Displaying publications 1 - 20 of 24 in total

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  1. Tan ES, Ying-Yuan N, Gan CY
    Food Chem, 2014;152:447-55.
    PMID: 24444960 DOI: 10.1016/j.foodchem.2013.12.008
    Optimisation of protein extraction yield from pinto bean was investigated using response surface methodology. The maximum protein yield of 54.8 mg/g was obtained with the optimal conditions of: temperature=25 °C, time=1 h and buffer-to-sample ratio=20 ml/g. PBPI was found to obtain high amount of essential amino acids such as leucine, lysine, and phenylalanine compared to SPI. The predominant proteins of PBPI were vicilin and phytohemagglutinins whereas the predominant proteins of SPI were glycinin and conglycinins. Significantly higher emulsifying capacity was found in PBPI (84.8%) compared to SPI (61.9%). Different isoelectric points were found in both PBPI (4.0-5.5) and SPI (4.0-5.0). Also, it was found that PBPI obtained a much higher denaturation temperature of 110.2 °C compared to SPI (92.5 °C). Other properties such as structural information, gelling capacity, water- and oil-holding capacities, emulsion stability as well as digestibility were also reported.
  2. Tan EH, Batchelor P, Sheiham A
    Int Dent J, 2006 Oct;56(5):277-82.
    PMID: 17069070
    OBJECTIVES: To reassess the recall frequency interval for dental examinations for children, based on annual caries increments.

    METHODS: Cross sectional data collected on school children in eight rural and urban schools through the national Incremental Dental Care Programme (IDCP) for one district in Malaysia were analysed to assess their annual caries increment and trend lines. The Restorative Index was calculated to assess the success of the IDCP in rendering children dentally fit.

    RESULTS: The annual caries increments were low; the current caries levels were between 0.65 and 1.50 for 12 year-old children in Kota Tinggi District. Most of the caries experience was on pits and fissures. From 7 to 12 years old, the overall annual caries increment for the total study population was 0.19. The mean annual caries increment increased slightly between the ages of 12 to 14 years and 14 to 16 years and was 0.24 and 0.25 respectively. Two distinct caries incremental trend lines were observed for children aged 7 to 16 years. One group reached a mean DMFT of about 0.75 while the other group a mean DMFT of about 1.4 at 12 years. The trend lines continued over the next 4 years until the children were 16 years old. The Restorative Index was higher in urban schools that also had low DMFT levels.

    CONCLUSIONS: Based on the low annual caries increments of between 0.65 and 1.50, yearly dental examination intervals can safely be extended to 2-yearly intervals or even longer. Such a change of screening recall intervals would help improve resource allocation. Resources saved by extending recall intervals can be redirected to the small proportion of children with higher disease levels. This will help render more school children dentally fit and reduce inequalities in oral health.

  3. Ling TE, Othman K, Yan OP, Rashid RA, Tet CM, Yaakob A, et al.
    Open Ophthalmol J, 2017;11:31-39.
    PMID: 28400889 DOI: 10.2174/1874364101711010031
    OBJECTIVE: To evaluate the incidence of ocular surface disease (OSD) and to determine the effects of topical pressure-lowering drugs on ocular surface disease in primary angle closure patients.

    METHODS: This was a cross-sectional comparative study comparing primary angle closure glaucoma (PACG) patients (Group A) with primary angle closure and primary angle closure suspect (Group B). Group A was treated with topical pressure-lowering drugs; Group B was not. Data on ocular diagnosis and details of treatment were obtained from medical records. Ocular surface disease incidence was assessed using the Ocular Surface Disease Index (OSDI) questionnaire and from clinical signs using Schirmer's test, tear break-up time and corneal fluorescein stain. Predictive Analytic Software 20 and STATA analysis software were used for statistical analyses.

