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Fulltext Insight into different environmental niches adaptation and allergenicity from the Cladosporium sphaerospermum genome, a common human allergy-eliciting Dothideomycetes

Yew SM, Chan CL, Ngeow YF, Toh YF, Na SL, Lee KW, et al.

Sci Rep, 2016 05 31;6:27008.
PMID: 27243961 DOI: 10.1038/srep27008

Cladosporium sphaerospermum, a dematiaceous saprophytic fungus commonly found in diverse environments, has been reported to cause allergy and other occasional diseases in humans. However, its basic biology and genetic information are largely unexplored. A clinical isolate C. sphaerospermum genome, UM 843, was re-sequenced and combined with previously generated sequences to form a model 26.89 Mb genome containing 9,652 predicted genes. Functional annotation on predicted genes suggests the ability of this fungus to degrade carbohydrate and protein complexes. Several putative peptidases responsible for lung tissue hydrolysis were identified. These genes shared high similarity with the Aspergillus peptidases. The UM 843 genome encodes a wide array of proteins involved in the biosynthesis of melanin, siderophores, cladosins and survival in high salinity environment. In addition, a total of 28 genes were predicted to be associated with allergy. Orthologous gene analysis together with 22 other Dothideomycetes showed genes uniquely present in UM 843 that encode four class 1 hydrophobins which may be allergens specific to Cladosporium. The mRNA of these hydrophobins were detected by RT-PCR. The genomic analysis of UM 843 contributes to the understanding of the biology and allergenicity of this widely-prevalent species.
Fulltext A five-year survey of dematiaceous fungi in a tropical hospital reveals potential opportunistic species

Yew SM, Chan CL, Lee KW, Na SL, Tan R, Hoh CC, et al.

PLoS One, 2014;9(8):e104352.
PMID: 25098697 DOI: 10.1371/journal.pone.0104352

Dematiaceous fungi (black fungi) are a heterogeneous group of fungi present in diverse environments worldwide. Many species in this group are known to cause allergic reactions and potentially fatal diseases in humans and animals, especially in tropical and subtropical climates. This study represents the first survey of dematiaceous fungi in Malaysia and provides observations on their diversity as well as in vitro response to antifungal drugs. Seventy-five strains isolated from various clinical specimens were identified by morphology as well as an internal transcribed spacer (ITS)-based phylogenetic analysis. The combined molecular and conventional approach enabled the identification of three classes of the Ascomycota phylum and 16 genera, the most common being Cladosporium, Cochliobolus and Neoscytalidium. Several of the species identified have not been associated before with human infections. Among 8 antifungal agents tested, the azoles posaconazole (96%), voriconazole (90.7%), ketoconazole (86.7%) and itraconazole (85.3%) showed in vitro activity (MIC ≤ 1 µg/mL) to the largest number of strains, followed by anidulafungin (89.3%), caspofungin (74.7%) and amphotericin B (70.7%). Fluconazole appeared to be the least effective with only 10.7% of isolates showing in vitro susceptibility. Overall, almost half (45.3%) of the isolates showed reduced susceptibility (MIC >1 µg/mL) to at least one antifungal agent, and three strains (one Pyrenochaeta unguis-hominis and two Nigrospora oryzae) showed potential multidrug resistance.
Fulltext Draft Genome Sequence of Dematiaceous Coelomycete Pyrenochaeta sp. Strain UM 256, Isolated from Skin Scraping

Yew SM, Chan CL, Soo-Hoo TS, Na SL, Ong SS, Hassan H, et al.

Genome Announc, 2013;1(3).
PMID: 23723391 DOI: 10.1128/genomeA.00158-13

Pyrenochaeta, classified under the order Pleosporales, is known to cause diseases in plants and humans. Here, we report a draft genome sequence of a Pyrenochaeta sp. isolated from a skin scraping, with an estimated genome size of 39.4 Mb. Genes associated with the synthesis of proteases, toxins, plant cell wall degradation, and multidrug resistance were found.
Fulltext The genome of newly classified Ochroconis mirabilis: Insights into fungal adaptation to different living conditions

Yew SM, Chan CL, Kuan CS, Toh YF, Ngeow YF, Na SL, et al.

