MyMedR

Fulltext Reasons for visiting a hospital-based general medical clinic

Tan HS

Med J Malaysia, 1985 Sep;40(3):211-9.

The reasons why 860 patients visited the general medical clinic at the University Hospital, Kuala Lumpur were studied. 75.3% of the patients came for evaluation of symptoms; 12.4% sought checkups for chronic diseases; 4.9% requested diagnostic checkups and screening tests; 4.8% came to renew prescription. Few visits were made for evaluation of injuries, receiving test results or for administrative examination. This profile reflected the function of the clinic as an acute diagnostic centre. Other applications of the results are discussed.
Study site: General Medical Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

Mock grant application roleplay as an alternative to lab-based activities in molecular biology

Tan HS

Biochem Mol Biol Educ, 2021 07;49(4):518-520.

PMID: 33826248 DOI: 10.1002/bmb.21515

Many universities resort to online teaching due to COVID-19 pandemic. It is a challenging endeavor, especially in Molecular Biology courses that require lab access. Mock grant application roleplay is one alternative to lab-based activities. Students are engaged in three aspects: (i) targeted literature review, (ii) research proposal writing and (iii) 5-min project pitching. The design of this module is flexible and, other lab-based courses can adopt it. This module encourages undergraduate students to explore the lab techniques they learnt and concisely present their research proposal.

Family practice at the University Hospital

Tan HS

Family Practitioner, 1988;11(1):53-5.

The Department of Primary Care Medicine was established in UHKL in 1987. This article examines the philosophy of primary care, the clinical services provided by UHKL Family Practice Clinic and the quality assurance activities.

Fulltext Treatment failure of falciparum malaria with Fansidar in Tawau Sabah. January-June, 1982

Tan HS, Tan PE

Med J Malaysia, 1983 Sep;38(3):217-23.

PMID: 6369092

One hundred and ten consecutive patients with falciparum malaria were treated with Fansidar and primaquine. Of the 61 patients who were followed up at one week, 4 (6.5%) failed to clear their parasitemia (1 R III and 3 R Il treatment failures). Of the subsequent 40 patients who were seen again at one month, another 3 (7.5%) had recrudesced (R 1 treatment failure). A total of 7 patients thus experienced some form of treatment failure in the cohort of 40 who completed the one month follow up. Only 1 of these 7patients (with R III treatment) failure) failed to respond to repeat Fansidar treatment, and may be the only one with true Fansidar resistance. The overall treatment failure rate of 17.5% (95% confidence interval: 6-29%) in the cohort who completed the study is consistent with the known clinical efficacy of Fansidar. These results suggest no significant Fansidar resistance in falciparum malaria found in Sabah.

Clinical efficacy of sulfadoxine-pyrimethamine in the treatment of falciparum malaria in Sabah, Malaysia

Tan HS, Tan PE

Ann Acad Med Singap, 1984 Apr;13(2):170-4.

PMID: 6388486

One hundred and ten consecutive patients with falciparum malaria were treated with Fansidar and primaquine. Of the 61 patients who were followed up at one week, 4 (6.6%) failed to clear their parasitaemia (1 R III and 3 R II treatment failures). Of the subsequent 40 patients who were seen again at one month, another 3 (7.5%) had recrudesced (R I treatment failure). A total of 7 patients thus experienced some form of treatment failure in the cohort of 40 who completed the one month follow up. Only 1 of these 7 patients (with R III treatment failure) failed to respond to repeat Fansidar treatment, and may be the only one with true Fansidar resistance. The overall treatment failure rate of 17.5% (95% confidence interval: 6-29%) in the cohort who completed the study is consistent with the known clinical efficacy of Fansidar. These results suggest no significant Fansidar resistance in falciparum malaria found in Sabah.

First record of Rhopalophthalmus longipes Ii, 1964 from Malaysian waters (Crustacea, Mysida)

Tan HS, Azman BA

Zookeys, 2017.

PMID: 28138298 DOI: 10.3897/zookeys.642.10316

The marine mysid species Rhopalophthalmus longipes Ii, 1964 is reported from Malaysian waters for the first time. Specimens are described and illustrated in detail based on material collected by epibenthic sledge from the seagrass meadows of Pulau Tinggi, Johor. Specimens exhibit a slight difference from Ii's type material by possessing a rounded process bearing two small protrusions apically near the middle distal end of the third segment of antennal peduncle. In addition, its telson armed with 7-9 moderately strong setae at the lateral margin.

