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  1. 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.
  2. Letchumanan VP, Lim KF, Mohamad AB
    Med J Malaysia, 2013 Oct;68(5):405-9.
    PMID: 24632870 MyJurnal
    INTRODUCTION: Spontaneous rupture is a dramatic presentation of HCC and it carries high mortality rate. To study the outcomes of ruptured HCC patients managed at a tertiary referral centre in Malaysia.
    METHODS: A retrospective review of all ruptured HCC patients managed as inpatient at the Department of Hepatobiliary Surgery, Hospital Selayang between January 2001 and December 2010. Data was retrieved from the hospital electronic medical records, Powerchart (Cerner Corporation Inc., USA) and supplemented with registry from Interventional Radiology record of chemoembolization and registry from hepatobiliary operative surgery records.
    RESULTS: There were 22 patients admitted with confirmed diagnosis of ruptured HCC over 10 years period. The common clinical findings on presentation were abdominal pain and presence of shock (36.4%). The mortality rate was 81.8% with only four patients noted to be alive during the follow up. One year overall survival for ER and DR are 40.0% and 72.7% respectively and the median survival in patients treated with DR was 433.3 days whereas it was 212.5 days in ER group.
    CONCLUSIONS: This study supports the clinical practice of TAE should be the first line treatment followed by staged surgery in suitable candidates with ruptured HCC.
  3. 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.
  4. 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.
  5. 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.
  6. 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.
  7. Johnson D, Letchumanan V, Thum CC, Thurairajasingam S, Lee LH
    Nutrients, 2023 Mar 13;15(6).
    PMID: 36986112 DOI: 10.3390/nu15061382
    Probiotics are currently the subject of intensive research pursuits and also represent a multi-billion-dollar global industry given their vast potential to improve human health. In addition, mental health represents a key domain of healthcare, which currently has limited, adverse-effect prone treatment options, and probiotics may hold the potential to be a novel, customizable treatment for depression. Clinical depression is a common, potentially debilitating condition that may be amenable to a precision psychiatry-based approach utilizing probiotics. Although our understanding has not yet reached a sufficient level, this could be a therapeutic approach that can be tailored for specific individuals with their own unique set of characteristics and health issues. Scientifically, the use of probiotics as a treatment for depression has a valid basis rooted in the microbiota-gut-brain axis (MGBA) mechanisms, which play a role in the pathophysiology of depression. In theory, probiotics appear to be ideal as adjunct therapeutics for major depressive disorder (MDD) and as stand-alone therapeutics for mild MDD and may potentially revolutionize the treatment of depressive disorders. Although there is a wide range of probiotics and an almost limitless range of therapeutic combinations, this review aims to narrow the focus to the most widely commercialized and studied strains, namely Lactobacillus and Bifidobacterium, and to bring together the arguments for their usage in patients with major depressive disorder (MDD). Clinicians, scientists, and industrialists are critical stakeholders in exploring this groundbreaking concept.
  8. Johnson D, Letchumanan V, Thurairajasingam S, Lee LH
    Nutrients, 2020 Jul 03;12(7).
    PMID: 32635373 DOI: 10.3390/nu12071983
    The study of human microbiota and health has emerged as one of the ubiquitous research pursuits in recent decades which certainly warrants the attention of both researchers and clinicians. Many health conditions have been linked to the gut microbiota which is the largest reservoir of microbes in the human body. Autism spectrum disorder (ASD) is one of the neurodevelopmental disorders which has been extensively explored in relation to gut microbiome. The utilization of microbial knowledge promises a more integrative perspective in understanding this disorder, albeit being an emerging field in research. More interestingly, oral and vaginal microbiomes, indicating possible maternal influence, have equally drawn the attention of researchers to study their potential roles in the etiopathology of ASD. Therefore, this review attempts to integrate the knowledge of microbiome and its significance in relation to ASD including the hypothetical aetiology of ASD and its commonly associated comorbidities. The microbiota-based interventions including diet, prebiotics, probiotics, antibiotics, and faecal microbial transplant (FMT) have also been explored in relation to ASD. Of these, diet and probiotics are seemingly promising breakthrough interventions in the context of ASD for lesser known side effects, feasibility and easier administration, although more studies are needed to ascertain the actual clinical efficacy of these interventions. The existing knowledge and research gaps call for a more expanded and resolute research efforts in establishing the relationship between autism and microbiomes.
