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  1. Ang GY, Yu CY, Subramaniam V, Abdul Khalid MI, Tuan Abdu Aziz TA, Johari James R, et al.
    PLoS One, 2016;11(10):e0164169.
    PMID: 27798644 DOI: 10.1371/journal.pone.0164169
    The human cytochrome P450 (CYP) is a superfamily of enzymes that have been a focus in research for decades due to their prominent role in drug metabolism. CYP2C is one of the major subfamilies which metabolize more than 10% of all clinically used drugs. In the context of CYP2C19, several key genetic variations that alter the enzyme's activity have been identified and catalogued in the CYP allele nomenclature database. In this study, we investigated the presence of well-established variants as well as novel polymorphisms in the CYP2C19 gene of 62 Orang Asli from the Peninsular Malaysia. A total of 449 genetic variants were detected including 70 novel polymorphisms; 417 SNPs were located in introns, 23 in upstream, 7 in exons, and 2 in downstream regions. Five alleles and seven genotypes were inferred based on the polymorphisms that were found. Null alleles that were observed include CYP2C19*3 (6.5%), *2 (5.7%) and *35 (2.4%) whereas allele with increased function *17 was detected at a frequency of 4.8%. The normal metabolizer genotype was the most predominant (66.1%), followed by intermediate metabolizer (19.4%), rapid metabolizer (9.7%) and poor metabolizer (4.8%) genotypes. Findings from this study provide further insights into the CYP2C19 genetic profile of the Orang Asli as previously unreported variant alleles were detected through the use of massively parallel sequencing technology platform. The systematic and comprehensive analysis of CYP2C19 will allow uncharacterized variants that are present in the Orang Asli to be included in the genotyping panel in the future.
  2. Abdul Hamid MF, Hasbullah AHH, Mohamad Jailaini MF, Nik Abeed NN, Ng BH, Haron H, et al.
    BMC Pulm Med, 2022 Nov 23;22(1):439.
    PMID: 36419155 DOI: 10.1186/s12890-022-02239-w
    BACKGROUND: Intrapleural fibrinolytic therapy (IPFT) is one of the treatment options for complex pleural effusion. In this study, the IPFT agent used was alteplase, a tissue plasminogen activator (t-PA). This study aims to determine the difference in the outcome of patients with complex pleural effusion between IPFT and surgery in terms of radiological improvement, inflammatory parameters, length of stay, and post-intervention complications.

    METHODS: A retrospective review of patients with complex pleural effusion treated at Universiti Kebangsaan Malaysia Medical Center from January 2012 to August 2020 was performed. Patient demographics, chest imaging, drainage chart, inflammatory parameters, length of hospital stay, and post-intervention and outcome were analyzed.

    RESULTS: Fifty-eight patients were identified (surgical intervention, n = 18; 31% and IPFT, n = 40, 69%). The mean age was 51.7 ± 18.2 years. Indication for surgical intervention was pleural infection (n = 18; 100%), and MPE (n = 0). Indications for IPFT was pleural infection (n = 30; 75%) and MPE (n = 10; 25%). The dosages of t-PA were one to five doses of 2-50 mg. The baseline chest radiograph in the IPFT group was worse than in the surgical intervention group. (119.96 ± 56.05 vs. 78.19 ± 55.6; p = 0.029) At week 1, the radiological success rate for IPFT and surgical intervention were 27% and 20%, respectively, and at weeks 4-8, the success rate was 56% and 80% respectively. IPFT was associated with lesser complications; fever (17.5%), chest pain (10%), and non-life-threatening bleeding (5%).

    CONCLUSION: IPFT was comparable to surgery in radiological outcome, inflammatory parameters, and length of stay with lesser reported complications.

  3. Abdul Rashid AM, Md Noh MSF, Yusof Khan AHK, Loh WC, Baharin J, Ibrahim A, et al.
    BMC Neurol, 2023 Feb 15;23(1):72.
    PMID: 36792988 DOI: 10.1186/s12883-023-03102-z
    BACKGROUND AND AIMS: The corononavirus 2019 (COVID-19) pandemic resulted in modifications in the workflow and redistribution of human resources, causing challenges in setting up of an acute stroke service. We would like to share our preliminary outcome amid this pandemic, to determine if the implementation of COVID-19 standard operating procedures (SOPs) affected the delivery of our hyperacute stroke service.

    METHODS: We retrospectively analyzed one-year data from our stroke registry that began with the establishment of our hyperacute stroke service at Universiti Putra Malaysia Teaching Hospital from April 2020 until May 2021.