    RESULTS: Group A demonstrated a higher rate of OSD (OSDI 52.3%, Schirmer's test 70.5%, tear break-up time (TBUT) 75%, corneal staining 77.3%) compared to Group B (OSDI 39.0%, Schirmer's test 73.2%, TBUT 58.5% and cornea staining 14.6%) except for Schirmer's test. There was a significant difference in mean score of OSDI (p=0.004), TBUT (p=0.008) and cornea staining (p<0.001) between two groups. Primary angle closure glaucoma treated with more than two medications and for more than three years had worse ocular surface disease parameters but without statistical significant difference.

    CONCLUSION: Ocular surface disease is common in PACG patients treated with topical pressure-lowering drugs. Topical pressure-lowering drugs caused significant OSD symptoms and signs except for tear production in PACG patients. Thorough evaluation of ocular surface disease is important to ensure appropriate treatment and intervention in PACG patients.

  4. Chong DWQ, Jawahir S, Tan EH, Sararaks S
    PMID: 33921985 DOI: 10.3390/ijerph18094435
    Since its inception in 1986, the contents of the National Health and Morbidity Survey (NHMS) have been periodically updated to support emerging health data needs for evidence-based policy and program development. In 2018, the healthcare demand questionnaire was redesigned to capture diverse and changing population demand for healthcare services and their utilization pattern. This paper describes the methods and processes undertaken in redesigning the questionnaire. We aim to highlight the systematic and inclusive approach, enabling all potential evidence users to be involved, indirectly encouraging research evidence uptake for policy and program planning. We applied a systematic approach of comprehensive literature search for national-level population survey instruments implemented globally and translated non-English tools to English. The development phases were iterative, conducted in parallel with active stakeholder engagements. Here, we detailed the processes in the planning and exploratory phase as well as a qualitative assessment of the questionnaire. We included instruments from 45 countries. The majority were from the Organisation for Economic Co-operation and Development (OECD) countries and focused on perceived health, health-related behavior, and healthcare use. Thirty-four stakeholders from 14 areas of expertise were involved. Stakeholders identified additional content areas required, such as chronic pain, alternative use of healthcare services (community pharmacy, home-visit, and private medical laboratory), family doctor, and informal caregiving. The questionnaire, redesigned based on existing literature with concordant involvement and iterative feedback from stakeholders, improved the choice of health topics through the identification of new topics and modification of existing questions to better meet future evidence needs on health problems, strategy, and program planning towards strengthening the nation's health systems.
  5. RUDNICK A, TAN EE, LUCAS JK, OMAR MB
    Br Med J, 1965 May 15;1(5445):1269-72.
    PMID: 14278815
  6. Hamidi N, Tan YR, Jawahir S, Tan EH
    BMC Health Serv Res, 2021 Jul 04;21(1):649.
    PMID: 34217293 DOI: 10.1186/s12913-021-06656-1
    BACKGROUND: Community pharmacies provide alternatives for medication procurement and other basic and minor health-related services in addition to mainstream hospitals and primary healthcare services. This study aimed to determine the characteristics of community pharmacy users and associated factors for community pharmacy utilisation in Malaysia.

    METHODS: Secondary data analysis was performed using data from the National Health and Morbidity Survey 2019, a nationwide cross-sectional household survey that used a two-stage stratified random sampling design. Adults aged 18 years and over were included in the analysis. Respondents who reported visiting the community pharmacy for health purposes two weeks prior to the study were considered as users. Complex sample descriptive statistics were used to describe the respondents' characteristics. Logistic regression analyses were employed to determine factors associated with community pharmacy utilisation.

    RESULTS: Of the 11,155 respondents interviewed, 10.3 % reported community pharmacy utilisation for health purposes. Females (OR = 1.41, 95 % CI = 1.14, 1.73), those with tertiary education (OR = 2.03, 95 % CI = 1.26, 3.29), urban dwellers (OR = 1.42, 95 % CI = 1.13, 1.79), and those with self-reported health problems (OR = 7.62, 95 % CI = 6.05, 9.59) were more likely to utilise the community pharmacy.

    CONCLUSIONS: Demographic and socioeconomic factors were important determinants of community pharmacy utilisation in Malaysia with sex, age, education level, locality, and self-reported health problems as the associated factors. These findings serve as evidence for policy interventions, crucial for improvements in accessibility to healthcare services.

