Browse publications by year: 2019

  1. Amran MHH, Zulfakar MH, Danik MF, Abdullah MSP, Shamsuddin AF
    Daru, 2019 Jun;27(1):191-201.
    PMID: 31020546 DOI: 10.1007/s40199-019-00262-7
    PURPOSE: Intravenous lipid emulsion (IVLE) was first used to prevent essential fatty acids deficiency. IVLE with α-tocopherol was reported to provide protection against parenteral nutrition-associated liver disease. This study aims to determine the optimal parameters and conditions in developing a physically stable IVLE from superolein palm oil (SoLE 20%) and its effect on lipid and liver profiles in an animal model.

    METHODS: SoLE 20% was prepared using superolein oil and MCT oil (1:1), stabilized with egg lecithin and homogenized using a high pressure homogenizer. Mean droplet size was used as the response variable and was measured using laser diffraction and dynamic light scattering method. Physical stability at 4 °C, 25 °C and 40 °C storage temperatures were determined based on particle size and distribution, polydispersity index, zeta potential, viscosity, vitamin E contents and pH. Sterility and pyrogenicity were also investigated. Rabbits were administered with 1.0 g/kg SoLE 20% for 5 h and repeated daily for 3 days to investigate its effect on blood lipid and liver enzymes profile.

    RESULTS: SoLE 20% was succesfully prepared using the optimized parameters of 800 psi, 7 cycles and 1.2 g lecithin. The IVLE prepared had a particle size of 252.60 ± 4.88 nm and was physically stable for 4 weeks at different storage temperatures. SoLE 20% had a high content of natural vitamin E, remained sterile and pyrogen free. It was also safe for intravenous administration and did not alter the blood lipid (p > 0.05) and liver enzymes profiles (p > 0.05) of the rabbits.

    CONCLUSION: The optimal parameters to develop a stable superolein based IVLE are 800 psi homogenization pressure, 7 homogenization cycles and using 1.2 g lecithin as the emulsifier. SoLE 20% is safe for intravenous administration and does not significantly alter lipid and liver enzymes profiles of the rabbits.

    MeSH terms: Animals; Drug Stability; Fat Emulsions, Intravenous/administration & dosage; Fat Emulsions, Intravenous/chemical synthesis*; Fat Emulsions, Intravenous/chemistry; Lipids/blood*; Liver/chemistry*; Male; Particle Size; Plant Oils/chemistry*; Rabbits; Models, Animal; Lecithins/chemistry; Parenteral Nutrition Solutions; Lipid Droplets
  2. Bui Van N, Vo Hoang L, Bui Van T, Anh HNS, Minh HT, Do Nam K, et al.
    High Blood Press Cardiovasc Prev, 2019 Jun;26(3):239-246.
    PMID: 31020550 DOI: 10.1007/s40292-019-00314-8
    INTRODUCTION: Hypertension (HT) is considered as a major determinant of cardiovascular complications. However, few studies have addressed HT prevalence among adults aged 60 years and older in the northern mountainous region of Vietnam.

    AIM: To determine the prevalence of HT and its risk factors in the elderly in that area.

    METHODS: A cross-sectional study was conducted in a study area in the northern of Vietnam. We interviewed 354 adults aged 60 years or over who were randomly selected, and then measured their blood pressure.

    RESULTS: The overall HT prevalence was 62.15%. The isolated systolic hypertension (ISH) prevalence was 22.88%. There was a slight decrease in the proportion of HT by stage 1, stage 2 and stage 3 respectively. The univariate and multivariate logistic regression analysis indicated some risk factors for HT including age groups, body mass index (BMI) and waist-hip ratio (WHR) (p 

    MeSH terms: Age Factors; Aged; Aged, 80 and over; Blood Pressure; Cross-Sectional Studies; Female; Health Surveys; Humans; Hypertension/diagnosis; Hypertension/ethnology*; Hypertension/physiopathology; Male; Middle Aged; Obesity/ethnology; Obesity/physiopathology; Risk Factors; Rural Health/ethnology*; Vietnam/epidemiology; Body Mass Index; Prevalence; Risk Assessment; Waist-Hip Ratio
  3. Al-Shabi M, Lan BL, Chan WY, Ng KH, Tan M
    Int J Comput Assist Radiol Surg, 2019 Oct;14(10):1815-1819.
    PMID: 31020576 DOI: 10.1007/s11548-019-01981-7
    PURPOSE: Lung nodules have very diverse shapes and sizes, which makes classifying them as benign/malignant a challenging problem. In this paper, we propose a novel method to predict the malignancy of nodules that have the capability to analyze the shape and size of a nodule using a global feature extractor, as well as the density and structure of the nodule using a local feature extractor.

    METHODS: We propose to use Residual Blocks with a 3 × 3 kernel size for local feature extraction and Non-Local Blocks to extract the global features. The Non-Local Block has the ability to extract global features without using a huge number of parameters. The key idea behind the Non-Local Block is to apply matrix multiplications between features on the same feature maps.

