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  1. Zakaria NH, Sthaneshwar P, Shanmugam H
    Malays J Pathol, 2017 Dec;39(3):317-320.
    PMID: 29279597 MyJurnal
    Hypophosphataemia is a metabolic disorder that is commonly encountered in critically ill patients. Phosphate has many roles in physiological functions, thus the depletion of serum phosphate could lead to impairment in multiple organ systems, which include the respiratory, cardiovascular, neurological and muscular systems and haematological and metabolic functions. Hypophosphataemia is defined as plasma phosphate level below 0.80 mmol per litre (mmol/L) and can be further divided into subgroups of mild (plasma phosphate of 0.66 to 0.79 mmol/L), moderate (plasma phosphate of 0.32 to 0.65 mmol/L) and severe (plasma phosphate of less than 0.32 mmol/L). The causes of hypophosphataemia include inadequate phosphate intake, decreased intestinal absorption, gastrointestinal or renal phosphate loss, and redistribution of phosphate into cells. Symptomatic hypophosphataemia associated with haematological malignancies has been reported infrequently. We report here a case of asymptomatic severe hypophosphataemia in a child with acute T-cell lymphoblastic leukaemia. A 14-year-old Chinese boy was diagnosed to have acute T cell lymphoblastic leukaemia (ALL). His serum biochemistry results were normal except inorganic phosphate and lactate dehydrogenase levels. The serum inorganic phosphate level was 0.1mmol/L and the level was low on repeated analysis. The child had no symptoms related to low phosphate levels. The possible causes of low phosphate were ruled out and urine Tmp/GFR was normal. Chemotherapy regime was started and the serum phosphate levels started to increase. Hypophosphataemia in leukaemia was attributed to shift of phosphorus into leukemic cells and excessive cellular phosphate consumption by rapidly proliferating cells. Several reports of symptomatic hypophosphataemia in myelogenous and lymphoblastic leukaemia in adults have been reported. To our knowledge this is the first case of severe asymptomatic hypophosphataemia in a child with ALL.
  2. Zakaria NH, Mohamed Tap F, Aljohani GF, Abdul Majid FA
    J Biomol Struct Dyn, 2024 Jan 02.
    PMID: 38165434 DOI: 10.1080/07391102.2023.2298726
    Honey-iQfood is an herbal supplement made of a mixture of polyherbal extracts and wild honey. The mixture is traditionally claimed to improve various conditions related to brain cells and functions including dementia and Alzheimer's disease. Glycogen synthase kinase-3 beta (GSK-3β) and cyclin-dependent kinase 5 (CDK5) have been identified as being involved in the pathological hyperphosphorylation of tau proteins, which leads to the formation of neurofibrillary tangles and causes Alzheimer's disease. Therefore, this study was conducted to confirm the traditional claims by detection of active compounds, namely curcumin, gallic acid, catechin, rosmarinic acid, and andrographolide in the raw materials of Honey-iQfood through HPLC analysis, molecular docking, and dynamic simulations. Two potential compounds, andrographolide, and rosmarinic acid, produced the best binding affinities following the molecular docking of the active compounds against the GSK-3β and CDK5 targets. Andrographolide binds with GSK-3β at -8.2 kcal/mol, whereas rosmarinic acid binds to CDK5 targets at -8.6 kcal/mol. Molecular dynamics was further carried out to confirm the docking results and clarify their dynamic properties such as RMSD, RMSF, rGyr, SASA, PSA, and binding free energy. CDK5-andrographolide complexes had the best MM-GBSA score (-83.63 kcal/mol) compared to other complexes, indicating the better interaction profile and stability of the complex. These findings warrant further research into andrographolide and rosmarinic acid as efficient inhibitors of tau protein hyperphosphorylation to verify their therapeutic potential in brain-related illnesses.Communicated by Ramaswamy H. Sarma.
