Browse publications by year: 2018

  1. Gan CS, Wong JJ, Samransamruajkit R, Chuah SL, Chor YK, Qian S, et al.
    Pediatr Crit Care Med, 2018 10;19(10):e504-e513.
    PMID: 30036234 DOI: 10.1097/PCC.0000000000001667
    OBJECTIVES: Extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome are poorly described in the literature. We aimed to describe and compare the epidemiology, risk factors for mortality, and outcomes in extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome.

    DESIGN: This is a secondary analysis of a multicenter, retrospective, cohort study. Data on epidemiology, ventilation, therapies, and outcomes were collected and analyzed. Patients were classified into two mutually exclusive groups (extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome) based on etiologies. Primary outcome was PICU mortality. Cox proportional hazard regression was used to identify risk factors for mortality.

    SETTING: Ten multidisciplinary PICUs in Asia.

    PATIENTS: Mechanically ventilated children meeting the Pediatric Acute Lung Injury Consensus Conference criteria for pediatric acute respiratory distress syndrome between 2009 and 2015.

    INTERVENTIONS: None.

    MEASUREMENTS AND MAIN RESULTS: Forty-one of 307 patients (13.4%) and 266 of 307 patients (86.6%) were classified into extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome groups, respectively. The most common causes for extrapulmonary pediatric acute respiratory distress syndrome and pulmonary pediatric acute respiratory distress syndrome were sepsis (82.9%) and pneumonia (91.7%), respectively. Children with extrapulmonary pediatric acute respiratory distress syndrome were older, had higher admission severity scores, and had a greater proportion of organ dysfunction compared with pulmonary pediatric acute respiratory distress syndrome group. Patients in the extrapulmonary pediatric acute respiratory distress syndrome group had higher mortality (48.8% vs 24.8%; p = 0.002) and reduced ventilator-free days (median 2.0 d [interquartile range 0.0-18.0 d] vs 19.0 d [0.5-24.0 d]; p = 0.001) compared with the pulmonary pediatric acute respiratory distress syndrome group. After adjusting for site, severity of illness, comorbidities, multiple organ dysfunction, and severity of acute respiratory distress syndrome, extrapulmonary pediatric acute respiratory distress syndrome etiology was not associated with mortality (adjusted hazard ratio, 1.56 [95% CI, 0.90-2.71]).

    CONCLUSIONS: Patients with extrapulmonary pediatric acute respiratory distress syndrome were sicker and had poorer clinical outcomes. However, after adjusting for confounders, it was not an independent risk factor for mortality.

