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  1. Fulltext Ozone exposure induces respiratory barrier biphasic injury and inflammation controlled by IL-33
    Michaudel C, Mackowiak C, Maillet I, Fauconnier L, Akdis CA, Sokolowska M, et al.
    J Allergy Clin Immunol, 2018 09;142(3):942-958.
    PMID: 29331644 DOI: 10.1016/j.jaci.2017.11.044
    BACKGROUND: IL-33 plays a critical role in regulation of tissue homeostasis, injury, and repair. Whether IL-33 regulates neutrophil recruitment and functions independently of airways hyperresponsiveness (AHR) in the setting of ozone-induced lung injury and inflammation is unclear.

    OBJECTIVE: We sought to examine the role of the IL-33/ST2 axis in lung inflammation on acute ozone exposure in mice.

    METHODS: ST2- and Il33-deficient, IL-33 citrine reporter, and C57BL/6 (wild-type) mice underwent a single ozone exposure (1 ppm for 1 hour) in all studies. Cell recruitment in lung tissue and the bronchoalveolar space, inflammatory parameters, epithelial barrier damage, and airway hyperresponsiveness (AHR) were determined.

    RESULTS: We report that a single ozone exposure causes rapid disruption of the epithelial barrier within 1 hour, followed by a second phase of respiratory barrier injury with increased neutrophil recruitment, reactive oxygen species production, AHR, and IL-33 expression in epithelial and myeloid cells in wild-type mice. In the absence of IL-33 or IL-33 receptor/ST2, epithelial cell injury with protein leak and myeloid cell recruitment and inflammation are further increased, whereas the tight junction proteins E-cadherin and zonula occludens 1 and reactive oxygen species expression in neutrophils and AHR are diminished. ST2 neutralization recapitulated the enhanced ozone-induced neutrophilic inflammation. However, myeloid cell depletion using GR-1 antibody reduced ozone-induced lung inflammation, epithelial cell injury, and protein leak, whereas administration of recombinant mouse IL-33 reduced neutrophil recruitment in Il33-deficient mice.

    CONCLUSION: Data demonstrate that ozone causes an immediate barrier injury that precedes myeloid cell-mediated inflammatory injury under the control of the IL-33/ST2 axis. Thus IL-33/ST2 signaling is critical for maintenance of intact epithelial barrier and inflammation.

