Browse publications by year: 2017

  1. Wan Mohamad WAF, Buckow R, Augustin M, McNaughton D
    Food Chem, 2017 Oct 15;233:197-203.
    PMID: 28530566 DOI: 10.1016/j.foodchem.2017.04.086
    Confocal Raman microscopy (CRM) was able to quantify the β-carotene concentration in oil droplets and determine the partitioning characteristics of β-carotene within the emulsion system in situ. The results were validated by a conventional method involving solvent extraction of β-carotene separately from the total emulsion as well as the aqueous phase separated by centrifugation, and quantification by absorption spectrophotometry. CRM also enabled the localization of β-carotene in an emulsion. From the Raman image, the β-carotene partitioning between the aqueous and oil phases of palm olein-in-water emulsions stabilized by whey protein isolate (WPI) was observed. Increasing the concentration of β-carotene in an emulsion (from 0.1 to 0.3g/kg emulsion) with a fixed gross composition (10% palm olein:2% WPI) decreased the concentration of β-carotene in the oil droplet. CRM is a powerful tool for in situ analyses of components in heterogeneous systems such as emulsions.
    MeSH terms: Whey Proteins; Emulsions; Water; Microscopy, Confocal*; beta Carotene
  2. Howson JMM, Zhao W, Barnes DR, Ho WK, Young R, Paul DS, et al.
    Nat Genet, 2017 Jul;49(7):1113-1119.
    PMID: 28530674 DOI: 10.1038/ng.3874
    Coronary artery disease (CAD) is a leading cause of morbidity and mortality worldwide. Although 58 genomic regions have been associated with CAD thus far, most of the heritability is unexplained, indicating that additional susceptibility loci await identification. An efficient discovery strategy may be larger-scale evaluation of promising associations suggested by genome-wide association studies (GWAS). Hence, we genotyped 56,309 participants using a targeted gene array derived from earlier GWAS results and performed meta-analysis of results with 194,427 participants previously genotyped, totaling 88,192 CAD cases and 162,544 controls. We identified 25 new SNP-CAD associations (P < 5 × 10-8, in fixed-effects meta-analysis) from 15 genomic regions, including SNPs in or near genes involved in cellular adhesion, leukocyte migration and atherosclerosis (PECAM1, rs1867624), coagulation and inflammation (PROCR, rs867186 (p.Ser219Gly)) and vascular smooth muscle cell differentiation (LMOD1, rs2820315). Correlation of these regions with cell-type-specific gene expression and plasma protein levels sheds light on potential disease mechanisms.
    MeSH terms: Arteries/pathology*; Cell Adhesion/genetics; Chemotaxis, Leukocyte/genetics; Coronary Artery Disease/genetics*; Coronary Artery Disease/pathology; Coronary Artery Disease/physiopathology; Energy Metabolism/genetics; Female; Genotype; Humans; Male; Muscle, Smooth, Vascular/pathology; Risk Factors; Genetic Predisposition to Disease; Polymorphism, Single Nucleotide; Quantitative Trait Loci; Histone Code; Atherosclerosis/genetics; Genome-Wide Association Study*
  3. Gaaz TS, Sulong AB, Kadhum AAH, Al-Amiery AA, Nassir MH, Jaaz AH
    Molecules, 2017 May 20;22(5).
    PMID: 28531126 DOI: 10.3390/molecules22050838
    Nanotubular clay minerals, composed of aluminosilicate naturally structured in layers known as halloysite nanotubes (HNTs), have a significant reinforcing impact on polymer matrixes. HNTs have broad applications in biomedical applications, the medicine sector, implant alloys with corrosion protection and manipulated transportation of medicines. In polymer engineering, different research studies utilize HNTs that exhibit a beneficial enhancement in the properties of polymer-based nanocomposites. The dispersion of HNTs is improved as a result of pre-treating HNTs with acids. The HNTs' percentage additive up to 7% shows the highest improvement of tensile strength. The degradation of the polymer can be also significantly improved by doping a low percentage of HNTs. Both the mechanical and thermal properties of polymers were remarkably improved when mixed with HNTs. The effects of HNTs on the mechanical and thermal properties of polymers, such as ultimate strength, elastic modulus, impact strength and thermal stability, are emphasized in this study.
    MeSH terms: Aluminum Silicates/chemistry*; Animals; Delayed-Action Preparations/chemistry*; Humans; Materials Testing; Polymers/chemistry*; Tensile Strength; Nanocomposites/ultrastructure; Nanocomposites/chemistry*; Elastic Modulus
