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Clinical update on deep vein thrombosis in Singapore

Lee LH

Ann Acad Med Singap, 2002 Mar;31(2):248-52.
PMID: 11957569

Venous thromboembolism (VTE) is thought to be a rare occurrence in Asian patients. The clinical features of VTE are elusive and the disease often unsuspected. Objective testing such as the duplex ultrasound scans and pulmonary imaging are necessary as clinical diagnosis alone is inaccurate. Fatality can occur in untreated patients not suspected of the disease as shown by our post-mortem studies. Indeed VTE is one of the leading causes of maternal mortality in Singapore. There is a rising trend in the incidence of VTE in Asia. Initial studies found an incidence of about 3 per 10,000 hospital admissions in Hong Kong and Malaysia in 1988 and 1990, respectively; rising to 8 and 15.8 per 10,000 hospital admissions in Singapore 1992 and 2000, respectively. The major risk factors for developing deep vein thrombosis (DVT) in our patients are immobilisation, surgery and malignancy. While Factor V Leiden mutation and mutation at position 20,210 in the prothrombin gene are found to be extremely rare in Chinese, the rest of the thrombophilia has not been formally studied. Studies in Singapore reported rates of 3% to 7% of DVT after general surgery, 9.7% after hip surgery and 14% after total knee replacement surgery. It is difficult to compare with studies from other centres because of differences in patient selection and diagnostic criteria. Studies in Singapore showed that the use of prophylactic low molecular weight heparin completely abolished the occurrence of DVT for patients undergoing total knee replacement and colorectal surgery without an increase in bleeding complications. In conclusion, VTE is not an uncommon problem here. Major acquired risk factors do not differ from the Caucasian populations. VTE is a preventable disease and a better understanding of its epidemiology, patient-risk factors and biological factors will allow better management of this condition.
Fulltext Editorial: Vibrionaceae Diversity, Multidrug Resistance and Management

Lee LH, Raghunath P

Front Microbiol, 2018;9:563.
PMID: 29632526 DOI: 10.3389/fmicb.2018.00563
A serological investigation of six encephalitis viruses isolated in Malaya

HALE JH, LEE LH

Br J Exp Pathol, 1954 Oct;35(5):426-33.
PMID: 13208931
Serological evidence of the incidence of Japanese B encephalitis virus infection in Malaysia

HALE JH, LEE LH

Ann Trop Med Parasitol, 1955 Oct;49(3):293-8.
PMID: 13259442
Fulltext Vibrio parahaemolyticus: a review on the pathogenesis, prevalence, and advance molecular identification techniques

Letchumanan V, Chan KG, Lee LH

Front Microbiol, 2014;5:705.
PMID: 25566219 DOI: 10.3389/fmicb.2014.00705

Vibrio parahaemolyticus is a Gram-negative halophilic bacterium that is found in estuarine, marine and coastal environments. V. parahaemolyticus is the leading causal agent of human acute gastroenteritis following the consumption of raw, undercooked, or mishandled marine products. In rare cases, V. parahaemolyticus causes wound infection, ear infection or septicaemia in individuals with pre-existing medical conditions. V. parahaemolyticus has two hemolysins virulence factors that are thermostable direct hemolysin (tdh)-a pore-forming protein that contributes to the invasiveness of the bacterium in humans, and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. In addition, the bacterium is also encodes for adhesions and type III secretion systems (T3SS1 and T3SS2) to ensure its survival in the environment. This review aims at discussing the V. parahaemolyticus growth and characteristics, pathogenesis, prevalence and advances in molecular identification techniques.
Fulltext An insight of traditional plasmid curing in Vibrio species

Letchumanan V, Chan KG, Lee LH

Front Microbiol, 2015;6:735.
PMID: 26347714 DOI: 10.3389/fmicb.2015.00735

As the causative agent of foodborne related illness, Vibrio species causes a huge impact on the public health and management. Vibrio species is often associated with seafood as the latter plays a role as a vehicle to transmit bacterial infections. Hence, antibiotics are used not to promote growth but rather to prevent and treat bacterial infections. The extensive use of antibiotics in the aquaculture industry and environment has led to the emerging of antibiotic resistant strains. This phenomenon has triggered an alarming public health concern due to the increase number of pathogenic Vibrio strains that are resistant to clinically used antibiotics and is found in the environment. Antibiotic resistance and the genes location in the strains can be detected through plasmid curing assay. The results derived from plasmid curing assay is fast, cost effective, sufficient in providing insights, and influence the antibiotic management policies in the aquaculture industry. This presentation aims in discussing and providing insights on various curing agents in Vibrio species. To our best of knowledge, this is a first review written discussing on plasmid curing in Vibrio species.
Fulltext Molecular Markers of Diabetic Retinopathy: Potential Screening Tool of the Future?

