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  1. Siew GY, Ng WL, Tan SW, Alitheen NB, Tan SG, Yeap SK
    PeerJ, 2018;6:e4266.
    PMID: 29511604 DOI: 10.7717/peerj.4266
    Durian (Durio zibethinus) is one of the most popular tropical fruits in Asia. To date, 126 durian types have been registered with the Department of Agriculture in Malaysia based on phenotypic characteristics. Classification based on morphology is convenient, easy, and fast but it suffers from phenotypic plasticity as a direct result of environmental factors and age. To overcome the limitation of morphological classification, there is a need to carry out genetic characterization of the various durian types. Such data is important for the evaluation and management of durian genetic resources in producing countries. In this study, simple sequence repeat (SSR) markers were used to study the genetic variation in 27 durian types from the germplasm collection of Universiti Putra Malaysia. Based on DNA sequences deposited in Genbank, seven pairs of primers were successfully designed to amplify SSR regions in the durian DNA samples. High levels of variation among the 27 durian types were observed (expected heterozygosity,H
    E
     = 0.35). The DNA fingerprinting power of SSR markers revealed by the combined probability of identity (PI) of all loci was 2.3×10-3. Unique DNA fingerprints were generated for 21 out of 27 durian types using five polymorphic SSR markers (the other two SSR markers were monomorphic). We further tested the utility of these markers by evaluating the clonal status of shared durian types from different germplasm collection sites, and found that some were not clones. The findings in this preliminary study not only shows the feasibility of using SSR markers for DNA fingerprinting of durian types, but also challenges the current classification of durian types, e.g., on whether the different types should be called "clones", "varieties", or "cultivars". Such matters have a direct impact on the regulation and management of durian genetic resources in the region.
  2. Yap HY, Tan NH, Ng ST, Tan CS, Fung SY
    Front Pharmacol, 2018;9:103.
    PMID: 29491836 DOI: 10.3389/fphar.2018.00103
    Naturally occurring anti-glycation compounds have drawn much interest in recent years as they show potential in reducing or preventing the risk of chronic complications for diabetic patients. In this study, annotation of the genome-transcriptome data from tiger milk mushroom (Lignosus rhinocerus, syn.Lignosus rhinocerotis) to PlantCyc enzymes database identified transcripts that are related to anti-diabetic properties, and these include genes that are involved in carotenoid and abscisic acid biosynthesis as well as genes that code for glyoxalase I, catalase-peroxidases, and superoxide dismutases. The existence of these genes suggests thatL. rhinocerusmay contain bioactive compound(s) with anti-glycation properties that can be exploited for management of diabetic complications. A medium-molecular-weight (MMW) fraction which was obtained from a combination of cold water extraction and Sephadex®G-50 (fine) gel filtration chromatography ofL. rhinocerussclerotia powder was demonstrated to exhibit potent anti-glycation activity. The fraction specifically inhibited the formation of N𝜀-(carboxymethyl)lysine, pentosidine, and other advanced glycation end-product (AGE) structures in a human serum albumin-glucose system, with an IC50value of 0.001 mg/ml, almost 520 times lower than that of the positive control, aminoguanidine hydrochloride (IC50= 0.52 mg/ml). Its ability to suppress protein glycation may be partly associated with its strong superoxide anion radical scavenging activity (10.16 ± 0.12 mmol TE/g). Our results suggest that the MMW fraction ofL. rhinocerusshows potential to be developed into a potent glycation inhibitor for preventing AGE-mediated diabetic complications.
  3. Liew LK, Tan MP, Tan PJ, Mat S, Majid LA, Hill KD, et al.
    J Geriatr Phys Ther, 2018 1 31;42(3):123-129.
    PMID: 29381526 DOI: 10.1519/JPT.0000000000000155
    BACKGROUND AND PURPOSE: Exercise-based interventions, such as the Otago Exercise Program (OEP), are effective in preventing falls in the older adult. Previous studies evaluating the OEP have determined falls, lower limb strength, or balance outcomes but with lack of assessment of hand grip strength. The objective of this study is to evaluate the effect of OEP on hand grip strength alongside mobility and balance outcomes.