  7. Tan EW, Simon SE, Numan A, Khalid M, Tan KO
    Colloids Surf B Biointerfaces, 2024 Mar;235:113793.
    PMID: 38364521 DOI: 10.1016/j.colsurfb.2024.113793
    Breast cancer is a global health concern that requires personalized therapies to prevent relapses, as conventional treatments may develop resistance over time. Photothermal therapy using spectral radiation or intense light emission is a broad-spectrum treatment that induces hyperthermia-mediated cancer cell death. MXene, a two-dimensional material, has been reported to have potential biological applications in photothermal therapy for cancer treatment. In this study, we investigated the apoptotic activity of MXene and UV-irradiated MXene in MCF-7 breast cancer cells by treating them with varying concentrations of MXene. The cytotoxicity of MXene and UV was evaluated by analyzing cellular morphology, nuclei condensation, caspase activation, and apoptotic cell death. We also assessed the effect of the combined treatment on the expression and cellular distribution of Tubulin, a key component of microtubules required for cell division. At low concentrations of MXene (up to 100 µg/ml), the level of cytotoxicity in MCF-7 cells was low. However, the combined treatment of MXene and UV resulted in a synergistic increase in cytotoxicity, causing rounded cellular morphology, condensed nuclei, caspase activation, and apoptotic cell death. Furthermore, the treatment reduced Tubulin protein expression and cellular distribution, indicating a potent inducer of cell death with potential application for cancer treatment. The study demonstrates that the combined treatment of MXene and UVB irradiation is a promising strategy for inducing apoptotic cell death in breast cancer cells, suggesting its potential as a therapeutic intervention for breast cancer.
  8. Tan EW, Tan KY, Phang LV, Kumar PV, In LLA
    PLoS One, 2019;14(7):e0219912.
    PMID: 31335895 DOI: 10.1371/journal.pone.0219912
    Vaccine administration via the oral route is preferable to parenteral routes due to ease of administration. To date, most available oral vaccines comprises of live attenuated pathogens as oppose to peptide-based vaccines due to its low bioavailability within the gastrointestinal (GI) tract. Over the years, probiotic-based peptide delivery vehicles comprising of lactic acid bacteria such as Lactococcus lactis has emerged as an interesting alternative due to its generally recognized as safe (GRAS) status, a fully sequenced genome, transient gut colonization time, and is an efficient cellular factory for heterologous protein production. However, its survivability through the GI tract is low, thus better delivery approaches are being explored to improve its bioavailability. In this study, we employ the incorporation of a double coated mucoadhesive film consisting of sodium alginate and Lycoat RS 720 film as the inner coat. The formulated film exhibits good mechanical properties of tensile strength and percent elongation for manipulation and handling with an entrapment yield of 93.14±2.74%. The formulated mucoadhesive film is subsequently loaded into gelatin capsules with an outer enteric Eudragit L100-55 coating capable of a pH-dependent breakdown above pH 5.5 to protect against gastric digestion. The final product and unprotected controls were subjected to in vitro simulated gastrointestinal digestions to assess its survivability. The product demonstrated enhanced protection with an increase of 69.22±0.67% (gastric) and 40.61±8.23% (intestinal) survivability compared to unprotected controls after 6 hours of sequential digestion. This translates to a 3.5 fold increase in overall survivability. Owing to this, the proposed oral delivery system has shown promising potential as a live gastrointestinal vaccine delivery host. Further studies involving in vivo gastrointestinal survivability and mice immunization tests are currently being carried out to assess the efficacy of this novel oral delivery system in comparison to parenteral routes.
  9. Tan YR, Tan EH, Jawahir S, Mohd Hanafiah AN, Mohd Yunos MH
    BMC Oral Health, 2021 01 19;21(1):34.
    PMID: 33468125 DOI: 10.1186/s12903-020-01388-w
    BACKGROUND: Throughout the years, oral healthcare utilisation in Malaysia has been low despite various efforts by the Ministry of Health Malaysia for improvement. This study aimed to determine the prevalence of oral healthcare utilisation and identify factors associated with oral healthcare utilisation among adults in Malaysia.

