Displaying publications 241 - 260 of 2515 in total

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  1. Fulltext Plasmodium vivax population structure and transmission dynamics in Sabah Malaysia
    Abdullah NR, Barber BE, William T, Norahmad NA, Satsu UR, Muniandy PK, et al.
    PLoS One, 2013;8(12):e82553.
    PMID: 24358203 DOI: 10.1371/journal.pone.0082553
    Despite significant progress in the control of malaria in Malaysia, the complex transmission dynamics of P. vivax continue to challenge national efforts to achieve elimination. To assess the impact of ongoing interventions on P. vivax transmission dynamics in Sabah, we genotyped 9 short tandem repeat markers in a total of 97 isolates (8 recurrences) from across Sabah, with a focus on two districts, Kota Marudu (KM, n = 24) and Kota Kinabalu (KK, n = 21), over a 2 year period. STRUCTURE analysis on the Sabah-wide dataset demonstrated multiple sub-populations. Significant differentiation (F ST  = 0.243) was observed between KM and KK, located just 130 Km apart. Consistent with low endemic transmission, infection complexity was modest in both KM (mean MOI  = 1.38) and KK (mean MOI  = 1.19). However, population diversity remained moderate (H E  = 0.583 in KM and H E  = 0.667 in KK). Temporal trends revealed clonal expansions reflecting epidemic transmission dynamics. The haplotypes of these isolates declined in frequency over time, but persisted at low frequency throughout the study duration. A diverse array of low frequency isolates were detected in both KM and KK, some likely reflecting remnants of previous expansions. In accordance with clonal expansions, high levels of Linkage Disequilibrium (I A (S) >0.5 [P<0.0001] in KK and KM) declined sharply when identical haplotypes were represented once (I A (S)  = 0.07 [P = 0.0076] in KM, and I A (S) = -0.003 [P = 0.606] in KK). All 8 recurrences, likely to be relapses, were homologous to the prior infection. These recurrences may promote the persistence of parasite lineages, sustaining local diversity. In summary, Sabah's shrinking P. vivax population appears to have rendered this low endemic setting vulnerable to epidemic expansions. Migration may play an important role in the introduction of new parasite strains leading to epidemic expansions, with important implications for malaria elimination.
  2. Fulltext Detailed analysis of the microbial population in Malaysian spontaneous cocoa pulp fermentations reveals a core and variable microbiota
    Meersman E, Steensels J, Mathawan M, Wittocx PJ, Saels V, Struyf N, et al.
    PLoS One, 2013;8(12):e81559.
    PMID: 24358116 DOI: 10.1371/journal.pone.0081559
    The fermentation of cocoa pulp is one of the few remaining large-scale spontaneous microbial processes in today's food industry. The microbiota involved in cocoa pulp fermentations is complex and variable, which leads to inconsistent production efficiency and cocoa quality. Despite intensive research in the field, a detailed and comprehensive analysis of the microbiota is still lacking, especially for the expanding Asian production region. Here, we report a large-scale, comprehensive analysis of four spontaneous Malaysian cocoa pulp fermentations across two time points in the harvest season and two fermentation methods. Our results show that the cocoa microbiota consists of a "core" and a "variable" part. The bacterial populations show a remarkable consistency, with only two dominant species, Lactobacillus fermentum and Acetobacter pasteurianus. The fungal diversity is much larger, with four dominant species occurring in all fermentations ("core" yeasts), and a large number of yeasts that only occur in lower numbers and specific fermentations ("variable" yeasts). Despite this diversity, a clear pattern emerges, with early dominance of apiculate yeasts and late dominance of Saccharomyces cerevisiae. Our results provide new insights into the microbial diversity in Malaysian cocoa pulp fermentations and pave the way for the selection of starter cultures to increase efficiency and consistency.
  3. Fulltext Molecular epidemiology of coxsackievirus A16: intratype and prevalent intertype recombination identified
    Chen X, Tan X, Li J, Jin Y, Gong L, Hong M, et al.