BMC Genomics, 2016 Feb 03;17:91.
PMID: 26842951 DOI: 10.1186/s12864-016-2409-8

Ochroconis mirabilis, a recently introduced water-borne dematiaceous fungus, is occasionally isolated from human skin lesions and nails. We identified an isolate of O. mirabilis from a skin scraping with morphological and molecular studies. Its genome was then sequenced and analysed for genetic features related to classification and biological characteristics.
Fulltext Molecular epidemiology of respiratory viruses among Malaysian Young children with a confirmed respiratory infection during 2014-2015

Yew SM, Tan KL, Yeo SK, Ng KP, Kuan CS

J Thorac Dis, 2019 Nov;11(11):4626-4633.
PMID: 31903251 DOI: 10.21037/jtd.2019.10.69

BACKGROUND: In many developing countries, acute respiratory tract infections (ARTIs) are the main cause of morbidity and mortality among young children. This study aims to evaluate the molecular epidemiology of respiratory viruses among Malaysian children with confirmed respiratory infections between July 2014 and July 2015.
METHODS: A total of 394 nasopharyngeal swabs were collected prospectively from children age 0-5 years old with ARTIs from hospitals in Kuala Lumpur. Respiratory viral panel (RVP) assay was used to identify the viral aetiology of respiratory infections.
RESULTS: From a total of 394 samples, the positive detection rate was 79.9% (n=315). A total of 15 types of RNA viruses and a single type of DNA virus were detected. Enterovirus/rhinovirus (n=112, 28.4%), respiratory syncytial virus (RSV) (n=85, 21.6%), adenovirus (n=64, 16.2%), human bocavirus (n=34, 8.6%), and human metapneumovirus (n=29, 7.4%) were the five predominant viruses. Enterovirus/rhinovirus and RSV constituted most of the viral respiratory infections among young children, especially among children less than 1 year old. No coronavirus was detected among children between 3 and 5 years old. Co-infection caused by 2 or 3 respiratory viruses were detected in 52 patients (13.2%). Enterovirus/rhinovirus, adenovirus, and human bocavirus demonstrated pronounced seasonality. The infection rate peaked during mid-year, while the lowest activity occurred during early of the year.
CONCLUSIONS: The use of molecular assay as a routine diagnostic in the hospitals can improve the diagnosis and management of respiratory tract infections among children.
Fulltext Draft genome sequence of Mycobacterium bolletii strain M24, a rapidly growing mycobacterium of contentious taxonomic status

Wong YL, Choo SW, Tan JL, Ong CS, Ng KP, Ngeow YF

J Bacteriol, 2012 Aug;194(16):4475.
PMID: 22843600 DOI: 10.1128/JB.00916-12

The whole-genome sequence of Mycobacterium bolletii M24, isolated from the bronchoalveolar lavage fluid of a Malaysian patient, is reported here. The circular chromosome of 5,507,730 bp helped to clarify the taxonomic position of this organism within the M. abscessus complex and revealed the presence of proteins potentially important for pathogenicity in a human host.
Association between plasma soluble RAGE and renal function is unaffected by medication usage and enzymatic antioxidants in chronic kidney disease with type 2 diabetes

Wong FN, Tan JA, Keng TC, Ng KP, Chua KH, Kuppusamy UR

Clin Chim Acta, 2016 Jan 30;453:56-61.
PMID: 26657980 DOI: 10.1016/j.cca.2015.12.002

BACKGROUND: This study aimed to investigate the relationship between soluble RAGE and estimated glomerular filtration rate (eGFR) in patients with chronic kidney disease (CKD) after controlling for the potential confounding factors such as medication usage and enzymatic antioxidants.
METHODS: A total of 222 CKD patients whose eGFR is less than 60ml/min/1.73m(2) and 111 non-CKD individuals were recruited. The study subjects were classified based on their diabetes status. The plasma glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities as well as plasma soluble RAGE level were measured.
RESULTS: The plasma GPx and SOD activities were significantly lower and the plasma soluble RAGE level was significantly higher in the CKD patients than in the non-CKD individuals, regardless of the diabetes status. Soluble RAGE was significantly correlated with eGFR in both diabetic CKD (D-CKD) and non-diabetic CKD (ND-CKD) patients. The association between soluble RAGE and eGFR remained largely unaffected by the confounding factors in D-CKD patients. However, the confounding effect of enzymatic antioxidants in the relationship between eGFR and soluble RAGE was observed in ND-CKD patients.
CONCLUSION: The increased plasma level of soluble RAGE is a better indicator of renal function decline in diabetic CKD patients instead of non-diabetic CKD patients.
KEYWORDS: Chronic kidney disease; Diabetes; Enzymatic antioxidants; Glomerular filtration rate; Medications; Soluble RAGE
Impact of interventional nephrology on outcome and penetration rate of a CAPD program

