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  1. Fulltext Loss-of-function HSD17B13 variants, non-alcoholic steatohepatitis and adverse liver outcomes: Results from a multi-ethnic Asian cohort
    Ting YW, Kong AS, Zain SM, Chan WK, Tan HL, Mohamed Z, et al.
    Clin Mol Hepatol, 2021 Jul;27(3):486-498.
    PMID: 33618508 DOI: 10.3350/cmh.2020.0162
    BACKGROUND/AIMS: 17β-hydroxysteroid dehydrogenase 13 (HSD17B13) variants were recently reported to have significantly lower odds of non-alcoholic fatty liver disease (NAFLD). This is a two-part study that aimed to evaluate the association of HSD17B13 variants with NAFLD and its histological severity, and to identify the association of the variants with clinical outcomes in a cohort of biopsy-proven NAFLD patients.

    METHODS: Consecutive biopsy-proven NAFLD patients and controls without fatty liver were recruited for this study between 2009 and 2014. Genotyping for HSD17B13 variants was performed using rhAmp assays. A total of 165 patients with NAFLD were monitored up until August 2019. Clinical outcomes were recorded.

    RESULTS: HSD17B13 rs72613567 TA allele and rs6834314 G allele were associated with lower odds of non-alcoholic steatohepatitis (NASH) in the overall cohort and among ethnic Chinese, but not among ethnic Malays or Indians (P<0.05). During a mean follow-up of 89 months, 32 patients (19.4%) experienced at least one clinical outcome (cardiovascular events, n=22; liver-related complications, n=6; extra-hepatic malignancy, n=5; and mortality, n=6). The rs72613567 homozygous TA allele and the rs6834314 homozygous G allele were independently associated with a lower incidence of liver-related complications (hazard ratio [HR], 0.004; 95% confidence interval [CI], 0.00-0.64; P=0.033 and HR, 0.01; 95% CI, 0.00-0.97; P=0.048, respectively) and were associated with lower grade of hepatocyte ballooning among the ethnic Chinese.

    CONCLUSION: HSD17B13 rs72613567 and rs6834314 variants were inversely associated with NAFLD and NASH, and were associated with lower incidence of adverse liver outcomes in a cohort of multi-ethnic Asian patients with NAFLD.