    PLoS One, 2013;8(12):e82861.
    PMID: 24340064 DOI: 10.1371/journal.pone.0082861
    Coxsackievirus A16 (CVA16) is responsible for nearly 50% of all the confirmed hand, foot, and mouth disease (HFMD) cases in mainland China, sometimes it could also cause severe complications, and even death. To clarify the genetic characteristics and the epidemic patterns of CVA16 in mainland China, comprehensive bioinfomatics analyses were performed by using 35 CVA16 whole genome sequences from 1998 to 2011, 593 complete CVA16 VP1 sequences from 1981 to 2011, and prototype strains of human enterovirus species A (EV-A). Analysis on complete VP1 sequences revealed that subgenotypes B1a and B1b were prevalent strains and have been co-circulating in many Asian countries since 2000, especially in mainland China for at least 13 years. While the prevalence of subgenotype B1c (totally 20 strains) was much limited, only found in Malaysia from 2005 to 2007 and in France in 2010. Genotype B2 only caused epidemic in Japan and Malaysia from 1981 to 2000. Both subgenotypes B1a and B1b were potential recombinant viruses containing sequences from other EV-A donors in the 5'-untranslated region and P2, P3 non-structural protein encoding regions.
  4. Fulltext Influence of age on patellar tendon reflex response
    Chandrasekhar A, Abu Osman NA, Tham LK, Lim KS, Wan Abas WA
    PLoS One, 2013;8(11):e80799.
    PMID: 24260483 DOI: 10.1371/journal.pone.0080799
    BACKGROUND: A clinical parameter commonly used to assess the neurological status of an individual is the tendon reflex response. However, the clinical method of evaluation often leads to subjective conclusions that may differ between examiners. Moreover, attempts to quantify the reflex response, especially in older age groups, have produced inconsistent results. This study aims to examine the influence of age on the magnitude of the patellar tendon reflex response.

    METHODOLOGY/PRINCIPAL FINDINGS: This study was conducted using the motion analysis technique with the reflex responses measured in terms of knee angles. Forty healthy subjects were selected and categorized into three different age groups. Patellar reflexes were elicited from both the left and right patellar tendons of each subject at three different tapping angles and using the Jendrassik maneuver. The findings suggested that age has a significant effect on the magnitude of the reflex response. An angle of 45° may be the ideal tapping angle at which the reflex can be elicited to detect age-related differences in reflex response. The reflex responses were also not influenced by gender and were observed to be fairly symmetrical.

    CONCLUSIONS/SIGNIFICANCE: Neurologically normal individuals will experience an age-dependent decline in patellar reflex response.

  5. Fulltext Geographical pattern and environmental correlates of regional-scale general flowering in Peninsular Malaysia
    Numata S, Yasuda M, Suzuki RO, Hosaka T, Noor NS, Fletcher CD, et al.
    PLoS One, 2013;8(11):e79095.
    PMID: 24260159 DOI: 10.1371/journal.pone.0079095
    In South-East Asian dipterocarp forests, many trees synchronize their reproduction at the community level, but irregularly, in a phenomenon known as general flowering (GF). Several proximate cues have been proposed as triggers for the synchronization of Southeast Asian GF, but the debate continues, as many studies have not considered geographical variation in climate and flora. We hypothesized that the spatial pattern of GF forests is explained by previously proposed climatic cues if there are common cues for GF among regions. During the study, GF episodes occurred every year, but the spatial occurrence varied considerably from just a few forests to the whole of Peninsular Malaysia. In 2001, 2002 and 2005, minor and major GF occurred widely throughout Peninsular Malaysia (GF2001, GF2002, and GF2005), and the geographical patterns of GF varied between the episodes. In the three regional-scale GF episodes, most major events occurred in regions where prolonged drought (PD) had been recorded prior, and significant associations between GF scores and PD were found in GF2001 and GF2002. However, the frequency of PD was higher than that of GF throughout the peninsula. In contrast, low temperature (LT) was observed during the study period only before GF2002 and GF2005, but there was no clear spatial relationship between GF and LT in the regional-scale episodes. There was also no evidence that last GF condition influenced the magnitude of GF. Thus, our results suggest that PD would be essential to trigger regional-scale GF in the peninsula, but also that PD does not fully explain the spatial and temporal patterns of GF. The coarse relationships between GF and the proposed climatic cues may be due to the geographical variation in proximate cues for GF, and the climatic and floristic geographical variations should be considered to understand the proximate factors of GF.
