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  1. Zamzuri M'IA, Jamhari MN, Faisal Ghazi H, Muhamad Hasani MH, Mohd Ali NK, Abd Rashid MF, et al.
    PLoS One, 2021;16(8):e0256636.
    PMID: 34428257 DOI: 10.1371/journal.pone.0256636
    INTRODUCTION/BACKGROUND: Dengue fever remains a public health threat despite being preventable. A solution to the constant problem of dengue infection will require active intervention and a paradigm shift. Assessing perceived risk and correlating it with the attitude and practice of the community will help in designing appropriate measures. However, possible instruments for these assessments come with limitations.

    OBJECTIVE: The aim is to develop and validate a new scoring-based questionnaire, using dual statistical approaches to measure risk perception, attitude, and practices (RPAP) related to dengue in the community.

    METHODS: The RPAP questionnaire was developed bilingually using the International Society for Pharmacoeconomics and Outcome Research (ISPOR) guidelines. Content analysis was reviewed scrupulously by four expert panels. The initial 35-item scale was tested among 253 Malaysian respondents recruited non-probabilistically via multiple online platforms. Two statistical methods were employed to measure the construct validity: Exploratory Factor Analysis (EFA) as part of the Classical Test Theory (CTT) measurement, while Rasch Measurement Analysis (Rasch) was performed for the Item Response Theory (IRT) measurement. All results were cross-validated with their counterpart to ensure stability. Confirmatory Factor Analysis (CFA) was used to obtain a model fit index.

    RESULTS: 29 questions were retained after the final analysis. Both EFA and Rasch analysis detect multidimensionality. Nine latent factors were extracted from EFA, while only eight factors remained in the final model following CFA: 1) perceived susceptibility; 2) perceived severity; 3) perceived barrier; 4) perceived benefit; 5) cues to action; 6) self-efficacy; 7) attitude; and 8) practice. All items had adequate factor loadings and showed good internal consistency. The final model after CFA achieved a good fit with an RMSEA value of 0.061, SRMR of 0.068, PNFI of 0.649, and GFI of 0.996.

    CONCLUSION: The RPAP questionnaire contains 29 items and is a reliable and accurate psychometric instrument for measuring the risk perception of dengue fever, attitude, and practice of the community in dengue prevention. The Rasch measurement provides additional rigour to complement the CTT analysis. This RPAP questionnaire is suitable for use in studies related to dengue prevention in the community.

  2. Zamri EN, Moy FM, Hoe VC
    PLoS One, 2017;12(2):e0172195.
    PMID: 28234933 DOI: 10.1371/journal.pone.0172195
    BACKGROUND: Musculoskeletal pain is common among teachers. Work-related psychosocial factors are found to be associated with the development of musculoskeletal pain, however psychological distress may also play an important role.

    OBJECTIVES: To assess the prevalence of self-reported low back pain (LBP), and neck and/or shoulder pain (NSP) among secondary school teachers; and to evaluate the association of LBP and NSP with psychological distress and work-related psychosocial factors.

    METHODS: This was a cross-sectional study conducted among teachers in the state of Penang, Malaysia. The participants were recruited via a two stage sampling method. Information on demographic, psychological distress, work-related psychosocial factors, and musculoskeletal pain (LBP and NSP) in the past 12 months was collected using a self-administered questionnaire. Poisson regression was used to estimate the prevalence ratio (PR) for the associations between psychological distress and work-related psychosocial factors with LBP and NSP.

    RESULTS: The prevalence of self-reported LBP and NSP among 1482 teachers in the past 12 months was 48.0% (95% Confidence Interval (CI) 45.2%, 50.9%) and 60.1% (95% CI 57.4%, 62.9%) respectively. From the multivariate analysis, self-reported LBP was associated with teachers who reported severe to extremely severe depression (PR: 1.71, 95% CI 1.25, 2.32), severe to extremely severe anxiety (1.46, 95% CI 1.22, 1.75), high psychological job demand (1.29, 95% CI 1.06, 1.57), low skill discretion (1.28, 95% CI 1.13, 1.47) and poorer mental health (0.98, 95% CI 0.97, 0.99). Self-reported NSP was associated with mild to moderate anxiety (1.18, 95% CI 1.06, 1.33), severe to extremely severe anxiety (1.25, 95% CI 1.09, 1.43), low supervisory support (1.13, 95% CI 1.03, 1.25) and poorer mental health (0.98, 95% CI 0.97, 0.99).

