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Fulltext Management and Clinical Outcome of Children with Transfusion-Dependent Thalassaemia in Hospital Tuanku Ja'afar Seremban

Aina Mariana AM, Yap SH

Med J Malaysia, 2014 Aug;69(4):178-83.
PMID: 25500846 MyJurnal

The aim of this study was to evaluate the management and clinical outcome of transfusion-dependent thalassaemia children receiving care in the Paediatric Ambulatory Care Centre, Hospital Tuanku Ja'afar Seremban in comparison to The Malaysian Clinical Practice Guidelines. The demography, management and clinical outcome of the patients were documented using a checklist. Information on compliance to chelation agents was obtained through interview. There were twenty-six patients recruited in this study out of thirty seven patients registered in the centre. This study showed that more effort and vigilance should be given to ensure that the management of these patients adheres to the guidelines and clinical outcome of these patients monitored closely.

Study site: Paediatric Ambulatory Care Centre, Hospital Tunku Ja'afar, Seremban.
Imaging bicipitoradial bursitis: a pictorial essay

Yap SH, Griffith JF, Lee RKL

Skeletal Radiol, 2019 Jan;48(1):5-10.
PMID: 29797016 DOI: 10.1007/s00256-018-2970-0

Although bicipitoradial bursitis is not commonly seen, when it does occur, it can frequently lead to diagnostic difficulty, mimicking either a soft-tissue tumor or infection. Lack of awareness of this uncommon entity can lead to unnecessary anxiety or tissue biopsy. This pictorial essay discusses the normal anatomy of the bicipitoradial bursa and the spectrum of imaging findings of bicipital bursitis.
MicroRNAs associated with tumour migration, invasion and angiogenic properties in A549 and SK-Lu1 human lung adenocarcinoma cells

Ho CS, Yap SH, Phuah NH, In LL, Hasima N

Lung Cancer, 2014 Feb;83(2):154-62.
PMID: 24360396 DOI: 10.1016/j.lungcan.2013.11.024

Dysregulation in miRNA expression contributes towards the initiation and progression of metastasis by regulating multiple target genes. In this study, variations in miRNA expression profiles were investigated between high and low invasive NSCLC cell lines followed by identification of miRNAs with targets governing NSCLC's metastatic potential.
Fulltext Molecular characterization of two Malaysian patients with Wiskott-Aldrich syndrome

Baharin MF, Kader Ibrahim SB, Yap SH, Abdul Manaf AM, Mat Ripen A, Dhaliwal JS

Malays J Pathol, 2015 Aug;37(2):153-8.
PMID: 26277674 MyJurnal

The Wiskott-Aldrich Syndrome (WAS) is an X-linked immunodeficiency condition characterized by microthrombocytopenia, eczema and recurrent infections. It is caused by mutations in the Wiskott-Aldrich Syndrome protein (WASP) gene. We investigated two Malay boys who presented with congenital thrombocytopenia, eczema and recurrent infections. Here we report two cases of WASP mutation in Malaysia from two unrelated families. One had a novel missense mutation in exon 1 while the other had a nonsense mutation in exon 2. Both patients succumbed to diseaserelated complications. A differential diagnosis of WAS should be considered in any male child who present with early onset thrombocytopenia, especially when this is associated with eczema and recurrent infections.
Fulltext HIV-Infected Individuals on ART With Impaired Immune Recovery Have Altered Plasma Metabolite Profiles

Nyström S, Govender M, Yap SH, Kamarulzaman A, Rajasuriar R, Larsson M

Open Forum Infect Dis, 2021 Jul;8(7):ofab288.
PMID: 34258318 DOI: 10.1093/ofid/ofab288

Background: Multiple host factors may influence immune reconstitution in HIV-infected people after the initiation of suppressive antiretroviral therapy (ART). Aberrant metabolic pathways have been reported in people with HIV (PWH) on ART. We hypothesized that alterations in plasma metabolites were associated with immune recovery following ART.
Methods: In this cross-sectional study, the plasma metabolomic profiles of PWH on ART were evaluated. PWH of slow and fast immune recovery were classified by increase in CD4 T cells following 2 years of ART. Targeted plasma metabolite profiling by liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry to determine metabolite signatures for HIV recovery identified >200 metabolites.
Results: Notably, indole-3-propionic acid was downregulated during HIV, possibly reflecting impaired gastrointestinal epithelium homeostasis. The most important metabolite discriminating between the PWH with fast and slow immune recovery was cysteine. Upregulated cysteine and cysteine pathways may contribute to redox-balance maintenance and T-cell function in PWH with fast immune recovery. Additionally, serine and glycine metabolism and bile acid biosynthesis were the most perturbed metabolic pathways in PWH.
Conclusions: These results provide a starting point for developing biomarker candidates for immune recovery in PWH on ART and provide insight into the interplay of metabolism and immune response in HIV infection.
Fulltext Are Indians and females less tolerant to pain? An observational study using a laboratory pain model

Das Gupta E, Zailinawati AH, Lim AW, Chan JB, Yap SH, Hla YY, et al.