    MeSH terms: Child; Child, Preschool; Female; Humans; Infant; Male; Multiple Organ Failure/epidemiology; Pneumonia/epidemiology; Respiration, Artificial/statistics & numerical data; Respiratory Distress Syndrome, Adult/classification; Respiratory Distress Syndrome, Adult/etiology; Respiratory Distress Syndrome, Adult/mortality*; Retrospective Studies; Intensive Care Units, Pediatric/statistics & numerical data*; Comorbidity; Proportional Hazards Models; Hospital Mortality*; Risk Assessment; Sepsis/epidemiology; Organ Dysfunction Scores
  2. Batumalaie K, Khalili E, Mahat NA, Huyop F, Wahab RA
    Biochimie, 2018 Sep;152:198-210.
    PMID: 30036604 DOI: 10.1016/j.biochi.2018.07.011
    Spectroscopic and calorimetric methods were employed to assess the stability and the folding aspect of a novel recombinant alkaline-stable lipase KV1 from Acinetobacter haemolyticus under varying pH and temperature. Data on far ultraviolet-circular dichroism of recombinant lipase KV1 under two alkaline conditions (pH 8.0 and 12.0) at 40 °C reveal strong negative ellipticities at 208, 217, 222 nm, implying its secondary structure belonging to a α + β class with 47.3 and 39.0% ellipticity, respectively. Results demonstrate that lipase KV1 adopts its most stable conformation at pH 8.0 and 40 °C. Conversely, the protein assumes a random coil structure at pH 4.0 and 80 °C, evident from a strong negative peak at ∼ 200 nm. This blue shift suggests a general decline in enzyme activity in conjunction with the partially or fully unfolded state that invariably exposed more hydrophobic surfaces of the lipase protein. The maximum emission at ∼335 nm for pH 8.0 and 40 °C indicates the adoption of a favorable protein conformation with a high number of buried tryptophan residues, reducing solvent exposure. Appearance of an intense Amide I absorption band at pH 8.0 corroborates an intact secondary structure. A lower enthalpy value for pH 4.0 over pH 8.0 and 12.0 in the differential scanning calorimetric data corroborates the stability of the lipase at alkaline conditions, while a low Km (0.68 ± 0.03 mM) for tributyrin verifies the high affinity of lipase KV1 for the substrate. The data, herein offer useful insights into future structure-based tunable catalytic activity of lipase KV1.
    MeSH terms: Acinetobacter/enzymology*; Biophysics; Calorimetry, Differential Scanning; Fluorescence; Hydrogen-Ion Concentration*; Lipase/metabolism*; Lipase/chemistry; Recombinant Proteins/metabolism; Recombinant Proteins/chemistry; Spectrum Analysis/methods; Structure-Activity Relationship; Temperature*; Protein Folding; Hydrophobic and Hydrophilic Interactions
  3. Nourouzi MM, Chamani A, Shirani M, Malekpouri P, Chuah AL
    Bull Environ Contam Toxicol, 2018 Sep;101(3):320-325.
    PMID: 30030595 DOI: 10.1007/s00128-018-2401-x
    Environmental pollution of aquatic ecosystems leads to an interference in several fundamental biochemical and physiological functions. In this study the interference of Cd and Pb pollutions on the physiological growth and subsequently on the age determination was investigated. The hermit crab, Coenobita scaevola (C.s) was selected as a bioaccumulator in this study. The direct and indirect age determination methods were carried out using annual band counts and carapace length, respectively. The results showed that, there was very low correlation (R2  0.95). In addition, it was concluded that the environmental pollution had interaction with the growth physiology such as weight and length.
    MeSH terms: Animals; Cadmium/toxicity*; Environmental Monitoring/methods; Environmental Pollution; Lead/toxicity*; Water Pollutants, Chemical/toxicity*; Neural Networks (Computer)*; Anomura/drug effects*; Anomura/growth & development; Anomura/metabolism
  4. 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.

    MeSH terms: Adolescent; Adult; Aged; Cross-Sectional Studies; Female; Humans; Sleep Initiation and Maintenance Disorders/epidemiology; Sleep Initiation and Maintenance Disorders/psychology*; Male; Middle Aged; Surveys and Questionnaires; Young Adult; Type D Personality*
  5. Faust O, Shenfield A, Kareem M, San TR, Fujita H, Acharya UR
    Comput Biol Med, 2018 11 01;102:327-335.
    PMID: 30031535 DOI: 10.1016/j.compbiomed.2018.07.001
    Atrial Fibrillation (AF), either permanent or intermittent (paroxysnal AF), increases the risk of cardioembolic stroke. Accurate diagnosis of AF is obligatory for initiation of effective treatment to prevent stroke. Long term cardiac monitoring improves the likelihood of diagnosing paroxysmal AF. We used a deep learning system to detect AF beats in Heart Rate (HR) signals. The data was partitioned with a sliding window of 100 beats. The resulting signal blocks were directly fed into a deep Recurrent Neural Network (RNN) with Long Short-Term Memory (LSTM). The system was validated and tested with data from the MIT-BIH Atrial Fibrillation Database. It achieved 98.51% accuracy with 10-fold cross-validation (20 subjects) and 99.77% with blindfold validation (3 subjects). The proposed system structure is straight forward, because there is no need for information reduction through feature extraction. All the complexity resides in the deep learning system, which gets the entire information from a signal block. This setup leads to the robust performance for unknown data, as measured with the blind fold validation. The proposed Computer-Aided Diagnosis (CAD) system can be used for long-term monitoring of the human heart. To the best of our knowledge, the proposed system is the first to incorporate deep learning for AF beat detection.
    MeSH terms: Machine Learning; Atrial Fibrillation; Diagnosis, Computer-Assisted; Heart Rate; Humans; Memory, Short-Term; Probability; Stroke
  6. Narasimhan M, Pillay Y, García PJ, Allotey P, Gorna R, Welbourn A, et al.
    Lancet Glob Health, 2018 10;6(10):e1058-e1059.
    PMID: 30031731 DOI: 10.1016/S2214-109X(18)30316-4
    MeSH terms: Female; Financial Support*; Goals; Humans; HIV Infections/prevention & control*; Universal Coverage/organization & administration*; Reproductive Health Services/economics*; Reproductive Rights/economics*
  7. Lee YT, Tan YJ, Oon CE
    Eur J Pharmacol, 2018 Sep 05;834:188-196.
    PMID: 30031797 DOI: 10.1016/j.ejphar.2018.07.034
    Molecular targeted therapies are revolutionized therapeutics which interfere with specific molecules to block cancer growth, progression, and metastasis. Many molecular targeted therapies approved by the Food and Drug Administration (FDA), have demonstrated remarkable clinical success in the treatment of a myriad of cancer types including breast, leukemia, colorectal, lung, and ovarian cancers. This review provides an update on the different types of molecular targeted therapies used in the treatment of cancer, focusing on the fundamentals of molecular targeted therapy, its mode of action in cancer treatment, as well as its advantages and limitations.
    MeSH terms: Animals; Humans; Neoplasms/drug therapy*; Neoplasms/genetics; Neoplasms/immunology; Neoplasms/pathology; Genetic Therapy; Cancer Vaccines/immunology; Molecular Targeted Therapy/methods*; Tumor Microenvironment/drug effects
  8. Lim YC, Hoe VCW, Darus A, Bhoo-Pathy N
    Occup Environ Med, 2018 10;75(10):716-723.
    PMID: 30032104 DOI: 10.1136/oemed-2018-105104
    OBJECTIVES: Occupational factors, particularly night-shift work, are attracting growing interest as a possible determinant of metabolic syndrome (MetS). This study aimed to determine the association between night-shift work and MetS, and assess whether sleep quality is a mediating factor.

