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Fulltext New insights of Microsporidial infection among asymptomatic aboriginal population in Malaysia

Shahrul Anuar T, M Al-Mekhlafi H, Md Salleh F, Moktar N

PLoS ONE, 2013;8(8):e71870.
PMID: 24014078 DOI: 10.1371/journal.pone.0071870

Studies on microsporidial infection mostly focus on immunodeficiency or immunosuppressive individuals. Therefore, this cross-sectional study describes the prevalence and risk factors of microsporidiosis among asymptomatic individuals in Malaysia.
Fulltext Are there gender differences in coronary artery disease? The Malaysian National Cardiovascular Disease Database - Percutaneous Coronary Intervention (NCVD-PCI) Registry

Lee CY, Hairi NN, Wan Ahmad WA, Ismail O, Liew HB, Zambahari R, et al.

PLoS ONE, 2013;8(8):e72382.
PMID: 24015238 DOI: 10.1371/journal.pone.0072382

To assess whether gender differences exist in the clinical presentation, angiographic severity, management and outcomes in patients with coronary artery disease (CAD).
Fulltext Prevalence of PALB2 mutations in breast cancer patients in multi-ethnic Asian population in Malaysia and Singapore

Phuah SY, Lee SY, Kang P, Kang IN, Yoon SY, Thong MK, et al.

PLoS ONE, 2013;8(8):e73638.
PMID: 23977390 DOI: 10.1371/journal.pone.0073638

The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.
Fulltext Efficacy and safety of dihydroartemisinin-piperaquine for treatment of Plasmodium vivax malaria in endemic countries: meta-analysis of randomized controlled studies

Naing C, Racloz V, Whittaker MA, Aung K, Reid SA, Mak JW, et al.

PLoS ONE, 2013;8(12):e78819.
PMID: 24312446 DOI: 10.1371/journal.pone.0078819

This study aimed to synthesize available evidence on the efficacy of dihydroartemisinin-piperaquine (DHP) in treating uncomplicated Plasmodium vivax malaria in people living in endemic countries.
Fulltext Phylodynamic profile of HIV-1 subtype B, CRF01_AE and the recently emerging CRF51_01B among men who have sex with men (MSM) in Singapore

Ng KT, Ng KY, Khong WX, Chew KK, Singh PK, Yap JK, et al.

PLoS ONE, 2013;8(12):e80884.
PMID: 24312505 DOI: 10.1371/journal.pone.0080884

HIV-1 subtype B and CRF01_AE are the predominant infecting subtypes among men who have sex with men (MSM) in Singapore. The genetic history, population dynamics and pattern of transmission networks of these genotypes remain largely unknown. We delineated the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and the recently characterized CRF51_01B strains circulating among the MSM population in Singapore. A total of 105 (49.5%) newly-diagnosed treatment-naïve MSM were recruited between February 2008 and August 2009. Phylogenetic reconstructions of the protease gene (HXB2: 2239 - 2629), gp120 (HXB2: 6942 - 7577) and gp41 (HXB2: 7803 - 8276) of the env gene uncovered five monophyletic transmission networks (two each within subtype B and CRF01_AE and one within CRF51_01B lineages) of different sizes (involving 3 - 23 MSM subjects, supported by posterior probability measure of 1.0). Bayesian coalescent analysis estimated that the emergence and dissemination of multiple sub-epidemic networks occurred between 1995 and 2005, driven largely by subtype B and later followed by CRF01_AE. Exponential increase in effective population size for both subtype B and CRF01_AE occurred between 2002 to 2007 and 2005 to 2007, respectively. Genealogical estimates suggested that the novel CRF51_01B lineages were probably generated through series of recombination events involving CRF01_AE and multiple subtype B ancestors. Our study provides the first insight on the phylodynamic profiles of HIV-1 subtype B, CRF01_AE and CRF51_01B viral strains circulating among MSM in Singapore.
Fulltext Exploring patient values in medical decision making: a qualitative study