    CONCLUSIONS: Self-reported LBP and NSP were common among secondary school teachers. Interventions targeting psychological distress and work-related psychosocial characteristics may reduce musculoskeletal pain among school teachers.

  3. Zamli KZ, Din F, Ahmed BS, Bures M
    PLoS One, 2018;13(5):e0195675.
    PMID: 29771918 DOI: 10.1371/journal.pone.0195675
    The sine-cosine algorithm (SCA) is a new population-based meta-heuristic algorithm. In addition to exploiting sine and cosine functions to perform local and global searches (hence the name sine-cosine), the SCA introduces several random and adaptive parameters to facilitate the search process. Although it shows promising results, the search process of the SCA is vulnerable to local minima/maxima due to the adoption of a fixed switch probability and the bounded magnitude of the sine and cosine functions (from -1 to 1). In this paper, we propose a new hybrid Q-learning sine-cosine- based strategy, called the Q-learning sine-cosine algorithm (QLSCA). Within the QLSCA, we eliminate the switching probability. Instead, we rely on the Q-learning algorithm (based on the penalty and reward mechanism) to dynamically identify the best operation during runtime. Additionally, we integrate two new operations (Lévy flight motion and crossover) into the QLSCA to facilitate jumping out of local minima/maxima and enhance the solution diversity. To assess its performance, we adopt the QLSCA for the combinatorial test suite minimization problem. Experimental results reveal that the QLSCA is statistically superior with regard to test suite size reduction compared to recent state-of-the-art strategies, including the original SCA, the particle swarm test generator (PSTG), adaptive particle swarm optimization (APSO) and the cuckoo search strategy (CS) at the 95% confidence level. However, concerning the comparison with discrete particle swarm optimization (DPSO), there is no significant difference in performance at the 95% confidence level. On a positive note, the QLSCA statistically outperforms the DPSO in certain configurations at the 90% confidence level.
  4. Zamiri R, Ahangar HA, Kaushal A, Zakaria A, Zamiri G, Tobaldi D, et al.
    PLoS One, 2015;10(4):e0122989.
    PMID: 25910071 DOI: 10.1371/journal.pone.0122989
    A template-free precipitation method was used as a simple and low cost method for preparation of CeO2 nanoparticles. The structure and morphology of the prepared nanoparticle samples were studied in detail using X-ray diffraction, Raman spectroscopy and Scanning Electron Microscopy (SEM) measurements. The whole powder pattern modelling (WPPM) method was applied on XRD data to accurately measure the crystalline domain size and their size distribution. The average crystalline domain diameter was found to be 5.2 nm, with a very narrow size distribution. UV-visible absorbance spectrum was used to calculate the optical energy band gap of the prepared CeO2 nanoparticles. The FT-IR spectrum of prepared CeO2 nanoparticles showed absorption bands at 400 cm(-1) to 450 cm(-1) regime, which correspond to CeO2 stretching vibration. The dielectric constant (εr) and dielectric loss (tan δ) values of sintered CeO2 compact consolidated from prepared nanoparticles were measured at different temperatures in the range from 298 K (room temperature) to 623 K, and at different frequencies from 1 kHz to 1 MHz.
  5. Zaman Huri H, Permalu V, Vethakkan SR
    PLoS One, 2014;9(9):e106505.
    PMID: 25181406 DOI: 10.1371/journal.pone.0106505
    Sliding-scale and basal-bolus insulin regimens are two options available for the treatment of severe or acute hyperglycemia in type 2 diabetes mellitus patients. Although its use is not recommended, sliding-scale insulin therapy is still being used widely. The aims of the study were to compare the glycemic control achieved by using sliding-scale or basal-bolus regimens for the management of severe or acute hyperglycemia in patients with type 2 diabetes and to analyze factors associated with the types of insulin therapy used in the management of severe or acute hyperglycemia. This retrospective study was conducted using the medical records of patients with acute or severe hyperglycemia admitted to a hospital in Malaysia from January 2008 to December 2012. A total of 202 patients and 247 admissions were included. Patients treated with the basal-bolus insulin regimen attained lower fasting blood glucose (10.8 ± 2.3 versus 11.6 ± 3.5 mmol/L; p = 0.028) and mean glucose levels throughout severe/acute hyperglycemia (12.3 ± 1.9 versus 12.8 ± 2.2; p = 0.021) compared with sliding-scale insulin regimens. Diabetic ketoacidosis (p = 0.043), cardiovascular diseases (p = 0.005), acute exacerbation of bronchial asthma (p = 0.010), and the use of corticosteroids (p = 0.037) and loop diuretics (p = 0.016) were significantly associated with the type of insulin regimen used. In conclusion, type 2 diabetes patients with severe and acute hyperglycemia achieved better glycemic control with the basal-bolus regimen than with sliding-scale insulin, and factors associated with the insulin regimen used could be identified.
  6. Zaman Huri H, Hui Xin C, Sulaiman CZ