Pusparajah P, Lee LH, Abdul Kadir K

Front Physiol, 2016;7:200.
PMID: 27313539 DOI: 10.3389/fphys.2016.00200

Diabetic retinopathy (DR) is among the leading causes of new onset blindness in adults. Effective treatment may delay the onset and progression of this disease provided it is diagnosed early. At present retinopathy can only be diagnosed via formal examination of the eye by a trained specialist, which limits the population that can be effectively screened. An easily accessible, reliable screening biomarker of diabetic retinopathy would be of tremendous benefit in detecting the population in need of further assessment and treatment. This review highlights specific biomarkers that show promise as screening markers to detect early diabetic retinopathy or even to detect patients at increased risk of DR at the time of diagnosis of diabetes. The pathobiology of DR is complex and multifactorial giving rise to a wide array of potential biomarkers. This review provides an overview of these pathways and looks at older markers such as advanced glycation end products (AGEs), inflammatory markers, vascular endothelial growth factor (VEGF) as well as other newer proteins with a role in the pathogenesis of DR including neuroprotective factors such as brain derived neurotrophic factor (BDNF) and Pigment Epithelium Derived Factor (PEDF); SA100A12, pentraxin 3, brain natriuretic peptide, apelin 3, and chemerin as well as various metabolites such as lipoprotein A, folate, and homocysteine. We also consider the possible role of proteins identified through proteomics work whose levels are altered in the sera of patients with DR as screening markers though their role in pathophysiology remains to be characterized. The role of microRNA as a promising new screening marker is also discussed.
Fulltext Editorial: Actinobacteria: Prolific Producers of Bioactive Metabolites

Lee LH, Goh BH, Chan KG

Front Microbiol, 2020;11:1612.
PMID: 32973689 DOI: 10.3389/fmicb.2020.01612
Fulltext Can Mindfulness Help to Alleviate Loneliness? A Systematic Review and Meta-Analysis

Teoh SL, Letchumanan V, Lee LH

Front Psychol, 2021;12:633319.
PMID: 33716901 DOI: 10.3389/fpsyg.2021.633319

Objective: Mindfulness-based intervention (MBI) has been proposed to alleviate loneliness and improve social connectedness. Several randomized controlled trials (RCTs) have been conducted to evaluate the effectiveness of MBI. This study aimed to critically evaluate and determine the effectiveness and safety of MBI in alleviating the feeling of loneliness. Methods: We searched Medline, Embase, PsycInfo, Cochrane CENTRAL, and AMED for publications from inception to May 2020. We included RCTs with human subjects who were enrolled in MBI with loneliness as an outcome. The quality of evidence was assessed using Cochrane's Risk of Bias (ROB) tool and Grading of Recommendations Assessment, Development, and Evaluation (GRADE). A random-effects model was used for meta-analysis. Results: Out of 92 articles identified, eight studies involving 815 participants were included in this study. Most (7/8) trials conducted a minimum of 8 weeks of MBI. Most of the trials (5/8) used UCLA-Loneliness Scale. A pooled analysis combining three trials and compared with wait-list showed significant improvement in loneliness score reduction using the UCLA-R scale with MD of -6.33 [95% confidence interval (CI): -9.39, -3.26]. Subgroup analysis with only two Cognitively-Based Compassion Training (CBCT) trials also showed similar MD of -6.05 (95% CI: -9.53, 2.58). The overall quality of evidence (GRADE) was low. Conclusions: Mindfulness intervention with an average length of 8-week duration significantly improved the population's loneliness level with no mental health issue. However, this evidence had a low GRADE level.
The Effect of Green Tea Consumption on Prostate Cancer Risk and Progression: A Systematic Review

Jacob SA, Khan TM, Lee LH

Nutr Cancer, 2017 Apr;69(3):353-364.
PMID: 28287319 DOI: 10.1080/01635581.2017.1285037

