Browse publications by year: 2019

  1. Mandary MB, Masomian M, Poh CL
    Int J Mol Sci, 2019 Sep 19;20(18).
    PMID: 31546962 DOI: 10.3390/ijms20184657
    RNA viruses are known to replicate by low fidelity polymerases and have high mutation rates whereby the resulting virus population tends to exist as a distribution of mutants. In this review, we aim to explore how genetic events such as spontaneous mutations could alter the genomic organization of RNA viruses in such a way that they impact virus replications and plaque morphology. The phenomenon of quasispecies within a viral population is also discussed to reflect virulence and its implications for RNA viruses. An understanding of how such events occur will provide further evidence about whether there are molecular determinants for plaque morphology of RNA viruses or whether different plaque phenotypes arise due to the presence of quasispecies within a population. Ultimately this review gives an insight into whether the intrinsically high error rates due to the low fidelity of RNA polymerases is responsible for the variation in plaque morphology and diversity in virulence. This can be a useful tool in characterizing mechanisms that facilitate virus adaptation and evolution.
    MeSH terms: Animals; Humans; DNA-Directed RNA Polymerases/genetics*; Viral Proteins/genetics*; Virulence; Evolution, Molecular*
  2. Mohajerani A, Burnett L, Smith JV, Kurmus H, Milas J, Arulrajah A, et al.
    Materials (Basel), 2019 Sep 20;12(19).
    PMID: 31547011 DOI: 10.3390/ma12193052
    Nanoparticles are defined as ultrafine particles sized between 1 and 100 nanometres in diameter. In recent decades, there has been wide scientific research on the various uses of nanoparticles in construction, electronics, manufacturing, cosmetics, and medicine. The advantages of using nanoparticles in construction are immense, promising extraordinary physical and chemical properties for modified construction materials. Among the many different types of nanoparticles, titanium dioxide, carbon nanotubes, silica, copper, clay, and aluminium oxide are the most widely used nanoparticles in the construction sector. The promise of nanoparticles as observed in construction is reflected in other adoptive industries, driving the growth in demand and production quantity at an exorbitant rate. The objective of this study was to analyse the use of nanoparticles within the construction industry to exemplify the benefits of nanoparticle applications and to address the short-term and long-term effects of nanoparticles on the environment and human health within the microcosm of industry so that the findings may be generalised. The benefits of nanoparticle utilisation are demonstrated through specific applications in common materials, particularly in normal concrete, asphalt concrete, bricks, timber, and steel. In addition, the paper addresses the potential benefits and safety barriers for using nanomaterials, with consideration given to key areas of knowledge associated with exposure to nanoparticles that may have implications for health and environmental safety. The field of nanotechnology is considered rather young compared to established industries, thus limiting the time for research and risk analysis. Nevertheless, it is pertinent that research and regulation precede the widespread adoption of potentially harmful particles to mitigate undue risk.
    MeSH terms: Aluminum Silicates; Construction Materials; Copper; Cosmetics; Humans; Hydrocarbons; Silicon Dioxide; Steel; Time; Titanium; Nanotechnology; Nanotubes, Carbon; Nanostructures; Nanoparticles; Construction Industry
  3. Kavi Rajan R, Hussein MZ, Fakurazi S, Yusoff K, Masarudin MJ
    Int J Mol Sci, 2019 Sep 20;20(19).
