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  1. Molecular identification and in vitro assessment of zoonotic-potential of a novel Orthobunyavirus isolated from broiler chicken in Malaysia
    M M, Azmi MA, Sani NI, Gilbert G, Reduan MHF
    Trop Biomed, 2023 Jun 01;40(2):194-198.
    PMID: 37650407 DOI: 10.47665/tb.40.2.011
    We have previously isolated a novel avian Orthobunyavirus, Kedah Fatal Kidney Syndrome (KFKS) virus from a broiler farm in Kedah, Malaysia in 2020 with a severe kidney lesion in chickens. The virus was designated as KFKS2_CS virus. Sequence analysis of partial nucleocapsid (N) and nonstructural (NSs) sequence of this virus showed the highest sequence identity with previous KFKS1 from Malaysia (100%) and 97% with a zoonotic Umbre (UMB) virus, which was reported to cause encephalitis in immunocompromised humans in India. Phylogenetic analysis revealed that this virus was clustered together with previous KFKS1 virus from Malaysia, UMB and Cristoli viruses. This study aimed to assess the zoonotic potential of this KFKS2_CS virus in vitro by determining its ability to inhibit the production of interferon (IFN) in human glioblastoma multiforme (GBM) brain cells using reverse-transcriptase polymerase reaction (RT-PCR). This virus blocked the production of interferon-a in this human brain cells. In conclusion, this KFKS2_CS virus may have a zoonotic potential and become a public health concern in the future.
  2. Fulltext Peripheral Intravenous Catheterisation in Obstetric Patients in the Hand or Forearm Vein: A Randomised Trial
    Tan PC, Mackeen A, Khong SY, Omar SZ, Noor Azmi MA
    Sci Rep, 2016 Mar 18;6:23223.
    PMID: 26987593 DOI: 10.1038/srep23223
    A peripheral intravenous catheter is often inserted as part of care during labour. The catheter is inserted into the back of the hand or lower forearm vein in usual practice. There is no trial data to guide the care provider on which is the better insertion site in any clinical setting. 307 women admitted to the labour ward who required insertion of intravenous catheter were randomised to back of hand or lower forearm vein catheter insertion. Catheter insertion is by junior to mid-grade providers. We evaluated insertion success at the first attempt, pain during insertion and catheter replacement due to malfunction as main outcomes. After catheter removal, we recorded patient satisfaction with site, future site preference and insertion site swelling, bruising, tenderness, vein thrombosis and pain. Insertion of a catheter into back of hand vein is more likely to be successful at the first attempt. Insertion pain score, catheter replacement rate, patient satisfaction, patient fidelity to site in a future insertion and insertion site complications rate are not different between trial arms. In conclusion, both insertion sites are suitable; the back of the hand vein maybe easier to cannulate and seems to be preferred by our frontline providers.
  3. Prevalence and risk factors of Toxoplasma infection - an update in Malaysian pregnant women
    Chemoh W, Nur Farhana MN, Noor Azmi MA, Si Lay K, Sawangjaroen N, Tan TC, et al.
    Trop Biomed, 2019 Sep 01;36(3):694-702.
    PMID: 33597491
    Toxoplasma gondii is a protozoan parasite that is capable of causing a zoonotic disease, known as toxoplasmosis. Vertical transmission of T. gondii from the mother to the fetus, during pregnancy may cause severe complications to the developing fetus. This current study aimed to determine the seroprevalence and investigate the associated risk factors of Toxoplasma infection in pregnant women (n=219) visiting the antenatal clinic at UMMC. While the elevated level of anti-Toxoplasma IgG and IgM antibodies indicates the presence of infection, it fails to differentiate between a past and a recent infection. Thus, the study also demonstrates the usefulness of IgG avidity in validating the timing of infection. The serum samples were tested for the presence of anti-Toxoplasma IgG and IgM antibodies by ELISA test, and the seropositive samples for both anti-Toxoplasma IgG and IgM antibodies were further evaluated by IgG avidity. The results showed that the overall prevalence of T. gondii seropositivity was 34.7%. Of these, 30.6% (67/219) were positive for anti-Toxoplasma IgG antibody only, 2.3% (5/219) were positive for anti-Toxoplasma IgM only, and the remaining 1.8% (4/219) was positive for both anti-Toxoplasma IgG and IgM antibodies. All of the pregnant women who were positive for both anti-Toxoplasma IgG and IgM antibody were found to have past infection when evaluated by IgG avidity. In this study, Malay ethnicity and the number of existing previous children were significantly associated with T. gondii seropositivity (p<0.05). Based on these findings, information and education on the transmission and prevention of congenital toxoplasmosis are very crucial as a public health effort towards a healthier society.
  4. Fulltext Immediate compared with on-demand maternal full feeding after planned caesarean delivery: a randomised trial
    Tan PC, Alzergany MM, Adlan AS, Noor Azmi MA, Omar SZ
    BJOG, 2017 Jan;124(1):123-131.
    PMID: 27418179 DOI: 10.1111/1471-0528.14211
    OBJECTIVE: To evaluate immediate compared with on-demand full maternal oral feeding after caesarean delivery STUDY DESIGN: A randomised trial.