  2. Fulltext Chimeric Virus-Like Particles of Prawn Nodavirus Displaying Hepatitis B Virus Immunodominant Region: Biophysical Properties and Cytokine Response
    Ninyio NN, Ho KL, Yong CY, Chee HY, Hamid M, Ong HK, et al.
    Int J Mol Sci, 2021 Feb 15;22(4).
    PMID: 33672018 DOI: 10.3390/ijms22041922
    Hepatitis B is a major global health challenge. In the absence of an effective treatment for the disease, hepatitis B vaccines provide protection against the viral infection. However, some individuals do not have positive immune responses after being vaccinated with the hepatitis B vaccines available in the market. Thus, it is important to develop a more protective vaccine. Previously, we showed that hepatitis B virus (HBV) 'a' determinant (aD) displayed on the prawn nodavirus capsid (Nc) and expressed in Spodoptera frugiperda (Sf9) cells (namely, Nc-aD-Sf9) self-assembled into virus-like particles (VLPs). Immunisation of BALB/c mice with the Nc-aD-Sf9 VLPs showed significant induction of humoral, cellular and memory B-cell immunity. In the present study, the biophysical properties of the Nc-aD-Sf9 VLPs were studied using dynamic light scattering (DLS) and circular dichroism (CD) spectroscopy. Enzyme-linked immunosorbent assay (ELISA) was used to determine the antigenicity of the Nc-aD-Sf9 VLPs, and multiplex ELISA was employed to quantify the cytokine response induced by the VLPs administered intramuscularly into BALB/c mice (n = 8). CD spectroscopy of Nc-aD-Sf9 VLPs showed that the secondary structure of the VLPs predominantly consisted of beta (β)-sheets (44.8%), and they were thermally stable up to ~52 °C. ELISA revealed that the aD epitope of the VLPs was significantly antigenic to anti-HBV surface antigen (HBsAg) antibodies. In addition, multiplex ELISA of serum samples from the vaccinated mice showed a significant induction (p < 0.001) of IFN-γ, IL-4, IL-5, IL-6, IL-10, and IL-12p70. This cytokine profile is indicative of natural killer cell, macrophage, dendritic cell and cytotoxic T-lymphocyte activities, which suggests a prophylactic innate and adaptive cellular immune response mediated by Nc-aD-Sf9 VLPs. Interestingly, Nc-aD-Sf9 induced a more robust release of the aforementioned cytokines than that of Nc-aD VLPs produced in Escherichia coli and a commercially used hepatitis B vaccine. Overall, Nc-aD-Sf9 VLPs are thermally stable and significantly antigenic, demonstrating their potential as an HBV vaccine candidate.
  3. Fulltext Impact of Microplastics and Nanoplastics on Human Health
    Yee MS, Hii LW, Looi CK, Lim WM, Wong SF, Kok YY, et al.
    Nanomaterials (Basel), 2021 Feb 16;11(2).
    PMID: 33669327 DOI: 10.3390/nano11020496
    Plastics have enormous impacts to every aspect of daily life including technology, medicine and treatments, and domestic appliances. Most of the used plastics are thrown away by consumers after a single use, which has become a huge environmental problem as they will end up in landfill, oceans and other waterways. These plastics are discarded in vast numbers each day, and the breaking down of the plastics from micro- to nano-sizes has led to worries about how toxic these plastics are to the environment and humans. While, there are several earlier studies reported the effects of micro- and nano-plastics have on the environment, there is scant research into their impact on the human body at subcellular or molecular levels. In particular, the potential of how nano-plastics move through the gut, lungs and skin epithelia in causing systemic exposure has not been examined thoroughly. This review explores thoroughly on how nanoplastics are created, how they behave/breakdown within the environment, levels of toxicity and pollution of these nanoplastics, and the possible health impacts on humans, as well as suggestions for additional research. This paper aims to inspire future studies into core elements of micro- and nano-plastics, the biological reactions caused by their specific and unusual qualities.
  4. Fulltext Focused Review: Potential Rare and Atypical Symptoms as Indicator for Targeted COVID-19 Screening
    Ng SL, Ong YS, Khaw KY, Teh SP, Tan CS, Ming LC, et al.
    Medicina (Kaunas), 2021 Feb 23;57(2).
    PMID: 33672384 DOI: 10.3390/medicina57020189
    The global pandemic of the coronavirus disease 2019 is a known consequence of infection of severe respiratory syndrome coronavirus-2 (SARS-CoV-2). It has affected nations worldwide with soaring number of cases daily. Symptoms such as fever, cough, and shortness of breath, diarrhea, nausea and vomiting are commonly presented in COVID-19 patients. This focused review aims to discuss these uncommon and atypical COVID-19 symptoms that may be presented which might affect neurological, cardiovascular, cutaneous and ocular systems and their possible mode of actions. Nonetheless, there are some cases of reported uncommon or atypical symptoms which may warrant healthcare professionals to be aware of, especially when in contact with patients. The knowledge and information concerning these symptoms might be able to provide additional cues for healthcare professional by subjecting patients to COVID-19 screening. Meanwhile, it might be able to further enhance the alertness and additional precautions being taken by healthcare personnel, which eventually lead to reduced risk of infections.
  5. Fulltext Molecular Dynamics Simulation of Nanocellulose-Stabilized Pickering Emulsions
    Lee KK, Low DYS, Foo ML, Yu LJ, Choong TSY, Tang SY, et al.
    Polymers (Basel), 2021 Feb 23;13(4).
    PMID: 33672331 DOI: 10.3390/polym13040668