    METHODS: A cross-sectional study was conducted among Malaysian manufacturing workers, aged 40-65 years old. They completed a self-administered questionnaire on sociodemographics, lifestyle and family history, and the Pittsburgh Sleep Quality Index (PSQI) questionnaire. Waist circumference, blood pressure, fasting blood sugar, triglycerides and high-density lipoprotein levels were measured. Baron and Kenny's method, Sobel test and multiple mediation models with bootstrapping were used to determine whether the PSQI global score or its components mediated the association between night-shift work and MetS.

    RESULTS: Of the 494 participants, 177 (36%) worked night shift and 51% were men. The prevalence of MetS was 37%. Night-shift work was independently associated with a twofold increase in the risk of MetS (adjusted OR: 1.92, 95% CI 1.24 to 2.97). However, the association between night-shift work and MetS did not appear to be modified by sex. Night-shift workers also reported significantly poorer sleep quality, longer sleep latency, shorter sleep duration, sleep disturbances and daytime dysfunction. Robust mediation analysis nonetheless showed that neither PSQI global score nor its components mediated the association between night-shift work and MetS.

    CONCLUSION: Early screening and management of MetS and the development of programmes to improve sleep quality should be carried out among night-shift workers. Future research should investigate other modifiable mediators linking night-shift work and MetS.

    MeSH terms: Adult; Aged; Cross-Sectional Studies; Female; Humans; Sleep Initiation and Maintenance Disorders/physiopathology*; Life Style; Malaysia/epidemiology; Male; Middle Aged; Risk Factors; Sleep/physiology*; Socioeconomic Factors; Work Schedule Tolerance/physiology*; Prevalence; Metabolic Syndrome X/epidemiology; Metabolic Syndrome X/physiopathology*
  9. Abdul-Razak S, Ramli AS, Badlishah-Sham SF, Haniff J, EMPOWER-PAR Investigators
    BMC Fam Pract, 2018 07 19;19(1):119.
    PMID: 30025525 DOI: 10.1186/s12875-018-0807-5
    BACKGROUND: Majority of patients with chronic illnesses such as diabetes, receive care at primary care setting. Efforts have been made to restructure diabetes care in the Malaysian primary care setting in accordance with the Chronic Care Model (CCM). The Patient Assessment on Chronic Illness Care (PACIC) is a validated self-report tool to measure the extent to which patients with chronic illness receive care that aligns with the CCM. To date, no validated tool is available to evaluate healthcare delivery based on the CCM in the Malay language. Thus, the study aimed to translate the PACIC into the Malay language and validate the questionnaire among patients with diabetes in the Malaysian public primary care setting.