Med J Malaysia, 2009 Jun;64(2):111-3.
PMID: 20058568 MyJurnal

In Malaysia, it is a common belief among health care workers that females and Indians have lower pain threshold. This experience, although based on anecdotal experience in the healthcare setting, does not allow differentiation between pain tolerance, and pain expression. To determine whether there is a difference in the tolerance to pain between the three main ethnic groups, namely the Malays, Chinese and Indians as well as between males and females. This was a prospective study, using a laboratory pain model (ischaemic pain tolerance) to determine the pain tolerance of 152 IMU medical students. The mean age of the students was 21.8 years (range 18-29 years). All of them were unmarried. The median of ischaemic pain tolerance for Malays, Chinese and Indians were 639s, 695s and 613s respectively (p = 0.779). However, statistically significant difference in ischaemic pain tolerance for males and females Indian students were observed. Possible ethnic difference in pain tolerance in casual observation is not verified by this laboratory pain model. Difference in pain tolerance between genders is shown only for Indians.
Fulltext Attitudes and factors affecting acceptability of self-administered cervicovaginal sampling for human papillomavirus (HPV) genotyping as an alternative to Pap testing among multiethnic Malaysian women

Ma'som M, Bhoo-Pathy N, Nasir NH, Bellinson J, Subramaniam S, Ma Y, et al.

BMJ Open, 2016 08 04;6(8):e011022.
PMID: 27491667 DOI: 10.1136/bmjopen-2015-011022

OBJECTIVE: The objective of this study was to determine the attitudes and acceptability of self-administered cervicovaginal sampling compared with conventional physician-acquired Papanicolaou (Pap) smear among multiethnic Malaysian women.

METHOD: A cross-sectional study was carried out via interviewer-administered surveys from August 2013 through August 2015 at five government-run, urban health clinics in the state of Selangor. Subjects were participants from an ongoing community-based human papillomavirus (HPV) prevalence study who answered a standard questionnaire before and after self-sampling. The cervicovaginal self-sampling for HPV genotyping was performed using a simple brush ('Just for Me'; Preventive Oncology International, Hong Kong). Detailed data on sociodemographics, previous Pap smear experience, and attitudes towards self-administered cervicovaginal sampling were collected and analysed. Acceptability was inferred using a five-item Likert scale that included six different subjective descriptives: experience, difficulty, convenience, embarrassment, discomfort or pain, and confidence in collecting one's own sample.

RESULTS: Of the 839 participants, 47.9% were Malays, followed by 30.8% Indians, 18.8% Chinese and 2.5% from other ethnicities. The median age of the participants was 38 years (IQR 30-48). Some 68.2% of participants indicated a preference for self-sampling over the Pap test, with 95% indicating willingness to follow-up a positive result at the hospital. Age, ethnicity and previous Pap test experience were significant independent factors associated with preference for self-sampling. The older the individual, the less likely they were to prefer self-sampling (adjusted OR 0.94, 95% CI 0.90 to 0.98). The Chinese were less likely to prefer self-sampling (72.6%) than the Malays (85.1%) (adjusted OR 0.57, 95% CI 0.33 to 0.98, p=0.004). Participants who had never undergone a Pap smear were also more likely to prefer self-sampling (88.5%) than women who had undergone a previous Pap (80.9%) (adjusted OR 0.06, 95% CI 0.35 to 0.87).

CONCLUSIONS: Overall, urban Malaysian women from multiethnic backgrounds found self-sampling to be an acceptable alternative to Pap smear.
A comparison of dabigatran and warfarin for stroke prevention in elderly Asian population with nonvalvular atrial fibrillation: An audit of current practice in Malaysia

Yap SH, Ng YP, Roslan A, Kolanthaivelu J, Koh KW, P'ng HS, et al.