    RESULTS: Setting up acute stroke services during the pandemic with constrained manpower and implementation of COVID-19 SOPs, was challenging. There was a significant dip of stroke admission from April to June 2020 due to the Movement Control Order (MCO) implemented by the government to curb the spread of COVID-19. However, the numbers of stroke admission steadily rose approaching 2021, after the implementation of recovery MCO. We managed to treat 75 patients with hyperacute stroke interventions i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT) or both. Despite implementing COVID-19 SOPs and using magnetic resonance imaging (MRI) as our first line acute stroke imaging modality, clinical outcomes in our cohort were encouraging; almost 40% of patients who underwent hyperacute stroke treatment had early neurological recovery (ENR), and only 33% of patients had early neurological stability (ENS). In addition, we were able to maintain our door-to-imaging (DTI) and door-to-needle (DTN) time in line with international recommendations.

    CONCLUSIONS: Our data reflects that COVID-19 SOPs did not deter successful delivery of hyperacute stroke services in our center. However, bigger and multi center studies are required to support our findings.

  4. Abdullah-Fauzi NAF, Karuppannan KV, Mohd-Radzi NHS, Gani M, Mohd-Ridwan AR, Othman N, et al.
    Zool Stud, 2022;61:e60.
    PMID: 37007822 DOI: 10.6620/ZS.2022.61-60
    The world's largest terrestrial mammal, Asian elephants, are known to have enormous feeding needs. Several factors such as season, sex, age, and daily activities influence the amount of food required by an individual. Generally, captive elephants have a limited choice of food on a daily basis compared with that of elephants in the wild. Elephants in captivity are fed according to a prepared feeding schedule, whereas wild elephants are free to choose the type of plants that they consume in their natural habitat. In the past, ecological observations have been widely used to determine the diet of wild elephants. However, the molecular approach has never been carried out. In the present study, we aimed to; 1) identify the plant diet of wild Asian elephants in Taman Negara National Park (TNNP) according to their sex and age using high-throughput DNA metabarcoding; and 2) determine the dietary formulation of captive elephants based on the generated plant metabarcoding database. DNA was extracted from 24 individual fecal samples collected using noninvasive sampling techniques from TNNP and the National Elephant Conservation Centre (NECC) Kuala Gandah. Seven pooled samples from male adult, female adult, male subadult, female subadult, male juvenile, female juvenile, and captive elephants were amplified and sequenced targeting the trnL region (50-150 base pairs). The CLC Genomic Workbench and PAST 4.02 software were used for data analysis. In total, 24 orders, 41 families, 233 genera, and 306 species of plants were successfully detected in the diet of the Asian elephants. The most abundant plant genera consumed were Sporobolus (21.88%), Musa (21.48%), and Ficus (10.80%). Plant variation was lower in samples from male elephants than in those from female elephants. The plant species identified were correlated with the nutrient benefits required by elephants. Adults and subadults consumed more plant species than were consumed by juvenile elephants. However, there was no significant difference between ages and sexes. The findings of this study can be used as guidance by the Department of Wildlife and National Parks for the management of captive elephants, especially in NECC Kuala Gandah.
  5. Md Hanif SA, Hassan MR, Rafi'i MR, Abdul Halim AFN, Ahmad Zamzuri M'I, Ismail M, et al.
    PLoS Negl Trop Dis, 2024 May 06;18(5):e0012147.
    PMID: 38709822 DOI: 10.1371/journal.pntd.0012147
    BACKGROUND: Melioidosis, a tropical infectious disease caused by Burkholderia pseudomallei, is epidemic in most region in Southeast Asia with high case fatality. However, there is scanty information regarding the disease's epidemiological pattern, demographics, and underlying risk factors.

    METHOD: This 5-year retrospective study of 185 confirmed cases which were taken from the Negeri Sembilan Melioidosis Registry between 2018 and 2022. We aim to describe the incidence, mortality rate, case fatality, relationship with meteorology, and factors that influence mortality in this central region of Peninsular Malaysia.

    RESULTS: Incidence rate (IR) of melioidosis in Negeri Sembilan is varied at 1.9 to 5.1 with mean of 3.1 in 100,000 population per year. IR varied between districts in the state from zero to 22.01 in 100,000 population per year. Mortality rate were ranged from 0.17 to 0.74 cases with mean of 0.44 cases in 100,000 population per year. The case fatality rate of this state scattered from 8.70% to 16.67%. There were no significant linear associations between cases and deaths with monthly rainfall and humidity. The mean age of patients was 52.8 years, predominated with age around 41-60 years old. Males (77.8%) predominated, and the majority of cases were Malays (88.9%) and had exposed to soil related activities (74.6%). Mortality from melioidosis was more likely in Bumiputera and non-Malaysians (p<0.05). Patients who had at least one comorbidity were at a higher risk of death from melioidosis (p<0.05). Diabetes mellitus was found in 41.1% of all identified cases, making it a major underlying risk factor for both developing and dying from melioidosis (aOR:19.32, 95%CI:1.91-195.59, p<0.05). Hypertension and mortality status in melioidosis are also significantly correlated (aOR: 7.75, 95% CI: 2.26-26.61, p<0.05).