This systematic review aimed to assess the clinical benefits of green tea consumption on the progression and prevention of prostate cancer (PCa). A systematic search was performed across the following databases: PubMed, Excerpta Medica dataBASE, Database of Abstracts of Reviews of Effects, Current Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials. We included studies from database inception to September 2015. Studies must report on the effect of green tea consumption on PCa. The quality of observational studies was assessed using the Newcastle-Ottawa Scale (NOS), while randomized controlled trials (RCTs) were assessed for quality using the Jadad scale. A total of 15 articles were included, with 11 reporting on the effect of green tea consumption on PCa prevention, and four reporting on the effect of green tea on treatment. Mean NOS for observational studies was 7.4 (SD±1.3), with a range from 6 to 9, while all three RCTs scored 5 on the Jadad scale. Findings demonstrate that green tea appears to be an effective chemopreventive agent, particularly in those with high-grade prostate intraepithelial neoplasia. However, evidence of efficacy in the treatment of PCa is currently lacking. Given the limitations in current studies, more well-designed RCTs should be undertaken to determine if green tea indeed has a role in the prevention and treatment of PCa.
Fulltext Editorial: Roles of microbes in esophageal disease

Lee LH, Gao X, Sun G

Front Cell Infect Microbiol, 2023;13:1339579.
PMID: 38094747 DOI: 10.3389/fcimb.2023.1339579
Fulltext Prevalence and antimicrobial susceptibility of Vibrio parahaemolyticus isolated from retail shrimps in Malaysia

Letchumanan V, Yin WF, Lee LH, Chan KG

Front Microbiol, 2015;6:33.
PMID: 25688239 DOI: 10.3389/fmicb.2015.00033

Vibrio parahaemolyticus is a marine and estuarine bacterium that has been the leading cause of foodborne outbreaks which leads to a significant threat to human health worldwide. Consumption of seafood contaminated with V. parahaemolyticus causes acute gastroenteritis in individuals. The bacterium poses two main virulence factor including the thermostable direct hemolysin (tdh) which is a pore-forming protein that contributes to the invasiveness of the bacterium in humans and TDH-related hemolysin (trh), which plays a similar role as tdh in the disease pathogenesis. This study aimed to investigate the antimicrobial resistance V. parahaemolyticus strains in shrimps purchased from wetmarkets and supermarkets. The toxR-based PCR assay indicated that a total of 57.8% (185/320) isolates were positive for V. parahaemolyticus. Only 10% (19/185) toxR-positive isolate exhibit the trh gene and none of the isolates were tested positive for tdh. The MAR index was measured for 14 common antimicrobial agents. The results indicated 98% of the isolates were highly susceptible to imipenem, ampicillin sulbactam (96%), chloramphenicol (95%), trimethoprim-sulfamethoxazole (93%), gentamicin (85%), levofloxacin (83%), and tetracycline (82%). The chloramphenicol (catA2) and kanamycin (aphA-3) resistance genes were detected in the resistant V. parahaemolyticus isolates. Our results demonstrate that shrimps are contaminated with V. parahaemolyticus, some of which carry the trh-gene thus being potential to cause food borne illness. The occurrence of multidrug resistance strains in the environment could be an indication of excessive usage of antibiotics in agriculture and aquaculture fields.
Active incremental Support Vector Machine for oil and gas pipeline defects prediction system using long range ultrasonic transducers

Akram NA, Isa D, Rajkumar R, Lee LH

Ultrasonics, 2014 Aug;54(6):1534-44.
PMID: 24792683 DOI: 10.1016/j.ultras.2014.03.017

This work proposes a long range ultrasonic transducers technique in conjunction with an active incremental Support Vector Machine (SVM) classification approach that is used for real-time pipeline defects prediction and condition monitoring. Oil and gas pipeline defects are detected using various techniques. One of the most prevalent techniques is the use of "smart pigs" to travel along the pipeline and detect defects using various types of sensors such as magnetic sensors and eddy-current sensors. A critical short coming of "smart pigs" is the inability to monitor continuously and predict the onset of defects. The emergence of permanently installed long range ultrasonics transducers systems enable continuous monitoring to be achieved. The needs for and the challenges of the proposed technique are presented. The experimental results show that the proposed technique achieves comparable classification accuracy as when batch training is used, while the computational time is decreased, using 56 feature data points acquired from a lab-scale pipeline defect generating experimental rig.
Molecular diversity of fungal endophytes isolated from Garcinia mangostana and Garcinia parvifolia

