Displaying publications 21 - 40 of 74 in total

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  1. Ng KP, Yew SM, Chan CL, Chong J, Tang SN, Soo-Hoo TS, et al.
    Genome Announc, 2013 Jan;1(1).
    PMID: 23405310 DOI: 10.1128/genomeA.00056-12
    The emergence of the global threat of extensively drug-resistant (XDR) Mycobacterium tuberculosis reveals weaknesses in tuberculosis management and diagnostic services. We report the draft genome sequence of the first extensively drug-resistant Mycobacterium tuberculosis strain isolated in Malaysia. The sequence was also compared against a reference strain to elucidate the polymorphism that is related to their extensive resistance.
  2. Ng KP, Ngeow YF, Yew SM, Hassan H, Soo-Hoo TS, Na SL, et al.
    Eukaryotic Cell, 2012 May;11(5):703-4.
    PMID: 22544898 DOI: 10.1128/EC.00074-12
    Daldinia eschscholzii is an invasive endophyte that is most commonly found in plant tissues rich in secondary metabolites. We report the draft genome sequence of D. eschscholzii isolated from blood culture. The draft genome is 35,494,957 bp in length, with 42,898,665 reads, 61,449 contigs, and a G+C content of 46.8%. The genome was found to contain a high abundance of genes associated with plant cell wall degradation enzymes, mycotoxin production, and antifungal drug resistance.
  3. Lee KW, Devaraj NK, Ching SM, Veettil SK, Hoo FK, Deuraseh I, et al.
    Oman Med J, 2021 May;36(3):e273.
    PMID: 34239714 DOI: 10.5001/omj.2021.62
    Objectives: Non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH) is a common problem associated with obesity and type 2 diabetes mellitus (T2DM). There have been anecdotal reports of the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2Is) in improving liver function parameters in those with concomitant T2DM and NAFLD/NASH. We sought to systematically evaluate the evidence of SGLT2Is in improving liver function parameters in T2DM patients with NAFLD, considering the risks of random error based on trial sequential analysis (TSA). We also performed a meta-analysis based on a random-effects model.

    Methods: A systematic literature search was performed using the Medline, Cochrane, and Embase databases from inception to 20 October 2018. Primary outcome for meta-analyses was the changes in hepatic enzyme levels (alanine transaminase, aspartate transaminase, and gamma-glutamyl transpeptidase). We also performed a meta-analysis on changes in insulin resistance, glycemic, and lipid parameters using SGLT2Is as a secondary objective.

    Results: Eight eligible randomized controlled studies were eligible for analysis. Meta-analysis showed the efficacy of two SLT2Is, dapagliflozin, and canagliflozin in reducing these enzymes level. TSA showed that canagliflozin significantly reduced the gamma-glutamyl transpeptidase level by weighted mean difference (-5.474, 95% confidence interval (CI): -6.289??-4.659) compared to others comparators, and the evidence is conclusive. Dapagliflozin also had a statistically significant reduction in glycated hemoglobin, which is a parameter of glycemic control and homeostatic model assessment for insulin sensitivity (HOMA-IR), which is a parameter of insulin sensitivity by a weight mean difference, -0.732 (95% CI: -1.087??-0.378) and -0.804 (95% CI: -1.336??0.272), respectively.

    Conclusions: This study indicated that canagliflozin effectively improves liver function parameters among patients with diabetes, while dapagliflozin is more effective in improving glycemic indices and insulin sensitivity.

  4. Lee KW, Tan SF, Omar A, Nasir NH, Ching SM, Mohd Noor MK, et al.
    Gynecol Endocrinol, 2022 Jan;38(1):55-62.
    PMID: 34636710 DOI: 10.1080/09513590.2021.1988561
    AIM: The objective of this study was to determine the effectiveness of system-based intervention in reducing the incidence of diabetes and to improve the postnatal metabolic profiles among women with gestational diabetes mellitus (GDM).

    MATERIALS AND METHODS: For women in the intervention arm (n = 130), they received one session of individualized health education at 36 gestational weeks, a booklet of diabetes prevention, five-session of postpartum booster educational program which were conducted including 1 session of dietary and exercise counseling by dietician and physiotherapist at 6 weeks postpartum. For women in the control group (n = 168), standard treatment whereby they had received group therapy on diet and physical activity modification by dietician and staff nurses during the antenatal period.