  3. Safar HF, Ali AH, Zakaria NH, Kamal N, Hassan NI, Agustar HK, et al.
    Trop Biomed, 2022 Dec 01;39(4):552-558.
    PMID: 36602215 DOI: 10.47665/tb.39.4.011
    Diplazium esculentum is an edible fern commonly consumed by the local community in Malaysia either as food or medicine. Isolation work on the ethyl acetate extract of the stem of D. esculentum resulted in the purification of two steroids, subsequently identified as stigmasterol (compound 1) and ergosterol5,8-endoperoxide (compound 2). Upon further testing, compound 2 displayed strong inhibitory activity against the Plasmodium falciparum 3D7 (chloroquine-sensitive) strain, with an IC50 of 4.27±1.15 µM, while compound 1 was inactive. In silico data revealed that compound 2 showed good binding affinity to P. falciparum-Sarco endoplasmic reticulum calcium-dependent ATPase (PfATP6); however, compound 1 did not show an antiplasmodial effect due to the lack of a peroxide moiety in the chemical structure. Our data suggested that the antiplasmodial activity of compound 2 from D. esculentum might be due to the inhibition of PfATP6, which resulted in both in vitro and in silico inhibitory properties.
  4. Wong TS, Mohamed Tap F, Hashim Z, Abdul Majid FA, Zakaria NH, Siahaan P, et al.
    J Tradit Complement Med, 2023 Jan;13(1):11-19.
    PMID: 36685073 DOI: 10.1016/j.jtcme.2022.09.002
    Common treatments for the management of diabetes have limitations due to side effects, hence the need for continuous research to discover new remedies with better therapeutic efficacy. Previously, we have reported that the combination treatment of gallic acid (20 mg/kg) and andrographolide (10 mg/kg) for 15 days demonstrated synergistic hypoglycemic activity in the streptozotocin (STZ)-induced insulin-deficient diabetes rat model. Here, we attempt to further elucidate the effect of this combination therapy at the biochemical, histological and molecular levels. Our biochemical analyses showed that the combination treatment significantly increased the serum insulin level and decreased the total cholesterol and triglyceride level of the diabetic animals. Histological examinations of H&E stained pancreas, liver, kidney and adipose tissues of combination-treated diabetic animals showed restoration to the normalcy of the tissues. Besides, the combination treatment significantly enhanced the level of glucose transporter-4 (GLUT4) protein expression in the skeletal muscle of treated diabetic animals compared to single compound treated and untreated diabetic animals. The molecular docking analysis on the interaction of gallic acid and/or andrographolide with the adiponectin receptor 1 (AdipoR1), a key component in the regulation of pancreatic insulin secretion, revealed a greater binding affinity of AdipoR1 to both compounds compared to individual compounds. Taken together, these findings suggest the combination of gallic acid and andrographolide as a potent therapy for the management of diabetes mellitus.
  5. Meli AM, Zakaria NH, Mohd Yusof H, Kamarudin KS, Ali A
    J Taibah Univ Med Sci, 2023 Dec;18(6):1273-1284.
    PMID: 37275954 DOI: 10.1016/j.jtumed.2023.05.004
    OBJECTIVES: Low cognitive performance is a major concern among fishermen's children in Malaysia. Thus, this study was aimed at assessing dietary intake, nutritional status, physical activity, and socio-economic status, and their associations with cognitive performance among fishermen's children in Terengganu, Malaysia. We also investigated the risk associated with low cognitive performance.

