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  1. Zainal Abidin N, Noorizhab MNF, Teh LK, Lim WF, Mohd Noordin N, Aziz ZA, et al.
    Microbiol Resour Announc, 2021 Jun 24;10(25):e0035221.
    PMID: 34165334 DOI: 10.1128/MRA.00352-21
    In the battle against tuberculosis (TB), plasticity of the Mycobacterium tuberculosis genome is believed to contribute to the pathogen's virulence and drug resistance. Here, we report 10 draft genome sequences of clinical M. tuberculosis isolated in Malaysia as the basis for understanding the genome plasticity of the M. tuberculosis isolates.
  2. Yap WY, Che Ab Aziz ZA, Azami NH, Al-Haddad AY, Khan AA
    Med Princ Pract, 2017;26(5):464-469.
    PMID: 28934753 DOI: 10.1159/000481623
    OBJECTIVE: To evaluate the push-out bond strength and failure modes of different sealers/obturation systems to intraradicular dentin at 2 weeks and 3 months after obturation compared to AH Plus®/gutta-percha.

    MATERIALS AND METHODS: A total of 180 root slices from 60 single-canal anterior teeth were prepared and assigned to 5 experimental groups (n = 36 in each group), designated as G1 (AH Plus®/gutta-percha), G2 (TotalFill BC™ sealer/BC-coated gutta-percha), G3 (TotalFill BC™ sealer/gutta-percha), G4 (EndoREZ® sealer/EndoREZ®-coated gutta-percha), and G5 (EndoREZ® sealer/gutta-percha). Push-out bond strengths of 18 root slices in each group were assessed at 2 weeks and the other 18 at 3 months after obturation using a universal testing machine. Data were analyzed using repeated measures ANOVA. An independent t test was used to compare the mean push-out bond strength for each group at 2 weeks and 3 months after obturation.

    RESULTS: The mean push-out bond strengths of G4 and G5 were significantly lower than those of G1, G2, and G3 (p < 0.05) at both 2 weeks (G1: 1.46 ± 0.29 MPa, G2: 1.74 ± 0.43 MPa, G3: 1.74 ± 0.43 MPa, G4: 0.66 ± 0.31 MPa, G5: 0.74 ± 0.47 MPa) and 3 months after obturation (G1: 1.70 ± 1.05 MPa, G2: 3.69 ± 1.20 MPa, G3: 2.84 ± 0.83 MPa, G4: 0.14 ± 0.05 MPa, G5: 0.24 ± 0.10 MPa). The mean push-out bond strengths of G2 (3.69 ± 1.20 MPa) and G3 (2.84 ± 0.83 MPa) were higher at 3 months compared to 2 weeks after obturation (G2: 1.74 ± 0.43 MPa, G3: 1.33 ± 0.29 MPa).

    CONCLUSION: The TotalFill BC™ obturation system (G2) and the TotalFill BC™ sealer/gutta-percha (G3) showed comparable bond strength to AH Plus®. Their bond strength increased over time, whereas the EndoREZ® obturation system (G4) and EndoREZ sealer (G5) had low push-out bond strength which decreased over time.

  3. Wei LK, Au A, Menon S, Griffiths LR, Kooi CW, Irene L, et al.
    J Stroke Cerebrovasc Dis, 2017 Nov;26(11):2482-2493.
    PMID: 28760411 DOI: 10.1016/j.jstrokecerebrovasdis.2017.05.048
    INTRODUCTION: The association between ischemic stroke and genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR; 677C>T and 1298A>C), endothelial nitric oxide synthase (eNOS; -786T>C, +894G>T, and variable number tandem repeat [VNTR]), phosphodiesterase 4D (PDE4D; SNPs 83 and 87), angiotensin-converting enzyme (ACE) I/D, angiotensinogen (AGT) 235M>T, paraoxonase 1 (PON1) 192Q>R, and apolipoprotein E (ApoE) ε2ε3ε4 remains inconclusive. Therefore, this updated meta-analysis aimed to clarify the presumed influence of genetic polymorphisms on ischemic stroke by meta-analyzing the comprehensive coverage of all individual association studies.