  6. 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.
  7. Fulltext Construction and evaluation of V. cholerae O139 mutant, VCUSM21P, as a safe live attenuated cholera vaccine
    Murugaiah C, Nik Mohd Noor NZ, Mustafa S, Manickam R, Pattabhiraman L
    PLoS One, 2014;9(2):e81817.
    PMID: 24505241 DOI: 10.1371/journal.pone.0081817
    Cholera is a major infectious disease, affecting millions of lives annually. In endemic areas, implementation of vaccination strategy against cholera is vital. As the use of safer live vaccine that can induce protective immunity against Vibrio cholerae O139 infection is a promising approach for immunization, we have designed VCUSM21P, an oral cholera vaccine candidate, which has ctxA that encodes A subunit of ctx and mutated rtxA/C, ace and zot mutations. VCUSM21P was found not to disassemble the actin of HEp2 cells. It colonized the mice intestine approximately 1 log lower than that of the Wild Type (WT) strain obtained from Hospital Universiti Sains Malaysia. In the ileal loop assay, unlike WT challenge, 1×10⁶ and 1×10⁸ colony forming unit (CFU) of VCUSM21P was not reactogenic in non-immunized rabbits. Whereas, the reactogenicity caused by the WT in rabbits immunized with 1×10¹⁰ CFU of VCUSM21P was found to be reduced as evidenced by absence of fluid in loops administered with 1×10²-1×10⁷ CFU of WT. Oral immunization using 1×10¹⁰ CFU of VCUSM21P induced both IgA and IgG against Cholera Toxin (CT) and O139 lipopolysaccharides (LPS). The serum vibriocidal antibody titer had a peak rise of 2560 fold on week 4. Following Removable Intestinal Tie Adult Rabbit Diarrhoea (RITARD) experiment, the non-immunized rabbits were found not to be protected against lethal challenge with 1×10⁹ CFU WT, but 100% of immunized rabbits survived the challenge. In the past eleven years, V. cholerae O139 induced cholera has not been observed. However, attenuated VCUSM21P vaccine could be used for vaccination program against potentially fatal endemic or emerging cholera caused by V. cholerae O139.
  8. Fulltext Diversity of global rice markets and the science required for consumer-targeted rice breeding
    Calingacion M, Laborte A, Nelson A, Resurreccion A, Concepcion JC, Daygon VD, et al.
    PLoS One, 2014;9(1):e85106.
    PMID: 24454799 DOI: 10.1371/journal.pone.0085106
    With the ever-increasing global demand for high quality rice in both local production regions and with Western consumers, we have a strong desire to understand better the importance of the different traits that make up the quality of the rice grain and obtain a full picture of rice quality demographics. Rice is by no means a 'one size fits all' crop. Regional preferences are not only striking, they drive the market and hence are of major economic importance in any rice breeding / improvement strategy. In this analysis, we have engaged local experts across the world to perform a full assessment of all the major rice quality trait characteristics and importantly, to determine how these are combined in the most preferred varieties for each of their regions. Physical as well as biochemical characteristics have been monitored and this has resulted in the identification of no less than 18 quality trait combinations. This complexity immediately reveals the extent of the specificity of consumer preference. Nevertheless, further assessment of these combinations at the variety level reveals that several groups still comprise varieties which consumers can readily identify as being different. This emphasises the shortcomings in the current tools we have available to assess rice quality and raises the issue of how we might correct for this in the future. Only with additional tools and research will we be able to define directed strategies for rice breeding which are able to combine important agronomic features with the demands of local consumers for specific quality attributes and hence, design new, improved crop varieties which will be awarded success in the global market.