  2. Improving pathology and laboratory medicine in low-income and middle-income countries: roadmap to solutions
    Sayed S, Cherniak W, Lawler M, Tan SY, El Sadr W, Wolf N, et al.
    Lancet, 2018 05 12;391(10133):1939-1952.
    PMID: 29550027 DOI: 10.1016/S0140-6736(18)30459-8
    Insufficient awareness of the centrality of pathology and laboratory medicine (PALM) to a functioning health-care system at policy and governmental level, with the resultant inadequate investment, has meant that efforts to enhance PALM in low-income and middle-income countries have been local, fragmented, and mostly unsustainable. Responding to the four major barriers in PALM service delivery that were identified in the first paper of this Series (workforce, infrastructure, education and training, and quality assurance), this second paper identifies potential solutions that can be applied in low-income and middle-income countries (LMICs). Increasing and retaining a quality PALM workforce requires access to mentorship and continuing professional development, task sharing, and the development of short-term visitor programmes. Opportunities to enhance the training of pathologists and allied PALM personnel by increasing and improving education provision must be explored and implemented. PALM infrastructure must be strengthened by addressing supply chain barriers, and ensuring laboratory information systems are in place. New technologies, including telepathology and point-of-care testing, can have a substantial role in PALM service delivery, if used appropriately. We emphasise the crucial importance of maintaining PALM quality and posit that all laboratories in LMICs should participate in quality assurance and accreditation programmes. A potential role for public-private partnerships in filling PALM services gaps should also be investigated. Finally, to deliver these solutions and ensure equitable access to essential services in LMICs, we propose a PALM package focused on these countries, integrated within a nationally tiered laboratory system, as part of an overarching national laboratory strategic plan.
  3. Automated diagnosis of focal liver lesions using bidirectional empirical mode decomposition features
    Acharya UR, Koh JEW, Hagiwara Y, Tan JH, Gertych A, Vijayananthan A, et al.
    Comput Biol Med, 2018 03 01;94:11-18.
    PMID: 29353161 DOI: 10.1016/j.compbiomed.2017.12.024
    Liver is the heaviest internal organ of the human body and performs many vital functions. Prolonged cirrhosis and fatty liver disease may lead to the formation of benign or malignant lesions in this organ, and an early and reliable evaluation of these conditions can improve treatment outcomes. Ultrasound imaging is a safe, non-invasive, and cost-effective way of diagnosing liver lesions. However, this technique has limited performance in determining the nature of the lesions. This study initiates a computer-aided diagnosis (CAD) system to aid radiologists in an objective and more reliable interpretation of ultrasound images of liver lesions. In this work, we have employed radon transform and bi-directional empirical mode decomposition (BEMD) to extract features from the focal liver lesions. After which, the extracted features were subjected to particle swarm optimization (PSO) technique for the selection of a set of optimized features for classification. Our automated CAD system can differentiate normal, malignant, and benign liver lesions using machine learning algorithms. It was trained using 78 normal, 26 benign and 36 malignant focal lesions of the liver. The accuracy, sensitivity, and specificity of lesion classification were 92.95%, 90.80%, and 97.44%, respectively. The proposed CAD system is fully automatic as no segmentation of region-of-interest (ROI) is required.
  4. Measurement of coronary bifurcation angle with coronary CT angiography: A phantom study
    Givehchi S, Safari MJ, Tan SK, Md Shah MNB, Sani FBM, Azman RR, et al.
    Phys Med, 2018 Jan;45:198-204.
    PMID: 29373248 DOI: 10.1016/j.ejmp.2017.09.137
    PURPOSE: Accurate determination of the bifurcation angle and correlation with plaque buildup may lead to the prediction of coronary artery disease (CAD). This work evaluates two techniques to measure bifurcation angles in 3D space using coronary computed tomography angiography (CCTA).

    MATERIALS AND METHODS: Nine phantoms were fabricated with different bifurcation angles ranging from 55.3° to 134.5°. General X-ray and CCTA were employed to acquire 2D and 3D images of the bifurcation phantoms, respectively. Multiplanar reformation (MPR) and volume rendering technique (VRT) were used to measure the bifurcation angle between the left anterior descending (LAD) and left circumflex arteries (LCx). The measured angles were compared with the true values to determine the accuracy of each measurement technique. Inter-observer variability was evaluated. The two techniques were further applied on 50 clinical CCTA cases to verify its clinical value.

    RESULTS: In the phantom setting, the mean absolute differences calculated between the true and measured angles by MPR and VRT were 2.4°±2.2° and 3.8°±2.9°, respectively. Strong correlation was found between the true and measured bifurcation angles. Furthermore, no significant differences were found between the bifurcation angles measured using either technique. In clinical settings, large difference of 12.0°±10.6° was found between the two techniques.

    CONCLUSION: In the phantom setting, both techniques demonstrated a significant correlation to the true bifurcation angle. Despite the lack of agreement of the two techniques in the clinical context, our findings in phantoms suggest that MPR should be preferred to VRT for the measurement of coronary bifurcation angle by CCTA.