    While the economy is rapidly expanding in most emerging countries, issues coupled with a higher population has created foreseeable tension among food, water, and energy. It is crucial for more sustainable valorization of resources, for instance, nanocellulose, to address the core challenges in environmental sustainability. As the complexity of the system evolved, the timescale of project development has increased exponentially. However, research on the design and operation of integrated nanomaterials, along with energy supply, monitoring, and control infrastructure, has seriously lagged. The development cost of new materials can be significantly reduced by utilizing molecular simulation technology in the design of nanostructured materials. To realize its potential, nanocellulose, an amphiphilic biopolymer with the presence of rich -OH and -CH structural groups, was investigated via molecular dynamics simulation to reveal its full potential as Pickering emulsion stabilizer at the molecular level. This work has successfully quantified the Pickering stabilization mechanism profiles by nanocellulose, and the phenomenon could be visualized in three stages, namely the initial homogenous phase, rapid formation of micelles and coalescence, and lastly the thermodynamic equilibrium of the system. It was also observed that the high bead order was always coupled with a high volume of phase separation activities, through a coarse-grained model within 20,000 time steps. The outcome of this work would be helpful to provide an important perspective for the future design and development of nanocellulose-based emulsion products, which cater for food, cosmeceutical, and pharmaceutical industries.
  6. Fulltext In Vitro Efficacy of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae Associated with Urinary Tract Infections in Malaysia
    Ngoi ST, Teh CSJ, Chong CW, Abdul Jabar K, Tan SC, Yu LH, et al.
    Antibiotics (Basel), 2021 Feb 11;10(2).
    PMID: 33670224 DOI: 10.3390/antibiotics10020181
    The increasing prevalence of extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae has greatly affected the clinical efficacy of β-lactam antibiotics in the management of urinary tract infections (UTIs). The limited treatment options have resulted in the increased use of carbapenem. However, flomoxef could be a potential carbapenem-sparing strategy for UTIs caused by ESBL-producers. Here, we compared the in vitro susceptibility of UTI-associated ESBL-producers to flomoxef and established β-lactam antibiotics. Fifty Escherichia coli and Klebsiella pneumoniae strains isolated from urine samples were subjected to broth microdilution assay, and the presence of ESBL genes was detected by polymerase chain reactions. High rates of resistance to amoxicillin-clavulanate (76-80%), ticarcillin-clavulanate (58-76%), and piperacillin-tazobactam (48-50%) were observed, indicated by high minimum inhibitory concentration (MIC) values (32 µg/mL to 128 µg/mL) for both species. The ESBL genes blaCTX-M and blaTEM were detected in both E. coli (58% and 54%, respectively) and K. pneumoniae (88% and 74%, respectively), whereas blaSHV was found only in K. pneumoniae (94%). Carbapenems remained as the most effective antibiotics against ESBL-producing E. coli and K. pneumoniae associated with UTIs, followed by flomoxef and cephamycins. In conclusion, flomoxef may be a potential alternative to carbapenem for UTIs caused by ESBL-producers in Malaysia.
  7. Effect of Vessel Tortuosity on Stress Concentration at the Distal Stent-Vessel Interface: Possible Link With New Entry Formation Through Biomechanical Simulation
    Tan WT, Liew YM, Mohamed Mokhtarudin MJ, Pirola S, Wan Ab Naim WN, Amry Hashim S, et al.
    J Biomech Eng, 2021 Aug 01;143(8).
    PMID: 33764388 DOI: 10.1115/1.4050642
    A computational approach is used to investigate potential risk factors for distal stent graft-induced new entry (dSINE) in aortic dissection (AD) patients. Patient-specific simulations were performed based on computed tomography images acquired from six AD patients (three dSINE and three non-dSINE) to analyze the correlation between anatomical characteristics and stress/strain distributions. Sensitivity analysis was carried out using idealized models to independently assess the effect of stent graft length, stent tortuosity and wedge apposition angle at the landing zone on key biomechanical variables. Mismatch of biomechanical properties between the stented and nonstented regions led to high stress at the distal stent graft-vessel interface in all patients, as well as shear strain in the neighboring region, which coincides with the location of tear formation. Stress was observed to increase with the increase of stent tortuosity (from 263 kPa at a tortuosity angle of 50 deg to 313 kPa at 30 deg). It was further amplified by stent graft landing at the inflection point of a curve. Malapposition of the stent graft led to an asymmetrical segment within the aorta, therefore changing the location and magnitude of the maximum von Mises stress substantially (up to +25.9% with a +25 deg change in the distal wedge apposition angle). In conclusion, stent tortuosity and wedge apposition angle serve as important risk predictors for dSINE formation in AD patients.
  8. Fulltext Pharmacy preparedness in handling COVID-19 pandemic: a sharing experience from a Malaysian tertiary hospital
    Thong KS, Selvaratanam M, Tan CP, Cheah MF, Oh HL, Lee PM, et al.
    J Pharm Policy Pract, 2021 Jul 19;14(1):61.
    PMID: 34275491 DOI: 10.1186/s40545-021-00343-6
    This commentary shares the experience of a hospital pharmacy department in providing healthcare services during the COVID-19 outbreak in Malaysia. During this pandemic, the medication delivery system is redesigned to minimize contact among patients and the health care providers. Also, the remote medication monitoring system was implemented to deliver pharmaceutical care for inpatients. Communication technology was used to assist the pharmacist in medication counseling. QR codes to access videos demonstrating the use of devices were made available for patients. Pharmacists were also tasked with the procurement of personal protective equipment and medications needed requiring special approval from the Ministry of Health.
  9. Research trends in gestational diabetes mellitus in Southeast Asia: A bibliometric analysis (1975-2020)
    Tantengco OAG, Aquino IMC, Asis JLB, Tan JJE, Uy MNAR, Pacheco EP
    Diabetes Metab Syndr, 2021 07 08;15(4):102202.
    PMID: 34265490 DOI: 10.1016/j.dsx.2021.102202
    AIMS: To determine the characteristics and trends of published articles in the field of gestational diabetes mellitus (GDM) in Southeast Asia (SEA) through a bibliometric analysis.