    METHODS: The English version of the PACIC questionnaire is a 20-item scale measuring five key components, which are patient activation, decision support, goal setting, problem solving and follow-up care. The PACIC underwent forward - backward translation and cross cultural adaptation process to produce the PACIC-Malay version (PACIC-M). Reliability was tested using internal consistencies and test-retest reliability analyses, while construct validity was tested using the exploratory factor analysis (EFA).

    RESULTS: The content of PACIC-M and the original version were conceptually equivalent. Overall, the internal consistency by Cronbach's α was .94 and the intra-class correlation coefficient was .93. One item was deleted (item 1) when the factor loading was

  10. Lim WY, Hss AS, Ng LM, John Jasudass SR, Sararaks S, Vengadasalam P, et al.
    BMC Fam Pract, 2018 07 19;19(1):120.
    PMID: 30025534 DOI: 10.1186/s12875-018-0808-4
    BACKGROUND: To evaluate the effectiveness of a structured prescription review and prescriber feedback program in reducing prescribing errors in government primary care clinics within an administrative region in Malaysia.

    METHODS: This was a three group, pragmatic, cluster randomised trial. In phase 1, we randomised 51 clinics to a full intervention group (prescription review and league tables plus authorised feedback letter), a partial intervention group (prescription review and league tables), and a control group (prescription review only). Prescribers in these clinics were the target of our intervention. Prescription reviews were performed by pharmacists; 20 handwritten prescriptions per prescriber were consecutively screened on a random day each month, and errors identified were recorded in a standardised data collection form. Prescribing performance feedback was conducted at the completion of each prescription review cycle. League tables benchmark prescribing errors across clinics and individual prescribers, while the authorised feedback letter detailed prescribing performance based on a rating scale. In phase 2, all clinics received the full intervention. Pharmacists were trained on data collection, and all data were audited by researchers as an implementation fidelity strategy. The primary outcome, percentage of prescriptions with at least one error, was displayed in p-charts to enable group comparison.

    RESULTS: A total of 32,200 prescriptions were reviewed. In the full intervention group, error reduction occurred gradually and was sustained throughout the 8-month study period. The process mean error rate of 40.7% (95% CI 27.4, 29.5%) in phase 1 reduced to 28.4% (95% CI 27.4, 29.5%) in phase 2. In the partial intervention group, error reduction was not well sustained and showed a seasonal pattern with larger process variability. The phase 1 error rate averaging 57.9% (95% CI 56.5, 59.3%) reduced to 44.8% (95% CI 43.3, 46.4%) in phase 2. There was no evidence of improvement in the control group, with phase 1 and phase 2 error rates averaging 41.1% (95% CI 39.6, 42.6%) and 39.3% (95% CI 37.8, 40.9%) respectively.

    CONCLUSIONS: The rate of prescribing errors in primary care settings is high, and routine prescriber feedback comprising league tables and a feedback letter can effectively reduce prescribing errors.

    TRIAL REGISTRATION: National Medical Research Register: NMRR-12-108-11,289 (5th March 2012).
    MeSH terms: Ambulatory Care; Feedback*; Humans; Malaysia; Medication Errors/prevention & control*; Practice Patterns, Physicians'*; Drug Prescriptions/standards; Primary Health Care*
  11. Hiew MSY, Cheng HP, Huang CJ, Chong KY, Cheong SK, Choo KB, et al.
    J Biomed Sci, 2018 Jul 19;25(1):57.
    PMID: 30025541 DOI: 10.1186/s12929-018-0461-1
    BACKGROUND: Induced pluripotency in cancer cells by ectopic expression of pluripotency-regulating factors may be used for disease modeling of cancers. MicroRNAs (miRNAs) are negative regulators of gene expression that play important role in reprogramming somatic cells. However, studies on the miRNA expression profile and the expression patterns of the mesenchymal-epithelial transition (MET)/epithelial-mesenchymal transition (EMT) genes in induced pluripotent cancer (iPC) cells are lacking.

    METHODS: iPC clones were generated from two colorectal cancer (CRC) cell lines by retroviral transduction of the Yamanaka factors. The iPC clones obtained were characterized by morphology, expression of pluripotency markers and the ability to undergo in vitro tri-lineage differentiation. Genome-wide miRNA profiles of the iPC cells were obtained by microarray analysis and bioinformatics interrogation. Gene expression was done by real-time RT-PCR and immuno-staining; MET/EMT protein levels were determined by western blot analysis.