    METHODS: All case-control studies published in different languages such as English, Japanese, Korean, Spanish, Chinese, Hungarian, Ukrainian, or Russian were identified from databases. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated via fixed- and random-effect models. Sensitivity analysis, heterogeneity test, Hardy Weinberg Equilibrium, and Egger's regression analyses were performed in this study.

    RESULTS: A total of 490 case-control studies with 138,592 cases and 159,314 controls were included in this meta-analysis. Pooled ORs from all the genetic models indicated that MTHFR 677TT and 1298CC, eNOS +894TT and VNTR, PDE4D SNP 83, ACE DD, AGT 235TT, PON1 192RR, and ApoE ε4 polymorphisms were increasing the risks of ischemic stroke. Nevertheless, PDE4D SNP 87 and eNOS -786T>C polymorphisms are not associated with ischemic stroke risks.

    CONCLUSIONS: Hence, the evidence from this meta-analysis concluded that MTHFR (677C>T and 1298A>C), eNOS (+894G>T and VNTR), PDE4D SNP 83, ACE I/D, AGT 235M>T, PON1 192Q>R, and ApoE ε2ε3ε4 polymorphisms predispose individuals to ischemic stroke.

  4. Tan AH, Lohmann K, Tay YW, Lim JL, Ahmad-Annuar A, Ramli N, et al.
    Parkinsonism Relat Disord, 2020 10;79:34-39.
    PMID: 32861104 DOI: 10.1016/j.parkreldis.2020.08.015
    BACKGROUND: An improved understanding of the genetic determinants of Parkinson's disease (PD) in underrepresented populations, and better characterization of genotype-phenotype correlations in monogenic PD, are needed. Scarce literature exists regarding the genetic aetiology of PD in Malays, who comprise 200 million individuals in South-East Asia. Phenotypic data regarding PARK-PINK1 are also limited.

    METHODS: A multi-ethnic cohort of PD patients from Malaysia (n = 499, including 185 Malays) were tested using a next-generation sequencing-based PD gene panel. The prevalence and clinico-radiological features of patients with the PINK1 p. Leu347Pro mutation are described. This mutation has previously only been reported in people of Filipino or Chamorro (native Guamanian) ancestry.

    RESULTS: Homozygous p. Leu347Pro mutations were found in five unrelated Malay patients, yielding a prevalence of 6.9% among Malays with PD onset ≤50 years (2.7% of the Malay group overall). This variant was not detected in the homozygous state in 300 Malay controls, but two were heterozygous carriers (0.67%) indicating a relatively high population frequency in keeping with the high frequency of PARK-PINK1 among Malay patients. Interesting clinical features were observed, e.g., differences in the age at PD onset and clinical progression, despite having the same point mutations. Previously unreported brain MRI abnormalities involving the corticospinal tract and hypothalamus, and "loss of the swallow tail" sign, were documented.

    CONCLUSIONS: This report contributes to the very limited literature on PD genetics in the Malay population, and more broadly to the epidemiological, phenotypic and neuroimaging characterization of PARK-PINK1. It also further supports the pathogenicity of the p. Leu347Pro variant.

  5. Senin A, Noordin NM, Sani JAM, Mahat D, Donadel M, Scobie HM, et al.
    PLoS One, 2024;19(3):e0298730.
    PMID: 38483868 DOI: 10.1371/journal.pone.0298730
    INTRODUCTION: A lateral flow rapid diagnostic test (RDT) enables detection of measles specific immunoglobulin M (IgM) antibody in serum, capillary blood, and oral fluid with accuracy consistent with enzyme immunoassay (EIA). The objectives of the study were: 1) to assess measles RDT inter-reader agreement between two clinic staff; 2) to assess the sensitivity and specificity of the measles RDT relative to standard surveillance testing in a low transmission setting; 3) to evaluate the knowledge, attitudes, and practices of staff in clinics using the RDT; and 4) to assess the impact of RDT testing on the measles public health response in Malaysia.