    METHODS: Systematic review of literature on GDM in SEA countries was performed using the Ovid MEDLINE®, Scopus, and WPRIM databases between 1975 and 2020. All published studies on GDM conducted in or published by authors from any SEA country were included in our analysis. Bibliometric information was obtained from Scopus and bibliometrics diagrams were created using VOSviewer software.

    RESULTS: A total of 322 articles were obtained in this study. The number of publications showed an upward trend starting 2011. The country with the greatest number of publications was Malaysia while The National University of Singapore was the most productive institution in GDM research in SEA. The focus of GDM research in SEA were on the prevalence, prevention, diagnosis, and pregnancy outcomes. GDP, research expenditure, and researchers per million people were positively correlated with research productivity and impact in GDM research in SEA.

    CONCLUSIONS: This is the first bibliometric analysis on GDM in SEA countries. GDM research in SEA continued to increase in the past years but still lagged behind that of other regions. The SEA countries should consider increasing support for research to produce substantial research that can serve as basis for evidence-based and locally applicable GDM interventions.

  10. Fulltext Molecular Phylogenesis and Spatiotemporal Spread of SARS-CoV-2 in Southeast Asia
    Zhu M, Shen J, Zeng Q, Tan JW, Kleepbua J, Chew I, et al.
    Front Public Health, 2021 07 30;9:685315.
    PMID: 34395364 DOI: 10.3389/fpubh.2021.685315
    Background: The ongoing coronavirus disease 2019 (COVID-19) pandemic has posed an unprecedented challenge to public health in Southeast Asia, a tropical region with limited resources. This study aimed to investigate the evolutionary dynamics and spatiotemporal patterns of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the region. Materials and Methods: A total of 1491 complete SARS-CoV-2 genome sequences from 10 Southeast Asian countries were downloaded from the Global Initiative on Sharing Avian Influenza Data (GISAID) database on November 17, 2020. The evolutionary relationships were assessed using maximum likelihood (ML) and time-scaled Bayesian phylogenetic analyses, and the phylogenetic clustering was tested using principal component analysis (PCA). The spatial patterns of SARS-CoV-2 spread within Southeast Asia were inferred using the Bayesian stochastic search variable selection (BSSVS) model. The effective population size (Ne) trajectory was inferred using the Bayesian Skygrid model. Results: Four major clades (including one potentially endemic) were identified based on the maximum clade credibility (MCC) tree. Similar clustering was yielded by PCA; the first three PCs explained 46.9% of the total genomic variations among the samples. The time to the most recent common ancestor (tMRCA) and the evolutionary rate of SARS-CoV-2 circulating in Southeast Asia were estimated to be November 28, 2019 (September 7, 2019 to January 4, 2020) and 1.446 × 10-3 (1.292 × 10-3 to 1.613 × 10-3) substitutions per site per year, respectively. Singapore and Thailand were the two most probable root positions, with posterior probabilities of 0.549 and 0.413, respectively. There were high-support transmission links (Bayes factors exceeding 1,000) in Singapore, Malaysia, and Indonesia; Malaysia involved the highest number (7) of inferred transmission links within the region. A twice-accelerated viral population expansion, followed by a temporary setback, was inferred during the early stages of the pandemic in Southeast Asia. Conclusions: With available genomic data, we illustrate the phylogeography and phylodynamics of SARS-CoV-2 circulating in Southeast Asia. Continuous genomic surveillance and enhanced strategic collaboration should be listed as priorities to curb the pandemic, especially for regional communities dominated by developing countries.
  11. Fulltext Sodium lignosulfonate improves shoot growth of Oryza sativa via enhancement of photosynthetic activity and reduced accumulation of reactive oxygen species
    Kok AD, Wan Abdullah WMAN, Tang CN, Low LY, Yuswan MH, Ong-Abdullah J, et al.
    Sci Rep, 2021 06 24;11(1):13226.
    PMID: 34168171 DOI: 10.1038/s41598-021-92401-x
    Lignosulfonate (LS) is a by-product obtained during sulfite pulping process and is commonly used as a growth enhancer in plant growth. However, the underlying growth promoting mechanism of LS on shoot growth remains largely unknown. Hence, this study was undertaken to determine the potential application of eco-friendly ion-chelated LS complex [sodium LS (NaLS) and calcium LS (CaLS)] to enhance recalcitrant indica rice MR 219 shoot growth and to elucidate its underlying growth promoting mechanisms. In this study, the shoot apex of MR 219 rice was grown on Murashige and Skoog medium supplemented with different ion chelated LS complex (NaLS and CaLS) at 100, 200, 300 and 400 mg/L The NaLS was shown to be a better shoot growth enhancer as compared to CaLS, with optimum concentration of 300 mg/L. Subsequent