    METHODS: This was a single-center, prospective, and single-blind randomized controlled trial conducted at the University Malaya Medical Centre. Patients older than 65 years presenting to the hospital emergency department or geriatric clinic with 1 injurious fall or 2 falls in the past year and with impaired functional mobility were included in the study. The intervention group received a modified OEP intervention (n = 34) for 3 months, while the control group received conventional care (n = 33). All participants were assessed at baseline and 6 months.

    RESULTS: Twenty-four participants in both OEP and control groups completed the 6-month follow-up assessments. Within-group analyses revealed no difference in grip strength in the OEP group (P = 1.00, right hand; P = .55, left hand), with significant deterioration in grip strength in the control group (P = .01, right hand; P = .005, left hand). Change in grip strength over 6 months significantly favored the OEP group (P = .047, right hand; P = .004, left hand). Significant improvements were also observed in mobility and balance in the OEP group.

    CONCLUSIONS: In addition to benefits in mobility and balance, the OEP also prevents deterioration in upper limb strength. Additional benefits of exercise interventions for secondary prevention of falls in term of sarcopenia and frailty should also be evaluated in the future.

  4. Ratanabanangkoon K, Simsiriwong P, Pruksaphon K, Tan KY, Chantrathonkul B, Eursakun S, et al.
    Sci Rep, 2018 06 26;8(1):9716.
    PMID: 29946111 DOI: 10.1038/s41598-018-27794-3
    In order to facilitate/expedite the production of effective and affordable snake antivenoms, a novel in vitro potency assay was previously developed. The assay is based on an antiserum's ability to bind to postsynaptic neurotoxin (PSNT) and thereby inhibit the PSNT binding to the nicotinic acetylcholine receptor (nAChR). The assay was shown to work well with antiserum against Thai Naja kaouthia which produces predominantly the lethal PSNTs. In this work, the assay is demonstrated to work well with antiserum/antivenom against Bungarus candidus (BC), which also produces lethal presynaptic neurotoxins, as well as antivenom against Sri Lankan Naja naja (NN), which produces an abundance of cytotoxins. The in vitro and in vivo median effective ratios (ER50s) for various batches of antisera against BC showed a correlation (R2) of 0.8922 (p 
  5. Fung SY, Cheong PCH, Tan NH, Ng ST, Tan CS
    Int J Med Mushrooms, 2018;20(5):459-469.
    PMID: 29953361 DOI: 10.1615/IntJMedMushrooms.2018026252
    A cultivar of fruiting bodies of Ophiocordyceps sinensis (FBOS; OCS02) was analyzed for nutrients, bioactive compounds, and heavy metal content to showcase its potential as a competitive, sustainable, and safe alternative to wild types and other cultivars. A previous 28-day subacute toxicity study showed that doses up to 1 g · kg-1 did not cause any adverse effects in Sprague-Dawley rats. The OCS02 cultivar contained large amounts of cordycepin, polysaccharides, and essential and semi-essential amino acids (0.66, 482.80, 99.02, and 101.04 g · kg-1, respectively) compared with levels reported in wild types and in cultivated mycelia. β-1,3/1,6-glucan content was considerably high at 342.50 g · kg-1. The potassium level (5.14 g kg-1) tied in well with the low sodium content (0.121 g · kg-1)-6 times lower than amounts in wild types. We found no detectable levels of heavy metals such as lead, arsenic, cadmium, and mercury. The major amino acids found in FBOS (0CS02 cultivar) were arginine, lysine, serine, and threonine at 45.20, 20.30, 18.60, and 18.20 g · kg-1, respectively. The cultivated FBOS (OCS02 cultivar) is a comparable alternative to wild-type and other cultivated strains of O. sinensis. It has potential as a nutraceutical to meet market demand.
  6. Tan JH, Mohamad Y, Tan CLH, Kassim M, Warkentin TE
    J Med Case Rep, 2018 May 19;12(1):131.
    PMID: 29776439 DOI: 10.1186/s13256-018-1684-1
    BACKGROUND: Symmetrical peripheral gangrene is characterized as acral (distal extremity) ischemic limb injury affecting two or more extremities, without large vessel obstruction, typically in a symmetrical fashion. Risk factors include hypotension, disseminated intravascular coagulation, and acute ischemic hepatitis ("shock liver"). In contrast, venous limb gangrene is characterized by acral ischemic injury occurring in a limb with deep vein thrombosis. Both symmetrical peripheral gangrene and venous limb gangrene present as acral limb ischemic necrosis despite presence of arterial pulses. The coexistence of symmetrical peripheral gangrene and venous limb gangrene is rare, with potential to provide pathophysiological insights.

