Displaying publications 81 - 93 of 93 in total

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  1. Roy J, Yin Wong K, Aquili L, Sahab Uddin M, Chin Heng B, Lim Tipoe G, et al.
    Front Neuroendocrinol, 2022 Feb 12.
    PMID: 35167824 DOI: 10.1016/j.yfrne.2022.100986
    Melatonin and novel melatonin-based therapies such as melatonin-containing hybrid molecules, melatonin analogues, and melatonin derivatives have been investigated as potential therapeutics against Alzheimer's disease (AD) pathogenesis. In this review, we examine the developmental trends of melatonin therapies for AD from 1997 to 2021. We then highlight the neuroprotective mechanisms of melatonin therapy derived from preclinical studies. These mechanisms include the alleviation of amyloid-related burden, neurofibrillary tangle accumulation, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, and impaired neuroplasticity and neurotransmission. We further illustrate the beneficial effects of melatonin on behavior in animal models of AD. Next, we discuss the clinical effects of melatonin on sleep, cognition, behavior, psychiatric symptoms, electroencephalography findings, and molecular biomarkers in patients with mild cognitive impairment and AD. We then explore the effectiveness of novel melatonin-based therapies. Lastly, we discuss the limitations of current melatonin therapies for AD and suggest two emerging research themes for future study.
  2. Cahyanto A, Rath P, Teo TX, Tong SS, Malhotra R, Cavalcanti BN, et al.
    J Dent Res, 2023 Dec;102(13):1425-1433.
    PMID: 37861249 DOI: 10.1177/00220345231198185
    Calcium silicate (C3S) cements are available in kits that do not account for patients' specific needs or clinicians' preferences regarding setting time, radiopacity, mechanical, and handling properties. Moreover, slight variations in powder components and liquid content affect cement's properties and bioactivity. Unfortunately, it is virtually impossible to optimize several cement properties simultaneously via the traditional "one variable at a time" strategy, as inputs often induce trade-offs in properties (e.g., a higher water-to-powder ratio [W/P] increases flowability but decreases mechanical properties). Herein, we used Taguchi's methods and genetic algorithms (GAs) to simultaneously analyze the effect of multiple inputs (e.g., powder composition, radiopacifier concentration, and W/P) on setting time, pH, flowability, diametral tensile strength, and radiopacity, as well as prescribe recipes to produce cements with predicted properties. The properties of cements designed with GAs were experimentally tested, and the results matched the predictions. Finally, we show that the cements increased the genetic expression of odonto/osteogenic genes, alkaline phosphatase activity, and mineralization potential of dental pulp stem cells. Hence, GAs can produce cements with tailor-made properties and differentiation potential for personalized endodontic treatment.
  3. Ooi MH, Lewthwaite P, Lai BF, Mohan A, Clear D, Lim L, et al.
    Clin Infect Dis, 2008 Aug 15;47(4):458-68.
    PMID: 18616397 DOI: 10.1086/590008
    BACKGROUND: Japanese encephalitis is a major public health problem in Asia. However, there is little data on the long-term outcome of Japanese encephalitis survivors.

    METHODS: We prospectively evaluated children with serologically confirmed Japanese encephalitis over an 8.3-year period. The patients were assessed and their outcomes were graded with a functional outcome score at hospital discharge and at follow-up appointments. We examined how patient outcome at hospital discharge compared with that at long-term follow-up visits, when changes in outcome occurred, and the prognostic indicators of the eventual outcome.

    RESULTS: One hundred and eighteen patients were recruited into the study, and 10 (8%) died during the acute phase of illness. At hospital discharge, 44 (41%) of the 108 patients who survived had apparent full recovery; 3 (3%) had mild, 28 (26%) had moderate, and 33 (31%) had severe neurological sequelae. Eighty six of the 108 patients were followed up for a median duration of 52.9 months (range, 0.9-114.9 months). During follow-up, 31 patients experienced improvement, but 15 patients experienced deterioration in their outcome grade. In most cases, assessment during the first 3-6 months after hospital discharge was predictive of the long-term outcome. More than one-half of the patients continued to experience neuropsychological sequelae and behavioral disorders. A combination of poor perfusion, Glasgow coma score < or =8, and > or =2 witnessed seizures predicted a poor long-term outcome with 65% sensitivity and 92% specificity.