    RESULTS: We trained and validated the proposed method on the LIDC-IDRI dataset which contains 1018 computed tomography scans. We followed a rigorous procedure for experimental setup, namely tenfold cross-validation, and ignored the nodules that had been annotated by

    MeSH terms: Humans; Image Processing, Computer-Assisted/methods*; Tomography, X-Ray Computed/methods*; Neural Networks (Computer)*
  4. Kua KP, Saw PS, Lee SWH
    Int J Clin Pharm, 2019 Jun;41(3):793-803.
    PMID: 31020599 DOI: 10.1007/s11096-019-00829-z
    Background Deprescribing describes a process of medication regimen optimization with the aim to reduce adverse events and improve quality of life. There is limited research on perceptions of older adults, defined as those 60 years of age and older, about their willingness to cease a medication in developing countries. Objective To ascertain patients' attitudes, beliefs, perceptions, and experiences regarding the number of medications they were taking and their opinions regarding deprescribing. Setting A primary care health clinic and three community pharmacies in Malaysia. Method A multicenter cross-sectional study was conducted by administering the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire to older adults aged 60 years and over or caregivers attending a health clinic and three community pharmacies in Malaysia. Descriptive results were reported for participants' characteristics and questionnaire responses. Analysis of correlation between participant characteristics and their responses was performed using Spearman's correlation. Main outcome measure Patients' and caregivers' attitudes and beliefs towards reducing medications and characteristics of patients such as age, gender, education level, number of medication taken and number of medical center managing the patient. Results 650 participants were approached and the response rate was 85.2%. A total of 554 participants completed the questionnaire (502 older adults and 52 caregivers). Older adults in the study were taking a median of three medications and/or supplements compared to four in caregiver recipients. 88.1% of older adults were satisfied with their current medication regimen and 67.7% would like to try stopping or reducing the dose of their medicines when their doctor recommended. 82.7% of caregivers were satisfied with their care recipient's current medications and 65.4% were willing to stop taking or reduce the number of drugs taken by their care recipient's upon doctor's recommendation. Older adults (p = 0.003) and those with lower education level (p 
    MeSH terms: Potentially Inappropriate Medication List; Deprescriptions*; Aged; Aged, 80 and over; Cross-Sectional Studies; Ethnic Groups/psychology*; Female; Humans; Health Knowledge, Attitudes, Practice*; Malaysia/ethnology; Male; Middle Aged; Surveys and Questionnaires*; Caregivers/psychology*; Independent Living/psychology*
  5. Abu N, Hon KW, Jeyaraman S, Yahaya A, Abdullah NM, Mustangin M, et al.
    Epigenomics, 2019 06;11(8):875-884.
    PMID: 31020847 DOI: 10.2217/epi-2019-0042
    Aim: Chemoresistance in colorectal cancer (CRC) has become a burden in treating the disease effectively. Circular RNAs (circRNAs) are a type of noncoding RNA that were found to be important in cellular homeostasis. The involvement of circRNAs in relation to chemoresistance in other types of cancers has also been reported. This study aims to identify the differentially expressed circRNAs between chemoresistant and chemosensitive CRC cells. Materials & methods: We developed a chemoresistant cell line model and profiled the circRNAs via microarray. We further validated the expression of two circRNAs in 25 formalin-fixed paraffin-embedded (FFPE) tissue specimens (13 nonresponders and 12 responders) via quantitative polymerase chain reaction (qPCR).  Results & conclusion: We found that there were 773 upregulated and 732 downregulated circRNAs between the chemoresistant and chemosensitive HCT-116 cells. We found that hsa_circ_32883 could be a promising biotarget.
    MeSH terms: Antineoplastic Agents/pharmacology*; Colonic Neoplasms/genetics*; Female; Humans; Male; Middle Aged; Colorectal Neoplasms/genetics*; Down-Regulation; Up-Regulation; Drug Resistance, Neoplasm; RNA, Untranslated/genetics*; MicroRNAs/genetics*; Cell Line, Tumor
  6. Jamaludin N, Gedye K, Collins-Emerson J, Benschop J, Nulsen M
    Microb Drug Resist, 2019 Sep;25(7):1003-1011.
    PMID: 31021281 DOI: 10.1089/mdr.2018.0111
    Aim:
    To characterize mutations in penA, mtrR, ponA, and porBIB, considered target genes for antimicrobial resistance, in Neisseria gonorrhoeae isolates with elevated minimum inhibitory concentrations (MICs) of ceftriaxone cultured from patients in New Zealand.
    Results:
    Out of 28 isolates supplied by the Institute of Environmental Science and Research Limited (ESR), Porirua, New Zealand, 14 were found to show reduced susceptibility to ceftriaxone (MIC of 0.06 mg/L) according to criteria used by the ESR and the Australian Gonococcal Surveillance Programme (AGSP) when tested in our laboratory. Rates of resistance to ciprofloxacin, azithromycin, penicillin, and tetracycline were 100% (28/28), 7% (2/28), 36% (10/28), and 25% (7/28), respectively. Ten different penA (Penicillin binding protein 2 [PBP2]) sequences were observed. The most common mosaic penA M-1 resembled mosaic penA XXXIV, which has been associated with ceftriaxone treatment failures in other countries. Four semimosaic PBP2 sequences were observed and may be novel PBP sequences, while four out of five nonmosaic PBP2 sequences were similar to PBP2 sequences reported in Australia. Twenty-one isolates harbored mutations in all 4 genes (penA, mtrR, porBIB, and ponA), and 13 of these exhibited reduced susceptibility to ceftriaxone.
    Conclusion:
    Mutations in penA, mtrR, porBIB, and ponA observed in this study may have contributed to reduced susceptibility to ceftriaxone among New Zealand gonococcal isolates. Over half (16/22) of mosaic penA sequences from the gonococcal isolates resembled penA XXXIV.
    MeSH terms: Amino Acid Sequence; Anti-Bacterial Agents/pharmacology*; Bacterial Proteins/genetics; Ceftriaxone/pharmacology*; Ciprofloxacin/pharmacology; Genotype; Humans; Microbial Sensitivity Tests/methods; Neisseria gonorrhoeae/drug effects*; Neisseria gonorrhoeae/genetics*; Neisseria gonorrhoeae/isolation & purification; New Zealand; Penicillins/pharmacology; Phenotype; Tetracycline/pharmacology; Azithromycin/pharmacology; Penicillin-Binding Proteins/genetics
  7. Devarbhavi H, Choudhury AK, Sharma MK, Maiwall R, Al Mahtab M, Rahman S, et al.
    Am J Gastroenterol, 2019 06;114(6):929-937.
    PMID: 31021832 DOI: 10.14309/ajg.0000000000000201
    OBJECTIVES: Acute insults from viruses, infections, or alcohol are established causes of decompensation leading to acute-on-chronic liver failure (ACLF). Information regarding drugs as triggers of ACLF is lacking. We examined data regarding drugs producing ACLF and analyzed clinical features, laboratory characteristics, outcome, and predictors of mortality in patients with drug-induced ACLF.