    METHODS: This cross-sectional study included 94 children 7-11 years of age in Terengganu. Dietary adequacy was assessed with two 24-h dietary recall surveys. Anthropometric measurements were assessed by calculation of the body mass index (BMI)-for-age Z-score and height-for-age Z-score. In addition, median urinary iodine tests were conducted to determine iodine concentrations. Physical activity was measured with the Physical Activity Questionnaire for Children (PAQ-C). Raven's coloured progressive matrices were used to determine cognitive performance. Binominal logistic regressions were performed on factors associated with cognitive performance, to identify the risk factors with the strongest association with cognitive performance.

    RESULTS: The children of fishermen had adequate intake of all necessary nutrients except for fat, dietary fibre, thiamine, folate, vitamin C, vitamin E, calcium, zinc, and potassium. Most of the children had normal BMI-for-age [median = -0.86 (2.11)] and height-for-age (mean = -1.01 ± 1.03). However, more than half had iodine deficiency [median = 83.9 (102)]. In addition, 16% had low physical activity levels, and their cognitive performance was classified with a low average score [median = 80.0 (21.0)]. The mother's education level (p = 0.037), children's BMI-for-age (p = 0.012), protein (p = 0.020), and niacin (p = 0.032), exhibited significant relationships with cognitive performance (p 

  6. Rosilan NF, Waiho K, Fazhan H, Sung YY, Zakaria NH, Afiqah-Aleng N, et al.
    Fish Shellfish Immunol, 2023 Nov;142:109171.
    PMID: 37858788 DOI: 10.1016/j.fsi.2023.109171
    Protein-protein interactions (PPIs) are essential for understanding cell physiology in normal and pathological conditions, as they might involve in all cellular processes. PPIs have been widely used to elucidate the pathobiology of human and plant diseases. Therefore, they can also be used to unveil the pathobiology of infectious diseases in shrimp, which is one of the high-risk factors influencing the success or failure of shrimp production. PPI network analysis, specifically host-pathogen PPI (HP-PPI), provides insights into the molecular interactions between the shrimp and pathogens. This review quantitatively analyzed the research trends within this field through bibliometric analysis using specific keywords, countries, authors, organizations, journals, and documents. This analysis has screened 206 records from the Scopus database for determining eligibility, resulting in 179 papers that were retrieved for bibliometric analysis. The analysis revealed that China and Thailand were the driving forces behind this specific field of research and frequently collaborated with the United States. Aquaculture and Diseases of Aquatic Organisms were the prominent sources for publications in this field. The main keywords identified included "white spot syndrome virus," "WSSV," and "shrimp." We discovered that studies on HP-PPI are currently quite scarce. As a result, we further discussed the significance of HP-PPI by highlighting various approaches that have been previously adopted. These findings not only emphasize the importance of HP-PPI but also pave the way for future researchers to explore the pathogenesis of infectious diseases in shrimp. By doing so, preventative measures and enhanced treatment strategies can be identified.
  7. Sheikh HI, Zakaria NH, Abdul Majid FA, Zamzuri F, Fadhlina A, Hairani MAS
    J Agric Food Res, 2023 Dec;14:100680.
    PMID: 37346755 DOI: 10.1016/j.jafr.2023.100680
    Zingiber officinale, Curcuma longa, and Momordica charantia are medicinal plants that are commonly used in the form of herbal tea, which is formulated to strengthen the immune system, especially against COVID-19 infection. Excellent antioxidant, anti-inflammatory, and immunostimulatory properties have been reported for their bioactive compounds, which have been shown to aid in stimulating immune systems as well as lowering the risk of severe COVID-19 such as lung injury. Yet, no bibliometric study on the subject is available. Hence, the purpose of this study is to quantitatively examine the existing articles related to the therapeutic potential of these three herbs, as well as their mechanisms of action in combating the SARS-CoV-2 virus. A total of 121 papers were retrieved from Scopus database up to 14th March 2023. The bibliometric analysis was conducted using VOSviewer software. Based on the literature search, Z. officinale was the most researched plant. India appeared as the most prolific country, with the highest number of articles contributed by two authors from India (Rathi, R. and Gayatri Devi, R.). In terms of keywords, the plants were associated with immune modulation, management of symptoms, antioxidant, anti-inflammatory and antiviral activities. Several important bioactive compounds were responsible for these effects such as gingerol, paradol, shogaol, curcumin, calebin A, momordicoside, karaviloside and cucurbitadienol. These compounds were hypothesized to prevent and cure COVID-19 by regulating inflammatory response, downregulating oxidative stress and modulating immunostimulatory activity. This review paper therefore supports the potential of Z. officinale, C. longa, and M. charantia to be formulated as a herbal blend for treating and preventing COVID-19 infection.
  8. Jinah N, Lee KY, Zakaria NH, Zakaria N, Ismail M, Mohmad S
    PLoS One, 2023;18(9):e0292213.
    PMID: 37768943 DOI: 10.1371/journal.pone.0292213
    Contract appointment policy for newly graduated medical officers was implemented by the Ministry of Health Malaysia in 2016 to overcome the lack of permanent posts. Contract officers faced disadvantages in terms of salary, leave provision, and career prospects. A nationwide strike, Hartal Doktor Kontrak (HDK) was organised on 26th July 2021. Besides generating widespread public attention, HDK was also closely scrutinised by the medical fraternity and stakeholders. This content analysis aimed to explore how the medical fraternity and stakeholders viewed the strike as their perception would offer vital insights into the fundamental causes and viable solutions to the contract appointment policy. A qualitative content analysis of Facebook (FB) posts on the HDK strike was conducted from 1st June 2021 until 28th February 2022. A total of 182 FB posts were retrieved from stakeholders, medical fraternity groups, and medical key opinion personnel. Inductive coding was used in the thematic analysis to identify pertinent themes. Three main themes emerged: triggering factors, reactions to the strike, and outcomes of the strike. Factors that led to the strike included unequal treatment faced by contract officers, frustration with the government's lack of long-term solutions, and aggravation by the COVID-19 pandemic. In terms of reactions, there was a mixture of supportive and opposing voices. No substantial negative impact on the healthcare service resulted from the strike. Instead, it generated widespread attention that propelled the government into implementing solutions to prevent adverse short and long-term consequences. Various suggestions were proposed, including the reform of human resource planning and undergraduate medical education. The results highlight the importance of proactive systemic measures by the government to prevent further strikes that may jeopardise healthcare provision. In summary, social media was found to influence the progress and outcome of HDK, thus demonstrating the impact of media influence on similar issues.
  9. Zakaria N, Zakaria NH, Bin Abdul Rassip MNA, Lee KY
    BMJ Open, 2022 Oct 10;12(10):e064687.
    PMID: 36216421 DOI: 10.1136/bmjopen-2022-064687
    OBJECTIVE: This national-level study aimed to determine the prevalence and risk factors of burnout, as well as the coping strategies among nurses in the Ministry of Health (MOH) Malaysia.