    RESULTS: The CRC-iPC cells showed embryonic stem cell-like features and tri-lineage differentiation abilities. The spontaneously-differentiated post-iPC cells obtained were highly similar to the parental CRC cells. However, down-regulated pluripotency gene expression and failure to form teratoma indicated that the CRC-iPC cells had only attained partial pluripotency. The CRC-iPC cells shared similarities in the genome-wide miRNA expression profiles of both cancer and pluripotent embryonic stem cells. One hundred and two differentially-expressed miRNAs were identified in the CRC-iPC cells, which were predicted by bioinformatics analysis be closely involved in regulating cellular pluripotency and the expression of the MET/EMT genes, possibly via the phosphatidylinositol-3 kinases-protein kinase B (PI3K-Akt) and transforming growth factor beta (TGF-β) signaling pathways. Irregular and inconsistent expression patterns of the EMT vimentin and Snai1 and MET E-cadherin and occludin proteins were observed in the four CRC-iPC clones analyzed, which suggested an epithelial/mesenchymal hybrid phenotype in the partially reprogrammed CRC cells. MET/EMT gene expression was also generally reversed on re-differentiation, also suggesting epigenetic regulation.

    CONCLUSIONS: Our data support the elite model for cancer cell-reprogramming in which only a selected subset of cancer may be fully reprogrammed; partial cancer cell reprogramming may also elicit an epithelial-mesenchymal mixed phenotype, and highlight opportunities and challenges in cancer cell-reprogramming.