    CASE PRESENTATION: A 42-year-old Chinese man presented with polytrauma (severe head injury, lung contusions, and right femur fracture). Emergency craniotomy and debridement of right thigh wound were performed on presentation. Intraoperative hypotension secondary to bleeding was complicated by transient need for vasopressors and acute liver enzyme elevation indicating shock liver. Beginning on postoperative day 5, he developed an acute platelet count fall (from 559 to 250 × 109/L over 3 days) associated with left iliofemoral deep vein thrombosis that evolved to bilateral lower limb ischemic necrosis; ultimately, the extent of limb ischemic injury was greater in the left (requiring below-knee amputation) versus the right (transmetatarsal amputation). As the presence of deep vein thrombosis is a key feature known to localize microthrombosis and hence ischemic injury in venous limb gangrene, the concurrence of unilateral lower limb deep vein thrombosis in a typical clinical setting of symmetrical peripheral gangrene (hypotension, proximate shock liver, platelet count fall consistent with disseminated intravascular coagulation) helps to explain asymmetric limb injury - manifesting as a greater degree of ischemic necrosis and extent of amputation in the limb affected by deep vein thrombosis - in a patient whose clinical picture otherwise resembled symmetrical peripheral gangrene.

    CONCLUSIONS: Concurrence of unilateral lower limb deep vein thrombosis in a typical clinical setting of symmetrical peripheral gangrene is a potential explanation for greater extent of acral ischemic injury in the limb affected by deep vein thrombosis.

  7. Yap HYY, Tan NH, Ng ST, Tan CS, Fung SY
    PeerJ, 2018;6:e4940.
    PMID: 29888137 DOI: 10.7717/peerj.4940
    Background: The highly valued medicinal tiger milk mushroom (also known as Lignosus rhinocerus) has the ability to cure numerous ailments. Its anticancer activities are well explored, and recently a partially purified cytotoxic protein fraction termed F5 from the mushroom's sclerotial cold water extract consisting mainly of fungal serine proteases was found to exhibit potent selective cytotoxicity against a human breast adenocarcinoma cell line (MCF7) with IC50 value of 3.00 μg/ml. However, characterization of its cell death-inducing activity has yet to be established.

    Methods: The mechanism involved in the cytotoxic activities of F5 against MCF7 cells was elucidated by flow cytometry-based apoptosis detection, caspases activity measurement, and expression profiling of apoptosis markers by western blotting. Molecular attributes of F5 were further mined from L. rhinocerus's published genome and transcriptome for future exploration.

    Results and Discussion: Apoptosis induction in MCF7 cells by F5 may involve a cross-talk between the extrinsic and intrinsic apoptotic pathways with upregulation of caspase-8 and -9 activities and a marked decrease of Bcl-2. On the other hand, the levels of pro-apoptotic Bax, BID, and cleaved BID were increased accompanied by observable actin cleavage. At gene level, F5 composed of three predicted non-synonymous single nucleotide polymorphisms (T > C) and an alternative 5' splice site.