    RESULTS: There were no significant differences in baseline characteristics between groups for most of the variables examined except for educational level which the control group had a higher education than the intervention group. The women assigned to system-based intervention have a significant difference to GDM women who were assigned to the control group for LDL and HDL but not in anthropometric measurements, blood pressure, glucose index, total cholesterol, and triglyceride. In addition, it was found that the incidence of Type 2 diabetes mellitus (T2DM) 2 years after delivery was 20% in the intervention arm compared to 17% in the control arm.

    CONCLUSION: The system-based intervention was not statistically superior to the control intervention as there is no difference in terms of incidence of T2DM between the intervention and control group. We, therefore, suggested that more intensive interventions are needed to prevent GDM from developing into T2DM.

  5. Nakamoto H, Yu XQ, Kim S, Origasa H, Zheng H, Chen J, et al.
    Ther Apher Dial, 2020 Feb;24(1):42-55.
    PMID: 31119846 DOI: 10.1111/1744-9987.12840
    TRK-100STP, a sustained-release preparation of the orally active prostacyclin analogue beraprost sodium, targets renal hypoxia. This study aimed to show the superiority of TRK-100STP over placebos in patients with chronic kidney disease (with either primary glomerular disease or nephrosclerosis) to determine the recommended dose. CASSIOPEIR (Chronic Renal Failure Asian Study with Oral PGI2 Derivative for Evaluating Improvement of Renal Function) was a randomized, double-blind, placebo-controlled study conducted at 160 sites in seven Asia-Pacific countries and regions. Eligible patients (n = 892) were randomized to TRK-100STP 120, 240 μg, or placebo for a treatment period of up to 4 years. The primary efficacy endpoint was time to first occurrence of a renal composite: doubling of serum creatinine or occurrence of end-stage renal disease. No significant differences were observed in composite endpoints between TRK-100STP and placebo (P = 0.5674). Hazard ratios (95% CI) in the TRK-100STP 120 and 240 μg vs. placebo groups were 0.98 (0.78, 1.22) and 0.91 (0.72, 1.14), respectively. The overall incidence of adverse events and adverse drug reactions was comparable between treatment arms.
  6. 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.
  7. Ching SM, Mokshashri NR, Kannan MM, Lee KW, Sallahuddin NA, Ng JX, et al.
    BMC Complement Med Ther, 2021 Jan 06;21(1):8.
    PMID: 33407414 DOI: 10.1186/s12906-020-03172-3
    BACKGROUND: The benefits of qigong for systolic and diastolic blood pressure (BP) reduction have been noted in previously published systematic reviews; however, the data on its effectiveness has been at best scarce. We aimed to update the evidence of qigong on blood pressure reduction after taking into consideration the risks of random error and reliability of data in the cumulative meta-analysis using trial sequential analysis (TSA).

    METHODS: Included trials were assessed using Cochrane risk of bias instrument. We performed meta-analysis with random-effects model and random errors were evaluated with TSA. We performed the search for the eligible randomized controlled trial (RCT) through Medline, Cinahl, Cochrane Central Register of Controlled Trials and also PubMed.

    RESULTS: A total of 370 subjects sourced from seven eligible RCTs were entered into the analysis. The pooled results demonstrated the significant reduction with the use of qigong of the systolic blood pressure [weighted mean difference (WMD), - 10.66 mmHg (95% confidence interval (CI) = - 17.69,-3.62, p 