    CONCLUSION: The epidemiological patterns of cases reported from Negeri Sembilan are consistent for the most part from previous studies in other states in Malaysia and global with regard to its incidence, case fatality, demographic and predisposing chronic diseases. Diabetes mellitus and hypertension were significantly linked to increased mortality among all determinants.

  6. Abdullah SR, Wan Mohd Zin RM, Azizul NH, Sulaiman NS, Khalid NM, Mohd Salim Mullahi Jahn RJ, et al.
    JMIR Form Res, 2024 Apr 10;8:e51542.
    PMID: 38598283 DOI: 10.2196/51542
    BACKGROUND: Adult obesity and overweight pose a substantial risk to global public health and are associated with various noncommunicable diseases. Although intermittent fasting (IF) is increasingly used as a relatively new dietary strategy for weight loss, the effectiveness of 2 days per week of dry fasting remains unknown.

    OBJECTIVE: This study aims to evaluate the effectiveness of a combined dry IF and healthy plate (IFHP) and healthy plate (HP) intervention in improving anthropometric outcomes and body composition.

    METHODS: This nonrandomized controlled trial involved 177 adults who were overweight and obese. Among them, 91 (51.4%) were allocated to the IFHP group and 86 (48.6%) were allocated to the HP group. The overall study duration was 6 months (October 2020 to March 2021). The intervention was divided into 2 phases: supervised (3 months) and unsupervised (3 months). The data were collected at baseline, after the supervised phase (month 3), and after the unsupervised phase (month 6). Anthropometric (weight, height, waist circumference, and hip circumference) and body composition (body fat percentage, body fat mass, skeletal muscle mass, and visceral fat area) data were measured at all 3 data collection points. Sociodemographic data were obtained using a questionnaire at baseline.

    RESULTS: Most participants were female (147/177, 83.1%) and Malay (141/177, 79.7%). After 3 months, there were significant reductions in weight (difference -1.68; P.05).

    CONCLUSIONS: A combined IFHP intervention was effective in improving anthropometric outcomes and body composition in adults with overweight and obesity.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/33801.

  7. Cescon DW, Schmid P, Rugo HS, Im SA, Md Yusof M, Gallardo C, et al.
    J Natl Cancer Inst, 2024 May 08;116(5):717-727.
    PMID: 38070159 DOI: 10.1093/jnci/djad240
    BACKGROUND: In KEYNOTE-355 (NCT02819518), the addition of pembrolizumab to chemotherapy led to statistically significant improvements in progression-free survival and overall survival in patients with advanced triple-negative breast cancer with tumor programmed cell death ligand 1 (PD-L1) combined positive score of at least 10. We report patient-reported outcomes from KEYNOTE-355.

    METHODS: Patients were randomly assigned 2:1 to pembrolizumab 200 mg or placebo every 3 weeks for up to 35 cycles plus investigator's choice chemotherapy (nab-paclitaxel, paclitaxel, or gemcitabine plus carboplatin). The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30), Breast Cancer-Specific Quality of Life Questionnaire, and EuroQol 5-Dimension questionnaire visual analog scale were prespecified. Patient-reported outcomes were analyzed for patients who received at least 1 dose of study treatment and completed at least 1 patient-reported outcome assessment. Changes in patient-reported outcome scores from baseline were assessed at week 15 (latest time point at which completion and compliance rates were at least 60% and at least 80%, respectively). Time to deterioration in patient-reported outcomes was defined as time to first onset of at least a 10-point worsening in score from baseline.

    RESULTS: Patient-reported outcome analyses included 317 patients with tumor PD-L1 combined positive score of at least 10 (pembrolizumab plus chemotherapy: n = 217; placebo plus chemotherapy: n = 100). There were no between-group differences in change from baseline to week 15 in QLQ-C30 global health status/quality of life (QOL; least-squares mean difference = -1.81, 95% confidence interval [CI] = -6.92 to 3.30), emotional functioning (least-squares mean difference = -1.43, 95% CI = -7.03 to 4.16), physical functioning (least-squares mean difference = -1.05, 95% CI = -6.59 to 4.50), or EuroQol 5-Dimension questionnaire visual analog scale (least-squares mean difference = 0.18, 95% CI = -5.04 to 5.39) and no between-group difference in time to deterioration in QLQ-C30 global health status/QOL, emotional functioning, or physical functioning.