  4. Zainol Abidin AS, Rahim RA, Md Arshad MK, Fatin Nabilah MF, Voon CH, Tang TH, et al.
    Sensors (Basel), 2017 May 22;17(5).
    PMID: 28531146 DOI: 10.3390/s17051180
    Anxiety is a psychological problem that often emerges during the normal course of human life. The detection of anxiety often involves a physical exam and a self-reporting questionnaire. However, these approaches have limitations, as the data might lack reliability and consistency upon application to the same population over time. Furthermore, there might be varying understanding and interpretations of the particular question by the participant, which necessitating the approach of using biomarker-based measurement for stress diagnosis. The most prominent biomarker related to stress, hormone cortisol, plays a key role in the fight-or-flight situation, alters the immune response, and suppresses the digestive and the reproductive systems. We have taken the endeavour to review the available aptamer-based biosensor (aptasensor) for cortisol detection. The potential point-of-care diagnostic strategies that could be harnessed for the aptasensing of cortisol were also envisaged.
    MeSH terms: Humans; Hydrocortisone; Surveys and Questionnaires; Stress, Psychological; Reproducibility of Results; Biosensing Techniques; Point-of-Care Systems*
  5. Sadri R, Hosseini M, Kazi SN, Bagheri S, Zubir N, Solangi KH, et al.
    J Colloid Interface Sci, 2017 Oct 15;504:115-123.
    PMID: 28531649 DOI: 10.1016/j.jcis.2017.03.051
    In this study, we propose an innovative, bio-based, environmentally friendly approach for the covalent functionalization of multi-walled carbon nanotubes using clove buds. This approach is innovative because we do not use toxic and hazardous acids which are typically used in common carbon nanomaterial functionalization procedures. The MWCNTs are functionalized in one pot using a free radical grafting reaction. The clove-functionalized MWCNTs (CMWCNTs) are then dispersed in distilled water (DI water), producing a highly stable CMWCNT aqueous suspension. The CMWCNTs are characterized using Raman spectroscopy, X-ray photoelectron spectroscopy and transmission electron microscopy. The electrostatic interactions between the CMWCNT colloidal particles in DI water are verified via zeta potential measurements. UV-vis spectroscopy is also used to examine the stability of the CMWCNTs in the base fluid. The thermo-physical properties of the CMWCNT nano-fluids are examined experimentally and indeed, this nano-fluid shows remarkably improved thermo-physical properties, indicating its superb potential for various thermal applications.
    MeSH terms: Free Radicals; Spectrum Analysis, Raman; Syzygium; Nanotubes, Carbon; Microscopy, Electron, Transmission; Static Electricity; Photoelectron Spectroscopy
  6. Azam MA, Alias FM, Tack LW, Seman RNAR, Taib MFM
    J Mol Graph Model, 2017 08;75:85-93.
    PMID: 28531817 DOI: 10.1016/j.jmgm.2017.05.003
    Carbon nanotubes (CNTs) have received enormous attention due to their fascinating properties to be used in various applications including electronics, sensing, energy storage and conversion. The first principles calculations within density functional theory (DFT) have been carried out in order to investigate the structural, electronic and optical properties of un-doped and doped CNT nanostructures. O2, CO2, and CH3OH have been chosen as gas molecules to study the adsorption properties based on zigzag (8,0) SWCNTs. The results demonstrate that the adsorption of O2, CO2, and CH3OH gas molecules on pristine, Si-doped and B-doped SWCNTs are either physisorption or chemisorption. Moreover, the electronic properties indicating SWCNT shows significant improvement toward gas adsorption which provides the impact of selecting the best gas sensor materials towards detecting gas molecule. Therefore, these pristine, Si-, and B-doped SWCNTs can be considered to be very good potential candidates for sensing application.
    MeSH terms: Adsorption; Boron/chemistry*; Electrons*; Gases/chemistry*; Models, Molecular; Molecular Conformation; Silicon/chemistry*; Thermodynamics; Nanotubes, Carbon/chemistry*
  7. Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al.
    J Am Coll Cardiol, 2017 Jul 04;70(1):1-25.
    PMID: 28527533 DOI: 10.1016/j.jacc.2017.04.052
    BACKGROUND: The burden of cardiovascular diseases (CVDs) remains unclear in many regions of the world.