Lee YK, Low WY, Ng CJ

PLoS ONE, 2013;8(11):e80051.
PMID: 24282518 DOI: 10.1371/journal.pone.0080051

BACKGROUND: Patient decisions are influenced by their personal values. However, there is a lack of clarity and attention on the concept of patient values in the clinical context despite clear emphasis on patient values in evidence-based medicine and shared decision making. The aim of the study was to explore the concept of patient values in the context of making decisions about insulin initiation among people with type 2 diabetes.
METHODS AND FINDINGS: We conducted individual in-depth interviews with people with type 2 diabetes who were making decisions about insulin treatment. Participants were selected purposively to achieve maximum variation. A semi-structured topic guide was used to guide the interviews which were audio-recorded and analysed using a thematic approach. We interviewed 21 participants between January 2011 and March 2012. The age range of participants was 28-67 years old. Our sample comprised 9 women and 12 men. Three main themes, 'treatment-specific values', 'life goals and philosophies', and 'personal and social background', emerged from the analysis. The patients reported a variety of insulin-specific values, which were negative and/or positive beliefs about insulin. They framed insulin according to their priorities and philosophies in life. Patients' decisions were influenced by sociocultural (e.g. religious background) and personal backgrounds (e.g. family situations).
CONCLUSIONS: This study highlighted the need for expanding the current concept of patient values in medical decision making. Clinicians should address more than just values related to treatment options. Patient values should include patients' priorities, life philosophy and their background. Current decision support tools, such as patient decision aids, should consider these new dimensions when clarifying patient values.
Fulltext Building a DNA barcode reference library for the true butterflies (Lepidoptera) of Peninsula Malaysia: what about the subspecies?

Wilson JJ, Sing KW, Sofian-Azirun M

PLoS ONE, 2013;8(11):e79969.
PMID: 24282514 DOI: 10.1371/journal.pone.0079969

The objective of this study was to build a DNA barcode reference library for the true butterflies of Peninsula Malaysia and assess the value of attaching subspecies names to DNA barcode records. A new DNA barcode library was constructed with butterflies from the Museum of Zoology, University of Malaya collection. The library was analysed in conjunction with publicly available DNA barcodes from other Asia-Pacific localities to test the ability of the DNA barcodes to discriminate species and subspecies. Analyses confirmed the capacity of the new DNA barcode reference library to distinguish the vast majority of species (92%) and revealed that most subspecies possessed unique DNA barcodes (84%). In some cases conspecific subspecies exhibited genetic distances between their DNA barcodes that are typically seen between species, and these were often taxa that have previously been regarded as full species. Subspecies designations as shorthand for geographically and morphologically differentiated groups provide a useful heuristic for assessing how such groups correlate with clustering patterns of DNA barcodes, especially as the number of DNA barcodes per species in reference libraries increases. Our study demonstrates the value in attaching subspecies names to DNA barcode records as they can reveal a history of taxonomic concepts and expose important units of biodiversity.
Fulltext Common oncogenic mutations are infrequent in oral squamous cell carcinoma of Asian origin

Zanaruddin SN, Yee PS, Hor SY, Kong YH, Ghani WM, Mustafa WM, et al.

PLoS ONE, 2013;8(11):e80229.
PMID: 24224046 DOI: 10.1371/journal.pone.0080229

The frequency of common oncogenic mutations and TP53 was determined in Asian oral squamous cell carcinoma (OSCC).
Fulltext Time trends and inequalities of under-five mortality in Nepal: a secondary data analysis of four demographic and health surveys between 1996 and 2011

Sreeramareddy CT, Harsha Kumar HN, Sathian B

PLoS ONE, 2013;8(11):e79818.
PMID: 24224010 DOI: 10.1371/journal.pone.0079818

Inequalities in progress towards achievement of Millennium Development Goal four (MDG-4) reflect unequal access to child health services.
Fulltext Assessing the status of wild felids in a highly-disturbed commercial forest reserve in Borneo and the implications for camera trap survey design