    PLoS One, 2014;9(1):e86215.
    PMID: 24475089 DOI: 10.1371/journal.pone.0086215
    Benign Prostatic Hyperplasia (BPH) patients are at risk of acquiring drug-related problems (DRPs), as it is present in the majority of aging men. To date, DRPs among BPH patients have not been well studied. We conducted this retrospective study in a tertiary hospital in Malaysia from January 2009 to June 2012 with the aim of identifying the factors associated with DRPs among BPH patients. The Pharmaceutical Care Network Europe Classification Version (PCNE) 5.01 was used as a tool to classify DRPs. We enrolled 203 patients from 259 hospital admissions. A total of 390 DRPs were found and there was an average of 1.5±1.3 problems per hospitalization. 76.1% of hospital admissions included at least one DRP. The most common DRP categories encountered were drug choice problems (45.9%), drug interactions (24.9%), and dosing problems (13.3%). Factors such as advanced age (p = 0.005), a hospital stay of more than 6 days (p = 0.001), polydrug treatments (p<0.001), multiple comorbidities (p<0.001), and comorbid cardiovascular disease (p = 0.011), diabetes mellitus(p = 0.001), hypertension (p<0.001) and renal impairment (p = 0.011) were significantly associated with the occurrence of DRPs. These data indicated that the prevalence of DRPs is high among BPH patients. The identification of different subtypes of DRPs and the factors associated with DRPs may facilitate risk reduction for BPH patients.
  7. Zaki R, Bulgiba A, Ismail R, Ismail NA
    PLoS One, 2012;7(5):e37908.
    PMID: 22662248 DOI: 10.1371/journal.pone.0037908
    Accurate values are a must in medicine. An important parameter in determining the quality of a medical instrument is agreement with a gold standard. Various statistical methods have been used to test for agreement. Some of these methods have been shown to be inappropriate. This can result in misleading conclusions about the validity of an instrument. The Bland-Altman method is the most popular method judging by the many citations of the article proposing this method. However, the number of citations does not necessarily mean that this method has been applied in agreement research. No previous study has been conducted to look into this. This is the first systematic review to identify statistical methods used to test for agreement of medical instruments. The proportion of various statistical methods found in this review will also reflect the proportion of medical instruments that have been validated using those particular methods in current clinical practice.
  8. Zaki R, Roffeei SN, Hii YL, Yahya A, Appannan M, Said MA, et al.
    PLoS One, 2019;14(2):e0212497.
    PMID: 30818394 DOI: 10.1371/journal.pone.0212497
    An early warning system for dengue is meant to predict outbreaks and prevent dengue cases by aiding timely decision making and deployment of interventions. However, only a system which is accepted and utilised by the public would be sustainable in the long run. This study aimed to explore the perception and attitude of the Malaysian public towards a dengue early warning system. The sample consisted of 847 individuals who were 18 years and above and living/working in the Petaling District, an area adjacent to Kuala Lumpur, Malaysia. A questionnaire consisting of personal information and three sub-measures of; i) perception, ii) attitude towards dengue early warning and iii) response towards early warning; was distributed to participants. We found that most of the respondents know about dengue fever (97.1%) and its association with climate factors (90.6%). Most of them wanted to help reduce the number of dengue cases in their area (91.5%). A small percentage of the respondents admitted that they were not willing to be involved in public activities, and 64% of them admitted that they did not check dengue situations or hotspots around their area regularly. Despite the high awareness on the relationship between climate and dengue, about 45% of respondents do not know or are not sure how this can be used to predict dengue. Respondents would like to know more about how climate data can be used to predict a dengue outbreak (92.7%). Providing more information on how climate can influence dengue cases would increase public acceptability and improve response towards climate-based warning system. The most preferred way of communicating early warning was through the television (66.4%). This study shows that the public in Petaling District considers it necessary to have a dengue warning system to be necessary, but more education is required.
  9. Zakaria H, Hussain I, Zulkifli NS, Ibrahim N, Noriza NJ, Wong M, et al.
    PLoS One, 2023;18(7):e0283862.
    PMID: 37506072 DOI: 10.1371/journal.pone.0283862
    BACKGROUND AND AIMS: There is growing evidence on the contribution of psychological factors to internet addiction; yet it remains inconsistent and deserves further exploration. The aim of this study was to determine the relationship between the psychological symptoms (Attention Deficit Hyperactivity Disorder (ADHD) symptoms, stress, depression, anxiety and loneliness) and internet addiction (IA) among the university students in Malaysia.