    OBJECTIVES: The GBD (Global Burden of Disease) 2015 study integrated data on disease incidence, prevalence, and mortality to produce consistent, up-to-date estimates for cardiovascular burden.

    METHODS: CVD mortality was estimated from vital registration and verbal autopsy data. CVD prevalence was estimated using modeling software and data from health surveys, prospective cohorts, health system administrative data, and registries. Years lived with disability (YLD) were estimated by multiplying prevalence by disability weights. Years of life lost (YLL) were estimated by multiplying age-specific CVD deaths by a reference life expectancy. A sociodemographic index (SDI) was created for each location based on income per capita, educational attainment, and fertility.

    RESULTS: In 2015, there were an estimated 422.7 million cases of CVD (95% uncertainty interval: 415.53 to 427.87 million cases) and 17.92 million CVD deaths (95% uncertainty interval: 17.59 to 18.28 million CVD deaths). Declines in the age-standardized CVD death rate occurred between 1990 and 2015 in all high-income and some middle-income countries. Ischemic heart disease was the leading cause of CVD health lost globally, as well as in each world region, followed by stroke. As SDI increased beyond 0.25, the highest CVD mortality shifted from women to men. CVD mortality decreased sharply for both sexes in countries with an SDI >0.75.

    CONCLUSIONS: CVDs remain a major cause of health loss for all regions of the world. Sociodemographic change over the past 25 years has been associated with dramatic declines in CVD in regions with very high SDI, but only a gradual decrease or no change in most regions. Future updates of the GBD study can be used to guide policymakers who are focused on reducing the overall burden of noncommunicable disease and achieving specific global health targets for CVD.

    MeSH terms: Adult; Aged; Cardiovascular Diseases/epidemiology*; Cause of Death/trends; Female; Humans; Life Expectancy/trends*; Male; Middle Aged; Morbidity/trends; Prospective Studies; Retrospective Studies; Risk Factors; Global Health; Prevalence; Survival Rate/trends; Sex Distribution; Risk Assessment/methods*; Young Adult
  8. Poniah P, Mohd Zain S, Abdul Razack AH, Kuppusamy S, Karuppayah S, Sian Eng H, et al.
    Urol Oncol, 2017 09;35(9):545.e1-545.e11.
    PMID: 28527622 DOI: 10.1016/j.urolonc.2017.04.017
    BACKGROUND: Two key issues in prostate cancer (PCa) that demand attention currently are the need for a more precise and minimally invasive screening test owing to the inaccuracy of prostate-specific antigen and differential diagnosis to distinguish advanced vs. indolent cancers. This continues to pose a tremendous challenge in diagnosis and prognosis of PCa and could potentially lead to overdiagnosis and overtreatment complications. Copy number variations (CNVs) in the human genome have been linked to various carcinomas including PCa. Detection of these variants may improve clinical treatment as well as an understanding of the pathobiology underlying this complex disease.

    METHODS: To this end, we undertook a pilot genome-wide CNV analysis approach in 36 subjects (18 patients with high-grade PCa and 18 controls that were matched by age and ethnicity) in search of more accurate biomarkers that could potentially explain susceptibility toward high-grade PCa. We conducted this study using the array comparative genomic hybridization technique. Array results were validated in 92 independent samples (46 high-grade PCa, 23 benign prostatic hyperplasia, and 23 healthy controls) using polymerase chain reaction-based copy number counting method.

    RESULTS: A total of 314 CNV regions were found to be unique to PCa subjects in this cohort (P<0.05). A log2 ratio-based copy number analysis revealed 5 putative rare or novel CNV loci or both associated with susceptibility to PCa. The CNV gain regions were 1q21.3, 15q15, 7p12.1, and a novel CNV in PCa 12q23.1, harboring ARNT, THBS1, SLC5A8, and DDC genes that are crucial in the p53 and cancer pathways. A CNV loss and deletion event was observed at 8p11.21, which contains the SFRP1 gene from the Wnt signaling pathway. Cross-comparison analysis with genes associated to PCa revealed significant CNVs involved in biological processes that elicit cancer pathogenesis via cytokine production and endothelial cell proliferation.

    CONCLUSION: In conclusion, we postulated that the CNVs identified in this study could provide an insight into the development of advanced PCa.

    MeSH terms: Aged; Aged, 80 and over; Humans; Male; Middle Aged; Prostatic Neoplasms/genetics*; Prostatic Neoplasms/pathology; Genetic Predisposition to Disease/genetics*; Genome-Wide Association Study/methods*; Genetic Loci/genetics*; DNA Copy Number Variations/genetics*
  9. Lee YK, Ng CJ
    Z Evid Fortbild Qual Gesundhwes, 2017 Jun;123-124:66-68.
    PMID: 28527637 DOI: 10.1016/j.zefq.2017.05.019
    Shared decision making (SDM) activities in Malaysia began around 2010. Although the concept is not widespread, there are opportunities to implement SDM in both the public and private healthcare sectors. Malaysia has a multicultural society and cultural components (such as language differences, medical paternalism, strong family involvement, religious beliefs and complementary medicine) influence medical decision making. In terms of policy, the Ministry of Health has increasingly mentioned patient-centered care as a component of healthcare delivery while the Malaysian Medical Council's guidelines on doctors' duties mentioned collaborative partnerships as a goal of doctor-patient relationships. Current research on SDM comprises baseline surveys of decisional role preferences, development and implementation of locally developed patient decision aids, and conducting of SDM training workshops. Most of this research is carried out by public research universities. In summary, the current state of SDM in Malaysia is still at its infancy. However, there are increasing recognition and efforts from the academic institutions and Ministry of Health to conduct research in SDM, develop patient decision support tools and initiate national discussion on patient involvement in decision making.
    MeSH terms: Decision Making*; Decision Support Techniques; Health Policy*; Humans; Malaysia; Patient Participation*; Patient-Centered Care
  10. Tenekecioglu E, Serruys PW, Onuma Y, Costa R, Chamié D, Sotomi Y, et al.
    JACC Cardiovasc Interv, 2017 06 12;10(11):1115-1130.
    PMID: 28527768 DOI: 10.1016/j.jcin.2017.03.015
    OBJECTIVES: The primary objective of this study was to evaluate the safety and effectiveness of the Mirage (Manli Cardiology, Singapore) bioresorbable microfiber sirolimus-eluting scaffold compared with the Absorb (Abbott Vascular, Santa Clara, California) bioresorbable vascular scaffold in the treatment of stenotic target lesions located in native coronary arteries, ranging from ≥2.25 to ≤4.0 mm in diameter. Secondary objectives were to establish the medium-term safety, effectiveness, and performance of the Mirage device.

