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  1. Lim CW, Cheng J, Tay ELT, Teo HY, Wong EPY, Yong VKY, et al.
    BMC Ophthalmol, 2018 Dec 10;18(1):315.
    PMID: 30526537 DOI: 10.1186/s12886-018-0976-y
    BACKGROUND: Despite the potential usefulness of optical coherence tomography angiography in retinal and optic disc conditions, the reliability of the imaging modality remains unclear. This study set out to measure the microvascular density of macula and optic disc by mean of optical coherence tomography angiography and report the repeatability of the vessel density measurements.

    METHODS: Cross sectional observational cohort study. Subjects with normal eyes were recruited. Two sets of optical coherence tomography angiography images of macula and optic nerve head were acquired during one visit. Novel in-house developed software was used to count the pixels in each images and to compute the microvessel density of the macula and optic disc. Data were analysed to determine the measurement repeatability.

    RESULTS: A total of 176 eyes from 88 consecutive normal subjects were recruited. For macular images, the mean vessel density at superficial retina, deep retina, outer retina and choriocapillaries segment was OD 0.113 and OS 0.111, OD 0.239 and OS 0.230, OD 0.179 and OS 0.164, OD 0.237 and OS 0.215 respectively. For optic disc images, mean vessel density at vitreoretinal interface, radial peripapillary capillary, superficial nerve head and disc segment at the level of choroid were OD 0.084 and OS 0.085, OD 0.140 and OS 0.138, OD 0.216 and OS 0.209, OD 0.227 and OS 0.236 respectively. The measurement repeatability tests showed that the coefficient of variation of macular scans, for right and left eyes, ranged from 6.4 to 31.1% and 5.3 to 59.4%. Likewise, the coefficient of variation of optic disc scans, for right and left eyes, ranged from 14.3 to 77.4% and 13.5 to 75.3%.

    CONCLUSIONS: Optical coherence tomography angiography is a useful modality to visualise the microvasculature plexus of macula and optic nerve head. The vessel density measurement of macular scan by mean of optical coherence tomography angiography demonstrated good repeatability. The optic disc scan, on the other hand, showed a higher coefficient of variation indicating a lower measurement repeatability than macular scan. Interpretation of optical coherence tomography angiography should take into account test-retest repeatability of the imaging system.

    TRIAL REGISTRATION: National Healthcare Group Domain Specific Review Board ( NHG DSRB ) Singapore. DSRB Reference: 2015/00301.

    Matched MeSH terms: Macula Lutea/blood supply*; Optic Disk/blood supply*
  2. Lee SH, Atiya N, Wang SM, Manikam R, Raju CS, Sekaran SD
    Intervirology, 2018;61(4):193-203.
    PMID: 30541013 DOI: 10.1159/000495180
    OBJECTIVE: Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier.

    METHOD: An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection.

    RESULTS: Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells.

    CONCLUSION: This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.

    Matched MeSH terms: Blood-Brain Barrier/physiology*; Blood-Brain Barrier/virology*
  3. Ooi MH, Ngu SJ, Chor YK, Li J, Landersdorfer CB, Nation RL
    Clin Infect Dis, 2019 11 13;69(11):1962-1968.
    PMID: 30722017 DOI: 10.1093/cid/ciz067
    BACKGROUND: Intravenous colistin is widely used to treat infections in pediatric patients. Unfortunately, there is a paucity of pharmacological information to guide the selection of dosage regimens. The daily dose recommended by the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) is the same body weight-based dose traditionally used in adults. The aim was to increase our understanding of the patient factors that influence the plasma concentration of colistin, and assess the likely appropriateness of the FDA and EMA dosage recommendations.

    METHODS: There were 5 patients, with a median age of 1.75 (range 0.1-6.25) years, a median weight of 10.7 (2.9-21.5) kg, and a median creatinine clearance of 179 (44-384) mL/min/1.73m2, who received intravenous infusions of colistimethate each 8 hours. The median daily dose was 0.21 (0.20-0.21) million international units/kg, equivalent to 6.8 (6.5-6.9) mg of colistin base activity per kg/day. Plasma concentrations of colistimethate and formed colistin were subjected to population pharmacokinetic modeling to explore the patient factors influencing the concentration of colistin.