  9. Fulltext Molecular epidemiology of enterovirus 71 infection in the central region of Taiwan from 2002 to 2012
    Wu WH, Kuo TC, Lin YT, Huang SW, Liu HF, Wang J, et al.
    PLoS One, 2013;8(12):e83711.
    PMID: 24391812 DOI: 10.1371/journal.pone.0083711
    Enterovirus 71 (EV71), a causative agent of hand, foot, and mouth disease can be classified into three genotypes and many subtypes. The objectives of this study were to conduct a molecular epidemiological study of EV71 in the central region of Taiwan from 2002-2012 and to test the hypothesis that whether the alternative appearance of different EV71 subtypes in Taiwan is due to transmission from neighboring countries or from re-emergence of pre-existing local strains. We selected 174 EV71 isolates and used reverse transcription-polymerase chain reaction to amplify their VP1 region for DNA sequencing. Phylogenetic analyses were conducted using Neighbor-Joining, Maximum Likelihood and Bayesian methods. We found that the major subtypes of EV71 in Taiwan were B4 for 2002 epidemic, C4 for 2004-2005 epidemic, B5 for 2008-2009 epidemic, C4 for 2010 epidemic and B5 for 2011-2012 epidemic. Phylogenetic analysis demonstrated that the 2002 and 2008 epidemics were associated with EV71 from Malaysia and Singapore; while both 2010 and 2011-2012 epidemics originated from different regions of mainland China including Shanghai, Henan, Xiamen and Gong-Dong. Furthermore, minor strains have been identified in each epidemic and some of them were correlated with the subsequent outbreaks. Therefore, the EV71 infection in Taiwan may originate from pre-existing minor strains or from other regions in Asia including mainland China. In addition, 101 EV71 isolates were selected for the detection of new recombinant strains using the nucleotide sequences spanning the VP1-2A-2B region. No new recombinant strain was found. Analysis of clinical manifestations showed that patients infected with C4 had significantly higher rates of pharyngeal vesicles or ulcers than patients infected with B5. This is the first study demonstrating that different EV 71 genotypes may have different clinical manifestations and the association of EV71 infections between Taiwan and mainland China.
  10. Fulltext Non-density dependent pollen dispersal of Shorea maxwelliana (Dipterocarpaceae) revealed by a Bayesian mating model based on paternity analysis in two synchronized flowering seasons
    Masuda S, Tani N, Ueno S, Lee SL, Muhammad N, Kondo T, et al.
    PLoS One, 2013;8(12):e82039.
    PMID: 24391712 DOI: 10.1371/journal.pone.0082039
    Pollinator syndrome is one of the most important determinants regulating pollen dispersal in tropical tree species. It has been widely accepted that the reproduction of tropical forest species, especially dipterocarps that rely on insects with weak flight for their pollination, is positively density-dependent. However differences in pollinator syndrome should affect pollen dispersal patterns and, consequently, influence genetic diversity via the mating process. We examined the pollen dispersal pattern and mating system of Shorea maxwelliana, the flowers of which are larger than those of Shorea species belonging to section Mutica which are thought to be pollinated by thrips (weak flyers). A Bayesian mating model based on the paternity of seeds collected from mother trees during sporadic and mass flowering events revealed that the estimated pollen dispersal kernel and average pollen dispersal distance were similar for both flowering events. This evidence suggests that the putative pollinators - small beetles and weevils - effectively contribute to pollen dispersal and help to maintain a high outcrossing rate even during sporadic flowering events. However, the reduction in pollen donors during a sporadic event results in a reduction in effective pollen donors, which should lead to lower genetic diversity in the next generation derived from seeds produced during such an event. Although sporadic flowering has been considered less effective for outcrossing in Shorea species that depend on thrips for their pollination, effective pollen dispersal by the small beetles and weevils ensures outcrossing during periods of low flowering tree density, as occurs in a sporadic flowering event.