Med J Malaysia, 2017 12;72(6):360-364.
PMID: 29308774 MyJurnal

INTRODUCTION: Atrial fibrillation (AF) is the most common cardiac arrhythmia with significant morbidity and mortality in relation to thromboembolic stroke. Our study aimed to evaluate the safety and efficacy of dabigatran in stroke prevention in elderly patient with nonvalvular AF with regard to the risk of ischemic stroke and intracranial haemorrhage (ICH) in real-world setting.
METHODS: A retrospective cohort study of 200 patients on dabigatran and warfarin from January 2009 till September 2016 was carried out. Data were collected for 100 patients on dabigatran and 100 patients on warfarin.
RESULTS: The mean follow-up period was 340.7±322.3 days for dabigatran group and 410.5±321.2 days for warfarin group. The mean time in therapeutic range (TTR) was 52±18.7%. The mean CHA2DS2 -VASc score for dabigatran group was 4.4±1.1 while 5.0±1.5 for warfarin group. None in dabigatran group experienced ischemic stroke compared to one patient in warfarin group (p=0.316). There was one patient in dabigatran group suffered from ICH compared to none in warfarin group (p=0.316). Four patients in warfarin group experienced minor bleeding, while none from dabigatran group (p=0.043).
CONCLUSION: Overall bleeding events were significantly lower in dabigatran group compared to warfarin group. In the presence of suboptimal TTR rates and inconveniences with warfarin therapy, non-vitamin-K antagonist oral anticoagulants (NOAC) are the preferred agents for stroke prevention in elderly Asian patients for nonvalvular AF.
Modeling and computational characterization of a Xanthomonas sp. Hypothetical protein identifies a remote ortholog of Burkholderia lethal factor 1

Muhamad Ismail NAS, Yap SH, Mohamad Yussoff MA, Nor Muhammad NA, Firdaus-Raih M, Quay DHX

J Biomol Struct Dyn, 2023;41(13):6027-6039.
PMID: 35862639 DOI: 10.1080/07391102.2022.2100827

Burkholderia Lethal Factor 1 (BLF1) is a deamidase first characterized in Burkholderia pseudomallei. This enzyme inhibits cellular protein synthesis by deamidating a glutamine residue to a glutamic acid in its target protein, the eukaryotic translation initiation factor 4 A (eIF4A). In this work, we present the characterization of a hypothetical protein from Xanthomonas sp. Leaf131 as the first report of a BLF1 family ortholog outside of the Burkholderia genus. Although standard sequence similarity searches such as BLAST were not able to detect the homology between the Xanthomonas sp. Leaf131 hypothetical protein sequence and BLF1, our computed structure model for the Xanthomonas sp. hypothetical protein revealed structural similarities with an RMSD of 2.7 Å/164 Cα atoms and a TM-score of 0.72 when superposed. Structural comparisons of the Xanthomonas model structure against BLF1 and Escherichia coli cytotoxic necrotizing factor 1 (CNF1) revealed that the conserved signature LXGC motif and putative catalytic residues are structurally aligned thus signifying a level of functional or mechanistic similarity. Protein-protein docking analysis and molecular dynamics simulations also demonstrated that eIF4A could still be a possible target substrate for deamidation by XLF1 as it is for BLF1. We therefore propose that this Xanthomonas hypothetical protein be renamed as Xanthomonas Lethal Factor 1 (XLF1). Our work also provides further evidence of the utility of programs such as AlphaFold in bridging the computational function annotation transfer gap despite very low sequence identities of under 20%.Communicated by Ramaswamy H. Sarma.
Fulltext D-Amino acids differentially trigger an inflammatory environment in vitro

Yap SH, Lee CS, Zulkifli ND, Suresh D, Hamase K, Das KT, et al.

