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  1. Tengku Ariff, R.H., Mohd Nazi, M.Z., Mohd Rizam, M.Z., Mohd Shahriman, M.S., Zakaria, Y., Kamal Nazmir, K., et al.
    MyJurnal
    This study was conducted to determine the health status of aboriginal ("Orang Asli') children aged 0-12 years in Post Brooke, Gua Musang, Kelantan. This is done by appraising the environmental status, patterns of illnesses including communicable diseases and usage of health resources. Six villages were selected randomly from 12 villages in the area; 179 families were interviewed, 200 under-12-year-olds were examined and their blood samples taken for haemoglobin (HB) estimation as well as malarial screening. Water supply through Gravity Feed System (GFS) was used by 134 families (70.2%) whilst the rest obtained water direct from the river for the purpose. Only 63.6% of families boiled their drinking water 56.4% families threw rubbish indiscriminately, while 82.1% used the river as their toilets. Eighty-seven percent of the families saw the village medicine man first when ill. Forty (22.2%) children had had serious illnesses including malaria and 24 were admitted to hospitals. 15% of the children had never been immunized. A total of 102 (51%) children were pale and 90 (45%) had brown hair. Eighty nine (44.5%) of the children were anaemic (Hb < 10 gm/di). Sixty-nine children (34%) had dental caries. Forty-two (21%) had distended abdomen and 37 (18.5%) had hepatomegaly. Out of 84 stool samples examined, 67 (79.8%) had helminthic ova. Of all families, 47.1% gave a past history of at least one baby among their children who had died due to one reason or another. The health status of this community (especially children) was low that it warrants special attention.
  2. Nik Zainuddin NAS, Muhammad H, Nik Hassan NF, Othman NH, Zakaria Y
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S768-S776.
    PMID: 33828376 DOI: 10.4103/jpbs.JPBS_262_19
    Introduction: Cervical cancer is a leading cause of death in women. Current cancer treatment comes with side effects. Clinacanthus nutans has been known traditionally to treat cancer. This study was aimed to characterize C. nutans standardized fraction (SF1) and to investigate its anticancer mechanism against SiHa cells.

    Materials and Methods: SF1 was produced by optimized methodology for bioassay-guided fractionation. Fourier transform infrared (FTIR) spectroscopy and liquid chromatography-mass spectrometry (LC-MS) were carried out to characterize the SF1. SF1 was screened for cytotoxicity activity toward HeLa, SiHa, and normal cells (NIH) cells by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. The anticancer mechanism of SF1 was evaluated toward SiHa cells, which showed highest cytotoxicity toward SF1 treatment. The mechanism includes cell cycle progression and protein expression, which was detected using specific antibody-conjugated fluorescent dye, p53-FITC, by flow cytometry.

    Results: Major constituents of SF1 were alkaloids with amines as functional group. SF1 showed highest cytotoxic activity against SiHa (half-maximal inhibitory concentration [IC50] < 10 µg/mL) compared to HeLa cells. Cytoselectivity of SF1 was observed with no IC50 detected on normal NIH cells. On flow cytometry analysis, SF1 was able to induce apoptosis on SiHa cells by arresting cell cycle at G1/S and upregulation of p53 protein.

    Conclusion: SF1 showed anticancer activity by inducing apoptosis through arrested G1/S cell cycle checkpoint-mediated mitochondrial pathway.