    MeSH terms: Cell Differentiation/genetics; Cell Movement/genetics; Humans; Neoplasm Proteins/genetics*; Neoplastic Stem Cells/pathology; Colorectal Neoplasms/genetics*; Colorectal Neoplasms/pathology; Gene Expression Regulation, Neoplastic; Cell Lineage/genetics; Phosphatidylinositol 3-Kinases/genetics; MicroRNAs/genetics; Cell Line, Tumor; Induced Pluripotent Stem Cells/metabolism; Induced Pluripotent Stem Cells/pathology; Epithelial-Mesenchymal Transition/genetics*; Cellular Reprogramming/genetics*
  12. Nna VU, Abu Bakar AB, Md Lazin MRML, Mohamed M
    Food Chem Toxicol, 2018 Oct;120:305-320.
    PMID: 30026088 DOI: 10.1016/j.fct.2018.07.028
    Diabetes mellitus is characterized by hyperglycemia which causes oxidative stress. Propolis has been reported to have antihyperglycemic and antioxidant potentials. The present study therefore examined the anti-hyperglycemic, antioxidant and anti-inflammatory activities of Malaysian propolis (MP) using streptozotocin-induced diabetic rats. Ethanol extract of MP showed in vitro antioxidant (DPPH, FRAP and H2O2 radical scavenging) and α-glucosidase inhibition activities. Male Sprague Dawley rats were either treated with distilled water (normal control and diabetic control), MP (300 mg/kg b. w.), metformin (Met) (300 mg/kg b. w.) or both. After four weeks, fasting blood glucose decreased, while body weight change and serum insulin level increased significantly in MP, Met and MP + Met treated diabetic groups compared to diabetic control (DC) group. Furthermore, pancreatic antioxidant enzymes, total antioxidant capacity, interleukin (IL)-10 and proliferating cell nuclear antigen increased, while malondialdehyde, nuclear factor-kappa B (p65), tumor necrosis factor alpha, IL-1β and cleaved caspase-3 decreased significantly in the treated diabetic groups compared to DC group. Histopathology of the pancreas showed increased islet area and number of beta cells in the treated groups, compared to DC group, with D + MP + Met group comparable to normal control. We conclude that MP has anti-hyperglycemic, antioxidant, anti-inflammatory and antiapoptotic potentials, and exhibits synergistic effect with metformin.
    MeSH terms: Ethanol; alpha-Glucosidases; Animals; Anti-Inflammatory Agents; Antioxidants; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Fasting; Hydrogen Peroxide; Hyperglycemia; Hypoglycemic Agents; Interleukins; Male; Malondialdehyde; Metformin; Plant Extracts; Propolis; Streptozocin; Tumor Necrosis Factor-alpha; Water; NF-kappa B; Rats, Sprague-Dawley; Oxidative Stress; Proliferating Cell Nuclear Antigen; Rats; Caspase 3; Insulins
  13. Miyazaki H, Otake J, Mitsuno H, Ozaki K, Kanzaki R, Chui-Ting Chieng A, et al.
    Insect Biochem. Mol. Biol., 2018 Oct;101:32-46.
    PMID: 30026095 DOI: 10.1016/j.ibmb.2018.07.002
    The Oriental fruit fly, Bactrocera dorsalis, is a highly destructive pest of various fruits. The reproductive and host-finding behaviors of this species are affected by several plant semiochemicals that are perceived through chemosensory receptors. However, the chemosensory mechanisms by which this perception occurs have not been fully elucidated. We conducted RNA sequencing analysis of the chemosensory organs of B. dorsalis to identify the genes coding for chemosensory receptors. We identified 60 olfactory receptors (ORs), 17 gustatory receptors and 23 ionotropic receptors-including their homologs and variants-from the transcriptome of male antennae and proboscises. We functionally analyzed ten ORs co-expressed with the obligatory co-receptor ORCO in Xenopus oocytes to identify their ligands. We tested 24 compounds including attractants for several Bactrocera species and volatiles from the host fruits of B. dorsalis. We found that BdorOR13a co-expressed with ORCO responded robustly to 1-octen-3-ol. BdorOR82a co-expressed with ORCO responded significantly to geranyl acetate, but responded weakly to farnesenes (a mixture of isomers) and linalyl acetate. These four compounds were subsequently subjected to behavioral bioassays. When each of the aforementioned compound was presented in combination with a sphere model as a visual cue to adult flies, 1-octen-3-ol, geranyl acetate, and farnesenes significantly enhanced landing behavior in mated females, but not in unmated females or males. These results suggest that the ORs characterized in the present study are involved in the perception of plant volatiles that affect host-finding behavior in B. dorsalis.
  14. Kho S, Barber BE, Johar E, Andries B, Poespoprodjo JR, Kenangalem E, et al.
    Blood, 2018 Sep 20;132(12):1332-1344.
    PMID: 30026183 DOI: 10.1182/blood-2018-05-849307
    Platelets are understood to assist host innate immune responses against infection, although direct evidence of this function in any human disease, including malaria, is unknown. Here we characterized platelet-erythrocyte interactions by microscopy and flow cytometry in patients with malaria naturally infected with Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, or Plasmodium knowlesi Blood samples from 376 participants were collected from malaria-endemic areas of Papua, Indonesia, and Sabah, Malaysia. Platelets were observed binding directly with and killing intraerythrocytic parasites of each of the Plasmodium species studied, particularly mature stages, and was greatest in P vivax patients. Platelets preferentially bound to the infected more than to the uninfected erythrocytes in the bloodstream. Analysis of intraerythrocytic parasites indicated the frequent occurrence of platelet-associated parasite killing, characterized by the intraerythrocytic accumulation of platelet factor-4 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick-end labeling of parasite nuclei (PF4+TUNEL+ parasites). These PF4+TUNEL+ parasites were not associated with measures of systemic platelet activation. Importantly, patient platelet counts, infected erythrocyte-platelet complexes, and platelet-associated parasite killing correlated inversely with patient parasite loads. These relationships, taken together with the frequency of platelet-associated parasite killing observed among the different patients and Plasmodium species, suggest that platelets may control the growth of between 5% and 60% of circulating parasites. Platelet-erythrocyte complexes made up a major proportion of the total platelet pool in patients with malaria and may therefore contribute considerably to malarial thrombocytopenia. Parasite killing was demonstrated to be platelet factor-4-mediated in P knowlesi culture. Collectively, our results indicate that platelets directly contribute to innate control of Plasmodium infection in human malaria.
    MeSH terms: Adult; Blood Platelets/metabolism; Blood Platelets/parasitology*; Blood Platelets/pathology; Erythrocytes/metabolism; Erythrocytes/parasitology*; Erythrocytes/pathology; Female; Host-Parasite Interactions*; Humans; Indonesia/epidemiology; Malaria/blood*; Malaria/epidemiology; Malaria/parasitology; Malaria/pathology; Malaysia/epidemiology; Male; Plasmodium/physiology*; Platelet Factor 4/metabolism; Platelet Activation*; Young Adult
  15. Khalik MZ, Hendriks K, Vermeulen JJ, Schilthuizen M
    Zookeys, 2018.
    PMID: 30026659 DOI: 10.3897/zookeys.773.24878
    The Bornean hydrocenids have so far been understudied compared to other non-pulmonate snails in this region. In the present study, we review a first group of minute land snail species belonging to the genus Georissa (Gastropoda, Hydrocenidae) from Malaysian Borneo. This group is restricted to the species with conspicuous scale-like sculpture on the shell. Based on materials from recent fieldwork, museums, and personal collections, Malaysian Borneo hydrocenids are more complex and diverse in shell characters than previously anticipated. Here, a molecular, conchological, and biogeographic study of this "scaly group" is presented. We recognise 13 species of which six are new to science, namely Georissa anyiensissp. n., Georissa muluensissp. n., Georissa bauensissp. n., Georissa silaburensissp. n., Georissa kinabatanganensissp. n., and Georissa sepulutensissp. n.
    MeSH terms: Animals; Borneo; Helix (Snails); Museums; Sculpture; Skin; Snails
  16. Angers-Loustau A, Petrillo M, Bengtsson-Palme J, Berendonk T, Blais B, Chan KG, et al.
    F1000Res, 2018;7.
    PMID: 30026930 DOI: 10.12688/f1000research.14509.2
    Next-Generation Sequencing (NGS) technologies are expected to play a crucial role in the surveillance of infectious diseases, with their unprecedented capabilities for the characterisation of genetic information underlying the virulence and antimicrobial resistance (AMR) properties of microorganisms.  In the implementation of any novel technology for regulatory purposes, important considerations such as harmonisation, validation and quality assurance need to be addressed.  NGS technologies pose unique challenges in these regards, in part due to their reliance on bioinformatics for the processing and proper interpretation of the data produced.  Well-designed benchmark resources are thus needed to evaluate, validate and ensure continued quality control over the bioinformatics component of the process.  This concept was explored as part of a workshop on "Next-generation sequencing technologies and antimicrobial resistance" held October 4-5 2017.   Challenges involved in the development of such a benchmark resource, with a specific focus on identifying the molecular determinants of AMR, were identified. For each of the challenges, sets of unsolved questions that will need to be tackled for them to be properly addressed were compiled. These take into consideration the requirement for monitoring of AMR bacteria in humans, animals, food and the environment, which is aligned with the principles of a "One Health" approach.
    MeSH terms: Anti-Bacterial Agents/pharmacology*; Computational Biology/methods*; Benchmarking; Drug Resistance, Bacterial/genetics*; High-Throughput Nucleotide Sequencing*
  17. Saleh Samer M, Ali TT, Abdullah H
    Oral Health Prev Dent, 2018 7 22;16(3):249-257.
    PMID: 30027164 DOI: 10.3290/j.ohpd.a40758
    PURPOSE: To investigate the clinical performance and clinical survival rate of lithium disilicate-based core ceramic (IPS e.max Press) utilised in single crowns and to the accompanying periodontal health status.

