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Fulltext Dislodged levornogestrel-intrauterine system intra-abdominally without uterine perforation: is it possible?

Ng, Beng Kwang, Lim, PS, Shahizon AMM, Ng, YL, Shafiee MN, Omar MH

Journal of Surgical Academia, 2016;6(1):51-53.
MyJurnal

We report a case of dislodged Levornogestrel-intrauterine system (LNG-IUS, Mirena®) without evidence of uterine perforation. A 37-year-old Para 4+1presented with 3 months history of lower abdominal pain. Examination and imaging showed that the device was not present in the uterine cavity. She underwent laparoscopic retrieval of Mirena®. There was no evidence of uterine perforation intra-operatively. This case illustrated the rare possibility of dislodged Mirena®intra-abdominally without evidence of uterine perforation. The management for missing IUS was reviewed.
Genetic diversity of the full length apical membrane antigen-1 of Plasmodium knowlesi clinical isolates from Peninsular Malaysia

Ng YL, Fong MY, Lau YL

Trop Biomed, 2021 Jun 01;38(2):159-164.
PMID: 34172705 DOI: 10.47665/tb.38.2.052

The Plasmodium knowlesi apical membrane antigen-1 (PkAMA-1) plays an important role in the invasion of the parasite into its host erythrocyte, and it has been regarded as a potential vaccine candidate against human knowlesi malaria. This study investigates genetic diversity and natural selection of the full length PkAMA-1 of P. knowlesi clinical isolates from Peninsular Malaysia. Blood samples were collected from P. knowlesi malaria patients from Peninsular Malaysia. The PkAMA-1 gene was amplified from DNA samples using PCR, cloned into a plasmid vector and sequenced. Results showed that nucleotide diversity of the full length PkAMA-1 from Peninsular Malaysia isolates (π: 0.006) was almost similar to that of Sarawak (π: 0.005) and Sabah (π: 0.004) isolates reported in other studies. Deeper analysis revealed Domain I (π: 0.007) in the PkAMA-1 had the highest diversity as compared to Domain II (π: 0.004) and Domain III (π: 0.003). Z-test indicated negative (purifying) selection of the gene. Combined alignment analysis at the amino acid level for the Peninsular Malaysia and Sarawak PkAMA-1 sequences revealed 34 polymorphic sites. Thirty-one of these sites were dimorphic, and 3 were trimorphic. The amino acid sequences could be categorised into 31 haplotypes. In the haplotype network, PkAMA-1 from Peninsular Malaysia and Sarawak were separated into two groups.
Fulltext Prevalence and associated factors of undiagnosed glycaemic disorders in men with erectile dysfunction attending a primary care clinic

Ng YL, Teoh SH, Mohd Radzniwan AR, Syahnaz MH

J Taibah Univ Med Sci, 2019 Feb;14(1):88-94.
PMID: 31435395 DOI: 10.1016/j.jtumed.2018.12.002

Objectives: Undiagnosed glycaemic disorders remain a major health concern as in such cases the opportunity for early interventions that can potentially prevent complications is missed. Erectile dysfunction (ED) has been suggested as a predictor for glycaemic disorders in men. However, data on men with ED having undiagnosed glycaemic disorders is limited, especially in the Malaysian context. This study aimed to identify prevalence and associated factors of undiagnosed glycaemic disorders in men with ED.
Methods: We applied a cross-sectional purposive sampling technique on a group of 114 men with ED without underlying glycaemic disorders. They underwent a 2-h oral glucose tolerance test and the cases were then classified into two groups: normal and undiagnosed glycaemic disorders groups. The glycaemic disorders group consisted of patients with diabetes mellitus (DM), impaired glucose tolerance (IGT), and impaired fasting glucose (IFG). The patients were interviewed, and their medical records were reviewed for their sociodemographic and clinical profiles.
Results: Prevalence of undiagnosed glycaemic disorders in men with ED was 41.2%. Higher age (adjusted OR = 1.10, 95% CI: 1.03, 1.17, p = 0.002) and BMI (adjusted OR = 1.16, 95% CI: 1.05, 1.29, p = 0.003) were found to be significantly associated with undiagnosed glycaemic disorders.
Conclusion: This study found that men with ED had a high prevalence of undiagnosed glycaemic disorders. ED was associated with advancing age and higher BMI. Further research to validate the findings of this study is needed to increase the prevalence of DM screening among men with ED.
Study site: Klinik Kesihatan Kajang, Selangor, Malaysia
Fulltext The Impact of Geographical Variation in Plasmodium knowlesi Apical Membrane Protein 1 (PkAMA-1) on Invasion Dynamics of P. knowlesi