    DESIGN: Using a complex sampling design, a two-stage stratified cluster sampling was performed to recruit MOH nurses between August and November 2019.

    SETTING AND PARTICIPANTS: A total of 2428 nurses from 32 hospitals and 28 district health offices answered the questionnaires based on Maslach Burnout Inventory for Human Services and Brief COPE. Complex sampling analysis was applied.

    OUTCOME MEASURES: The outcome of interest was the prevalence of burnout and its three domains of emotional exhaustion (EE), depersonalisation (DP) and low personal accomplishment. ORs using 95% CIs were calculated. Significant factors at the univariate level were entered into the multivariate logistic regression to identify independent predictors of burnout.

    RESULTS: One in four (24.4%) nurses experienced burnout. Younger, single, and childless nurses had a higher prevalence of burnout. Shift working nurses were 1.6 times more likely to develop burnout. Those who performed >6 night shifts per month were 1.5 times more predisposed to burnout (95% CI 1.01 to 2.36; p<0.05). While encountering traumatic events at work led to 4.2 times (95% CI 2.31, 7.63; p<0.05) higher risk of burnout, those who received post-traumatic psychological support were better protected. The use of dysfunctional coping strategies was detrimental as it was positively correlated with EE and DP.

    CONCLUSION: Addressing modifiable stressors of burnout at individual and institutional levels identified in this study can be potentially beneficial in reducing burnout and its undesirable effects among nurses. Interventions that promote positive coping strategies should be implemented. Organisational-driven efforts must target the improvement of work schedules for nurses and the establishment of a structured debriefing service for post-trauma counselling.

