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Fulltext Reduced CD4+ terminally differentiated effector memory T cells in moderate-severe house dust mites sensitized allergic rhinitis patients

Sani MM, Ashari NSM, Abdullah B, Wong KK, Musa KI, Mohamud R, et al.

Asian Pac J Allergy Immunol, 2019 Sep;37(3):138-146.
PMID: 29981564 DOI: 10.12932/AP-191217-0220

BACKGROUND: Terminally differentiated effector memory (TEMRA) T cells exert potent effector function after activation. The proportions of CD4+ T cell subsets especially memory cells in allergic rhinitis (AR) patients sensitized to house dust mites (HDMs) have not been extensively studied.
OBJECTIVE: This study aimed to compare the mean percentages and absolute counts of CD4+ memory T cell subsets between: (i) non-allergic controls and AR patients; (ii) mild AR patients and moderate-severe AR patients.
METHODS: Sensitization to Dermatophagoides farinae and Dermatophagoides pteronyssinus were determined in 33 non -allergic controls, 28 mild AR and 29 moderate-severe AR patients. Flow cytometry was used to determine the percentage of CD4+ na?ve (TN; CD45RA+CCR7+), central memory (TCM; CD45RA-CCR7+), effector memory (TEM; CD45RA-CCR7-) and TEMRA (CD45RA+CCR7-) T cells from the peripheral blood. The absolute counts of CD4+ T cell subsets were obtained by dual platform method from flow cytometer and hematology analyzer.
RESULTS: There were no significant differences in the mean percentages and absolute counts of CD4+ T cell subsets between non-allergic controls and AR patients sensitized to HDMs. However, there were significant reduction in the mean percentage (p=0.0307) and absolute count (p=0.0309) of CD4+ TEMRA cells in moderate-severe AR patients compared to mild AR patients sensitized to HDMs and 13/24 (54.2%) moderate-severe AR patients sensitized to HDMs had persistent symptoms.
CONCLUSION: Reduction in the mean percentage and absolute count of CD4+CD45RA+CCR7- TEMRA cells were observed in moderate-severe AR patients compared to mild AR patients in our population of AR patients sensitized to HDMs.
Therapeutic Suppression of Nonsense Mutation: An Emerging Target in Multiple Diseases and Thrombotic Disorders

Asiful Islam M, Alam F, Kamal MA, Gan SH, Wong KK, Sasongko TH

Curr Pharm Des, 2017;23(11):1598-1609.
PMID: 27875971 DOI: 10.2174/1381612823666161122142950

Nonsense mutations contribute to approximately 10-30% of the total human inherited diseases via disruption of protein translation. If any of the three termination codons (UGA, UAG and UAA) emerges prematurely [known as premature termination codon (PTC)] before the natural canonical stop codon, truncated nonfunctional proteins or proteins with deleterious loss or gain-of-function activities are synthesized, followed by the development of nonsense mutation-mediated diseases. In the past decade, PTC-associated diseases captured much attention in biomedical research, especially as molecular therapeutic targets via nonsense suppression (i.e. translational readthrough) regimens. In this review, we highlighted different treatment strategies of PTC targeting readthrough therapeutics including the use of aminoglycosides, ataluren (formerly known as PTC124), suppressor tRNAs, nonsense-mediated mRNA decay, pseudouridylation and CRISPR/Cas9 system to treat PTC-mediated diseases. In addition, as thrombotic disorders are a group of disease with major burdens worldwide, 19 potential genes containing a total of 705 PTCs that cause 21 thrombotic disorders have been listed based on the data reanalysis from the 'GeneCards® - Human Gene Database' and 'Human Gene Mutation Database' (HGMD®). These PTC-containing genes can be potential targets amenable for different readthrough therapeutic strategies in the future.
Diagnostic performance of COVID-19 serology assays