Wong CM, Ng KP, Keng TC, Lim SK, Tan SY

Perit Dial Int, 2011 3 24;31(2):194-6.
PMID: 21427247 DOI: 10.3747/pdi.2009.00237
Complex patterns of the HIV-1 epidemic in Kuala Lumpur, Malaysia: evidence for expansion of circulating recombinant form CRF33_01B and detection of multiple other recombinants

Wang B, Lau KA, Ong LY, Shah M, Steain MC, Foley B, et al.

Virology, 2007 Oct 25;367(2):288-97.
PMID: 17604072

The HIV protease-reverse transcriptase (PR-RT) (1047 bp), gp120-env (891 bp) and gp41-env (547 bp) regions from the plasma of 115 HIV-1-infected patients in Kuala Lumpur (KL), Malaysia were sequenced. Detailed phylogenetic and bootscanning analyses were performed to determine the mosaic structure of the HIV-1 strains and their recombination breakpoint(s). Among the 50 patient samples in which all three regions could be amplified, the HIV-1 CRF01_AE subtype (46%) was predominant followed by subtypes B (10%) and B' (6%). A total of 9/50 (18%) patients were infected with a CRF01_AE/B inter-subtype recombinant, displaying a recombinant form (RF)(PR-RT), CRF01_AE(gp120-env) and CRF01_AE(gp41-env). This RF was derived from the Thai variants of CRF01_AE and B' subtype, with two distinct B' subtype segments in the backbone of CRF01_AE, similar to the newly identified CRF33_01B. In addition, one sample demonstrated a close structural relationship with the new CRF33_01B in the PR-RT region but displayed B' segment in part of the env region (RF(PR-RT), CRF01_AE/B'(gp120-env) and B'(gp41-env)) indicating continuing evolution of CRF33_01B. The remaining 18% of samples were identified as unique recombinant forms (URFs).
Do Family Members of Dialysis Patients Have a Positive Attitude Toward Organ Donation?

Tumin M, Tafran K, Zakaria RH, Satar NM, Ng KP, Lim SK

Ann. Transplant., 2015 Dec 22;20:752-6.
PMID: 26690676 DOI: 10.12659/aot.894427

BACKGROUND: Malaysia, which currently uses the informed consent system (ICS), is suffering from a severe shortage of organs for transplantation. Family members of dialysis patients (FMDPs) are expected to have a positive attitude toward deceased organ donation (DOD) because they have a close relative in need of a kidney donation. This study explores FMDPs' attitude toward DOD under the ICS and the presumed consent system (PCS).

MATERIAL/METHODS: The attitude of 350 FMDPs toward DOD under the ICS and PCS were sought between June and October 2013 in 3 dialysis institutions in Kuala Lumpur, Malaysia.

RESULTS: Under the ICS, 6.6% of respondents were registered donors, 6.6% were ready to register at the time of the survey, 38.6% were willing to donate but not ready to register at the time of the survey, and 48.2% were unwilling to donate organs upon death. If the PCS were implemented, 57.7% of respondents (28.7% of the willing donors and 88.7% of the unwilling respondents) stated that they would officially object to organ donation.

CONCLUSIONS: FMDPs' attitude toward DOD is not more positive or significantly better than that of the general public (based on earlier studies). The PCS may increase the number of donors, but it may also worsen the attitude of FMDPs toward DOD. Strategies aiming to promote DOD in Malaysia should be revised, and should perhaps be focused on enhancing trust of the medical system.
Fulltext A comparison of donor and control group quality of life

Tumin M, Abdul Talib Abdul Mutalib M, Mohd Satar N, Abdullah N, Chong CS, Ng KP, et al.

Ann. Transplant., 2014;19:112-8.
PMID: 24584108 DOI: 10.12659/AOT.889490

Informed consent of prospective donors should include information about the quality of life (QoL) of existing donors, especially those within the relevant country. This study aimed to provide information on Malaysian organ donors' QoL relative to a control group.
Strategies targeted at motivating unrelated living kidney donation

Tumin M, Noh A, Chong CS, Mohd Satar N, Lim SK, Abdullah N, et al.