  10. Almogahed A, Mahdin H, Omar M, Zakaria NH, Gu YH, Al-Masni MA, et al.
    PLoS One, 2023;18(11):e0293742.
    PMID: 37917752 DOI: 10.1371/journal.pone.0293742
    Refactoring, a widely adopted technique, has proven effective in facilitating and reducing maintenance activities and costs. Nonetheless, the effects of applying refactoring techniques on software quality exhibit inconsistencies and contradictions, leading to conflicting evidence on their overall benefit. Consequently, software developers face challenges in leveraging these techniques to improve software quality. Moreover, the absence of a categorization model hampers developers' ability to decide the most suitable refactoring techniques for improving software quality, considering specific design goals. Thus, this study aims to propose a novel refactoring categorization model that categorizes techniques based on their measurable impacts on internal quality attributes. Initially, the most common refactoring techniques used by software practitioners were identified. Subsequently, an experimental study was conducted using five case studies to measure the impacts of refactoring techniques on internal quality attributes. A subsequent multi-case analysis was conducted to analyze these effects across the case studies. The proposed model was developed based on the experimental study results and the subsequent multi-case analysis. The model categorizes refactoring techniques into green, yellow, and red categories. The proposed model, by acting as a guideline, assists developers in understanding the effects of each refactoring technique on quality attributes, allowing them to select appropriate techniques to improve specific quality attributes. Compared to existing studies, the proposed model emerges superior by offering a more granular categorization (green, yellow, and red categories), and its range is wide (including ten refactoring techniques and eleven internal quality attributes). Such granularity not only equips developers with an in-depth understanding of each technique's impact but also fosters informed decision-making. In addition, the proposed model outperforms current studies and offers a more nuanced understanding, explicitly highlighting areas of strength and concern for each refactoring technique. This enhancement aids developers in better grasping the implications of each refactoring technique on quality attributes. As a result, the model simplifies the decision-making process for developers, saving time and effort that would otherwise be spent weighing the benefits and drawbacks of various refactoring techniques. Furthermore, it has the potential to help reduce maintenance activities and associated costs.
  11. Shamsuddin AS, Syed Ismail SN, Othman NMI, Zakaria NH, Abd Manan TS, Ibrahim MA, et al.
    Environ Geochem Health, 2023 Nov;45(11):7741-7757.
    PMID: 37428425 DOI: 10.1007/s10653-023-01671-z
    Excessive nitrate intake via ingestion pathway and dermal absorption exposures has adverse health impacts on human health. This study evaluated groundwater (GW) nitrate concentrations and health risks which focused on ingestion and dermal exposures to residents in Bachok District, Kelantan, Malaysia. Three hundred (300) samples of private wells were collected and it is found that the nitrate concentrations ranging between 0.11 and 64.01 mg/L NO3-N with a mean value of 10.45 ± 12.67 mg/L NO3-N. The possible health hazards of nitrate by ingestion and dermal contact were assessed using USEPA human health risk assessment model for adult males and females. It is observed that the mean Hazard Quotient (HQ) values of adult males and females were 0.305 ± 0.364 and 0.261 ± 0.330, respectively. About 7.3% (n = 10) and 4.9% (n = 8) of adult males and females had HQ values more than 1, respectively. It was also observed that the mean of HQderm was lesser than HQoral for males and females. The spatial distribution of HQ by interpolation method showed high nitrate concentrations (> 10 mg/L NO3-N) were distributed from the centre to the southern part of the study location, which identified as an agricultural area, indicating the used of nitrogenous fertilizers as the main source of GW nitrate contamination in this area. The findings of this study are valuable for establishing private well water protection measures to stop further deterioration of GW quality caused by nitrate.
  12. Sharif R, Chong KH, Zakaria NH, Ong ML, Reilly JJ, Wong JE, et al.
    J Phys Act Health, 2016 11;13(11 Suppl 2):S201-S205.
    PMID: 27848721 DOI: 10.1123/jpah.2016-0404
    BACKGROUND: The 2016 Malaysia Active Healthy Kids Report Card aims to collect, assess, and grade current and comprehensive data on physical activity (PA) and associated factors in Malaysian children and adolescents aged 5 to 17 years.
    METHODS: This report card was developed following the Active Healthy Kids Canada Report Card protocol. The Research Working Group identified the core matrices, assessed the key data sources, and evaluated the evidence gathered for grade assignments. A grade was assigned to each indicator by comparing the best available evidence against relevant benchmark using a standardized grading scheme.
    RESULTS: Overall Physical Activity, Active Transportation, and Sedentary Behavior were assigned the D grade. The lowest grade of F was assigned to Diet, while School and Government Strategies and Investments were graded higher with a B. Five indicators were assigned INC (incomplete) due to a lack of representative data.
    CONCLUSIONS: The report card demonstrates that Malaysian children and adolescents are engaging in low levels of PA and active commuting, high levels of screen time, and have extremely low compliance with dietary recommendations. More efforts are needed to address the root causes of physical inactivity while increasing the opportunities for children and adolescents to be more physically active.
    MESH: screen time
  13. Anuar MNN, Ibrahim M, Zakaria NH, Ichwan SJA, Md Isa ML, Mat Alewi NA, et al.
    Malays J Med Sci, 2023 Feb;30(1):82-91.
    PMID: 36875196 DOI: 10.21315/mjms2023.30.1.7
    BACKGROUND: Head and neck cancer patients usually need nutritional support due to difficulties in swallowing and chewing. Therefore, this study aimed to formulate Musa paradisiaca and Trigona sp. honey jelly (MTJ) as a convenient functional food.