Fulltext A small RNA decreases the sensitivity of Shigella sonnei to norfloxacin

Gan IN, Tan HS

BMC Res Notes, 2019 Feb 21;12(1):97.

PMID: 30791948 DOI: 10.1186/s13104-019-4124-4

OBJECTIVES: Shigella is a human pathogen that causes shigellosis, an acute invasive intestinal infection. Recent studies in the model bacterium Escherichia coli (E. coli) provided evidence that small regulatory RNAs (sRNAs) can contribute to antimicrobial resistance or susceptibility. One of the sRNAs is SdsR, which increases sensitivity of E. coli against fluoroquinolone by repressing the drug efflux pump, TolC. However, no reports exist about the effect of SdsR on fluoroquinolone resistance in Shigella sonnei (S. sonnei). In this study, we established the effect of SdsR on the sensitivity of S. sonnei to norfloxacin.

DATA DESCRIPTION: We tested the effects of SdsR and SdsRv2 on fluoroquinolone resistance in S. sonnei in vivo. SdsRv2 is a synthetic version which promotes higher binding stability to tolC mRNA. Overexpression of either SdsR or SdsRv2 lowers the expression of tolC mRNA. Interestingly, SdsR and SdsRv2 promote the growth of S. sonnei in the presence of a sub-inhibitory concentration of norfloxacin. Mutant carrying SdsRv2 showed the highest growth advantage. This phenotype is opposite to the effect of SdsR reported in E. coli. This study is an example that demonstrates the difference in the phenotypic effect of a highly conserved sRNA in two closely related bacteria.

Acinetobacter baumannii subunit vaccines: recent progress and challenges

Lau YT, Tan HS

Crit Rev Microbiol, 2024 Aug;50(4):434-449.

PMID: 37211625 DOI: 10.1080/1040841X.2023.2215303

Acinetobacter baumannii is a Gram-negative, opportunistic pathogen that causes nosocomial infection with a high mortality rate in immunocompromised individuals. With the frequent emergence of multidrug-resistant A. baumannii strains that have rapidly gained resistance to most antibiotics, an extensive search for an effective A. baumannii vaccine is ongoing. Over the decade, many subunit vaccine candidates were identified using reverse vaccinology and in vivo animal studies for validation. Nineteen subunit vaccine candidates with a wide range of efficacy, from 14% to 100% preclinical survival rates, were included in this review. This article provides an updated review of several outer membrane proteins (Omp) that emerged as vaccine candidates with great potential, including OmpA, Omp34, Omp22 and BamA, based on their high conservancy, antigenicity, and immune protection against A. baumannii infection. However, there is still no licenced A. baumannii vaccine currently due to several practical issues that have yet to be resolved, such as inconsistencies between validation studies, antigen variability and insolubility. Moving forward, much investigation and innovation are still required to tackle these challenges for the regulatory approval of an A. baumannii subunit vaccine, including standardisation of immunisation study parameters, improving antigen solubility and the incorporation of nucleic acid vaccine technology.

Fulltext Antibiotic susceptibility of community-acquired Staphylococcus aureus

Tan HS, Ngeow YF, Jamal F

Med J Malaysia, 1986 Mar;41(1):24-9.

PMID: 3796343

55% of a sample of patients in a rural
community, and 76% of a sample of patients and
staff in the local district hospital were found to
be nasal carriers for Staphylococcus aureus. The
in vitro antibiotic susceptibility patterns of 46
strains of S. aureus isolated in nasal carriers as
well as of 43 strains in community-acquired skin
infections were characterised. High levels of
resistance were expressed to penicillin (73%),
cephalexin (64%) and tetracycline (46%).
Resistance to erythromycin (18%) was moderate.
A few strains showed resistance to methicillin
(5 isolates), vancomycin (4), [usidic acid (3),
cotrimoxazole (1), and none to gentamicin.
Penicillin can no longer be recommended for
treating community-acquired S. aureus infections.

Measuring the Ultrafast Correlation Dynamics between the Q x and Q y Bands in Chlorophyll Molecules

Khyasudeen MF, Nowakowski PJ, Tan HS

J Phys Chem B, 2019 02 14;123(6):1359-1364.

