the different dengue virus serotypes. In Malaysia, since the 1980s, the major outbreak cycles have involved dengue virus type 3 (DENV3), dengue virus type 1 (DENV1) and dengue virus type 2 (DENV2), occurring in that order (DENV3/DENV1/DENV2). Only limited information on the DENV3 cycles, however, have been described. In the current study, we examined the major outbreak cycle involving DENV3 using data from 1985 to 2016. We examined the genetic diversity of DENV3 isolates obtained during the period when DENV3 was the dominant serotype and during the inter-dominant transmission period. Results obtained suggest that the typical DENV3/DENV1/DENV2 cyclical outbreak cycle in Malaysia has recently been disrupted. The last recorded major outbreak cycle involving DENV3 occurred in 2002, and the expected major outbreak cycle involving DENV3 in 2006-2012 did not materialize. DENV genome analyses revealed that DENV3 genotype II (DENV3/II) was the predominant DENV3 genotype (67%-100%) recovered between 1987 and 2002. DENV3 genotype I (DENV3/I) emerged in 2002 followed by the introduction of DENV3 genotype III (DENV3/III) in 2008. These newly emerged DENV3 genotypes replaced DENV3/II, but there was no major upsurge of DENV3 cases that accompanied the emergence of these viruses. DENV3 remained in the background of DENV1 and DENV2 until now. Virus genome sequence analysis suggested that intrinsic differences within the different dengue virus genotypes could have influenced the transmission efficiency of DENV3. Further studies and continuous monitoring of the virus are needed for better understanding of the DENV transmission dynamics in hyperendemic regions.
    MeSH terms: Dengue/epidemiology*; Dengue/virology*; Dengue Virus/classification; Dengue Virus/genetics*; Disease Outbreaks*; Genotype*; Humans; Malaysia/epidemiology; Phylogeny; Genetic Variation; Genome, Viral
  4. Kosaisavee V, Suwanarusk R, Chua ACY, Kyle DE, Malleret B, Zhang R, et al.
    Blood, 2017 09 14;130(11):1357-1363.
    PMID: 28698207 DOI: 10.1182/blood-2017-02-764787
    Two malaria parasites of Southeast Asian macaques, Plasmodium knowlesi and P cynomolgi, can infect humans experimentally. In Malaysia, where both species are common, zoonotic knowlesi malaria has recently become dominant, and cases are recorded throughout the region. By contrast, to date, only a single case of naturally acquired P cynomolgi has been found in humans. In this study, we show that whereas P cynomolgi merozoites invade monkey red blood cells indiscriminately in vitro, in humans, they are restricted to reticulocytes expressing both transferrin receptor 1 (Trf1 or CD71) and the Duffy antigen/chemokine receptor (DARC or CD234). This likely contributes to the paucity of detectable zoonotic cynomolgi malaria. We further describe postinvasion morphologic and rheologic alterations in P cynomolgi-infected human reticulocytes that are strikingly similar to those observed for P vivax These observations stress the value of P cynomolgi as a model in the development of blood stage vaccines against vivax malaria.
    MeSH terms: Animals; Duffy Blood-Group System/metabolism*; Erythrocytes/parasitology; Host-Parasite Interactions; Humans; Macaca; Plasmodium vivax/physiology; Receptors, Cell Surface/metabolism*; Receptors, Transferrin/metabolism*; Reticulocytes/parasitology*; Rheology; Zoonoses/parasitology*; Antigens, CD/metabolism*; Plasmodium cynomolgi/physiology*; Tropism*; Merozoites/physiology
  5. Mallhi TH, Khan AH, Sarriff A, Adnan AS, Khan YH
    BMJ Open, 2017 Jul 10;7(7):e016805.
    PMID: 28698348 DOI: 10.1136/bmjopen-2017-016805
    OBJECTIVES: Dengue imposes substantial economic, societal and personal burden in terms of hospital stay, morbidity and mortality. Early identification of dengue cases with high propensity of increased hospital stay and death could be of value in isolating patients in need of early interventions. The current study was aimed to determine the significant factors associated with dengue-related prolonged hospitalisation and death.

    DESIGN: Cross-sectional retrospective study.

    SETTING: Tertiary care teaching hospital.