    CONCLUSIONS: Together with the efficacy and safety findings, patient-reported outcome results from KEYNOTE-355 support pembrolizumab plus chemotherapy as a standard of care for patients with advanced triple-negative breast cancer with tumor PD-L1 expression (combined positive score ≥10).

  8. Leong HY, Abdul Azize NA, Chew HB, Keng WT, Thong MK, Mohd Khalid MKN, et al.
    Orphanet J Rare Dis, 2019 06 14;14(1):143.
    PMID: 31200731 DOI: 10.1186/s13023-019-1105-6
    BACKGROUND: Mucopolysaccharidosis IVA (MPS IVA) is an autosomal recessive lysosomal storage disease due to N-acetylgalactosamine-6-sulfatase (GALNS) deficiency. It results in accumulation of the glycosaminoglycans, keratan sulfate and chondroitin-6-sulfate, leading to skeletal and other systemic impairments. Data on MPS IVA in Asian populations are scarce.

    METHODS: This is a multicentre descriptive case series of 21 patients comprising all MPS IVA patients in Malaysia. Mutational analysis was performed by PCR and Sanger sequencing of the GALNS gene in 17 patients.

    RESULTS: The patients (15 females and 6 males) had a mean age (± SD) of 15.5 (± 8.1) years. Mean age at symptom onset was 2.6 (± 2.1) years and at confirmed diagnosis was 6.9 (± 4.5) years. The study cohort included patients from all the main ethnic groups in Malaysia - 57% Malay, 29% Chinese and 14% Indian. Common presenting symptoms included pectus carinatum (57%) and genu valgum (43%). Eight patients (38%) had undergone surgery, most commonly knee surgeries (29%) and cervical spine decompression (24%). Patients had limited endurance with lower mean walking distances with increasing age. GALNS gene analysis identified 18 distinct mutations comprising 13 missense, three nonsense, one small deletion and one splice site mutation. Of these, eight were novel mutations (Tyr133Ser, Glu158Valfs*12, Gly168*, Gly168Val, Trp184*, Leu271Pro, Glu320Lys, Leu508Pro). Mutations in exons 1, 5 and 9 accounted for 51% of the mutant alleles identified.

    CONCLUSIONS: All the MPS IVA patients in this study had clinical impairments. A better understanding of the natural history and the clinical and genetic spectrum of MPS IVA in this population may assist early diagnosis, improve management and permit timely genetic counselling and prenatal diagnosis.