  5. Fulltext Resveratrol-Potential Antibacterial Agent against Foodborne Pathogens
    Ma DSL, Tan LT, Chan KG, Yap WH, Pusparajah P, Chuah LH, et al.
    Front Pharmacol, 2018;9:102.
    PMID: 29515440 DOI: 10.3389/fphar.2018.00102
    Bacterial foodborne pathogens are a significant health burden and the recent emergence of pathogenic resistant strains due to the excessive use of antibiotics makes it more difficult to effectively treat infections as a result of contaminated food. Awareness of this impending health crisis has spurred the search for alternative antimicrobials with natural plant antimicrobials being among the more promising candidates as these substances have good acceptability and likely low toxicity levels as they have long been used in traditional medicines. Resveratrol (3,5,4'-trihydroxystilbene) is a naturally occurring stilbenoid which has been gaining considerable attention in medical field due to its diverse biological activities - it has been reported to exhibit antioxidant, cardioprotective, anti-diabetic, anticancer, and antiaging properties. Given that resveratrol is phytoalexin, with increased synthesis in response to infection by phytopathogens, there has been interest in exploring its antimicrobial activity. This review aims to provide an overview of the published data on the antibacterial activity of resveratrol against foodborne pathogens, its mechanisms of action as well as its possible applications in food packing and processing; in addition we also summarize the current data on its potential synergism with known antibacterials and future research and applications.
  6. Fulltext Focused Review: Cytotoxic and Antioxidant Potentials of Mangrove-Derived Streptomyces
    Ser HL, Tan LT, Law JW, Chan KG, Duangjai A, Saokaew S, et al.
    Front Microbiol, 2017;8:2065.
    PMID: 29163380 DOI: 10.3389/fmicb.2017.02065
    Human life expectancy is rapidly increasing with an associated increasing burden of chronic diseases, such as neurodegenerative diseases and cancer. However, there is limited progress in finding effective treatment for these conditions. For this reason, members of the genus Streptomyces have been explored extensively over the past decades as these filamentous bacteria are highly efficient in producing bioactive compounds with human health benefits. Being ubiquitous in nature, streptomycetes can be found in both terrestrial and marine environments. Previously, two Streptomyces strains (MUSC 137T and MUM 256) isolated from mangrove sediments in Peninsular Malaysia demonstrated potent antioxidant and cytotoxic activities against several human cancer cell lines on bioactivity screening. These results illustrate the importance of streptomycetes from underexplored regions aside from the terrestrial ecosystem. Here we provide the insights and significance of Streptomyces species in the search of anticancer and/or chemopreventive agents and highlight the impact of next generation sequencing on drug discovery from the Streptomyces arsenal.
  7. Ehrlichia and Anaplasma Infections: Serological Evidence and Tick Surveillance in Peninsular Malaysia
    Koh FX, Kho KL, Kisomi MG, Wong LP, Bulgiba A, Tan PE, et al.
    J Med Entomol, 2018 02 28;55(2):269-276.
    PMID: 29202206 DOI: 10.1093/jme/tjx204
    Little information is available on human anaplasmosis and ehrlichiosis in Southeast Asia despite increasing reports of the detection of Anaplasma spp. and Ehrlichia spp. in the ticks. We report herein the serological findings against the tick-borne pathogens in a group of animal farm workers (n = 87) and indigenous people (n = 102) in Peninsular Malaysia. IgG antibodies against Ehrlichia chaffeensis were detected from 29.9% and 34.3% of farm workers and indigenous people, respectively, using commercial indirect immunofluorescence assays. Comparatively, only 6.9% of the indigenous people but none of the animal farm workers were seropositive to Anaplasma phagocytophilum. A polymerase chain reaction (PCR) assay targeting the 16S rRNA gene of Anaplasmataceae was used to identify Anaplastamataceae in ticks collected from various locations adjacent to the areas where the serological survey was conducted. In this study, a total of 61.5% of ticks infesting farm animals, 37.5% of ticks infesting peri-domestic animals in rural villages, 27.3% of ticks collected from wildlife animals, and 29.1% of questing ticks collected from forest vegetation were positive for Anaplasmataceae DNA. Sequence analyses of 16S rRNA gene region (238 bp) provide the identification for Anaplasma marginale, Anaplasma bovis, Anaplasma platys, A. phagocytophilum, and Anaplasma spp. closely related to Candidatus Cryptoplasma californiense in ticks. E. chaffeensis DNA was not detected from any ticks, instead, Ehrlichia sp. strain EBm52, Ehrlichia mineirensis and Candidatus Ehrlichia shimanensis are the only Ehrlichia sp. identified from cattle ticks in this study. Further investigation is required to ascertain the occurrence of zoonotic transmission of Ehrlichia and Anaplasma infections in Peninsular Malaysia.
  8. Prevalence and sociodemographic correlates of cervicovaginal human papillomavirus (HPV) carriage in a cross-sectional, multiethnic, community-based female Asian population
    Khoo SP, Bhoo-Pathy N, Yap SH, Anwar Shafii MK, Hairizan Nasir N, Belinson J, et al.
    Sex Transm Infect, 2018 06;94(4):277-283.
    PMID: 29180538 DOI: 10.1136/sextrans-2017-053320
    OBJECTIVES: Cervical cancer is a largely preventable disease, and the strategic implementation of a cervical cancer prevention programme is partly dependent on the impact of human papillomavirus (HPV) infection interpreted within the context of the country's sociodemographic attributes. The objective of this study is to determine the prevalence of cervicovaginal HPV infection among a healthy, community-based, multiethnic Malaysian population. The HPV prevalence was subsequently correlated to the individual's sociodemographics and sexual/reproductive history. Of significance, the observed prevalence captured was in a birth cohort not included in the national school-based HPV vaccination programme.