    MATERIALS AND METHODS: A total of 47 patients with 88 IPS e.max Press single crowns were examined at the Faculty of Dentistry, University of Malaya, using modified United States Public Health Service evaluation criteria (USPHS). These 88 crowned teeth included 19 vital and 69 nonvital teeth that were restored with different post and core materials. The periodontal status was compared using the plaque index (PI), gingival recession (GR), modified papillary bleeding index (MPBI) and probing pocket depth (PPD) between the crowned teeth and contralateral control (sound) teeth.

    RESULTS: About 96.6% of the crowns exhibited satisfactory clinical performance. The mean survival rate at three years was 97.7%, and 100% at two years with a low incidence of fractures. There were no staitistically significant differences in the mean gingival recession (p = 0.182) and mean plaque scores (p = 0.102) between crowned and control teeth. The crowned teeth had higher mean MPBI (p = 0.000) and PPD (p = 0.051) compared to the contralateral sound teeth. Periodontal response in relation to subgingival crown margins, was statistically significantly lower regarding pocket depths (p = 0.01) and bleeding on probing (p = 0.00).

    CONCLUSION: IPS e.max Press crowns exhibited satisfactory clinical performance with high survival rate. No dentinal sensitivity was recorded. Plaque retention and gingival recession were similar to contralateral control teeth. Poor periodontal health was related to the subgingival crown margins.

    MeSH terms: Adolescent; Adult; Crowns*; Dental Plaque Index; Dental Porcelain*; Female; Follow-Up Studies; Gingival Recession; Humans; Male; Middle Aged; Periodontal Index; Periodontal Pocket; Retrospective Studies; Young Adult
  18. Ahmad A, Nazar Z, Swaminathan D
    Oral Health Prev Dent, 2018 7 22;16(3):281-289.
    PMID: 30027167 DOI: 10.3290/j.ohpd.a40759
    PURPOSE: To investigate the association between plasma CRP levels and periodontal disease during pregnancy.