  9. Ab Hamid N, Mohd Noor SN, Susubi J, Isa NR, Md Rodzay R, Bachtiar Effendi AM, et al.
    Heliyon, 2020 Jan;6(1):e03230.
    PMID: 31993521 DOI: 10.1016/j.heliyon.2020.e03230
    In recent decades, dengue incidence has trended upward worldwide causing urgent needs for new or modified vector control methods. We modified the existing indoor residual spraying (IRS) method by applying insecticide on the outer walls of building structures in an outdoor residual spraying (ORS) study. A semi-field study was conducted to investigate the bio-efficacy of two different deltamethrin formulations: K-Othrine® Polyzone, new polymer-enhanced deltamethrin formulated as a suspension concentrate (SC-PE), and K-Othrine® WG 250, traditional deltamethrin formulated as water dispersible granule (WG). The residual bio-efficacy of deltamethrin SC-PE was compared to deltamethrin WG on finished cement surfaces applied to the outer walls at the Institute for Medical Research (IMR), Malaysia. Standard WHO cone wall bioassays were adapted to evaluate the effective duration of action of these deltamethrin formulations against susceptible laboratory-reared and wild, free-flying Aedes aegypti and Ae. albopictus. Analyses of bioassay results showed that deltamethrin SC-PE 30 mg/m2 has improved longevity in comparison to deltamethrin WG 30 mg/m2. Deltamethrin SC-PE 30 mg/m2 was effective until week 17 (producing > 80% mortality), surpassing deltamethrin WG 30 mg/m2 which only lasted until week 10. This was supported by post-hoc test analyses which demonstrated that deltamethrin SC-PE 30 mg/m2 produced the highest mean of mortality in laboratory-reared Aedes species and the wild Ae. albopictus. However, the effective duration of action of deltamethrin SC-PE (17 weeks) was less than the recommended period by WHO (6 months) but was reasonable given that the spraying was undertaken outdoor. This preliminary data could be of use for the deployment of locally adapted ORS operation in controlling dengue.
  10. Wong LP, Alias H, Md Fuzi AA, Omar IS, Mohamad Nor A, Tan MP, et al.
    PLoS One, 2021;16(3):e0248916.
    PMID: 33765039 DOI: 10.1371/journal.pone.0248916
    Since the first nationwide movement control order was implemented on 18 March 2020 in Malaysia to contain the coronavirus disease 2019 (COVID-19) outbreak, to what extent the uncertainty and continuous containment measures have imposed psychological burdens on the population is unknown. This study aimed to measure the level of mental health of the Malaysian public approximately 2 months after the pandemic's onset. Between 12 May and 5 September 2020, an anonymous online survey was conducted. The target group included all members of the Malaysian population aged 18 years and above. The Depression Anxiety Stress Scale (DASS-21) was used to assess mental health. There were increased depressive, anxiety and stress symptoms throughout the study period, with the depression rates showing the greatest increase. During the end of the data collection period (4 August-5 September 2020), there were high percentages of reported depressive (59.2%) and anxiety (55.1%) symptoms compared with stress (30.6%) symptoms. Perceived health status was the strongest significant predictor for depressive and anxiety symptoms. Individuals with a poorer health perception had higher odds of developing depression (odds ratio [OR] = 5.68; 95% confidence interval [CI] 3.81-8.47) and anxiety (OR = 3.50; 95%CI 2.37-5.17) compared with those with a higher health perception. By demographics, young people-particularly students, females and people with poor financial conditions-were more vulnerable to mental health symptoms. These findings provide an urgent call for increased attention to detect and provide intervention strategies to combat the increasing rate of mental health problems in the ongoing COVID-19 pandemic.
  11. Ramli AH, Swain P, Mohd Fahmi MSA, Abas F, Leong SW, Tejo BA, et al.
    Heliyon, 2024 Mar 15;10(5):e27462.
    PMID: 38495201 DOI: 10.1016/j.heliyon.2024.e27462
    Malaria remains a major public health problem worldwide, including in Southeast Asia. Chemotherapeutic agents such as chloroquine (CQ) are effective, but problems with drug resistance and toxicity have necessitated a continuous search for new effective antimalarial agents. Here we report on a virtual screening of ∼300 diarylpentanoids and derivatives, in search of potential Plasmodium falciparum lactate dehydrogenase (PfLDH) inhibitors with acceptable drug-like properties. Several molecules with binding affinities comparable to CQ were chosen for in vitro validation of antimalarial efficacy. Among them, MS33A, MS33C and MS34C are the most promising against CQ-sensitive (3D7) with EC50 values of 1.6, 2.5 and 3.1 μM, respectively. Meanwhile, MS87 (EC50 of 1.85 μM) shown the most active against the CQ-resistant Gombak A strain, and MS33A and MS33C the most effective P. knowlesi inhibitors (EC50 of 3.6 and 5.1 μM, respectively). The in vitro cytotoxicity of selected diarylpentanoids (MS33A, MS33C, MS34C and MS87) was tested on Vero mammalian cells to evaluate parasite selectivity (SI), showing moderate to low cytotoxicity (CC50 > 82 μM). In addition, MS87 exhibited a high SI and the lowest resistance index (RI), suggesting that MS87 may exert effective parasite inhibition with low resistance potential in the CQ-resistant P. falciparum strain. Furthermore, the in vivo toxicity of the molecules on early embryonic development, the cardiovascular system, heart rate, motor activity and apoptosis were assessed in a zebrafish animal model. The overall results indicate the preliminary potential of diarylpentanoids, which need further investigation for their development as new antimalarial agents.