    MATERIALS AND METHODS: The clinic-based prospective evaluation included all suspected measles cases captured by routine measles surveillance at 34 purposely selected clinics in 15 health districts in Malaysia between September 2019 and June 2020, following day-long regional trainings on RDT use. Following informed consent, four specimens were collected from each suspected case, including those routinely collected for standard surveillance [serum for EIA and throat swabs for quantitative reverse transcriptase polymerase chain reaction (RT-qPCR)] together with capillary blood and oral fluid tested with RDTs during the study. RDT impact was evaluated by comparing the rapidity of measles public health response between the pre-RDT implementation (December 2018 to August 2019) and RDT implementation periods (September 2019 to June 2020). To assess knowledge, attitudes, and practices of RDT use, staff involved in the public health management of measles at the selected sites were surveyed.

    RESULTS: Among the 436 suspect cases, agreement of direct visual readings of measles RDT devices between two health clinic staff was 99% for capillary blood (k = 0.94) and 97% for oral fluid (k = 0.90) specimens. Of the total, 45 (10%) were positive by measles IgM EIA (n = 44, including five also positive by RT-qPCR) or RT-qPCR only (n = 1), and 38 were positive by RDT (using either capillary blood or oral fluid). Using measles IgM EIA or RT-qPCR as reference, RDT sensitivity using capillary blood was 43% (95% CI: 30%-58%) and specificity was 98% (95% CI: 96%-99%); using oral fluid, sensitivity (26%, 95% CI: 15%-40%) and specificity (97%, 95% CI: 94%-98%) were lower. Nine months after training, RDT knowledge was high among staff involved with the public health management of measles (average quiz score of 80%) and was highest among those who received formal training (88%), followed by those trained during supervisory visits (83%). During the RDT implementation period, the number of days from case confirmation until initiation of public response decreased by about 5 days.

    CONCLUSION: The measles IgM RDT shows >95% inter-reader agreement, high retention of RDT knowledge, and a more rapid public health response. However, despite ≥95% RDT specificity using capillary blood or oral fluid, RDT sensitivity was <45%. Higher-powered studies using highly specific IgM assays and systematic RT-qPCR for case confirmation are needed to establish the role of RDT in measles elimination settings.

  6. Ramadan NS, Wessjohann LA, Mocan A, Vodnar DC, El-Sayed NH, El-Toumy SA, et al.
    Molecules, 2020 May 22;25(10).
    PMID: 32455938 DOI: 10.3390/molecules25102423
    Averrhoa carambola L. is a tropical tree with edible fruit that grows at different climatic conditions. Despite its nutritive value and reported health benefits, it is a controversial fruit owing to its rich oxalate content. The present study aimed at investigating aroma and nutrient primary metabolites distribution in A. carambola fruits grown in Indonesia, Malaysia (its endemic origin) versus Egypt, and at different ripening stages. Two techniques were employed to assess volatile and non-volatile metabolites including headspace solid-phase micro-extraction (HS-SPME) joined with gas chromatography coupled with mass-spectrometry (GC-MS) and GC-MS post silylation, respectively. Twenty-four volatiles were detected, with esters amounting for the major class of volatiles in Egyptian fruit at ca. 66%, with methyl caproate as the major component, distinguishing it from other origins. In contrast, aldehydes predominated tropically grown fruits with the ether myristicin found exclusively in these. Primary metabolites profiling led to the identification of 117 metabolites viz. sugars, polyols and organic acids. Fructose (38-48%) and glucose (21-25%) predominated sugar compositions in ripe fruits, whereas sorbitol was the major sugar alcohol (2.4-10.5%) in ripe fruits as well. Oxalic acid, an anti-nutrient with potential health risks, was the major organic acid detected in all the studied fruits (1.7-2.7%), except the Malaysian one (0.07%). It increases upon fruit ripening, including considerable amounts of volatile oxalate esters detected via SPME, and which must not be omitted in total oxalate determinations for safety assessments.
  7. Noorizhab Fakhruzzaman MN, Abidin NZ, Aziz ZA, Lim WF, Richard JJ, Noorliza MN, et al.
    Int J Mycobacteriol, 2019 12 4;8(4):320-328.
    PMID: 31793500 DOI: 10.4103/ijmy.ijmy_144_19
    Background: Tuberculosis (TB) is still a major health problem in Malaysia with thousands of cases reported yearly. This is further burdened with the emergence of multidrug-resistant TB (MDR-TB). Whole-genome sequencing (WGS) provides high-resolution molecular epidemiological data for the accurate determination of Mycobacterium tuberculosis complex (MTBC) lineages and prediction of the drug-resistance patterns. This study aimed to investigate the diversity of MTBC in Malaysia in terms of lineage and drug-resistance patterns of the clinical MTBC isolates using WGS approach.