    MATERIALS AND METHODS: Fifty-six pregnant women attending the Antenatal Clinic, UMMC for their first antenatal check-up consented and were recruited for this study: 28 subjects with diseased periodontium (test group) and 28 subjects with healthy periodontium (control). The test group underwent nonsurgical periodontal therapy and the control group was given oral hygiene education. Periodontal parameters and CRP levels were evaluated at baseline and 6 weeks. Pregnancy outcome data were recorded from the Antenatal Clinic, UMMC.

    RESULTS: Plasma CRP levels in the test group were statistically significantly elevated compared to the control group (8.55 ± 5.28 mg/l vs 5.66 ± 2.91 mg/l). After nonsurgical periodontal therapy, a statistically significant reduction in the CRP level in the test group (2.06 mg/l) along with statistically significant improvement in periodontal status in both groups was observed. The mean birth weight for infants of both groups showed no statistically significant difference.

    CONCLUSIONS: Plasma CRP levels in pregnant women with diseased periodontium were statistically significantly reduced after nonsurgical periodontal therapy. However, no association between CRP levels and adverse pregnancy outcome was observed.

    MeSH terms: Adult; C-Reactive Protein/analysis*; Dental Polishing; Female; Humans; Malaysia/epidemiology; Periodontal Diseases/epidemiology; Periodontal Diseases/therapy*; Pregnancy/blood; Pregnancy Outcome*; Prospective Studies; Dental Scaling; Case-Control Studies; Root Planing
  19. Hung SKY, Hiew FL, Viswanathan S, Puvanarajah S
    J Peripher Nerv Syst, 2018 Sep;23(3):183-189.
    PMID: 30027593 DOI: 10.1111/jns.12282
    Intravenous immunoglobulin (IVIG), corticosteroids and therapeutic plasma exchange (TPE) are evidence-based conventional treatments for chronic inflammatory demyelinating polyneuropathy (CIDP). In many centres, unconventional treatments are frequently used as alternatives. We evaluated the outcome of conventional and unconventional therapies in 31 CIDP patients. Overall response rate with conventional first-line immunotherapies was 77% (20/26), comparable between IVIG and corticosteroids (80% vs 70%). Use of TPE was limited. Treatment response among typical and atypical CIDP were comparable (76 vs 80%). Non-responders were patients with progressive form of typical CIDP and DADS. Majority (21/26, 81%) of patients with persistent neurological deficits received maintenance therapy. Two subgroups of patients frequently treated with maintenance immunosuppressants were those with improving or stable disease following first-line treatment (12, 57%) and those with progressive form of CIDP (2, 10%). Primary indications for immunosuppressant use were corticosteroids-sparing and additional immunosuppression effects. Nine (64%) patients with improving or stable disease given azathioprine were taken off corticosteroids after a median duration of 14 months (range 12-108). Two (14%) eventually achieved cure or clinical remission without treatment. Maintenance IVIg was given to 6 (29%) relapsing CIDP patients; none of achieved cure or remission after similar median duration of treatment. Less potent immunosuppressant drugs (azathioprine, mycophenolate mofetil, and methotrexate) were frequently used, with moderate adverse effect profiles. In resource limited setting, unconventional treatments were commonly used among CIDP patients with different clinical course of progression. In most cases, careful risk-benefit re-assessment is required to justify its further use.
    MeSH terms: Adrenal Cortex Hormones/therapeutic use*; Adult; Aged; Female; Humans; Immunosuppressive Agents/therapeutic use*; Immunotherapy/methods*; Male; Middle Aged; Plasma Exchange/methods; Retrospective Studies; Immunoglobulins, Intravenous/therapeutic use*; Treatment Outcome; Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/therapy*
  20. Abdullah A, Ramly R, Mohammad Ridzwan MS, Sudirwan F, Abas A, Ahmad K, et al.
    J Fish Dis, 2018 Sep;41(9):1459-1462.
    PMID: 30027657 DOI: 10.1111/jfd.12843
    MeSH terms: Animals; Cyprinidae*; Fish Diseases/virology*; Malaysia; Orthomyxoviridae/isolation & purification*; Orthomyxoviridae Infections/veterinary; Tilapia
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