Zainol Rashid Z, Othman SN, Abdul Samat MN, Ali UK, Wong KK

Malays J Pathol, 2020 Apr;42(1):13-21.
PMID: 32342927

INTRODUCTION: The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19.
MATERIALS AND METHODS: A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently.
RESULTS: From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed.
CONCLUSIONS: There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.
Fulltext CD3+CD4+gp130+ T Cells Are Associated With Worse Disease Activity in Systemic Lupus Erythematosus Patients

Mohd Shukri ND, Farah Izati A, Wan Ghazali WS, Che Hussin CM, Wong KK

Front Immunol, 2021;12:675250.
PMID: 34149710 DOI: 10.3389/fimmu.2021.675250

The receptors for IL-35, IL-12Rβ2 and gp130, have been implicated in the inflammatory pathophysiology of autoimmune diseases. In this study, we set out to investigate the serum IL-35 levels and the surface levels of IL-12Rβ2 and gp130 in CD3+CD4+, CD3+CD4─ and CD3─CD4─ lymphocyte subpopulations in systemic lupus erythematosus (SLE) patients (n=50) versus healthy controls (n=50). The potential T cell subsets associated with gp130 transcript (i.e. IL6ST) expression in CD4+ T cells of SLE patients was also examined in publicly-available gene expression profiling (GEP) datasets. Here, we report that serum IL-35 levels were significantly higher in SLE patients than healthy controls (p=0.038) but it was not associated with SLEDAI-2K scores. The proportions of IL-12Rβ2+ and gp130+ cells in SLE patients did not differ significantly with those of healthy controls in all lymphocyte subpopulations investigated. Essentially, higher SLEDAI-2K scores were positively correlated with increased proportion of gp130+ cells, but not IL-12Rβ2+ cells, on CD3+CD4+ T cells (r=0.425, p=0.002, q=0.016). Gene Set Enrichment Analysis (GSEA) of a GEP dataset of CD4+ T cells isolated from SLE patients (n=8; GSE4588) showed that IL6ST expression was positively associated with genes upregulated in CD4+ T cells vs myeloid or B cells (q<0.001). In an independent GEP dataset of CD4+ T cells isolated from SLE patients (n=9; GSE1057), IL6ST expression was induced upon anti-CD3 stimulation, and that Treg, TCM and CCR7+ T cells gene sets were significantly enriched (q<0.05) by genes highly correlated with IL6ST expression (n=92 genes; r>0.75 with IL6ST expression) upon anti-CD3 stimulation in these SLE patients. In conclusion, gp130 signaling in CD3+CD4+ T cell subsets may contribute to increased disease activity in SLE patients, and it represents a promising therapeutic target for inhibition in the disease.
Fulltext Increased IL-23R+ Th Cells Population Exhibits Higher SLEDAI-2K Scores in Systemic Lupus Erythematosus Patients