    Methods: The genomes of 24 MTBC isolated from sputum and pus samples were sequenced. The phenotypic drug susceptibility testing (DST) of the isolates was determined for ten anti-TB drugs. Bioinformatic analysis comprising genome assembly and annotation and single-nucleotide polymorphism (SNP) analysis in genes associated with resistance to the ten anti-TB drugs were done on each sequenced genome.

    Results: The draft assemblies covered an average of 97% of the expected genome size. Eleven isolates were aligned to the Indo-Oceanic lineage, eight were East-Asian lineage, three were East African-Indian lineage, and one was of Euro-American and Bovis lineages, respectively. Twelve of the 24 MTBC isolates were phenotypically MDR M. tuberculosis: one is polyresistance and another one is monoresistance. Twenty-six SNPs across nine genes associated with resistance toward ten anti-TB drugs were detected where some of the mutations were found in isolates that were previously reported as pan-susceptible using DST. A haplotype consisting of 65 variants was also found among the MTBC isolates with drug-resistance traits.

    Conclusions: This study is the first effort done in Malaysia to utilize 24 genomes of the local clinical MTBC isolates. The high-resolution molecular epidemiological data obtained provide valuable insights into the mechanistic and epidemiological qualities of TB within the vicinity of Southeast Asia.

  8. Nogueira RG, Qureshi MM, Abdalkader M, Martins SO, Yamagami H, Qiu Z, et al.
    Neurology, 2021 Jun 08;96(23):e2824-e2838.
    PMID: 33766997 DOI: 10.1212/WNL.0000000000011885
    OBJECTIVE: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods.

    METHODS: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases.

    RESULTS: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions.