    Conclusions: Findings from this study provide an advanced framework for further investigations on cancer therapeutics development from L. rhinocerus.

  8. Tan CY, Shahrizaila N, Yeoh KY, Goh KJ, Tan MP
    Clin Auton Res, 2019 06;29(3):339-348.
    PMID: 29654380 DOI: 10.1007/s10286-018-0525-z
    OBJECTIVE: The current study aimed to investigate autonomic dysfunction in Guillain-Barré syndrome (GBS) patients and describe the results of computational heart rate variability (HRV)/baroreflex sensitivity (BRS) and autonomic challenge tests.

    METHODS: GBS patients were consecutively recruited and the results were compared to age- and gender-matched healthy controls. A series of autonomic function tests including computation-dependent tests (power spectrum analysis of HRV and BRS at rest) and challenge maneuvers (deep breathing, eyeball compression, active standing, the Valsalva maneuver, sustained handgrip, and the cold pressor test) were performed.

    RESULTS: Ten GBS patients (six men; mean age = 40.1 ± 13.9 years) and ten gender- and age-matched healthy controls were recruited. The mean GBS functional grading scale at disease plateau was 3.4 ± 1.0. No patients required intensive care unit admission or mechanical ventilation. Low-frequency HRV (p = 0.027), high-frequency HRV (p = 0.008), and the total power spectral density of HRV (p = 0.015) were significantly reduced in patients compared to controls. The mean up slope (p = 0.034), down slope (p = 0.011), and total slope (p = 0.024) BRS were significantly lower in GBS patients. The diastolic rise in blood pressure in the cold pressor test was significantly lower in GBS patients compared to controls (p = 0.008).

    INTERPRETATION: Computation-dependent tests (HRV and BRS) were more useful for detecting autonomic dysfunction in GBS patients, whereas the cold pressor test was the only reliable challenge test, making it useful as a bedside measure of autonomic function in GBS patients.

  9. Tan GW, Visser L, Tan LP, van den Berg A, Diepstra A
    Pathogens, 2018 04 13;7(2).
    PMID: 29652813 DOI: 10.3390/pathogens7020040
    The Epstein–Barr virus (EBV) can cause a wide variety of cancers upon infection of different cell types and induces a highly variable composition of the tumor microenvironment (TME). This TME consists of both innate and adaptive immune cells and is not merely an aspecific reaction to the tumor cells. In fact, latent EBV-infected tumor cells utilize several specific mechanisms to form and shape the TME to their own benefit. These mechanisms have been studied largely in the context of EBV+ Hodgkin lymphoma, undifferentiated nasopharyngeal carcinoma, and EBV+ gastric cancer. This review describes the composition, immune escape mechanisms, and tumor cell promoting properties of the TME in these three malignancies. Mechanisms of susceptibility which regularly involve genes related to immune system function are also discussed, as only a small proportion of EBV-infected individuals develops an EBV-associated malignancy.
  10. Goh YK, Marzuki NF, Tan SY, Tan SS, Tung HJ, Goh YK, et al.
    Mycology, 2016;7(1):36-44.
    PMID: 30123614 DOI: 10.1080/21501203.2015.1137985
    The influence of different medium components (glucose, sucrose, and fructose) on the growth of different Ganoderma isolates and species was investigated using mixture design. Ten sugar combinations based on three simple sugars were generated with two different concentrations, namely 3.3% and 16.7%, which represented low and high sugar levels, respectively. The media were adjusted to either pH 5 or 8. Ganoderma isolates (two G. boninense from oil palm, one Ganoderma species from coconut palm, G. lingzhi, and G. australe from tower tree) grew faster at pH 8. Ganoderma lingzhi proliferated at the slowest rate compared to all other tested Ganoderma species in all the media studied. However, G. boninense isolates grew the fastest. Different Ganoderma species were found to have different sugar preferences. This study illustrated that the mixture design can be used to determine the optimal combinations of sugar or other nutrient/chemical components of media for fungal growth.
  11. Tan YJ, Lee YT, Yeong KY, Petersen SH, Kono K, Tan SC, et al.
    Future Med Chem, 2018 Sep 01;10(17):2039-2057.
    PMID: 30066578 DOI: 10.4155/fmc-2018-0052
    AIM: This study aims to investigate the mode of action of a novel sirtuin inhibitor (BZD9L1) and its associated molecular pathways in colorectal cancer (CRC) cells.