Ann. Transplant., 2013;18:314-9.
PMID: 23792535 DOI: 10.12659/AOT.883957

This paper aimed to assess the willingness of Malaysians with post-secondary education to be living kidney donors.
Living kidney donation: the importance of public education

Tumin M, Rasiah R, Noh A, Satar NM, Chong CS, Lim SK, et al.

Clin Transplant, 2014 Apr;28(4):423-7.
PMID: 24617562 DOI: 10.1111/ctr.12334

A sample of Malaysians in the Klang Valley indicating their decision on becoming unrelated living kidney donors was surveyed regarding huge amounts of financial incentives to be rewarded to them. From the 1310 respondents, 72.1% said "no" on becoming a living donor. The reason "I don't think humans can live with only one kidney" scored the highest (35.6%), and from the 27.9% of the respondents who are willing to donate their organ with the right financial incentive, most of the respondents picked the reasons "I want to do something noble in life" (50%), and monetary reason scored the lowest (6.2%), indicating that financial incentive is not a major reason guiding individuals' decision on becoming living donors. We suggest that the government should put priority at targeting public education to raise the understanding on the risk, safety and the quality of life of donation and transplantation, and improving the public trust on the donation and the surgical methods to carry out transplantation.
Non-organ donors' attitudes toward incentives

Tumin M, Noh A, Chong CS, Lim SK, Abdullah N, Ng KP

Clin Transplant, 2013 May-Jun;27(3):E316-9.
PMID: 23600843 DOI: 10.1111/ctr.12132

Malaysians indicating that they did not intend to become organ donors upon their death were surveyed regarding interest in non-fungible financial incentives to be granted to surviving family members. Among the 730 (56% of the total sample of 1311) indicating unwillingness to be donors, 29.6% (216/730) subsequently indicated that they would be willing donors if the government introduced policies that, upon their death, "rewarded your (their) family with incentives for your (their) deeds." Among the 69% (504/730) who insisted that they would not become organ donor even with incentive, nearly 80% (404/501) of them were able to identify relevant incentives they thought should be provided by the state to those who make organ donations upon death. The majority of both groups preferred the state provide medical benefits to a surviving family member, suggesting this may be an attractive policy option for the state to raise the deceased organ donation pool.
Fulltext Organ donation campaigns: perspective of dialysis patient's family members

Tumin M, Raja Ariffin RN, Mohd Satar N, Ng KP, Lim SK, Chong CS

Iran J Public Health, 2014 Jul;43(7):926-35.
PMID: 25909060

BACKGROUND:
Solving the dilemma of the organ shortage in Malaysia requires educating Malaysians about organ donation and transplantation. This paper aims at exploring the average Malaysian households ' preferred channels of campaigns and the preferred campaigners in a family setting, targeting at the dialysis family members.

METHODS:
We analyzed the responses of 350 respondents regarding organ donation campaigns. The respondents are 2 family members of 175 dialysis patients from 3 different institutions. The information on respondents' willingness to donate and preferred method and channel of organ donation campaign were collected through questionnaire.

RESULTS:
Malaysian families have a good tendency to welcome campaigns in both the public and private (their homes) spheres. We also found that campaigns facilitated by the electronic media (Television and Radio) and executed by experienced doctors are expected to optimize the outcomes of organ donation, in general. Chi-square tests show that there are no significant differences in welcoming campaigns among ethnics. However, ethnics preferences over the campaign methods and campaigners are significantly different (P <0.05).

CONCLUSION:
Ethnic differences imply that necessary modifications on the campaign channels and campaigners should also be taken under consideration. By identifying the preferred channel and campaigners, this study hopes to shed some light on the ways to overcome the problem of organ shortage in Malaysia.