  3. Ali EZ, Zakaria Y, Mohd Radzi MA, Ngu LH, Jusoh SA
    Biomed Res Int, 2018;2018:4320831.
    PMID: 30175132 DOI: 10.1155/2018/4320831
    Ornithine transcarbamylase deficiency (OTCD), an X-linked disorder that results from mutations in the OTC gene, causes hyperammonemia and leads to various clinical manifestations. Mutations occurring close to the catalytic site of OTCase can cause severe OTCD phenotypes compared with those caused by mutations occurring on the surface of this protein. In this study, we report two novel OTC missense mutations, Q171H and N199H, found in Malaysian patients. Q171H and N199H caused neonatal onset OTCD in a male and late OTCD in a female, respectively. In silico predictions and molecular docking were performed to examine the effect of these novel mutations, and the results were compared with other 30 known OTC mutations. In silico servers predicted that Q171H and N199H, as well as 30 known missense mutations, led to the development of OTCD. Docking analysis indicated that N-(phosphonoacetyl)-L-ornithine (PALO) was bound to the catalytic site of OTCase mutant structure with minimal conformational changes. However, the mutations disrupted interatomic interactions in the catalytic site. Therefore, depending on the severity of disruption occurring at the catalytic site, the mutation may affect the efficiency of mechanism and functions of OTCase.
  4. Zakaria Y, Rahmat A, Pihie AH, Abdullah NR, Houghton PJ
    Cancer Cell Int, 2009;9:16.
    PMID: 19508737 DOI: 10.1186/1475-2867-9-16
    Eurycomanone is a cytotoxic compound found in Eurycoma longifolia Jack. Previous studies had noted the cytotoxic effect against various cancer cell lines. The aim of this study is to investigate the cytotoxicity against human hepato carcinoma cell in vitro and the mode of action. The cytotoxicity of eurycomanone was evaluated using MTT assay and the mode of cell death was detected by Hoechst 33258 nuclear staining and flow cytometry with Annexin-V/propidium iodide double staining. The protein expression Bax, Bcl-2, p53 and cytochrome C were studied by flow cytometry using a spesific antibody conjugated fluorescent dye to confirm the up-regulation of p53 and Bax in cancer cells.
  5. Othman FA, Mat Zin AA, Zakaria Y, Nik Salleh NNH, Tan SC
    Data Brief, 2023 Aug;49:109411.
    PMID: 37520653 DOI: 10.1016/j.dib.2023.109411
    Oroxylum indicum is a medicinal herb that garnered enormous attention in drug discovery for human diseases such as neurodegenerative, cardiovascular, arthritis and hepatitis diseases. Pharmacokinetic study confirmed that the pharmacological actions of this herb are associated with its prominent flavonoid bioactive components. Here, the data set of liquid chromatography-mass spectroscopy (LC-MS), neurological functions, relative organ weight (ROW), hematological, biochemical and histopathological parameters of flavonoid-enriched fraction (FEF)-treated Sprague Dawley (SD) rats were presented. The data set was generated from three study groups namely: Sighting Study, Acute Toxicity Study and Subacute Neurotoxicity Study with study duration of 14 days (for Sighting Study and Acute Toxicity Study) and 28 days (for Subacute Neurotoxicity Study) by strictly following the procedures set in Organisation for Economic Co-operation and Development (OECD) Guidelines 420 and 424 in vivo. Rats in sighting study were treated with dosage of 5, 50, 300 and 2000 mg/kg FEF (n = 1/dosage/gender), respectively, and were observed for mortality, toxicity signs and behavioural changes. The highest dosage at which none of the animal showed sign of mortality in the sighting study was selected as the test dosage for subsequent acute toxicity study (n = 5/dosage/gender). Meanwhile, for subacute neurotoxicity study, SD rats (n = 5/dosage/gender) were treated with repeated dosage of 50 mg/kg for 28 days. Neurological behaviours of treated rats were observed daily, while their body weight were measured weekly. Whole blood was collected at the end of the study via cardiac puncture into ethylenediaminetetraacetic acid (EDTA) tubes for hematological evaluation that included the measurements of red blood cells (RBC), hemoglobin (Hb), packed cell volumes (PCV), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular haemoglobin concentration (MCHC), platelet, white blood cells (WBC) count and WBC differentials. Meanwhile, blood serum were collected into slow sand filter (SST) tubes for biochemical evaluation that included measurements of total protein (TP), albumin, bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT). Vital organs such as brain, liver, kidneys, heart, lungs and reproductive organs also were collected, sliced and stained with hematoxylin and eosin (H&E) at the end of the study for histopathological assessments.
  6. Awaluddin SM, Ismail N, Yasin SM, Zakaria Y, Mohamed Zainudin N, Kusnin F, et al.
    Front Public Health, 2020;8:577407.
    PMID: 33384977 DOI: 10.3389/fpubh.2020.577407
    Introduction: The trends of tuberculosis (TB) treatment success rate among children in Malaysia plateaued at 90% from 2014 to 2017. Malaysia sets a higher treatment success target of 95% to be achieved in line with an affordable, accessible, and holistic approach in managing TB among children. Objective: This study aims to explore the parents' experiences and perspectives toward achieving treatment success among children who were diagnosed with TB in two districts in Selangor state, Malaysia. Methods: The study was conducted using phenomenology study design via an in-depth interview of 15 mothers who were purposively sampled from the list of pediatric TB cases in the MyTB version 2.1 database in Klang and Petaling Districts of Selangor state. The R-based qualitative data analysis package of R version 0.2-8 was used to perform the thematic analysis. Results: Two main themes were identified from this study. The first theme was trust toward the healthcare services with the subthemes of acceptance, self-efficacy, holistic care, and perceived benefits. The second theme was the motivation to take or continue medication. The subthemes were support from family, healthcare workers' (HCWs') support, the convenience of healthcare services, community support, personal strength, and child's character. Conclusion: TB treatment success for children can be achieved when parents develop trust in healthcare services and have strong motivational factors to remain steadfast in achieving a successful treatment goal. Psychosocial support should be provided to the primary caregiver who faced any difficulty, while good relationships between parents and HCWs should be maintained. These results will inform the TB program managers to strengthen the holistic approach and identify the motivational factors among parents of children with TB disease.
  7. Awaluddin SM, Ismail N, Zakaria Y, Yasin SM, Razali A, Mutalip MHA, et al.
    BMC Public Health, 2020 Dec 10;20(1):1903.
    PMID: 33302908 DOI: 10.1186/s12889-020-10005-y
    BACKGROUND: Tuberculosis (TB) among children remains a significant public health problem in many parts of the world. The objective of this study was to describe the characteristics of TB patients and to determine the predictors of treatment success among children in Malaysia.