Izati AF, Mohd Shukri ND, Wan Ghazali WS, Che Hussin CM, Wong KK

Front Immunol, 2021;12:690908.
PMID: 34484186 DOI: 10.3389/fimmu.2021.690908

The IL-23/IL-17 axis plays causative roles in the development and progression of systemic lupus erythematosus (SLE). However, it remains unclear if the IL-17RA+ and IL-23R+ T helper (Th) cells populations are associated with the serum IL-17 and IL-23 levels, or with the immunological parameters and disease activities in SLE patients. Herein, we examined the proportion of IL-17RA+ and IL-23R+ Th cells and serum levels of IL-17 and IL-23 in established SLE patients (n = 50) compared with healthy controls (n = 50). The associations of these interleukins and their receptors with immunological parameters [anti-nuclear antibody (ANA), anti-dsDNA antibody, and C-reactive protein (CRP)] and SLE disease activity (SLEDAI-2K scores) in SLE patients were assessed. CD3+CD4+ Th cells of SLE patients demonstrated significantly elevated IL-17RA+ (p = 1.12 x 10-4) or IL-23R+ (p = 1.98 x 10-29) populations compared with the healthy controls. Serum IL-17 levels were significantly lower in SLE patients compared with the healthy controls (p = 8.32 x 10-5), while no significant difference was observed for the IL-23 serum levels between both groups. IL-23R+ Th cells population was significantly associated with higher SLEDAI-2K scores (p = 0.017). In multivariate analysis, the proportion of IL-23R+ Th cells remained significantly associated with higher SLEDAI-2K scores independent of prednisolone intake (p = 0.027). No associations were observed between the interleukin parameters (i.e., IL-17, IL-23, IL-17RA+ Th cells, and IL-23R+ Th cells) with ANA, anti-dsDNA, and CRP status, suggesting that the IL-17/IL-23 axis acts independently of these immunological parameters. In conclusion, our results support that therapeutic inhibition of the IL-23/IL-17 axis receptors on Th cells, particularly IL-23R, is potentially relevant in SLE patients.
'Non-criteria' neurologic manifestations of antiphospholipid syndrome: a hidden kingdom to be discovered

Islam MA, Alam F, Kamal MA, Wong KK, Sasongko TH, Gan SH

CNS Neurol Disord Drug Targets, 2016;15(10):1253-1265.
PMID: 27658514 DOI: 10.2174/1871527315666160920122750

Neurological manifestations or disorders associated with the central nervous system are among the most common and important clinical characteristics of antiphospholipid syndrome (APS). Although in the most recently updated (2006) APS classification criteria, the neurological manifestations encompass only transient ischemic attack and stroke, diverse 'non-criteria' neurological disorders or manifestations (i.e., headache, migraine, bipolar disorder, transverse myelitis, dementia, chorea, epileptic seizures, multiple sclerosis, psychosis, cognitive impairment, Tourette's syndrome, parkinsonism, dystonia, transient global amnesia, obsessive compulsive disorder and leukoencephalopathy) have been observed in APS patients. To date, the underlying mechanisms responsible for these abnormal neurological manifestations in APS remain unclear. In vivo experiments and human observational studies indicate the involvement of thrombotic events and/or high titers of antiphospholipid antibodies in the neuro-pathogenic cascade of APS. Although different types of neurologic manifestations in APS patients have successfully been treated with therapies involving anti-thrombotic regimens (i.e., anticoagulants and/or platelet antiaggregants), antineuralgic drugs (i.e., antidepressants, antipsychotics and antiepileptics) and immunosuppressive drugs alone or in combination, evidence-based guidelines for the management of the neurologic manifestations of APS remain unavailable. Therefore, further experimental, clinical and retrospective studies with larger patient cohorts are warranted to elucidate the pathogenic linkage between APS and the central nervous system in addition to randomized controlled trials to facilitate the discovery of appropriate medications for the 'non-criteria' neurologic manifestations of APS.
Fulltext Maternal and umbilical cord blood polymorphonuclear leukocytes showed moderate oxidative burst at phagocytosis of Gardnerella vaginalis

Swaminathan A, Abd Aziz NH, Ayub NA, Wong KK, Cheah FC

BMC Res Notes, 2021 Nov 22;14(1):420.
PMID: 34809696 DOI: 10.1186/s13104-021-05842-y

OBJECTIVE: Pregnant women with bacterial vaginosis due to Gardnerella vaginalis (GV) infection presents with a wide-ranging disease symptomatology. We speculate this may be due to interaction that varies between host immune response and the pathogen. We studied the oxidative burst in polymorphonuclear leukocytes (PMNL)s from maternal blood (MB) and cord blood (CB) upon phagocytosis of GV and compared against E. coli and Group B Streptococcus (GBS).
RESULTS: The PHAGOBURST™ assay detects fluorescence from oxidized dihydrorhodamine during oxidative burst. The average percentage of PMNL showing oxidative burst was almost two-fold greater with GBS (99.5%) and E. coli (98.2%) than GV (56.9%) (p
Immunomodulatory effects of a bioactive fraction of Strobilanthes crispus in NMU-induced rat mammary tumor model