  11. Fulltext Acquisition of HIV by African-born residents of Victoria, Australia: insights from molecular epidemiology
    Lemoh C, Ryan CE, Sekawi Z, Hearps AC, Aleksic E, Chibo D, et al.
    PLoS One, 2013;8(12):e84008.
    PMID: 24391866 DOI: 10.1371/journal.pone.0084008
    African-born Australians are a recognised "priority population" in Australia's Sixth National HIV/AIDS Strategy. We compared exposure location and route for African-born people living with HIV (PLHIV) in Victoria, Australia, with HIV-1 pol subtype from drug resistance assays and geographical origin suggested by phylogenetic analysis of env gene. Twenty adult HIV positive African-born Victorian residents were recruited via treating doctors. HIV exposure details were obtained from interviews and case notes. Viral RNA was extracted from participant stored plasma or whole blood. The env V3 region was sequenced and compared to globally representative reference HIV-1 sequences in the Los Alamos National Library HIV Database. Twelve participants reported exposure via heterosexual sex and two via iatrogenic blood exposures; four were men having sex with men (MSM); two were exposed via unknown routes. Eight participants reported exposure in their countries of birth, seven in Australia, three in other countries and two in unknown locations. Genotype results (pol) were available for ten participants. HIV env amplification was successful in eighteen cases. HIV-1 subtype was identified in all participants: eight both pol and env; ten env alone and two pol alone. Twelve were subtype C, four subtype B, three subtype A and one subtype CRF02_AG. Reported exposure location was consistent with the phylogenetic clustering of env sequences. African Australians are members of multiple transnational social and sexual networks influencing their exposure to HIV. Phylogenetic analysis may complement traditional surveillance to discern patterns of HIV exposure, providing focus for HIV prevention programs in mobile populations.
  12. 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.
  13. Fulltext Gate length variation effect on performance of gate-first self-aligned In₀.₅₃Ga₀.₄₇As MOSFET
    Mohd Razip Wee MF, Dehzangi A, Bollaert S, Wichmann N, Majlis BY
    PLoS One, 2013;8(12):e82731.
    PMID: 24367548 DOI: 10.1371/journal.pone.0082731
    A multi-gate n-type In₀.₅₃Ga₀.₄₇As MOSFET is fabricated using gate-first self-aligned method and air-bridge technology. The devices with different gate lengths were fabricated with the Al2O3 oxide layer with the thickness of 8 nm. In this letter, impact of gate length variation on device parameter such as threshold voltage, high and low voltage transconductance, subthreshold swing and off current are investigated at room temperature. Scaling the gate length revealed good enhancement in all investigated parameters but the negative shift in threshold voltage was observed for shorter gate lengths. The high drain current of 1.13 A/mm and maximum extrinsic transconductance of 678 mS/mm with the field effect mobility of 364 cm(2)/Vs are achieved for the gate length and width of 0.2 µm and 30 µm, respectively. The source/drain overlap length for the device is approximately extracted about 51 nm with the leakage current in order of 10(-8) A. The results of RF measurement for cut-off and maximum oscillation frequency for devices with different gate lengths are compared.
  14. Fulltext An inverse finite element method for determining the tissue compressibility of human left ventricular wall during the cardiac cycle
    Hassaballah AI, Hassan MA, Mardi AN, Hamdi M
    PLoS One, 2013;8(12):e82703.