  9. Letchumanan V, Pusparajah P, Tan LT, Yin WF, Lee LH, Chan KG
    Front Microbiol, 2015;6:1417.
    PMID: 26697003 DOI: 10.3389/fmicb.2015.01417
    High consumer demand for shellfish has led to the need for large-scale, reliable shellfish supply through aquaculture or shellfish farming. However, bacterial infections which can spread rapidly among shellfish poses a major threat to this industry. Shellfish farmers therefore often resort to extensive use of antibiotics, both prophylactically and therapeutically, in order to protect their stocks. The extensive use of antibiotics in aquaculture has been postulated to represent a major contributing factor in the rising incidence of antimicrobial resistant pathogenic bacteria in shellfish. This study aimed to investigate the incidence of pathogenic Vibrio parahaemolyticus and determine the antibiotic resistance profile as well as to perform plasmid curing in order to determine the antibiotic resistance mediation. Based on colony morphology, all 450 samples tested were positive for Vibrio sp; however, tox-R assay showed that only 44.4% (200/450) of these were V. parahaemolyticus. Out of these 200 samples, 6.5% (13/200) were trh-positive while none were tdh-positive. Antibiotic resistance was determined for all V. parahaemolyticus identified against 14 commonly used antibiotics and the multiple antibiotic resistance index (MAR) was calculated. The isolates demonstrated high resistance to several antibiotics tested- including second and third-line antibiotics- with 88% resistant to ampicillin, 81% to amikacin,70.5% to kanamycin, 73% to cefotaxime, and 51.5% to ceftazidime. The MAR index ranged from 0.00 to 0.79 with the majority of samples having an index of 0.36 (resistant to five antibiotics). Among the 13 trh-positive strains, almost 70% (9/13) demonstrated resistance to 4 or more antibiotics. Plasmid profiling for all V. parahaemolyticus isolates revealed that 86.5% (173/200) contained plasmids - ranging from 1 to 7 plasmids with DNA band sizes ranging from 1.2 kb to greater than 10 kb. 6/13 of the pathogenic V. pathogenic strains contained plasmid. After plasmid curing, the plasmid containing pathogenic strains isolated in our study have chromosomally mediated ampicillin resistance while the remaining resistance phenotypes are plasmid mediated. Overall, our results indicate that while the incidence of pathogenic V. parahaemolyticus in shellfish in Selangor still appears to be at relatively reassuring levels, antibiotic resistance is a real concern and warrants ongoing surveillance.
  10. Leow VM, Faizah MS, Mohd Sharifudin S, Letchumanan VP, Yang KF, Manisekar KS
    Med J Malaysia, 2014 Jun;69(3):129-32.
    PMID: 25326354 MyJurnal
    OBJECTIVE: Conventional laparoscopic cholecystectomy (LC) involves the use of four ports, but the number of ports has gradually been reduced to one for cosmetic reasons. however, single-incision LC is technically demanding, and there is a substantial learning curve associated with its successful application. The aim of this clinical study was to evaluate the safety and feasibility of a less demanding alternative LC technique with a faster learning curve.

    METHODS: This prospective descriptive study was performed from September 2009 to February 2011 at Sultanah Bahiyah hospital in Kedah, Malaysia. A total of 58 patients underwent two-incision threeport laparoscopic cholecystectomy (TILC), which was performed by the senior consultant hepato-pancreato-biliary surgeon and two hepato-pancreato-biliary trainees. Study end points included operative time, postoperative pain, length of hospital stay and early postoperative complications. The follow-up period was 4 weeks.

    RESULTS: The overall operative time taken was 44 ± 18 minutes. none of the patients had major complication or incisional hernia postoperatively. All but one of the patients were discharged within 24 h. nonsteroidal anti-inflammatory drugs were the main postoperative analgesic used.

    CONCLUSION: TILC is feasible and safe cholecystectomy technique.
  11. Letchumanan V, Chan KG, Khan TM, Bukhari SI, Ab Mutalib NS, Goh BH, et al.
    Front Microbiol, 2017;8:728.