Yankuzo HM, Baraya YS, Mustapha Z, Wong KK, Yaacob NS

J Ethnopharmacol, 2018 Mar 01;213:31-37.
PMID: 29100935 DOI: 10.1016/j.jep.2017.10.024

ETHNOPHARMACOLOGICAL RELEVANCE: Strobilanthes crispus Blume is traditionally consumed among local Malay and indigenous communities for the treatment of cancer and other ailments such as gastrointestinal disorders, inflammatory wounds of snake bite and immune system activation amongst others. We previously demonstrated that a bioactive fraction of S. crispus leaves (F3) was cytotoxic to breast cancer cells in vitro and inhibited tumor growth in N-methyl-N-nitrosourea (NMU)-induced breast cancer rat model. F3 also normalized the white blood cell count in the tumor-bearing animals, indicating its potential immuno-stimulatory effect.
AIM OF THE STUDY: To evaluate the immune stimulatory effects of F3 from S. crispus in NMU-induced rat mammary tumor model.
MATERIALS AND METHODS: Immunohistochemistry analysis of cellular immune parameters (CD4+ or CD8+ T cells, CIITA, MHC-II and CD68) was performed on NMU-induced rat mammary tumor nodules, followed by evaluation of the serum level of 34 cytokines using the cytokine antibody array.
RESULTS: Significant increase in MHC-II, CD4+ and CD8+ T cell and CIITA expression by tumor cells was observed in F3-treated rats compared to the tumor control group. F3-treated rats also displayed a significant decrease in the serum level of CCL2 and CD68+ infiltrating macrophages. Serum IFN-γ level in this group was increased by 1.7-fold suggesting enhanced infiltration of T cells, and upregulation of CIITA and MHC-II expression in the tumor cells might be triggered by F3-induced production of IFN-γ.
CONCLUSION: Our findings demonstrated for the first time that a subfraction from S. crispus, F3, is capable of activating the immune system in rats-bearing NMU-induced mammary tumor, which may contribute to the anticancer effects of F3, and additionally support the traditional use of S. crispus leaves to boost the immune system.
Fulltext Association of anti-CLIC2 and anti-HMGB1 autoantibodies with higher disease activity in systemic lupus erythematosus patients

Syahidatulamali CS, Wan Syamimee WG, Azwany YN, Wong KK, Che Maraina CH

J Postgrad Med, 2017 9 2;63(4):257-261.
PMID: 28862243 DOI: 10.4103/jpgm.JPGM_499_16

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by numerous autoantibodies. In this study, we investigated the presence of anti-chloride intracellular channel 2 (anti-CLIC2) and anti-high mobility group box 1 (anti-HMGB1) autoantibodies in SLE patients (n = 43) versus healthy controls ([HCs] n = 43), and their association with serological parameters (antinuclear antibody [ANA], anti-double-stranded DNA [anti-dsDNA], and C-reactive protein [CRP]) and disease activity using Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score (active or inactive).
SETTINGS AND DESIGN: Case-control study at Rheumatology Clinic of Universiti Sains Malaysia Hospital.
SUBJECTS AND METHODS: The sera of SLE patients and HCs were tested for the presence of anti-CLIC2 and anti-HMGB1 autoantibodies using human recombinant proteins and ELISA methodologies. Other serological parameters were evaluated according to routine procedures, and patients' demographic and clinical data were obtained.
STATISTICAL ANALYSIS: Mann-Whitney U-test, Chi-square test, Fisher's exact test, and receiver operating characteristic analysis.
RESULTS: Anti-CLIC2 autoantibody levels were significantly higher in SLE patients compared to HCs (P = 0.0035), whereas anti-HMGB1 autoantibody levels were not significantly elevated (P = 0.7702). Anti-CLIC2 and anti-HMGB1 autoantibody levels were not associated with ANA pattern, anti-dsDNA, and CRP. Interestingly, SLEDAI score (≥6) was associated with anti-CLIC2 (P = 0.0046) and with anti-HMGB1 (P = 0.0091) autoantibody levels.
CONCLUSION: Our findings support the potential of using anti-CLIC2 autoantibodies as a novel biomarker for SLE patients. Both anti-CLIC2 and anti-HMGB1 autoantibody levels demonstrated potential in monitoring SLE disease activity.
Coexistence of antiphospholipid antibodies and cephalalgia