    SETTING: Obstetric unit of a university hospital in Kuala Lumpur, Malaysia.

    POPULATION: Women admitted for a planned caesarean under spinal anaesthesia.

    METHODS: Participants were randomised to a sandwich meal served immediately on return to the ward or on-demand.

    MAIN OUTCOME MEASURES: Primary outcomes were patient satisfaction VAS (visual analog scale of 100 mm) on the feeding regimen and vomiting at 24 hours.

    RESULTS: 453 women were initially enrolled, 395 were randomised and available for analysis. Median (full range) patient satisfaction VAS scores were 82 (15-100) versus 84 (0-100) mm, P = 0.88 and vomiting rates were 1/197 (0.5%) versus 2/198 (1.0%), P > 0.99 for immediate compared with on-demand feeding, respectively. The immediate versus on-demand arms first ate at a median of 105 (35-210) versus 165 (45-385) minutes, P 

  5. First toddler mesenteric lymphatic malformation in Malaysia - A case report
    Soh CH, Emmanuel J, Rahizan MI, Azmi MA, Thillainayagam SD, Nurdaliza MB, et al.
    Med J Malaysia, 2022 Jan;77(1):104-106.
    PMID: 35087006
    This is the first reported case of a mesenteric lymphatic malformation in a toddler in Malaysia. It is a rare benign condition with incidence of 1 in 250,000 populations. Our patient presented to us at 2 years 11months old complaining of abdominal distension for 6 months without obstructive symptoms. Clinically there was a vague soft central abdominal mass. CT abdomen done revealed a large multiloculated intraperitoneal mesentery cystic mass within the central abdomen extending to pelvis. A semi-emergency laparotomy was performed. Intra-operatively the multiloculated mesenteric cyst measured 20cm x 30cm, adherent to the small bowel beginning at 12cm from duodeno-jejunal junction. Resection of the mesenteric cyst with adherent small bowel and primary anastomosis was done. Histopathological examination revealed multiple large lymphatic channels of various sizes in the mucosa and submucosa. Our patient has no signs of recurrence and remains symptom-free after 1 year since his surgery. Surgery with clear margins of resection is the recommended gold standard based on available literature. Type of surgical resection required will depend on the type of mesenteric lymphatic malformation. An awareness of this rare pathology is required to ensure proper management is given to these patients.
  6. Impact of low oxygen tension on stemness, proliferation and differentiation potential of human adipose-derived stem cells
    Choi JR, Pingguan-Murphy B, Wan Abas WA, Noor Azmi MA, Omar SZ, Chua KH, et al.
    Biochem Biophys Res Commun, 2014 May 30;448(2):218-24.
    PMID: 24785372 DOI: 10.1016/j.bbrc.2014.04.096
    Adipose-derived stem cells (ASCs) have been found adapted to a specific niche with low oxygen tension (hypoxia) in the body. As an important component of this niche, oxygen tension has been known to play a critical role in the maintenance of stem cell characteristics. However, the effect of O2 tension on their functional properties has not been well determined. In this study, we investigated the effects of O2 tension on ASCs stemness, differentiation and proliferation ability. Human ASCs were cultured under normoxia (21% O2) and hypoxia (2% O2). We found that hypoxia increased ASC stemness marker expression and proliferation rate without altering their morphology and surface markers. Low oxygen tension further enhances the chondrogenic differentiation ability, but reduces both adipogenic and osteogenic differentiation potential. These results might be correlated with the increased expression of HIF-1α under hypoxia. Taken together, we suggest that growing ASCs under 2% O2 tension may be important in expanding ASCs effectively while maintaining their functional properties for clinical therapy, particularly for the treatment of cartilage defects.