  12. Tan YC, Mustangin M, Rosli N, Wan Ahmad Kammal WSE, Md Isa N, Low TY, et al.
    Cryobiology, 2024 Mar;114:104843.
    PMID: 38158171 DOI: 10.1016/j.cryobiol.2023.104843
    Coolant-assisted liquid nitrogen (LN) flash freezing of frozen tissues has been widely adopted to preserve tissue morphology for histopathological annotations in mass spectrometry-based spatial proteomics techniques. However, existing coolants pose health risks upon inhalation and are expensive. To overcome this challenge, we present our pilot study by introducing the EtOH-LN workflow, which demonstrates the feasibility of using 95 % ethanol as a safer and easily accessible alternative to existing coolants for LN-based cryoembedding of frozen tissues. Our study reveals that both the EtOH-LN and LN-only cryoembedding workflows exhibit significantly reduced freezing artifacts compared to cryoembedding in cryostat (p 
  13. Abu Bakar N, Wan Ibrahim WN, Zulkiflli AR, Saleh Hodin NA, Kim TY, Ling YS, et al.
    Ecotoxicol Environ Saf, 2023 May;256:114862.
    PMID: 37004432 DOI: 10.1016/j.ecoenv.2023.114862
    The widespread presence of mercury, a heavy metal found in the environment and used in numerous industries and domestic, raises concerns about its potential impact on human health. Nevertheless, the adverse effects of this environmental toxicant at low concentrations are often underestimated. There are emerging studies showing that accumulation of mercury in the eye may contribute to visual impairment and a comorbidity between autism spectrum disorders (ASD) trait and visual impairment. However, the underlying mechanism of visual impairment in humans and rodents is challenging. In response to this issue, zebrafish larvae with a cone-dominated retinal visual system were exposed to 100 nM mercury chloride (HgCl2), according to our previous study, followed by light-dark stimulation, a social assay, and color preference to examine the functionality of the visual system in relation to ASD-like behavior. Exposure of embryos to HgCl2 from gastrulation to hatching increased locomotor activity in the dark, reduced shoaling and exploratory behavior, and impaired color preference. Defects in microridges as the first barrier may serve as primary tools for HgCl2 toxicity affecting vision. Depletion of polyunsaturated fatty acids (PUFAs), linoleic acid, arachidonic acid (ARA), alpha-linoleic acid, docosahexaenoic acid (DHA), stearic acid, L-phenylalanine, isoleucine, L-lysine, and N-acetylputrescine, along with the increase of gamma-aminobutyric acid (GABA), sphingosine-1-phosphate, and citrulline assayed by liquid chromatography-mass spectrometry (LC-MS) suggest that these metabolites serve as biomarkers of retinal impairments that affect vision and behavior. Although suppression of adsl, shank3a, tsc1b, and nrxn1a gene expression was observed, among these tsc1b showed more positive correlation with ASD. Collectively, these results contribute new insights into the possible mechanism of mercury toxicity give rise to visual, cognitive, and social deficits in zebrafish.
  14. Sekar P, Ventura EF, Dhanapal ACTA, Cheah ESG, Loganathan A, Quen PL, et al.
    Nutrients, 2023 Jun 29;15(13).
    PMID: 37447274 DOI: 10.3390/nu15132948
    Diabetes and obesity are chronic diseases that are a burden to low- and middle-income countries. We conducted this systematic review to understand gene-diet interactions affecting the Southeast Asian population's risk of obesity and diabetes. The literature search was performed on Google Scholar and MEDLINE (PubMed) search engines independently by four reviewers who evaluated the eligibility of articles based on inclusion criteria. Out of 19,031 articles, 20 articles examining gene-diet interactions on obesity and/or diabetes-related traits met the inclusion criteria. Three (Malaysia, Indonesia, and Singapore) out of eleven Association of Southeast Asian Nations (ASEAN) countries have conducted studies on gene-diet interactions on obesity and diabetes. From the 20 selected articles, the most common interactions were observed between macronutrients and genetic risk score (GRS) on metabolic disease-related traits in the Malay, Chinese, and Indian ethnicities. Overall, we identified 29 significant gene-diet interactions in the Southeast Asian population. The results of this systematic review demonstrate ethnic-specific gene-nutrient interactions on metabolic-disease-related traits in the Southeast Asian population. This is the first systematic review to explore gene-diet interactions on obesity and diabetes in the Southeast Asian population and further research using larger sample sizes is required for better understanding and framing nutrigenetic approaches for personalized nutrition.
  15. Robson RC, Thomas SM, Langlois ÉV, Mijumbi R, Kawooya I, Antony J, et al.
    Health Res Policy Syst, 2023 Jun 06;21(1):45.
    PMID: 37280697 DOI: 10.1186/s12961-023-00992-w
    BACKGROUND: Demand for rapid evidence-based syntheses to inform health policy and systems decision-making has increased worldwide, including in low- and middle-income countries (LMICs). To promote use of rapid syntheses in LMICs, the WHO's Alliance for Health Policy and Systems Research (AHPSR) created the Embedding Rapid Reviews in Health Systems Decision-Making (ERA) Initiative. Following a call for proposals, four LMICs were selected (Georgia, India, Malaysia and Zimbabwe) and supported for 1 year to embed rapid response platforms within a public institution with a health policy or systems decision-making mandate.