  8. 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.
  9. Pheh KS, Tan CS, Lee KW, Tay KW, Ong HT, Yap SF
    PLoS One, 2023;18(5):e0285435.
    PMID: 37167230 DOI: 10.1371/journal.pone.0285435
    Generalized anxiety disorder (GAD) is one of the most common mental disorders in Malaysia. Psychometrically sound measurements are urgently needed to assess anxiety symptoms. The extensively used Generalized Anxiety Disorder 7-item (GAD-7) is a promising candidate. However, studies on its factorial validity show mixed findings. While the one-factor solution has been replicated in different cultural contexts, some studies found different factorial structures instead. This study aimed to clarify the factorial validity of the English version of the GAD-7 in the Malaysian context. The responses collected from 1272 emerging to older adults in Malaysia were randomly divided into two halves and submitted to exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) respectively. Four acceptable models were explored in EFA ranging from unidimensional factor with 7 items to 3-factor models with 6 items. The four models revealed in EFA and the other competing models found in past studies were then examined and compared using CFA. The 6-item second-order model with a general factor of anxiety and three first-order factors with two items respectively (i.e., GAD-6) showed a more harmonic result and hence, is preferable. Moreover, the GAD-6 and its three subscales also showed satisfactory internal consistency and construct validity. This study uncovers a new and unique factorial structure of the GAD screening tool that fits in the Malaysian context. The scale may reveal GAD symptomatic dimensions that guide clinical interventions.
  10. Lee KW, Ching SM, Hoo FK, Ramachandran V, Chong SC, Tusimin M, et al.
    Qual Life Res, 2020 Oct;29(10):2725-2736.
    PMID: 32430781 DOI: 10.1007/s11136-020-02532-3
    PURPOSE: This study aimed to identify factors associated with poor-to-moderate quality of life (QOL) among women with gestational diabetes mellitus (GDM) in two tertiary hospitals in Malaysia.

    METHODS: A cross-sectional study was conducted among 526 pregnant women with GDM in two tertiary hospitals in Malaysia. Diabetes-related QOL was assessed using the Asian Diabetes Quality of Life Scale (AsianDQoL). Socio-demographic characteristics, glucose monitoring treatments for GDM, past obstetric history, concurrent medical problems and a family history of diseases were captured from patient records. A multiple logistic regression was used for analysis.

    RESULTS: A total of 526 respondents with GDM entered the analysis. The median age of the respondents was 32 (interquartile range = 7) while 82.3% were Malay women. More than half of the respondents (69.5%) received an oral hypoglycaemic agent (OHA), and/or diet modification in controlling their GDM. The study reported that 23.2% of the respondents had poor-to-moderate QOL. Those with a family history of depression and/or anxiety (adjusted Odds ratio [AOR] 6.934, 95% confidence interval [CI] 2.280-21.081), and a family history of GDM (AOR 1.814, 95% CI 1.185-2.778) were at higher odds of suffering from poor-to-moderate QOL compared to those without a family history. Similarly, those who received insulin, with or without OHA, and/or are on diet modification (AOR 1.955, 95% CI 1.243-3.074) were at higher odds of suffering from poor-to-moderate QOL compared to those receiving OHA and/or diet modification.

    CONCLUSION: Nearly one-quarter of Malaysian women with GDM have poor-to-moderate QOL. GDM women with a family history of depression and/or anxiety, family history of GDM, and those who received insulin, with or without OHA, and/or are on diet modification were associated with poor-to-moderate QOL.

    TRIAL REGISTRATION: NMRR-17-2264-37814.

  11. Zohari Z, Barkham T, Mohamad Maswan N, Chen SL, Muthanna A, Lee KW, et al.
    J Med Microbiol, 2023 Jun;72(6).
    PMID: 37389575 DOI: 10.1099/jmm.0.001729
    In South East Asia, Streptococcus agalactiae ST283 causes sepsis in healthy adults. Raw freshwater fish consumption is the only known risk factor. These two case reports are the first from Malaysia. Although they cluster with Singapore ST283, the epidemiology is complicated by the flow of people and fish across borders.
  12. Tan KK, Tan YC, Chang LY, Lee KW, Nore SS, Yee WY, et al.
    BMC Genomics, 2015;16:93.
    PMID: 25888205 DOI: 10.1186/s12864-015-1294-x
    Brucellosis is an important zoonotic disease that affects both humans and animals. We sequenced the full genome and characterised the genetic diversity of two Brucella melitensis isolates from Malaysia and the Philippines. In addition, we performed a comparative whole-genome single nucleotide polymorphism (SNP) analysis of B. melitensis strains collected from around the world, to investigate the potential origin and the history of the global spread of B. melitensis.
  13. Lee KW, Ching SM, Devaraj NK, Hoo FK
    Ann Transl Med, 2020 Sep;8(17):1060.
    PMID: 33145279 DOI: 10.21037/atm-20-1579
    Background: Certain candidate genes have been associated with obesity. The goal of this study is to determine the association between thirteen neuroendocrine disorder-related candidate genes and pre-pregnancy obesity among gestational diabetes mellitus (GDM) patients using the stratification approach defined the Asian and International criteria-based body mass index (BMI).