  7. Highly sensitive covalently functionalised integrated silicon nanowire biosensor devices for detection of cancer risk biomarker
    Mohd Azmi MA, Tehrani Z, Lewis RP, Walker KA, Jones DR, Daniels DR, et al.
    Biosens Bioelectron, 2014 Feb 15;52:216-24.
    PMID: 24060972 DOI: 10.1016/j.bios.2013.08.030
    In this article we present ultra-sensitive, silicon nanowire (SiNW)-based biosensor devices for the detection of disease biomarkers. An electrochemically induced functionalisation method has been employed to graft antibodies targeted against the prostate cancer risk biomarker 8-hydroxydeoxyguanosine (8-OHdG) to SiNW surfaces. The antibody-functionalised SiNW sensor has been used to detect binding of the 8-OHdG biomarker to the SiNW surface within seconds of exposure. Detection of 8-OHdG concentrations as low as 1 ng/ml (3.5 nM) has been demonstrated. The active device has been bonded to a disposable printed circuit which can be inserted into an electronic readout system as part of an integrated Point of Care (POC) diagnostic. The speed, sensitivity and ease of detection of biomarkers using SiNW sensors render them ideal for eventual POC diagnostics.
  8. Toxoplasmosis: prevalence and risk factors
    Nissapatorn V, Noor Azmi MA, Cho SM, Fong MY, Init I, Rohela M, et al.
    J Obstet Gynaecol, 2003 Nov;23(6):618-24.
    PMID: 14617462
    A total of 200 pregnant women were recruited in this cross-sectional study. The overall seroprevalence of toxoplasmosis in pregnant women was found to be 49%, in which 39%, 4% and 6% for anti-Toxoplasma IgG, IgM and both anti-Toxoplasma IgG and IgM antibodies, respectively. We found the differences in Toxoplasma seroprevalence rates among the races were significant: the highest rate was in the Malays (55.7%), followed by the Indian (55.3%) and the Chinese (19.4%) (P<0.05) populations. An increase in Toxoplasma seroprevalence with increasing parity was detected (P<0.05). Women with no children had a prevalence of 39.7%, while women with one or more than two children had a prevalence of 44.2% and 62.9%, respectively. In this study, there was no significant association between Toxoplasma seroprevalence and various possible risk factors in pregnant women (P>0.05). When multivariate analysis was performed, no significant association between Toxoplasma seroprevalence and history of contact with cats, consumption of undercooked meat and blood transfusion was found (P>0.05). We did not find any newly diagnosed cases of acute acquired toxoplasmosis in pregnancy during the study period.
  9. Fulltext Induction of labor compared to expectant management in term nulliparas with a latent phase of labor of more than 8 hours: a randomized trial
    Sargunam PN, Bak LLM, Tan PC, Vallikkannu N, Noor Azmi MA, Zaidi SN, et al.
    BMC Pregnancy Childbirth, 2019 Dec 11;19(1):493.
    PMID: 31829138 DOI: 10.1186/s12884-019-2602-2
    BACKGROUND: Prolonged latent phase of labor is associated with adverse maternal and neonatal outcomes. Preliminary data indicate that labor induction for prolonged latent phase may reduce cesarean delivery. We performed a study powered to Cesarean delivery to evaluate labor induction compared to expectant management in full term nulliparas hospitalized for persistent contractions but non-progressive to established labor after an overnight stay.

    METHODS: From 2015 and 2017, nulliparas, ≥ 39 weeks' gestation with prolonged latent phase of labor (persistent contractions after overnight hospitalization > 8 h), cervical dilation ≤3 cm, intact membranes and reassuring cardiotocogram were recruited. Participants were randomized to immediate induction of labor (with vaginal dinoprostone or amniotomy or oxytocin as appropriate) or expectant management (await labor for at least 24 h unless indicated intervention as directed by care provider). Primary outcome measure was Cesarean delivery.