    PARTICIPANTS: Patients with confirmed dengue diagnosis were stratified into two categories on the basis of prolonged hospitalisation (≤3 days and >3 days) and mortality (fatal cases and non-fatal cases). Clinico-laboratory characteristics between these categories were compared by using appropriate statistical methods.

    RESULTS: Of 667 patients enrolled, 328 (49.2%) had prolonged hospitalisation. The mean hospital stay was 4.88±2.74 days. Multivariate analysis showed that dengue haemorrhagic fever (OR 2.3), elevated alkaline phosphatase (ALP) (OR 2.3), prolonged prothrombin time (PT) (OR 1.7), activated partial thromboplastin time (aPTT) (OR 1.9) and multiple-organ dysfunctions (OR 2.1) were independently associated with prolonged hospitalisation. Overall case fatality rate was 1.1%. Factors associated with dengue mortality were age >40 years (p=0.004), secondary infection (p=0.040), comorbidities (p<0.05), acute kidney injury (p<0.001), prolonged PT (p=0.022), multiple-organ dysfunctions (p<0.001), haematocrit >20% (p=0.001), rhabdomyolosis (p<0.001) and respiratory failure (p=0.007). Approximately half of the fatal cases in our study had prolonged hospital stay of greater than three days.

    CONCLUSIONS: The results underscore the high proportion of dengue patients with prolonged hospital stay. Early identification of factors relating to prolonged hospitalisation and death will have obvious advantages in terms of appropriate decisions about treatment and management in high dependency units.