    CONCLUSIONS: Neurological assessment of Japanese encephalitis survivors at hospital discharge does not predict long-term outcome. Seizures and shock are treatable risk factors for a poor outcome at hospital discharge and at long-term follow-up visits.

  4. Paramasivam SS, Chinna K, Singh AKK, Ratnasingam J, Ibrahim L, Lim LL, et al.
    Diabet Med, 2018 08;35(8):1118-1129.
    PMID: 29663517 DOI: 10.1111/dme.13649
    AIMS: To determine if therapeutic, retrospective continuous glucose monitoring (CGM) improves HbA1c with less hypoglycaemia in women with insulin-treated gestational diabetes mellitus (GDM).

    METHODS: This prospective, randomized controlled, open-label trial evaluated 50 women with insulin-treated GDM randomized to either retrospective CGM (6-day sensor) at 28, 32 and 36 weeks' gestation (Group 1, CGM, n = 25) or usual antenatal care without CGM (Group 2, control, n = 25). All women performed seven-point capillary blood glucose (CBG) profiles at least 3 days per week and recorded hypoglycaemic events (symptomatic and asymptomatic CBG l; non-fasting l). HbA1c was measured at 28, 33 and 37 weeks. In Group 1, both CGM and CBG data were used to manage diabetes, whereas mothers in Group 2 were managed based on CBG data alone.

    RESULTS: Baseline characteristics (age, pre-pregnancy BMI, HbA1c , total insulin dose) were similar between groups. There was a lower increase in HbA1c from 28 to 37 weeks' gestation in the CGM group [∆HbA1c : CGM + 1 mmol/mol (0.09%), control + 3mmol/mol (0.30%); P = 0.024]. Mean HbA1c remained unchanged throughout the trial in the CGM group, but increased significantly in controls as pregnancy advanced. Mean HbA1c in the CGM group was lower at 37 weeks compared with controls [33 ± 4 mmol/mol (5.2 ± 0.4%) vs. 38 ± 7 mmol/mol (5.6 ± 0.6%), P 

  5. Sit NW, Chan YS, Lai SC, Lim LN, Looi GT, Tay PL, et al.
    J Mycol Med, 2018 Sep;28(3):561-567.
    PMID: 30060991 DOI: 10.1016/j.mycmed.2018.07.001
    OBJECTIVES: This study was conducted to evaluate the antidermatophytic activity of 48 extracts obtained from medicinal plants (Cibotium barometz, Melastoma malabathricum, Meuhlenbeckia platyclada, Rhapis excelsa, Syzygium myrtifolium, Vernonia amygdalina) and marine algae (Caulerpa sertularioides, Kappaphycus alvarezii) against Trichophyton rubrum and Trichophyton interdigitale (ATCC reference strains), and the cytotoxicity using African monkey kidney epithelial (Vero) cells. Active plant extracts were screened for the presence of phytochemicals and tested against clinical isolates of Trichophyton tonsurans.

    METHODS: Six different extracts (hexane, chloroform, ethyl acetate, ethanol, methanol and water) were obtained from each plant or algae sample using sequential solvent extraction. The antidermatophytic activity for the extracts was assessed using a colourimetric broth microdilution method. The viability of Vero cells was measured by Neutral Red uptake assay.

    RESULTS: All the extracts (except the water extracts of V. amygdalina, C. sertularioides and K. alvarezii) showed antidermatophytic activity against Trichophyton spp. The minimum fungicidal concentration (MFC) ranges for the plant extracts against T. rubrum and T. interdigitale are 0.0025-2.50 and 0.005-2.50mg/mL, respectively. The algae extracts exhibited lower potency against both species, showing MFC ranges of 0.08-2.50 and 0.31-2.50mg/mL, respectively. The ethanol and methanol extracts from the leaves of R. excelsa, and the methanol and water extracts from the leaves of S. myrtifolium were highly active (MFC<0.1mg/mL) and with high selectivity indices (SI>2.8) against reference strains of T. rubrum and T. interdigitale, and most of the clinical isolates of T. tonsurans. Phytochemical analysis indicates the presence of alkaloids, anthraquinones, flavonoids, saponins, tannins, phenolics and triterpenoids in the extracts.