    RESULTS: The median, average, steady-state plasma concentration of colistin (Css,avg) was 0.88 mg/L; individual values ranged widely (0.41-3.50 mg/L), even though all patients received the same body weight-based daily dose. Although the daily doses were ~33% above the upper limit of the FDA- and EMA-recommended dose range, only 2 patients achieved Css,avg ≥2mg/L; the remaining 3 patients had Css,avg <1mg/L. The pharmacokinetic covariate analysis revealed that clearances of colistimethate and colistin were related to creatinine clearance.

    CONCLUSIONS: The FDA and EMA dosage recommendations may be suboptimal for many pediatric patients. Renal functioning is an important determinant of dosing in these patients.

    Matched MeSH terms: Anti-Bacterial Agents/blood; Colistin/blood
  4. Willmott AGB, Hayes M, James CA, Dekerle J, Gibson OR, Maxwell NS
    Physiol Rep, 2018 Dec;6(24):e13936.
    PMID: 30575321 DOI: 10.14814/phy2.13936
    This experiment aimed to investigate the efficacy of twice-daily, nonconsecutive heat acclimation (TDHA) in comparison to once-daily heat acclimation (ODHA) and work matched once- or twice-daily temperate exercise (ODTEMP, TDTEMP) for inducing heat adaptations, improved exercise tolerance, and cytokine (immune) responses. Forty males, matched biophysically and for aerobic capacity, were assigned to ODHA, TDHA, ODTEMP, or TDTEMP. Participants completed a cycling-graded exercise test, heat acclimation state test, and a time to task failure (TTTF) at 80% peak power output in temperate (TTTFTEMP : 22°C/40% RH) and hot conditions (TTTFHOT : 38°C/20% RH), before and after 10-sessions (60 min of cycling at ~2 W·kg-1 ) in 45°C/20% RH (ODHA and TDHA) or 22°C/40% RH (ODTEMP or TDTEMP). Plasma IL-6, TNF-α, and cortisol were measured pre- and postsessions 1, 5, and 10. ODHA and TDHA induced equivalent heat adaptations (P  0.05) following ODHA (+14 ± 4%), TDHA (14 ± 8%), ODTEMP (9 ± 10%) or TDTEMP (8 ± 13%). Acute (P  0.05) increases were observed in IL-6, TNF-α, or cortisol during ODHA and TDHA, or ODTEMP and TDTEMP. Once- and twice-daily heat acclimation conferred similar magnitudes of heat adaptation and exercise tolerance improvements, without differentially altering immune function, thus nonconsecutive TDHA provides an effective, logistically flexible method of HA, benefitting individuals preparing for exercise-heat stress.
    Matched MeSH terms: Hydrocortisone/blood; Cytokines/blood*
  5. Alia SN, Joseph N, Philip N, Azhari NN, Garba B, Masri SN, et al.
    J Infect Public Health, 2018 11 27;12(2):263-269.
    PMID: 30502041 DOI: 10.1016/j.jiph.2018.10.137
    BACKGROUND: Leptospirosis is often misdiagnosed with several other tropical febrile illnesses in Malaysia due to similarities in clinical manifestations. Although treatment regimens could be started based on clinical judgments, early diagnosis has become paramount as a guide to chemotherapeutic interventions. Confirmed laboratory diagnosis through MAT or PCR is time consuming and usually available only in reference laboratories and not practical in healthcare settings. Rapid and easy to perform diagnostic tests are widely used in these settings as the point of care diagnosis. The present study was undertaken to compare the diagnostic performance of two IgM based immunodiagnostic assay kits for acute leptospirosis.

    METHODS: A total of 50 serum samples were collected from patients clinically suspected for acute leptospirosis on admission in the Hospital Serdang, from June 2016 to June 2017. All the samples were subjected to MAT, lipL32 PCR and the two rapid tests (Leptocheck-WB and ImmuneMed Leptospira IgM Duo Rapid test).