comparative proteomic analysis revealed an increase of photosynthesis-related proteins [photosystem II (PSII) CP43 reaction center protein, photosystem I (PSI) iron-sulfur center, PSII CP47 reaction center protein, PSII protein D1], ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), carbohydrate metabolism-related proteins (glyceraldehyde-3-phosphate dehydrogenase 3, fructose-bisphosphate aldolase) and stress regulator proteins (peptide methionine sulfoxide reductase A4, delta-1-pyrroline-5-carboxylate synthase 1) abundance in NaLS-treated rice as compared to the control (MSO). Consistent with proteins detected, a significant increase in biochemical analyses involved in photosynthetic activities, carbohydrate metabolism and protein biosynthesis such as total chlorophyll, rubisco activity, total sugar and total protein contents were observed in NaLS-treated rice. This implies that NaLS plays a role in empowering photosynthesis activities that led to plant growth enhancement. In addition, the increased in abundance of stress regulator proteins were consistent with low levels of peroxidase activity, malondialdehyde content and phenylalanine ammonia lyase activity observed in NaLS-treated rice. These results suggest that NaLS plays a role in modulating cellular homeostasis to provide a conducive cellular environment for plant growth. Taken together, NaLS improved shoot growth of recalcitrant MR 219 rice by upregulation of photosynthetic activities and reduction of ROS accumulation leading to better plant growth.
  12. Molecular typing of multi-drug resistant Candida albicans isolated from the Segamat community, Malaysia
    Huët MAL, Muzahid NH, Lee CZ, Goh CBS, Dwiyanto J, Rahman S, et al.
    Braz J Microbiol, 2021 Dec;52(4):2351-2356.
    PMID: 34235705 DOI: 10.1007/s42770-021-00558-4
    In the past decade, researchers have focused on the emergence of drug resistance in fungal pathogens such as Candida albicans, also considered as pathobionts that occur harmlessly in the human body but could potentially be triggered to cause diseases. The increasing rate of antifungal resistance in commensal gut fungi is alarming and should be further investigated. Here, we report seven novel MLST (Multi Locus Sequence Typing) genotypes of multi-drug resistant C. albicans isolates obtained from participants of a community study in Segamat, a district in the state of Johor, Malaysia. A total of eight C. albicans were isolated from four individuals, which were found to express high resistance against fluconazole, itraconazole, voriconazole and 5-fluorocytosine antifungals. MLST was performed to assess the clonal relatedness of these drug resistant isolates among themselves and against other strains isolated from other geographical regions. The novel MLST C. albicans sequence types suggest significant genetic changes compared to previous genotypes.
  13. Antimicrobial peptides as potential therapeutics for breast cancer
    Aghamiri S, Zandsalimi F, Raee P, Abdollahifar MA, Tan SC, Low TY, et al.
    Pharmacol Res, 2021 09;171:105777.
    PMID: 34298112 DOI: 10.1016/j.phrs.2021.105777
    Breast cancer is the most common and deadliest cancer in women worldwide. Although notable advances have been achieved in the treatment of breast cancer, the overall survival rate of metastatic breast cancer patients is still considerably low due to the development of resistance to breast cancer chemotherapeutic agents and the non-optimal specificity of the current generation of cancer medications. Hence, there is a growing interest in the search for alternative therapeutics with novel anticancer mechanisms. Recently, antimicrobial peptides (AMPs) have gained much attention due to their cost-effectiveness, high specificity of action, and robust efficacy. However, there are no clinical data available about their efficacy. This warrants the increasing need for clinical trials to be conducted to assess the efficacy of this new class of drugs. Here, we will focus on the recent progress in the use of AMPs for breast cancer therapy and will highlight their modes of action. Finally, we will discuss the combination of AMP-based therapeutics with other breast cancer therapy strategies, including nanotherapy and chemotherapy, which may provide a potential avenue for overcoming drug resistance.
  14. Fulltext Effects of tocotrienols supplementation on markers of inflammation and oxidative stress: A systematic review and meta-analysis of randomized controlled trials
    Khor BH, Tiong HC, Tan SC, Wong SK, Chin KY, Karupaiah T, et al.
    PLoS One, 2021;16(7):e0255205.
    PMID: 34297765 DOI: 10.1371/journal.pone.0255205