    PMID: 28484445 DOI: 10.3389/fmicb.2017.00728
    Bacteria must develop resistance to various inhospitable conditions in order to survive in the human gastrointestinal tract. Bile, which is secreted by the liver, and plays an important role in food digestion also has antimicrobial properties and is able to disrupt cellular homeostasis. Paradoxically, although bile is one of the guts defenses, many studies have reported that bacteria such as Vibrio parahaemolyticus can sense bile and use its presence as an environmental cue to upregulate virulence genes during infection. This article aims to discuss how bile is detected by V. parahaemolyticus and its role in regulating type III secretion system 2 leading to human infection. This bile-bacteria interaction pathway gives us a clearer understanding of the biochemical and structural analysis of the bacterial receptors involved in mediating a response to bile salts which appear to be a significant environmental cue during initiation of an infection.
  12. Ser HL, Letchumanan V, Goh BH, Wong SH, Lee LH
    Front Microbiol, 2021;12:519836.
    PMID: 34054740 DOI: 10.3389/fmicb.2021.519836
    Fecal microbiome transplant (FMT) has gained popularity over the past few years, given its success in treating several gastrointestinal diseases. At the same time, microbial populations in the gut have been shown to have more physiological effects than we expected as "habitants" of the gut. The imbalance in the gut microbiome or dysbiosis, particularly when there are excessive harmful pathogens, can trigger not just infections but can also result in the development of common diseases, such as cancer and cardiometabolic diseases. By using FMT technology, the dysbiosis of the gut microbiome in patients can be resolved by administering fecal materials from a healthy donor. The current review summarizes the history and current uses of FMT before suggesting potential ideas for its high-quality application in clinical settings.
  13. Lee LH, Ab Mutalib NS, Law JW, Wong SH, Letchumanan V
    Front Microbiol, 2018;9:2513.
    PMID: 30410472 DOI: 10.3389/fmicb.2018.02513
    Vibrio parahaemolyticus, a Gram-negative halophilic bacterium is often associated with fish and fishery products, thus causing gastroenteritis in humans upon ingestion of contaminated food. V. parahaemolyticus has become a globally well-known pathogen with yearly reported cases in many countries. This study aimed to discover the antibiotic resistance patterns of V. parahaemolyticus as well as detect Carbapenem resistant isolates from marine and freshwater fish in Selangor. A total of 240 freshwater and marine fish samples collected from wet market and supermarket in Selangor were tested for the presence of V. parahaemolyticus. All the fish samples were determined positive for V. parahaemolyticus using conventional microbiological culture-based method. The toxR gene were detected via polymerase chain reaction (PCR) in 165/240 (69%) isolates. The two-virulence factor of V. parahaemolyticus, thermostable direct hemolysin (tdh) and TDH-related hemolysin (trh) was screened via PCR. As such, four isolates were trh+and none were tdh+. Majority of the isolates presented high resistance to ampicillin (88%), amikacin (64%), and kanamycin (50%). In addition, this study identified 19-imipenem resistant isolates isolated from freshwater and marine fish samples. Further analysis of these 19-imipenem resistant isolates revealed that the resistance toward imipenem was plasmid mediated after plasmid curing assay. The multiple antibiotics resistance index was >0.2 for 70% of the isolates. In summary, the results confirm the presence of V. parahaemolyticus in freshwater and marine fish samples in Selangor, Malaysia. To our best knowledge, this is the first report discovering the antibiotic resistant patterns and Carbapenem-resistant isolates of V. parahaemolyticus isolated from marine and freshwater fish samples in Selangor.
  14. Kher HL, Krishnan T, Letchumanan V, Hong KW, How KY, Lee LH, et al.
    Gene, 2019 Feb 05;684:58-69.
    PMID: 30321658 DOI: 10.1016/j.gene.2018.10.031
    In the phylum of Proteobacteria, quorum sensing (QS) system is widely driven by synthesis and response of N-acyl homoserine lactone (AHL) signalling molecules. AHL is synthesized by LuxI homologue and sensed by LuxR homologue. Once the AHL concentration achieves a threshold level, it triggers the regulation of target genes. In this study, QS activity of Citrobacter amalonaticus strain YG6 which was isolated from clams was investigated. In order to characterise luxI/R homologues, the genome of C. amalonaticus strain YG6 (4.95 Mbp in size) was sequenced using Illumina MiSeq sequencer. Through in silico analysis, a pair of canonical luxI/R homologues and an orphan luxR homologue were identified and designated as camI, camR, and camR2, respectively. A putative lux box was identified at the upstream of camI. The camI gene was cloned and overexpressed in E. coli BL21 (DE3)pLysS. High-resolution triple quadrupole liquid chromatography mass spectrometry (LC-MS/MS) analysis verified that the CamI is a functional AHL synthase which produced multiple AHL species, namely N‑butyryl‑l‑homoserine lactone (C4-HSL), N‑hexanoyl‑l‑homoserine lactone (C6-HSL), N‑octanoyl‑l‑homoserine lactone (C8-HSL), N‑tetradecanoyl‑l‑homoserine lactone (C14-HSL) and N‑hexadecanoyl‑l‑homoserine lactone (C16-HSL) in C. amalonaticus strain YG6 and camI gene in recombinant E. coli BL21(DE3)pLysS. To our best knowledge, this is the first functional study report of camI as well as the first report describing the production of C14-HSL by C. amalonaticus.