    METHODS: Secondary data analysis of adults aged 18 years and over from the National Health and Morbidity Survey 2019 was conducted in this study. Characteristics of respondents and those who utilised oral healthcare were described using complex sample descriptive statistics. Logistic regression analysis was performed to examine the association between the dependent and independent variables. Dependent variable was oral healthcare utilisation in the last 12 months. Independent variables were demographic and socioeconomic factors (predisposing, enabling and need characteristics) based on Andersen's Behavioural Model.

    RESULTS: A total of 11,308 respondents, estimated to represent 21.7 million adults aged 18 years and over in Malaysia were included in the analysis. Prevalence of oral healthcare utilisation in the last 12 months was 13.2%. Demographic factors of sex, age, marital status, and socioeconomic factors of education level and occupation as well as health belief such as medical check-up were significantly related to oral healthcare utilisation. Enabling factor of household income quintile had significant association with oral healthcare utilisation. Inequalities were observed; females (OR = 1.57, 95% CI = 1.25, 1.96), younger adults (OR = 1.64, 95% CI = 1.15, 2.33), those who were married (OR = 1.65, 95% CI = 1.23, 2.22), those with higher education (OR = 2.21, 95% CI = 1.23, 3.99), those who had medical check-up in the last 12 months (OR = 1.86, 95% CI = 1.53, 2.25) and those with higher income (OR = 1.43, 95% CI = 1.04, 1.96) were more likely to utilise oral healthcare.

    CONCLUSION: Understanding factors associated with utilisation of oral healthcare could help in formulating effective interventions to improve oral healthcare utilisation. Demographic and socioeconomic factors are strong determinants of oral healthcare utilisation in Malaysia. Appropriate interventions to strengthen the existing programmes aimed to promote regular and timely oral health check-ups are needed to improve oral healthcare utilisation.

  10. Kong YL, Anis-Syakira J, Jawahir S, R'ong Tan Y, Rahman NHA, Tan EH
    BMC Public Health, 2021 Jun 01;21(1):1033.
    PMID: 34074275 DOI: 10.1186/s12889-021-11022-1
    BACKGROUND: The increase in the elderly population, chronic and degenerative diseases, as well as accidents at work and on the road in Malaysia would result in an increased demand for informal care. This paper aimed to determine the associated factors of informal caregiving and its effects on health, work and social activities of adult informal caregivers in Malaysia.

    METHODS: The data from the 2019 National Health and Morbidity Survey (NHMS), a nationwide cross-sectional survey with a two-stage stratified random sampling design, was used in this research. The study included respondents who were 18 years and older (n = 11,674). Data were obtained via face-to-face interviews using validated questionnaires. Descriptive and complex sample logistic regression analyses were employed as appropriate.

    RESULTS: 5.7% of the adult population were informal caregivers. Provision of informal care were significantly associated with the female sex (OR = 1.52, 95% CI [1.21, 1.92]), those aged 36-59 years (OR = 1.61, 95% CI [1.15, 2.25]), and those who reported illness in the past 2 weeks (OR = 1.79, 95% CI [1.38, 2.33]). The risk of having their health affected were associated with female caregivers (OR = 3.63, 95% CI [1.73, 7.61]), those who received training (OR = 2.10, 95% CI [1.10, 4.00]) and those who provided care for 2 years or more (OR = 1.91, 95% CI [1.08, 3.37]). The factors associated with the effects on work were ethnicity, received training and had no assistance to provide the care. In terms of effect on social activities, female caregivers (OR = 1.96, 95% CI [1.04, 3.69]) and caregivers who received training were more likely (OR = 2.19, 95% CI [1.22, 3.93]) to have their social activities affected.

    CONCLUSION: Our study revealed that sex, age, and self-reported illness were factors associated with being an informal caregiver in Malaysia. Informal caregivers faced effects on their health, work, and social activities which may be detrimental to their well-being. This understanding is crucial for planning support for caregivers.