    Study site: Hospital Universiti Sains Malaysia (HUSM), Kelantan
    MeSH terms: Adolescent; Adult; Cross-Sectional Studies; Female; Humans; Length of Stay/statistics & numerical data*; Malaysia/epidemiology; Male; Middle Aged; Multiple Organ Failure/etiology; Retrospective Studies; Risk Factors; ROC Curve; Comorbidity; Multivariate Analysis; Logistic Models; Hospital Mortality/trends*; Severe Dengue/complications*; Severe Dengue/mortality*; Young Adult; Acute Kidney Injury/etiology; Tertiary Care Centers
  6. Phyu WK, Ong KC, Wong KT
    Emerg Microbes Infect, 2017 Jul 12;6(7):e62.
    PMID: 28698666 DOI: 10.1038/emi.2017.49
    Enterovirus A71 (EV-A71) causes hand-foot-and-mouth disease (HFMD), which may be complicated by fatal encephalomyelitis. Although fecal-oral or oral-oral routes are important in person-to-person transmission, how viral shedding and exposure may predispose individuals to infection remains unknown. We investigated person-to-person transmission by using a model of HFMD and encephalomyelitis based on EV-A71 oral infection of 2-week-old hamsters. Animals (index animals) infected with 104 50% cell culture infective doses of virus uniformly developed severe disease four days post-infection (dpi), whereas littermate contacts developed severe disease after six to seven days of exposure to index animals. Virus was detected in oral washes and feces at 3-4 dpi in index animals and at three to eight days after exposure to index animals in littermate contact animals. In a second experiment, non-littermate contact animals exposed for 8 or 12 h to index animals developed the disease six and four days post-exposure, respectively. Tissues from killed index and contact animals, studied by light microscopy, immunohistochemistry and in situ hybridization, exhibited mild inflammatory lesions and/or viral antigens/RNA in the squamous epithelia of the oral cavity, tongue, paws, skin, esophagus, gastric epithelium, salivary glands, lacrimal glands, central nervous system neurons, muscles (skeletal, cardiac and smooth muscles) and liver. Orally shed viruses were probably derived from infected oral mucosa and salivary glands, whereas fecal viruses may have derived from these sites as well as from esophageal and gastric epithelia. Asymptomatic seroconversion in exposed mother hamsters was demonstrated. Our hamster model should be useful in studying person-to-person EV-A71 transmission and how drugs and vaccines may interrupt transmission.
    MeSH terms: Animals; Central Nervous System Infections/virology; Disease Models, Animal*; Encephalomyelitis/virology*; Enterovirus Infections/transmission*; Enterovirus Infections/virology; Epithelial Cells/virology; Feces/virology; Cricetinae; Hand, Foot and Mouth Disease/complications; Hand, Foot and Mouth Disease/physiopathology*; Hand, Foot and Mouth Disease/transmission*; Hand, Foot and Mouth Disease/virology; Humans; Immunohistochemistry; Inflammation/pathology; Mothers; Mouth/virology; Mouth Mucosa/virology; Muscles/virology; Salivary Glands/virology; Skin/virology; Virus Shedding; In Situ Hybridization; Asymptomatic Infections
  7. Neoh CF, Senol E, Kara A, Dinleyici EC, Turner SJ, Kong DCM
    Mycoses, 2017 Nov;60(11):714-722.
    PMID: 28699297 DOI: 10.1111/myc.12651
    Anidulafungin has been shown to be non-inferior to, and possibly more efficacious, than fluconazole in treating patients with invasive candidiasis (IC). This study aimed to determine the cost-effectiveness of anidulafungin vs fluconazole for treatment of IC in the Turkish setting. A decision analytic model was constructed to depict downstream economic consequences of using anidulafungin or fluconazole for treatment of IC in the Turkish hospitals. Transition probabilities (ie treatment success, observed or indeterminate treatment failures) were obtained from a published randomised clinical trial. Cost inputs were from the latest Turkish resources. Data not available in the literature were estimated by expert panels. Sensitivity analyses were performed to assess the robustness of the model outcome. While anidulafungin [TL 17 171 (USD 4589)] incurred a higher total cost than fluconazole [TL 8233 (USD 2200) per treated patient, treatment with anidulafungin was estimated to save an additional 0.58 life-years, with an incremental cost-effectiveness ratio of TL 15 410 (USD 4118) per life-years saved. Drug acquisition cost and hospitalisation were the main cost drivers for anidulafungin and fluconazole arms respectively. The model findings were robust over a wide range of input variables except for anidulafungin drug cost. Anidulafungin appears to be a cost-effective therapy in treating IC from the Turkish hospital perspective.
    MeSH terms: Antifungal Agents/economics; Antifungal Agents/therapeutic use*; Cost-Benefit Analysis; Decision Support Techniques; Double-Blind Method; Humans; Turkey; Fluconazole/economics; Fluconazole/therapeutic use*; Randomized Controlled Trials as Topic; Treatment Outcome; Treatment Failure; Echinocandins/economics; Echinocandins/therapeutic use*; Candidiasis, Invasive/drug therapy*; Candidiasis, Invasive/microbiology
  8. Hughes TP, Munhoz E, Aurelio Salvino M, Ong TC, Elhaddad A, Shortt J, et al.
    Br J Haematol, 2017 10;179(2):219-228.
    PMID: 28699641 DOI: 10.1111/bjh.14829
    The Evaluating Nilotinib Efficacy and Safety in Clinical Trials-Extending Molecular Responses (ENESTxtnd) study was conducted to evaluate the kinetics of molecular response to nilotinib in patients with newly diagnosed chronic myeloid leukaemia in chronic phase and the impact of novel dose-optimization strategies on patient outcomes. The ENESTxtnd protocol allowed nilotinib dose escalation (from 300 to 400 mg twice daily) in the case of suboptimal response or treatment failure as well as dose re-escalation for patients with nilotinib dose reductions due to adverse events. Among 421 patients enrolled in ENESTxtnd, 70·8% (95% confidence interval, 66·2-75·1%) achieved major molecular response (BCR-ABL1 ≤ 0·1% on the International Scale) by 12 months (primary endpoint). By 24 months, 81·0% of patients achieved major molecular response, including 63·6% (56 of 88) of those with dose escalations for lack of efficacy and 74·3% (55 of 74) of those with dose reductions due to adverse events (including 43 of 54 patients with successful re-escalation). The safety profile of nilotinib was consistent with prior studies. The most common non-haematological adverse events were headache, rash, and nausea; cardiovascular events were reported in 4·5% of patients (grade 3/4, 3·1%). The study was registered at clinicaltrials.gov (NCT01254188).
    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Cardiovascular Diseases/chemically induced; Cardiovascular Diseases/epidemiology; Female; Humans; Male; Middle Aged; Prospective Studies; Pyrimidines/administration & dosage*; Pyrimidines/adverse effects; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy*; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/epidemiology
  9. Ahmadi A, Mustaffa MS, Haghdoost AA, Mansor SMS
    Trends Psychiatry Psychother, 2017 7 13;39(2):88-97.
    PMID: 28700038 DOI: 10.1590/2237-6089-2016-0047
    Introduction: Anxiety disorders in primary school-aged children negatively affect their mental health and psychological development. Available non-medical treatments for these conditions are time-consuming and expensive. In this context, eclectic therapy is a therapeutic approach that incorporates some therapeutic techniques and philosophies to create the ideal treatment. In this study, eclectic therapy consisted of art therapy and cognitive-behavioral therapy designed for children suffering from high level of anxiety in their middle childhood years. The therapy also included group guidance sessions for their mothers. The effectiveness of this intervention was examined in the study.