    MATERIALS & METHODS: BZD9L1 was tested against metastatic CRC cell lines to evaluate cytotoxicity, cell cycle and apoptosis, senescence, apoptosis related genes and protein expressions, as well as effect against major cancer signaling pathways.

    RESULTS & CONCLUSION: BZD9L1 reduced the viability, cell migration and colony forming ability of both HCT 116 and HT-29 metastatic CRC cell lines through apoptosis. BZD9L1 regulated major cancer pathways differently in CRC with different mutation profiles. BZD9L1 exhibited anticancer activities as a cytotoxic drug in CRC and as a promising therapeutic strategy in CRC treatment.

  12. Cheong AM, Tan ZW, Patrick NO, Tan CP, Lim YM, Nyam KL
    Food Sci Biotechnol, 2018 Aug;27(4):1175-1184.
    PMID: 30263848 DOI: 10.1007/s10068-018-0342-0
    Kenaf seed oil-in-water nanoemulsions (KSON) and kenaf seed oil-in-water macroemulsions were produced to access their gastroprotective effect against indomethacin- and ethanol-induced ulcers in comparison with non-emulsified kenaf seed oil (KSO). Emulsifier mixture (EM) that used to emulsify KSO was also included in the study. Ulcer index, stomach tissue oxidative status, and histopathological changes in indomethacin-induced and ethanol-induced ulcer models were both evaluated. KSON had demonstrated good gastroprotective effect against both ulcer models than non-emulsified KSO and KSOM. In addition, the gastroprotective effect of KSON was comparable to the standard drug, Omeprazole. EM also exhibited gastroprotective effect, especially in indomethacin-induced ulcers. This may be attributed to its high antioxidant activity and cytoprotective effect of sodium caseinate contained in the EM. Results supported that KSON enhanced the bioavailability of native KSO; therefore it offers gastroprotective effect for the prevention of gastric ulceration as a natural alternative to the synthetic drug.
  13. Suppiah TSS, Sundram TKM, Tan ESS, Lee CK, Bustami NA, Tan CK
    Asia Pac J Clin Nutr, 2018 10 3;27(5):1141-1145.
    PMID: 30272862 DOI: 10.6133/apjcn.072018.01
    BACKGROUND AND OBJECTIVES: Acne vulgaris is a common skin condition among adolescents and young adults. Its relationship with the dietary intake is highly debatable and equivocal. This study aimed to identify the association between acne vulgaris and dietary intake among Malaysians.

    METHODS AND STUDY DESIGN: A case-control study was conducted involving 57 acne vulgaris patients and 57 age-, gender- and ethnicity-matched controls. All participants were aged 14 and above. The Comprehensive Acne Severity Scale (CASS) was used to categorise patients (grades 2 to 5) and controls (grades 0 to 1). Information such as the demographics, family history, smoking habits and dietary intake were collected using a self-administered questionnaire.

    RESULTS: In the patient arm, the gender ratio of male to female was 1.5:1. 43 patients (75.4%) had a family history of acne vulgaris. No significant association was found for acne in patients with a history of smoking. Milk consumption was significantly higher in patients (63.2%, n=36) versus controls (43.9%, n=25), (OR=2.19, p<0.05). In addition, chocolate consumption was also significantly higher in patients (43.9%, n=25) versus controls (24.6%, n=14), (OR=2.4, p<0.05). No significant association was found with the intakes of sweets, potatoes, chips, nuts, yoghurt, ice-cream or carbonated drinks.