KEYWORDS:
Campaigns; Dialysis patients; Family; Malaysia; Organ donation
Fulltext Genome Anatomy of Pyrenochaeta unguis-hominis UM 256, a Multidrug Resistant Strain Isolated from Skin Scraping

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.
The Utility of Combined Urine Urea and Creatinine Clearance for Pretransplant Renal Function Assessment

Thye CK, Lee YW, Jalalonmuhali M, Lim SK, Ng KP

Transplant Proc, 2022 Feb 02.
PMID: 35123793 DOI: 10.1016/j.transproceed.2021.12.023

BACKGROUND: Evaluation of donor renal function as glomerular filtration rate (GFR) is a crucial part of pretransplant workup. Most guidelines recommend measured GFR (mGFR) using exogenous markers with creatinine clearance (CrCl) as an alternative. However, exogenous markers are difficult to obtain and perform, and CrCl may overestimate GFR.
OBJECTIVE: We explore the use of CrCl and combined urea and creatinine clearance as an alternative for GFR assessment.
METHODS: A retrospective study involving 81 kidney donors from 2007 to 2020, with mGFR collected by chromium 51-labeled ethylenediaminetetraacetic acid (51Cr-EDTA) and CrCl and combined urea and creatinine clearance. We analyzed the performance of CrCl and combined urea and creatinine clearance against 51Cr-EDTA. Adequacy of urine volume was taken into consideration.
RESULTS: A total of 81 candidates with a mean age of 44.80 ± 10.77 years were enrolled. Mean mGFR from 51Cr-EDTA was 123.66 ± 26.91 mL/min/1.73 m2, and combined urea and creatinine clearance and CrCl were 122.13 ± 47.07 and 133.40 ± 36.32 mL/min/1.73 m2, respectively. CrCl overestimated 51Cr-EDTA. Though combined urea and creatinine clearance had minimal bias, it had a lower correlation coefficient (0.25 vs 0.43), lower precision (49.51 vs 38.10), and slightly lower accuracy within 30% of 51Cr-EDTA (74.07% vs 76.54%).
CONCLUSIONS: Combined urea and creatinine clearance did not improve the performance of CrCl. Nevertheless, it can potentially be used as first-line GFR assessment, followed by mGFR in selected donors, to ascertain threshold of safe kidney donation. A stringent urine collection method is essential to ensure accurate measurement.
Creatinine clearance in selection of living kidney donor among the Malaysian population: is it safe?

Thye CK, Lee YW, Jalalonmuhali M, Lim SK, Ng KP

BMC Nephrol, 2023 Sep 11;24(1):267.
PMID: 37691129 DOI: 10.1186/s12882-023-03057-w

BACKGROUND: Assessment of donor renal function is made by the measurement of Glomerular Filtration Rate (GFR). Exogenous markers are preferred over creatinine clearance and are widely used for measuring GFR. However, they are difficult to obtain, costly and laborious. This is a study to look into the safety and accuracy of creatinine clearance for renal assessment among the living kidney donors in the Malaysian population.
METHODS: This is a retrospective, single-centre study comprising 105 living kidney donor candidates from the year 2007 to 2020. By comparing against 51-Chromium ethylenediamine-tetraacetic acid (51Cr-EDTA), we analysed creatinine clearance for correlation, bias, precision and accuracy.
RESULTS: The study group had a mean age of 45.68 ± 10.97 years with a mean serum creatinine of 64.43 ± 17.68 µmol/L and a urine volume of 2.06 ± 0.83 L. Mean measured GFR from 51Cr-EDTA was 124.37 ± 26.83 ml/min/1.73m2 whereas mean creatinine clearance was 132.35 ± 38.18 ml/min/1.73m2. Creatinine clearance overestimated 51Cr-EDTA significantly with a correlation coefficient of 0.48 (p
Detection of 10 medically important Candida species by seminested polymerase chain reaction

Than LT, Chong PP, Ng KP, Seow HF

Diagn Microbiol Infect Dis, 2012 Feb;72(2):196-8.
PMID: 22154674 DOI: 10.1016/j.diagmicrobio.2011.10.008

A seminested PCR detecting ten medically important Candida species were achieved. Analytical sensitivity and specificity were not compromised.
Fulltext Detection of medically important Candida species by absolute quantitation real-time polymerase chain reaction

Than LT, Chong PP, Ng KP, Seow HF

Jundishapur J Microbiol, 2015 Jan;8(1):e14940.
PMID: 25789129 DOI: 10.5812/jjm.14940

The number of invasive candidiasis cases has risen especially with an increase in the number of immunosuppressed and immunocom promised patients. The early detection of Candida species which is specific and sensitive is important in determining the correct administration of antifungal drugs to patients.

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