    Studies investigating the effects of tocotrienols on inflammation and oxidative stress have yielded inconsistent results. This systematic review and meta-analysis aimed to evaluate the effects of tocotrienols supplementation on inflammatory and oxidative stress biomarkers. We searched PubMed, Scopus, and Cochrane Central Register of Controlled Trials from inception until 13 July 2020 to identify randomized controlled trials supplementing tocotrienols and reporting circulating inflammatory or oxidative stress outcomes. Weighted mean difference (WMD) and corresponding 95% confidence interval (CI) were determined by pooling eligible studies. Nineteen studies were included for qualitative analysis, and 13 studies were included for the meta-analyses. A significant reduction in C-reactive protein levels (WMD: -0.52 mg/L, 95% CI: -0.73, -0.32, p < 0.001) following tocotrienols supplementation was observed, but this finding was attributed to a single study using δ-tocotrienols, not mixed tocotrienols. There were no effects on interleukin-6 (WMD: 0.03 pg/mL, 95% CI: -1.51, 1.58, p = 0.966), tumor necrosis factor-alpha (WMD: -0.28 pg/mL, 95% CI: -1.24, 0.68, p = 0.571), and malondialdehyde (WMD: -0.42 μmol/L, 95% CI: -1.05, 0.21, p = 0.189). A subgroup analysis suggested that tocotrienols at 400 mg/day might reduce malondialdehyde levels (WMD: -0.90 μmol/L, 95% CI: -1.20, -0.59, p < 0.001). Future well-designed studies are warranted to confirm the effects of tocotrienols on inflammatory and oxidative stress biomarkers, particularly on different types and dosages of supplementation. PROSPERO registration number: CRD42020198241.
  15. Fulltext Candida Chorioamnionitis in Mothers with Gestational Diabetes Mellitus: A Report of Two Cases
    Shazniza Shaaya E, Halim SAA, Leong KW, Ku KBP, Lim PS, Tan GC, et al.
    Int J Environ Res Public Health, 2021 07 13;18(14).
    PMID: 34299901 DOI: 10.3390/ijerph18147450
    Background:Candida chorioamnionitis is rarely encountered, even though vulvovaginal candidiasis incidence is about 15%. Interestingly, it has characteristic gross and histological findings on the umbilical cord that are not to be missed. Case Report: We report two cases of Candida chorioamnionitis with presence of multiple yellowish and red spots of the surface of the umbilical cord. Microscopically, these consist of microabscesses with evidence of fungal yeasts and pseudohyphae. The yeasts and pseudohyphae were highlighted by periodic acid- Schiff and Grocott methenamine silver histochemical stains. Both cases were associated with a history of gestational diabetes mellitus. Discussion: Peripheral funisitis is a characteristic feature of Candida chorioamnionitis. It is associated with high risk of adverse perinatal and neonatal outcomes, such as preterm delivery, stillbirth and neonatal death. We recommend careful examination of the umbilical cord of mothers with gestational diabetes mellitus.
  16. Strategic hazard mitigation of waste furniture boards via pyrolysis: Pyrolysis behavior, mechanisms, and value-added products
    Foong SY, Liew RK, Lee CL, Tan WP, Peng W, Sonne C, et al.
    J Hazard Mater, 2022 01 05;421:126774.
    PMID: 34364214 DOI: 10.1016/j.jhazmat.2021.126774
    Waste furniture boards (WFBs) contain hazardous formaldehyde and volatile organic compounds when left unmanaged or improperly disposed through landfilling and open burning. In this study, pyrolysis was examined as a disposal and recovery approach to convert three types of WFBs (i.e., particleboard, plywood, and fiberboard) into value-added chemicals using thermogravimetric analysis coupled with Fourier-transform infrared spectrometry (TG-FTIR) and pyrolysis coupled with gas chromatography/mass spectrometry (Py-GC/MS). TG-FTIR analysis shows that pyrolysis performed at an optimum temperature of 250-550 °C produced volatile products mainly consisting of carbon dioxide, carbon monoxide, and light hydrocarbons, such as methane. Py-GC/MS shows that pyrolysis at different final temperatures and heating rates recovered mainly phenols (25.9-54.7%) for potential use as additives in gasoline, colorants, and food. The calorific value of WFBs ranged from 16 to 18 MJ/kg but the WFBs showed high H/C (1.7-1.8) and O/C (0.8-1.0) ratios that provide low chemical energy during combustion. This result indicates that WFBs are not recommended to be burned directly as fuel, however, they can be pyrolyzed and converted into solid pyrolytic products such as biochar with improved properties for fuel application. Hazardous components, such as cyclopropylmethanol, were removed and converted into value-added compounds, such as 1,4:3,6-dianhydro-d-glucopyranose, for use in pharmaceuticals. These results show that the pyrolysis of WFBs at high temperature and low heating rate is a promising feature to produce value-added chemicals and reduce the formation of harmful chemical species. Thus, the release of hazardous formaldehyde and greenhouse gases into the environment is redirected.
  17. Fulltext α-Amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory effects of Melicope latifolia bark extracts and identification of bioactive constituents using in vitro and in silico approaches
    Quek A, Kassim NK, Lim PC, Tan DC, Mohammad Latif MA, Ismail A, et al.
    Pharm Biol, 2021 Dec;59(1):964-973.
    PMID: 34347568 DOI: 10.1080/13880209.2021.1948065
    CONTEXT: Melicope latifolia (DC.) T. G. Hartley (Rutaceae) was reported to contain various phytochemicals including coumarins, flavonoids, and acetophenones.