    METHODS: Secondary data from MyTB version 2.1, a national database, were analysed using R version 3.6.1. Descriptive analysis and multivariable logistic regression were conducted to identify treatment success and its determinants.

    RESULTS: In total, 3630 cases of TB cases were registered among children in Malaysia between 2013 and 2017. The overall treatment success rate was 87.1% in 2013 and plateaued between 90.1 and 91.4% from 2014 to 2017. TB treatment success was positively associated with being a Malaysian citizen (aOR = 3.43; 95% CI = 2.47, 4.75), being a child with BCG scars (aOR = 1.93; 95% CI = 1.39, 2.68), and being in the older age group (aOR = 1.06; 95% CI = 1.03, 1.09). Having HIV co-infection (aOR = 0.31; 95% CI = 0.16, 0.63), undergoing treatment in public hospitals (aOR = 0.38; 95% CI =0.25, 0.58), having chest X-ray findings of advanced lesion (aOR = 0.48; 95% CI = 0.33, 0.69), having EPTB (aOR = 0.58; 95% CI = 0.41, 0.82) and having sputum-positive PTB (aOR = 0.58; 95% CI = 0.43, 0.79) were negatively associated with TB treatment success among children.

    CONCLUSIONS: The overall success rate of treatment among children with TB in Malaysia has achieved the target of 90% since 2014 and remained plateaued until 2017. The socio-demographic characteristics of children, place of treatment, and TB disease profile were associated with the likelihood of TB treatment success among children. The treatment success rate can be increased by strengthening contact tracing activities and promoting early identification targeting the youngest children and non-Malaysian children.

  8. Abas SA, Ismail N, Zakaria Y, Yasin SM, Ibrahim K, Ismail I, et al.
    BMC Public Health, 2024 Jan 22;24(1):249.
    PMID: 38254065 DOI: 10.1186/s12889-023-17561-z
    BACKGROUND: Finding innovative methods to enhance Tuberculosis treatment adherence in Malaysia is imperative, given the rising trend of non-adhere TB patients. Direct Observed Therapy (DOTS) has been used to ensure Tuberculosis (TB) drug compliance worldwide. However, due to its inconvenience, digitalizing this system into a virtual monitoring system via a mobile app can help deliver a more efficient tuberculosis management system. A gamified video-observed therapy is developed that connects three users the patient, supervisor, and administrator, allowing drug monitoring and patient loss to follow up with the patient tracking system. Thus, the objective of this study is to determine the impact of Gamified Real-time Video Observed Therapy (GRVOTS) mobile apps on patient medication adherence rates and motivation.

    METHODS: 71 patients from 18 facilities participated in the 8-week single-arm intervention study. GRVOTS mobile apps were installed in their mobile apps, and patients were expected to fulfill tasks such as providing Video Direct Observe Therapy (VDOTS) daily as well as side effect reporting. At 3-time intervals of baseline,1-month, and 2-month intervals, the number of VDOT taken, the Malaysian Medication Adherence Assessment Tool (MyMAAT), and the Intrinsic Motivation Inventory (IMI) questionnaire were collected. One-sample t-test was conducted comparing the VDOT video adherence to the standard rate of 80%. RM ANOVA was used to analyze any significant differences in MyMAAT and IMI scores across three-time intervals.

    RESULTS: This study involved 71 numbers of patients from 18 healthcare facilities who showed a significantly higher treatment adherence score of 90.87% than a standard score of 80% with a mean difference of 10.87(95% CI: 7.29,14.46; p 

  9. Zin NNINM, Mohamad MN, Roslan K, Abdul Wafi S, Abdul Moin NI, Alias A, et al.
    Malays J Med Sci, 2020 Jul;27(4):36-50.
    PMID: 32863744 MyJurnal DOI: 10.21315/mjms2020.27.4.4
    BACKGROUND: The spread of Plasmodium falciparum resistance in common antimalarial drugs, including artemisinin-based combination therapies, has necessitated the discovery of new drugs with novel mechanisms of action. In the present study, the in vitro antimalarial and toxicological activities of acetone, methanol, ethanol and aqueous extracts of Quercus infectoria (Q. infectoria) galls were investigated.