    RESULTS: Three hundred eighteen women were randomized (159 to each arm). Data from 308 participants were analyzed. Cesarean delivery rate was 24.2% (36/149) vs. 23.3%, (37/159) RR 1.0 95% CI 0.7-1.6; P = 0.96 in induction of labor vs. expectant arms. Interval from intervention to delivery was 17.1 ± 9.9 vs. 40.1 ± 19.8 h; P 

  10. Enhancing coastal ecosystem resilience: Investigating the interplay between safety criteria and ferry employee's perceptions to address climate change impacts
    Azmi MA, Mokhtar K, Osnin NA, Razali Chan S, Albasher G, Ali A, et al.
    Environ Res, 2023 Dec 01;238(Pt 1):117074.
    PMID: 37678506 DOI: 10.1016/j.envres.2023.117074
    Coastal ecosystems play an important part in mitigating the effects of climate change. Coastal ecosystems are becoming more susceptible to climate change impacts due to human activities and maritime accidents. The global shipping industry, especially in Southeast Asia, has witnessed numerous accidents, particularly involving passenger ferries, resulting in injuries and fatalities in recent years. In order to mitigate the impact of climate change on coastal ecosystems, this study aimed to evaluate the relationship between employees' perceptions of safety criteria and their own safety behaviour on Langkawi Island, Malaysia. A straightforward random sampling technique was employed to collect data from 112 ferry employees aboard Malaysian-registered passenger boats by administering questionnaires. The findings shed light on the strong connection between providing safety instructions for passengers and safety behaviour among ferry workers. Safety instructions should contain climate-related information to successfully address the effects of climate change. The instructions might include guidance on responding to extreme weather events and understanding the potential consequences of sea-level rise on coastal communities. The ferry company staff should also expand their safe behaviour concept to include training and preparation for climate-related incidents. The need to recognise the interconnectedness between climate change, ferry safety and the protection of coastal ecosystems is emphasised in this study. The findings can be utilised by policymakers, regulatory agencies and ferry operators to design holistic policies that improve safety behaviour, minimise maritime mishaps and preserve the long-term sustainability of coastal ecosystems in the face of difficulties posed by climate change.
  11. Fulltext In situ normoxia enhances survival and proliferation rate of human adipose tissue-derived stromal cells without increasing the risk of tumourigenesis
    Choi JR, Pingguan-Murphy B, Wan Abas WA, Yong KW, Poon CT, Noor Azmi MA, et al.
    PLoS One, 2015;10(1):e0115034.
    PMID: 25615717 DOI: 10.1371/journal.pone.0115034
    Adipose tissue-derived stromal cells (ASCs) natively reside in a relatively low-oxygen tension (i.e., hypoxic) microenvironment in human body. Low oxygen tension (i.e., in situ normoxia), has been known to enhance the growth and survival rate of ASCs, which, however, may lead to the risk of tumourigenesis. Here, we investigated the tumourigenic potential of ASCs under their physiological condition to ensure their safe use in regenerative therapy. Human ASCs isolated from subcutaneous fat were cultured in atmospheric O2 concentration (21% O2) or in situ normoxia (2% O2). We found that ASCs retained their surface markers, tri-lineage differentiation potential, and self-renewal properties under in situ normoxia without altering their morphology. In situ normoxia displayed a higher proliferation and viability of ASCs with less DNA damage as compared to atmospheric O2 concentration. Moreover, low oxygen tension significantly up-regulated VEGF and bFGF mRNA expression and protein secretion while reducing the expression level of tumour suppressor genes p16, p21, p53, and pRb. However, there were no significant differences in ASCs telomere length and their relative telomerase activity when cultured at different oxygen concentrations. Collectively, even with high proliferation and survival rate, ASCs have a low tendency of developing tumour under in situ normoxia. These results suggest 2% O2 as an ideal culture condition for expanding ASCs efficiently while maintaining their characteristics.