    PMID: 24367544 DOI: 10.1371/journal.pone.0082703
    The determination of the myocardium's tissue properties is important in constructing functional finite element (FE) models of the human heart. To obtain accurate properties especially for functional modeling of a heart, tissue properties have to be determined in vivo. At present, there are only few in vivo methods that can be applied to characterize the internal myocardium tissue mechanics. This work introduced and evaluated an FE inverse method to determine the myocardial tissue compressibility. Specifically, it combined an inverse FE method with the experimentally-measured left ventricular (LV) internal cavity pressure and volume versus time curves. Results indicated that the FE inverse method showed good correlation between LV repolarization and the variations in the myocardium tissue bulk modulus K (K = 1/compressibility), as well as provided an ability to describe in vivo human myocardium material behavior. The myocardium bulk modulus can be effectively used as a diagnostic tool of the heart ejection fraction. The model developed is proved to be robust and efficient. It offers a new perspective and means to the study of living-myocardium tissue properties, as it shows the variation of the bulk modulus throughout the cardiac cycle.
  15. Fulltext Bcl-xL silencing induces alterations in hsa-miR-608 expression and subsequent cell death in A549 and SK-LU1 human lung adenocarcinoma cells
    Othman N, In LL, Harikrishna JA, Hasima N
    PLoS One, 2013;8(12):e81735.
    PMID: 24339958 DOI: 10.1371/journal.pone.0081735
    Bcl-xL is an anti-apoptotic protein that is frequently found to be overexpressed in non-small cell lung cancer leading to an inhibition of apoptosis and poor prognosis. Recently, the role of miRNAs in regulating apoptosis and cell survival during tumorigenesis has become evident, with cancer cells showing perturbed expression of various miRNAs. In this study, we utilized miRNA microarrays to determine if miRNA dysregulation in bcl-xL silenced lung adenocarcinoma cells could be involved in regulating cell death. Short interfering RNA-based transfection of A549 and SK-LU1 lung adenocarcinoma cells was successful in inducing a reduction in bcl-xL expression levels, resulting in a decrease in cell viability. A total of 10 miRNAs were found to be significantly differentially expressed when compared between siRNA-transfected and non-transfected cells including hsa-miR-181a, hsa-miR-769-5p, hsa-miR-361-5p, hsa-miR-1304 and hsa-miR-608. When overexpression studies on hsa-miR-608 was performed via transfection of miRNA mimics, cell death was found to be induced in A549 and SK-LU1 cells in comparison to untreated cells. This effect was reversed when knockdown studies involving anti-sense inhibitors were introduced. Combination of siRNA based silencing of bcl-xL (siBcl-xL) followed by anti-sense inhibitor transfection led to a decrease in the apoptotic population of A549 and SK-LU1 cells in comparison to cells only treated with siBcl-xL, illustrating the connection between bcl-xL, hsa-miR-608 and cell death. Gene target prediction analysis implicated the PI3K/AKT, WNT, TGF-β, and ERK signaling pathways as targets of bcl-xL induced miRNA alterations. We have demonstrated that bcl-xL silencing in A549 and SK-LU1 cells leads to the occurrence of cell death through the dysregulation of specific miRNAs. This study also provides a platform for anti-sense gene therapy whereby miRNA expression can be exploited to increase the apoptotic properties in lung adenocarcinoma cells.
  16. Fulltext Role of exercise in the management of diabetes mellitus: the global scenario
    Thent ZC, Das S, Henry LJ
    PLoS One, 2013;8(11):e80436.
    PMID: 24236181 DOI: 10.1371/journal.pone.0080436
    Background: Exercise training programs have emerged as a useful therapeutic regimen for the management of type 2 diabetes mellitus (T2DM). Majority of the Western studies highlighted the effective role of exercise in T2DM. Therefore, the main aim was to focus on the extent, type of exercise and its clinical significance in T2DM in order to educate the clinicians from developing countries, especially in Asians.

    Methods: Pubmed, Science Direct, Scopus, ISI Web of Knowledge and Google scholar were searched using the terms "type 2 diabetes mellitus," "type 2 DM," "exercise," and/or "physical activity," and "type 2 diabetes mellitus with exercise." Only clinical or human studies published in English language between 2000 and 2012 were included. Certain criteria were assigned to achieve appropriate results.