Islam MA, Alam F, Gan SH, Cavestro C, Wong KK

Cephalalgia, 2018 03;38(3):568-580.
PMID: 28952322 DOI: 10.1177/0333102417694881

Background The occurrence of antiphospholipid antibodies (aPLs) and headache comorbidity in the presence or absence of underlying autoimmune diseases remains unclear. Aim The aim of this review was to summarize the relationship between headache and aPLs based on evidences from cohort studies and case reports, in addition to examining the treatment strategies that resolved headache in aPLs-positive individuals.
Methods A comprehensive literature search was conducted through PubMed, ISI Web of Science and Google Scholar. A total of 559 articles were screened and the appropriate articles were selected based on quality and level of evidence.
Results Cohort studies (n = 27) from Europe, North America and Asia demonstrated comorbidity of aPLs and headache in antiphospholipid syndrome, systemic lupus erythematosus (SLE) and neuropsychiatric SLE patients. Significantly higher association between migraine and aPLs was observed (n = 170/779; p
Fulltext A 15-year single centre retrospective study of antiphospholipid syndrome patients from Northern Malaysia

Islam MA, Alam F, Gan SH, Sasongko TH, Wan Ghazali WS, Wong KK

Malays J Pathol, 2017 08;39(2):123-133.
PMID: 28866693 MyJurnal

BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPLs) based on the Sydney criteria. We aimed to explore the clinico-laboratory features and treatment strategies of APS patients retrospectively.
METHODOLOGY: The medical records of APS patients registered under Hospital Universiti Sains Malaysia (Kelantan state) between 2000 and 2015 were reviewed.
RESULTS: A total of 17 APS subjects (age 40.7 ± 12.8 years) including 11 primary (64.7%) and six secondary APS (35.3%) patients were identified. The follow-up period was 9.5 ± 6.7 years with male:female ratio of 1.0:4.7. Pregnancy morbidity was the most common clinical manifestation (11/14; 78.6%) followed by recurrent venous thrombosis (10/17; 58.8%). For other clinical features, menorrhagia was the most frequently observed manifestation (4/14; 28.6%) followed by aPLs-associated thrombocytopenia (4/17; 23.5%) and ovarian cyst (3/14; 21.4%). LA and aCL were positive in 94.1% (16/17) and 81.8% (9/11) of the patients, respectively. APTT value (76.7 ± 17.0 sec) was significantly high (p < 0.05). Low intensity warfarin alone was successful to maintain target INR (2.0 - 3.0) and prevent recurrence of thrombosis.
CONCLUSION: The tendency of pregnancy morbidity in this cohort of Malaysian Kelantanese APS patients was high compared to other previously reported APS cohorts. Low intensity warfarin was successful in preventing recurrence of thrombosis, however, APS women receiving long-term anticoagulants should be monitored for possible occurrence of menorrhagia and ovarian cysts.
Fulltext Presence of anticardiolipin antibodies in patients with dementia: A systematic review and meta-analysis