    METHODS: While the selected platforms had experience in health policy and systems research and evidence syntheses, platforms were less confident conducting rapid evidence syntheses. A technical assistance centre (TAC) was created from the outset to develop and lead a capacity-strengthening program for rapid syntheses, tailored to the platforms based on their original proposals and needs as assessed in a baseline questionnaire. The program included training in rapid synthesis methods, as well as generating synthesis demand, engaging knowledge users and ensuring knowledge uptake. Modalities included live training webinars, in-country workshops and support through phone, email and an online platform. LMICs provided regular updates on policy-makers' requests and the rapid products provided, as well as barriers, facilitators and impacts. Post-initiative, platforms were surveyed.

    RESULTS: Platforms provided rapid syntheses across a range of AHPSR themes, and successfully engaged national- and state-level policy-makers. Examples of substantial policy impact were observed, including for COVID-19. Although the post-initiative survey response rate was low, three quarters of those responding felt confident in their ability to conduct a rapid evidence synthesis. Lessons learned coalesced around three themes - the importance of context-specific expertise in conducting reviews, facilitating cross-platform learning, and planning for platform sustainability.

    CONCLUSIONS: The ERA initiative successfully established rapid response platforms in four LMICs. The short timeframe limited the number of rapid products produced, but there were examples of substantial impact and growing demand. We emphasize that LMICs can and should be involved not only in identifying and articulating needs but as co-designers in their own capacity-strengthening programs. More time is required to assess whether these platforms will be sustained for the long-term.

  16. Noor Azhar M, Bustam A, Poh K, Ahmad Zahedi AZ, Mohd Nazri MZA, Azizah Ariffin MA, et al.
    Emerg Med J, 2021 Feb;38(2):111-117.
    PMID: 33219133 DOI: 10.1136/emermed-2020-210514
    BACKGROUND: Concerns over high transmission risk of SARS-CoV-2 have led to innovation and usage of an aerosol box to protect healthcare workers during airway intubation in patients with COVID-19. Its efficacy as a barrier protection in addition to the use of a standard personal protective equipment (PPE) is not fully known. We performed a simulated study to investigate the relationship between aerosol box usage during intubation and contaminations on healthcare workers pre-doffing and post-doffing of PPE.

    METHODS: This was a randomised cross-over study conducted between 9 April to 5 May 2020 in the ED of University Malaya Medical Centre. Postgraduate Emergency Medicine trainees performed video laryngoscope-assisted intubation on an airway manikin with and without an aerosol box in a random order. Contamination was simulated by nebulised Glo Germ. Primary outcome was number of contaminated front and back body regions pre-doffing and post-doffing of PPE of the intubator and assistant. Secondary outcomes were intubation time, Cormack-Lehane score, number of intubation attempts and participants' feedback.

    RESULTS: Thirty-six trainees completed the study interventions. The number of contaminated front and back body regions pre-doffing of PPE was significantly higher without the aerosol box (all p values<0.001). However, there was no significant difference in the number of contaminations post-doffing of PPE between using and not using the aerosol box, with a median contamination of zero. Intubation time was longer with the aerosol box (42.5 s vs 35.5 s, p<0.001). Cormack-Lehane scores were similar with and without the aerosol box. First-pass intubation success rate was 94.4% and 100% with and without the aerosol box, respectively. More participants reported reduced mobility and visibility when intubating with the aerosol box.

    CONCLUSIONS: An aerosol box may significantly reduce exposure to contaminations but with increased intubation time and reduced operator's mobility and visibility. Furthermore, the difference in degree of contamination between using and not using an aerosol box could be offset by proper doffing of PPE.