    RESULTS: Out of the 50 clinically suspected patients sampled, 19 were confirmed positive for leptospirosis. Six (12%) were confirmed by MAT and 13 (26%) by PCR. Similarly, of the 50 clinically suspected cases, 17 (34%) showed positivity for Leptocheck-WB and 7 (14%) for ImmuneMed Leptospira IgM Duo Rapid test. The overall sensitivity and specificity was 47.37% and 80.65% for Leptocheck-WB, and 21.05% and 90.32% for ImmuneMed Leptospira IgM Duo Rapid test. In another set of previously confirmed MAT positive samples (1:400-1:3600) obtained from a reference laboratory, Leptocheck-WB showed higher sensitivity (90.72%) than ImmuneMed Leptospira IgM Duo Rapid test (40.21%), and comparable specificity for ImmuneMed Leptospira IgM Duo Rapid test (88.89%) and Leptocheck-WB (82.86%).

    CONCLUSION: The sensitivity was higher for Leptocheck-WB and had a comparable specificity with ImmuneMed Leptospira IgM Duo Rapid test. Therefore, based on the present study, Leptocheck-WB is found to be a more sensitive rapid immunodiagnostic test for acute leptospirosis screening in hospital settings.

    Matched MeSH terms: Antibodies, Bacterial/blood*; Immunoglobulin M/blood*
  6. Travis RC, Perez-Cornago A, Appleby PN, Albanes D, Joshu CE, Lutsey PL, et al.
    Cancer Res, 2019 Jan 01;79(1):274-285.
    PMID: 30425058 DOI: 10.1158/0008-5472.CAN-18-2318
    Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; P trend < 0.001). However, this association varied by disease aggressiveness (P heterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.
    Matched MeSH terms: Prostatic Neoplasms/blood*; Vitamin D/blood
  7. Nanthasurasak P, See HH, Zhang M, Guijt RM, Breadmore MC
    Angew Chem Int Ed Engl, 2019 03 18;58(12):3790-3794.
    PMID: 30614157 DOI: 10.1002/anie.201812077
    An electrokinetic platform was developed for extracting small-molecule pharmaceuticals from a dried blood spot. Through the exclusion of liquid reagents and use of low field strength (6 V cm-1 ), the electroextraction of a drug from a dried blood spot, deposited on a polymer inclusion membrane (PIM), could be realised while in transit in the mail. In transit sample preparation provides a potential solution to in situ sample degradation and may accelerate the workflow upon arrival of a patient sample at the analytical facility. The electroextraction method was enabled through our discovery of the use of 15-20 μm thin PIMs as electrophoretic separation medium in absence of liquid reagents. Here, a PIM consisting of cellulose triacetate as polymer base, 2-nitrophenyl octyl ether as plasticizer and 1-ethyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide as carrier was used. The PIM, was packaged with two 12 V batteries to supply the separation voltage. A blood spot containing berberine chloride was deposited and dried before the applying the separation potential, allowing for the electroextraction while the packaged device was shipped in internal mail. Upon arrival in the analytical laboratory, the PIM was analysed using a fluorescence microscope with photon multiplier tube, quantifying the berberine extracted away from the sample matrix. This platform represents a new opportunity for processing clinical samples during transport to the laboratory, saving time and manual handling to accelerate the time to result.
    Matched MeSH terms: Berberine/blood*; Dried Blood Spot Testing
  8. Abdullah B, Lim EH, Mohamad H, Husain S, Aziz ME, Snidvongs K, et al.
    Surg Radiol Anat, 2019 May;41(5):543-550.
    PMID: 30542929 DOI: 10.1007/s00276-018-2157-3
    PURPOSE: The variations of the anterior ethmoidal artery (AEA) in different populations should be recognized by surgeons to prevent unwarranted complications during surgery. The aim of this study was to assess the anatomical variations of AEA in Asian population.

    METHODS: A cross-sectional study of 252 AEA identified by computed tomography (CT) of the paranasal sinuses. The multiplanar CT images were acquired from SOMATOM® Definition AS+ and reconstructed to axial, coronal and sagittal view at 1 mm slice thickness.