Islam MA, Alam F, Kamal MA, Gan SH, Sasongko TH, Wong KK

Front Aging Neurosci, 2017;9:250.
PMID: 28824414 DOI: 10.3389/fnagi.2017.00250

Growing evidences are supporting towards the involvement of antiphospholipid antibodies [aPLs e.g., lupus anticoagulant (LA), anticardiolipin (aCL) and anti-β2-glycoprotein I (anti-β2-GPI) antibodies] in various neurological manifestations including migraine, epilepsy and dementia in the presence or absence of autoimmune diseases such as antiphospholipid syndrome or systemic lupus erythematosus. The aim of this systematic review and meta-analysis was to assess the presence of aPLs in dementia patients without a diagnosis of any autoimmune disease. Electronic databases (e.g., PubMed, Web of Science, Scopus, ScienceDirect and Google Scholar) were searched without any year or language restrictions and based on the inclusion criteria, nine prospective case-control studies assessing only aCL were included involving 372 dementia patients and 337 healthy controls. No studies were found to assess the presence of both LA or anti-β2-GPI. The study-specific odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. We observed the prevalence of aCL in dementia was higher (32.80%) than that of controls (9.50%) e.g., 3.45 times higher risk of presenting with dementia than the controls, and significant presence of aCL antibodies was detected in dementia patients compared to controls (OR: 4.94, 95% CI: 2.66 - 9.16, p < 0.00001; I2 = 32%, p = 0.16). Publication bias was not observed from Egger's (p = 0.081) and Begg's tests (p = 0.180). Based on the study quality assessment using modified Newcastle-Ottawa Scale for case-control studies, seven of nine studies were of high methodological quality scoring ≥ 7 (median value). In summary, aCL antibodies were significantly present in dementia patients suggesting that aCL antibodies are generated due to the autoimmune-derived effects of dementia or there might be a potential causative role of this autoantibody in dementia pathogenesis.
Fulltext Zonula occludens-1 expression is reduced in nasal epithelial cells of allergic rhinitis patients

Siti Sarah CO, Nur Husna SM, Md Shukri N, Wong KK, Mohd Ashari NS

PeerJ, 2022;10:e13314.
PMID: 35480562 DOI: 10.7717/peerj.13314

Allergic rhinitis (AR) is a common allergic disease characterized by disruption of nasal epithelial barrier. In this study, we investigated the mRNA expression of zonula occludens-1 (ZO-1), ZO-2 and ZO-3 and histone deacetylase 1 (HDAC1) and HDAC2 in AR patients compared to healthy controls. RNA samples were extracted from nasal epithelial cells of house dust mites (HDMs)-sensitized AR patients and healthy controls (n = 28 in each group). The RNAs were reverse transcribed into cDNAs for measurement of ZO-1, ZO-2, ZO-3, HDAC1 and HDAC2 expression levels by quantitative PCR. The mRNA expression of ZO-1 was significantly decreased in AR patients compared to healthy controls (p = 0.010). No significant difference was observed in the expression levels of ZO-2, ZO-3, HDAC1 and HDAC2 in AR patients compared to healthy controls. We found significant associations of higher HDAC2 levels in AR patients with lower frequency of changing bedsheet (p = 0.043) and with AR patients sensitized to Dermatophagoides farinae (p = 0.041). Higher expression of ZO-2 was observed in AR patients who had pets (p = 0.007). In conclusion, our data indicated that ZO-1 expression was lower in AR patients contributing to decreased integrity of nasal epithelial barrier integrity, and HDAC2 may be involved in the pathogenesis of the disease.
Fulltext IL-4/IL-13 axis as therapeutic targets in allergic rhinitis and asthma

Nur Husna SM, Md Shukri N, Mohd Ashari NS, Wong KK

PeerJ, 2022;10:e13444.
PMID: 35663523 DOI: 10.7717/peerj.13444

Allergic rhinitis (AR) is a common disorder of the upper airway, while asthma is a disease affecting the lower airway and both diseases are usually comorbid. Interleukin (IL)-4 and IL-13 are critical cytokines in the induction of the pathogenic Th2 responses in AR and asthma. Targeting the IL-4/IL-13 axis at various levels of its signaling pathway has emerged as promising targeted therapy in both AR and asthma patient populations. In this review, we discuss the biological characteristics of IL-4 and IL-13, their signaling pathways, and therapeutic antibodies against each cytokine as well as their receptors. In particular, the pleiotropic roles of IL-4 and IL-13 in orchestrating Th2 responses in AR and asthma patients indicate that dual IL-4/IL-13 blockade is a promising therapeutic strategy for both diseases.
Fulltext Development of an effective clustering algorithm for older fallers