    METHODS: We identified drugs as precipitants of ACLF among prospective cohort of patients with ACLF from the Asian Pacific Association of Study of Liver (APASL) ACLF Research Consortium (AARC) database. Drugs were considered precipitants after exclusion of known causes together with a temporal association between exposure and decompensation. Outcome was defined as death from decompensation.

    RESULTS: Of the 3,132 patients with ACLF, drugs were implicated as a cause in 329 (10.5%, mean age 47 years, 65% men) and other nondrug causes in 2,803 (89.5%) (group B). Complementary and alternative medications (71.7%) were the commonest insult, followed by combination antituberculosis therapy drugs (27.3%). Alcoholic liver disease (28.6%), cryptogenic liver disease (25.5%), and non-alcoholic steatohepatitis (NASH) (16.7%) were common causes of underlying liver diseases. Patients with drug-induced ACLF had jaundice (100%), ascites (88%), encephalopathy (46.5%), high Model for End-Stage Liver Disease (MELD) (30.2), and Child-Turcotte-Pugh score (12.1). The overall 90-day mortality was higher in drug-induced (46.5%) than in non-drug-induced ACLF (38.8%) (P = 0.007). The Cox regression model identified arterial lactate (P < 0.001) and total bilirubin (P = 0.008) as predictors of mortality.

    DISCUSSION: Drugs are important identifiable causes of ACLF in Asia-Pacific countries, predominantly from complementary and alternative medications, followed by antituberculosis drugs. Encephalopathy, bilirubin, blood urea, lactate, and international normalized ratio (INR) predict mortality in drug-induced ACLF.