Ng YL, Lee WC, Lau YL, Fong MY

Trop Med Infect Dis, 2023 Jan 10;8(1).
PMID: 36668963 DOI: 10.3390/tropicalmed8010056

Plasmodium knowlesi has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages of the parasites, which start from the invasion of erythrocytes by the blood stage merozoites. The apical membrane protein 1 (AMA-1) plays an important role in the invasion. In this study, we constructed and expressed recombinant PkAMA-1 domain II (PkAMA-1-DII) representing the predominant haplotypes from Peninsular Malaysia and Malaysian Borneo and raised specific antibodies against the recombinant proteins in rabbits. Despite the minor amino acid sequence variation, antibodies raised against haplotypes from Peninsular Malaysia and Malaysian Borneo demonstrated different invasion inhibition (46.81% and 39.45%, respectively) to P. knowlesi A1-H.1, a reference strain derived from Peninsular Malaysia. Here, we demonstrated how a minor variation in a conserved parasite protein could cast a significant impact on parasite invasion biology, suggesting a complex host-switching of P. knowlesi from different locations. This may challenge the implementation of a standardized One Health approach against the transmission of knowlesi malaria.
Fulltext Rodent Species Distribution and Hantavirus Seroprevalence in Residential and Forested areas of Sarawak, Malaysia

Hamdan NE, Ng YL, Lee WB, Tan CS, Khan FA, Chong YL

Trop Life Sci Res, 2017 Jan;28(1):151-159.
PMID: 28228923 MyJurnal DOI: 10.21315/tlsr2017.28.1.11

Rodents belong to the order Rodentia, which consists of three families in Borneo (i.e., Muridae, Sciuridae and Hystricidae). These include rats, mice, squirrels, and porcupines. They are widespread throughout the world and considered pests that harm humans and livestock. Some rodent species are natural reservoirs of hantaviruses (Family: Bunyaviridae) that can cause zoonotic diseases in humans. Although hantavirus seropositive human sera were reported in Peninsular Malaysia in the early 1980s, information on their infection in rodent species in Malaysia is still lacking. The rodent populations in residential and forested areas in Sarawak were sampled. A total of 108 individuals from 15 species of rodents were collected in residential (n = 44) and forested ( n = 64) areas. The species diversity of rodents in forested areas was significantly higher (H = 2.2342) compared to rodents in residential areas (H = 0.64715) (p < 0.001 of Zar-t test based on the Shannon index). Rattus rattus and Sundamys muelleri were present at high frequencies in both localities. An enzyme-linked immunosorbent assay (ELISA) showed that hantavirus-targeting antibodies were absent from 53 tested serum samples. This is the first report of hantavirus seroprevalence surveillance in rodent populations in Sarawak, East Malaysia. The results suggested that hantavirus was not circulating in the studied rodent populations in Sarawak, or it was otherwise at a low prevalence that is below the detection threshold. It is important to remain vigilant because of the zoonotic potential of this virus and its severe disease outcome. Further studies, such as molecular detection of viral genetic materials, are needed to fully assess the risk of hantavirus infection in rodents and humans in this region of Malaysia.
Fulltext Entamoeba histolytica: Quantitative Proteomics Analysis Reveals Putative Virulence-Associated Differentially Abundant Membrane Proteins

Ng YL, Olivos-García A, Lim TK, Noordin R, Lin Q, Othman N

Am J Trop Med Hyg, 2018 12;99(6):1518-1529.
PMID: 30298805 DOI: 10.4269/ajtmh.18-0415