  17. Lee HC, Hamzah H, Leong MP, Md Yusof H, Habib O, Zainal Abidin S, et al.
    Sci Rep, 2021 Feb 15;11(1):3847.
    PMID: 33589712 DOI: 10.1038/s41598-021-83222-z
    Ruxolitinib is the first janus kinase 1 (JAK1) and JAK2 inhibitor that was approved by the United States Food and Drug Administration (FDA) agency for the treatment of myeloproliferative neoplasms. The drug targets the JAK/STAT signalling pathway, which is critical in regulating the gliogenesis process during nervous system development. In the study, we assessed the effect of non-maternal toxic dosages of ruxolitinib (0-30 mg/kg/day between E7.5-E20.5) on the brain of the developing mouse embryos. While the pregnant mice did not show any apparent adverse effects, the Gfap protein marker for glial cells and S100β mRNA marker for astrocytes were reduced in the postnatal day (P) 1.5 pups' brains. Gfap expression and Gfap+ cells were also suppressed in the differentiating neurospheres culture treated with ruxolitinib. Compared to the control group, adult mice treated with ruxolitinib prenatally showed no changes in motor coordination, locomotor function, and recognition memory. However, increased explorative behaviour within an open field and improved spatial learning and long-term memory retention were observed in the treated group. We demonstrated transplacental effects of ruxolitinib on astrogenesis, suggesting the potential use of ruxolitinib to revert pathological conditions caused by gliogenic-shift in early brain development such as Down and Noonan syndromes.
  18. Ashhar Z, Ahmad Fadzil MF, Md Safee Z, Aziz F, Ibarhim UH, Nik Afinde NMF, et al.
    Appl Radiat Isot, 2024 Mar;205:111161.
    PMID: 38163386 DOI: 10.1016/j.apradiso.2023.111161
    Due to increased demand, cyclotron has an expanding role in producing Gallium-68 (68Ga) radiopharmaceuticals using solid and liquid targets. Though the liquid target produces lower end-of-bombardment activity compared to the solid target, our study presents the performance of 68Ga radiopharmaceuticals production using the liquid target by evaluating the end-of-bombardment activity and the end-of-purification activity of [68Ga]GaCl3. We also present the effect of increasing irradiation time, which significantly improves the end-of-synthesis yield. From the result obtained, the end-of-bombardment activity produced was 4.48 GBq, and the [68Ga]GaCl3 end-of-purification activity produced was 2.51 GBq with below-limit metallic impurities. Increasing the irradiation time showed a significant increase in the end-of-synthesis activity from 1.33 GBq to 1.95 GBq for [68Ga]Ga-PSMA-11 and from 1.13 GBq to 1.74 GBq for [68Ga]Ga-DOTA-TATE. Based on the improvements made, the liquid target production of 68Ga radiopharmaceuticals is feasible and reproducible to accommodate up to 5 patients per production. In addition, this work also discusses the issues encountered, together with the possible corrective and preventative measures.
  19. Kamarudin SAA, Ahmad F, Hasan N, Hisham SN, Yusof SN, Abu Hassan A, et al.
    Data Brief, 2024 Feb;52:109974.
    PMID: 38229927 DOI: 10.1016/j.dib.2023.109974
    In Malaysia, rice mutant varieties that are genetically altered to confer resistance against blast disease have been substantially developed through mutational breeding program. However, due to the limited accessible information on the mutant lines, mutant gene variants corresponding to the disease resistance and other useful agronomic traits are yet to be exploited. Here, we conducted whole genome re-sequencing of blast resistance with kernel elongation traits in mutant line, Mahsuri Mutant (87,639,446 bp raw reads), and its parental line, Mahsuri (85,156,783 bp raw reads) using Illumina Novaseq 6000 sequencing platform with 30x sequencing coverage. The generated genome sequences are aimed to facilitate the discovery of causal mutation and single nucleotide polymorphisms (SNPs) related to the intended traits. The identified SNPs can be further employed to develop allele-specific SNP molecular markers to locate the mutant gene regions. The NGS data obtained (FASTQ format) of the parental and mutant lines have been deposited in the National Center for Biotechnology Information (NCBI) database under sequence read archive (SRA) xwith accession numbers SRR24388814 (Mahsuri) and SRR22952097 (Mahsuri Mutant) respectively.
  20. Othman MF, Zakaria AD, Yahya MM, Md Hashim MN, Wan Mokhter WM, Wan Zain WZ, et al.
    Malays J Med Sci, 2023 Oct;30(5):106-115.
    PMID: 37928791 DOI: 10.21315/mjms2023.30.5.9
    BACKGROUND: Polyethylene glycol (PEG) solution is widely used as a colonoscopic bowel cleaning agent, although some patients are intolerant due to the need for ingesting large solution volumes and unpleasant taste. A low-volume solution may enhance patient tolerability and compliance in bowel preparation. Accordingly, this study compared the effectiveness of two difference PEG volumes for bowel preparation before colonoscopy in terms of bowel cleanliness, completeness of colonoscopy, patient tolerability and colonoscopy duration.

    METHODS: Using a prospective randomised controlled single-blinded study design, 164 patients scheduled for colonoscopy were allocated to two groups (n = 82 patients in each) to receive either the conventional PEG volume (3 L, control group) or the low volume (2 L, intervention group). The Boston Bowel Preparation Scale (BBPS), a validated scale for assessing bowel cleanliness during colonoscopy, was used to score bowel cleanliness in three colon segments. Secondarily, colonoscopy completeness, tolerability to drinking PEG and the duration of colonoscopy were compared between the groups.

    RESULTS: There were no statistically significant differences between the two intervention groups in terms of bowel cleanliness (P = 0.119), colonoscopy completion (P = 0.535), tolerability (P = 0.190) or the amount of sedation/analgesia required (midazolam, P = 0.162; pethidine, P = 0.708). Only the duration of colonoscopy differed between the two groups (longer duration in the control group, P = 0.039).

    CONCLUSION: Low-volume (2 L) PEG is as effective as the standard 3 L solution in bowel cleaning before colonoscopy; however, the superiority of either solution could not be established.

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