    MeSH terms: Adolescent; Adult; Aged; Asia/epidemiology; Biopsy; Female; Follow-Up Studies; Humans; Liver/drug effects; Liver/pathology*; Male; Middle Aged; Morbidity/trends; Prognosis; Prospective Studies; Time Factors; Survival Rate/trends; Young Adult; Drug-Induced Liver Injury/complications*; Drug-Induced Liver Injury/epidemiology; Acute-On-Chronic Liver Failure/chemically induced*; Acute-On-Chronic Liver Failure/diagnosis; Acute-On-Chronic Liver Failure/epidemiology
  8. Molineros JE, Looger LL, Kim K, Okada Y, Terao C, Sun C, et al.
    PLoS Genet, 2019 04;15(4):e1008092.
    PMID: 31022184 DOI: 10.1371/journal.pgen.1008092
    Human leukocyte antigen (HLA) is a key genetic factor conferring risk of systemic lupus erythematosus (SLE), but precise independent localization of HLA effects is extremely challenging. As a result, the contribution of specific HLA alleles and amino-acid residues to the overall risk of SLE and to risk of specific autoantibodies are far from completely understood. Here, we dissected (a) overall SLE association signals across HLA, (b) HLA-peptide interaction, and (c) residue-autoantibody association. Classical alleles, SNPs, and amino-acid residues of eight HLA genes were imputed across 4,915 SLE cases and 13,513 controls from Eastern Asia. We performed association followed by conditional analysis across HLA, assessing both overall SLE risk and risk of autoantibody production. DR15 alleles HLA-DRB1*15:01 (P = 1.4x10-27, odds ratio (OR) = 1.57) and HLA-DQB1*06:02 (P = 7.4x10-23, OR = 1.55) formed the most significant haplotype (OR = 2.33). Conditioned protein-residue signals were stronger than allele signals and mapped predominantly to HLA-DRB1 residue 13 (P = 2.2x10-75) and its proxy position 11 (P = 1.1x10-67), followed by HLA-DRB1-37 (P = 4.5x10-24). After conditioning on HLA-DRB1, novel associations at HLA-A-70 (P = 1.4x10-8), HLA-DPB1-35 (P = 9.0x10-16), HLA-DQB1-37 (P = 2.7x10-14), and HLA-B-9 (P = 6.5x10-15) emerged. Together, these seven residues increased the proportion of explained heritability due to HLA to 2.6%. Risk residues for both overall disease and hallmark autoantibodies (i.e., nRNP: DRB1-11, P = 2.0x10-14; DRB1-13, P = 2.9x10-13; DRB1-30, P = 3.9x10-14) localized to the peptide-binding groove of HLA-DRB1. Enrichment for specific amino-acid characteristics in the peptide-binding groove correlated with overall SLE risk and with autoantibody presence. Risk residues were in primarily negatively charged side-chains, in contrast with rheumatoid arthritis. We identified novel SLE signals in HLA Class I loci (HLA-A, HLA-B), and localized primary Class II signals to five residues in HLA-DRB1, HLA-DPB1, and HLA-DQB1. These findings provide insights about the mechanisms by which the risk residues interact with each other to produce autoantibodies and are involved in SLE pathophysiology.
    MeSH terms: Alleles; Amino Acid Sequence*; Histocompatibility Antigens Class II/genetics; Histocompatibility Antigens Class II/immunology*; Histocompatibility Antigens Class II/chemistry*; Autoantibodies/immunology*; Disease Susceptibility*; Female; Humans; Lupus Erythematosus, Systemic/etiology*; Male; Genetic Variation; Histocompatibility Antigens Class I/genetics; Histocompatibility Antigens Class I/immunology*; Histocompatibility Antigens Class I/chemistry*; Odds Ratio; Amino Acid Substitution; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Asian Continental Ancestry Group
  9. Wen WX, Leong CO
    PLoS One, 2019;14(4):e0215381.
    PMID: 31022191 DOI: 10.1371/journal.pone.0215381
    Immune checkpoint inhibitors have demonstrated effective anti-tumour response in cancer types with high mutation burden (e.g. melanoma) and in subset of cancers with features of genomic instability (e.g. mismatch-repair deficiency). One possible explanation for this effect is the increased expression of immune checkpoint molecules and pre-existing adaptive immune response in these cancers. Given that BRCA1 and BRCA2 are integral in maintaining genomic integrity, we hypothesise that the inactivation of these genes may give rise to breast cancers with such immunogenic phenotype. Therefore, using two large series of publicly available breast cancer datasets, namely that from The Cancer Genome Atlas and Wellcome Trust Institute, we sought to investigate the association between BRCA1- and BRCA2-deficiency with features of genomic instability, expression of PD-L1 and PD-1, landscape of inferred tumour-infiltrating immune cells, and T-cell inflamed signature in breast cancers. Here, we report that BRCA1 and BRCA2-deficient breast cancers were associated with features of genomic instability including increased mutation burden. Interestingly, BRCA1-, but not BRCA2-, deficient breast cancers were associated with increased expression of PD-L1 and PD-1, higher abundance of tumour-infiltrating immune cells, and enrichment of T cell-inflamed signature. The differences in immunophenotype between BRCA1- and BRCA2-deficient breast cancers can be attributed, in part, to PTEN gene mutation. Therefore, features of genomic instability such as that mediated by BRCA1- and BRCA2- deficiency in breast cancer were necessary, but not always sufficient, for yielding T cell-inflamed tumour microenvironment, and by extension, predicting clinical benefit from immunotherapy.
    MeSH terms: Breast/pathology; Breast Neoplasms/genetics*; Breast Neoplasms/immunology; Breast Neoplasms/pathology; Female; Humans; Gene Expression Regulation, Neoplastic/immunology*; Lymphocytes, Tumor-Infiltrating/immunology; Computational Biology; BRCA1 Protein/deficiency*; BRCA1 Protein/genetics; Gene Expression Profiling; BRCA2 Protein/deficiency*; BRCA2 Protein/genetics; Genomic Instability/immunology; Tumor Microenvironment/genetics; Tumor Microenvironment/immunology; Transcriptome/genetics; Antigens, CD274/immunology; Antigens, CD274/metabolism; Programmed Cell Death 1 Receptor/immunology; Programmed Cell Death 1 Receptor/metabolism; Datasets as Topic
  10. Ng CA, Ho JJ, Lee ZH
    PLoS One, 2019;14(4):e0215869.
    PMID: 31022227 DOI: 10.1371/journal.pone.0215869
    BACKGROUND: The benefits of six months exclusive breastfeeding are well established for both mother and infant. One of the 10 steps of the Baby Friendly Hospital Initiative is rooming-in (mother and baby together in the same room throughout hospitalisation). A Cochrane review found only one randomised controlled trial (RCT) examining the effects of continuous rooming-in versus nursery care on breastfeeding duration, and concluded there was insufficient evidence to support or refute either practice. We aimed to examine the effect of continuous or intermittent rooming-in on breastfeeding duration.

    METHODS AND FINDINGS: We included all prospective controlled studies (randomised and non-randomised) comparing rooming-in to nursery care that reported full or partial breastfeeding up to six months. We used the 2016 search results of the Cochrane review and updated the search to August 2018 using OVID MEDLINE. Duplicate data extraction and assessment of risk of bias were performed. Meta-analyses were performed using REVMAN 5. The GRADE approach was used to assess quality of evidence. Seven studies were included, five had 24-hour-per-day, one daytime only and one 8-hours-per-day rooming-in. Four studies had at least one additional co-intervention: Differences in delivery room management, and educational packages. All studies contributing to meta-analyses had 24-hour rooming-in. There was no difference in the proportion of infants on full breastfeeding at 3 months (RR 1.14; 95% CI 0.84 to 1.54; very-low-quality evidence), 4 months (RR 0.99; 95% CI 0.73 to 1.33; very-low-quality evidence) and 6 months (RR 0.95; 95% CI 0.57 to 1.58; low-quality evidence). The proportion of infants on partial breastfeeding at 3-4 months was higher with rooming-in (RR 1.31; 95% CI 1.06 to 1.61; very-low-quality evidence).