Entamoeba histolytica is a protozoan parasite that causes amebiasis and poses a significant health risk for populations in endemic areas. The molecular mechanisms involved in the pathogenesis and regulation of the parasite are not well characterized. We aimed to identify and quantify the differentially abundant membrane proteins by comparing the membrane proteins of virulent and avirulent variants of E. histolytica HM-1:IMSS, and to investigate the potential associations among the differentially abundant membrane proteins. We performed quantitative proteomics analysis using isobaric tags for relative and absolute quantitation labeling, in combination with two mass spectrometry instruments, that is, nano-liquid chromatography (nanoLC)-matrix-assisted laser desorption/ionization-mass spectrometry/mass spectrometry and nanoLC-electrospray ionization tandem mass spectrometry. Overall, 37 membrane proteins were found to be differentially abundant, whereby 19 and 18 membrane proteins of the virulent variant of E. histolytica increased and decreased in abundance, respectively. Proteins that were differentially abundant include Rho family GTPase, calreticulin, a 70-kDa heat shock protein, and hypothetical proteins. Analysis by Protein ANalysis THrough Evolutionary Relationships database revealed that the differentially abundant membrane proteins were mainly involved in catalytic activities (29.7%) and metabolic processes (32.4%). Differentially abundant membrane proteins that were found to be involved mainly in the catalytic activities and the metabolic processes were highlighted together with their putative roles in relation to the virulence. Further investigations should be performed to elucidate the roles of these proteins in E. histolytica pathogenesis.
Preoperative free access to water compared to fasting for planned cesarean under spinal anesthesia: a randomized controlled trial

Ng YL, Segaran S, Yim CCW, Lim BK, Hamdan M, Gan F, et al.

Am J Obstet Gynecol, 2024 Mar 21.
PMID: 38521233 DOI: 10.1016/j.ajog.2024.03.018

BACKGROUND: Contemporary guidance for preoperative feeding allows solids up to 6 hours and clear fluids up to 2 hours before anesthesia. Clinical trial evidence to support this approach for cesarean delivery is lacking. Many medical practitioners continue to follow conservative policies of no intake from midnight to the time of surgery, especially in pregnant women.
OBJECTIVE: This study aimed to evaluate the pragmatic approach of permitting free access to water up to the call to dispatch to the operating theater vs fasting from midnight in preoperative oral intake restriction for planned cesarean delivery under spinal anesthesia on perioperative vomiting and maternal satisfaction.
STUDY DESIGN: A randomized controlled trial was conducted in the obstetrical unit of the University of Malaya Medical Centre from October 2020 to May 2022. A total of 504 participants scheduled for planned cesarean delivery were randomized: 252 undergoing preoperative free access to water up to the call to dispatch to the operating theater (intervention group) and 252 undergoing fasting from midnight (fasting arm). The primary outcomes were perioperative vomiting and maternal satisfaction. Analyses were performed using t test, Mann-Whitney U test, and chi-square test, as appropriate.
RESULTS: Of note, 9 of 252 patients (3.6%) in the intervention group and 24 of 252 patients (9.5%) in the control group had vomiting at up to 6 hours after completion of cesarean delivery (relative risk, 0.38; 95% confidence interval, 0.18-0.79; P=.007), and the maternal satisfaction scores (0-10 visual numerical rating scale) were 9 (interquartile range, 8-10) in the intervention group and 5 (interquartile range, 3-7) in the control group (P
Fulltext Genetic polymorphism of the thrombospondin-related apical merozoite protein (TRAMP) of Plasmodium knowlesi in Malaysia

Ng YL, Lau YL, Hamid MHA, Jelip J, Ooi CH, Mudin RN, et al.