    PMID: 31547100 DOI: 10.3390/ijms20194667
    Naturally existing Chlorogenic acid (CGA) is an antioxidant-rich compound reported to act a chemopreventive agent by scavenging free radicals and suppressing cancer-causing mechanisms. Conversely, the compound's poor thermal and pH (neutral and basic) stability, poor solubility, and low cellular permeability have been a huge hindrance for it to exhibit its efficacy as a nutraceutical compound. Supposedly, encapsulation of CGA in chitosan nanoparticles (CNP), nano-sized colloidal delivery vector, could possibly assist in enhancing its antioxidant properties, in vitro cellular accumulation, and increase chemopreventive efficacy at a lower concentration. Hence, in this study, a stable, monodispersed, non-toxic CNP synthesized via ionic gelation method at an optimum parameter (600 µL of 0.5 mg/mL of chitosan and 200 µL of 0.7 mg/mL of tripolyphosphate), denoted as CNP°, was used to encapsulate CGA. Sequence of physicochemical analyses and morphological studies were performed to discern the successful formation of the CNP°-CGA hybrid. Antioxidant property (studied via DPPH (1,1-diphenyl-2-picrylhydrazyl) assay), in vitro antiproliferative activity of CNP°-CGA, and in vitro accumulation of fluorescently labeled (FITC) CNP°-CGA in cancer cells were evaluated. Findings revealed that successful formation of CNP°-CGA hybrid was reveled through an increase in particle size 134.44 ± 18.29 nm (polydispersity index (PDI) 0.29 ± 0.03) as compared to empty CNP°, 80.89 ± 5.16 nm (PDI 0.26 ± 0.01) with a maximal of 12.04 μM CGA loaded per unit weight of CNP° using 20 µM of CGA. This result correlated with Fourier-Transform Infrared (FTIR) spectroscopic analysis, transmission Electron Microscopy (TEM) and field emission scanning (FESEM) electron microscopy, and ImageJ evaluation. The scavenging activity of CNP°-CGA (IC50 5.2 ± 0.10 µM) were conserved and slightly higher than CNP° (IC50 6.4±0.78 µM). An enhanced cellular accumulation of fluorescently labeled CNP°-CGA in the human renal cancer cells (786-O) as early as 30 min and increased time-dependently were observed through fluorescent microscopic visualization and flow cytometric assessment. A significant concentration-dependent antiproliferation activity of encapsulated CGA was achieved at IC50 of 16.20 µM as compared to CGA itself (unable to determine from the cell proliferative assay), implying that the competent delivery vector, chitosan nanoparticle, is able to enhance the intracellular accumulation, antiproliferative activity, and antioxidant properties of CGA at lower concentration as compared to CGA alone.
    MeSH terms: Biphenyl Compounds; Chlorogenic Acid; Free Radicals; Humans; Kidney Neoplasms; Microscopy, Electron, Scanning; Particle Size; Permeability; Polyphosphates; Solubility; Fluorescein-5-isothiocyanate; Spectroscopy, Fourier Transform Infrared; Dietary Supplements; Inhibitory Concentration 50; Microscopy, Electron, Transmission; Chitosan; Nanoparticles
  4. Mawazi SM, Al-Mahmood SMA, Chatterjee B, Hadi HA, Doolaanea AA
    Pharmaceutics, 2019 Sep 20;11(10).
    PMID: 31547112 DOI: 10.3390/pharmaceutics11100488
    This study aimed to develop a carbamazepine (CBZ) sustained release formulation suitable for pediatric use with a lower risk of precipitation. The CBZ was first prepared as sustained release microparticles, and then the microparticles were embedded in alginate beads, and finally, the beads were suspended in a gel vehicle. The microparticles were prepared by a solvent evaporation method utilizing ethyl cellulose as a sustained release polymer and were evaluated for particle size, encapsulation efficiency, and release profile. The beads were fabricated by the dropwise addition of sodium alginate in calcium chloride solution and characterized for size, shape, and release properties. The gel was prepared using iota carrageenan as the gelling agent and evaluated for appearance, syneresis, drug content uniformity, rheology, release profile, and stability. The microparticles exhibited a particle size of 135.01 ± 0.61 µm with a monodisperse distribution and an encapsulation efficiency of 83.89 ± 3.98%. The beads were monodispersed with an average size of 1.4 ± 0.05 mm and a sphericity factor of less than 0.05. The gel was prepared using a 1:1 ratio (gel vehicle to beads) and exhibited no syneresis, good homogeneity, and good shear-thinning properties. The release profile from the beads and from the gel was not significantly affected, maintaining similarity to the tablet form. The gel properties were maintained for one month real time stability, but the accelerated stability showed reduced viscosity and pH with time. In conclusion, CBZ in a gel sustained release dosage form combines the advantages of the suspension form in terms of dosing flexibility, and the advantages of the tablet form in regards to the sustained release profile. This dosage form should be further investigated in vivo in animal models before being considered in clinical trials.
    MeSH terms: Alginates; Animals; Calcium Chloride; Carbamazepine; Carrageenan; Cellulose; Child; Delayed-Action Preparations; Hexuronic Acids; Humans; Particle Size; Polymers; Rheology; Solvents; Tablets; Viscosity; Glucuronic Acid; Models, Animal
  5. Lal LPJ, Ramesh S, Parasuraman S, Natarajan E, Elamvazuthi I
    Materials (Basel), 2019 Sep 20;12(19).