    METHODS: This was a cross-sectional study where 1293 healthy women aged between 18 and 60 years were recruited via convenience sampling from five community-based clinics in Selangor, Malaysia. Cervicovaginal self-samples were obtained and DNA was extracted for HPV detection and genotyping. A comprehensive questionnaire was administered to determine the sociodemographics and behavioural patterns of participants.

    RESULTS: The median age at enrolment was 37 years old (IQR: 30-47). In total, 86/1190 (7.2%) of the samples collected were positive for HPV infection, with the highest HPV prevalence (11.9%) detected in the subgroup of 18-24 years old. The top three most prevalent HPV genotypes were HPV 16, 52 and 58. The independent risk factors associated with higher rates of HPV infection included Indian ethnicity, widowed status and women with partners who are away from home for long periods and/or has another sexual partner.

    CONCLUSIONS: The overall prevalence of HPV infection in this Malaysian multiethnic population was 7.2%, with 6.5% being high-risk genotypes. The top three most common high-risk HPV types were HPV 16, 52 and 58. This information is important for the planning of primary (HPV vaccination) and secondary (screening) cervical cancer prevention programmes in Malaysia.

  9. Planococcus versutus sp. nov., isolated from soil
    See-Too WS, Ee R, Madhaiyan M, Kwon SW, Tan JY, Lim YL, et al.
    Int J Syst Evol Microbiol, 2017 Apr;67(4):944-950.
    PMID: 27959786 DOI: 10.1099/ijsem.0.001721
    A taxonomic study was performed on a novel Gram-stain-positive, coccus-shaped, orange-pigmented motile bacterium, designated as strain L10.15T. The organism was isolated from a soil sample collected in Lagoon Island (close to Adelaide Island, western Antarctic Peninsula) using a quorum-quenching enrichment medium. Growth occurred at 4-30 °C, pH 6-11 and at moderately high salinity (0-15 %, w/v, NaCl), with optimal growth at 26 °C, at pH 7-8 and with 6 % (w/v) NaCl. 16S rRNA gene sequence analysis showed that strain L10.15T belonged to the genus Planococcus and was closely related to Planococcus halocryophilus Or1T (99.3 % similarity), Planococcus donghaensis JH1T (99.0 %), Planococcus antarcticus DSM 14505T (98.3 %), Planococcus plakortidis AS/ASP6 (II)T (97.6 %), Planococcus maritimus TF-9T (97.5 %), Planococcus salinarum ISL-6T (97.5 %) and Planococcus kocurii NCIMB 629T (97.5 %). However, the average nucleotide identity-MUMmer analysis showed low genomic relatedness values of 71.1-81.7 % to the type strains of these closely related species of the genus Planococcus. The principal fatty acids were anteiso-C15 : 0, C16 : 1ω7c and anteiso-C17 :  0, and the major menaquinones of strain L10.15T were MK-5 (48 %), MK-6 (6 %) and MK-7 (44 %). Polar lipid analysis revealed the presence of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and aminophospholipid. The DNA G+C content was 39.4 mol%. The phenotypic and genotypic data indicate that strain L10.15T represents a novel species of the genus Planococcus, for which the name Planococcus versutus sp. nov. is proposed. The type strain is L10.15T (=DSM 101994T=KACC 18918T).
  10. Thymoma-associated myasthenia gravis and LGI1-encephalitis, with nephrotic syndrome post-thymectomy
    Hor JY, Lim TT, Cheng MC, Chia YK, Wong CK, Lim SM, et al.
    J Neuroimmunol, 2018 04 15;317:100-102.
    PMID: 29395322 DOI: 10.1016/j.jneuroim.2018.01.011
    Thymoma is associated with a wide spectrum of autoimmune paraneoplastic syndromes, though it is uncommon for multiple paraneoplastic syndromes to be present in a single individual. We report a rare case of an elderly gentleman who was found to have thymoma-associated myasthenia gravis and LGI1-encephalitis with myokymia, who presented with nephrotic syndrome (minimal change glomerulopathy) after thymectomy. The latter two paraneoplastic syndromes had manifested when prednisolone was tapered down to low dose. This case serves to remind neurologists that apart from paraneoplastic neurological manifestations, thymoma may also be associated with renal disease. Nephropathy in myasthenia patients with thymoma should be properly evaluated, as it is treatable with immunotherapy, and it may even occur post-thymectomy.