Wearn OR, Rowcliffe JM, Carbone C, Bernard H, Ewers RM

PLoS ONE, 2013;8(11):e77598.
PMID: 24223717 DOI: 10.1371/journal.pone.0077598

The proliferation of camera-trapping studies has led to a spate of extensions in the known distributions of many wild cat species, not least in Borneo. However, we still do not have a clear picture of the spatial patterns of felid abundance in Southeast Asia, particularly with respect to the large areas of highly-disturbed habitat. An important obstacle to increasing the usefulness of camera trap data is the widespread practice of setting cameras at non-random locations. Non-random deployment interacts with non-random space-use by animals, causing biases in our inferences about relative abundance from detection frequencies alone. This may be a particular problem if surveys do not adequately sample the full range of habitat features present in a study region. Using camera-trapping records and incidental sightings from the Kalabakan Forest Reserve, Sabah, Malaysian Borneo, we aimed to assess the relative abundance of felid species in highly-disturbed forest, as well as investigate felid space-use and the potential for biases resulting from non-random sampling. Although the area has been intensively logged over three decades, it was found to still retain the full complement of Bornean felids, including the bay cat Pardofelis badia, a poorly known Bornean endemic. Camera-trapping using strictly random locations detected four of the five Bornean felid species and revealed inter- and intra-specific differences in space-use. We compare our results with an extensive dataset of >1,200 felid records from previous camera-trapping studies and show that the relative abundance of the bay cat, in particular, may have previously been underestimated due to the use of non-random survey locations. Further surveys for this species using random locations will be crucial in determining its conservation status. We advocate the more wide-spread use of random survey locations in future camera-trapping surveys in order to increase the robustness and generality of inferences that can be made.
Fulltext In vivo biochemical and gene expression analyses of the antioxidant activities and hypocholesterolaemic properties of Tamarindus indica fruit pulp extract

Lim CY, Mat Junit S, Abdulla MA, Abdul Aziz A

PLoS ONE, 2013;8(7):e70058.
PMID: 23894592 DOI: 10.1371/journal.pone.0070058

Tamarindus indica (T. indica) is a medicinal plant with many biological activities including anti-diabetic, hypolipidaemic and anti-bacterial activities. A recent study demonstrated the hypolipidaemic effect of T. indica fruit pulp in hamsters. However, the biochemical and molecular mechanisms responsible for these effects have not been fully elucidated. Hence, the aims of this study were to evaluate the antioxidant activities and potential hypocholesterolaemic properties of T. indica, using in vitro and in vivo approaches.
Fulltext Inhibitory potency of 8-methoxypsoralen on cytochrome P450 2A6 (CYP2A6) allelic variants CYP2A6 15, CYP2A6 16, CYP2A6 21 and CYP2A6 22: differential susceptibility due to different sequence locations of the mutations

Tiong KH, Mohammed Yunus NA, Yiap BC, Tan EL, Ismail R, Ong CE

PLoS ONE, 2014;9(1):e86230.
PMID: 24475091 DOI: 10.1371/journal.pone.0086230

Human cytochrome P450 2A6 (CYP2A6) is a highly polymorphic isoform of CYP2A subfamily. Our previous kinetic study on four CYP2A6 allelic variants (CYP2A6 15, CYP2A6 16, CYP2A6 21 and CYP2A6 22) have unveiled the functional significance of sequence mutations in these variants on coumarin 7-hydroxylation activity. In the present study, we further explored the ability of a typical CYP2A6 inhibitor, 8-methoxypsoralen (8-MOP), in inhibition of these alleles and we hypothesized that translational mutations in these variants are likely to give impact on 8-MOP inhibitory potency. The CYP2A6 variant and the wild type proteins were subjected to 8-MOP inhibition to yield IC50 values. In general, a similar trend of change in the IC50 and Km values was noted among the four mutants towards coumarin oxidation. With the exception of CYP2A6 16, differences in IC50 values were highly significant which implied compromised interaction of the mutants with 8-MOP. Molecular models of CYP2A6 were subsequently constructed and ligand-docking experiments were performed to rationalize experimental data. Our docking study has shown that mutations have induced enlargement of the active site volume in all mutants with the exception of CYP2A6 16. Furthermore, loss of hydrogen bond between 8-MOP and active site residue Asn297 was evidenced in all mutants. Our data indicate that the structural changes elicited by the sequence mutations could affect 8-MOP binding to yield differential enzymatic activities in the mutant CYP2A6 proteins.
Fulltext Nasal epithelial cells can act as a physiological surrogate for paediatric asthma studies