    CONCLUSION: The addition of non-randomised prospective controlled studies to existing evidence did not add further information on the effects of rooming-in on breastfeeding duration but resulted in lower quality of evidence. Uncertainty about the effects of rooming-in on breastfeeding duration remains.

    MeSH terms: Breast Feeding*; Female; Humans; Infant; Infant, Newborn; Prospective Studies; Risk; Time Factors; Randomized Controlled Trials as Topic*; Publication Bias
  11. Islam MA, Mamun A, Hossain MM, Bharati P, Saw A, Lestrel PE, et al.
    PLoS One, 2019;14(4):e0215733.
    PMID: 31022237 DOI: 10.1371/journal.pone.0215733
    BACKGROUND: Early initiation of breastfeeding (EIBF) is associated with better health of the mothers and reduced risk of neonatal mortality. The objective of this study was to determine the prevalence of EIBF and associated factors among Bangladeshi mothers.

    METHODS: The data was extracted from the Bangladesh Demographic and Health Survey (BDHS)-2014. A total of 4,092 married non-pregnant Bangladeshi mothers who had at least one child aged 2 years or younger were included in this study. A two-level logistic regression model was used to remove the clustering effect for finding the impact of socio-economic and demographic factors on EIBF.

    RESULTS: The prevalence of EIBF among Bangladeshi mothers was 51.4% (urban: 47.1% and rural: 53.4%). A two -level logistic regression model showed that mothers living in the Sylhet division (p<0.01) and rural environment (p<0.05) were more likely to practice EIBF. Mothers who were obese or overweight (p<0.01), had secondary (p<0.05) or higher education (p<0.01) were less likely to provide early breastfeeding to their newborn babies compared to their counterparts. Those who delivered by caesarian-section (p<0.01) were less likely to perform EIBF while those who attended an antenatal care clinic more than 3 times (p<0.05) were more likely to do so.

    CONCLUSIONS: About half of the Bangladeshi mothers did not start breast-feeding within one hour after birth. This study identified several geographical and socio-demographic factors that were associated with EIBF, and hope that this information will help the government to focus their resources to promote early breastfeeding.