    BACKGROUND: The current generation of bioresorbable scaffolds has several limitations, such as thick square struts with large footprints that preclude their deep embedment into the vessel wall, resulting in protrusion into the lumen with microdisturbance of flow. The Mirage sirolimus-eluting bioresorbable microfiber scaffold is designed to address these concerns.

    METHODS: In this prospective, single-blind trial, 60 patients were randomly allocated in a 1:1 ratio to treatment with a Mirage sirolimus-eluting bioresorbable microfiber scaffold or an Absorb bioresorbable vascular scaffold. The clinical endpoints were assessed at 30 days and at 6 and 12 months. In-device angiographic late loss at 12 months was quantified. Secondary optical coherence tomographic endpoints were assessed post-scaffold implantation at 6 and 12 months.

    RESULTS: Median angiographic post-procedural in-scaffold minimal luminal diameters of the Mirage and Absorb devices were 2.38 mm (interquartile range [IQR]: 2.06 to 2.62 mm) and 2.55 mm (IQR: 2.26 to 2.71 mm), respectively; the effect size (d) was -0.29. At 12 months, median angiographic in-scaffold minimal luminal diameters of the Mirage and Absorb devices were not statistically different (1.90 mm [IQR: 1.57 to 2.31 mm] vs. 2.29 mm [IQR: 1.74 to 2.51 mm], d = -0.36). At 12-month follow-up, median in-scaffold late luminal loss with the Mirage and Absorb devices was 0.37 mm (IQR: 0.08 to 0.72 mm) and 0.23 mm (IQR: 0.15 to 0.37 mm), respectively (d = 0.20). On optical coherence tomography, post-procedural diameter stenosis with the Mirage was 11.2 ± 7.1%, which increased to 27.4 ± 12.4% at 6 months and remained stable (31.8 ± 12.9%) at 1 year, whereas the post-procedural optical coherence tomographic diameter stenosis with the Absorb was 8.4 ± 6.6%, which increased to 16.6 ± 8.9% and remained stable (21.2 ± 9.9%) at 1-year follow-up (Mirage vs. Absorb: dpost-procedure = 0.41, d6 months = 1.00, d12 months = 0.92). Angiographic median in-scaffold diameter stenosis was significantly different between study groups at 12 months (28.6% [IQR: 21.0% to 40.7%] for the Mirage, 18.2% [IQR: 13.1% to 31.6%] for the Absorb, d = 0.39). Device- and patient-oriented composite endpoints were comparable between the 2 study groups.

    CONCLUSIONS: At 12 months, angiographic in-scaffold late loss was not statistically different between the Mirage and Absorb devices, although diameter stenosis on angiography and on optical coherence tomography was significantly higher with the Mirage than with the Absorb. The technique of implantation was suboptimal for both devices, and future trials should incorporate optical coherence tomographic guidance to allow optimal implantation and appropriate assessment of the new technology, considering the novel mechanical properties of the Mirage.