    CONCLUSIONS: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

  9. Mustafa S, Bahar A, Aziz ZA, Suratman S
    J Environ Manage, 2016 Jan 01;165:159-166.
    PMID: 26433356 DOI: 10.1016/j.jenvman.2015.09.026
    Analytical study of the influence of both the pumping well discharge rate and pumping time on contaminant transport and attenuation is significant for hydrological and environmental science applications. This article provides an analytical solution for investigating the influence of both pumping time and travelling time together for one-dimensional contaminant transport in riverbank filtration systems by using the Green's function approach. The basic aim of the model is to understand how the pumping time and pumping rate, which control the travelling time, can affect the contaminant concentration in riverbank filtration systems. Results of analytical solutions are compared with the results obtained using a MODFLOW numerical model. Graphically, it is found that both analytical and numerical solutions have almost the same behaviour. Additionally, the graphs indicate that any increase in the pumping rate or simulation pumping time should increase the contamination in groundwater. The results from the proposed analytical model are well matched with the data collected from a riverbank filtration site in France. After this validation, the model is then applied to the first pilot project of a riverbank filtration system conducted in Malaysia. Sensitivity analysis results highlight the importance of degradation rates of contaminants on groundwater quality, for which higher utilization rates lead to the faster consumption of pollutants.
  10. Mustafa S, Bahar A, Aziz ZA, Darwish M
    J Contam Hydrol, 2020 Aug;233:103662.
    PMID: 32569923 DOI: 10.1016/j.jconhyd.2020.103662
    This article provides an analytical solute transport model to investigate the potential of groundwater contamination by polluted surface water in a two dimensional domain. The clogging of streambed which makes the aquifer partially penetrated by the stream, is considered in the model. The impacts of pumping process, hydraulic conductivity and clogging layer on the quality of water produced from nearby drinking water wells are evaluated. It is found that results are consistent with numerical simulation conducted by MODFLOW software. Moreover, the model is applied using data of contamination occurrence in Malaysia, where high contaminants concentrations are found close to streams. Results show that the pumping activities (rate and time period) are crucial factors when evaluating the risk of groundwater contamination from surface water. Additionally, this study illustrates that the increase in either hydraulic conductivity or leakance coefficient parameters due to the clogging layer will enlarge the area of contamination. The model is able to determine the suitable pumping rate and location of the well so that the contamination plume never reaches the extraction well, which is useful in constructing riverbank filtration sites.
  11. Mustafa S, Darwish M, Bahar A, Aziz ZA
    Ground Water, 2019 09;57(5):756-763.
    PMID: 30740693 DOI: 10.1111/gwat.12868
    Analytical studies for well design adjacent to river banks are the most significant practical task in cases involving the efficiency of riverbank filtration systems. In times when high pollution of river water is joined with increasing water demand, it is necessary to design pumping wells near the river that provide acceptable amounts of river water with minimum contaminant concentrations. This will guarantee the quality and safety of drinking water supplies. This article develops an analytical solution based on the Green's function approach to solve an inverse problem: based on the required level of contaminant concentration and planned pumping time period, the shortest distance to the riverbank that has the maximum percentage of river water is determined. This model is developed in a confined and homogenous aquifer that is partially penetrated by the stream due to the existence of clogging layers. Initially, the analytical results obtained at different pumping times, rates and with different values of initial concentration are checked numerically using the MODFLOW software. Generally, the distance results obtained from the proposed model are acceptable. Then, the model is validated by data related to two pumping wells located at the first riverbank filtration pilot project conducted in Malaysia.
  12. Mustafa S, Bahar A, Aziz ZA, Darwish M
    Environ Sci Pollut Res Int, 2022 Dec;29(58):87114-87131.
    PMID: 35802329 DOI: 10.1007/s11356-022-21402-8
