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  1. Fulltext No evidence for association between DRD3 and COMT with schizophrenia in a Malay population
    Tee SF, Tang PY, Loh HC
    Genet. Mol. Res., 2011;10(3):1850-5.
    PMID: 21948748 DOI: 10.4238/vol10-3gmr1237
    Molecular components of the dopamine D3 receptor (DRD3) may play an important role in the pathophysiology of schizophrenia. Previous studies have demonstrated an association between DRD3 Ser9Gly and cathechol-o-methyltransferase (COMT, SNP = rs165656) polymorphisms and schizophrenia but the results were inconclusive. We investigated this apparent association between Ser9Gly (A/G) polymorphism and an intronic SNP (dbSNP or rs165656) in 261 Malay patients diagnosed with schizophrenia and 216 controls, using PCR-RFLP. The genotype distribution of the polymorphism DRD3 Ser9Gly was in Hardy-Weinberg equilibrium (HWE) for patients (P = 0.1251) and out of HWE for controls (P = 0.0137). However, both healthy controls and schizophrenia patients were out of HWE for the polymorphism COMT rs165656. Based on allele and genotype frequencies in both groups, we found no significant association of DRD3 Ser9Gly polymorphisms and COMT (rs165656) with schizophrenia in Malays. Further studies should examine the association between other dopamine-related genes and the behavioral phenotypes of schizophrenia.
  2. COMT haplotype analyses in Malaysians with schizophrenia
    Tee SF, Tang PY, Loh HC
    Psychiatry Res, 2012 Jan 30;195(1-2):83-4.
    PMID: 21872942 DOI: 10.1016/j.psychres.2011.07.039
    The present study included a total 261 patients with schizophrenia and 261 healthy controls to replicate the genetic association between the cathechol-o-methyltransferase gene and schizophrenia using a haplotype block-based gene-tagging. The G-G-G haplotype was found to show a highly significant association with schizophrenia.
  3. Genetic Association Analysis of Dopamine DRD3 Ser9Gly Polymorphism and Schizophrenia in Malay Population
    Tee S, Tang P, Loh H
    Iran J Public Health, 2011;40(2):6-10.
    PMID: 23113067
    BACKGROUND: Molecular components of the dopamine receptor (DRD3) play an important role in the pathophysiology of schizophrenia (SCZ). Previous studies have demonstrated an association between the DRD3 Ser9Gly polymorphism and SCZ but the results have been inconclusive.

    METHOD: In this study, we investigated this controversial association between the Ser9Gly (A/G) polymorphism and SCZ using Malay cases-control (261 cases/157 controls) samples. PCR-RFLP was performed to genotype the distribution of the DRD3 Ser9Gly polymorphism.

    RESULTS: Both healthy control and SCHZ patient groups were in of Hardy-Weinberg equilibrium for the analyzed genetic variability. There was a significant association between the genotype distribution DRD3 polymorphisms and SCZ (χ(2)= 9.359; df = 2; P = 0.009).

    CONCLUSION: We believe that further studies are required to examine the association between others dopamine-related genes and the behavioral phenotypes of SCZ.

  4. No association between AKT1 gene variants and schizophrenia: a Malaysian case-control study and meta-analysis
    Loh HC, Chow TJ, Tang PY, Yong HS
    Psychiatry Res, 2013 Oct 30;209(3):732-3.
    PMID: 23747160 DOI: 10.1016/j.psychres.2013.05.017
    We aim to replicate AKT1 gene variants studies using Malaysian samples. Seven AKT1 single nucleotide polymorphisms (SNPs) were studied in 417 patients and 429 controls. Haplotype showed significant association (p=0.036) with schizophrenia, especially in Malays and Indians. Meta-analysis of rs2494732 showed significant association worldwide (p=0.018) and in Asians (p=0.023).
  5. Evaluation of carotenoid level in schizophrenic patients using non-invasive measurement
    Chow TJ, Loh HC, Tee SF, Tang PY
    Asian J Psychiatr, 2010 Dec;3(4):190-3.