Amino Acids, 2024 Feb 03;56(1):6.
PMID: 38310167 DOI: 10.1007/s00726-023-03360-8

Studies in vivo have demonstrated that the accumulation of D-amino acids (D-AAs) is associated with age-related diseases and increased immune activation. However, the underlying mechanism(s) of these observations are not well defined. The metabolism of D-AAs by D-amino oxidase (DAO) produces hydrogen peroxide (H2O2), a reactive oxygen species involved in several physiological processes including immune response, cell differentiation, and proliferation. Excessive levels of H2O2 contribute to oxidative stress and eventual cell death, a characteristic of age-related pathology. Here, we explored the molecular mechanisms of D-serine (D-Ser) and D-alanine (D-Ala) in human liver cancer cells, HepG2, with a focus on the production of H2O2 the downstream secretion of pro-inflammatory cytokine and chemokine, and subsequent cell death. In HepG2 cells, we demonstrated that D-Ser decreased H2O2 production and induced concentration-dependent depolarization of mitochondrial membrane potential (MMP). This was associated with the upregulation of activated NF-кB, pro-inflammatory cytokine, TNF-α, and chemokine, IL-8 secretion, and subsequent apoptosis. Conversely, D-Ala-treated cells induced H2O2 production, and were also accompanied by the upregulation of activated NF-кB, TNF-α, and IL-8, but did not cause significant apoptosis. The present study confirms the role of both D-Ser and D-Ala in inducing inflammatory responses, but each via unique activation pathways. This response was associated with apoptotic cell death only with D-Ser. Further research is required to gain a better understanding of the mechanisms underlying D-AA-induced inflammation and its downstream consequences, especially in the context of aging given the wide detection of these entities in systemic circulation.
Fulltext Prevalence and sociodemographic correlates of anogenital Human Papillomavirus (HPV) carriage in a cross-sectional, multi-ethnic, community-based Asian male population

Khoo SP, Shafii MKA, Bhoo-Pathy N, Yap SH, Subramaniam S, Nasir NH, et al.

PLoS One, 2021;16(1):e0245731.
PMID: 33471825 DOI: 10.1371/journal.pone.0245731

BACKGROUND: Addressing the burden of HPV-associated diseases among men is increasingly becoming a public health issue. The main objective of this study was to determine HPV prevalence among a healthy community-based Malaysian men.
METHOD: This was a cross-sectional study that recruited 503 healthy males from 3 community-based clinics in Selangor, Malaysia. Genital and anal samples were collected from each participant for 14 high risk and 2 low risk HPV DNA detection and genotyping. All participants responded to a set of detailed sociodemographic and sexual behaviour questionnaire.
RESULTS: The median age at enrolment was 40 years old (IQR: 31-50). The anogenital HPV6/11 prevalence was 3.2% whereas high risk HPV prevalence was 27.1%. The genital HPV prevalence for HPV6/11 was 2.9% while high risk HPV was 18.8%. HPV6/11 prevalence in the anal canal was 1.6% and high risk HPV was 12.7%. HPV 18 was the most prevalent genotype detected in the anogenital area. There was a significant independent association between genital and anal HPV infections.
CONCLUSION: Anogenital HPV infection is common among Malaysian men. These findings emphasize the ubiquity of HPV infection and thus the value of population-wide access to HPV prevention.
Fulltext Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections

Kared H, Martelli S, Tan SW, Simoni Y, Chong ML, Yap SH, et al.

Front Immunol, 2018;9:686.
PMID: 29731749 DOI: 10.3389/fimmu.2018.00686

Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.
Fulltext Enrichment of gut-derived Fusobacterium is associated with suboptimal immune recovery in HIV-infected individuals

Lee SC, Chua LL, Yap SH, Khang TF, Leng CY, Raja Azwa RI, et al.

Sci Rep, 2018 09 24;8(1):14277.
PMID: 30250162 DOI: 10.1038/s41598-018-32585-x

We explored the gut microbiota profile among HIV-infected individuals with diverse immune recovery profiles following long-term suppressive ART and investigated the relationship between the altered bacteria with markers of immune dysfunction. The microbiota profile of rectal swabs from 26 HIV-infected individuals and 20 HIV-uninfected controls were examined. Patients were classified as suboptimal responders, sIR (n = 10, CD4 T-cell <350 cells/ul) and optimal responders, oIR (n = 16, CD4 T-cell >500 cells/ul) after a minimum of 2 years on suppressive ART. Canonical correlation analysis(CCA) and multiple regression modelling were used to explore the association between fecal bacterial taxa abundance and immunological profiles in optimal and suboptimal responders. We found Fusobacterium was significantly enriched among the HIV-infected and the sIR group. CCA results showed that Fusobacterium abundance was negatively correlated with CD4 T-cell counts, but positively correlated with CD4 T-cell activation and CD4 Tregs. Multiple linear regression analysis adjusted for age, baseline CD4 T-cell count, antibiotic exposure and MSM status indicated that higher Fusobacterium relative abundance was independently associated with poorer CD4 T-cell recovery following ART. Enrichment of Fusobacterium was associated with reduced immune recovery and persistent immune dysfunction following ART. Modulating the abundance of this bacterial taxa in the gut may be a viable intervention to improve immune reconstitution in our setting.
Prevalence and sociodemographic correlates of cervicovaginal human papillomavirus (HPV) carriage in a cross-sectional, multiethnic, community-based female Asian population

Khoo SP, Bhoo-Pathy N, Yap SH, Anwar Shafii MK, Hairizan Nasir N, Belinson J, et al.