  11. Simon SE, Lim HS, Jayakumar FA, Tan EW, Tan KO
    PMID: 35082905 DOI: 10.1155/2022/7548191
    α-Mangostin, one of the major constituents of Garcinia mangostana, has been reported to possess several biological activities, including antioxidant, anti-inflammatory, antibacterial, and cytotoxic activities associated with the inhibition of cell proliferation and activation of apoptosis. However, the cellular signaling pathway mediated by α-mangostin has not been firmly established. To investigate the cellular activities of α-mangostin, human cancer cells, MCF-7 and MCF-7-CR cells, were treated with α-mangostin to measure the cellular responses, including cytotoxicity, protein-protein interaction, and protein expression. Cancer cells stably expressed Myc-BCL-XL and HA-MOAP-1 were also included in the studies to delineate the cell signaling events mediated by α-mangostin. Our results showed that the apoptosis signaling mediated by α-mangostin involves the upregulation of endogenous MOAP-1, which interacts with α-mangostin activated BAX (act-BAX) while downregulating the expression of BCL-XL. Moreover, α-mangostin was found to induce BAX oligomerization, the release of mitochondrial cytochrome C, and activation of caspase in MCF-7 cells. In overexpression studies, MCF-7 cells and spheroids stably expressed HA-MOAP-1 and Myc-BCL-XL exhibited differential chemosensitivity toward α-mangostin in which the stable clones expressing HA-MOAP-1 and MYC-BCL-XL were chemosensitive and chemoresistant to the apoptosis signaling events mediated by α-mangostin, respectively, when compared to untreated cells. Together, the data suggest that the cytotoxicity of α-mangostin involves the activation of MOAP-1 tumor suppressor and its interaction with act-BAX, leading to mitochondria dysfunction and cell death.
  12. Jawahir S, Tan EH, Tan YR, Mohd Noh SN, Ab Rahim I
    BMC Health Serv Res, 2021 Apr 27;21(1):391.
    PMID: 33906646 DOI: 10.1186/s12913-021-06412-5
    BACKGROUND: Provision of informal care may adversely affect health, daily and social activities of the informal caregivers, but few studies have examined these effects in relation to caregiving intensity. This study examined the predictive factors associated with the effects of caregiving roles on health, daily and social activities of informal caregivers, accounting for caregiving intensity.

    METHODS: Data of adults aged 18 years and over from the National Health and Morbidity Survey 2019 were used. Respondent's demographic, socioeconomic, health, and caregiving-related characteristics were described using complex samples analysis. Logistic regression analysis was performed to examine the factors affecting health, daily and social activities of caregivers, accounting for caregiving intensity.

    RESULTS: Five point one percent of adults in Malaysia provided informal care. High intensity caregivers were more likely to be actively employed and provided longer duration of care compared with low intensity caregivers. For low intensity caregiving, females, those aged 35-59 years, and those with long-term condition were more likely to have negative effects on health. Daily activities of non-Malays were more likely to be affected, while no factor was found significantly associated with effect on social activities. For high intensity caregiving, caregivers aged 60 and over, those received training and those without assistance were more likely to have negative effects on health. Daily activities of those without assistance were more likely to be affected. Social activities of non-Malays, those received training and those providing care for 2 years or more were more likely to be affected.

    CONCLUSIONS: Our study indicates that both low- and high-intensity caregivers have common features, with the exception of employment status and care duration. Caregiving, regardless of intensity, has a significant impact on caregivers. In order to reduce the negative consequences of caregiving responsibilities, all caregivers need assistance from the community and government, that is customised to their needs. By addressing the factors contributing to the negative effects of caregiving, a continuation of informal caregiving can be sustained through policies supporting the growing demand for informal care necessitated by an ageing population and higher life expectancy in Malaysia.