    RESULTS: 42.5% of AEA was within skull base (grade I), 20.2% at skull base (grade II) and 37.3% coursed freely below skull base (grade III). The prevalence of supraorbital ethmoid cell (SOEC) and suprabullar cell (SBC) was 29.8% and 48.0%. The position of AEA at skull base has significant association with SOEC (p 

    Matched MeSH terms: Ethmoid Bone/blood supply*; Skull Base/blood supply*
  9. Barden A, Phillips M, Hill LM, Fletcher EM, Mas E, Loh PS, et al.
    PMID: 30471772 DOI: 10.1016/j.plefa.2018.11.004
    INTRODUCTION: The synthetic glucocorticoid dexamethasone is a commonly administered antiemetic. It has immunosuppressive effects and may alter postoperative blood glucose concentrations. Dexamethasone can effect key enzymes involved in inflammation resolution that is an active process driven by specialised lipid mediators of inflammation resolution (SPM). The purpose of this study in healthy volunteers was to examine whether dexamethasone effects cell populations and synthesis of SPM that are critical for the resolution of inflammation.

    METHODS: Thirty-two healthy volunteers were randomly allocated to receive saline (Control) or dexamethasone 2 mg, 4 mg or 8 mg intravenously. Venous blood samples were collected at baseline before administration of treatment, and at 4 h, 24 h and one-week post-treatment. At each time point, measurements included blood glucose and macrophage migration inhibition factor (MMIF), full blood count including lymphocyte subsets, monocytes, neutrophils, eosinophils and basophils by flow cytometry, and plasma SPM using liquid chromatography tandem mass spectrometry. The effect of dexamethasone dose and time on all measures was analysed using linear mixed models.

    RESULTS: There was a dose-dependent increase in neutrophil count after dexamethasone that persisted for 24 h. In contrast, there was a dose-dependent reduction in counts of monocytes, lymphocytes, basophils and eosinophils 4 h after dexamethasone, followed by a rebound increase in cell counts at 24 h. Seven days after administration of dexamethasone, all cell counts were similar to baseline levels. MMIF concentration, glucose and natural killer cell counts were not significantly affected by dexamethasone. There was a significant gender effect on plasma SPM such that levels of 17-HDHA, RvD1, 17R-RvD1 and RvE2 in females were on average 14%-50% lower than males. In a linear mixed model that adjusted for neutrophil count, there was a significant interaction between the dose of dexamethasone and time, on plasma 17R-RvD1 such that plasma 17R-RvD1 fell in a dose-dependent manner until 4 h after administration of dexamethasone. There were no significant effects of dexamethasone on the other plasma SPM (18-HEPE, RvE2, 17-HDHA, RvD1, RvD2 and 14-HDHA) measured.

    DISCUSSION: This is the first study in healthy volunteers to demonstrate that commonly employed antiemetic doses of dexamethasone affect immune cell populations and plasma levels of 17R-RvD1 an SPM with anti-nociceptive properties. If similar changes occur in surgical patients, then this may have implications for acute infection risk in the post-operative period.

    Matched MeSH terms: Macrophage Migration-Inhibitory Factors/blood; Intramolecular Oxidoreductases/blood
  10. Dianita R, Jantan I
    Molecules, 2019 Apr 13;24(8).
    PMID: 31013947 DOI: 10.3390/molecules24081469
    Many Premna species have been used in traditional medicine to treat hypertension and cardiac insufficiency, and as a tonic for cardiac-related problems. Some have been reported to possess cardiovascular protective activity through several possible mechanisms, but not Premna foetida. In the present study, the methanol extract of P. foetida leaves (PFM) and its isolated compounds were evaluated for their ability to inhibit copper-mediated human low-density lipoprotein (LDL) oxidation and arachidonic acid (AA)- and adenosine diphosphate (ADP)-induced platelet aggregation. Six flavonoids, three triterpenoids, vanillic acid and stigmasterol were successfully isolated from PFM. Of the isolated compounds, quercetin was the most active against LDL oxidation (IC50 4.25 µM). The flavonols were more active than the flavones against LDL oxidation, suggesting that hydroxyl group at C-3 and the catechol moiety at B-ring may play important roles in protecting LDL from oxidation. Most tested flavonoids showed stronger inhibition towards AA-induced than the ADP-induced platelet aggregation with apigenin exhibiting the strongest effect (IC50 52.3 and 127.4 µM, respectively) while quercetin and kaempferol showed moderate activity. The results suggested that flavonoids, especially quercetin, apigenin and kaempferol were among the major constituents of P. foetida responsible for anti-LDL oxidation and anti-platelet aggregation.
    Matched MeSH terms: Blood Platelets/cytology; Blood Platelets/metabolism*
  11. Yii RSL, Lim J, Sothilingam S, Yeoh WS, Fadzli AN, Ong TA, et al.
    Asian J Surg, 2020 Jan;43(1):87-94.
    PMID: 30962017 DOI: 10.1016/j.asjsur.2019.02.014
    OBJECTIVES: To identify the associated factors determining prostate cancer detection using transrectal ultrasound (TRUS)-guided prostate biopsy, within a multi-ethnic Malaysian population with prostate specific antigen (PSA) between 4.0 and 10.0 ng/ml.