    MATERIALS AND METHODS: A total of 480 students from different faculties in a Malaysian public university participated in this study. They were selected by simple random sampling method. They completed self-administered questionnaires including the Malay Version of Internet Addiction Test (MVIAT)) to measure internet addiction and Adult Self-Report Scale (ASRS) Symptom Checklist, Depression Anxiety Stress Scales (DASS) and UCLA Loneliness Scale (Version 3) to assess for ADHD symptoms, depression, anxiety, stress, and loneliness respectively.

    RESULTS: The prevalence of IA among university students was 33.33% (n = 160). The respondents' mean age was 21.01 ± 1.29 years old and they were predominantly females (73.1%) and Malays (59.4%). Binary logistic regression showed that gender (p = 0.002; OR = 0.463, CI = 0.284-0.754), ADHD inattention (p = 0.003; OR = 2.063, CI = 1.273-3.345), ADHD hyperactivity (p<0.0001; OR = 2.427, CI = 1.495-3.939), stress (p = 0.048; OR = 1.795, CI = 1.004-3.210) and loneliness (p = 0.022; OR = 1.741, CI = 1.084-2.794) were significantly associated with IA.

    CONCLUSION: A third of university students had IA. In addition, we found that those who were at risk of IA were males, with ADHD symptoms of inattention and hyperactivity, who reported stress and loneliness. Preventive strategy to curb internet addiction and its negative sequelae may consider these factors in its development and implementation.