  13. Brett M, McPherson J, Zang ZJ, Lai A, Tan ES, Ng I, et al.
    PLoS One, 2014;9(4):e93409.
    PMID: 24690944 DOI: 10.1371/journal.pone.0093409
    Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81-84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.
  14. Song AA, Abdullah JO, Abdullah MP, Shafee N, Othman R, Tan EF, et al.
    PLoS One, 2012;7(12):e52444.
    PMID: 23300671 DOI: 10.1371/journal.pone.0052444
    Isoprenoids are a large and diverse group of metabolites with interesting properties such as flavour, fragrance and therapeutic properties. They are produced via two pathways, the mevalonate pathway or the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway. While plants are the richest source of isoprenoids, they are not the most efficient producers. Escherichia coli and yeasts have been extensively studied as heterologous hosts for plant isoprenoids production. In the current study, we describe the usage of the food grade Lactococcus lactis as a potential heterologous host for the production of sesquiterpenes from a local herbaceous Malaysian plant, Persicaria minor (synonym Polygonum minus). A sesquiterpene synthase gene from P. minor was successfully cloned and expressed in L. lactis. The expressed protein was identified to be a β-sesquiphellandrene synthase as it was demonstrated to be functional in producing β-sesquiphellandrene at 85.4% of the total sesquiterpenes produced based on in vitro enzymatic assays. The recombinant L. lactis strain developed in this study was also capable of producing β-sesquiphellandrene in vivo without exogenous substrates supplementation. In addition, overexpression of the strain's endogenous 3-hydroxy-3-methylglutaryl coenzyme-A reductase (HMGR), an established rate-limiting enzyme in the eukaryotic mevalonate pathway, increased the production level of β-sesquiphellandrene by 1.25-1.60 fold. The highest amount achieved was 33 nM at 2 h post-induction.
  15. Rannan-Eliya RP, Anuranga C, Manual A, Sararaks S, Jailani AS, Hamid AJ, et al.
    Health Aff (Millwood), 2016 May 01;35(5):838-46.
    PMID: 27140990 DOI: 10.1377/hlthaff.2015.0863
    Malaysia has made substantial progress in providing access to health care for its citizens and has been more successful than many other countries that are better known as models of universal health coverage. Malaysia's health care coverage and outcomes are now approaching levels achieved by member nations of the Organization for Economic Cooperation and Development. Malaysia's results are achieved through a mix of public services (funded by general revenues) and parallel private services (predominantly financed by out-of-pocket spending). We examined the distributional aspects of health financing and delivery and assessed financial protection in Malaysia's hybrid system. We found that this system has been effective for many decades in equalizing health care use and providing protection from financial risk, despite modest government spending. Our results also indicate that a high out-of-pocket share of total financing is not a consistent proxy for financial protection; greater attention is needed to the absolute level of out-of-pocket spending. Malaysia's hybrid health system presents continuing unresolved policy challenges, but the country's experience nonetheless provides lessons for other emerging economies that want to expand access to health care despite limited fiscal resources.
  16. Ker DS, Pang SL, Othman NF, Kumaran S, Tan EF, Krishnan T, et al.
    PeerJ, 2017;5:e2961.
    PMID: 28265494 DOI: 10.7717/peerj.2961
    BACKGROUND: Sesquiterpenes are 15-carbon terpenes synthesized by sesquiterpene synthases using farnesyl diphosphate (FPP) as a substrate. Recently, a sesquiterpene synthase gene that encodes a 65 kDa protein was isolated from the aromatic plant Persicaria minor. Here, we report the expression, purification and characterization of recombinant P. minor sesquiterpene synthase protein (PmSTS). Insights into the catalytic active site were further provided by structural analysis guided by multiple sequence alignment.

    METHODS: The enzyme was purified in two steps using affinity and size exclusion chromatography. Enzyme assays were performed using the malachite green assay and enzymatic product was identified using gas chromatography-mass spectrometry (GC-MS) analysis. Sequence analysis of PmSTS was performed using multiple sequence alignment (MSA) against plant sesquiterpene synthase sequences. The homology model of PmSTS was generated using I-TASSER server.