  11. Phylogeny and species delineation in the marine diatom Pseudo-nitzschia (Bacillariophyta) using cox1, LSU, and ITS2 rRNA genes: A perspective in character evolution
    Lim HC, Tan SN, Teng ST, Lundholm N, Orive E, David H, et al.
    J Phycol, 2018 04;54(2):234-248.
    PMID: 29377161 DOI: 10.1111/jpy.12620
    Analyses of the mitochondrial cox1, the nuclear-encoded large subunit (LSU), and the internal transcribed spacer 2 (ITS2) RNA coding region of Pseudo-nitzschia revealed that the P. pseudodelicatissima complex can be phylogenetically grouped into three distinct clades (Groups I-III), while the P. delicatissima complex forms another distinct clade (Group IV) in both the LSU and ITS2 phylogenetic trees. It was elucidated that comprehensive taxon sampling (sampling of sequences), selection of appropriate target genes and outgroup, and alignment strategies influenced the phylogenetic accuracy. Based on the genetic divergence, ITS2 resulted in the most resolved trees, followed by cox1 and LSU. The morphological characters available for Pseudo-nitzschia, although limited in number, were overall in agreement with the phylogenies when mapped onto the ITS2 tree. Information on the presence/absence of a central nodule, number of rows of poroids in each stria, and of sectors dividing the poroids mapped onto the ITS2 tree revealed the evolution of the recently diverged species. The morphologically based species complexes showed evolutionary relevance in agreement with molecular phylogeny inferred from ITS2 sequence-structure data. The data set of the hypervariable region of ITS2 improved the phylogenetic inference compared to the cox1 and LSU data sets. The taxonomic status of P. cuspidata and P. pseudodelicatissima requires further elucidation.
  12. Fulltext Breakfast consumption among Malaysian primary and secondary school children and relationship with body weight status - Findings from the MyBreakfast Study
    Tee ES, Nurliyana AR, Norimah AK, Mohamed HJBJ, Tan SY, Appukutty M, et al.
    Asia Pac J Clin Nutr, 2018 2 1;27(2):421-432.
    PMID: 29384332 DOI: 10.6133/apjcn.062017.12
    BACKGROUND AND OBJECTIVES: This study aimed to determine the relationship between breakfast consumption and body weight status among primary and secondary school children in Malaysia.

    METHODS AND STUDY DESIGN: This nationwide cross-sectional study involved 5,332 primary school children aged 6 to 12 years and 3,000 secondary school children aged 13 to 17 years. Height and weight were measured and BMI-for-age was determined. Socio-demographic backgrounds, breakfast habits and physical activity levels were assessed using questionnaires. Breakfast frequency was defined as follows: breakfast skippers (ate breakfast 0-2 days/week), irregular breakfast eaters (ate breakfast 3-4 days/week) and regular breakfast eaters (ate breakfast ≥5 days/week).

    RESULTS: The overall prevalence of breakfast skippers and irregular breakfast eaters was 11.7% and 12.7% respectively. Breakfast skipping was related to age, sex, ethnicity, income and physical activity level. Among primary school boys and secondary school girls, the proportion of overweight/obesity was higher among breakfast skippers (boys: 43.9%, girls: 30.5%) than regular breakfast eaters (boys: 31.2%, girls: 22.7%). Among primary school children, only boys who skipped breakfast had a higher mean BMI-for-age z-score than regular breakfast eaters. Among secondary school boys and girls, BMI-for-age z-score was higher among breakfast skippers than regular breakfast eaters. Compared to regular breakfast eaters, primary school boys who skipped breakfast were 1.71 times (95% CI=1.26-2.32, p=0.001) more likely to be overweight/obese, while the risk was lower in primary school girls (OR=1.36, 95% CI=1.02-1.81, p=0.039) and secondary school girls (OR=1.38, 95% CI=1.01-1.90, p=0.044).