    Modeling three-dimensional contaminant transport released from arbitrary shape source geometries is useful in hydrological and environmental sciences. This article produces several analytical solutions for three-dimensional contaminant transport in a homogeneous and isotropic aquifer by using Green's function with the groundwater flow which is assumed to be in three directions. The solutions are obtained for both finite depth aquifer and semi-infinite depth aquifer. Various types of sources are discussed: point, line, plane, or cuboid sources. The continuous and instantaneous sources are also investigated. A MATLAB coding is developed to calculate the numerical integrals which occur at the solutions. Some solutions are verified with the solutions obtained in the literature. This study confirms the effect of groundwater velocities in all directions on the degree and the directions of contaminant spreading. Additionally, the results highlight the significant effect of the geometrical shape of the contaminant sources on contaminant concentrations for instantaneous and continuous sources. In particular, the cuboid source and the horizontal rectangular source provide the highest concentrations. The analytical solutions developed in this article can be applied for a wide range of contaminant transport.
  13. Moses LB, Abu Bakar MF, Mamat H, Aziz ZA
    PMID: 33603822 DOI: 10.1155/2021/8811236
    The present study was conducted to determine the cytotoxicity effect of Eurycoma longifolia (Jack.) leaf extracts and also its possible anticancer mechanism of action against breast cancer cell lines: non-hormone-dependent MDA-MB-231 and hormone-dependent MCF-7. The leaves of E. longifolia were processed into unfermented and fermented batches before drying using freeze and microwave-oven drying techniques. Obtained extracts were tested for cytotoxicity effect using MTT assay and phenolic determination using HPLC-DAD technique. The most toxic sample was analyzed for its apoptotic cell quantification, cell cycle distribution, and the expression of caspases and apoptotic protein using flow cytometry technique. Fragmentation of DNA was tested using an agarose gel electrophoresis system. The results determined that the unfermented freeze-dried leaf extract was the most toxic towards MDA-MB-231 and MCF-7 cells, in a dose-dependent manner. This extract contains the highest phenolics of gallic acid, chlorogenic acid, ECG, and EGCG. The DNA fragmentation was observed in both cell lines, where cell cycle was arrested at the G 2/M phase in MCF-7 cells and S phase in MDA-MB-231 cells. The number of apoptotic cells for MDA-MB-231 was increased when the treatment was prolonged from 24 h to 48 h but slightly decreased at 72 h, whereas apoptosis in MCF-7 cells occurred in a time-dependent manner. There were significant activities of cytochrome c, caspase-3, Bax, and Bcl-2 apoptotic protein in MDA-MB-231 cells, whereas MCF-7 cells showed significant activities for caspase-8, cytochrome c, Bax, p53, and Bcl-2 apoptotic protein. These results indicate the ability of unfermented freeze-dried leaf extract of E. longifolia to induce apoptosis cell death on MDA-MB-231 and MCF-7, as well as real evidence on sample preparation effect towards its cytotoxicity level.
  14. Mohamad Azranyi M, Aziz ZA, Ishak D, Mohd Nais NF, Elias ZA, Sulaiman NAF, et al.
    J Med Microbiol, 2024 Feb;73(2).
    PMID: 38380521 DOI: 10.1099/jmm.0.001809
    Introduction. Non-tuberculous Mycobacteria (NTM) is a group of mycobacteria distinct from the Mycobacterium tuberculosis complex. They can cause opportunistic infections, especially in immunocompromised individuals.Gap Statement. Over the last few years, there has been a growing concern regarding the distribution and antimicrobial resistance of NTM in Malaysia. however, a comprehensive study to fully grasp the NTM situation has yet to be conducted.Aim. This study aimed to investigate the species distribution and antimicrobial susceptibility patterns of NTM isolated from clinical samples in Malaysia from 2018 to 2022.Methodology. A retrospective analysis was conducted on NTM isolates obtained from various clinical specimens over a span of five years. The isolates were identified using phenotypic and molecular techniques, and antimicrobial susceptibility profiles for clinically significant isolates were determined using minimum inhibitory concentration.Results. The study revealed a diverse distribution of NTM species in Malaysia, with Mycobacteroides abscessus complex and Mycobacterium avium complex emerging as the most predominant. Furthermore, the antimicrobial susceptibility patterns showed varying degrees of resistance to commonly used antibiotics, highlighting the significance of treatment tailored to susceptibility testing results.Conclusion. This study provides valuable perspective into the epidemiology of NTM in Malaysia. The information gained from this study should prove useful for empirically treating serious NTM infections prior to species identification and the availability of antimicrobial susceptibility testing results.
  15. Mat Yudin Z, Ali K, Wan Ahmad WMA, Ahmad A, Khamis MF, Brian Graville Monteiro N', et al.
    Eur J Dent Educ, 2020 Feb;24(1):163-168.
    PMID: 31698535 DOI: 10.1111/eje.12480
    AIMS: To evaluate the self-perceived preparedness of final-year dental undergraduate students in dental public universities in Malaysia.