    METHODS: Study subjects included men with initial PSA between 4.0 and 10.0 ng/ml that have undergone 12-core TRUS-guided prostate biopsy between 2009 and 2016. The prostate cancer detection rate was calculated, while potential factors associated with detection were investigated via univariable and multivariable analysis.

    RESULTS: A total of 617 men from a multi-ethnic background encompassing Chinese (63.5%), Malay (23.1%) and Indian (13.3%) were studied. The overall cancer detection rate was 14.3% (88/617), which included cancers detected at biopsy 1 (first biopsy), biopsy 2 (second biopsy with previous negative biopsy) and biopsy ≥ 3 (third or more biopsies with prior negative biopsies). Indian men displayed higher detection rate (23.2%) and increased risk of prostate cancer development (OR 1.85, 95% CI 1.03-3.32, p 

    Matched MeSH terms: Biomarkers, Tumor/blood*; Prostate-Specific Antigen/blood*
  12. Benchoula K, Khatib A, Quzwain FMC, Che Mohamad CA, Wan Sulaiman WMA, Abdul Wahab R, et al.
    Molecules, 2019 Apr 17;24(8).
    PMID: 30999617 DOI: 10.3390/molecules24081506
    A standard protocol to develop type 1 diabetes in zebrafish is still uncertain due to unpredictable factors. In this study, an optimized protocol was developed and used to evaluate the anti-diabetic activity of Psychotria malayana leaf. The aims of this study were to develop a type 1 diabetic adult zebrafish model and to evaluate the anti-diabetic activity of the plant extract on the developed model. The ability of streptozotocin and alloxan at a different dose to elevate the blood glucose levels in zebrafish was evaluated. While the anti-diabetic activity of P. malayana aqueous extract was evaluated through analysis of blood glucose and LC-MS analysis fingerprinting. The results indicated that a single intraperitoneal injection of 300 mg/kg alloxan was the optimal dose to elevate the fasting blood glucose in zebrafish. Furthermore, the plant extract at 1, 2, and 3 g/kg significantly reduced blood glucose levels in the diabetic zebrafish. In addition, LC-MS-based fingerprinting indicated that 3 g/kg plant extract more effective than other doses. Phytosterols, sugar alcohols, sugar acid, free fatty acids, cyclitols, phenolics, and alkaloid were detected in the extract using GC-MS. In conclusion, P. malayana leaf aqueous extract showed anti-diabetic activity on the developed type 1 diabetic zebrafish model.
    Matched MeSH terms: Diabetes Mellitus, Experimental/blood*; Zebrafish/blood*
  13. Czamara D, Eraslan G, Page CM, Lahti J, Lahti-Pulkkinen M, Hämäläinen E, et al.
    Nat Commun, 2019 06 11;10(1):2548.
    PMID: 31186427 DOI: 10.1038/s41467-019-10461-0
    Epigenetic processes, including DNA methylation (DNAm), are among the mechanisms allowing integration of genetic and environmental factors to shape cellular function. While many studies have investigated either environmental or genetic contributions to DNAm, few have assessed their integrated effects. Here we examine the relative contributions of prenatal environmental factors and genotype on DNA methylation in neonatal blood at variably methylated regions (VMRs) in 4 independent cohorts (overall n = 2365). We use Akaike's information criterion to test which factors best explain variability of methylation in the cohort-specific VMRs: several prenatal environmental factors (E), genotypes in cis (G), or their additive (G + E) or interaction (GxE) effects. Genetic and environmental factors in combination best explain DNAm at the majority of VMRs. The CpGs best explained by either G, G + E or GxE are functionally distinct. The enrichment of genetic variants from GxE models in GWAS for complex disorders supports their importance for disease risk.