PMID: 30657672 DOI: 10.1021/acs.jpcb.9b00099

We use two-dimensional electronic spectroscopy to measure the ultrafast correlation dynamics between the Q x and Q y transitions in chlorophyll molecules. We derive a variation to the center line slope method to quantify the frequency fluctuation cross-correlation function, C xy( Tw). Compared with the frequency fluctuation correlation function of the Q y transition, we observe that there is only a minimal correlation between the Q x and Q y transition, even at the ultrashort timescale of ∼100 fs, which then decays to zero in a time scale of ∼2 ps.

Transcriptomic insights into the virulence of Acinetobacter baumannii during infection-role of iron uptake and siderophore production genes

Ten KE, Rahman S, Tan HS

FEBS Lett, 2024 Nov 21.

PMID: 39572900 DOI: 10.1002/1873-3468.15061

Acinetobacter baumannii, a top-priority WHO pathogen, causes life-threatening infections in immunocompromised patients, leading to prolonged hospitalisation and high mortality. Here, we used the Galleria mellonella model to investigate community strain C98 (Ab-C98) virulence via transcriptomic analysis. Ab-C98 showed greater killing and faster colonisation in larvae than the clinical reference strain (ATCC BAA1605). Genes in three iron clusters, acinetobactin, baumannoferrin and the Feo system, were significantly up-regulated. Targeted knockout of siderophore genes (basC, bfnD, and the gene encoding isochorismatase) significantly increased the survival of infected larvae by at least 35.16%, identifying these genes as potential targets for developing anti-virulence agents against A. baumannii.

Fulltext Uncovering the transcriptome-wide RNA modifications in Acinetobacter baumannii

Ten KE, Rahman S, Tan HS

Microb Genom, 2024 Nov;10(11).

PMID: 39565092 DOI: 10.1099/mgen.0.001327

Despite being a major human pathogen, limited studies have reported RNA modifications in Acinetobacter baumannii. These post-transcriptional modifications play crucial regulatory roles in bacteria and have also been shown to modulate bacterial virulence. Using nanopore sequencing, we characterized RNA modifications in a virulent A. baumannii strain (Ab-C98) under free-living (mid-exponential phase in vitro culture) and during an early stage of infection (3 h post-infection) in Galleria mellonella larvae. Analysis revealed that m5C methylations are essential for ribosome synthesis, while m6A and Ψ are involved in metabolic pathways and translation processes. Iron-chelating genes exbD (m5C and m6A) and feoB (m6A and Ψ) and RNA polymerase subunit rpoC (m6A and Ψ) were selectively modified during infection. This first transcriptome-wide study highlights the potential regulatory roles of m5C, m6A and Ψ modifications in A. baumannii during infection.

Fulltext Paediatric Palliative Care during the COVID-19 Pandemic: A Malaysian Perspective

Chong LA, Khoo EJ, Kamar AA, Tan HS

Asian Bioeth Rev, 2020 Aug 13.

PMID: 32837563 DOI: 10.1007/s41649-020-00142-2

Malaysia had its first four patients with COVID-19 on 25 January 2020. In the same week, the World Health Organization declared it as a public health emergency of international concern. The pandemic has since challenged the ethics and practice of medicine. There is palpable tension from the conflict of interest between public health initiatives and individual's rights. Ensuring equitable care and distribution of health resources for patients with and without COVID-19 is a recurring ethical challenge for clinicians. Palliative care aims to mitigate suffering caused by a life-limiting illness, and this crisis has led to the awareness and urgency to ensure it reaches all who needs it. We share here the palliative care perspectives and ethical challenges during the COVID-19 pandemic in Malaysia.

Fulltext Characterization of multidrug-resistant Acinetobacter baumannii strain ATCC BAA1605 using whole-genome sequencing

Ten KE, Md Zoqratt MZH, Ayub Q, Tan HS

BMC Res Notes, 2021 Mar 04;14(1):83.

PMID: 33663564 DOI: 10.1186/s13104-021-05493-z

OBJECTIVE: The nosocomial pathogen, Acinetobacter baumannii, has acquired clinical significance due to its ability to persist in hospital settings and survive antibiotic treatment, which eventually resulted in the rapid spread of this bacterium with antimicrobial resistance (AMR) phenotypes. This study used a multidrug-resistant A. baumannii (strain ATCC BAA1605) as a model to study the genomic features of this pathogen.