    METHODS: Final-year dental undergraduate students from six dental public universities in Malaysia were invited to participate in an online study using a validated Dental Undergraduates Preparedness Assessment Scale DU-PAS.

    RESULTS: In total, about 245 students responded to the online questionnaire yielding a response rate of 83.05%. The age range of the respondents was 23-29 years with a mean age of 24.36 (SD 0.797). The total score obtained by the respondents was ranged from 48 to 100 with a mean score of 79.56 (SD 13.495). Weaknesses were reported in several clinical skills, cognitive and behavioural attributes.

    CONCLUSIONS: The preparedness of undergraduate students at six dental institutions in Malaysia was comparable to students from developed countries. The dental undergraduate preparedness assessment scale is a useful tool, and dental institutions may be used for self-assessment as well as to obtain feedback from the supervisors.

  16. Inoue Y, Kaneko S, Hsieh PF, Meshram C, Lee SA, Aziz ZA, et al.
    Epilepsia, 2019 03;60 Suppl 1:60-67.
    PMID: 30869167 DOI: 10.1111/epi.14645
    This post hoc analysis assessed the long-term safety, tolerability, and efficacy of perampanel in Asian patients with refractory focal seizures; an additional analysis assessed the effect of perampanel on focal impaired awareness seizures (FIAS) with focal to bilateral tonic-clonic (FBTC) seizures. In this subanalysis, data from Asian patients ≥12 years of age who had focal seizures with FBTC seizures despite taking one to 3 concomitant antiepileptic drugs at baseline, and who had entered either the long-term extension phase of 3 phase-3 perampanel trials (study 307) or the 10-week extension phase of study 335, were analyzed for the effect of perampanel on duration of exposure, safety, and seizure outcomes. Of 874 Asian patients included in the analysis, 205 had previously received placebo during the double-blind phase-3 trials and 669 had previously received perampanel 2-12 mg/day; 313 had FIAS with FBTC seizures at core study baseline. The median duration of exposure to perampanel was 385.0 days, and the retention rate at one year was 62.6%. Overall, during the first 52 weeks of perampanel treatment, 777 patients (88.9%) had treatment-emergent adverse events (TEAEs), most of which were mild to moderate in severity. The most frequent TEAEs were dizziness (47.1%), somnolence (22.3%), and nasopharyngitis (17.4%). During the first 52 weeks of perampanel treatment, median percent change in seizure frequency per 28 days from pre-perampanel baseline for all focal seizures was -28.1%, and -51.7% for FIAS with FBTC seizures. The 50% responder rate relative to pre-perampanel baseline for all focal seizures was 33.8%, and 51.1% for FIAS with FBTC seizures. Long-term treatment with perampanel in Asian patients had safety, tolerability, and efficacy similar to that of the global population in the phase-3 trials and extension study 307. The safety profile and response rate suggest benefit for an Asian population of patients with refractory epilepsy.
  17. Govindasamy V, Ronald VS, Abdullah AN, Ganesan Nathan KR, Aziz ZA, Abdullah M, et al.
    Cytotherapy, 2011 Nov;13(10):1221-33.
    PMID: 21929379 DOI: 10.3109/14653249.2011.602337
    BACKGROUND AIMS. Dental pulp stromal cells (DPSC) are considered to be a promising source of stem cells in the field of regenerative therapy. However, the usage of DPSC in transplantation requires large-scale expansion to cater for the need for clinical quantity without compromising current good manufacturing practice (cGMP). Existing protocols for cell culturing make use of fetal bovine serum (FBS) as a nutritional supplement. Unfortunately, FBS is an undesirable additive to cells because it carries the risk of transmitting viral and prion diseases. Therefore, the present study was undertaken to examine the efficacy of human platelet lysate (HPL) as a substitute for FBS in a large-scale set-up. METHODS. We expanded the DPSC in Dulbecco's modified Eagle's medium-knock-out (DMEM-KO) with either 10% FBS or 10% HPL, and studied the characteristics of DPSC at pre- (T25 culture flask) and post- (5-STACK chamber) large-scale expansion in terms of their identity, quality, functionality, molecular