    Matched MeSH terms: DNA/blood*; Fetal Blood
  14. Yee YC, Hashim R, Mohd Yahya AR, Bustami Y
    Sensors (Basel), 2019 May 31;19(11).
    PMID: 31159318 DOI: 10.3390/s19112511
    Glucose oxidase (EC 1.1.3.4) sensors that have been developed and widely used for glucose monitoring have generally relied on electrochemical principle. In this study, the potential use of colorimetric method for glucose detection utilizing glucose oxidase-magnetic cellulose nanocrystals (CNCs) is explored. Magnetic cellulose nanocrystals (magnetic CNCs) were fabricated using iron oxide nanoparticles (IONPs) and cellulose nanocrystals (CNCs) via electrostatic self-assembly technique. Glucose oxidase was successfully immobilized on magnetic CNCs using carbodiimide-coupling reaction. About 33% of GOx was successfully attached on magnetic CNCs, and the affinity of GOx-magnetic CNCs to glucose molecules was slightly higher than free enzymes. Furthermore, immobilization does not affect the specificity of GOx-magnetic CNCs towards glucose and can detect glucose from 0.25 mM to 2.5 mM. Apart from that, GOx-magnetic CNCs stored at 4 °C for 4 weeks retained 70% of its initial activity and can be recycled for at least ten consecutive cycles.
    Matched MeSH terms: Blood Glucose/analysis; Blood Glucose Self-Monitoring
  15. Karupaiah T, Chuah KA, Chinna K, Pressman P, Clemens RA, Hayes AW, et al.
    Sci Rep, 2019 09 20;9(1):13666.
    PMID: 31541144 DOI: 10.1038/s41598-019-49911-6
    We conducted this cross-sectional population study with a healthy multi-ethnic urban population (n = 577) in Malaysia, combining nutritional assessments with cardiometabolic biomarkers defined by lipid, atherogenic lipoproteins, inflammation and insulin resistance. We found diametrically opposing associations of carbohydrate (246·6 ± 57·7 g, 54·3 ± 6·5%-TEI) and fat (total = 64·5 ± 19·8 g, 31·6 ± 5·5%-TEI; saturated fat = 14·1 ± 2·7%-TEI) intakes as regards waist circumference, HDL-C, blood pressure, glucose, insulin and HOMA2-IR as well as the large-LDL and large-HDL lipoprotein particles. Diets were then differentiated into either low fat (LF, <30% TEI or <50 g) or high fat (HF, >35% TEI or >70 g) and low carbohydrate (LC, <210 g) or high carbohydrate (HC, >285 g) which yielded LFLC, LFHC, HFLC and HFHC groupings. Cardiometabolic biomarkers were not significantly different (P > 0.05) between LFLC and HFLC groups. LFLC had significantly higher large-LDL particle concentrations compared to HFHC. HOMA-IR2 was significantly higher with HFHC (1·91 ± 1·85, P 1.7 in the HFHC group was 2.43 (95% CI: 1·03, 5·72) times more compared to LFLC while odds of having large-LDL <450 nmol/L in the HFHC group was 1.91 (95% CI: 1·06, 3·44) more compared to latter group. Our data suggests that a HFHC dietary combination in Malaysian adults is associated with significant impact on lipoprotein particles and insulin resistance.
    Matched MeSH terms: Lipoproteins/blood*; Biomarkers/blood*
  16. Yunus MH, Arifin N, Balachandra D, Anuar NS, Noordin R
    Am J Trop Med Hyg, 2019 08;101(2):432-435.
    PMID: 31218996 DOI: 10.4269/ajtmh.19-0053