    MeSH terms: Adolescent; Adult; Bangladesh; Breast Feeding/statistics & numerical data*; Child, Preschool; Cross-Sectional Studies; Demography/statistics & numerical data*; Female; Health Surveys/statistics & numerical data; Humans; Infant; Infant, Newborn; Middle Aged; Mothers/statistics & numerical data*; Pregnancy; Rural Population/statistics & numerical data; Socioeconomic Factors*; Time Factors; Urban Population/statistics & numerical data; Prevalence; Young Adult
  12. Reuben U, Ismail AF, Ahmad AL, Maina HM, Daud A
    PMID: 31013942 DOI: 10.3390/ijerph16081334
    : The chemicals from laboratories pose a significant risk forinducing erythema, an abnormal redness of the skin, as a result of poor occupational and environmental factors that promote hypersensitivity to a chemical agent. The aim of this present study was to determine the occupational and environmental risk factors influencing the inducement of erythema in laboratory workers due to exposure to chemicals. This was a cross-sectional study on a population-based sample of Nigerian university laboratory workers. Data were collected using the erythema index meter and an indoor air control meter. The study included 287 laboratory workers. The laboratory workers who properly used personal protective equipment (PPE) were 60% less likely to have induced erythema (adjusted odds ratio (AOR) = 0.40; 95% confidence interval CI: 0.22-0.77; probability value p = 0.011). The chemical mixture exceeding the permissible exposure limit (PEL) was found to have a small effect in inducing the erythema (AOR = 4.22; 95%CI: 2.88-12.11; p = 0.004). Most of the sampled laboratories where the respondents worked had unsuitable temperatures (AOR = 8.21; 95% CI: 4.03-15.01; p = 0.001). Erythema was more frequently found in the respondents who spent 4-5h in the laboratory (AOR = 3.11; 95%CI: 1.77-9.23; p = 0.001). However, high levels of ventilation reduce the likelihood of erythema in a laboratory by 82% (0.18). Multiple logistic regressions revealed that PPE, PEL, exposure time, temperature, and ventilation were the probable predictive factors associated with the inducement of erythema. Providing better educational knowledge and improving the attitude towards hazards and safety in a laboratory would lead to reduced rates of new cases.
    MeSH terms: Personal Protective Equipment*; Cross-Sectional Studies; Environmental Monitoring/methods; Erythema/chemically induced*; Humans; Laboratories; Nigeria; Risk Factors; Universities*; Ventilation; Hazardous Substances/toxicity*; Odds Ratio; Occupational Exposure/analysis*; Workplace/standards; Inhalation Exposure; Confined Spaces
  13. Dianita R, Jantan I
    Molecules, 2019 Apr 13;24(8).
    PMID: 31013947 DOI: 10.3390/molecules24081469
    Many Premna species have been used in traditional medicine to treat hypertension and cardiac insufficiency, and as a tonic for cardiac-related problems. Some have been reported to possess cardiovascular protective activity through several possible mechanisms, but not Premna foetida. In the present study, the methanol extract of P. foetida leaves (PFM) and its isolated compounds were evaluated for their ability to inhibit copper-mediated human low-density lipoprotein (LDL) oxidation and arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation. Six flavonoids, three triterpenoids, vanillic acid and stigmasterol were successfully isolated from PFM. Of the isolated compounds, quercetin was the most active against LDL oxidation (IC50 4.25 µM). The flavonols were more active than the flavones against LDL oxidation, suggesting that hydroxyl group at C-3 and the catechol moiety at B-ring may play important roles in protecting LDL from oxidation. Most tested flavonoids showed stronger inhibition towards AA-induced than the ADP-induced platelet aggregation with apigenin exhibiting the strongest effect (IC50 52.3 and 127.4 µM, respectively) while quercetin and kaempferol showed moderate activity. The results suggested that flavonoids, especially quercetin, apigenin and kaempferol were among the major constituents of P. foetida responsible for anti-LDL oxidation and anti-platelet aggregation.
    MeSH terms: Adenosine Diphosphate/pharmacology; Blood Platelets/cytology; Blood Platelets/metabolism*; Humans; Lipoproteins, LDL/metabolism*; Lipoproteins, LDL/chemistry; Platelet Aggregation/drug effects*; Arachidonic Acid/pharmacology; Plant Leaves/chemistry*; Lamiaceae/chemistry*
  14. Chiroma SM, Baharuldin MTH, Mat Taib CN, Amom Z, Jagadeesan S, Ilham Adenan M, et al.
    Int J Mol Sci, 2019 Apr 16;20(8).
    PMID: 31014012 DOI: 10.3390/ijms20081871
    Alzheimer's disease (AD) is a progressive neurodegenerative disorder more prevalent among the elderly population. AD is characterised clinically by a progressive decline in cognitive functions and pathologically by the presence of neurofibrillary tangles (NFTs), deposition of beta-amyloid (Aβ) plaque and synaptic dysfunction in the brain. Centella asiatica (CA) is a valuable herb being used widely in African, Ayurvedic, and Chinese traditional medicine to reverse cognitive impairment and to enhance cognitive functions. This study aimed to evaluate the effectiveness of CA in preventing d-galactose/aluminium chloride (d-gal/AlCl3) induced AD-like pathologies and the underlying mechanisms of action were further investigated for the first time. Results showed that co-administration of CA to d-gal/AlCl3 induced AD-like rat models significantly increased the levels of protein phosphatase 2 (PP2A) and decreased the levels of glycogen synthase kinase-3 beta (GSK-3β). It was further observed that, CA increased the expression of mRNA of Bcl-2, while there was minimal effect on the expression of caspase 3 mRNA. The results also showed that, CA prevented morphological aberrations in the connus ammonis 3 (CA 3) sub-region of the rat's hippocampus. The results clearly demonstrated for the first time that CA could alleviate d-gal/AlCl3 induced AD-like pathologies in rats via inhibition of hyperphosphorylated tau (P-tau) bio-synthetic proteins, anti-apoptosis and maintenance of cytoarchitecture.
    MeSH terms: Alzheimer Disease/etiology; Alzheimer Disease/prevention & control*; Alzheimer Disease/veterinary; Animals; Galactose/toxicity; Galactose/chemistry; Hippocampus/drug effects; Hippocampus/metabolism*; Male; Plant Extracts; Triterpenes/pharmacology*; Triterpenes/therapeutic use; Triterpenes/chemistry; Signal Transduction/drug effects*; Rats, Wistar; Apoptosis/drug effects; Apoptosis/genetics; Proto-Oncogene Proteins c-bcl-2/genetics; Proto-Oncogene Proteins c-bcl-2/metabolism; Centella/metabolism; Centella/chemistry*; Rats; Protein Phosphatase 2/metabolism; Glycogen Synthase Kinase 3 beta/metabolism
  15. Wang L, Xu J, Yan Y, Liu H, Karunakaran T, Li F
    Artif Cells Nanomed Biotechnol, 2019 Dec;47(1):1617-1627.
    PMID: 31014134 DOI: 10.1080/21691401.2019.1594862
    Nanotechnology has been materialized as a proficient technology for the development of anticancer nanoparticles all the way through an environment-friendly approach. Conventionally, nanoparticles have been assembled by dissimilar methods, but regrettably rely on the negative impact on the natural environment. Amalgamation of nanoparticles by means of plant extract is alternate conservative methods. Scutellaria barbata species was used majorly as food or as medicines against various diseases, and extensive research was conducted for their therapeutic properties. The present research was mainly focused on the synthesis of gold nanoparticles from the Scutellaria barbata by green route method and evaluation of its anticancer activity against pancreatic cancer cell lines (PANC-1). The gold nanoparticles have been characterized by UV-visible spectroscopy, TEM, SAED, AFM, and FTIR analysis. The synthesized gold nanoparticles (AuNPs) possessed effective anticancer activity against pancreatic cancer cell lines (PANC-1). Hence, further research on this plant may lead to the development of novel anticancer drugs which can be used to combat pancreatic cancer.
    MeSH terms: Antineoplastic Agents/chemical synthesis; Antineoplastic Agents/pharmacology; Antineoplastic Agents/chemistry; Gold/pharmacology*; Gold/chemistry*; Humans; Pancreatic Neoplasms/pathology*; Particle Size; Plant Extracts/chemistry*; Gene Expression Regulation, Neoplastic/drug effects; Apoptosis/drug effects; Reactive Oxygen Species/metabolism; Scutellaria/chemistry*; Nanotechnology; Cell Line, Tumor; Metal Nanoparticles*; Green Chemistry Technology; Chemistry Techniques, Synthetic
  16. Gamalo LE, Dimalibot J, Kadir KA, Singh B, Paller VG
    Malar J, 2019 Apr 24;18(1):147.
    PMID: 31014342 DOI: 10.1186/s12936-019-2780-4
    BACKGROUND: Macaca fascicularis (long-tailed macaque) is the most widespread species of macaque in Southeast Asia and the only species of monkey found naturally in the Philippines. The species is the natural host for the zoonotic malaria species, Plasmodium knowlesi and Plasmodium cynomolgi and for the potentially zoonotic species, Plasmodium inui. Moreover, other Plasmodium species such as Plasmodium coatneyi and Plasmodium fieldi are also natural parasites of M. fascicularis. The aims of this study were to identify and determine the prevalence of Plasmodium species infecting wild and captive long-tailed macaques from the Philippines.