    CONCLUSION: Regular breakfast consumption was associated with a healthier body weight status and is a dietary behaviour which should be encouraged.

  13. Water quality variation during a strong El Niño event in 2016: a case study in Kampar River, Malaysia
    Ng CK, Goh CH, Lin JC, Tan MS, Bong W, Yong CS, et al.
    Environ Monit Assess, 2018 Jun 15;190(7):402.
    PMID: 29904816 DOI: 10.1007/s10661-018-6784-2
    El Niño and Southern Oscillation (ENSO) is a natural forcing that affects global climate patterns, thereon influencing freshwater quality and security. In the advent of a strong El Niño warming event in 2016 which induced an extreme dry weather in Malaysia, water quality variation was investigated in Kampar River which supplies potable water to a population of 92,850. Sampling points were stratified into four ecohydrological units and 144 water samples were examined from October 2015 to March 2017. The Malaysian Water Quality Index (WQI) and some supplementary parameters were analysed in the context of reduced precipitation. Data shows that prolonged dry weather, episodic and sporadic pollution incidents have caused some anomalies in dissolved oxygen (DO), total suspended solids (TSS), turbidity and ammoniacal nitrogen (AN) values recorded and the possible factors are discussed. The month of March and August 2016 recorded the lowest precipitation, but the overall resultant WQI remained acceptable. Since the occurrence of a strong El Niño event is infrequent and far between in decadal time scale, this paper gives some rare insights that may be central to monitoring and managing freshwater resource that has a crucial impact to the mass population in the region of Southeast Asia.
  14. The relationship between Type D personality and insomnia
    Akram U, McCarty K, Akram A, Gardani M, Tan A, Villarreal D, et al.
    Sleep Health, 2018 08;4(4):360-363.
    PMID: 30031529 DOI: 10.1016/j.sleh.2018.04.005
    OBJECTIVES: Type D personality is characterized by the combination of social inhibition and negative affectivity. This study examined the relationship between Type D personality and insomnia symptoms amongst a sample of the general-population.

    METHODS: Adults from the general-population (n = 392) completed online measures of Type D personality (DS14) and insomnia severity.

    RESULTS: Individuals with the Type D personality trait reported significantly greater symptoms of insomnia relative to Non-Type Ds. Moreover, insomnia-symptoms were independently related to negative affectivity (NA) and social inhibition (SI) and the Type D interaction (i.e. synergistic product of SI and NA). Linear regression analysis determined that NA but not SI significantly predicted insomnia symptoms after controlling for age and sex. However, after accounting for the Type D interaction, negative affectivity remained the only significant predictor of insomnia-symptoms.

    CONCLUSIONS: The Type D personality type appears to be related to insomnia-symptoms, both as a categorical and dimensional construct. These outcomes support prior research evidencing that whilst Type D personality is related to poor sleep in adolescents, NA appears to be the main contributor.