    RESULTS: Our findings suggest that the recombinant PmSTS is mainly expressed as inclusion bodies and soluble aggregate in the E. coli protein expression system. However, the addition of 15% (v/v) glycerol to the protein purification buffer and the removal of N-terminal 24 amino acids of PmSTS helped to produce homogenous recombinant protein. Enzyme assay showed that recombinant PmSTS is active and specific to the C15 substrate FPP. The optimal temperature and pH for the recombinant PmSTS are 30 °C and pH 8.0, respectively. The GC-MS analysis further showed that PmSTS produces β-sesquiphellandrene as a major product and β-farnesene as a minor product. MSA analysis revealed that PmSTS adopts a modified conserved metal binding motif (NSE/DTE motif). Structural analysis suggests that PmSTS may binds to its substrate similarly to other plant sesquiterpene synthases.

    DISCUSSION: The study has revealed that homogenous PmSTS protein can be obtained with the addition of glycerol in the protein buffer. The N-terminal truncation dramatically improved the homogeneity of PmSTS during protein purification, suggesting that the disordered N-terminal region may have caused the formation of soluble aggregate. We further show that the removal of the N-terminus disordered region of PmSTS does not affect the product specificity. The optimal temperature, optimal pH, Km and kcat values of PmSTS suggests that PmSTS shares similar enzyme characteristics with other plant sesquiterpene synthases. The discovery of an altered conserved metal binding motif in PmSTS through MSA analysis shows that the NSE/DTE motif commonly found in terpene synthases is able to accommodate certain level of plasticity to accept variant amino acids. Finally, the homology structure of PmSTS that allows good fitting of substrate analog into the catalytic active site suggests that PmSTS may adopt a sesquiterpene biosynthesis mechanism similar to other plant sesquiterpene synthases.

  17. Fun WH, Sararaks S, Tan EH, Tang KF, Chong DWQ, Low LL, et al.
    BMC Health Serv Res, 2019 Apr 24;19(1):248.
    PMID: 31018843 DOI: 10.1186/s12913-019-4072-7
    BACKGROUND: Health Research Priority Setting (HRPS) in the Ministry of Health (MOH) Malaysia was initiated more than a decade ago to drive effort toward research for informed decision and policy-making. This study assessed the impact of funded prioritised research and identified research gaps to inform future priority setting initiatives for universal access and quality healthcare in Malaysia.

    METHODS: Research impact of universal access and quality healthcare projects funded by the National Institutes of Health Malaysia were assessed based on the modified Payback Framework, addressing categories of informing policy, knowledge production, and benefits to health and health sector. For the HRPS process, the Child Health and Nutrition Research Initiative methodology was adapted and adopted, with the incorporation of stakeholder values using weights and monetary allocation survey. Workshop discussions and interviews with stakeholders and research groups were conducted to identify research gaps, with the use of conceptual frameworks to guide the search.

    RESULTS: Seventeen ongoing and 50 completed projects were identified for research funding impact analysis. Overall, research fund allocation differed from stakeholders' expectation. For research impact, 48 out of 50 completed projects (96.0%) contributed to some form of policy-making efforts. Almost all completed projects resulted in outputs that contributed to knowledge production and were expected to lead to health and health sector benefits. The HRPS process led to the identification of research priority areas that stemmed from ongoing and new issues identified for universal access and quality healthcare.

    CONCLUSION: The concerted efforts of evaluation of research funding impact, prioritisation, dissemination and policy-maker involvement were valuable for optimal health research resource utilisation in a resource constrained developing country. Embedding impact evaluation into a priority setting process and funding research based on national needs could facilitate health research investment to reach its potential.

  18. Ng AWR, Tan PJ, Hoo WPY, Liew DS, Teo MYM, Siak PY, et al.
    PeerJ, 2018;6:e5056.
    PMID: 30042874 DOI: 10.7717/peerj.5056
    Background: Somatic point substitution mutations in the KRAS proto-oncogene primarily affect codons 12/13 where glycine is converted into other amino acids, and are highly prevalent in pancreatic, colorectal, and non-small cell lung cancers. These cohorts are non-responsive to anti-EGFR treatments, and are left with non-specific chemotherapy regimens as their sole treatment options. In the past, the development of peptide vaccines for cancer treatment was reported to have poor AT properties when inducing immune responses. Utilization of bioinformatics tools have since become an interesting approach in improving the design of peptide vaccines based on T- and B-cell epitope predictions.

