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Fulltext Thalassemia major is a major risk factor for pediatric melioidosis in Kota Kinabalu, Sabah, Malaysia

Fong SM, Wong KJ, Fukushima M, Yeo TW

Clin Infect Dis, 2015 Jun 15;60(12):1802-7.
PMID: 25767257 DOI: 10.1093/cid/civ189

Melioidosis is an important cause of community-acquired infection in Southeast Asia and northern Australia. Studies from endemic countries have demonstrated differences in the epidemiology and clinical features among children diagnosed with melioidosis. This suggests that local data are needed to determine the risk factors and outcome in specific areas.
Fulltext Multisystem inflammatory syndrome in children and Kawasaki disease in infants: 2 sides of the same coin?

Kok HC, Nair D, Wong KJ, Fong SM

Clin Exp Pediatr, 2021 Nov;64(11):599-601.
PMID: 34619823 DOI: 10.3345/cep.2021.00913
Fulltext Moisture Absorption Effects on Mode II Delamination of Carbon/Epoxy Composites

Wong KJ, Johar M, Koloor SSR, Petrů M, Tamin MN

Polymers (Basel), 2020 Sep 22;12(9).
PMID: 32971855 DOI: 10.3390/polym12092162

It is necessary to consider the influence of moisture damage on the interlaminar fracture toughness for composite structures that are used for outdoor applications. However, the studies on the progressive variation of the fracture toughness as a function of moisture content M (%) is rather limited. In this regard, this study focuses on the characterization of mode II delamination of carbon/epoxy composites conditioned at 70 °C/85% relative humidity (RH). End-notched flexure test is conducted for specimens aged at various moisture absorption levels. Experimental results reveal that mode II fracture toughness degrades with the moisture content, with a maximum of 23% decrement. A residual property model is used to predict the variation of the fracture toughness with the moisture content. Through numerical simulations, it is found that the approaches used to estimate the lamina and cohesive properties are suitable to obtain reliable simulation results. In addition, the damage initiation is noticed during the early loading stage; however, the complete damage is only observed when the numerical peak load is achieved. Results from the present research could serve as guidelines to predict the residual properties and simulate the mode II delamination behavior under moisture attack.
Fulltext Thermal Delamination Modelling and Evaluation of Aluminium-Glass Fibre-Reinforced Polymer Hybrid

Chow ZP, Ahmad Z, Wong KJ, Koloor SSR, Petrů M

Polymers (Basel), 2021 Feb 04;13(4).
PMID: 33557350 DOI: 10.3390/polym13040492

This paper aims to propose a temperature-dependent cohesive model to predict the delamination of dissimilar metal-composite material hybrid under Mode-I and Mode-II delamination. Commercial nonlinear finite element (FE) code LS-DYNA was used to simulate the material and cohesive model of hybrid aluminium-glass fibre-reinforced polymer (GFRP) laminate. For an accurate representation of the Mode-I and Mode-II delamination between aluminium and GFRP laminates, cohesive zone modelling with bilinear traction separation law was implemented. Cohesive zone properties at different temperatures were obtained by applying trends of experimental results from double cantilever beam and end notched flexural tests. Results from experimental tests were compared with simulation results at 30, 70 and 110 °C to verify the validity of the model. Mode-I and Mode-II FE models compared to experimental tests show a good correlation of 5.73% and 7.26% discrepancy, respectively. Crack front stress distribution at 30 °C is characterised by a smooth gradual decrease in Mode-I stress from the centre to the edge of the specimen. At 70 °C, the entire crack front reaches the maximum Mode-I stress with the exception of much lower stress build-up at the specimen's edge. On the other hand, the Mode-II stress increases progressively from the centre to the edge at 30 °C. At 70 °C, uniform low stress is built up along the crack front with the exception of significantly higher stress concentrated only at the free edge. At 110 °C, the stress distribution for both modes transforms back to the similar profile, as observed in the 30 °C case.
Fulltext Displacement Rate Effects on the Mode II Shear Delamination Behavior of Carbon Fiber/Epoxy Composites

Low KO, Johar M, Israr HA, Gan KW, Rahimian Koloor SS, Petrů M, et al.

Polymers (Basel), 2021 Jun 06;13(11).
PMID: 34204033 DOI: 10.3390/polym13111881

This paper studies the influence of displacement rate on mode II delamination of unidirectional carbon/epoxy composites. End-notched flexure test is performed at displacement rates of 1, 10, 100 and 500 mm/min. Experimental results reveal that the mode II fracture toughness GIIC increases with the displacement, with a maximum increment of 45% at 100 mm/min. In addition, scanning electron micrographs depict that fiber/matrix interface debonding is the major damage mechanism at 1 mm/min. At higher speeds, significant matrix-dominated shear cusps are observed contributing to higher GIIC. Besides, it is demonstrated that the proposed rate-dependent model is able to fit the experimental data from the current study and the open literature generally well. The mode II fracture toughness measured from the experiment or deduced from the proposed model can be used in the cohesive element model to predict failure. Good agreement is found between the experimental and numerical results, with a maximum difference of 10%. The numerical analyses indicate crack jump occurs suddenly after the peak load is attained, which leads to the unstable crack propagation seen in the experiment.
Fulltext Case Report: Unusual High-Grade Diffuse Leptomeningeal Glioneuronal Tumor Mimicking Tuberculous Meningitis in a Child From an Endemic Region