    PMID: 31547117 DOI: 10.3390/ma12193057
    Nanosilica particles were utilized as secondary reinforcement to enhance the strength of the epoxy resin matrix. Thin glass fibre reinforced polymer (GFRP) composite laminates of 3 ± 0.25 mm were developed with E-Glass mats of 610 GSM and LY556 epoxy resin. Nanosilica fillers were mixed with epoxy resin in the order of 0.25, 0.5, 0.75 and 1 wt% through mechanical stirring followed by an ultrasonication method. Thereafter, the damage was induced on toughened laminates through low-velocity drop weight impact tests and the induced damage was assessed through an image analysis tool. The residual compression strength of the impacted laminates was assessed through compression after impact (CAI) experiments. Laminates with nanosilica as secondary reinforcement exhibited enhanced compression strength, stiffness, and damage suppression. Results of Fourier-transform infrared spectroscopy revealed that physical toughening mechanisms enhanced the strength of the nanoparticle-reinforced composite. Failure analysis of the damaged area through scanning electron microscopy (SEM) evidenced the presence of key toughening mechanisms like damage containment through micro-cracks, enhanced fiber-matrix bonding, and load transfer.
    MeSH terms: Epoxy Resins; Glass; Microscopy, Electron, Scanning; Polymers; Spectroscopy, Fourier Transform Infrared; Compressive Strength; Nanoparticles
  6. Loh CY, Chai JY, Tang TF, Wong WF, Sethi G, Shanmugam MK, et al.
    Cells, 2019 Sep 20;8(10).
    PMID: 31547193 DOI: 10.3390/cells8101118
    Epithelial-to-Mesenchymal Transition (EMT) has been shown to be crucial in tumorigenesis where the EMT program enhances metastasis, chemoresistance and tumor stemness. Due to its emerging role as a pivotal driver of tumorigenesis, targeting EMT is of great therapeutic interest in counteracting metastasis and chemoresistance in cancer patients. The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin, and this process is regulated by a complex network of signaling pathways and transcription factors. In this review, we summarized the recent understanding of the roles of E- and N-cadherins in cancer invasion and metastasis as well as the crosstalk with other signaling pathways involved in EMT. We also highlighted a few natural compounds with potential anti-EMT property and outlined the future directions in the development of novel intervention in human cancer treatments. We have reviewed 287 published papers related to this topic and identified some of the challenges faced in translating the discovery work from bench to bedside.
    MeSH terms: Animals; Antineoplastic Agents/isolation & purification; Antineoplastic Agents/therapeutic use; Multigene Family/genetics; Humans; Signal Transduction/genetics; Cadherins/genetics*; Gene Expression Regulation, Neoplastic; Drug Discovery/methods; Drug Discovery/trends; Epithelial-Mesenchymal Transition/genetics*; Molecular Targeted Therapy/methods; Molecular Targeted Therapy/standards; Molecular Targeted Therapy/trends; Carcinogenesis/genetics*
  7. Nusrat T, Akter N, Haque M, Rahman NAA, Dewanjee AK, Ahmed S, et al.
    Pathogens, 2019 Sep 12;8(3).
    PMID: 31547453 DOI: 10.3390/pathogens8030151
    BACKGROUND: Ventilator-associated pneumonia (VAP) is the most common nosocomial infection in intensive care units (ICU), which accounts for 25% of all ICU infection. Documenting carbapenem-resistant gram-negative bacilli is very important as these strains may often cause outbreaks in the ICU setting and are responsible for the increased mortality and morbidity or limiting therapeutic options. The classical phenotypic method cannot provide an efficient means of diagnosis of the metallo-β-lactamases (MBLs) producer. Polymerase chain reaction (PCR) assays have lessened the importance of the phenotypic approach by detecting metallo-β-lactamase resistance genes such as New Delhi metallo-β-lactamase (NDM), Imipenemase (IMP), Verona integron-encoded metallo-β-lactamase (VIM), Sao Paulo metallo-β-lactamase (SPM), Germany Imipenemase (GIM).

    OBJECTIVE: To compare the results of the Combined Disc Synergy Test (CDST) with that of the multiplex PCR to detect MBL-producing gram-negative bacilli.