Sim JH, Khoo CH, Lee LH, Cheah YK

J Microbiol Biotechnol, 2010 Apr;20(4):651-8.
PMID: 20467234

Garcinia is commonly found in Malaysia, but limited information is available regarding endophytic fungi associated with this plant. In this study, 24 endophytic fungi were successfully recovered from different parts of two Garcinia species. Characterization of endophytic fungi was performed based on the conserved internal transcribed spacer (ITS) region sequence analysis and the antimicrobial properties. Results revealed that fruits of the plant appeared to be the highest inhabitation site (38 %) as compared with others. Glomerella sp., Guignardia sp., and Phomopsis sp. appeared to be the predominant endophytic fungi group in Garcinia mangostana and Garcinia parvifolia. Phylogenetic relationships of the isolated endophytic fungi were estimated from the sequences of the ITS region. On the other hand, antibacterial screening showed 11 of the isolates possessed positive response towards pathogenic and nonpathogenic bacteria. However, there was no direct association between certain antibacterial properties with the specific genus observed.
Fulltext An overview of the characteristics of the novel avian influenza A H7N9 virus in humans

Tan KX, Jacob SA, Chan KG, Lee LH

Front Microbiol, 2015;6:140.
PMID: 25798131 DOI: 10.3389/fmicb.2015.00140

The novel avian influenza A H7N9 virus which caused the first human infection in Shanghai, China; was reported on the 31st of March 2013 before spreading rapidly to other Chinese provinces and municipal cities. This is the first time the low pathogenic avian influenza A virus has caused human infections and deaths; with cases of severe respiratory disease with pneumonia being reported. There were 440 confirmed cases with 122 fatalities by 16 May 2014; with a fatality risk of ∼28%. The median age of patients was 61 years with a male-to-female ratio of 2.4:1. The main source of infection was identified as exposure to poultry and there is so far no definitive evidence of sustained person-to-person transmission. The neuraminidase inhibitors, namely oseltamivir, zanamivir, and peramivir; have shown good efficacy in the management of the novel H7N9 virus. Treatment is recommended for all hospitalized patients, and for confirmed and probable outpatient cases; and should ideally be initiated within 48 h of the onset of illness for the best outcome. Phylogenetic analysis found that the novel H7N9 virus is avian in origin and evolved from multiple reassortments of at least four origins. Indeed the novel H7N9 virus acquired human adaptation via mutations in its eight RNA gene segments. Enhanced surveillance and effective global control are essential to prevent pandemic outbreaks of the novel H7N9 virus.
Fulltext A comparison of thrombotic thrombocytopenic purpura in an inception cohort of patients with and without systemic lupus erythematosus

Letchumanan P, Ng HJ, Lee LH, Thumboo J

Rheumatology (Oxford), 2009 Apr;48(4):399-403.
PMID: 19202160 DOI: 10.1093/rheumatology/ken510

To compare the clinical presentation, response to therapy and outcome of thrombotic thrombocytopenic purpura (TTP) in an inception cohort of patients with and without SLE.
Fulltext Endophthalmitis with bilateral deafness from disseminated Streptococcus suis infection

Rayanakorn A, Katip W, Lee LH, Oberdorfer P

BMJ Case Rep, 2019 Feb 26;12(2).
PMID: 30814105 DOI: 10.1136/bcr-2018-228501

Streptococcus suis is a Gram-positive cocci bacterium that are found mainly in pigs and can be transmitted to human through pigs or pork exposure. The disease is mainly found among occupations involving swine contact in western countries whereas in Asia the disease is usually contracted through raw pork consumption. In this case report, we present a case of a middle-aged Thai man who acquired the infection from raw pork consumption. He presented with endogenous endophthalmitis with infective spondylodiscitis, sepsis and meningitis and later developed blindness of the right eye and permanent bilateral hearing loss disseminated from S. suis infection. Our report suggests that S. suis infection be considered as a causative factor in patient presenting with established clinical symptoms and predisposing factors. Cultural habit of eating raw pork should be taken into account especially in Asian countries.
IRF5-mediated immune responses and its implications in immunological disorders

Kaur A, Lee LH, Chow SC, Fang CM

Int Rev Immunol, 2018;37(5):229-248.
PMID: 29985675 DOI: 10.1080/08830185.2018.1469629