    MeSH terms: Cardiovascular Agents/administration & dosage*; Cardiovascular Agents/adverse effects; Female; Humans; Indonesia; Malaysia; Male; Middle Aged; Predictive Value of Tests; Prospective Studies; Prosthesis Design; Risk Factors; Time Factors; Single-Blind Method; Treatment Outcome; Coronary Angiography*; Coated Materials, Biocompatible*; Sirolimus/administration & dosage*; Sirolimus/adverse effects; Absorbable Implants*; Coronary Restenosis/etiology; Coronary Stenosis/therapy*; Tomography, Optical Coherence*; Percutaneous Coronary Intervention/adverse effects; Percutaneous Coronary Intervention/instrumentation*; Multimodal Imaging/methods*
  11. Hafid HS, Nor 'Aini AR, Mokhtar MN, Talib AT, Baharuddin AS, Umi Kalsom MS
    Waste Manag, 2017 Sep;67:95-105.
    PMID: 28527863 DOI: 10.1016/j.wasman.2017.05.017
    In Malaysia, the amount of food waste produced is estimated at approximately 70% of total municipal solid waste generated and characterised by high amount of carbohydrate polymers such as starch, cellulose, and sugars. Considering the beneficial organic fraction contained, its utilization as an alternative substrate specifically for bioethanol production has receiving more attention. However, the sustainable production of bioethanol from food waste is linked to the efficient pretreatment needed for higher production of fermentable sugar prior to fermentation. In this work, a modified sequential acid-enzymatic hydrolysis process has been developed to produce high concentration of fermentable sugars; glucose, sucrose, fructose and maltose. The process started with hydrothermal and dilute acid pretreatment by hydrochloric acid (HCl) and sulphuric acid (H2SO4) which aim to degrade larger molecules of polysaccharide before accessible for further steps of enzymatic hydrolysis by glucoamylase. A kinetic model is proposed to perform an optimal hydrolysis for obtaining high fermentable sugars. The results suggested that a significant increase in fermentable sugar production (2.04-folds) with conversion efficiency of 86.8% was observed via sequential acid-enzymatic pretreatment as compared to dilute acid pretreatment (∼42.4% conversion efficiency). The bioethanol production by Saccharomyces cerevisiae utilizing fermentable sugar obtained shows ethanol yield of 0.42g/g with conversion efficiency of 85.38% based on the theoretical yield was achieved. The finding indicates that food waste can be considered as a promising substrate for bioethanol production.
    MeSH terms: Ethanol; Carbohydrates*; Fermentation*; Food*; Hydrolysis; Malaysia; Refuse Disposal*; Biofuels*
  12. Abdullah N, Abdul Murad NA, Mohd Haniff EA, Syafruddin SE, Attia J, Oldmeadow C, et al.
    Public Health, 2017 Aug;149:31-38.
    PMID: 28528225 DOI: 10.1016/j.puhe.2017.04.003
    OBJECTIVE: Malaysia has a high and rising prevalence of type 2 diabetes (T2D). While environmental (non-genetic) risk factors for the disease are well established, the role of genetic variations and gene-environment interactions remain understudied in this population. This study aimed to estimate the relative contributions of environmental and genetic risk factors to T2D in Malaysia and also to assess evidence for gene-environment interactions that may explain additional risk variation.
    STUDY DESIGN: This was a case-control study including 1604 Malays, 1654 Chinese and 1728 Indians from the Malaysian Cohort Project.
    METHODS: The proportion of T2D risk variance explained by known genetic and environmental factors was assessed by fitting multivariable logistic regression models and evaluating McFadden's pseudo R(2) and the area under the receiver-operating characteristic curve (AUC). Models with and without the genetic risk score (GRS) were compared using the log likelihood ratio Chi-squared test and AUCs. Multiplicative interaction between genetic and environmental risk factors was assessed via logistic regression within and across ancestral groups. Interactions were assessed for the GRS and its 62 constituent variants.
    RESULTS: The models including environmental risk factors only had pseudo R(2) values of 16.5-28.3% and AUC of 0.75-0.83. Incorporating a genetic score aggregating 62 T2D-associated risk variants significantly increased the model fit (likelihood ratio P-value of 2.50 × 10(-4)-4.83 × 10(-12)) and increased the pseudo R(2) by about 1-2% and AUC by 1-3%. None of the gene-environment interactions reached significance after multiple testing adjustment, either for the GRS or individual variants. For individual variants, 33 out of 310 tested associations showed nominal statistical significance with 0.001 
    MeSH terms: Diabetes Mellitus, Type 2; Malaysia; Risk Factors; ROC Curve; Genetic Variation; Cohort Studies; Prevalence; Chi-Square Distribution; Logistic Models; Case-Control Studies; Area Under Curve; Gene-Environment Interaction
  13. Maidur SR, Patil PS, Ekbote A, Chia TS, Quah CK
    Spectrochim Acta A Mol Biomol Spectrosc, 2017 Sep 05;184:342-354.
    PMID: 28528255 DOI: 10.1016/j.saa.2017.05.015