    Methods: This was a post-hoc case-control exploratory sub-analysis of a cross-sectional study among GDM women to determine which candidate single nucleotide polymorphisms (SNPs) related to neuroendocrine disorders may be associated with obesity. Factors were adjusted for socio-demographic characteristics and concurrent medical problems in this particular population. Pre-pregnancy BMI and concurrent medical profiles were obtained from maternal health records. Obesity is defined as BMI of ≥27.5 kg/m2 for Asian criteria-based BMI and >30 kg/m2 for International criteria-based BMI. Thirteen candidate genes were genotyped using Agena® MassARRAY and examined for association with pre-pregnancy obesity using multiple logistic regression analysis. The significant difference threshold was set at P value <0.05.

    Results: Three hundred and twelve GDM women were included in this study; 60.9% and 44.2% of GDM patients were obese using Asian and International criteria-based BMI, respectively. GDM patients with AA or AG genotypes in specific SNP of brain-derived neurotrophic factor (BDNF) (G > A in rs6265) are more likely to be obese (adjusted odd ratio =2.209, 95% CI, 1.305, 3.739, P=0.003) compared to those who carry the GG genotype in the SNP adjusted for parity, underlying with asthma, heart disease, anaemia, education background in the International criteria-based BMI stratification group. On the other hand, there were no associations between other candidate genes (NRG1, FKBP5, RORA, OXTR, PLEKHG1, HTR2C, LHPP, SDK2, TEX51, EPHX2, NPY5R and ANO2) and maternal obesity.

    Conclusions: In summary, BDNF rs6265 is significantly associated with pre-pregnancy obesity among GDM patients. The exact role of BDNF adjusted for diet intake and lifestyle factors merits further investigation.

  14. Kuan CS, Chan CL, Yew SM, Toh YF, Khoo JS, Chong J, et al.
    PLoS One, 2015;10(6):e0131694.
    PMID: 26110649 DOI: 10.1371/journal.pone.0131694
    The outbreak of extensively drug-resistant tuberculosis (XDR-TB) has become an increasing problem in many TB-burdened countries. The underlying drug resistance mechanisms, including the genetic variation favored by selective pressure in the resistant population, are partially understood. Recently, the first case of XDR-TB was reported in Malaysia. However, the detailed genotype family and mechanisms of the formation of multiple drugs resistance are unknown. We sequenced the whole genome of the UM 1072388579 strain with a 2-kb insert-size library and combined with that from previously sequenced 500-bp-insert paired-end reads to produce an improved sequence with maximal sequencing coverage across the genome. In silico spoligotyping and phylogenetic analyses demonstrated that UM 1072388579 strain belongs to an ancestral-like, non-Beijing clade of East Asia lineage. This is supported by the presence of a number of lineage-specific markers, including fadD28, embA, nuoD and pks7. Polymorphism analysis showed that the drug-susceptibility profile is correlated with the pattern of resistance mutations. Mutations in drug-efflux pumps and the cell wall biogenesis pathway such as mmpL, pks and fadD genes may play an important role in survival and adaptation of this strain to its surrounding environment. In this work, fifty-seven putative promoter SNPs were identified. Among them, we identified a novel SNP located at -4 T allele of TetR/acrR promoter as an informative marker to recognize strains of East Asian lineage. Our work indicates that the UM 1072388579 harbors both classical and uncommon SNPs that allow it to escape from inhibition by many antibiotics. This study provides a strong foundation to dissect the biology and underlying resistance mechanisms of the first reported XDR M. tuberculosis in Malaysia.
  15. Toh YF, Yew SM, Chan CL, Na SL, Lee KW, Hoh CC, et al.
    PLoS One, 2016;11(9):e0162095.
    PMID: 27626635 DOI: 10.1371/journal.pone.0162095
    Pyrenochaeta unguis-hominis is a rare human pathogen that causes infection in human skin and nail. P. unguis-hominis has received little attention, and thus, the basic biology and pathogenicity of this fungus is not fully understood. In this study, we performed in-depth analysis of the P. unguis-hominis UM 256 genome that was isolated from the skin scraping of a dermatitis patient. The isolate was identified to species level using a comprehensive multilocus phylogenetic analysis of the genus Pyrenochaeta. The assembled UM 256 genome has a size of 35.5 Mb and encodes 12,545 putative genes, and 0.34% of the assembled genome is predicted transposable elements. Its genomic features propose that the fungus is a heterothallic fungus that encodes a wide array of plant cell wall degrading enzymes, peptidases, and secondary metabolite biosynthetic enzymes. Antifungal drug resistance genes including MDR, CDR, and ERG11/CYP51 were identified in P. unguis-hominis UM 256, which may confer resistance to this fungus. The genome analysis of P. unguis-hominis provides an insight into molecular and genetic basis of the fungal lifestyles, understanding the unrevealed biology of antifungal resistance in this fungus.
  16. Chan CL, Yew SM, Ngeow YF, Na SL, Lee KW, Hoh CC, et al.
    BMC Genomics, 2015 Nov 18;16:966.
    PMID: 26581579 DOI: 10.1186/s12864-015-2200-2
    BACKGROUND: Daldinia eschscholtzii is a wood-inhabiting fungus that causes wood decay under certain conditions. It has a broad host range and produces a large repertoire of potentially bioactive compounds. However, there is no extensive genome analysis on this fungal species.