    METHODS: A total of 95 blood samples from long-tailed macaques in the Philippines were collected from three locations; 30 were from captive macaques at the National Wildlife Rescue and Rehabilitation Center (NWRRC) in Luzon, 25 were from captive macaques at the Palawan Wildlife Rescue and Conservation Center (PWRCC) in Palawan and 40 were from wild macaques from Puerto Princesa Subterranean River National Park (PPSRNP) in Palawan. The Plasmodium spp. infecting the macaques were identified using nested PCR assays on DNA extracted from these blood samples.

    RESULTS: All 40 of the wild macaques from PPSRNP in Palawan and 5 of 25 captive macaques from PWRCC in Palawan were Plasmodium-positive; while none of the 30 captive macaques from the NWRRC in Luzon had any malaria parasites. Overall, P. inui was the most prevalent malaria parasite (44.2%), followed by P. fieldi (41.1%), P. cynomolgi (23.2%), P. coatneyi (21.1%), and P. knowlesi (19%). Mixed species infections were also observed in 39 of the 45 Plasmodium-positive macaques. There was a significant difference in the prevalence of P. knowlesi among the troops of wild macaques from PPSRNP.

    CONCLUSION: Wild long-tailed macaques from the island of Palawan, the Philippines are infected with P. knowlesi, P. inui, P. coatneyi, P. fieldi and P. cynomolgi. The prevalence of these Plasmodium spp. varied among the sites of collection and among troops of wild macaques at one site. The presence of these simian Plasmodium parasites, especially P. knowlesi and P. cynomolgi in the long-tailed macaques in Palawan presents risks for zoonotic transmission in the area.