signatures and cytogenetic stability. RESULTS. In both pre- and post-large-scale expansion, DPSC expanded in HPL showed extensive proliferation of cells (c. 2-fold) compared with FBS; the purity, immune phenotype, colony-forming unit potential and differentiation were comparable. Furthermore, to understand the gene expression profiling, the transcriptomes and cytogenetics of DPSC expanded under HPL and FBS were compared, revealing similar expression profiles. CONCLUSIONS. We present a highly economized expansion of DPSC in HPL, yielding double the amount of cells while retaining their basic characteristics during a shorter time period under cGMP conditions, making it suitable for therapeutic applications.
  18. Govindasamy V, Abdullah AN, Ronald VS, Musa S, Ab Aziz ZA, Zain RB, et al.
    J Endod, 2010 Sep;36(9):1504-15.
    PMID: 20728718 DOI: 10.1016/j.joen.2010.05.006
    Lately, several new stem cell sources and their effective isolation have been reported that claim to have potential for therapeutic applications. However, it is not yet clear which type of stem cell sources are most potent and best for targeted therapy. Lack of understanding of nature of these cells and their lineage-specific propensity might hinder their full potential. Therefore, understanding the gene expression profile that indicates their lineage-specific proclivity is fundamental to the development of successful cell-based therapies.
  19. Govindasamy V, Ronald VS, Abdullah AN, Nathan KR, Ab Aziz ZA, Abdullah M, et al.
    J Dent Res, 2011 May;90(5):646-52.
    PMID: 21335539 DOI: 10.1177/0022034510396879
    The post-natal dental pulp tissue contains a population of multipotent mesenchymal progenitor cells known as dental pulp stromal/stem cells (DPSCs), with high proliferative potential for self-renewal. In this investigation, we explored the potential of DPSCs to differentiate into pancreatic cell lineage resembling islet-like cell aggregates (ICAs). We isolated, propagated, and characterized DPSCs and demonstrated that these could be differentiated into adipogenic, chondrogenic, and osteogenic lineage upon exposure to an appropriate cocktail of differentiating agents. Using a three-step protocol reported previously by our group, we succeeded in obtaining ICAs from DPSCs. The identity of ICAs was confirmed as islets by dithiozone-positive staining, as well as by expression of C-peptide, Pdx-1, Pax4, Pax6, Ngn3, and Isl-1. There were several-fold up-regulations of these transcription factors proportional to days of differentiation as compared with undifferentiated DPSCs. Day 10 ICAs released insulin and C-peptide in a glucose-dependent manner, exhibiting in vitro functionality. Our results demonstrated for the first time that DPSCs could be differentiated into pancreatic cell lineage and offer an unconventional and non-controversial source of human tissue that could be used for autologous stem cell therapy in diabetes.
  20. Gopalai AA, Lim SY, Aziz ZA, Lim SK, Tan LP, Chong YB, et al.
    Ann Acad Med Singap, 2013 May;42(5):237-40.
    PMID: 23771111
    INTRODUCTION: The G2385R and R1628P LRRK2 gene variants have been associated with an increased risk of Parkinson's disease (PD) in the Asian population. Recently, a new LRRK2 gene variant, A419V, was reported to be a third risk variant for PD in Asian patients. Our objective was to investigate this finding in our cohort of Asian subjects.

    MATERIALS AND METHODS: Eight hundred and twenty-eight subjects (404 PD patients, and 424 age and gender-matched control subjects without neurological disorders) were recruited. Genotyping was done by Taqman® allelic discrimination assay on an Applied Biosystems 7500 Fast Real-Time PCR machine.

    RESULTS: The heterozygous A419V genotype was found in only 1 patient with PD, compared to 3 in the control group (0.4% vs 1.3%), giving an odds ratio of 0.35 (95% confidence interval (CI), 0.01 to 3.79; P = 0.624).

    CONCLUSION: A419V is not an important LRRK2 risk variant in our Asian cohort of patients with PD. Our data are further supported by a literature review which showed that 4 out of 6 published studies reported a negative association of this variant in PD.

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