    The conventional method of detecting Strongyloides stercoralis in fecal samples has poor diagnostic sensitivity. Detection of Strongyloides-specific antibodies increases the sensitivity; however, most tests are ELISAs that use parasite extract which may cross-react with the sera of other helminth infections. To improve the serological diagnosis of strongyloidiasis, this study aimed at developing a sensitive and specific lateral flow rapid dipstick test. Two recombinant proteins, recombinant NIE (rNIE) and recombinant Ss1a (rSs1a), were used in preparing the dipstick, with gold-conjugated antihuman IgG4 as detector reagent. In parallel, the corresponding ELISA was performed. Both assays demonstrated diagnostic sensitivity of 91.3% (21/23) when tested with serum samples of patients with Strongyloides infection, and 100% specificity with 82 sera of asymptomatic (healthy) and those with other parasitic infections. The ELISA and dipstick test results were positively correlated to each other (r = 0.6114, P = 0.0019). The developed lateral flow dipstick test may improve the serodiagnosis of strongyloidiasis and merit further validation studies.
    Matched MeSH terms: Antibodies, Helminth/blood*; Immunoglobulin G/blood
  17. Megahed AA, Hiew M, Grünberg W, Trefz FM, Constable PD
    J Dairy Sci, 2019 Aug;102(8):7435-7444.
    PMID: 31202658 DOI: 10.3168/jds.2018-16198
    A portable ion-selective electrode (ISE) meter (LAQUAtwin B-722; Horiba Instruments Inc., Irvine, CA) is available for measuring the sodium ion concentration ([Na]) in biological fluids. The objective of this study was to characterize the analytical performance of the ISE meter in measuring [Na] in whole-blood, plasma, milk, abomasal fluid, and urine samples from cattle. Method comparison studies were performed using whole-blood and plasma samples from 106 sick calves and 11 sick cows admitted to a veterinary teaching hospital, 80 milk and 206 urine samples from 16 lactating Holstein-Friesian cows with experimentally induced free water, electrolyte, and acid-base imbalances, and 67 abomasal fluid samples from 7 healthy male Holstein-Friesian calves fed fresh milk with or without an oral electrolyte solution. Deming regression and Bland-Altman plots were used to determine the accuracy of the meter against reference methods. The meter used in direct mode on undiluted samples measured whole-blood [Na] 9.7 mmol/L (7.3%) lower than a direct ISE reference method and plasma [Na] 16.7 mmol/L (12.7%) lower than an indirect ISE reference method. The meter run in direct mode measured milk [Na] 3.1 mmol/L lower and abomasal fluid [Na] 9.0% lower than indirect ISE reference methods. The meter run in indirect mode on diluted samples accurately measured urine [Na] compared with an indirect ISE reference method. We conclude that, after adjustment for the bias determined from Bland-Altman plots, the LAQUAtwin ISE meter provides a clinically useful and low-cost cow-side instrument for measuring [Na] in whole blood, plasma, milk, and abomasal fluid.
    Matched MeSH terms: Cattle Diseases/blood*; Sodium/blood
  18. Ang WJ, Zunaina E, Norfadzillah AJ, Raja-Norliza RO, Julieana M, Ab-Hamid SA, et al.
    PLoS One, 2019;14(8):e0221481.
    PMID: 31437234 DOI: 10.1371/journal.pone.0221481
    OBJECTIVE: Detection of vascular endothelial growth factor (VEGF) levels in ocular tissue may perhaps provide insight into the role of VEGF in the pathogenesis and progression of diabetic retinopathy (DR). The aim of this study was to evaluate the levels of VEGF in tears and serum amongst type 2 diabetes mellitus (DM) patients.