    RESULTS: Two fungal isolates (UM 1400 and UM 1020) from human specimens were identified as Daldinia eschscholtzii by morphological features and ITS-based phylogenetic analysis. Both genomes were similar in size with 10,822 predicted genes in UM 1400 (35.8 Mb) and 11,120 predicted genes in UM 1020 (35.5 Mb). A total of 751 gene families were shared among both UM isolates, including gene families associated with fungus-host interactions. In the CAZyme comparative analysis, both genomes were found to contain arrays of CAZyme related to plant cell wall degradation. Genes encoding secreted peptidases were found in the genomes, which encode for the peptidases involved in the degradation of structural proteins in plant cell wall. In addition, arrays of secondary metabolite backbone genes were identified in both genomes, indicating of their potential to produce bioactive secondary metabolites. Both genomes also contained an abundance of gene encoding signaling components, with three proposed MAPK cascades involved in cell wall integrity, osmoregulation, and mating/filamentation. Besides genomic evidence for degrading capability, both isolates also harbored an array of genes encoding stress response proteins that are potentially significant for adaptation to living in the hostile environments.

    CONCLUSIONS: Our genomic studies provide further information for the biological understanding of the D. eschscholtzii and suggest that these wood-decaying fungi are also equipped for adaptation to adverse environments in the human host.

  17. Ng KP, Yew SM, Chan CL, Soo-Hoo TS, Na SL, Hassan H, et al.
    Eukaryotic Cell, 2012 Jun;11(6):828.
    PMID: 22645233 DOI: 10.1128/EC.00133-12
    Pleosporales is the largest order in the fungal class Dothideomycetes. We report the 36,814,818-bp draft genome sequence and gene annotation of UM1110, a Pleosporales isolate associated with unclassified genera that is potentially a new fungal species. Analysis of the genome sequence led to the finding of genes associated with fungal adhesive proteins, secreted proteases, allergens, and pseudohyphal development.
  18. Kuan CS, Cham CY, Singh G, Yew SM, Tan YC, Chong PS, et al.
    PLoS One, 2016;11(8):e0161008.
    PMID: 27570972 DOI: 10.1371/journal.pone.0161008
    Cladophialophora bantiana is a dematiaceous fungus with a predilection for causing central nervous system (CNS) infection manifesting as brain abscess in both immunocompetent and immunocompromised patients. In this paper, we report comprehensive genomic analyses of C. bantiana isolated from the brain abscess of an immunocompetent man, the first reported case in Malaysia and Southeast Asia. The identity of the fungus was determined using combined morphological analysis and multilocus phylogeny. The draft genome sequence of a neurotrophic fungus, C. bantiana UM 956 was generated using Illumina sequencing technology to dissect its genetic fundamental and basic biology. The assembled 37.1 Mb genome encodes 12,155 putative coding genes, of which, 1.01% are predicted transposable elements. Its genomic features support its saprophytic lifestyle, renowned for its versatility in decomposing hemicellulose and pectin components. The C. bantiana UM 956 was also found to carry some important putative genes that engaged in pathogenicity, iron uptake and homeostasis as well as adaptation to various stresses to enable the organism to survive in hostile microenvironment. This wealth of resource will further catalyse more downstream functional studies to provide better understanding on how this fungus can be a successful and persistent pathogen in human.
  19. Tan KK, Tan YC, Chang LY, Lee KW, Nor'e SS, Yee WY, et al.
    J Infect Dev Ctries, 2017 Jun 01;11(5):420-425.
    PMID: 30943180 DOI: 10.3855/jidc.7598
    INTRODUCTION: Currently available tests have limitations for the identification of Brucella species and strains, and their genetic lineage. The genome sequence of the rpoB gene encoding the β-subunit of DNA-dependent RNA polymerase was investigated for its use in genotyping Brucella melitensis.