  15. Pusparajah P, Letchumanan V, Law JW, Ab Mutalib NS, Ong YS, Goh BH, et al.
    Int J Mol Sci, 2021 Aug 28;22(17).
    PMID: 34502269 DOI: 10.3390/ijms22179360
    Biofilms formed by methicillin-resistant S. aureus (MRSA) are among the most frequent causes of biomedical device-related infection, which are difficult to treat and are often persistent and recurrent. Thus, new and effective antibiofilm agents are urgently needed. In this article, we review the most relevant literature of the recent years reporting on promising anti-MRSA biofilm agents derived from the genus Streptomyces bacteria, and discuss the potential contribution of these newly reported antibiofilm compounds to the current strategies in preventing biofilm formation and eradicating pre-existing biofilms of the clinically important pathogen MRSA. Many efforts are evidenced to address biofilm-related infections, and some novel strategies have been developed and demonstrated encouraging results in preclinical studies. Nevertheless, more in vivo studies with appropriate biofilm models and well-designed multicenter clinical trials are needed to assess the prospects of these strategies.
  16. Thye AY, Law JW, Tan LT, Pusparajah P, Ser HL, Thurairajasingam S, et al.
    Biology (Basel), 2022 Jan 02;11(1).
    PMID: 35053059 DOI: 10.3390/biology11010061
    There is growing evidence of studies associating COVID-19 survivors with increased mental health consequences. Mental health implications related to a COVID-19 infection include both acute and long-term consequences. Here we discuss COVID-19-associated psychiatric sequelae, particularly anxiety, depression, and post-traumatic stress disorder (PTSD), drawing parallels to past coronavirus outbreaks. A literature search was completed across three databases, using keywords to search for relevant articles. The cause may directly correlate to the infection through both direct and indirect mechanisms, but the underlying etiology appears more complex and multifactorial, involving environmental, psychological, and biological factors. Although most risk factors and prevalence rates vary across various studies, being of the female gender and having a history of psychiatric disorders seem consistent. Several studies will be presented, demonstrating COVID-19 survivors presenting higher rates of mental health consequences than the general population. The possible mechanisms by which the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters the brain, affecting the central nervous system (CNS) and causing these psychiatric sequelae, will be discussed, particularly concerning the SARS-CoV-2 entry via the angiotensin-converting enzyme 2 (ACE-2) receptors and the implications of the immune inflammatory signaling on neuropsychiatric disorders. Some possible therapeutic options will also be considered.
  17. Law JW, Law LN, Letchumanan V, Tan LT, Wong SH, Chan KG, et al.
    Molecules, 2020 Nov 17;25(22).
    PMID: 33212836 DOI: 10.3390/molecules25225365
    Worldwide cancer incidence and mortality have always been a concern to the community. The cancer mortality rate has generally declined over the years; however, there is still an increased mortality rate in poorer countries that receives considerable attention from healthcare professionals. This suggested the importance of the prompt detection, effective treatment, and prevention strategies. The genus Streptomyces has been documented as a prolific producer of biologically active secondary metabolites. Streptomycetes from mangrove environments attract researchers' attention due to their ability to synthesize diverse, interesting bioactive metabolites. The present review highlights research on mangrove-derived streptomycetes and the production of anticancer-related compounds from these microorganisms. Research studies conducted between 2008 and 2019, specifically mentioning the isolation of streptomycetes from mangrove areas and described the successful purification of compound(s) or generation of crude extracts with cytotoxic activity against human cancer cell lines, were compiled in this review. It is anticipated that there will be an increase in prospects for mangrove-derived streptomycetes as one of the natural resources for the isolation of chemotherapeutic agents.
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