Goh CH, Wong KK, Tan MP, Ng SC, Chuah YD, Kwan BH

PLoS One, 2022;17(11):e0277966.
PMID: 36441703 DOI: 10.1371/journal.pone.0277966

Falls are common and often lead to serious physical and psychological consequences for older persons. The occurrence of falls are usually attributed to the interaction between multiple risk factors. The clinical evaluation of falls risks is time-consuming as a result, hence limiting its availability. The purpose of this study was, therefore, to develop a clustering-based algorithm to determine falls risk. Data from the Malaysian Elders Longitudinal Research (MELoR), comprising 1411 subjects aged ≥55 years, were utilized. The proposed algorithm was developed through the stages of: data pre-processing, feature identification and extraction with either t-Distributed Stochastic Neighbour Embedding (t-SNE) or principal component analysis (PCA)), clustering (K-means clustering, Hierarchical clustering, and Fuzzy C-means clustering) and characteristics interpretation with statistical analysis. A total of 1279 subjects and 9 variables were selected for clustering after the data pre-possessing stage. Using feature extraction with the t-SNE and the K-means clustering algorithm, subjects were clustered into low, intermediate A, intermediate B and high fall risk groups which corresponded with fall occurrence of 13%, 19%, 21% and 31% respectively. Slower gait, poorer balance, weaker muscle strength, presence of cardiovascular disorder, poorer cognitive performance, and advancing age were the key variables identified. The proposed fall risk clustering algorithm grouped the subjects according to features. Such a tool could serve as a case identification or clinical decision support tool for clinical practice to enhance access to falls prevention efforts.
Fulltext Anti-carbamylated protein antibodies in rheumatoid arthritis patients and their association with rheumatoid factor

Othman MA, Ghazali WSW, Hamid WZWA, Wong KK, Yahya NK

Saudi Med J, 2017 Sep;38(9):934-941.
PMID: 28889152 DOI: 10.15537/smj.2017.9.20841

OBJECTIVES: To evaluate levels of anti-carbamylated protein (anti-CarP) antibodies in rheumatoid arthritis (RA) patients and to determine their association with serological parameters and disease activity. Methods: A cross-sectional study involving 105 multiethnic RA patients (48 rheumatoid factor [RF]-positive and 57 RF-negative patients) was conducted at Hospital Universiti Sains Malaysia, Kelantan, Malaysia, from January 2015 to February 2016. Fifty healthy controls (HCs) were included. C-reactive protein (CRP), RF, anti-cyclic citrullinated peptide (anti-CCP) and anti-CarP antibodies were measured. A health assessment questionnaire (HAQ) was administered to the study participants and 28-joint Disease Activity Score (DAS28) were obtained. Results: The level of anti-CarP antibodies was significantly increased in the RA patients compared with HCs (p=0.042). The presence of anti-CarP antibodies was significantly associated with RF (p=0.019) and the HAQ (p=0.010). A significant association between the presence of anti-CarP antibodies and the DAS28 was not found (p=0.632). Conclusion: Our study provides further evidence that the level of anti-CarP antibodies is significantly elevated in RA patients.

Study site: Rheumatology clinic, Hospital Universiti Sains Malaysia
Performance evaluation of two multiplex qualitative RT-PCR assays for detection of respiratory infection in paediatric population

Ali U, Zainal M, Zainol Z, Tai CW, Tang SF, Lee PC, et al.