    In the present work, the title chalcone, (2E)-3-(4-fluorophenyl)-1-(4-{[(1E)-(4-fluorophenyl) methylene]amino}phenyl)prop-2-en-1-one (abbreviated as FAMFC), was synthesized and structurally characterized by single-crystal X-ray diffraction. The compound is crystallized in the monoclinic system with non-centrosymmetric space group P21 and hence it satisfies the essential condition for materials to exhibit second-order nonlinear optical properties. The molecular structure was further confirmed by using FT-IR and 1H NMR spectroscopic techniques. The title crystal is transparent in the Vis-NIR region and has a direct band gap. The third-order nonlinear optical properties were investigated in solution (0.01M) by Z-scan technique using a continuous wave (CW) DPSS laser at the wavelength of 532nm. The title chalcone exhibited significant two-photon absorption (β=35.8×10-5cmW-1), negative nonlinear refraction (n2=-0.18×10-8cm2W-1) and optical limiting (OL threshold=2.73kJcm-2) under the CW regime. In support of the experimental results, a comprehensive theoretical study was carried out on the molecule of FAMFC using density functional theory (DFT). The optimized geometries and frontier molecular orbitals were calculated by employing B3LYP/6-31+G level of theory. The optimized molecular structure was confirmed computationally by IR vibrational and 1H NMR spectral analysis. The experimental UV-Vis-NIR spectrum was interpreted using computational chemistry under time-dependent DFT. The static and dynamic NLO properties such as dipole moments (μ), polarizability (α), and first hyperpolarizabilities (β) were computed by using finite field method. The obtained dynamic first hyperpolarizability β(-2ω;ω,ω) at input frequency ω=0.04282a.u. is predicted to be 161 times higher than urea standard. The electronic excitation energies and HOMO-LUMO band gap for FAMFC were also evaluated by DFT. The experimental and theoretical results are in good agreement, and the NLO study suggests that FAMFC molecule can be a potential candidate in the nonlinear optical applications.
    MeSH terms: Chalcone; Models, Theoretical; Radiography; Urea; Vibration; X-Ray Diffraction; Molecular Structure; Spectroscopy, Fourier Transform Infrared; Crystallography, X-Ray; Chalcones; Proton Magnetic Resonance Spectroscopy
  14. Othman AS, Marin-Mogollon C, Salman AM, Franke-Fayard BM, Janse CJ, Khan SM
    Expert Rev Vaccines, 2017 Jul;16(7):1-13.
    PMID: 28525963 DOI: 10.1080/14760584.2017.1333426
    INTRODUCTION: Transgenic malaria parasites expressing foreign genes, for example fluorescent and luminescent proteins, are used extensively to interrogate parasite biology and host-parasite interactions associated with malaria pathology. Increasingly transgenic parasites are also exploited to advance malaria vaccine development. Areas covered: We review how transgenic malaria parasites are used, in vitro and in vivo, to determine protective efficacy of different antigens and vaccination strategies and to determine immunological correlates of protection. We describe how chimeric rodent parasites expressing P. falciparum or P. vivax antigens are being used to directly evaluate and rank order human malaria vaccines before their advancement to clinical testing. In addition, we describe how transgenic human and rodent parasites are used to develop and evaluate live (genetically) attenuated vaccines. Expert commentary: Transgenic rodent and human malaria parasites are being used to both identify vaccine candidate antigens and to evaluate both sub-unit and whole organism vaccines before they are advanced into clinical testing. Transgenic parasites combined with in vivo pre-clinical testing models (e.g. mice) are used to evaluate vaccine safety, potency and the durability of protection as well as to uncover critical protective immune responses and to refine vaccination strategies.
    MeSH terms: Animals; Antigens, Protozoan/genetics; Antigens, Protozoan/immunology; Antigens, Protozoan/therapeutic use*; Gene Expression Regulation; Humans; Plasmodium falciparum/genetics; Plasmodium falciparum/immunology*; Plasmodium vivax/genetics; Plasmodium vivax/immunology*; Vaccination; Protozoan Proteins/genetics; Protozoan Proteins/immunology; Protozoan Proteins/therapeutic use*; Malaria, Falciparum/immunology; Malaria, Falciparum/parasitology; Malaria, Falciparum/prevention & control*; Malaria, Falciparum/transmission; Malaria, Vivax/immunology; Malaria, Vivax/parasitology; Malaria, Vivax/prevention & control*; Malaria, Vivax/transmission; Malaria Vaccines/genetics; Malaria Vaccines/immunology; Malaria Vaccines/therapeutic use*; Vaccines, DNA/genetics; Vaccines, DNA/immunology; Vaccines, DNA/therapeutic use; Drug Discovery/methods*; Immunogenicity, Vaccine
  15. Abbas K, Amin M, Hussain MA, Sher M, Bukhari SNA, Jantan I, et al.
    Int J Biol Macromol, 2017 Oct;103:441-450.
    PMID: 28526350 DOI: 10.1016/j.ijbiomac.2017.05.061
    This deals with fabrication of macromolecular prodrugs (MPDs) of salicylic acid (SA) and aspirin (ASP) based on a hydrophilic cellulose ether, hydroxyethyl cellulose (HEC). Degrees of substitution (DS) of SA and ASP per HEC repeating unit (HEC-RU) were achieved ranging from 0.60 to 2.18 and 0.53 to1.50, respectively. The amphiphilic HEC-SA conjugate 2 assembled into nanowire-like structures, while HEC-ASP conjugate 6 formed nanoparticles (diameter 300-00nm) at a water/DMSO interface. After oral administration in rabbit models, conjugates 2 and 6 showed plasma half-life of 6.96 and 7.01h with maximum plasma concentration (Cmax) of 15.27 and 23.01μg L-1, respectively, and each reached peak plasma concentration (tmax) at 4.0h. Immunomodulatory assays (interleukin 6 and tumor necrosis factor-α values) revealed that anti-inflammatory properties of SA and ASP were unaltered in conjugates. Swelling inhibition of 61 and 71% was observed for conjugates 2 and 6, respectively, in a carrageenan induced paw edema test. Cytotoxic profiling (MTT assay) showed that conjugates were safe for administration in the concentration range of 2-10mM up to 24h. Thermal analyses revealed that Tdm values of SA and ASP conjugates were increased by 99 and 154̊C, respectively, indicating extraordinary thermal stability imparted to drugs after MPD formation.