    PMID: 23050886 DOI: 10.1016/j.ajp.2010.09.006
    Free radicals are produced as part of the body immune response triggered by exogenous oxidants. In excess, they impair antioxidant defence system and cause oxidative stress. Antioxidants are hypothesised as antidotes to counteract oxidative stress and improve immune function. Carotenoids serve as a reliable indicator of overall antioxidant level in humans. This study investigated the possible relationship of carotenoid antioxidant levels in schizophrenia. A total of 351 schizophrenic subjects from Hospital Bahagia Ulu Kinta, Malaysia and 247 healthy controls were recruited. Subjects' skin carotenoid levels were measured using a non-invasive technique, Raman spectroscopy. The results showed significant (P<0.01) reduction of carotenoid level in patient compared to healthy controls, suggesting higher levels of oxidative stress in schizophrenia. Comparison between gender, age, subtypes, antipsychotic drug treatments, and duration of illness was investigated, but none was significantly associated with carotenoid score. Antipsychotics were suggested to be the possible causes of reduced antioxidant level in schizophrenia.
  6. Fulltext Linkage of schizophrenia with TPH2 and 5-HTR2A gene polymorphisms in the Malay population
    Tee SF, Chow TJ, Tang PY, Loh HC
    Genet. Mol. Res., 2010;9(3):1274-8.
    PMID: 20623453 DOI: 10.4238/vol9-3gmr789
    The serotoninergic system has been implicated in the etiology of schizophrenia and other behavioral disorders. Association studies have focused on the tryptophan hydroxylase 2 gene (TPH2) and the 5-hydroxytryptamine receptor 2A gene (5-HTR2A). We genotyped two single-nucleotide polymorphisms, A1438G of 5-HTR2A and intronic rs1386494 of TPH2 in the Malay population, using a sample size of 289 schizophrenic patients and 130 healthy controls. We found a significant association of A1438G of 5-HTR2A with schizophrenia in Malays. On the other hand, TPH2 polymorphism was not associated with schizophrenia. This is the first genetic association study concerning schizophrenia in the Malay population.
  7. Fulltext BDNF and DARPP-32 genes are not risk factors for schizophrenia in the Malay population
    Loh HC, Tang PY, Tee SF, Chow TJ, Cheah YC, Singh SS
    Genet. Mol. Res., 2012;11(1):725-30.
    PMID: 22576830 DOI: 10.4238/2012.March.22.2
    A number of studies have pointed to the association of BDNF (brain-derived neurotrophic factor) and DARPP-32 (dopamine- and cAMP-regulated phosphoprotein, 32 kDa) with schizophrenia. The purpose of this study was to determine whether these two genes are involved in the pathogenesis of schizophrenia in the Malay population. Two single nucleotide polymorphisms Val66Met of BDNF, -2036C>G and g.1238delG of DARPP-32 were genotyped in the Malay population in 200 patients with schizophrenia and 256 healthy controls. Analysis of allele and genotype frequencies in these two groups revealed no significant association of BDNF or DARPP-32 polymorphisms with schizophrenia in Malays. This is the first such association study in the Malay population.
  8. Neuregulin-1 (NRG-1) and its susceptibility to schizophrenia: a case-control study and meta-analysis
    Loh HC, Tang PY, Tee SF, Chow TJ, Choong CY, Lim SY, et al.
    Psychiatry Res, 2013 Jul 30;208(2):186-8.
    PMID: 23489597 DOI: 10.1016/j.psychres.2013.01.022
    Neuregulin-1 is widely investigated due to its hypothesised association with schizophrenia. Single-nucleotide polymorphisms rs764059, rs2954041 and rs3924999 were investigated (417 patients with schizophrenia and 429 controls). We failed to demonstrate a significant association between rs2954041 and rs3924999 with schizophrenia in the three ethnic groups studied (Malay, Chinese, and Indian), while rs764059 was found to be monomorphic.
  9. Fulltext Effects of Vegetarian Diets on Blood Pressure Lowering: A Systematic Review with Meta-Analysis and Trial Sequential Analysis
    Lee KW, Loh HC, Ching SM, Devaraj NK, Hoo FK
    Nutrients, 2020 May 29;12(6).