    Methods: 61 students aged 9-12 years with high levels of anxiety participated in the study. Intervention A (n = 20) consisted of 9-hour eclectic therapy for children with 3-hour group guidance sessions for their mothers. Intervention B (n = 20) consisted of 9-hour eclectic therapy for children. There was also a control group (n = 21).

    Results: Teacher ratings of children's mental health difficulties and self-report ratings of anxiety disorders indicated a significant difference from pretest to posttest, revealing a large effect size between the two interventions. Higher levels of pretest scores significantly predicted higher posttest scores for all domains of anxiety and mental health difficulties. Furthermore, age, gender, mothers working a 15-hour day, mother's educational level, parental divorce rates, parental death, and family monthly income predicted therapy outcomes.

    Conclusion: Results provide support for the effectiveness of eclectic art and CBT to improve children's mental health and reduce anxiety through changing thoughts, beliefs, emotions, and behaviors that may cause fear and anxiety.

    MeSH terms: Analysis of Variance; Anxiety Disorders/therapy*; Child; Counseling; Cross-Sectional Studies; Female; Humans; Male; Mothers; Rural Population; Severity of Illness Index; Socioeconomic Factors; Treatment Outcome; Self Report; School Teachers
  10. Acharya UR, Bhat S, Koh JEW, Bhandary SV, Adeli H
    Comput Biol Med, 2017 Sep 01;88:72-83.
    PMID: 28700902 DOI: 10.1016/j.compbiomed.2017.06.022
    Glaucoma is an optic neuropathy defined by characteristic damage to the optic nerve and accompanying visual field deficits. Early diagnosis and treatment are critical to prevent irreversible vision loss and ultimate blindness. Current techniques for computer-aided analysis of the optic nerve and retinal nerve fiber layer (RNFL) are expensive and require keen interpretation by trained specialists. Hence, an automated system is highly desirable for a cost-effective and accurate screening for the diagnosis of glaucoma. This paper presents a new methodology and a computerized diagnostic system. Adaptive histogram equalization is used to convert color images to grayscale images followed by convolution of these images with Leung-Malik (LM), Schmid (S), and maximum response (MR4 and MR8) filter banks. The basic microstructures in typical images are called textons. The convolution process produces textons. Local configuration pattern (LCP) features are extracted from these textons. The significant features are selected using a sequential floating forward search (SFFS) method and ranked using the statistical t-test. Finally, various classifiers are used for classification of images into normal and glaucomatous classes. A high classification accuracy of 95.8% is achieved using six features obtained from the LM filter bank and the k-nearest neighbor (kNN) classifier. A glaucoma integrative index (GRI) is also formulated to obtain a reliable and effective system.
    MeSH terms: Algorithms*; Diagnostic Techniques, Ophthalmological; Humans; Image Interpretation, Computer-Assisted/methods*; Pattern Recognition, Automated/methods*
  11. Azbel L, Rozanova J, Michels I, Altice FL, Stöver H
    Harm Reduct J, 2017 07 10;14(1):43.
    PMID: 28693573 DOI: 10.1186/s12954-017-0168-8
    BACKGROUND: Kyrgyzstan, where HIV is concentrated in prisons and driven by injection drug use, provides a prison-based methadone maintenance therapy program as well as abstinence-oriented therapeutic community based on the 12-step model called the "Clean Zone." We aimed to qualitatively assess how prisoners navigate between these treatment options to understand the persistence of the Clean Zone despite a lack of evidence to support its effectiveness in treating opioid use disorders.