Teh YG, Azizan N, Mohd Naim NA, Ng CY, Wong KJ, Mohd Zaki F

Front Pediatr, 2021;9:767614.
PMID: 34956980 DOI: 10.3389/fped.2021.767614

Background: Diffuse leptomeningeal glioneuronal tumor (DL-GNT) is a new entity described in the 2016 World Health Organization (WHO) classification of brain tumors. While DL-GNT is predominantly an indolent tumor that affects young boys, high-grade DL-GNT is unusual and seldom reported in children. Case Presentation: In this report, we describe the challenges and pitfalls associated with diagnosing this high-grade variant in a tuberculosis-endemic region. We highlight the importance of identifying non-typical imaging findings, i.e., non-enhancing cystic lesions with high T2 signal along the leptomeningeal surface, that may expedite the diagnosis of this condition. Histopathologic correlations with MR spectroscopy findings are also discussed. Conclusion: We provide the first clinical imaging report of utilizing MR spectroscopy to distinguish DL-GNT from tuberculosis with histopathologic correlation.
Fulltext An Extended Thickness-Dependent Moisture Absorption Model for Unidirectional Carbon/Epoxy Composites

Azizan A, Johar M, Karam Singh SS, Abdullah S, Koloor SSR, Petrů M, et al.

Polymers (Basel), 2021 Jan 30;13(3).
PMID: 33573112 DOI: 10.3390/polym13030440

Moisture absorption tests for materials that exhibit non-Fickian behavior generally require a relatively long period to reach saturation. Therefore, it would be beneficial to establish a relationship between the moisture content and the thickness to minimize the experimental time and cost. This research characterizes the moisture absorption behavior of AS4/8552 carbon/epoxy composites. Specimens were prepared at 4, 8, and 16 plies and immersed in distilled water at 60 °C. The relationship between the non-Fickian parameters (Fickian to non-Fickian maximum moisture content ratio ϕ, non-Fickian diffusivity per square thickness α, and non-Fickian initiation time to) and thickness was characterized using a thickness-dependent model. A comparison with other materials revealed that all three non-Fickian parameters are able to be fitted using a power law. Nevertheless, the upper boundary for the applicability of this model was not determined in this study. The Weibull distribution plots indicate that the probability of non-Fickian moisture absorption is influenced by ϕ and α at approximately 62% within a normalized thickness range of 2-3. In regards to to, it is 82% at a normalized thickness of 6. Therefore, the Weibull distribution is proposed for the assessment of non-Fickian moisture absorption based on the material's thickness.
Hyperexcretion of homocitrulline in a Malaysian patient with lysinuric protein intolerance

Habib A, Md Yunus Z, Azize NA, Ch'ng GS, Ong WP, Chen BC, et al.

Eur J Pediatr, 2013 Sep;172(9):1277-81.
PMID: 23358709 DOI: 10.1007/s00431-013-1947-1

Lysinuric protein intolerance (LPI; MIM 222700) is an inherited aminoaciduria with an autosomal recessive mode of inheritance. Biochemically, affected patients present with increased excretion of the cationic amino acids: lysine, arginine, and ornithine. We report the first case of LPI diagnosed in Malaysia presented with excessive excretion of homocitrulline. The patient was a 4-year-old male who presented with delayed milestones, recurrent diarrhea, and severe failure to thrive. He developed hyperammonemic coma following a forced protein-rich diet. Plasma amino acid analysis showed increased glutamine, alanine, and citrulline but decreased lysine, arginine and ornithine. Urine amino acids showed a marked excretion of lysine and ornithine together with a large peak of unknown metabolite which was subsequently identified as homocitrulline by tandem mass spectrometry. Molecular analysis confirmed a previously unreported homozygous mutation at exon 1 (235 G > A, p.Gly79Arg) in the SLC7A7 gene. This report demonstrates a novel mutation in the SLC7A7 gene in this rare inborn error of diamino acid metabolism. It also highlights the importance of early and efficient treatment of infections and dehydration in these patients.
CONCLUSION: The diagnosis of LPI is usually not suspected by clinical findings alone, and specific laboratory investigations and molecular analysis are important to get a definitive diagnosis.
A single-center pilot study in Malaysia on the clinical utility of whole-exome sequencing for inborn errors of immunity

Ripen AM, Chear CT, Baharin MF, Nallusamy R, Chan KC, Kassim A, et al.