RESULTS: One circular chromosome and one circular plasmid were discovered in the complete genome of A. baumannii ATCC BAA1605 using whole-genome sequencing. The chromosome is 4,039,171 bp long with a GC content of 39.24%. Many AMR genes, which confer resistance to major classes of antibiotics (beta-lactams, aminoglycosides, tetracycline, sulphonamides), were found on the chromosome. Two genomic islands were predicted on the chromosome, one of which (Genomic Island 1) contains a cluster of AMR genes and mobile elements, suggesting the possibility of horizontal gene transfer. A subtype I-F CRISPR-Cas system was also identified on the chromosome of A. baumannii ATCC BAA1605. This study provides valuable genome data that can be used as a reference for future studies on A. baumannii. The genome of A. baumannii ATCC BAA1605 has been deposited at GenBank under accession no. CP058625 and CP058626.

The role of artificial intelligence in the battle against antimicrobial-resistant bacteria

Lau HJ, Lim CH, Foo SC, Tan HS

Curr Genet, 2021 Jun;67(3):421-429.

PMID: 33585980 DOI: 10.1007/s00294-021-01156-5

Antimicrobial resistance (AMR) in bacteria is a global health crisis due to the rapid emergence of multidrug-resistant bacteria and the lengthy development of new antimicrobials. In light of this, artificial intelligence in the form of machine learning has been viewed as a potential counter to delay the spread of AMR. With the aid of AI, there are possibilities to predict and identify AMR in bacteria efficiently. Furthermore, a combination of machine learning algorithms and lab testing can help to accelerate the process of discovering new antimicrobials. To date, many machine learning algorithms for antimicrobial-resistance discovery had been created and vigorously validated. Most of these algorithms produced accurate results and outperformed the traditional methods which relied on sequence comparison within a database. This mini-review will provide an updated overview of antimicrobial design workflow using the latest machine-learning antimicrobial discovery algorithms in the last 5 years. With this review, we hope to improve upon the current AMR identification and antimicrobial development techniques by introducing the use of AI into the mix, including how the algorithms could be made more effective.

RNA-cleaving DNAzymes as a diagnostic and therapeutic agent against antimicrobial resistant bacteria

Wong BC, Abu Bakar J, Dhanoa A, Tan HS

Curr Genet, 2022 Feb;68(1):27-38.

PMID: 34505182 DOI: 10.1007/s00294-021-01212-0

The development of nucleic-acid-based antimicrobials such as RNA-cleaving DNAzyme (RCD), a short catalytically active nucleic acid, is a promising alternative to the current antibiotics. The current rapid spread of antimicrobial resistance (AMR) in bacteria renders some antibiotics useless against bacterial infection, thus creating the need for alternative antimicrobials such as DNAzymes. This review summarizes recent advances in the use of RCD as a diagnostic and therapeutic agent against AMR. Firstly, the recent diagnostic application of RCD for the detection of bacterial cells and the associated resistant gene(s) is discussed. The next section summarises the therapeutic application of RCD in AMR bacterial infections which includes direct targeting of the resistant genes and indirect targeting of AMR-associated genes. Finally, this review extends the discussion to challenges of utilizing RCD in real-life applications, and the potential of combining both diagnostic and therapeutic applications of RCD into a single agent as a theranostic agent.

Fulltext Severity and Hospitalization Cost Related to Warfarin-Related Adverse Events in a Tertiary Malaysian Hospital

George D, Wong CA, Thanimalai S, Tan HS

Hosp Pharm, 2022 Oct;57(5):633-638.

PMID: 36081534 DOI: 10.1177/00185787211070182

Introduction: Oral anticoagulant is essential for the treatment and prevention of thromboembolism. Warfarin is an effective oral anticoagulant in prevention and treatment of thromboembolism. However, warfarin is frequently associated with adverse event (AE) requiring hospitalization. Method: We performed a retrospective cohort study of all patients admitted to a large tertiary public hospital for warfarin-related AEs. Patients were grouped based on bleeding severity and the direct medical cost was also calculated. Results: During the 4 years study period, a total of 224 patients were admitted for warfarin-related AEs. Mean age of patients admitted was 65.1 years (standard deviation [SD] = 11.5). More than half, 59.6%, of them were on warfarin for prevention of stroke in atrial fibrillation or atrial flutter. Major bleeding occurred among 50.9% of the patients with gastrointestinal bleed, 34 (29.8%), as the common site of bleed. Patients with major bleed had longer median hospital stay of 4 days (interquartile range [IQR] = 5) compared to 3 (IQR = 3) days in non-major bleed. There were 17 (14.9%) death among the major bleeders. Mean medical cost for managing warfarin-related AEs was USD 708.08. Conclusion: The admitted patients were equally distributed in terms of bleeding severity. Medical cost incurred for managing warfarin-related AEs increased with the severity of bleeding.