    PMID: 32486102 DOI: 10.3390/nu12061604
    The beneficial effects of a vegetarian diet on blood pressure (BP) control have been reported in previous systematic reviews; however, so far, their relative effectiveness is not well established. Here, we performed a systematic review together with trial sequential analysis to determine the effect of a vegetarian diet on the reduction of blood pressure. We searched the randomized controlled trial (RCT) through Medline, PubMed and Cochrane Central Register. Fifteen eligible RCTs with 856 subjects were entered into the analysis. The pooled results demonstrated that vegetarian diet consumption significantly lowered the systolic blood pressure (weighted mean difference (WMD), -2.66 mmHg (95% confidence interval (CI) = -3.76, -1.55, p < 0.001) and diastolic BP was WMD, -1.69 95% CI = -2.97, -0.41, p < 0.001) as compared to an omnivorous diet. In subgroup analysis, a vegan diet demonstrated a greater reduction in systolic BP (WMD, -3.12 mm Hg; 95% CI = -4.54, -1.70, p < 0.001) as compared with a lacto-ovo-vegetarian diet (WMD, -1.75 mm Hg, 95% CI -5.38, 1.88, p = 0.05). The vegan diet has showed a similar trend in terms of diastolic blood pressure reduction (WMD, -1.92 mm Hg (95% CI = -3.18, -0.66, p < 0.001) but those with a lacto-ovo-vegetarian diet showed no changes in diastolic BP reduction (WMD, 0.00, 95% CI = 0.00, 0.00), p =0.432). In conclusion, vegetarian diets are associated with significant reductions in BP compared with omnivorous diets, suggesting that they may play a key role in the primary prevention and overall management of hypertension.
  10. Fulltext Diabetes in Pregnancy and Risk of Antepartum Depression: A Systematic Review and Meta-Analysis of Cohort Studies
    Lee KW, Ching SM, Devaraj NK, Chong SC, Lim SY, Loh HC, et al.
    Int J Environ Res Public Health, 2020 05 26;17(11).
    PMID: 32466479 DOI: 10.3390/ijerph17113767
    Previous literature has reported that patients with diabetes in pregnancy (DIP) are at risk of developing antepartum depression but the results have been inconsistent in cohort studies. We conducted a systematic review and performed a meta-analysis to quantify the association between DIP and risk of antepartum depression in cohort studies. Medline, Cinahl, and PubMed databases were searched for studies investigating DIP involving pregnant women with pre-existing diabetes and gestational diabetes mellitus and their risk of antepartum depression that were published in journals from inception to 27 December 2019. We derived the summary estimates using a random-effects model and reported the findings as pooled relative risks (RR) and confidence interval (CI). Publication bias was assessed using a funnel plot and was quantified by Egger and Begg's tests. Ten studies, involving 71,036 pregnant women were included in this meta-analysis. The pooled RR to develop antepartum depression was (RR = 1.430, 95% CI: 1.251-1.636) among women with gestational diabetes mellitus. Combining pregnant women with pre-existing diabetes mellitus and gestational diabetes mellitus, they had a significant increased risk of developing antepartum depression (RR = 1.431, 95% CI: 1.205-1.699) compared with those without it. In comparison, we found no association between pre-existing diabetes mellitus in pregnancy (RR = 1.300, 95% CI: 0.736-2.297) and the risk of developing antepartum depression. This study has a few limitations: first, different questionnaire and cut-off points were used in evaluation of depression across the studies. Second, there was a lack of data on history of depression prior to pregnancy, which lead to confounding bias that could not be solved by this meta-analysis. Third, data were dominated by studies in Western countries; this is due to the studies from Eastern countries failing to meet our inclusion criteria for statistical analysis. Women with gestational diabetes mellitus have an increased risk of developing antepartum depression compared to those without the disease. Therefore, more attention on the mental health status should be given on pregnant women diagnosed with pre-existing diabetes mellitus and gestational diabetes mellitus.
  11. Fulltext Reheating of soy oil is detrimental to bone metabolism in oestrogen deficient rats
    Ima-Nirwana S, Ahmad SN, Yee LJ, Loh HC, Yew SF, Norazlina M, et al.
    Singapore Med J, 2007 Mar;48(3):200-6.
    PMID: 17342287
    The short-term and long- term effects of heated soy oil on bone metabolism in ovariectomised Sprague-Dawley rats were studied.