Thavagnanam S, Parker JC, McBrien ME, Skibinski G, Shields MD, Heaney LG

PLoS ONE, 2014;9(1):e85802.
PMID: 24475053 DOI: 10.1371/journal.pone.0085802

Differentiated paediatric epithelial cells can be used to study the role of epithelial cells in asthma. Nasal epithelial cells are easier to obtain and may act as a surrogate for bronchial epithelium in asthma studies. We assessed the suitability of nasal epithelium from asthmatic children to be a surrogate for bronchial epithelium using air-liquid interface cultures.
Fulltext Drug-related problems in patients with benign prostatic hyperplasia: a cross sectional retrospective study

Zaman Huri H, Hui Xin C, Sulaiman CZ

PLoS ONE, 2014;9(1):e86215.
PMID: 24475089 DOI: 10.1371/journal.pone.0086215

Benign Prostatic Hyperplasia (BPH) patients are at risk of acquiring drug-related problems (DRPs), as it is present in the majority of aging men. To date, DRPs among BPH patients have not been well studied. We conducted this retrospective study in a tertiary hospital in Malaysia from January 2009 to June 2012 with the aim of identifying the factors associated with DRPs among BPH patients. The Pharmaceutical Care Network Europe Classification Version (PCNE) 5.01 was used as a tool to classify DRPs. We enrolled 203 patients from 259 hospital admissions. A total of 390 DRPs were found and there was an average of 1.5±1.3 problems per hospitalization. 76.1% of hospital admissions included at least one DRP. The most common DRP categories encountered were drug choice problems (45.9%), drug interactions (24.9%), and dosing problems (13.3%). Factors such as advanced age (p = 0.005), a hospital stay of more than 6 days (p = 0.001), polydrug treatments (p<0.001), multiple comorbidities (p<0.001), and comorbid cardiovascular disease (p = 0.011), diabetes mellitus(p = 0.001), hypertension (p<0.001) and renal impairment (p = 0.011) were significantly associated with the occurrence of DRPs. These data indicated that the prevalence of DRPs is high among BPH patients. The identification of different subtypes of DRPs and the factors associated with DRPs may facilitate risk reduction for BPH patients.
Fulltext 3D mapping of safe and danger zones in the maxilla and mandible for the placement of intermaxillary fixation screws

Purmal K, Alam MK, Pohchi A, Abdul Razak NH

PLoS ONE, 2013;8(12):e84202.
PMID: 24367643 DOI: 10.1371/journal.pone.0084202

Intermaxillary (IMF) screws feature several advantages over other devices used for intermaxillary fixation, but using cone beam computed tomography (CBCT) scans to determine the safe and danger zones to place these devices for all patients can be expensive. This study aimed to determine the optimal interradicular and buccopalatal/buccolingual spaces for IMF screw placement in the maxilla and mandible. The CBCT volumetric data of 193 patients was used to generate transaxial slices between the second molar on the right to the second molar on the left in both arches. The mean interradicular and buccopalatal/buccolingual distances and standard deviation values were obtained at heights of 2, 5, 8 and 11 mm from the alveolar bone crest. An IMF screw with a diameter of 1.0 mm and length of 7 mm can be placed distal to the canines (2 - 11 mm from the alveolar crest) and less than 8 mm between the molars in the maxilla. In the mandible, the safest position is distal to the first premolar (more than 5 mm) and distal to the second premolar (more than 2 mm). There was a significant difference (p<0.05) between the right and left quadrants. The colour coding 3D template showed the safe and danger zones based on the mesiodistal, buccopalatal and buccolingual distances in the maxilla and mandible.The safest sites for IMF screw insertion in the maxilla were between the canines and first premolars and between the first and second molars. In the mandible, the safest sites were between the first and second premolars and between the second premolar and first molar. However, the IMF screw should not exceed 1.0 mm in diameter and 7 mm in length.
Fulltext Revisiting the single cell protein application of Cupriavidus necator H16 and recovering bioplastic granules simultaneously