    MATERIALS AND METHOD: A total of 105 endotracheal aspirates (ETA) samples were collected from the ICU of a public school in Bangladesh. This cross-sectional study was carried out in the Department of Microbiology, Chittagong for quantitative culture, CDST test, and multiplex PCR for blaIMP, blaVIM, blaNDM genes of MBL producers.

    RESULTS: Among the 105 clinically suspected VAP cases, the quantitative culture was positive in 95 (90%) and among 95 g-negative bacilli isolated from VAP patients, 46 (48.42%) were imipenem resistant, 30 (65.22%) were MBL producers by CDST, 21 (45.65%) were identified as MBL producers by multiplex PCR.

    CONCLUSION: PCR was highly sensitive and specific for the detection of MBL producers.

    MeSH terms: Bangladesh; beta-Lactamases; Cross Infection; Cross-Sectional Studies; Disease Outbreaks; Germany; Gram-Negative Bacteria; Humans; Intensive Care Units; Imipenem; Carbapenems; beta-Lactam Resistance; Integrons; Pneumonia, Ventilator-Associated; Multiplex Polymerase Chain Reaction
  8. Li Y, Wang Y, Liu Z, Zainal Abidin IM, Chen Z
    Sensors (Basel), 2019 Sep 23;19(19).
    PMID: 31547499 DOI: 10.3390/s19194102
    The cladded conductor is broadly utilized in engineering fields, such as aerospace, energy, and petrochemical; however, it is vulnerable to thickness loss occurring in the clad layer and nonconductive protection coating due to abrasive and corrosive environments. Such a flaw severely undermines the integrity and safety of the mechanical structures. Therefore, evaluating the thickness loss hidden inside cladded conductors via reliable nondestructive evaluation techniques is imperative. This paper intensively investigates the pulse-modulation eddy current technique (PMEC) for the assessment of thickness loss in a cladded conductor. An analytical model of the ferrite-cored probe is established for analyzing PMEC signals and characteristics of lift-off intersection (LOI) in testing signals. Experiments are conducted for evaluation of the thickness loss in cladded conductors. An inverse scheme based on LOI for estimation of the thickness-loss depth is proposed and further verified. Through simulations and experiments, it is found that the influences of the thickness loss in the clad layer and protective coating on the PMEC signals can be decoupled in virtue of the LOI characteristics. Based on LOI, the hidden thickness loss can be efficiently evaluated without much of a reduction in accuracy by using the PMEC probe for dedicated inspection of the cladded conductor.
    MeSH terms: Anniversaries and Special Events; Cardiovascular Physiological Phenomena; Engineering; Ferric Compounds; Virtues
  9. Ibrahim F, Mohan D, Sajab MS, Bakarudin SB, Kaco H
    Polymers (Basel), 2019 Sep 23;11(10).
    PMID: 31547544 DOI: 10.3390/polym11101544
    In this study, lignin has been extracted from oil palm empty fruit bunch (EFB) fibers via an organosolv process. The organosolv lignin obtained was defined by the presence of hydroxyl-containing molecules, such as guaiacyl and syringyl, and by the presence of phenolic molecules in lignin. Subsequently, the extracted organosolv lignin and graphene nanoplatelets (GNP) were utilized as filler and reinforcement in photo-curable polyurethane (PU), which is used in stereolithography 3D printing. The compatibility as well as the characteristic and structural changes of the composite were identified through the mechanical properties of the 3D-printed composites. Furthermore, the tensile strength of the composited lignin and graphene shows significant improvement as high as 27%. The hardness of the photo-curable PU composites measured by nanoindentation exhibited an enormous improvement for 0.6% of lignin-graphene at 92.49 MPa with 238% increment when compared with unmodified PU.
    MeSH terms: Fruit; Graphite; Hardness; Lignin; Polyurethanes; Tensile Strength; Hydroxyl Radical; Printing, Three-Dimensional
  10. Syafiq U, Ataollahi N, Maggio RD, Scardi P
    Molecules, 2019 Sep 23;24(19).
    PMID: 31547625 DOI: 10.3390/molecules24193454
    Cu2ZnSnS4 (CZTS) ink was synthesized from metal chloride precursors, sulfur, and oleylamine (OLA), as a ligand by a simple and low-cost hot-injection method. Thin films of CZTS were then prepared by spin coating, followed by thermal annealing. The effects of the fabrication parameters, such as ink concentration, spinning rate, and thermal treatment temperatures on the morphology and structural, optical, and electrical properties of the films were investigated. As expected, very thin films, for which the level of transmittance and band-gap values increase, can be obtained either by reducing the concentration of the inks or by increasing the rate of spinning. Moreover, the thermal treatment affects the phase formation and crystallinity of the film, as well as the electrical conductivity, which decreases at a higher temperature.