Malays J Pathol, 2023 Aug;45(2):215-227.
PMID: 37658531

INTRODUCTION: Acute respiratory infection (ARI) contributes to significant mortality and morbidity worldwide and is usually caused by a wide range of respiratory pathogens. This study aims to describe the performance of QIAstat-Dx® Respiratory Panel V2 (RP) and RespiFinder® 2SMART assays for respiratory pathogens detection.
MATERIALS AND METHODS: A total of 110 nasopharyngeal swabs (NPS) were collected from children aged one month to 12 years old who were admitted with ARI in UKMMC during a one-year period. The two qPCR assays were conducted in parallel.
RESULTS: Ninety-seven samples (88.2%) were positive by QIAstat-Dx RP and 86 (78.2%) by RespiFinder assay. The overall agreement on both assays was substantial (kappa value: 0.769) with excellent concordance rate of 96.95%. Using both assays, hRV/EV, INF A/H1N1 and RSV were the most common pathogens detected. Influenza A/H1N1 infection was significantly seen higher in older children (age group > 60 months old) (53.3%, p-value < 0.05). Meanwhile, RSV and hRV/EV infection were seen among below one-year-old children. Co-infections by two to four pathogens were detected in 17 (17.5%) samples by QIAstat-Dx RP and 12 (14%) samples by RespiFinder, mainly involving hRV/EV. Bacterial detection was observed only in 5 (4.5%) and 6 (5.4%) samples by QIAstat-Dx RP and RespiFinder, respectively, with Mycoplasma pneumoniae the most common detected.
CONCLUSION: The overall performance of the two qPCR assays was comparable and showed excellent agreement. Both detected various clinically important respiratory pathogens in a single test with simultaneous multiple infection detection. The use of qPCR as a routine diagnostic test can improve diagnosis and management.
WITHDRAWN: Adaptive Swarm Balancing Algorithms for rare-event prediction in imbalanced healthcare data

Li J, Liu LS, Fong S, Wong RK, Mohammed S, Fiaidhi J, et al.

Comput Med Imaging Graph, 2016 May 10.
PMID: 27236411 DOI: 10.1016/j.compmedimag.2016.05.001

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
WITHDRAWN: Improving classification of protein binders for virtual drug screening by novel swarm-based feature selection techniques

Li J, Fong S, Siu S, Mohammed S, Fiaidhi J, Wong KK

Comput Med Imaging Graph, 2016 Sep 30.
PMID: 27717712 DOI: 10.1016/j.compmedimag.2016.08.004

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Fulltext Peri-operative management of hysterostomy in a parturient with complete heart block, placenta accreta and intrauterine death

Rai V, Shariffuddin II, Chan YK, Muniandy RK, Wong KK, Singh S

BMC Anesthesiol, 2014;14:49.
PMID: 25002831 DOI: 10.1186/1471-2253-14-49

BACKGROUND: Complete heart block in pregnancy has serious implications particularly during the period of delivery. This is more so if the delivery is an operative one as the presence of heart block may produce haemodynamic instability in the intra operative period. We report a unique case of a pregnant mother with complete heart block undergoing hysterostomy, complicated by placenta accreta and intrauterine death.
CASE PRESENTATION: A 37 year old Malaysian Chinese parturient was admitted at 25 weeks gestation following a scan which suggested intrauterine death and placenta accreta. She was diagnosed to have congenital complete heart block after her first delivery eight years previously but a pacemaker was never inserted. These medical conditions make her extremely likely to experience massive bleeding and haemodynamic instability. Among the measures taken to optimise her pre-operatively were the insertion of a temporary intravenous pacemaker and embolization of the uterine arteries to minimize peri-operative blood loss. She successfully underwent surgery under general anesthesia, which was relatively uneventful and was discharged well on the fourth post-operative day.
CONCLUSION: Congenital heart block in pregnancies in the presence of potential massive bleeding is best managed by a team, with meticulous pre-operative optimization. Suggested strategies would include insertion of a temporary pacemaker and embolization of the uterine arteries to reduce the risk of the patient getting into life threatening situations.

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