    MeSH terms: Parks, Recreational; Animals; Animals, Wild/parasitology; Macaca fascicularis/parasitology*; Malaria/epidemiology; Malaria/veterinary*; Monkey Diseases; Philippines/epidemiology; Zoonoses/epidemiology; Zoonoses/parasitology; Prevalence; Plasmodium cynomolgi/isolation & purification; Plasmodium knowlesi/isolation & purification*; Islands/epidemiology
  17. Carroll RP, Deayton S, Emery T, Munasinghe W, Tsiopelas E, Fleet A, et al.
    Hum Immunol, 2019 Aug;80(8):573-578.
    PMID: 31014826 DOI: 10.1016/j.humimm.2019.04.005
    High levels of angiotensin receptor antibodies (ATRab) are associated with acute cellular and humoral rejection, vascular occlusion, de novo human leucocyte antigen donor specific antibody (HLA DSA) and poor graft survival in kidney transplant recipients (KTR). Since 2015 we proactively managed patients "at risk" (AR) with ATRab >17 U/ml with perioperative plasma exchange (PLEX) and/or angiotensin receptor blockade (ARB). 44 patients were treated with this protocol. 265 KTR with ATRab ≤17 U/ml deemed "low risk" (LR) were transplanted under standard conditions. PLEX and ARB were not associated with increased risk of: delayed graft function requiring haemodialysis (HDx), hyperkalaemia >5.5 mmol/l requiring HDx, and the combined clinical end-point of severe hypotension, blood transfusion and re-operation for bleeding. Rejection rates were similar at 90 days: 8/44 (18%) in the AR group and 36/265 (14%) in the LR group (p = 0.350). Death censored graft survival was the same between the AR and LR groups with a 94% 48-month graft survival - hazard ratio (log-rank) 1.16 [95% CI 0.2-5.8] p = 0.844. Proactive treatment of ATRab >17 U/ml with PLEX and/or ARB is not associated with increased rates of perioperative complications and comparable rates of rejection and death censored graft survival at 4 years compared to KTR <17 U/ml ATRab.
    MeSH terms: Adult; Aged; Australia; Autoantibodies/metabolism; Autoantibodies/therapeutic use*; Benzimidazoles/therapeutic use*; Female; Follow-Up Studies; Graft Rejection/immunology*; Graft Rejection/mortality; Graft Rejection/prevention & control; Graft Survival; Humans; Male; Middle Aged; Plasma Exchange/methods*; Receptors, Angiotensin/immunology*; Tetrazoles/therapeutic use*; Survival Analysis; Kidney Transplantation*; Angiotensin II Type 1 Receptor Blockers/therapeutic use*
  18. Phang CW, Gandah NA, Abd Malek SN, Karsani SA
    Eur J Pharmacol, 2019 Jun 15;853:388-399.
    PMID: 31014923 DOI: 10.1016/j.ejphar.2019.04.032
    Flavokawain C (FKC), a naturally occurring chalcone, has previously been shown to inhibit the growth of colon carcinoma HCT 116 cells through induction of apoptosis and cell cycle arrest. However, the possible underlying mechanisms of cell death as a response to FKC treatment remains unclear. In this study, we performed proteomic analysis of HCT 116 cells treated with FKC to identify proteins that change in abundance. This was followed by bioinformatic analysis to predict possible associated molecular targets or pathways involved in the observed effects of FKC. A total of 35 proteins that changed in abundance (17 increased and 18 decreased) were identified through two-dimensional gel electrophoresis followed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Using the Ingenuity Pathway Analysis (IPA), these proteins were predicted to be involved in cell death and survival, cell cycle, cellular growth and proliferation, protein synthesis, post-translational modification and amino acid metabolism by. Further analysis of the transcript levels of selected proteins using qPCR showed that some of the genes exhibited similar change of profile to that of the proteins'. Our results have provided novel insights into the potential molecular mechanisms underlying FKC-induced apoptosis or cell death in colon cancer cells.
    MeSH terms: Humans; Signal Transduction/drug effects; Cell Death/drug effects; Proteomics*; HCT116 Cells; Chalcones/pharmacology*
  19. Peter S, Abdul Rahman ZA, Pillai S
    Int J Oral Maxillofac Surg, 2019 Oct;48(10):1317-1322.
    PMID: 31014926 DOI: 10.1016/j.ijom.2019.03.896
    The aim of this study was to document differences in hypernasality during speaking and singing among children with cleft palate and to compare nasality score ratings of trained and untrained listeners. Twenty subjects with cleft palate aged between 7 and 12 years participated in this study. Audio recordings were made of the children reading a passage and singing a common local song, both in the Malay language. The degree of hypernasality was judged through perceptual assessment. Three trained listeners (a speech therapist, a classical singer, and a linguistic expert - all academicians) and two untrained listeners (a cleft volunteer worker and a national high school teacher) assessed the recordings using a visual analogue scale (VAS). Inter-rater and intra-rater reliability for hypernasality in both speaking and singing were verified using the intra-class correlation coefficient (ICC). A significant reduction in hypernasality was observed during singing as compared to speaking, indicating that hypernasality reduces when a child with cleft palate sings. The act of singing significantly reduces hypernasality. The outcome of this study suggests that children with cleft palate would benefit from singing exercises to ultimately reduce hypernasality. However, future research is needed to objectively measure nasality in singing compared to speaking.
    MeSH terms: Child; Cleft Palate*; Humans; Speech Perception*; Speech Production Measurement; Voice Quality; Reproducibility of Results; Singing*
  20. Saref A, Suraya S, Singh D, Grundmann O, Narayanan S, Swogger MT, et al.
    J Ethnopharmacol, 2019 Jun 28;238:111876.
    PMID: 31014959 DOI: 10.1016/j.jep.2019.111876
    ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa (Korth.) is a traditional medicinal plant widely used in Southeast Asia for its opioid-like effects. Although kratom produces analgesia through binding of mitragynine and other alkaloids at the mu-opioid receptor (MOR), the association of long-term kratom use with adverse opioid-like effects remains unknown.

    AIM OF THE STUDY: To determine the self-reported prevalence and severity of opioid-related adverse effects after kratom initiation in a cohort of illicit opioid users.

    MATERIALS AND METHODS: A total of 163 illicit opioid users with current kratom use history were recruited through convenience sampling from the northern states of Peninsular Malaysia. Face-to-face interviews were conducted using a semi-structured questionnaire.

    RESULTS: Respondents were all males, majority Malays (94%, n = 154/163), with a mean age of 37.10 years (SD = 10.9). Most were single (65%, n = 106/163), had 11 years of education (52%, n = 85/163) and employed (88%, n = 144/163). Half reported using kratom for over >6 years (50%, n = 81/163), and 41% consumed >3 glasses of kratom daily (n = 67/163). Results from Chi-square analysis showed kratom initiation was associated with decreased prevalence of respiratory depression, constipation, physical pain, insomnia, depression, loss of appetite, craving, decreased sexual performance, weight loss and fatigue.

    CONCLUSIONS: Our findings indicate that kratom initiation (approximately 214.29 mg of mitragynine) was associated with significant decreases in the prevalence and severity of opioid adverse effects.

    MeSH terms: Adolescent; Adult; Analgesics, Opioid/adverse effects*; Humans; Male; Opioid-Related Disorders; Peptide Fragments; Plant Extracts/adverse effects*; Plant Extracts/chemistry; Plants, Medicinal/adverse effects; Growth Hormone; Street Drugs; Prevalence; Mitragyna/chemistry*; Young Adult; Self Report*
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