  12. Fulltext Positive global environmental impacts of the COVID-19 pandemic lockdown: a review
    Loh HC, Looi I, Ch'ng ASH, Goh KW, Ming LC, Ang KH
    GeoJournal, 2021 Jul 23.
    PMID: 34316088 DOI: 10.1007/s10708-021-10475-6
    Global environmental change is mainly due to human behaviours and is a major threat to sustainability. Despite all the health and economic consequences, the impact of the COVID-19 pandemic lockdown on environmental health warrants the scientific community's attention. Thus, this article examined and narratively reviewed the impact of several drastic measures taken on the macro environment and holistic planetary health. We note that the amount of pollution in the air, water, soil, and noise showed a significant decline during the pandemic. Global air quality improved due to lower anthropogenic emissions of air pollutants and atmospheric particles. Water ecosystems also demonstrated signs of recuperation in many countries. Less commercial fishing internationally resulted in the restoration of some aquatic life. Additionally, significant reduction of solid and water waste led to less soil pollution. Some places experienced cleaner beaches and ocean water while wildlife sightings in urban areas across the world occurred more often. Lastly, the COVID-19 pandemic lockdown also led to a worldwide decline in noise pollution. However, the beneficial environmental effects will not be permanent as the world gradually returns to its pre-pandemic status quo. Therefore, behavioural changes such as adopting a lifestyle that reduces carbon footprint are needed to make a positive impact on the environment. In addition, world leaders should consider the national policy changes necessary to ensure continuity of as many of the positive environmental impacts from the COVID-19 pandemic lockdown as possible. Those changes would also serve to lessen the likelihood of another zoonotic calamity.
  13. Fulltext Effects of vitamin E on stroke: a systematic review with meta-analysis and trial sequential analysis
    Loh HC, Lim R, Lee KW, Ooi CY, Chuan DR, Looi I, et al.
    Stroke Vasc Neurol, 2021 Mar;6(1):109-120.
    PMID: 33109618 DOI: 10.1136/svn-2020-000519
    There are several previous studies on the association of vitamin E with prevention of stroke but the findings remain controversial. We have conducted a systematic review, meta-analysis together with trial sequential analysis of randomised controlled trials to evaluate the effect of vitamin E supplementation versus placebo/no vitamin E on the risk reduction of total, fatal, non-fatal, haemorrhagic and ischaemic stroke. Relevant studies were identified by searching online databases through Medline, PubMed and Cochrane Central Register of Controlled Trials. A total of 18 studies with 148 016 participants were included in the analysis. There was no significant difference in the prevention of total stroke (RR (relative risk)=0.98, 95% CI 0.92-1.04, p=0.57), fatal stroke (RR=0.96, 95% CI 0.77-1.20, p=0.73) and non-fatal stroke (RR=0.96, 95% CI 0.88-1.05, p=0.35). Subgroup analyses were performed under each category (total stroke, fatal stroke and non-fatal stroke) and included the following subgroups (types of prevention, source and dosage of vitamin E and vitamin E alone vs control). The findings in all subgroup analyses were statistically insignificant. In stroke subtypes analysis, vitamin E showed significant risk reduction in ischaemic stroke (RR=0.92, 95% CI 0.85-0.99, p=0.04) but not in haemorrhagic stroke (RR=1.17, 95% CI 0.98-1.39, p=0.08). However, the trial sequential analysis demonstrated that more studies were needed to control random errors. Limitations of this study include the following: trials design may not have provided sufficient power to detect a change in stroke outcomes, participants may have had different lifestyles or health issues, there were a limited number of studies available for subgroup analysis, studies were mostly done in developed countries, and the total sample size for all included studies was insufficient to obtain a meaningful result from meta-analysis. In conclusion, there is still a lack of statistically significant evidence of the effects of vitamin E on the risk reduction of stroke. Nevertheless, vitamin E may offer some benefits in the prevention of ischaemic stroke and additional well-designed randomised controlled trials are needed to arrive at a definitive finding. PROSPERO registration number: CRD42020167827.