    METHODS: We conducted an analysis of policy documents and over 60 h of participant observation in February 2016, which included focus groups with a convenience sample of 20 therapeutic community staff members, 110 prisoners across three male and one female prisons, and qualitative interviews with two former Clean Zone participants. Field notes containing verbatim quotes from participants were analyzed through iterative reading and discussion to understand how participants generally perceive the program, barriers to entry and retention, and implications for future treatment within prisons.

    RESULTS: Our analyses discerned three themes: pride in the mission of the Clean Zone, idealism regarding addiction treatment outcomes against all odds, and the demonization of methadone.

    CONCLUSION: Despite low enrollment and lack of an evidence base, the therapeutic community is buttressed by the strong support of the prison administration and its clients as an "ordered" alternative to what is seen as chaotic life outside of the Clean Zone. The lack of services for Clean Zone patients after release likely contributes to high rates of relapse to drug use. The Clean Zone would benefit from integration of stabilized methadone patients combined with a post-release program.

    MeSH terms: Adult; Attitude; Female; Humans; Kyrgyzstan/epidemiology; Male; Methadone/therapeutic use; Middle Aged; Opioid-Related Disorders/rehabilitation*; Patient Acceptance of Health Care; Prisoners*; Prisons; Recurrence; Therapeutic Community*; Treatment Outcome; Opiate Substitution Treatment
  12. Al-Zuaidy MH, Mumtaz MW, Hamid AA, Ismail A, Mohamed S, Razis AFA
    BMC Complement Altern Med, 2017 Jul 10;17(1):359.
    PMID: 28693595 DOI: 10.1186/s12906-017-1849-2
    BACKGROUND: Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by continuous hyperglycemia associated with insulin resistance and /or reduced insulin secretion. There is an emerging trend regarding the use of medicinal plants for the treatment of diabetes mellitus. Melicope lunu-ankenda (ML) is one of the Melicope species belonging to the family Rutaceae. In traditional medicines, its leaves and flowers are known to exhibit prodigious health benefits. The present study aimed at investigating anti-diabetic effect of Melicope lunu-ankenda (ML) leaves extract.

    METHODS: In this study, anti-diabetic effect of ML extract is investigated in vivo to evaluate the biochemical changes, potential serum biomarkers and alterations in metabolic pathways pertaining to the treatment of HFD/STZ induced diabetic rats with ML extract using 1H NMR based metabolomics approach. Type 2 diabetic rats were treated with different doses (200 and 400 mg/kg BW) of Melicope lunu-ankenda leaf extract for 8 weeks, and serum samples were examined for clinical biochemistry. The metabolomics study of serum was also carried out using 1H NMR spectroscopy in combination with multivariate data analysis to explore differentiating serum metabolites and altered metabolic pathways.

    RESULTS: The ML leaf extract (400 mg/kg BW) treatment significantly increased insulin level and insulin sensitivity of obese diabetic rats, with concomitant decrease in glucose level and insulin resistance. Significant reduction in total triglyceride, cholesterol and low density lipoprotein was also observed after treatment. Interestingly, there was a significant increase in high density lipoprotein of the treated rats. A decrease in renal injury markers and activities of liver enzymes was also observed. Moreover, metabolomics studies clearly demonstrated that, ML extract significantly ameliorated the disturbance in glucose metabolism, tricarboxylic acid cycle, lipid metabolism, and amino acid metabolism.

    CONCLUSION: ML leaf extract exhibits potent antidiabetic properties, hence could be a useful and affordable alternative option for the management of T2DM.