    OBJECTIVE: This study investigates the antidiabetic and antioxidant effects of M. latifolia bark extracts, fractions, and isolated constituents.

    MATERIALS AND METHODS: Melicope latifolia extracts (hexane, chloroform, and methanol), fractions, and isolated constituents with varying concentrations (0.078-10 mg/mL) were subjected to in vitro α-amylase and dipeptidyl peptidase-4 (DPP-4) inhibitory assay. Molecular docking was performed to study the binding mechanism of active compounds towards α-amylase and DPP-4 enzymes. The antioxidant activity of M. latifolia fractions and compounds were determined by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging and β-carotene bleaching assays.

    RESULTS: Melicope latifolia chloroform extract showed the highest antidiabetic activity (α-amylase IC50: 1464.32 μg/mL; DPP-4 IC50: 221.58 μg/mL). Fractionation of chloroform extract yielded four major fractions (CF1-CF4) whereby CF3 showed the highest antidiabetic activity (α-amylase IC50: 397.68 μg/mL; DPP-4 IC50: 37.16 μg/mL) and resulted in β-sitosterol (1), halfordin (2), methyl p-coumarate (3), and protocatechuic acid (4). Isolation of compounds 2-4 from the species and their DPP-4 inhibitory were reported for the first time. Compound 2 showed the highest α-amylase (IC50: 197.53 μM) and β-carotene (88.48%) inhibition, and formed the highest number of molecular interactions with critical amino acid residues of α-amylase. The highest DPP-4 inhibition was exhibited by compound 3 (IC50: 911.44 μM).