    MeSH terms: Animals; Anti-Inflammatory Agents, Non-Steroidal/metabolism; Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics; Anti-Inflammatory Agents, Non-Steroidal/pharmacology; Anti-Inflammatory Agents, Non-Steroidal/chemistry; Cell Line; Cellulose/analogs & derivatives*; Cellulose/chemistry; Drug Stability; Half-Life; Kinetics; Male; Prodrugs/metabolism; Rabbits; Salicylates/metabolism; Salicylates/pharmacokinetics; Salicylates/pharmacology*; Salicylates/chemistry*; Temperature; Tissue Distribution; Drug Design*; Cytokines/secretion; Hydrophobic and Hydrophilic Interactions
  16. Rokicki D, Pajdowska M, Trubicka J, Thong MK, Ciara E, Piekutowska-Abramczuk D, et al.
    Clin Chim Acta, 2017 Aug;471:95-100.
    PMID: 28526534 DOI: 10.1016/j.cca.2017.05.023
    The urea cycle disorder carbamoyl phosphate synthetase I deficiency is an important differential diagnosis in the encephalopathic neonate. This intoxication type inborn error of metabolism often leads to neonatal death or severe and irreversible damage of the central nervous system, even despite appropriate treatment. Timely diagnosis is crucial, but can be difficult on routine metabolite level. Here, we report ten neonates from eight families (finally) diagnosed with CPS1 deficiency at three tertiary metabolic centres. In seven of them the laboratory findings were dominated by significantly elevated urinary 3-methylglutaconic acid levels which complicated the diagnostic process. Our findings are both important for the differential diagnosis of patients with urea cycle disorders and also broaden the differential diagnosis of hyperammonemia associated with 3-methylglutaconic aciduria, which was earlier only reported in TMEM70 and SERAC1 defect.
    MeSH terms: Female; Glutarates/urine*; Humans; Infant, Newborn; Male; Mutation; Pedigree; Carbamoyl-Phosphate Synthase I Deficiency Disease/diagnosis; Carbamoyl-Phosphate Synthase I Deficiency Disease/genetics; Carbamoyl-Phosphate Synthase I Deficiency Disease/urine*
  17. Chin CF, Lai JY, Choong YS, Anthony AA, Ismail A, Lim TS
    Sci Rep, 2017 05 19;7(1):2176.
    PMID: 28526816 DOI: 10.1038/s41598-017-01987-8
    Hemolysin E (HlyE) is an immunogenic novel pore-forming toxin involved in the pathogenesis of typhoid fever. Thus, mapping of B-cell epitopes of Salmonella enterica serovar Typhi (S. Typhi) is critical to identify key immunogenic regions of HlyE. A random 20-mer peptide library was used for biopanning with enriched anti-HlyE polyclonal antibodies from typhoid patient sera. Bioinformatic tools were used to refine, analyze and map the enriched peptide sequences against the protein to identify the epitopes. The analysis identified both linear and conformational epitopes on the HlyE protein. The predicted linear GAAAGIVAG and conformational epitope PYSQESVLSADSQNQK were further validated against the pooled sera. The identified epitopes were then used to isolate epitope specific monoclonal antibodies by antibody phage display. Monoclonal scFv antibodies were enriched for both linear and conformational epitopes. Molecular docking was performed to elucidate the antigen-antibody interaction of the monoclonal antibodies against the epitopes on the HlyE monomer and oligomer structure. An in-depth view of the mechanistic and positional characteristics of the antibodies and epitope for HlyE was successfully accomplished by a combination of phage display and bioinformatic analysis. The predicted function and structure of the antibodies highlights the possibility of utilizing the antibodies as neutralizing agents for typhoid fever.
    MeSH terms: Antibodies, Bacterial/immunology; Antibodies, Bacterial/chemistry; Antibodies, Monoclonal/immunology; Antibodies, Monoclonal/therapeutic use; Antibodies, Monoclonal/chemistry; Cloning, Molecular; Enzyme-Linked Immunosorbent Assay; Hemolysin Proteins/genetics; Hemolysin Proteins/immunology*; Humans; Models, Molecular; Protein Conformation; Salmonella typhi/genetics; Salmonella typhi/immunology*; Structure-Activity Relationship; Typhoid Fever/drug therapy; Typhoid Fever/immunology*; Typhoid Fever/microbiology; Reproducibility of Results; Epitope Mapping; Epitopes, B-Lymphocyte/immunology*; Epitopes, B-Lymphocyte/chemistry; Peptide Library
  18. Kamangar S, Badruddin IA, Ameer Ahamad N, Soudagar MEM, Govindaraju K, Nik-Ghazali N, et al.
    Biomed Mater Eng, 2017;28(3):257-266.
    PMID: 28527189 DOI: 10.3233/BME-171672
    The current study investigates the effect of multi stenosis on the hemodynamic parameters such as wall pressure, velocity and wall shear stress in the realistic left coronary artery. Patients CT scan image data of normal and diseased left coronary artery was chosen for the reconstruction of 3D coronary artery models. The diseased 3D model of left coronary artery shows a narrowing of more than 70% and 80% of area stenosis (AS) at the left main stem (LMS) and left circumflex (LCX) respectively. The results show that the decrease in pressure was found downstream to the stenosis as compared to the coronary artery without stenosis. The maximum pressure drop was noted across the 80% AS at the left circumflex branch. The recirculation zone was also observed immediate to the stenosis and highest wall shear stress was found across the 80% area stenosis. Our analysis provides an insight into the distribution of wall shear stress and pressure drop, thus improving our understanding on the hemodynamics in realistic coronary artery.
    MeSH terms: Blood Flow Velocity; Coronary Circulation; Coronary Vessels/pathology; Coronary Vessels/physiology*; Hemodynamics; Humans; Models, Cardiovascular*; Coronary Stenosis/pathology*; Patient-Specific Modeling*
  19. Ang BH, Chen WS, Lee SWH
    Arch Gerontol Geriatr, 2017 Sep;72:32-38.
    PMID: 28527382 DOI: 10.1016/j.archger.2017.05.004
    PURPOSE OF THE STUDY: This study aims to estimate the burden of road traffic accidents and death among older adults.