    MeSH terms: Animals; Blood Glucose/metabolism*; Diabetes Mellitus, Experimental/blood; Diabetes Mellitus, Experimental/drug therapy*; Diabetes Mellitus, Experimental/etiology; Diabetes Mellitus, Type 2/blood; Diabetes Mellitus, Type 2/drug therapy; Diabetes Mellitus, Type 2/etiology; Hypoglycemic Agents/pharmacology; Hypoglycemic Agents/therapeutic use*; Insulin/blood; Insulin Resistance*; Kidney/drug effects; Lipids/blood*; Cholesterol, HDL/blood; Liver/drug effects; Liver/enzymology; Male; Phytotherapy*; Obesity/complications; Plant Extracts/pharmacology; Plant Extracts/therapeutic use; Triglycerides/blood; Rats, Sprague-Dawley; Plant Leaves; Rutaceae/chemistry*; Metabolomics; Proton Magnetic Resonance Spectroscopy
  13. Vaezzadeh V, Zakaria MP, Bong CW
    Mar Pollut Bull, 2017 Nov 15;124(1):33-42.
    PMID: 28693809 DOI: 10.1016/j.marpolbul.2017.07.008
    The Straits of Malacca is one of the world's busiest shipping routes where frequent oil spills occur. Rapid development in the west coast of Peninsular Malaysia is the other major source of petroleum pollution in this narrow waterway. In order to identify occurrence and origin of hydrocarbons in the Straits, mangrove oysters (Crassostrea belcheri) were collected from five sampling locations and analysed for n-alkanes and biomarkers. Soxhlet apparatus and two step column chromatography were used for extraction, purification and fractionation of the oysters. Petroleum origin n-alkanes were detected in majority of the sampling locations which is indicative of anthropogenic activities in this region. Using source and maturity diagnostic ratios for hopanes revealed used crankcase oil as the main source of petroleum hydrocarbons in oysters from all sampling locations except for the Pulau Merambong where signature of South East Asia crude oil (SEACO) was detected.
    MeSH terms: Alkanes/metabolism*; Animals; Malaysia; Triterpenes/metabolism*; Water Pollutants, Chemical/metabolism*; Biomarkers/metabolism; Crassostrea/metabolism*; Petroleum Pollution/analysis*
  14. Marcharchand S, Ting ASY
    J Environ Manage, 2017 Dec 01;203(Pt 1):542-549.
    PMID: 28693968 DOI: 10.1016/j.jenvman.2017.06.068
    Trichoderma asperellum (Ta) was first cultured in synthetic medium (Potato Dextrose Broth, PDB) of various concentrations (100, 75, 50, 25%). The biomass was harvested and inoculated into dye solutions (crystal violet, CV; methyl violet, MV; malachite green, MG; and cotton blue, CB). Reduced concentrations (20, 50, 75%) affected growth rate but their decolourization efficacies remained unaffected. This was attributed to similar numbers and types of functional groups (hydroxyl, amine, ester-lipid, alkane groups) found on the surface of fungal biomass, as revealed by the Fourier transformed infrared spectroscopy (FTIR) analysis. Their production of NADH-reductase for degradation, and their biosorption activities were also unaffected. In general, Ta cultured in reduced concentrations (20, 50, 75%) retained the ability to perform biosorption and biodegradation, similar to cultures from control (100% PDB). This suggested that reduced nutrient levels (as a cost-feasible strategy) could be used to cultivate biomass of Ta for dye removal activities.
    MeSH terms: Biodegradation, Environmental; Coloring Agents*; Gentian Violet; Trichoderma*; Spectroscopy, Fourier Transform Infrared; Biomass
  15. Osahor A, Deekonda K, Lee CW, Sim EU, Radu A, Narayanan K
    Anal Biochem, 2017 10 01;534:46-48.
    PMID: 28693990 DOI: 10.1016/j.ab.2017.07.008
    Sample preparation for scanning electron microscope analysis involves reagents and equipment that are expensive and often hazardous. Here we demonstrate a circumvention of Osmium tetroxide and critical point drying, greatly reducing the duration, complexity and cost of the process. We captured early stage interactions of invasive-bacteria and HeLa cells during the process of bacteria-mediated gene delivery and illustrate sufficient clarity can be obtained using this procedure to preserve and clearly visualize relevant cellular structures. This protocol is significantly cheaper and easier to adapt compared to conventional methods, and will allow routine preparation/viewing of eukaryotic or bacterial samples for basic morphological studies.
    MeSH terms: Escherichia coli/genetics*; Escherichia coli/isolation & purification; Genetic Vectors/genetics; HeLa Cells; Humans; Microscopy, Electron, Scanning; Osmium Tetroxide/chemistry; Gene Transfer Techniques*