  15. Effective Response Metric: a novel tool to predict relapse in childhood acute lymphoblastic leukaemia using time-series gene expression profiling
    Yeoh AE, Li Z, Dong D, Lu Y, Jiang N, Trka J, et al.
    Br J Haematol, 2018 Jun;181(5):653-663.
    PMID: 29808917 DOI: 10.1111/bjh.15252
    Accurate risk assignment in childhood acute lymphoblastic leukaemia is essential to avoid under- or over-treatment. We hypothesized that time-series gene expression profiles (GEPs) of bone marrow samples during remission-induction therapy can measure the response and be used for relapse prediction. We computed the time-series changes from diagnosis to Day 8 of remission-induction, termed Effective Response Metric (ERM-D8) and tested its ability to predict relapse against contemporary risk assignment methods, including National Cancer Institutes (NCI) criteria, genetics and minimal residual disease (MRD). ERM-D8 was trained on a set of 131 patients and validated on an independent set of 79 patients. In the independent blinded test set, unfavourable ERM-D8 patients had >3-fold increased risk of relapse compared to favourable ERM-D8 (5-year cumulative incidence of relapse 38·1% vs. 10·6%; P = 2·5 × 10-3 ). ERM-D8 remained predictive of relapse [P = 0·05; Hazard ratio 4·09, 95% confidence interval (CI) 1·03-16·23] after adjusting for NCI criteria, genetics, Day 8 peripheral response and Day 33 MRD. ERM-D8 improved risk stratification in favourable genetics subgroups (P = 0·01) and Day 33 MRD positive patients (P = 1·7 × 10-3 ). We conclude that our novel metric - ERM-D8 - based on time-series GEP after 8 days of remission-induction therapy can independently predict relapse even after adjusting for NCI risk, genetics, Day 8 peripheral blood response and MRD.
  16. Fulltext Patient and Physician Satisfaction with Analgesic Treatment: Findings from the Analgesic Treatment for Cancer Pain in Southeast Asia (ACE) Study
    Thinh DHQ, Sriraj W, Mansor M, Tan KH, Irawan C, Kurnianda J, et al.
    Pain Res Manag, 2018;2018:2193710.
    PMID: 29849841 DOI: 10.1155/2018/2193710
    Aim: The aim of this study was to examine patients' and physicians' satisfaction, and concordance of patient-physician satisfaction with patients' pain control status.

    Methods: This cross-sectional observational study involved 465 adults prescribed analgesics for cancer-related pain from 22 sites across Indonesia, Malaysia, Philippines, Singapore, Thailand, and Vietnam. Pain intensity, pain control satisfaction, and adequacy of analgesics for pain control were documented using questionnaires.

    Results: Most patients (84.4%) had stage III or IV cancer. On a scale of 0 (no pain) to 10 (worse pain), patients' mean worst pain intensity over 24 hours was 4.76 (SD 2.47). More physicians (19.0%) than patients (8.0%) reported dissatisfaction with patient's pain control. Concordance of patient-physician satisfaction was low (weighted kappa 0.36; 95% CI 0.03-0.24). Most physicians (71.2%) found analgesics to be adequate for pain control. Patients' and physicians' satisfaction with pain control and physician-assessed analgesic adequacy were significantly different across countries (P < 0.001 for all).

    Conclusions: Despite pain-related problems with sleep and quality of life, patients were generally satisfied with their pain control status. Interestingly, physicians were more likely to be dissatisfied with patients' pain control. Enhanced patient-physician communication, physicians' proactivity in managing opioid-induced adverse effects, and accessibility of analgesics have been identified to be crucial for successful cancer pain management. This study was registered at ClinicalTrials.gov (identifier NCT02664987).