  12. Fulltext Phenotypic and functional characterization of long-term cryopreserved human adipose-derived stem cells
    Yong KW, Pingguan-Murphy B, Xu F, Abas WA, Choi JR, Omar SZ, et al.
    Sci Rep, 2015;5:9596.
    PMID: 25872464 DOI: 10.1038/srep09596
    Cryopreservation represents an effective technique to maintain the functional properties of human adipose-derived stem cells (ASCs) and allows pooling of cells via long-term storage for clinical applications, e.g., cell-based therapies. It is crucial to reduce freezing injury during the cryopreservation process by loading the ASCs with the optimum concentration of suitable cryoprotective agents (CPAs). In this study, human ASCs were preserved for 3 months in different combinations of CPAs, including 1) 0.25 M trehalose; 2) 5% dimethylsulfoxide (DMSO); 3) 10% DMSO; 4) 5% DMSO + 20% fetal bovine serum (FBS); 5) 10% DMSO + 20% FBS; 6) 10% DMSO + 90% FBS. Interestingly, even with a reduction of DMSO to 5% and without FBS, cryopreserved ASCs maintained high cell viability comparable with standard cryomedium (10% DMSO + 90% FBS), with normal cell phenotype and proliferation rate. Cryopreserved ASCs also maintained their differentiation capability (e.g., to adipocytes, osteocytes and chondrocytes) and showed an enhanced expression level of stemness markers (e.g., NANOG, OCT-4, SOX-2 and REX-1). Our findings suggest that 5% DMSO without FBS may be an ideal CPA for an efficient long-term cryopreservation of human ASCs. These results aid in establishing standardized xeno-free long-term cryopreservation of human ASCs for clinical applications.
  13. Fulltext Cis-eQTL analysis and functional validation of candidate susceptibility genes for high-grade serous ovarian cancer
    Lawrenson K, Li Q, Kar S, Seo JH, Tyrer J, Spindler TJ, et al.
    Nat Commun, 2015 Sep 22;6:8234.
    PMID: 26391404 DOI: 10.1038/ncomms9234
    Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P≤10(-5)). For three cis-eQTL associations (P<1.4 × 10(-3), FDR<0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P=6 × 10(-10) for risk variants (P<10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
  14. Fulltext Common variants at the CHEK2 gene locus and risk of epithelial ovarian cancer
    Lawrenson K, Iversen ES, Tyrer J, Weber RP, Concannon P, Hazelett DJ, et al.
    Carcinogenesis, 2015 Nov;36(11):1341-53.
    PMID: 26424751 DOI: 10.1093/carcin/bgv138
    Genome-wide association studies have identified 20 genomic regions associated with risk of epithelial ovarian cancer (EOC), but many additional risk variants may exist. Here, we evaluated associations between common genetic variants [single nucleotide polymorphisms (SNPs) and indels] in DNA repair genes and EOC risk. We genotyped 2896 common variants at 143 gene loci in DNA samples from 15 397 patients with invasive EOC and controls. We found evidence of associations with EOC risk for variants at FANCA, EXO1, E2F4, E2F2, CREB5 and CHEK2 genes (P ≤ 0.001). The strongest risk association was for CHEK2 SNP rs17507066 with serous EOC (P = 4.74 x 10(-7)). Additional genotyping and imputation of genotypes from the 1000 genomes project identified a slightly more significant association for CHEK2 SNP rs6005807 (r (2) with rs17507066 = 0.84, odds ratio (OR) 1.17, 95% CI 1.11-1.24, P = 1.1×10(-7)). We identified 293 variants in the region with likelihood ratios of less than 1:100 for representing the causal variant. Functional annotation identified 25 candidate SNPs that alter transcription factor binding sites within regulatory elements active in EOC precursor tissues. In The Cancer Genome Atlas dataset, CHEK2 gene expression was significantly higher in primary EOCs compared to normal fallopian tube tissues (P = 3.72×10(-8)). We also identified an association between genotypes of the candidate causal SNP rs12166475 (r (2) = 0.99 with rs6005807) and CHEK2 expression (P = 2.70×10(-8)). These data suggest that common variants at 22q12.1 are associated with risk of serous EOC and CHEK2 as a plausible target susceptibility gene.
  15. Fulltext Identification of six new susceptibility loci for invasive epithelial ovarian cancer
    Kuchenbaecker KB, Ramus SJ, Tyrer J, Lee A, Shen HC, Beesley J, et al.
    Nat Genet, 2015 Feb;47(2):164-71.
    PMID: 25581431 DOI: 10.1038/ng.3185
    Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.
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