    METHODS: The antioxidant properties were analysed using 2,2'-diphenyl-1 picrylhydrazyl (DPPH), ferric reducing antioxidant potential (FRAP) and 2,2'-azinodi 3-ethylbenthiazolinesulfonate (ABTS) assays. Cytotoxicity was assayed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) test and the induction of apoptosis was observed via caspase-3/7 activity assay. The identification of phenolic compounds was done via ultra-high-performance-liquid chromatography coupled to mass spectrometer (UHPLC-MS/MS).

    RESULTS: The antioxidant analysis exhibited: the half inhibitory concentration (IC50) of DPPH inhibition, 54.10 (SD = 4.51) μg/mL; the FRAP value, 30.07 (SD = 0.93) mM TEQ/100 g; and the ABTS value, 131.79 (SD = 8.73) mg TEQ/100 g. Cinnamic acid was the most abundant phenolic compound, followed by maleic acid and salicylic acid. The IC50 for ORL115 and ORL188 were 35.51 mg/mL and 43.54 mg/mL, respectively. The cells became rounded and dissymmetrical which reduced in number and size. The apoptotic cell death in ORL115 and ORL188 was deduced as caspase-3/7 activities that significantly increased (P < 0.05).

    CONCLUSION: The study evidenced that the antioxidant activity of MTJ could influence the induction of apoptosis in ORL115 and ORL188 in future investigations and verifications.

  14. Shamsuddin MA, Ali AH, Zakaria NH, Mohammat MF, Hamzah AS, Shaameri Z, et al.
    Pharmaceuticals (Basel), 2021 Nov 17;14(11).
    PMID: 34832956 DOI: 10.3390/ph14111174
    Widespread resistance of Plasmodium falciparum to current artemisinin-based combination therapies necessitate the discovery of new medicines. Pharmacophoric hybridization has become an alternative for drug resistance that lowers the risk of drug-drug adverse interactions. In this study, we synthesized a new series of hybrids by covalently linking the scaffolds of pyrano[2,3-c]pyrazole with 4-aminoquinoline via an ethyl linker. All synthesized hybrid molecules were evaluated through in vitro screenings against chloroquine-resistant (K1) and -sensitive (3D7) P. falciparum strains, respectively. Data from in vitro assessments showed that hybrid 4b displayed significant antiplasmodial activities against the 3D7 strain (EC50 = 0.0130 ± 0.0002 μM) and the K1 strain (EC50 = 0.02 ± 0.01 μM), with low cytotoxic effect against Vero mammalian cells. The high selectivity index value on the 3D7 strain (SI > 1000) and the K1 strain (SI > 800) and the low resistance index value from compound 4b suggested that the pharmacological effects of this compound were due to selective inhibition on the 3D7 and K1 strains. Molecular docking analysis also showed that 4b recorded the highest binding energy on P. falciparum lactate dehydrogenase. Thus, P. falciparum lactate dehydrogenase is considered a potential molecular target for the synthesized compound.
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