    Methods: In this study, the region spanning exon 2 from the 4th to 18th codon within the peptide sequence of wtKRAS was chosen for sequence manipulation. Mutated G12V and G13D K-ras controls were generated in silico, along with additional single amino acid substitutions flanking the original codon 12/13 mutations. IEDB was used for assessing human and mouse MHC class I/II epitope predictions, as well as linear B-cell epitopes predictions, while RNA secondary structure prediction was performed via CENTROIDFOLD. A scoring and ranking system was established in order to shortlist top mimotopes whereby normalized and reducing weighted scores were assigned to peptide sequences based on seven immunological parameters. Among the top 20 ranked peptide sequences, peptides of three mimotopes were synthesized and subjected to in vitro and in vivo immunoassays. Mice PBMCs were treated in vitro and subjected to cytokine assessment using CBA assay. Thereafter, mice were immunized and sera were subjected to IgG-based ELISA.

    Results: In silico immunogenicity prediction using IEDB tools shortlisted one G12V mimotope (68-V) and two G13D mimotopes (164-D, 224-D) from a total of 1,680 candidates. Shortlisted mimotopes were predicted to promote high MHC-II and -I affinities with optimized B-cell epitopes. CBA assay indicated that: 224-D induced secretions of IL-4, IL-5, IL-10, IL-12p70, and IL-21; 164-D triggered IL-10 and TNF-α; while 68-V showed no immunological responses. Specific-IgG sera titers against mutated K-ras antigens from 164-D immunized Balb/c mice were also elevated post first and second boosters compared to wild-type and G12/G13 controls.

    Discussion: In silico-guided predictions of mutated K-ras T- and B-cell epitopes were successful in identifying two immunogens with high predictive scores, Th-bias cytokine induction and IgG-specific stimulation. Developments of such immunogens are potentially useful for future immunotherapeutic and diagnostic applications against KRAS(+) malignancies, monoclonal antibody production, and various other research and development initiatives.

  19. Lim PC, Tan HH, Mohd Noor NA, Chang CT, Wong TY, Tan EL, et al.
    J Pharm Policy Pract, 2023 Jul 05;16(1):83.
    PMID: 37408067 DOI: 10.1186/s40545-023-00583-8
    BACKGROUND: Pharmacist's involvement in optimizing medication adherence among diabetic patients has been implemented for over a decade. Diabetes Medication Therapy Adherence Clinic (DMTAC) was set up to educate diabetic patients, monitor treatment outcomes, and manage drug-related problems. While evidence shows that pharmacist-led DMTAC was effective in reducing HbA1c, there was limited data regarding the impact of different intervention types and default to follow-up on glycemic control.

    AIM: To assess the impact DMTAC on glycemic control and the difference in glycemic control between hospital and health clinic settings as well as defaulter and non-defaulter. In addition, the impact of pharmacist's interventions, DMTAC follow-up frequencies, and duration of diabetes on glycemic control were also determined.

    METHODS: A retrospective study was conducted among diabetes patients under DMTAC care between January 2019 and June 2020 in five hospitals and 23 primary health clinics. Patients' demographics data, treatment regimens, frequencies of DMTAC visits, defaulter (absent from DMTAC visits) and types of pharmacists' intervention were retrieved from patients' medical records and electronic database. HbA1c was collected at baseline, 4-6 months (post-1), and 8-12 months (post-2).

    RESULTS: We included 956 patients, of which 60% were females with a median age of 58.0 (IQR: 5.0) years. Overall, the HbA1c reduced significantly from baseline (median: 10.2, IQR: 3.0) to post-1 (median: 8.8, IQR: 2.7) and post-2 (median: 8.3, IQR: 2.6%) (p 

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