    CONCLUSIONS: The medicinal plant extracts exhibited stronger antidermatophytic activity compared to the algae extracts. The leaves of R. excelsa and S. myrtifolium are potential sources of new antidermatophytic agents against Trichophyton spp.

  6. Fong SL, Thuy Le MA, Lim KS, Khosama H, Ohnmar O, Savath S, et al.
    Epilepsia, 2023 Aug;64(8):2116-2125.
    PMID: 37243851 DOI: 10.1111/epi.17668
    OBJECTIVE: One of the objectives of the Intersectoral Global Action Plan on epilepsy and other neurological disorders for 2022 to 2031 is to ensure at least 80% of people with epilepsy (PWE) will have access to appropriate, affordable, and safe antiseizure medications (ASMs) by 2031. However, ASM affordability is a significant issue in low- and middle-income countries, preventing PWE from accessing optimal treatment. This study aimed to determine the affordability of the newer (second and third generation) ASMs in resource-limited countries in Asia.

    METHODS: We conducted a cross-sectional survey by contacting country representatives in lower-middle-income countries (LMICs) in Asia, including Indonesia, Lao People's Democratic Republic (PDR), Myanmar, Philippines, Vietnam, India, Bangladesh, and Pakistan, and the upper-middle-income country Malaysia, from March 2022 to April 2022. The affordability of each ASM was calculated by dividing the 30-day ASM cost by the daily wage of the lowest paid unskilled laborers. Treatment costing 1 day's wage or less for a 30-day supply of chronic disease is considered affordable.

    RESULTS: Eight LMICs and one upper-middle-income country were included in this study. Lao PDR had no newer ASM, and Vietnam had only three newer ASMs. The most frequently available ASMs were levetiracetam, topiramate, and lamotrigine, and the least frequently available was lacosamide. The majority of the newer ASMs were unaffordable, with the median number of days' wages for a 30-day supply ranging from 5.6 to 14.8 days.

    SIGNIFICANCE: All new generation ASMs, whether original or generic brands, were unaffordable in most Asian LMICs.

  7. Chong WH, Ong HY, Ooi JS, Eleen Khaw YY, Lim LM, Tew MM, et al.
    Med J Malaysia, 2024 Mar;79(2):184-190.
    PMID: 38553924
    INTRODUCTION: Hypoxic ischemic encephalopathy (HIE) is a clinically defined syndrome of disturbed neurologic function in the newborn with evidence of perinatal asphyxia. Stages of HIE are categorised into mild, moderate or severe based on the Sarnat classification. Neurological dysfunction constitutes a part of the wide spectrum of hypoxic ischemic insult as affected infants can have co-existing multi-organ dysfunction which further contributes to morbidities and mortality. This study aims to determine the relationship between the severity of HIE with multi-organ complications and early clinical outcomes.

    MATERIALS AND METHODS: All neonates who were admitted to the NICU at Hospital Sultan Abdul Halim between January 2018 to December 2022, who fulfilled the inclusion criteria were included. Demographic data, clinical course and investigation results were retrospectively obtained from the medical records.

    RESULTS: From a total of 90 infants (n = 90) who fulfilled our inclusion criteria, 31 (34%) were mild, 31 (34%) were moderate and 28 (31%) were severe HIE. The mean maternal age was 27 years. Common antenatal issues include diabetes mellitus (37.8%) and anaemia (22.2%). The Apgar scores at 1 and 5 minutes, initial resuscitation requiring intubation, chest compression and adrenaline were associated with higher severity of HIE (p < 0.05). Coagulation dysfunction was the most common complication (79.7%), followed by respiratory dysfunction (33.3%), cardiac dysfunction (28.9%), renal dysfunction (16.1%), haematological dysfunction (15.6%) and hepatic dysfunction (12%). Respiratory and haematological dysfunctions were significantly associated with higher mortality (p < 0.05). There was a significant longer hospital stay (p = 0.023), longer duration of ventilation (p < 0.001) and increase in frequency of seizures (p < 0.001) when comparing moderate and severe HIE patients to mild HIE patients. With increasing severity of HIE, there was also statistically significant higher mortality (p < 0.001).