  10. Zajmi A, Mohd Hashim N, Noordin MI, Khalifa SA, Ramli F, Mohd Ali H, et al.
    PLoS One, 2015;10(6):e0128157.
    PMID: 26030925 DOI: 10.1371/journal.pone.0128157
    Staphylococci are facultative anaerobes, perfectly spherical un-encapsulated cocci, with a diameter not exceeding 1 micrometer in diameter. Staphylococcus aureus are generally harmless and remain confined to the skin unless they burrow deep into the body, causing life-threatening infections in bones, joints, bloodstream, heart valves and lungs. Among the 20 medically important staphylococci species, Staphylococcus aureus is one of the emerging human pathogens. Streptomycin had its highest potency against Staphylococcus infections despite the likelihood of getting a resistant type of staphylococcus strains. Methicillin-resistant S. aureus (MRSA) is the persister type of Staphylococcus aureus and was evolved after decades of antibiotic misuse. Inadequate penetration of the antibiotic is one of the principal factors related to success/failure of the therapy. The active drug needs to reach the bacteria at concentrations necessary to kill or suppress the pathogen's growth. In turn the effectiveness of the treatment relied on the physical properties of Staphylococcus aureus. Thus understanding the cell integrity, shape and roughness is crucial to the overall influence of the therapeutic agent on S. aureus of different origins. Hence our experiments were designed to clarify ultrastructural changes of S. aureus treated with streptomycin (synthetic compound) in comparison to artonin E (natural compound). In addition to the standard in vitro microbial techniques, we used transmission electron microscopy to study the disrupted cell architecture under antibacterial regimen and we correlate this with scanning electron microscopy (SEM) to compare results of both techniques.
  11. Zainuri DA, Abdullah M, Zaini MF, Bakhtiar H, Arshad S, Abdul Razak I
    PLoS One, 2021;16(9):e0257808.
    PMID: 34582495 DOI: 10.1371/journal.pone.0257808
    The Ultraviolet-visible (UV-Vis) spectra indicate that anthracenyl chalcones (ACs) have high maximum wavelengths and good transparency windows for optical applications and are suitable for optoelectronic applications owing to their HOMO-LUMO energy gaps (2.93 and 2.76 eV). Different donor substituents on the AC affect their dipole moments and nonlinear optical (NLO) responses. The positive, negative, and neutral electrostatic potential regions of the molecules were identified using molecular electrostatic potential (MEP). The stability of the molecule on account of hyperconjugative interactions and accompanying charge delocalization was analyzed using natural bond orbital (NBO) analysis. Open and closed aperture Z-scans were performed using a continuous-wave frequency-doubled diode-pumped solid-state (DPSS) laser to measure the nonlinear absorption and nonlinear refractive index coefficients, respectively. The valley-to-peak profile of AC indicated a negative nonlinear refractive index coefficient. The obtained single crystals possess reverse saturation absorption due to excited-state absorption. The structural and nonlinear optical properties of the molecules have been discussed, along with the role of anthracene substitution for enhancing the nonlinear optical properties. The calculated third-order susceptibility value was 1.10 x10-4 esu at an intensity of 4.1 kW/cm2, higher than the reported values for related chalcone derivatives. The NLO response for both ACs offers excellent potential in optical switching and limiting applications.
  12. Zainulabid UA, Mat Yassim AS, Hussain M, Aslam A, Soffian SN, Mohd Ibrahim MS, et al.
    PLoS One, 2022;17(2):e0263678.
    PMID: 35213571 DOI: 10.1371/journal.pone.0263678
    SARS-CoV-2 has spread throughout the world since its discovery in China, and Malaysia is no exception. WGS has been a crucial approach in studying the evolution and genetic diversity of SARS-CoV-2 in the ongoing pandemic. Despite considerable number of SARS-CoV-2 genome sequences have been submitted to GISAID and NCBI databases, there is still scarcity of data from Malaysia. This study aims to report new Malaysian lineages of the virus, responsible for the sustained spikes in COVID-19 cases during the third wave of the pandemic. Patients with nasopharyngeal and/or oropharyngeal swabs confirmed COVID-19 positive by real-time RT-PCR with CT value < 25 were chosen for WGS. The selected SARS-CoV-2 isolates were then sequenced, characterized and analyzed along with 986 sequences of the dominant lineages of D614G variants currently circulating throughout Malaysia. The prevalence of clade GH and G formed strong ground for the presence of two Malaysian lineages of AU.2 and B.1.524 that has caused sustained spikes of cases in the country. Statistical analysis on the association of gender and age group with Malaysian lineages revealed a significant association (p <0.05). Phylogenetic analysis revealed dispersion of 41 lineages, of these, 22 lineages are still active. Mutational analysis showed presence of unique G1223C missense mutation in transmembrane domain of the spike protein. For better understanding of the SARS-CoV-2 evolution in Malaysia especially with reference to the reported lineages, large scale studies based on WGS are warranted.
  13. Zainordin NA, Eddy Warman NA, Mohamad AF, Abu Yazid FA, Ismail NH, Chen XW, et al.
    PLoS One, 2021;16(10):e0258507.
    PMID: 34644368 DOI: 10.1371/journal.pone.0258507
    INTRODUCTION: There is limited data on the effects of low carbohydrate diets on renal outcomes particularly in patients with underlying diabetic kidney disease. Therefore, this study determined the safety and effects of very low carbohydrate (VLCBD) in addition to low protein diet (LPD) on renal outcomes, anthropometric, metabolic and inflammatory parameters in patients with T2DM and underlying mild to moderate kidney disease (DKD).

    MATERIALS AND METHODS: This was an investigator-initiated, single-center, randomized, controlled, clinical trial in patients with T2DM and DKD, comparing 12-weeks of low carbohydrate diet (<20g daily intake) versus standard low protein (0.8g/kg/day) and low salt diet. Patients in the VLCBD group underwent 2-weekly monitoring including their 3-day food diaries. In addition, Dual-energy x-ray absorptiometry (DEXA) was performed to estimate body fat percentages.