Kunasundari B, Murugaiyah V, Kaur G, Maurer FH, Sudesh K

PLoS ONE, 2013;8(10):e78528.
PMID: 24205250 DOI: 10.1371/journal.pone.0078528

Cupriavidus necator H16 (formerly known as Hydrogenomonas eutropha) was famous as a potential single cell protein (SCP) in the 1970s. The drawback however was the undesirably efficient accumulation of non-nutritive polyhydroxybutyrate (PHB) storage compound in the cytoplasm of this bacterium. Eventually, competition from soy-based protein resulted in SCP not receiving much attention. Nevertheless, C. necator H16 remained in the limelight as a producer of PHB, which is a material that resembles commodity plastics such as polypropylene. PHB is a 100% biobased and biodegradable polyester. Although tremendous achievements have been attained in the past 3 decades in the efficient production of PHB, this bioplastic is still costly. One of the main problems has been the recovery of PHB from the cell cytoplasm. In this study, we showed for the first time that kilogram quantities of PHB can be easily recovered in the laboratory without the use of any solvents and chemicals, just by using the cells as SCP. In addition, the present study also demonstrated the safety and tolerability of animal model used, Sprague Dawley given lyophilized cells of C. necator H16. The test animals readily produced fecal pellets that were whitish in color, as would be expected of PHB granules. The pellets were determined to contain about 82-97 wt% PHB and possessed molecular mass of around 930 kg/mol. The PHB granules recovered biologically possessed similar molecular mass compared to chloroform extracted PHB [950 kg/mol]. This method now allows the production and purification of substantial quantities of PHB for various experimental trials. The method reported here is easy, does not require expensive instrumentation, scalable and does not involve extensive use of solvents and strong chemicals.
Fulltext A deformable generic 3D model of haptoral anchor of Monogenean

Teo BG, Dhillon SK, Lim LH

PLoS ONE, 2013;8(10):e77650.
PMID: 24204903 DOI: 10.1371/journal.pone.0077650

In this paper, a digital 3D model which allows for visualisation in three dimensions and interactive manipulation is explored as a tool to help us understand the structural morphology and elucidate the functions of morphological structures of fragile microorganisms which defy live studies. We developed a deformable generic 3D model of haptoral anchor of dactylogyridean monogeneans that can subsequently be deformed into different desired anchor shapes by using direct manipulation deformation technique. We used point primitives to construct the rectangular building blocks to develop our deformable 3D model. Point primitives are manually marked on a 2D illustration of an anchor on a Cartesian graph paper and a set of Cartesian coordinates for each point primitive is manually extracted from the graph paper. A Python script is then written in Blender to construct 3D rectangular building blocks based on the Cartesian coordinates. The rectangular building blocks are stacked on top or by the side of each other following their respective Cartesian coordinates of point primitive. More point primitives are added at the sites in the 3D model where more structural variations are likely to occur, in order to generate complex anchor structures. We used Catmull-Clark subdivision surface modifier to smoothen the surface and edge of the generic 3D model to obtain a smoother and more natural 3D shape and antialiasing option to reduce the jagged edges of the 3D model. This deformable generic 3D model can be deformed into different desired 3D anchor shapes through direct manipulation deformation technique by aligning the vertices (pilot points) of the newly developed deformable generic 3D model onto the 2D illustrations of the desired shapes and moving the vertices until the desire 3D shapes are formed. In this generic 3D model all the vertices present are deployed for displacement during deformation.
Fulltext A cardiovascular mathematical model of graded head-up tilt

Lim E, Chan GS, Dokos S, Ng SC, Latif LA, Vandenberghe S, et al.