    CONCLUSIONS: Dietary intake of milk and chocolate may play a role in acne vulgaris. Prospective cohort and intervention studies are recommended to explore whether a causal relationship might obtain.

  14. Fung SY, Cheong PCH, Tan NH, Ng ST, Tan CS
    IUBMB Life, 2019 07;71(7):821-826.
    PMID: 30629799 DOI: 10.1002/iub.2006
    Sclerotial powder of a cultivated species of the Tiger Milk Mushroom, Lignosus cameronensis was analysed for its nutritional components and compared against species of the same genus, Lignosus rhinocerus and Lignosus tigris. All three species have been used by indigenous tribes in Peninsular Malaysia as medicinal mushrooms. Content of carbohydrate, fibre, mineral, amino acid, palatable index, fat, ash and moisture were determined. L. cameronensis sclerotial material consists of carbohydrate (79.7%), protein (12.4%) and dietary fibre (5.4%) with low fat (1.7%) and no free sugar. It has the highest content of total carbohydrate (791 g kg-1 ), energy value (3,700 kcal kg-1 ) and calcium (0.85 g kg-1 ). The crude protein content (123 g kg-1 ) is comparable to that of L. rhinocerus with its main amino acids consisting of glutamic acid, aspartic acid and leucine. The umami index is determined to be 0.27. The total essential amino acid (45 g kg-1 ) is comparable to that of L. tigris. The main mineral is potassium (1.51 g kg-1 ) and the Na/K ratio was <0.6. Heavy metals such as mercury, cadmium, lead and arsenic were absent. L. cameronensis has the highest amount of food energy, total carbohydrate and calcium compared to those of both L. rhinocerus and L. tigris. The essential amino acids comprised almost 40% of the total amino acid content, slightly more than that reported from sclerotial powder of the L. tigris. © 2019 IUBMB Life, 9999(9999):1-6, 2019.
  15. Tan YJ, Tan YS, Yeo CI, Chew J, Tiekink ERT
    J Inorg Biochem, 2019 03;192:107-118.
    PMID: 30640150 DOI: 10.1016/j.jinorgbio.2018.12.017
    Four binuclear phosphanesilver(I) dithiocarbamates, {cyclohexyl3PAg(S2CNRR')}2 for R = R' = Et (1), CH2CH2 (2), CH2CH2OH (3) and R = Me, R' = CH2CH2OH (4) have been synthesised and characterised by spectroscopy and crystallography, and feature tri-connective, μ2-bridging dithiocarbamate ligands and distorted tetrahedral geometries based on PS3 donor sets. The compounds were evaluated for anti-bacterial activity against a total of 12 clinically important pathogens. Based on minimum inhibitory concentration (MIC) and cell viability tests (human embryonic kidney cells, HEK 293), 1-4 are specifically active against Gram-positive bacteria while demonstrating low toxicity; 3 and 4 are active against methicillin resistant S. aureus (MRSA). Across the series, 4 was most effective and was more active than the standard anti-biotic chloramphenicol. Time kill assays reveal 1-4 to exhibit both time- and concentration-dependent pharmacokinetics against susceptible bacteria. Compound 4 demonstrates rapid (within 2 h) bactericidal activity at 1 and 2 × MIC to reach a maximum decrease of 5.2 log10 CFU/mL against S. aureus (MRSA).
  16. Faheem NAA, Kwan Z, Yong ASW, Ch'ng CC, Tan KK, Naicker M, et al.
    Malays J Pathol, 2019 Apr;41(1):47-49.
    PMID: 31025637
    Naevus sebaceus is a cutaneous hamartoma with the potential of developing into benign or malignant neoplasms. Syringocystadenoma papilliferum (SCAP) have been reported to originate from naevus sebaceus. SCAP is a rare, benign adnexal skin tumour of apocrine or eccrine type of differentiation which typically presents as a nodule or a plaque on the scalp or face. We report a case of syringocystadenoma papilliferum arising in an undiagnosed pre-existing naevus sebaceus in a 56-year-old female.
  17. Mohd Fauzi NA, Abdullah S, Tan AH, Mohd Ramli N, Tan CY, Lim SY
    Parkinsonism Relat Disord, 2020 06;75:110-113.
    PMID: 30846242 DOI: 10.1016/j.parkreldis.2019.02.025
    We report a case of relapsing-remitting opsoclonus-myoclonus-ataxia syndrome (OMAS) in a patient with Hashimoto's encephalopathy, diagnosed after comprehensive evaluation. OMAS as a manifestation of Hashimoto's encephalopathy has been reported once previously. It is hoped that recognition of this entity and early initiation of immunotherapy will improve clinical outcomes for patients.
  18. Lim RZM, Ooi JY, Tan JH, Tan HCL, Sikin SM
    Int J Surg Oncol, 2019;2019:6109643.
    PMID: 30941211 DOI: 10.1155/2019/6109643
    Introduction: Therapeutic nodal dissection is still the mainstay of treatment for patients with lymph node metastases in many centres. The local data, however, on the outcome of therapeutic LND remains limited. Hence, this study aims to inform practice by presenting the outcomes of LND for thyroid cancer patients and our experience in a tertiary referral centre.