Fulltext Use of the waxworm Galleria mellonella larvae as an infection model to study Acinetobacter baumannii

Ten KE, Muzahid NH, Rahman S, Tan HS

PLoS One, 2023;18(4):e0283960.

PMID: 37018343 DOI: 10.1371/journal.pone.0283960

Galleria mellonella larvae have been increasingly used in research, including microbial infection studies. They act as suitable preliminary infection models to study host-pathogen interactions due to their advantages, such as the ability to survive at 37°C mimicking human body temperature, their immune system shares similarities with mammalian immune systems, and their short life cycle allowing large-scale studies. Here, we present a protocol for simple rearing and maintenance of G. mellonella without requiring special instruments and specialized training. This allows the continuous supply of healthy G. mellonella for research purposes. Besides, this protocol also provides detailed procedures on the (i) G. mellonella infection assays (killing assay and bacterial burden assay) for virulence studies and (ii) bacterial cell harvesting from infected larvae and RNA extraction for bacterial gene expression studies during infection. Our protocol could not only be used in the studies of A. baumannii virulence but can also be modified according to different bacterial strains.

Fulltext Acute impending compartment syndrome during elective spine surgery: a rare occurrence

Yeap TB, Shabani NS, Bong CP, Tan HS

BMJ Case Rep, 2021 Jul 13;14(7).

PMID: 34257132 DOI: 10.1136/bcr-2021-244358

Intraoperative impending compartment syndrome (ICS) is an extremely rare but lethal occurrence that can involve the upper and/or lower limb(s). It commonly occurs in patients who undergo anaesthesia in various special positions such as lithotomy, lateral decubitus or prone. We present a patient who developed an ICS of his left forearm during a cervical spine surgery in prone position. This devastating condition was fortunately identified when the pulse oximetry, intra-arterial wave form and motor-evoked potentials signal disappeared abruptly from our monitors. We discuss our perioperative challenges and management for the patient which had eventually saved the patient's limb.

Fulltext Unveiling the functional epitopes of cobra venom cytotoxin by immunoinformatics and epitope-omic analyses

Hiu JJ, Fung JKY, Tan HS, Yap MKK

Sci Rep, 2023 Jul 28;13(1):12271.

PMID: 37507457 DOI: 10.1038/s41598-023-39222-2

Approximate 70% of cobra venom is composed of cytotoxin (CTX), which is responsible for the dermonecrotic symptoms of cobra envenomation. However, CTX is generally low in immunogenicity, and the antivenom is ineffective in attenuating its in vivo toxicity. Furthermore, little is known about its epitope properties for empirical antivenom therapy. This study aimed to determine the epitope sequences of CTX using the immunoinformatic analyses and epitope-omics profiling. A conserved CTX was used in this study to determine its T-cell and B-cell epitope sequences using immunoinformatic tools and molecular docking simulation with different Human Leukocyte Antigens (HLAs). The potential T-cell and B-cell epitopes were 'KLVPLFY,' 'CPAGKNLCY,' 'MFMVSTPTK,' and 'DVCPKNSLL.' Molecular docking simulations disclosed that the HLA-B62 supertype exhibited the greatest binding affinity towards cobra venom cytotoxin. The namely L7, G18, K19, N20, M25, K33, V43, C44, K46, N47, and S48 of CTX exhibited prominent intermolecular interactions with HLA-B62. The multi-enzymatic-limited-digestion/liquid chromatography-mass spectrometry (MELD/LC-MS) also revealed three potential epitope sequences as 'LVPLFYK,' 'MFMVS,' and 'TVPVKR'. From different epitope mapping approaches, we concluded four potential epitope sites of CTX as 'KLVPLFYK', 'AGKNL', 'MFMVSTPKVPV' and 'DVCPKNSLL'. Site-directed mutagenesis of these epitopes confirmed their locations at the functional loops of CTX. These epitope sequences are crucial to CTX's structural folding and cytotoxicity. The results concluded the epitopes that resided within the functional loops constituted potential targets to fabricate synthetic epitopes for CTX-targeted antivenom production.

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