    CONCLUSIONS: There is a significant relationship between multiorgan dysfunction, the severity of HIE and mortality. Early anticipation of multi-organ injury is crucial for optimal early management which would reduce the mortality and improve the neurological outcome of the patients.

  8. Inoue Y, Tiamkao S, Zhou D, Cabral-Lim L, Lim KS, Lim SH, et al.
    Epilepsia Open, 2024 Apr 04.
    PMID: 38576178 DOI: 10.1002/epi4.12929
    OBJECTIVE: Evaluate efficacy, safety, and tolerability of adjunctive brivaracetam (BRV) in adult Asian patients with focal-onset seizures (FOS).

    METHODS: Phase III, randomized, double-blind, placebo-controlled study (EP0083; NCT03083665) evaluating BRV 50 mg/day and 200 mg/day in patients (≥16-80 years) with FOS with/without secondary generalization (focal to bilateral tonic-clonic seizures) despite current treatment with 1 or 2 concomitant antiseizure medications. Following an 8-week baseline, patients were randomized 1:1:1 to placebo, BRV 50 mg/day, or BRV 200 mg/day, and entered a 12-week treatment period. Efficacy outcomes: percent reduction over placebo in 28-day FOS frequency (primary); 50% responder rate in FOS frequency; median percent reduction in FOS frequency from baseline; seizure freedom during treatment period (secondary). Primary safety endpoints: incidences of treatment-emergent adverse events (TEAEs); TEAEs leading to discontinuation; serious TEAEs.

    RESULTS: In this study, 448/449 randomized patients (mean age, 34.5 years; 53.8% female) received ≥1 dose of study medication (placebo/BRV 50 mg/BRV 200 mg/day: n = 149/151/148). Percent reduction over placebo in 28-day adjusted FOS frequency was 24.5% (p = 0.0005) and 33.4% (p 

  9. Thuy Le MA, Fong SL, Lim KS, Gunadharma S, Sejahtera DP, Visudtibhan A, et al.
    Seizure, 2019 Jul;69:51-56.
    PMID: 30974407 DOI: 10.1016/j.seizure.2019.04.002
    PURPOSE: This survey was performed to determine the availability of epilepsy surgery, and understand the limiting factors to epilepsy surgery in ASEAN countries with total of 640 million population.

    METHOD: A cross-sectional survey was completed by national representatives in all ASEAN countries (Brunei, Cambodia, East Timor, Indonesia, Laos, Malaysia, Myanmar, Philippines, Singapore, Thailand, and Vietnam).

    RESULTS: Overall facilities for initial epilepsy pre-surgical evaluation are available in most countries, but further non-invasive and invasive investigations are limited. Three countries (Brunei, Cambodia, and East Timor) have no epilepsy center, and 2 countries (Laos, Myanmar) have level 2 centers doing tumor surgery only. Level-3 epilepsy centers are available in 6 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand, Vietnam); only 5 countries (Indonesia, Malaysia, Philippine, Singapore, Thailand) has at least one level-4 epilepsy care facility. Indonesia with 261 million population only has one level 3 and another level 4 center. The costs of presurgical evaluation and brain surgery vary within and among the countries. The main barriers towards epilepsy surgery in ASEAN include lack of expertise, funding and facilities.

    CONCLUSIONS: Epilepsy surgery is underutilized in ASEAN with low number of level 3 centers, and limited availability of advanced presurgical evaluation. Lack of expertise, facilities and funding may be the key factors contributing to the underutilization.

  10. Samsuddin S, Arumugam PA, Md Amin MS, Yahya A, Musa N, Lim LL, et al.
    BJOG, 2020 03;127(4):490-499.
    PMID: 31778255 DOI: 10.1111/1471-0528.16031
    OBJECTIVE: To determine the association between maternal lipaemia and neonatal anthropometrics in Malaysian mother-offspring pairs.

    DESIGN: Prospective observational cohort study.

    SETTING: Single tertiary multidisciplinary antenatal clinic in Malaysia.

    POPULATION: A total of 507 mothers: 145 with gestational diabetes mellitus (GDM); 94 who were obese with normal glucose tolerance (NGT) (pre-gravid body mass index, BMI ≥ 27.5 kg/m2 ), and 268 who were not obese with NGT.