    Results: Twenty five studies met the selected criteria. The majority of the studies were randomized controlled trial study design (65%). Most of the aerobic exercise based studies showed a beneficial effect in T2DM. Resistance exercise also proved to have positive effect on T2DM patients. Minimal studies related to other types of exercises such as yoga classes, joba riding and endurance-type exercise were found. On the other hand, United States of America (USA) showed strong interest of exercise management towards T2DM.

    Conclusion: Aerobic exercise is more common in clinical practice compared to resistance exercise in managing T2DM. Treatment of T2DM with exercise training showed promising role in USA. A large number of researches are mandatory in the developing countries for incorporating exercise in the effective management of T2DM.
  17. Fulltext The empirical analysis of cigarette tax avoidance and illicit trade in Vietnam, 1998-2010
    Nguyen MT, Denniston R, Nguyen HT, Hoang TA, Ross H, So AD
    PLoS One, 2014;9(1):e87272.
    PMID: 24489886 DOI: 10.1371/journal.pone.0087272
    Illicit trade carries the potential to magnify existing tobacco-related health care costs through increased availability of untaxed and inexpensive cigarettes. What is known with respect to the magnitude of illicit trade for Vietnam is produced primarily by the industry, and methodologies are typically opaque. Independent assessment of the illicit cigarette trade in Vietnam is vital to tobacco control policy. This paper measures the magnitude of illicit cigarette trade for Vietnam between 1998 and 2010 using two methods, discrepancies between legitimate domestic cigarette sales and domestic tobacco consumption estimated from surveys, and trade discrepancies as recorded by Vietnam and trade partners. The results indicate that Vietnam likely experienced net smuggling in during the period studied. With the inclusion of adjustments for survey respondent under-reporting, inward illicit trade likely occurred in three of the four years for which surveys were available. Discrepancies in trade records indicate that the value of smuggled cigarettes into Vietnam ranges from $100 million to $300 million between 2000 and 2010 and that these cigarettes primarily originate in Singapore, Hong Kong, Macao, Malaysia, and Australia. Notable differences in trends over time exist between the two methods, but by comparison, the industry estimates consistently place the magnitude of illicit trade at the upper bounds of what this study shows. The unavailability of annual, survey-based estimates of consumption may obscure the true, annual trend over time. Second, as surveys changed over time, estimates relying on them may be inconsistent with one another. Finally, these two methods measure different components of illicit trade, specifically consumption of illicit cigarettes regardless of origin and smuggling of cigarettes into a particular market. However, absent a gold standard, comparisons of different approaches to illicit trade measurement serve efforts to refine and improve measurement approaches and estimates.
  18. Fulltext Determinants of public attitudes to genetically modified salmon
    Amin L, Azad MA, Gausmian MH, Zulkifli F
    PLoS One, 2014;9(1):e86174.
    PMID: 24489695 DOI: 10.1371/journal.pone.0086174
    The objective of this paper is to assess the attitude of Malaysian stakeholders to genetically modified (GM) salmon and to identify the factors that influence their acceptance of GM salmon using a structural equation model. A survey was carried out on 434 representatives from various stakeholder groups in the Klang Valley region of Malaysia. Public attitude towards GM salmon was measured using self-developed questionnaires with seven-point Likert scales. The findings of this study have confirmed that public attitudes towards GM salmon is a complex issue and should be seen as a multi-faceted process. The most important direct predictors for the encouragement of GM salmon are the specific application-linked perceptions about religious acceptability of GM salmon followed by perceived risks and benefits, familiarity, and general promise of modern biotechnology. Encouragement of GM salmon also involves the interplay among other factors such as general concerns of biotechnology, threatening the natural order of things, the need for labeling, the need for patenting, confidence in regulation, and societal values. The research findings can serve as a database that will be useful for understanding the social construct of public attitude towards GM foods in a developing country.
  19. 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.
  20. 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.
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