    DISCUSSION AND CONCLUSIONS: The in vitro and in silico analyses indicated the potential of M. latifolia as an alternative source of α-amylase and DPP-4 inhibitors. Further pharmacological studies on the compounds are recommended.

  18. Fulltext First 2 Fabry Cases with Novel Mutation and Their Associated Clusters in Malaysia
    Tang ASO, Wong QY, Pao Lin Ting I, Selvesten P, Yeo ST, Chew LP, et al.
    Am J Case Rep, 2021 Aug 06;22:e932923.
    PMID: 34354036 DOI: 10.12659/AJCR.932923
    BACKGROUND No cases of Fabry disease (FD) have been reported thus far in Malaysia. We aimed to report the demographic characteristics, clinical manifestations, molecular results, and treatment outcomes of 2 FD cases. This study was a retrospective review of 2 family clusters of FD on follow-up in Sarawak, Malaysia. CASE REPORT Two index patients were confirmed to have FD. Index patient 1, who had nephrotic-range proteinuria and cornea verticillata, carried a variant within exon 4 of the GLA gene: c.610 T>C (p.Trp204Arg). Agalsidase beta (Fabrazyme®) enzyme replacement therapy was initiated, with the absence of neutralizing antibody after 24 months. No hypersensitivity or adverse reactions were reported. The patient's proteinuria and renal function remained stable. Other family members who carried the same mutation were asymptomatic. Index patient 2, who had residual activity of alpha-galactosidase A and a normal globotriaosylsphingosine level, carried a novel GLA mutation of c.548-5T>A. He was diagnosed with end-stage renal disease on regular dialysis and had nonspecific headache with 1 episode of seizure a few years prior to FD genetic screening. One brother had chronic neuropathic pain but refused further investigations. Other family members who had the same mutation were asymptomatic. This mutation has never been reported in literature, and its pathogenicity warrants further studies. CONCLUSIONS It is of utmost importance to increase awareness of FD among clinicians, so that appropriate screening may be done to determine its true prevalence and prompt treatment can be initiated early.
  19. The potentiation of beta-lactam and anti-bacterial activities of lipophilic constituents from Mesua ferrae leaves against methicillin-resistant Staphylococcus aureus
    Alagasamy SV, Ramanathan S, Chear NJ, Tan WN, Ramachandram DS, Ching-Ga AT, et al.
    J Complement Integr Med, 2021 Jan 01;18(2):339-345.
    PMID: 34187118 DOI: 10.1515/jcim-2019-0316
    OBJECTIVES: Mesua ferrae, from the family of Calophyllaceae, is traditionally used for the treatment of piles, fever and renal disorders. The present study was aimed to examine the antibacterial compounds from the leaves of M. ferrae and their β-lactam antibiotic potentiate activities against Staphylococcus aureus and methicillin-resistant Staphylococcus aureus (MRSA).

    METHODS: Stigmasterol (1) and β-caryophyllene oxide (2) were isolated from the n-hexane fraction of the leaves of M. ferrae using a bioassay-guided fractionation approach.

    RESULTS: The isolated compounds displayed anti-Staphylococcus and anti-MRSA activities. It is worth to note that both compounds demonstrated synergism with β-lactam antibiotics against S. aureus and MRSA. Gas chromatography-mass spectrometry (GC-MS) analysis indicated the n-hexane fraction was dominated by triterpenes and sesquiterpenes, suggesting the total antibacterial activity exhibited by the fraction.

    CONCLUSION: Based on the findings, it could conclude that M. ferrae is a promising natural source for the discovery of new anti-MRSA lead compounds.

  20. Fulltext Key social science priorities for long-term COVID-19 response
    Lees S, Sariola S, Schmidt-Sane M, Enria L, Tan KA, Aedo A, et al.
    BMJ Glob Health, 2021 Jul;6(7).
    PMID: 34312181 DOI: 10.1136/bmjgh-2021-006741
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