    RESULTS: The study population (n = 30) had a median age of 57 years old and a BMI of 30.68kg/m2. Both groups showed similar total calorie intake, i.e. 739.33 (IQR288.48) vs 789.92 (IQR522.4) kcal, by the end of the study. The VLCBD group showed significantly lower daily carbohydrate intake 27 (IQR25) g vs 89.33 (IQR77.4) g, p<0.001, significantly higher protein intake per day 44.08 (IQR21.98) g vs 29.63 (IQR16.35) g, p<0.05 and no difference in in daily fat intake. Both groups showed no worsening of serum creatinine at study end, with consistent declines in HbA1c (1.3(1.1) vs 0.7(1.25) %) and fasting blood glucose (1.5(3.37) vs 1.3(5.7) mmol/L). The VLCBD group showed significant reductions in total daily insulin dose (39(22) vs 0 IU, p<0.001), increased LDL-C and HDL-C, decline in IL-6 levels; with contrasting results in the control group. This was associated with significant weight reduction (-4.0(3.9) vs 0.2(4.2) kg, p = <0.001) and improvements in body fat percentages. WC was significantly reduced in the VLCBD group, even after adjustments to age, HbA1c, weight and creatinine changes. Both dietary interventions were well received with no reported adverse events.

    CONCLUSION: This study demonstrated that dietary intervention of very low carbohydrate diet in patients with underlying diabetic kidney disease was safe and associated with significant improvements in glycemic control, anthropometric measurements including weight, abdominal adiposity and IL-6. Renal outcomes remained unchanged. These findings would strengthen the importance of this dietary intervention as part of the management of patients with diabetic kidney disease.

  14. Zaini MA, Mohd Zain A, Din NM, Mustapha M, Sidi H
    PLoS One, 2023;18(8):e0290260.
    PMID: 37624864 DOI: 10.1371/journal.pone.0290260
    BACKGROUND: Since the enforcement of the Movement Control Order (MCO) to contain the spread of COVID -19 infection in Malaysia, most clinic appointments have been rescheduled and procedures and surgeries postponed to a later date. Clinic appointments including intravitreal endothelial growth factor (anti-VEGF) treatment for patients with diabetic macular edema (DME) were also no exception to the postponement. This measure takes a psychological toll on patients because of the overwhelming concern for their eye condition. This study was conducted to assess the psychological status of DME patients with delayed anti-VEGF treatment during the pandemic.

    METHODS: A cross-sectional study was conducted from September 2020 to March 2021 in Ophthalmology Clinic Hospital Canselor Tuanku Muhriz Universiti Kebangsaan Malaysia (HCTM UKM). Subjects diagnosed with center-involved DME aged between 20 to 80 years who experienced delayed anti-VEGF injection were recruited. Level of depression, anxiety and stress were assessed using DASS-21 questionnaire. Statistical analysis using non-parametric tests were performed to determine the relationship between the DASS-21 score and duration of last injection, in those whose vision was affected by delayed injection and the relationship to the impact of COVID-19 pandemic. Statistical significance was denoted as p < 0.05.

    RESULTS: A total of 86 respondents with median age of 69 years old participated in this study. Most respondents were Malays (n = 47,54.7%) males (n = 51, 59.3%), had education up to secondary level (n = 37, 43%), unemployed (n = 78, 90.7%), married (n = 72, 83.7%) and living with their family (n = 82, 95.3%). The number of intravitreal injections received was at least three times among the respondents (n = 81, 94.2%). More than half of the respondents (n = 46, 53.5%) had been postponed for more than 12 weeks and felt that their vision was affected after delayed intravitreal injection (n = 47, 54.7%). Most of the subjects did not experience depression, anxiety, or stress. However, there was a significant level of stress scores among those with delayed injection of 9 to 12 weeks (p = 0.004), and significant anxiety (p = 0.029) and stress (p = 0.014) scores found in subjects with vision affected due to delayed treatment.

    CONCLUSION: The level of anxiety and stress can be significant in DME patients who experienced delay in intravitreal anti-VEGF treatment. Assessment of psychosocial impacts is important to identify early mental health issues potentially leading to the onset of psychiatry illness, thus early intervention is indispensable.