Transcription factors are gene regulators that activate or repress target genes. One family of the transcription factors that have been extensively studied for their crucial role in regulating gene network in the immune system is the interferon regulatory factors (IRFs). IRFs possess a novel turn-helix turn motif that recognizes a specific DNA consensus found in the promoters of many genes that are involved in immune responses. IRF5, a member of IRFs has recently gained much attention for its role in regulating inflammatory responses and autoimmune diseases. Here, we discuss the role of IRF5 in regulating immune cells functions and how the dysregulation of IRF5 contributes to the pathogenesis of immune disorders. We also review the latest findings of potential IRF5 inhibitors that modulate IRF5 activity in the effort of developing therapeutic approaches for treating inflammatory disorders.
Fulltext Burden of disease and productivity impact of Streptococcus suis infection in Thailand

Rayanakorn A, Ademi Z, Liew D, Lee LH

PLoS Negl Trop Dis, 2021 01;15(1):e0008985.
PMID: 33481785 DOI: 10.1371/journal.pntd.0008985

BACKGROUND: Streptoccocus suis (S.suis) infection is a neglected zoonosis disease in humans mainly affects men of working age. We estimated the health and economic burden of S.suis infection in Thailand in terms of years of life lost, quality-adjusted life years (QALYs) lost, and productivity-adjusted life years (PALYs) lost which is a novel measure that adjusts years of life lived for productivity loss attributable to disease.
METHODS: A decision-analytic Markov model was developed to simulate the impact of S. suis infection and its major complications: death, meningitis and infective endocarditis among Thai people in 2019 with starting age of 51 years. Transition probabilities, and inputs pertaining to costs, utilities and productivity impairment associated with long-term complications were derived from published sources. A lifetime time horizon with follow-up until death or age 100 years was adopted. The simulation was repeated assuming that the cohort had not been infected with S.suis. The differences between the two set of model outputs in years of life, QALYs, and PALYs lived reflected the impact of S.suis infection. An annual discount rate of 3% was applied to both costs and outcomes. One-way sensitivity analyses and Monte Carlo simulation modeling technique using 10,000 iterations were performed to assess the impact of uncertainty in the model.
KEY RESULTS: This cohort incurred 769 (95% uncertainty interval [UI]: 695 to 841) years of life lost (14% of predicted years of life lived if infection had not occurred), 826 (95% UI: 588 to 1,098) QALYs lost (21%) and 793 (95%UI: 717 to 867) PALYs (15%) lost. These equated to an average of 2.46 years of life, 2.64 QALYs and 2.54 PALYs lost per person. The loss in PALYs was associated with a loss of 346 (95% UI: 240 to 461) million Thai baht (US$11.3 million) in GDP, which equated to 1.1 million Thai baht (US$ 36,033) lost per person.
CONCLUSIONS: S.suis infection imposes a significant economic burden both in terms of health and productivity. Further research to investigate the effectiveness of public health awareness programs and disease control interventions should be mandated to provide a clearer picture for decision making in public health strategies and resource allocations.
Fulltext Exploring the Role and Potential of Probiotics in the Field of Mental Health: Major Depressive Disorder

Johnson D, Thurairajasingam S, Letchumanan V, Chan KG, Lee LH

Nutrients, 2021 May 20;13(5).
PMID: 34065187 DOI: 10.3390/nu13051728

The field of probiotic has been exponentially expanding over the recent decades with a more therapeutic-centered research. Probiotics mediated microbiota modulation within the microbiota-gut-brain axis (MGBA) have been proven to be beneficial in various health domains through pre-clinical and clinical studies. In the context of mental health, although probiotic research is still in its infancy stage, the promising role and potential of probiotics in various mental disorders demonstrated via in-vivo and in-vitro studies have laid a strong foundation for translating preclinical models to humans. The exploration of the therapeutic role and potential of probiotics in major depressive disorder (MDD) is an extremely noteworthy field of research. The possible etio-pathological mechanisms of depression involving inflammation, neurotransmitters, the hypothalamic-pituitary-adrenal (HPA) axis and epigenetic mechanisms potentially benefit from probiotic intervention. Probiotics, both as an adjunct to antidepressants or a stand-alone intervention, have a beneficial role and potential in mitigating anti-depressive effects, and confers some advantages compared to conventional treatments of depression using anti-depressants.

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