PLoS ONE, 2013;8(10):e77357.
PMID: 24204817 DOI: 10.1371/journal.pone.0077357

A lumped parameter model of the cardiovascular system has been developed and optimized using experimental data obtained from 13 healthy subjects during graded head-up tilt (HUT) from the supine position to [Formula: see text]. The model includes descriptions of the left and right heart, direct ventricular interaction through the septum and pericardium, the systemic and pulmonary circulations, nonlinear pressure volume relationship of the lower body compartment, arterial and cardiopulmonary baroreceptors, as well as autoregulatory mechanisms. A number of important features, including the separate effects of arterial and cardiopulmonary baroreflexes, and autoregulation in the lower body, as well as diastolic ventricular interaction through the pericardium have been included and tested for their significance. Furthermore, the individual effect of parameter associated with heart failure, including LV and RV contractility, baseline systemic vascular resistance, pulmonary vascular resistance, total blood volume, LV diastolic stiffness and reflex gain on HUT response have also been investigated. Our fitted model compares favorably with our experimental measurements and published literature at a range of tilt angles, in terms of both global and regional hemodynamic variables. Compared to the normal condition, a simulated congestive heart failure condition produced a blunted response to HUT with regards to the percentage changes in cardiac output, stroke volume, end diastolic volume and effector response (i.e., heart contractility, venous unstressed volume, systemic vascular resistance and heart rate) with progressive tilting.
Fulltext Fatigue index and fatigue rate during an anaerobic performance under hypohydrations

Naharudin MN, Yusof A

PLoS ONE, 2013;8(10):e77290.
PMID: 24204790 DOI: 10.1371/journal.pone.0077290

BACKGROUND: Since hypohydration commonly occurs in sports, studies on anaerobic exercise performance under this condition have been extensively carried out. When describing anaerobic performance, authors usually refer to a drop in anaerobic performance as fatigue index (FI) which is conventionally calculated using peak and low power data points. Meanwhile, another possible method in explaining anaerobic fatigue is using the rate constant which is derived from the exponential decline of power output known as fatigue rate (FR). Few studies have demonstrated that there was no change in anaerobic performance under mild hypohydrations.
PURPOSE: This study aimed to compare the kinetics of power output using FI and FR of an anaerobic performance (Wingate test) under 2, 3 and 4% state of hypohydrations.
METHOD: Thirty two collegiate cyclists (age = 22 ± 2 years; body weight = 71.45 ± 3.43 kg; height = 173.23 ± 0.04 cm) were matched using their baseline anaerobic peak power (APP) then randomly divided into 4 groups of EU (euhydrated), 2H, 3H and 4H respectively.
RESULTS: As expected the, FI, APP, anaerobic lower power (ALP) and rating of perceived exertion (RPE) did not show significant differences between and within the groups. However, the FR in 3H (0.018 ± 0.005 s(-1)) and 4H (0.019 ± 0.010 s(-1)) were significantly lower than EU (0.033 ± 0.012 s(-1)). Post-test FR also showed significant reduction in 3H and 4H compared to their pre-test values (p<0.05).
CONCLUSION: Despite the lack of changes in APP and RPE, subjects in 3H and 4H showed evidence of lower reduction of power output over time. The findings support earlier reports which showed no change in anaerobic performance under mild hypohydrations. The relatively lower FR suggests higher drive in maintaining power output under hypohydrations of 3 and 4% body weight.
Fulltext Probing the interaction of a therapeutic flavonoid, pinostrobin with human serum albumin: multiple spectroscopic and molecular modeling investigations

Feroz SR, Mohamad SB, Bakri ZS, Malek SN, Tayyab S

PLoS ONE, 2013;8(10):e76067.
PMID: 24116089 DOI: 10.1371/journal.pone.0076067

Interaction of a pharmacologically important flavonoid, pinostrobin (PS) with the major transport protein of human blood circulation, human serum albumin (HSA) has been examined using a multitude of spectroscopic techniques and molecular docking studies. Analysis of the fluorescence quenching data showed a moderate binding affinity (1.03 × 10(5) M(-1) at 25°C) between PS and HSA with a 1∶1 stoichiometry. Thermodynamic analysis of the binding data (ΔS = +44.06 J mol(-1) K(-1) and ΔH = -15.48 kJ mol(-1)) and molecular simulation results suggested the involvement of hydrophobic and van der Waals forces, as well as hydrogen bonding in the complex formation. Both secondary and tertiary structural perturbations in HSA were observed upon PS binding, as revealed by intrinsic, synchronous, and three-dimensional fluorescence results. Far-UV circular dichroism data revealed increased thermal stability of the protein upon complexation with PS. Competitive drug displacement results suggested the binding site of PS on HSA as Sudlow's site I, located at subdomain IIA, and was well supported by the molecular modelling data.

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