    METHODS: The extracts were assessed for the antimalarial potential using a malarial SYBR Green I fluorescence-based (MSF) assay, while the toxicity was screened by using brine shrimp lethality test (BSLT), haemolytic assay, and cytotoxicity assay against normal embryo fibroblast cell line (NIH/3T3) and normal kidney epithelial cell line (Vero).

    RESULTS: The acetone extract showed the highest antimalarial activity (50% inhibitory concentration, IC50 = 5.85 ± 1.64 μg/mL), followed by the methanol extract (IC50 = 10.31 ± 1.90 μg/mL). Meanwhile, the ethanol and aqueous extracts displayed low antimalarial activity with IC50 values of 20.00 ± 1.57 and 30.95 μg/mL ± 1.27 μg/mL, respectively. The significant antimalarial activity was demonstrated in all extracts and artemisinin (P < 0.05). All extracts were non-toxic to brine shrimps (50% lethality concentration, LC50 > 1000 ppm). Furthermore, no occurrence of haemolysis (< 5%) was observed in normal erythrocytes when treated with all extracts compared to Triton X-100 that caused 100% haemolysis (P < 0.05). The acetone and methanol extracts were non-toxic to the normal cell lines and statistically significant to artemisinin (P < 0.05).

    CONCLUSION: Taken together with satisfactory selectivity index (SI) values, the acetone and methanol extracts of Q. infectoria galls could serve as an alternative, promising and safe antimalarial agents.

  10. Abas SA, Ismail N, Zakaria Y, Ismail I, Mat Zain NH, Yasin SM, et al.
    JMIR Serious Games, 2023 Mar 07;11:e43047.
    PMID: 36881449 DOI: 10.2196/43047
    BACKGROUND: The success rate of tuberculosis (TB) treatment in Malaysia remains below the recommended World Health Organization target of 90% despite the implementation of directly observed therapy, short-course, a physical drug monitoring system, since 1994. With increasing numbers of patients with TB in Malaysia defaulting on treatment, exploring another method to improve TB treatment adherence is vital. The use of gamification and real-time elements via video-observed therapies in mobile apps is one such method expected to induce motivation toward TB treatment adherence.

    OBJECTIVE: This study aimed to document the process of designing, developing, and validating the gamification, motivation, and real-time elements in the Gamified Real-time Video Observed Therapies (GRVOTS) mobile app.

    METHODS: The modified nominal group technique via a panel of 11 experts was used to validate the presence of the gamification and motivation elements inside the app, which were assessed based on the percentage of agreement among the experts.

    RESULTS: The GRVOTS mobile app, which can be used by patients, supervisors, and administrators, was successfully developed. For validation purposes, the gamification and motivation features of the app were validated as they achieved a total mean percentage of agreement of 97.95% (SD 2.51%), which was significantly higher than the minimum agreement score of 70% (P

  11. Clark CS, Rampal KG, Thuppil V, Roda SM, Succop P, Menrath W, et al.
    Environ Res, 2009 Oct;109(7):930-6.
    PMID: 19656507 DOI: 10.1016/j.envres.2009.07.002
    In 2006 a report on the analysis for lead in 80 new residential paints from four countries in Asia revealed high levels in three of the countries (China, India and Malaysia) and low levels in a fourth country (Singapore) where a lead in paint regulation was enforced. The authors warned of the possible export of lead-painted consumer products to the United States and other countries and the dangers the lead paint represented to children in the countries where it was available for purchase. The need for a worldwide ban on the use of lead in paints was emphasized to prevent an increase in exposure and disease from this very preventable environmental source. Since the earlier paper almost 300 additional new paint samples have been collected from the four initial countries plus 8 additional countries, three from Asia, three from Africa and two from South America. During the intervening time period two million toys and other items imported into the United States were recalled because the lead content exceeded the United States standard. High lead paints were detected in all 12 countries. The average lead concentration by country ranged from 6988 (Singapore) to 31,960ppm (Ecuador). One multinational company sold high lead paint in one country through January 2007 but sold low lead paint later in 2007 indicating that a major change to cease adding lead to their paints had occurred. However, the finding that almost one-third of the samples would meet the new United States standard for new paint of 90ppm, suggests that the technology is already available in at least 11 of the 12 countries to produce low lead enamel paints for domestic use. The need remains urgent to establish effective worldwide controls to prevent the needless poisoning of millions of children from this preventable exposure.
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