  17. Fulltext The epidemiological characteristics and molecular phylogeny of the dengue virus in Guangdong, China, 2015
    Sun J, Zhang H, Tan Q, Zhou H, Guan D, Zhang X, et al.
    Sci Rep, 2018 07 02;8(1):9976.
    PMID: 29967414 DOI: 10.1038/s41598-018-28349-2
    In 2015, an unexpected multiple outbreak of dengue occurred in Guangdong, China. In total, 1,699 cases were reported, of which 1,627 cases were verified to have DENV infections by nucleic acid or NS1 protein, including 44 DENV-1, 1126 DENV-2, 18 DENV-3 and 6 DENV-4, and the other cases were confirmed by NS1 ELISA. Phylogenetic analyses of DENV-1 isolates identified two genotypes (I and V). The predominant DENV-2 outbreak isolates were the Cosmopolitan genotypes, which likely originated from Malaysia. The DENV-3 isolates were assigned into genotype I and genotype III. All 6 DENV-4 isolates from imported cases were likely originally from Cambodia, Thailand and the Philippines. The entomological surveillance showed a moderate risk for the BI index in Chaozhou and Foshan and a low risk in Guangzhou. The imported cases were mostly detected in Guangzhou and Foshan. Surprisingly, the most serious outbreak occurred in Chaozhou, but not in Guangzhou or Foshan. A combined analyses demonstrated the multiple geographical origins of this outbreak, and highlight the detection of suspected cases after the alerting of imported cases, early implementation of control policies and reinforce the vector surveillance strategies were the key points in the chain of prevention and control of dengue epidemics.
  18. Fulltext Adaptive NKG2C+CD57+ Natural Killer Cell and Tim-3 Expression During Viral Infections
    Kared H, Martelli S, Tan SW, Simoni Y, Chong ML, Yap SH, et al.
    Front Immunol, 2018;9:686.
    PMID: 29731749 DOI: 10.3389/fimmu.2018.00686
    Repetitive stimulation by persistent pathogens such as human cytomegalovirus (HCMV) or human immunodeficiency virus (HIV) induces the differentiation of natural killer (NK) cells. This maturation pathway is characterized by the acquisition of phenotypic markers, CD2, CD57, and NKG2C, and effector functions-a process regulated by Tim-3 and orchestrated by a complex network of transcriptional factors, involving T-bet, Eomes, Zeb2, promyelocytic leukemia zinc finger protein, and Foxo3. Here, we show that persistent immune activation during chronic viral co-infections (HCMV, hepatitis C virus, and HIV) interferes with the functional phenotype of NK cells by modulating the Tim-3 pathway; a decrease in Tim-3 expression combined with the acquisition of inhibitory receptors skewed NK cells toward an exhausted and cytotoxic phenotype in an inflammatory environment during chronic HIV infection. A better understanding of the mechanisms underlying NK cell differentiation could aid the identification of new immunological targets for checkpoint blockade therapies in a manner that is relevant to chronic infection and cancer.
  19. In vivo monitoring of plant small GTPase activation using a Förster resonance energy transfer biosensor
    Wong HL, Akamatsu A, Wang Q, Higuchi M, Matsuda T, Okuda J, et al.
    Plant Methods, 2018;14:56.
    PMID: 30002723 DOI: 10.1186/s13007-018-0325-4
    Background: Small GTPases act as molecular switches that regulate various plant responses such as disease resistance, pollen tube growth, root hair development, cell wall patterning and hormone responses. Thus, to monitor their activation status within plant cells is believed to be the key step in understanding their roles.

    Results: We have established a plant version of a Förster resonance energy transfer (FRET) probe called Ras and interacting protein chimeric unit (Raichu) that can successfully monitor activation of the rice small GTPase OsRac1 during various defence responses in cells. Here, we describe the protocol for visualizing spatiotemporal activity of plant Rac/ROP GTPase in living plant cells, transfection of rice protoplasts with Raichu-OsRac1 and acquisition of FRET images.

    Conclusions: Our protocol should be adaptable for monitoring activation for other plant small GTPases and protein-protein interactions for other FRET sensors in various plant cells.

  20. A novel molecular and chromosomal lineage of the anthropophilic Simulium (Simulium) rufibasis subgroup (Diptera: Simuliidae) in Taiwan
    Low VL, Takaoka H, Adler PH, Tan TK, Weng FC, Chen CY, et al.
    Parasitol Res, 2018 Oct;117(10):3137-3143.
    PMID: 30006809 DOI: 10.1007/s00436-018-6011-7
    The Simulium rufibasis subgroup is one of three subgroups of the Simulium (Simulium) tuberosum species-group; it is characterized by a pair of clustered stout hairs on the ventral surface of female abdominal segment 7. A member of the S. rufibasis subgroup in Taiwan was investigated morphologically and genetically using the universal cytochrome c oxidase subunit I (COI) barcoding gene and polytene chromosomal banding pattern. The Taiwanese material is morphologically similar to S. rosliramlii Takaoka & Chen from Vietnam and represents the second species of the S. rufibasis subgroup known from Taiwan. It also represents a novel molecular lineage that is distinct from three other primary lineages identified as S. doipuiense, S. doipuiense/S. rufibasis, and S. weji previously reported from Thailand. The mitochondrial evidence for a distinct lineage in Taiwan is supported by chromosomal analysis, which revealed unique sex chromosomes. For nomenclatural stability, we associate the name S. arisanum Shiraki with the Taiwanese entity. Originally described from females from Taiwan, S. arisanum until now has remained an enigmatic species.
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