    METHODOLOGY: Complete rpoB gene sequences of globally distributed Brucella melitensis strains were analyzed. Single nucleotides polymorphisms (SNPs) of the rpoB gene sequences were identified and used to type Brucella melitensis strains.

    RESULTS: Six DNA polymorphisms were identified, of which two (nucleotides 3201 and 558) were novel. Analysis of the geographical distribution of the strains revealed a spatial clustering pattern with rpoB type 1 representing European and American strains, rpoB type 2 representing European, African, and Asian strains, rpoB type 3 representing Mediterranean strains, and rpoB type 4 representing African (C3201T) and European (C3201T/T558A) strains.

    CONCLUSIONS: We report the discovery of two novel SNPs of rpoB gene that can serve as useful markers for epidemiology and geographical tracking of B. melitensis.

  20. Mohamad Safiai NI, Mohamad NA, Basri H, Inche Mat LN, Hoo FK, Abdul Rashid AM, et al.
    PLoS One, 2021;16(6):e0251528.
    PMID: 34138860 DOI: 10.1371/journal.pone.0251528
    BACKGROUND: Migraine may lead to a negative impact on the patients' quality of life with a subsequent substantial burden to society. Therapy options for treatment and prevention of migraine have progressed over the years and repetitive transcranial magnetic stimulation (rTMS) is one of the promising non-pharmacological options. It induces and alters electric current in the brain via repetitive non-invasive brain stimulation in high frequency. In migraine patients, two common stimulation sites are the M1 cortex and dorsolateral prefrontal cortex (DLPFC). The mechanism on how rTMS exerts therapeutic effects on migraine is not fully established, but the main postulation is that the neuromodulation via high-frequency rTMS (hf-rTMS) might inhibit pain perception. However, evidence from studies has been conflicting, thus the usefulness of hf-rTMS as migraine preventive treatment is still uncertain at this moment.

    METHODS: This is a systematic review protocol describing essential reporting items based on the PRISMA for systematic review protocols (PRISMA-P) (Registration number: CRD42020220636). We aim to review the effectiveness, tolerability, and safety of hf-rTMS at DLPFC in randomised controlled trials (RCTs) as migraine prophylactic treatment. We will search Scopus, Cumulative Index to Nursing and Allied Health Literature Plus, PubMed, Cochrane Central Register of Controlled Trials and Biomed Central for relevant articles from randomised controlled clinical trials that used hf-rTMS applied at DLPFC for the treatment of migraine. The risk of bias will be assessed using the version 2 "Risk of bias" tool from Cochrane Handbook for Systematic Reviews of Interventions Version 6.1. We will investigate the evidence on efficacy, tolerability and safety and we will compare the outcomes between the hf-rTMS intervention and sham groups.

    DISCUSSION: This systematic review will further determine the efficacy, safety, and tolerability of hf-rTMS applied at DLPFC for migraine prophylaxis. It will provide additional data for health practitioners and policymakers about the usefulness of hf-rTMS for migraine preventive treatment.

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