Clin Exp Immunol, 2021 Nov;206(2):119-128.
PMID: 34060650 DOI: 10.1111/cei.13626

Primary immunodeficiency diseases refer to inborn errors of immunity (IEI) that affect the normal development and function of the immune system. The phenotypical and genetic heterogeneity of IEI have made their diagnosis challenging. Hence, whole-exome sequencing (WES) was employed in this pilot study to identify the genetic etiology of 30 pediatric patients clinically diagnosed with IEI. The potential causative variants identified by WES were validated using Sanger sequencing. Genetic diagnosis was attained in 46.7% (14 of 30) of the patients and categorized into autoinflammatory disorders (n = 3), diseases of immune dysregulation (n = 3), defects in intrinsic and innate immunity (n = 3), predominantly antibody deficiencies (n = 2), combined immunodeficiencies with associated and syndromic features (n = 2) and immunodeficiencies affecting cellular and humoral immunity (n = 1). Of the 15 genetic variants identified, two were novel variants. Genetic findings differed from the provisional clinical diagnoses in seven cases (50.0%). This study showed that WES enhances the capacity to diagnose IEI, allowing more patients to receive appropriate therapy and disease management.
Fulltext Disease Progression of WHIM Syndrome in an International Cohort of 66 Pediatric and Adult Patients

Geier CB, Ellison M, Cruz R, Pawar S, Leiss-Piller A, Zmajkovicova K, et al.

J Clin Immunol, 2022 Nov;42(8):1748-1765.
PMID: 35947323 DOI: 10.1007/s10875-022-01312-7

Warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) syndrome (WS) is a combined immunodeficiency caused by gain-of-function mutations in the C-X-C chemokine receptor type 4 (CXCR4) gene. We characterize a unique international cohort of 66 patients, including 57 (86%) cases previously unreported, with variable clinical phenotypes. Of 17 distinct CXCR4 genetic variants within our cohort, 11 were novel pathogenic variants affecting 15 individuals (23%). All variants affect the same CXCR4 region and impair CXCR4 internalization resulting in hyperactive signaling. The median age of diagnosis in our cohort (5.5 years) indicates WHIM syndrome can commonly present in childhood, although some patients are not diagnosed until adulthood. The prevalence and mean age of recognition and/or onset of clinical manifestations within our cohort were infections 88%/1.6 years, neutropenia 98%/3.8 years, lymphopenia 88%/5.0 years, and warts 40%/12.1 years. However, we report greater prevalence and variety of autoimmune complications of WHIM syndrome (21.2%) than reported previously. Patients with versus without family history of WHIM syndrome were diagnosed earlier (22%, average age 1.3 years versus 78%, average age 5 years, respectively). Patients with a family history of WHIM syndrome also received earlier treatment, experienced less hospitalization, and had less end-organ damage. This observation reinforces previous reports that early treatment for WHIM syndrome improves outcomes. Only one patient died; death was attributed to complications of hematopoietic stem cell transplantation. The variable expressivity of WHIM syndrome in pediatric patients delays their diagnosis and therapy. Early-onset bacterial infections with severe neutropenia and/or lymphopenia should prompt genetic testing for WHIM syndrome, even in the absence of warts.
ACORN (A Clinically-Oriented Antimicrobial Resistance Surveillance Network) II: protocol for case based antimicrobial resistance surveillance

Mo Y, Ding Y, Cao Y, Hopkins J, Ashley EA, Waithira N, et al.

Wellcome Open Res, 2023;8:179.
PMID: 37854055 DOI: 10.12688/wellcomeopenres.19210.2

Background: Antimicrobial resistance surveillance is essential for empiric antibiotic prescribing, infection prevention and control policies and to drive novel antibiotic discovery. However, most existing surveillance systems are isolate-based without supporting patient-based clinical data, and not widely implemented especially in low- and middle-income countries (LMICs). Methods: A Clinically-Oriented Antimicrobial Resistance Surveillance Network (ACORN) II is a large-scale multicentre protocol which builds on the WHO Global Antimicrobial Resistance and Use Surveillance System to estimate syndromic and pathogen outcomes along with associated health economic costs. ACORN-healthcare associated infection (ACORN-HAI) is an extension study which focuses on healthcare-associated bloodstream infections and ventilator-associated pneumonia. Our main aim is to implement an efficient clinically-oriented antimicrobial resistance surveillance system, which can be incorporated as part of routine workflow in hospitals in LMICs. These surveillance systems include hospitalised patients of any age with clinically compatible acute community-acquired or healthcare-associated bacterial infection syndromes, and who were prescribed parenteral antibiotics. Diagnostic stewardship activities will be implemented to optimise microbiology culture specimen collection practices. Basic patient characteristics, clinician diagnosis, empiric treatment, infection severity and risk factors for HAI are recorded on enrolment and during 28-day follow-up. An R Shiny application can be used offline and online for merging clinical and microbiology data, and generating collated reports to inform local antibiotic stewardship and infection control policies. Discussion: ACORN II is a comprehensive antimicrobial resistance surveillance activity which advocates pragmatic implementation and prioritises improving local diagnostic and antibiotic prescribing practices through patient-centred data collection. These data can be rapidly communicated to local physicians and infection prevention and control teams. Relative ease of data collection promotes sustainability and maximises participation and scalability. With ACORN-HAI as an example, ACORN II has the capacity to accommodate extensions to investigate further specific questions of interest.