  16. Moh TH, Lau NS, Furusawa G, Amirul AA
    Stand Genomic Sci, 2017;12:36.
    PMID: 28694917 DOI: 10.1186/s40793-017-0248-0
    Microbulbifer sp. CCB-MM1 is a halophile isolated from estuarine sediment of Matang Mangrove Forest, Malaysia. Based on 16S rRNA gene sequence analysis, strain CCB-MM1 is a potentially new species of genus Microbulbifer. Here we describe its features and present its complete genome sequence with annotation. The genome sequence is 3.86 Mb in size with GC content of 58.85%, harbouring 3313 protein coding genes and 92 RNA genes. A total of 71 genes associated with carbohydrate active enzymes were found using dbCAN. Ectoine biosynthetic genes, ectABC operon and ask_ect were detected using antiSMASH 3.0. Cell shape determination genes, mreBCD operon, rodA and rodZ were annotated, congruent with the rod-coccus cell cycle of the strain CCB-MM1. In addition, putative mreBCD operon regulatory gene, bolA was detected, which might be associated with the regulation of rod-coccus cell cycle observed from the strain.
  17. Azizan KA, Ressom HW, Mendoza ER, Baharum SN
    PeerJ, 2017;5:e3451.
    PMID: 28695065 DOI: 10.7717/peerj.3451
    Lactococcus lactis subsp. cremoris MG1363 is an important starter culture for dairy fermentation. During industrial fermentations, L. lactis is constantly exposed to stresses that affect the growth and performance of the bacterium. Although the response of L. lactis to several stresses has been described, the adaptation mechanisms at the level of in vivo fluxes have seldom been described. To gain insights into cellular metabolism, 13C metabolic flux analysis and gas chromatography mass spectrometry (GC-MS) were used to measure the flux ratios of active pathways in the central metabolism of L. lactis when subjected to three conditions varying in temperature (30°C, 37°C) and agitation (with and without agitation at 150 rpm). Collectively, the concentrations of proteinogenic amino acids (PAAs) and free fatty acids (FAAs) were compared, and Pearson correlation analysis (r) was calculated to measure the pairwise relationship between PAAs. Branched chain and aromatic amino acids, threonine, serine, lysine and histidine were correlated strongly, suggesting changes in flux regulation in glycolysis, the pentose phosphate (PP) pathway, malic enzyme and anaplerotic reaction catalysed by pyruvate carboxylase (pycA). Flux ratio analysis revealed that glucose was mainly converted by glycolysis, highlighting the stability of L. lactis' central carbon metabolism despite different conditions. Higher flux ratios through oxaloacetate (OAA) from pyruvate (PYR) reaction in all conditions suggested the activation of pyruvate carboxylate (pycA) in L. lactis, in response to acid stress during exponential phase. Subsequently, more significant flux ratio differences were seen through the oxidative and non-oxidative pentose phosphate (PP) pathways, malic enzyme, and serine and C1 metabolism, suggesting NADPH requirements in response to environmental stimuli. These reactions could play an important role in optimization strategies for metabolic engineering in L. lactis. Overall, the integration of systematic analysis of amino acids and flux ratio analysis provides a systems-level understanding of how L. lactis regulates central metabolism under various conditions.
    MeSH terms: Carbon Isotopes; Fatty Acids, Nonesterified; Fermentation; Glycolysis; Histidine; Lysine; Gas Chromatography-Mass Spectrometry; NADP; Pyruvate Carboxylase; Serine; Threonine; Pyruvic Acid; Metabolic Engineering; Metabolic Flux Analysis
  18. Chandrasekaran S, Kyaw NTT, Harries AD, Yee IA, Ellan P, Kurusamy T, et al.
    Public Health Action, 2017 Jun 21;7(2):155-160.
    PMID: 28695090 DOI: 10.5588/pha.17.0003