Sex Transm Infect, 2018 06;94(4):277-283.
PMID: 29180538 DOI: 10.1136/sextrans-2017-053320

OBJECTIVES: Cervical cancer is a largely preventable disease, and the strategic implementation of a cervical cancer prevention programme is partly dependent on the impact of human papillomavirus (HPV) infection interpreted within the context of the country's sociodemographic attributes. The objective of this study is to determine the prevalence of cervicovaginal HPV infection among a healthy, community-based, multiethnic Malaysian population. The HPV prevalence was subsequently correlated to the individual's sociodemographics and sexual/reproductive history. Of significance, the observed prevalence captured was in a birth cohort not included in the national school-based HPV vaccination programme.
METHODS: This was a cross-sectional study where 1293 healthy women aged between 18 and 60 years were recruited via convenience sampling from five community-based clinics in Selangor, Malaysia. Cervicovaginal self-samples were obtained and DNA was extracted for HPV detection and genotyping. A comprehensive questionnaire was administered to determine the sociodemographics and behavioural patterns of participants.
RESULTS: The median age at enrolment was 37 years old (IQR: 30-47). In total, 86/1190 (7.2%) of the samples collected were positive for HPV infection, with the highest HPV prevalence (11.9%) detected in the subgroup of 18-24 years old. The top three most prevalent HPV genotypes were HPV 16, 52 and 58. The independent risk factors associated with higher rates of HPV infection included Indian ethnicity, widowed status and women with partners who are away from home for long periods and/or has another sexual partner.
CONCLUSIONS: The overall prevalence of HPV infection in this Malaysian multiethnic population was 7.2%, with 6.5% being high-risk genotypes. The top three most common high-risk HPV types were HPV 16, 52 and 58. This information is important for the planning of primary (HPV vaccination) and secondary (screening) cervical cancer prevention programmes in Malaysia.
Fulltext HIV/Human herpesvirus co-infections: Impact on tryptophan-kynurenine pathway and immune reconstitution

Yap SH, Abdullah NK, McStea M, Takayama K, Chong ML, Crisci E, et al.

PLoS One, 2017;12(10):e0186000.
PMID: 29016635 DOI: 10.1371/journal.pone.0186000

BACKGROUND: Co-infections with human herpesvirus (HHV) have been associated with residual chronic inflammation in antiretroviral (ART)-treated human immunodeficiency virus (HIV)-infected individuals. However, the role of HHV in modulating the tryptophan-kynurenine pathway and clinical outcomes in HIV-infected individuals is poorly understood. Thus, we investigated the seroprevalence of four common HHVs among treated HIV-infected participants and their impact on kynurenine/tryptophan (K/T) ratio and long-term CD4 T-cell recovery in HIV/HHV co-infected participants.
METHOD: In this cross-sectional study, HIV-infected participants receiving suppressive ART for a minimum of 12 months were recruited from the University Malaya Medical Centre (UMMC), Malaysia. Stored plasma was analyzed for CMV, VZV, HSV-1 and HSV-2 IgG antibody levels, immune activation markers (interleukin-6, interferon-γ, neopterin and sCD14), kynurenine and tryptophan concentrations. The influence of the number of HHV co-infection and K/T ratio on CD4 T-cell recovery was assessed using multivariate Poisson regression.
RESULTS: A total of 232 HIV-infected participants were recruited and all participants were seropositive for at least one HHV; 96.1% with CMV, 86.6% with VZV, 70.7% with HSV-1 and 53.9% with HSV-2. K/T ratio had a significant positive correlation with CMV (rho = 0.205, p = 0.002), VZV (rho = 0.173, p = 0.009) and a tendency with HSV-2 (rho = 0.120, p = 0.070), with CMV antibody titer demonstrating the strongest modulating effect on K/T ratio among the four HHVs assessed in SOM analysis. In multivariate analysis, higher K/T ratio (p = 0.03) and increasing number of HHV co-infections (p<0.001) were independently associated with poorer CD4 T-cell recovery following 12 months of ART initiation.
CONCLUSION: Multiple HHV co-infections are common among ART-treated HIV-infected participants in the developing country setting and associated with persistent immune activation and poorer CD4 T-cell recovery.

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