  14. Fulltext Stroke Patients' Characteristics and Clinical Outcomes: A Pre-Post COVID-19 Comparison Study
    Loh HC, Neoh KK, Tang ASN, Chin CJ, Suppiah PD, Looi I, et al.
    Medicina (Kaunas), 2021 May 19;57(5).
    PMID: 34069433 DOI: 10.3390/medicina57050507
    Background and Objectives: The Coronavirus disease 2019 (COVID-19) pandemic caused significant disruption to established medical care systems globally. Thus, this study was aimed to compare the admission and outcome variables such as number of patient and its severity, acute recanalisation therapy given pre-post COVID-19 at a primary stroke centre located in Malaysia. Methods: This cross-sectional hospital-based study included adult ischaemic stroke patients. Variables of the study included the number of ischaemic stroke patients, the proportions of recanalisation therapies, stroke severity during admission based on the National Institutes of Health Stroke Scale, functional outcome at discharge based on the modified Rankin Scale, and relevant workflow metrics. We compared the outcome between two six-month periods, namely the pre-COVID-19 period (March 2019 to September 2019) and the COVID-19 period (March 2020 to September 2020). Results: There were 131 and 156 patients, respectively, from the pre-COVID-19 period and the COVID-19 period. The median door-to-scan time and the median door-to-reperfusion time were both significantly shorter in the COVID-19 period (24.5 min versus 12.0 min, p = 0.047) and (93.5 min versus 60.0 min, p = 0.015), respectively. There were also significantly more patients who received intravenous thrombolysis (7.6% versus 17.3%, p = 0.015) and mechanical thrombectomy (0.8% versus 6.4%, p = 0.013) in the COVID-19 period, respectively. Conclusions: The COVID-19 pandemic may not have caused disruptions of acute stroke care in our primary stroke centre. Our data indicated that the number of ischaemic stroke events remained stable, with a significant increase of recanalisation therapies and better in-hospital workflow metrics during the COVID-19 pandemic period. However, we would like to highlight that the burden of COVID-19 cases in the study area was very low. Therefore, the study may not have captured the true burden (and relevant delays in stroke patient management) during the COVID-19 pandemic. The effect of the pandemic crisis is ongoing and both pre-hospital and in-hospital care systems must continue to provide optimal, highly time-dependent stroke care services.
  15. Fulltext A Systematic Review of the Economic Burden of Type 2 Diabetes in Malaysia
    Ganasegeran K, Hor CP, Jamil MFA, Loh HC, Noor JM, Hamid NA, et al.
    Int J Environ Res Public Health, 2020 08 07;17(16).
    PMID: 32784771 DOI: 10.3390/ijerph17165723
    Diabetes causes significant disabilities, reduced quality of life and mortality that imposes huge economic burden on societies and governments worldwide. Malaysia suffers a high diabetes burden in Asia, but the magnitude of healthcare expenditures documented to aid national health policy decision-making is limited. This systematic review aimed to document the economic burden of diabetes in Malaysia, and identify the factors associated with cost burden and the methods used to evaluate costs. Studies conducted between 2000 and 2019 were retrieved using three international databases (PubMed, Scopus, EMBASE) and one local database (MyCite), as well as manual searches. Peer reviewed research articles in English and Malay on economic evaluations of adult type 2 diabetes conducted in Malaysia were included. The review was registered with PROSPERO (CRD42020151857), reported according to PRISMA and used a quality checklist adapted for cost of illness studies. Data were extracted using a data extraction sheet that included study characteristics, total costs, different costing methods and a scoring system to assess the quality of studies reviewed. The review identified twelve eligible studies that conducted cost evaluations of type 2 diabetes in Malaysia. Variation exists in the costs and methods used in these studies. For direct costs, four studies evaluated costs related to complications and drugs, and two studies were related to outpatient and inpatient costs each. Indirect and intangible costs were estimated in one study. Four studies estimated capital and recurrent costs. The estimated total annual cost of diabetes in Malaysia was approximately USD 600 million. Age, type of hospitals or health provider, length of inpatient stay and frequency of outpatient visits were significantly associated with costs. The most frequent epidemiological approach employed was prevalence-based (n = 10), while cost analysis was the most common costing approach used. The current review offers the first documented evidence on cost estimates of diabetes in Malaysia.
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