    Methods: This is a single-centre retrospective observational study in a Malaysian tertiary endocrine surgery referral centre. Patients who underwent total thyroidectomy with lymph node dissection between years 2013 and 2015 were included and electronic medical records over a 3-year follow-up period were reviewed. The outcomes of different lymph node dissection (LND), including central neck dissection, lateral neck dissection, or both, were compared.

    Results: Of the 43 subjects included, 28 (65.1%) had Stage IV cancer. Among the 43 subjects included, 8 underwent central LND, and 15 had lateral LND while the remaining 20 had dissection of both lateral and central lymph nodes. Locoregional recurrence was found in 16 (37.2%) of our subjects included, with no statistical difference between the central (2/8), lateral (7/15), and both (7/20). Postoperative hypocalcaemia occurred in 7 (16.3%) patients, and vocal cord palsy occurred in 5 (11.6%), whereas 9 patients (20.9%) required reoperation. Death occurred in 4 of our patients.

    Conclusion: High recurrence and reoperative rates were observed in our centre. While the routine prophylactic LND remains controversial, high risk patients may be considered for prophylactic LND. The long-term risk and benefit of prophylactic LND with individualised patient selection in the local setting deserve further studies.

  19. Yee PTI, Tan SH, Ong KC, Tan KO, Wong KT, Hassan SS, et al.
    Sci Rep, 2019 03 18;9(1):4805.
    PMID: 30886246 DOI: 10.1038/s41598-019-41285-z
    Besides causing mild hand, foot and mouth infections, Enterovirus A71 (EV-A71) is associated with neurological complications and fatality. With concerns about rising EV-A71 virulence, there is an urgency for more effective vaccines. The live attenuated vaccine (LAV) is a more valuable vaccine as it can elicit both humoral and cellular immune responses. A miRNA-based vaccine strain (pIY) carrying let-7a and miR-124a target genes in the EV-A71 genome which has a partial deletion in the 5'NTR (∆11 bp) and G64R mutation (3Dp°l) was designed. The viral RNA copy number and viral titers of the pIY strain were significantly lower in SHSY-5Y cells that expressed both let-7a and miR-124a. Inhibition of the cognate miRNAs expressed in RD and SHSY-5Y cells demonstrated de-repression of viral mRNA translation. A previously constructed multiply mutated strain, MMS and the pIY vaccine strain were assessed in their ability to protect 4-week old mice from hind limb paralysis. The MMS showed higher amounts of IFN-γ ex vivo than the pIY vaccine strain. There was absence of EV-A71 antigen in the skeletal muscles and spinal cord micrographs of mice vaccinated with the MMS and pIY strains. The MMS and pIY strains are promising LAV candidates developed against severe EV-A71 infections.
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