Parasitol Res, 2023 Jan;122(1):195-200.
PMID: 36378331 DOI: 10.1007/s00436-022-07716-z

Plasmodium knowlesi is a simian malaria parasite that causes significant zoonotic infections in Southeast Asia, particularly in Malaysia. The Plasmodium thrombospondin-related apical merozoite protein (TRAMP) plays an essential role in the invasion of the parasite into its host erythrocyte. The present study investigated the genetic polymorphism and natural selection of the full length PkTRAMP from P. knowlesi clinical isolates from Malaysia. Blood samples (n = 40) were collected from P. knowlesi malaria patients from Peninsular Malaysia and Malaysian Borneo. The PkTRAMP gene was amplified using PCR, followed by cloning into a plasmid vector and sequenced. Results showed that the nucleotide diversity of PkTRAMP was low (π: 0.009). Z-test results indicated negative (purifying) selection of PkTRAMP. The alignment of the deduced amino acid sequences of PkTRAMP of Peninsular Malaysia and Malaysian Borneo revealed 38 dimorphic sites. A total of 27 haplotypes were identified from the amino acid sequence alignment. Haplotype analysis revealed that there was no clustering of PkTRAMP from Peninsular Malaysia and Malaysian Borneo.
Synthesis and biological evaluation of hydantoin derivatives as potent antiplasmodial agents

Chin EZ, Chang WJ, Tan HY, Liew SY, Lau YL, Ng YL, et al.

Bioorg Med Chem Lett, 2024 May 01;103:129701.
PMID: 38484804 DOI: 10.1016/j.bmcl.2024.129701

Malaria, a devastating disease, has claimed numerous lives and caused considerable suffering, with young children and pregnant women being the most severely affected group. However, the emergence of multidrug-resistant strains of Plasmodium and the adverse side effects associated with existing antimalarial drugs underscore the urgent need for the development of novel, well-tolerated, and more efficient drugs to combat this global health threat. To address these challenges, six new hydantoins derivatives were synthesized and evaluated for their in vitro antiplasmodial activity. Notably, compound 2c exhibited excellent inhibitory activity against the tested Pf3D7 strain, with an IC50 value of 3.97 ± 0.01 nM, three-fold better than chloroquine. Following closely, compound 3b demonstrated an IC50 value of 27.52 ± 3.37 µM against the Pf3D7 strain in vitro. Additionally, all the hydantoins derivatives tested showed inactive against human MCR-5 cells, with an IC50 value exceeding 100 μM. In summary, the hydantoin derivative 2c emerges as a promising candidate for further exploration as an antiplasmodial compound.
Enantiomeric pairs of ternary copper(ii) complexes and their aldol-type condensation products: synthesis, characterization, and anticancer and epigenetic properties

Lee KY, Ng YL, Wang WS, Ng PY, Chan CW, Lai JW, et al.

Dalton Trans, 2019 Apr 09;48(15):4987-4999.
PMID: 30916098 DOI: 10.1039/c9dt00506d

Chiral enantiomers [Cu(phen)(l-ser)(H2O)]NO31 and [Cu(phen)(d-ser)(H2O)]NO32 (ser = serinato) underwent aldol-type condensation with formaldehyde, with retention of chirality, to yield their respective enantiomeric ternary copper(ii) complexes, viz. l- and d-[Cu(phen)(OCA)(H2O)]NO3·xH2O (3 and 4; phen = 1,10-phenanthroline; OCA = oxazolidine-4-carboxylate; x = 1/2, 0-2) respectively. These chiral complexes were characterized by FTIR, elemental analysis, circular dichroism, UV-visible spectroscopy, fluorescence spectroscopy (FL), molar conductivity measurement, ESI-MS and X-ray crystallography. The crystal structures of 1 and 3 showed both the cationic complexes to have a square pyramidal geometry. These complexes were about nine fold more potent than cisplatin against metastatic MDA-MB-231 breast cancer cells, inducing apoptotic cell death via ROS generation and a massive drop in mitochondrial membrane potential. The results of monitoring EZH1, EZH2 and H3K27me3 revealed that the mode of action of 1-4 also involved the downregulation of EZH2 and it seemed to be independent of the H3K27me3 status.
Fulltext Preliminary insight on diarylpentanoids as potential antimalarials: In silico, in vitro pLDH and in vivo zebrafish toxicity assessment

Ramli AH, Swain P, Mohd Fahmi MSA, Abas F, Leong SW, Tejo BA, et al.

Heliyon, 2024 Mar 15;10(5):e27462.
PMID: 38495201 DOI: 10.1016/j.heliyon.2024.e27462

Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 μM, respectively. Meanwhile, MS87 (EC50 of 1.85 μM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 μM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 μM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.

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