  15. Zainal H, Dahlui M, Soelar SA, Su TT
    PLoS One, 2019;14(6):e0211997.
    PMID: 31237874 DOI: 10.1371/journal.pone.0211997
    Preterm birth incidence has risen globally and remains a major cause of neonatal mortality despite improved survival. Demand and cost of initial hospitalization has also increased. This study assessed the cost of preterm birth during initial hospitalization from care provider perspective in neonatal intensive care units (NICU) of two hospitals in the state of Kedah, Malaysia. It utilized universal sampling and prospectively followed up preterm infants till discharge. Care provider cost was assessed using mixed method of top down approach and activity based costing. A total of 112 preterm infants were recruited from intensive care (93 infants) and minimal care (19 infants) units. Majority were from the moderate (23%) and late (36%) preterm groups followed by very preterm (32%) and extreme preterm (9%). Median cost per infant increased with level of care and degree of prematurity. Cost was dominated by overhead (fixed) costs for general (hospital), intermediate (clinical support services) and final (NICU) cost centers where it constituted at least three quarters of admission cost per infant while the remainder was consumables (variable) cost. Breakdown of overhead cost showed NICU specific overhead contributing at least two thirds of admission cost per infant. Personnel salary made up three quarters of NICU specific overhead. Laboratory investigation was the cost driver for consumables. Gender, birth weight and length of stay were significant factors and cost prediction was developed with these variables. This study demonstrated the inverse relation between resource utilization, cost and prematurity and identified personnel salary as the cost driver. Cost estimates and prediction provide in-depth understanding of provider cost and are applicable for further economic evaluations. Since gender is non-modifiable and reducing LOS alone is not effective, birth weight as a cost predictive factor in this study can be addressed through measures to prevent or delay preterm birth.
  16. Zainal Abidin SAI, Paterson IC, Hunt S, Lambert DW, Higginbotham S, Pink RC
    PLoS One, 2021;16(11):e0256812.
    PMID: 34762649 DOI: 10.1371/journal.pone.0256812
    Transforming growth factor-beta 1 (TGF-β1), a pro-fibrotic tumour-derived factor promotes fibroblast differentiation in the tumour microenvironment and is thought to contribute to the development of pro-tumourigenic cancer-associated fibroblasts (CAFs) by promoting myofibroblast differentiation. miRNA dysregulation has been demonstrated in myofibroblast transdifferentiation and CAF activation, however, their expression varies among cell types and with the method of fibroblast induction. Here, the expression profile of miRNA in human primary oral fibroblasts treated with TGF-β1, to derive a myofibroblastic, CAF-like phenotype, was determined compared to untreated fibroblasts. Myofibroblast transdifferentiation was determined by the expression of alpha-smooth muscle actin (α-SMA) and fibronectin-1 extra domain A (FN-EDA1) using quantitative real-time PCR (qRT-PCR) and western blot. The formation of stress fibres was assessed by fluorescence microscopy, and associated changes in contractility were assessed using collagen contraction assays. Extracellular vesicles (EVs) were purified by using size exclusion chromatography and ultracentrifugation and their size and concentration were determined by nanoparticle tracking analysis. miRNA expression profiling in oral fibroblasts treated with TGF-β1 and their extracellular vesicles was carried out using tiling low-density array cards. The Database for Annotation, Visualization, and Integrated Discovery (DAVID) was used to perform functional and pathway enrichment analysis of target genes. In this study, TGF-β1 induced a myofibroblastic phenotype in normal oral fibroblasts as assessed by expression of molecular markers, the formation of stress fibres and increased contractility. TaqMan Low-Density Array (TLDA) analysis demonstrated that miR-503 and miR-708 were significantly upregulated, while miR-1276 was significantly downregulated in TGF-β1-treated oral fibroblasts (henceforth termed experimentally-derived CAF, eCAF). The gene functional enrichment analysis showed that the candidate miRNAs have the potential to modulate various pathways; including the Ras associated protein 1 (Rap1), PI3K-Akt, and tumour necrosis factor (TNF) signalling pathways. In addition, altered levels of several miRNAs were detected in eCAF EV, including miR-142 and miR-222. No differences in size or abundance of EV were detected between eCAF and normal oral fibroblast (NOF). Little overlap was observed between changes in cellular and EV miRNA profiles, suggesting the possibility of selective loading of EV miRNA. The study reveals miRNA expression signature could be involved in myofibroblast transdifferentiation and the miRNA cargo of their EV, providing novel insight into the involvement of miRNA in CAF development and function.