    Setting: Needle and Syringe Exchange Programme (NSEP) implemented by non-governmental organisations in Malaysia. Objectives: To determine enrolment, characteristics and retention in the NSEP of people who inject drugs (PWID) between 2013 and 2015. Design: Retrospective cohort study. Results: There were 20 946 PWID, with a mean age of 38 years. The majority were male (98%) and of Malay ethnicity (92%). Follow-up data were available for 20 761 PWID. Annual retention of newly enrolled PWID for each year was respectively 85%, 87% and 78% for 2013, 2014 and 2015, although annual enrolment over these years declined from 10 724 to 6288 to 3749. Total person-years (py) of follow-up were 27 806, with loss to follow-up of 40 per 100 py. Cumulative probability of retention in NSEP was 66% at 12 months, 45% at 24 months and 26% at 36 months. Significantly higher loss to follow-up rates were observed in those aged 15-24 years or ⩾50 years, females, transgender people and non-Malay ethnic groups. Conclusion: Annual retention of new PWID on NSEP was impressive, although enrolment declined over the 3 years of the study and cumulative loss to follow-up was high. A better understanding of these programmatic outcomes is required.
  19. Hassan R, Lee SY, Morni WZW
    ScientificWorldJournal, 2017;2017:1489360.
    PMID: 28695188 DOI: 10.1155/2017/1489360
    Sea star (class Asteroidea, phylum Echinodermata) is one of the most successful marine organisms inhabiting a wide range of habitats. As one of the key stone species, sea stars are responsible for maintaining much of the local diversity of species within certain communities. Malaysian Exclusive Economic Zone (EEZ) Resource Survey had been carried out from 16th Aug to 6th Nov 2015 and one of the invertebrate by-catch organisms is sea star Stellaster childreni Gray, 1840. This study documents morphological characters and diet of the sea star, besides providing brief descriptions of the habitats based on particle size analysis and vessel log data sheet. A total of 217 individuals had been examined throughout this study. Fragments of flora and fauna were found in the gut including Mollusca (gastropod, bivalves, and scaphopods), sponge seagrass, and seaweed as well as benthic Foraminifera. Stellaster childreni were found at depth of 45 m to 185 m in the South China Sea off Sarawak Malaysia, with various sea bottom substrata. Approximately 41% of S. childreni were found at a mixture of sandy and muddy substratum, followed by mixture of sandy and coral (19.3%), muddy substratum (17.5%), coral substratum (11.5%), and sandy areas (10.6%). The widely distributed sea star on different types of sea beds suggested healthy deep sea ecosystem; thus Malaysia should explore further potential fisheries resources in the EEZ off Sarawak coast.
    MeSH terms: Animals; Borneo; China; Diet/veterinary; Fisheries; Malaysia; Starfish/physiology*; Ecosystem*
  20. Tan BE, Lim AL, Kan SL, Lim CH, Tsang EEL, Ch'ng SS, et al.
    Rheumatol Int, 2017 Oct;37(10):1719-1725.
    PMID: 28695274 DOI: 10.1007/s00296-017-3772-8
    The effect of biologic disease modifying anti-rheumatic drugs (bDMARDs) in treating rheumatoid arthritis (RA) in real-world clinical practice remains unknown in Southeast Asia. We aimed to assess the efficacy and safety of bDMARDs among Malaysian RA patients treated in routine clinical practice. A retrospective medical chart review of RA patients from 11 government hospitals were conducted from January 2003 to January 2014. A standardized questionnaire was used to abstract patient's demographic, clinical and treatment data. Level of disease activity was measured by DAS28 collected at baseline, 3, 6 and 12 months. Three hundred and one patients were available for analysis, mean age 41 (SD, 10.8) years, mean RA duration 12.3 (SD, 6.9) years and 98% had history of two or more conventional-synthetic DMARDs. There were 467 bDMARD courses prescribed with mean bDMARDs duration use of 12.9 months (SD 14.7). Tumour necrosis factor alpha inhibitors were the most common prescribed bDMARDs (77.1%), followed by Tocilizumab (14.6%) and Rituximab (8.4%). We observed significant improvement in mean DAS28 values from baseline to 3, 6 and 12 months (p 
    MeSH terms: Rituximab/adverse effects; Rituximab/therapeutic use; Adult; Arthritis, Rheumatoid/drug therapy*; Biological Products/adverse effects; Biological Products/therapeutic use*; Drug Therapy, Combination; Female; Humans; Hypersensitivity/etiology; Infection/etiology; Malaysia; Male; Methotrexate/adverse effects; Methotrexate/therapeutic use; Middle Aged; Retrospective Studies; Tumor Necrosis Factor-alpha/antagonists & inhibitors; Treatment Outcome; Antirheumatic Agents/adverse effects; Antirheumatic Agents/therapeutic use*; Antibodies, Monoclonal, Humanized/adverse effects; Antibodies, Monoclonal, Humanized/therapeutic use
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