    DESIGN AND METHODS: A systematic literature review was conducted on 10 electronic databases for articles describing Road Traffic Accident(RTA) mortality in older adults until September 2016. A random-effects meta-regression analyses was conducted to estimate the pooled rates of road traffic accidents and death.

    RESULTS: A total 5018 studies were identified and 23 studies were included. Most of the reported older adults were aged between 60 and 74 years, with majority being male gender and sustained minor trauma due to Motor-Vehicle Collision (MVC). The overall pooled mortality rate was 14% (95% Confidence Interval, CI: 11%, 16%), with higher mortality rates in studies conducted in North America (15%, 95% CI: 12%, 18%) and older adults admitted to trauma centers (17%, 95% CI: 14%, 21%). Secondary analysis showed that the very elderly adults (aged >75years) and pedestrians had higher odds of mortality death (Odds Ratio, OR: 2.05, 95% CI: 1.25, 3.38; OR: 2.08, 95% CI: 1.63, 2.66, respectively).

    IMPLICATION: A new comprehensive trauma management guidelines tailored to older adults should be established in low and middle-income countries where such guidelines are still lacking.

    MeSH terms: Accidents, Traffic/mortality; Accidents, Traffic/statistics & numerical data*; Adult; Aged; Female; Humans; Male; Middle Aged; Regression Analysis; Trauma Centers; Practice Guidelines as Topic
  20. Kumar H, Mishra G, Sharma AK, Gothwal A, Kesharwani P, Gupta U
    Pharm Nanotechnol, 2017;5(3):203-214.
    PMID: 28521670 DOI: 10.2174/2211738505666170515113936
    BACKGROUND: The convoluted pathophysiology of brain disorders along with penetration issue of drugs to brain represents major hurdle that requires some novel therapies. The blood-brain barrier (BBB) denotes a rigid barrier for delivery of therapeutics in vivo; to overcome this barrier, intranasal delivery is an excellent strategy to deliver the drug directly to brain via olfactory and trigeminal nerve pathways that originate as olfactory neuro-epithelium in the nasal cavity and terminate in brain.

    METHOD: Kind of therapeutics like low molecular weight drugs can be delivered to the CNS via this route. In this review, we have outlined the anatomy and physiological aspect of nasal mucosa, certain hurdles, various strategies including importance of muco-adhesive polymers to increase the drug delivery and possible clinical prospects that partly contribute in intranasal drug delivery.

    RESULTS: Exhaustive literature survey related to intranasal drug delivery system revealed the new strategy that circumvents the BBB, based on non-invasive concept for treating various CNS disorders. Numerous advantages like prompt effects, self-medication through wide-ranging devices, and the frequent as well protracted dosing are associated with this novel route.

    CONCLUSION: Recently few reports have proven that nasal to brain drug delivery system bypasses the BBB. This novel route is associated with targeting efficiency and less exposure of therapeutic substances to non-target site. Nevertheless, this route desires much more research into the safe transferring of therapeutics to the brain. Role of muco-adhesive polymer and surface modification with specific ligands are area of interest of researcher to explore more about this.

    MeSH terms: Administration, Intranasal; Animals; Blood-Brain Barrier/metabolism; Brain Diseases/drug therapy*; Dosage Forms; Pharmaceutical Preparations/administration & dosage*; Pharmaceutical Preparations/chemistry; Humans; Nasal Cavity/metabolism; Nasal Mucosa/innervation; Nasal Mucosa/metabolism; Olfactory Mucosa/metabolism; Trigeminal Nerve/metabolism; Drug Delivery Systems; Respiratory Mucosa/metabolism; Drug Liberation
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