  17. Zain SM, Mohamed R, Cooper DN, Razali R, Rampal S, Mahadeva S, et al.
    PLoS One, 2014;9(4):e95604.
    PMID: 24743702 DOI: 10.1371/journal.pone.0095604
    Between 10 and 25% of individuals with non-alcoholic fatty liver disease (NAFLD) develop hepatic fibrosis leading to cirrhosis and hepatocellular carcinoma (HCC). To investigate the molecular basis of disease progression, we performed a genome-wide analysis of copy number variation (CNV) in a total of 49 patients with NAFLD [10 simple steatosis and 39 non-alcoholic steatohepatitis (NASH)] and 49 matched controls using high-density comparative genomic hybridization (CGH) microarrays. A total of 11 CNVs were found to be unique to individuals with simple steatosis, whilst 22 were common between simple steatosis and NASH, and 224 were unique to NASH. We postulated that these CNVs could be involved in the pathogenesis of NAFLD progression. After stringent filtering, we identified four rare and/or novel CNVs that may influence the pathogenesis of NASH. Two of these CNVs, located at 13q12.11 and 12q13.2 respectively, harbour the exportin 4 (XPO4) and phosphodiesterase 1B (PDE1B) genes which are already known to be involved in the etiology of liver cirrhosis and HCC. Cross-comparison of the genes located at these four CNV loci with genes already known to be associated with NAFLD yielded a set of genes associated with shared biological processes including cell death, the key process involved in 'second hit' hepatic injury. To our knowledge, this pilot study is the first to provide CNV information of potential relevance to the NAFLD spectrum. These data could prove invaluable in predicting patients at risk of developing NAFLD and more importantly, those who will subsequently progress to NASH.
  18. Zain SM, Mohamed Z, Mahadeva S, Rampal S, Basu RC, Cheah PL, et al.
    PLoS One, 2013;8(3):e58538.
    PMID: 23484035 DOI: 10.1371/journal.pone.0058538
    Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.
  19. Zain NM, Ismail Z
    PLoS One, 2023;18(2):e0276576.
    PMID: 36780455 DOI: 10.1371/journal.pone.0276576
    This paper presents a numerical analysis of blood flow in a diseased vessel within the presence of an external magnetic field. The blood flow was considered to be incompressible and fully developed, in that the non-Newtonian nature of the fluid was characterised as a generalised power law model for shear-thinning, Newtonian, and shear-thickening fluids. The impact of a transverse directed external magnetic field on blood flow through a stenosed bifurcated artery was investigated. The arterial geometry was considered as a bifurcated channel with overlapping shaped stenosis. The problem was treated mathematically using the Galerkin Least-Squares (GLS) method. The implementation of this numerical method managed to overcome the numerical instability faced by the classical Galerkin technique when adopted to a highly viscous flow. The benefit of GLS in circumventing the Ladyzhenskaya-Babuška-Brezzi (LBB) condition was utilized by evaluating both the velocity and pressure components at corner nodes of a unstructured triangular element. The non-linearity that emerged from the convective terms was then treated using the Newton-Raphson method, while the numerical integrals were computed using a Gaussian quadrature rule with six quadrature points. The findings obtained from this study were then compared with available results from the literature as well as Comsol multiphysics software to verify the accuracy and validity of the numerical algorithms. It was found that the application of magnetic field was able to overcome flow reversal by 39% for a shear-thinning fluid, 26% for a Newtonian fluid, and 27% for a shear-thickening fluid. The negative pressure and steep wall shear stress which occurs at the extremities of an overlapping stenosis throat were diminished by rise in magnetic intensity. This prevented thrombosis occurrence and produced a uniform calm flow.
  20. Zaimi K, Ishak A, Pop I
    PLoS One, 2014;9(11):e111743.
    PMID: 25365118 DOI: 10.1371/journal.pone.0111743
    The steady two-dimensional flow and heat transfer over a stretching/shrinking sheet in a nanofluid is investigated using Buongiorno's nanofluid model. Different from the previously published papers, in the present study we consider the case when the nanofluid particle fraction on the boundary is passively rather than actively controlled, which make the model more physically realistic. The governing partial differential equations are transformed into nonlinear ordinary differential equations by a similarity transformation, before being solved numerically by a shooting method. The effects of some governing parameters on the fluid flow and heat transfer characteristics are graphically presented and discussed. Dual solutions are found to exist in a certain range of the suction and stretching/shrinking parameters. Results also indicate that both the skin friction coefficient and the local Nusselt number increase with increasing values of the suction parameter.
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