    METHODS: A comparative cross-sectional study was conducted between August 2016 and May 2018 involving type 2 DM patients with no DR, non-proliferative DR (NPDR), and proliferative DR (PDR). Tear samples were collected using no.41 Whatman filter paper (Schirmer strips) and 5 mL blood samples were drawn by venous puncture. VEGF levels in tears and serum were measured by enzyme-linked immunosorbent assay.

    RESULTS: A total of 88 type 2 DM patients (no DR: 30 patients, NPDR: 28 patients, PDR: 30 patients) were included in the study. Mean tear VEGF levels were significantly higher in the NPDR and PDR groups (114.4 SD 52.5 pg/mL and 150.8 SD 49.7 pg/mL, respectively) compared to the no DR group (40.4 SD 26.5 pg/mL, p < 0.001). There was no significant difference in the mean serum VEGF levels between the three groups. There was a fair correlation between serum and tear VEGF levels (p = 0.015, r = 0.263).

    CONCLUSION: VEGF levels in tears were significantly higher amongst diabetic patients with DR compared to those without DR and were significantly associated with the severity of DR. There was a fair correlation between serum and tear VEGF levels. Detection of VEGF in tears is a good non-invasive predictor test for the severity of DR. A large cohort study is needed for further evaluation.

    Matched MeSH terms: Diabetes Mellitus, Type 2/blood*; Vascular Endothelial Growth Factor A/blood*
  19. Kühn T, Stepien M, López-Nogueroles M, Damms-Machado A, Sookthai D, Johnson T, et al.
    J Natl Cancer Inst, 2020 May 01;112(5):516-524.
    PMID: 31435679 DOI: 10.1093/jnci/djz166
    BACKGROUND: Bile acids have been proposed to promote colon carcinogenesis. However, there are limited prospective data on circulating bile acid levels and colon cancer risk in humans.

    METHODS: Associations between prediagnostic plasma levels of 17 primary, secondary, and tertiary bile acid metabolites (conjugated and unconjugated) and colon cancer risk were evaluated in a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Bile acid levels were quantified by tandem mass spectrometry in samples from 569 incident colon cancer cases and 569 matched controls. Multivariable logistic regression analyses were used to estimate odds ratios (ORs) for colon cancer risk across quartiles of bile acid concentrations.

    RESULTS: Positive associations were observed between colon cancer risk and plasma levels of seven conjugated bile acid metabolites: the primary bile acids glycocholic acid (ORquartile 4 vs quartile 1= 2.22, 95% confidence interval [CI] = 1.52 to 3.26), taurocholic acid (OR = 1.78, 95% CI = 1.23 to 2.58), glycochenodeoxycholic acid (OR = 1.68, 95% CI = 1.13 to 2.48), taurochenodeoxycholic acid (OR = 1.62, 95% CI = 1.11 to 2.36), and glycohyocholic acid (OR = 1.65, 95% CI = 1.13 to 2.40), and the secondary bile acids glycodeoxycholic acid (OR = 1.68, 95% CI = 1.12 to 2.54) and taurodeoxycholic acid (OR = 1.54, 95% CI = 1.02 to 2.31). By contrast, unconjugated bile acids and tertiary bile acids were not associated with risk.

    CONCLUSIONS: This prospective study showed that prediagnostic levels of certain conjugated primary and secondary bile acids were positively associated with risk of colon cancer. Our findings support experimental data to suggest that a high bile acid load is colon cancer promotive.

    Matched MeSH terms: Bile Acids and Salts/blood*; Colonic Neoplasms/blood*
  20. Gunasekaran B, Shukor MY
    Methods Mol Biol, 2020;2089:245-250.
    PMID: 31773659 DOI: 10.1007/978-1-0716-0163-1_16
    The main strategy for lowering blood cholesterol levels is through the inhibition of the NADPH-dependent HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase). The enzyme catalyses the reduction of HMG-CoA to mevalonate and this process is inhibited by statins that form the bulk of the therapeutic agents to treat high cholesterol since the 1970s. Newer drugs that are safer than statins are constantly being developed. The inhibition of candidate drugs to HMG-CoA reductase remains the mainstay of drug development research. The determination of the enzyme activity is important for the correct assessment of potency of the enzyme as well as determining the inhibition of potential therapeutic agents from the plant and microbial extracts. Also, this chapter covers the use of the popular four-parameter logistics model that can yield accurate estimation of the IC50 values of therapeutic agents and their 95% confidence intervals.
    Matched MeSH terms: Cholesterol/blood; Hypercholesterolemia/blood
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