    METHODS: Maternal demographic, anthropometric, and clinical data were collected during an interview/examination using a structured questionnaire. Blood was drawn for insulin, C-peptide, triglyceride (Tg), and non-esterified fatty acid (NEFA) during the 75-g 2-hour oral glucose tolerance test (OGTT) screening, and again at 36 weeks of gestation. At birth, neonatal anthropometrics were assessed and data such as gestational weight gain (GWG) were extracted from the records.

    MAIN OUTCOME MEASURES: Macrosomia, large-for-gestational-age (LGA) status, cohort-specific birthweight (BW), neonatal fat mass (NFM), and sum of skinfold thickness (SSFT) > 90th centile.

    RESULTS: Fasting Tg > 95th centile (3.6 mmol/L) at screening for OGTT was independently associated with LGA (adjusted odds ratio, aOR 10.82, 95% CI 1.26-93.37) after adjustment for maternal glucose, pre-gravid BMI, and insulin sensitivity. Fasting glucose was independently associated with a birthweight ratio (BWR) of >90th centile (aOR 2.06, 95% CI 1.17-3.64), but not with LGA status, in this well-treated GDM cohort with pre-delivery HbA1c of 5.27%. In all, 45% of mothers had a pre-gravid BMI of <23 kg/m2 and 61% had a pre-gravid BMI of ≤ 25 kg/m2 , yet a GWG of >10 kg was associated with a 4.25-fold risk (95% CI 1.71-10.53) of BWR > 90th centile.

    CONCLUSION: Maternal lipaemia and GWG at a low threshold (>10 kg) adversely impact neonatal adiposity in Asian offspring, independent of glucose, insulin resistance and pre-gravid BMI. These may therefore be important modifiable metabolic targets in pregnancy.

    TWEETABLE ABSTRACT: Maternal lipids are associated with adiposity in Asian babies independently of pre-gravid BMI, GDM status, and insulin resistance.

  11. Schilthuizen M, Lim JP, van Peursen ADP, Alfano M, Jenging AB, Cicuzza D, et al.
    Biodivers Data J, 2020;8:e47484.
    PMID: 32132859 DOI: 10.3897/BDJ.8.e47484
    Background: Terrestrial Caenogastropoda form an important but threatened component of the Borneo tropical rainforest malacofauna, where the group is nearly as rich in species as the Stylommatophora. They are, however, more sensitive to drought, temperature extremes and forest degradation.

    New information: On a field course at Kuala Belalong Field Studies Centre in Brunei Darussalam (Borneo), a new caenogastropod species, belonging to the genus Craspedotropis, was discovered by the course participants. The participants decided to name the species Craspedotropis gretathunbergae n. sp., in honour of the climate change activist Greta Thunberg, as caenogastropod land snails, such as this species, are likely to suffer because of climate change.

  12. Lacroix R, McKemey AR, Raduan N, Kwee Wee L, Hong Ming W, Guat Ney T, et al.
    PLoS One, 2012;7(8):e42771.
    PMID: 22970102 DOI: 10.1371/journal.pone.0042771
    Dengue is the most important mosquito-borne viral disease. In the absence of specific drugs or vaccines, control focuses on suppressing the principal mosquito vector, Aedes aegypti, yet current methods have not proven adequate to control the disease. New methods are therefore urgently needed, for example genetics-based sterile-male-release methods. However, this requires that lab-reared, modified mosquitoes be able to survive and disperse adequately in the field.
  13. Brandt MJ, Kuppens T, Spears R, Andrighetto L, Autin F, Babincak P, et al.
    Eur J Soc Psychol, 2020 Aug;50(5):921-942.
    PMID: 32999511 DOI: 10.1002/ejsp.2694
    The relationships between subjective status and perceived legitimacy are important for understanding the extent to which people with low status are complicit in their oppression. We use novel data from 66 samples and 30 countries (N = 12,788) and find that people with higher status see the social system as more legitimate than those with lower status, but there is variation across people and countries. The association between subjective status and perceived legitimacy was never negative at any levels of eight moderator variables, although the positive association was sometimes reduced. Although not always consistent with hypotheses, group identification, self-esteem, and beliefs in social mobility were all associated with perceived legitimacy among people who have low subjective status. These findings enrich our understanding of the relationship between social status and legitimacy.
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