    MeSH terms: Amines/chemistry; Antineoplastic Agents/chemistry; Copper/chemistry*; Crystallization; Particle Size; Solutions; Sulfides/chemistry*; Surface Properties; Temperature; Tin/chemistry*; Zinc/chemistry*
  11. Dhillon H, Nordin RB, Ramadas A
    PMID: 31547629 DOI: 10.3390/ijerph16193561
    Diabetes complications, medication adherence, and psychosocial well-being have been associated with quality of life (QOL) among several Western and Asian populations with diabetes, however, there is little evidence substantiating these relationships among Malaysia's unique and diverse population. Therefore, a cross-sectional study was conducted in a Malaysian public primary care clinic among 150 patients diagnosed with type 2 diabetes mellitus (T2DM). Structured and validated questionnaires were used to investigate the associations between demographic, clinical, and psychological factors with QOL of the study participants. Approximately three-quarters of patients had a good-excellent QOL. Diabetes-related variables that were significantly associated with poor QOL scores included insulin containing treatment regimens, poor glycemic control, inactive lifestyle, retinopathy, neuropathy, abnormal psychosocial well-being, higher diabetes complication severity, and nonadherence (p < 0.05). The main predictors of a good-excellent QOL were HbA1c ≤ 6.5% (aOR = 20.78, 95% CI = 2.5175.9, p = 0.005), normal anxiety levels (aOR = 5.73, 95% CI = 1.8-18.5, p = 0.004), medication adherence (aOR = 3.35, 95% CI = 1.3-8.7, p = 0.012), and an aDCSI score of one and two as compared to those greater than or equal to four (aOR = 7.78, 95% CI = 1.5-39.2, p = 0.013 and aOR = 8.23, 95% CI = 2.1-32.8, p = 0.003), respectively. Medication adherence has also been found to be an effect modifier of relationships between HbA1c, depression, anxiety, disease severity, and QOL. These predictors of QOL are important factors to consider when managing patients with T2DM.
    MeSH terms: Anxiety; Anxiety Disorders; Cross-Sectional Studies; Depression; Diabetes Mellitus, Type 2; Humans; Life Style; Malaysia; Primary Health Care; Quality of Life; Surveys and Questionnaires; Diabetes Complications; Medication Adherence; Insulins
  12. Wu S, Gu W, Huang A, Li Y, Kumar M, Lim PE, et al.
    Microb Cell Fact, 2019 Sep 23;18(1):161.
    PMID: 31547820 DOI: 10.1186/s12934-019-1214-x
    BACKGROUND: Numerous studies have shown that stress induction and genetic engineering can effectively increase lipid accumulation, but lead to a decrease of growth in the majority of microalgae. We previously found that elevated CO2 concentration increased lipid productivity as well as growth in Phaeodactylum tricornutum, along with an enhancement of the oxidative pentose phosphate pathway (OPPP) activity. The purpose of this work directed toward the verification of the critical role of glucose-6-phosphate dehydrogenase (G6PDH), the rate-limiting enzyme in the OPPP, in lipid accumulation in P. tricornutum and its simultaneous rapid growth rate under high-CO2 (0.15%) cultivation.

    RESULTS: In this study, G6PDH was identified as a target for algal strain improvement, wherein G6PDH gene was successfully overexpressed and antisense knockdown in P. tricornutum, and systematic comparisons of the photosynthesis performance, algal growth, lipid content, fatty acid profiles, NADPH production, G6PDH activity and transcriptional abundance were performed. The results showed that, due to the enhanced G6PDH activity, transcriptional abundance and NAPDH production, overexpression of G6PDH accompanied by high-CO2 cultivation resulted in a much higher of both lipid content and growth in P. tricornutum, while knockdown of G6PDH greatly decreased algal growth as well as lipid accumulation. In addition, the total proportions of saturated and unsaturated fatty acid, especially the polyunsaturated fatty acid eicosapentaenoic acid (EPA; C20:5, n-3), were highly increased in high-CO2 cultivated G6PDH overexpressed strains.

    CONCLUSIONS: The successful of overexpression and antisense knockdown of G6PDH well demonstrated the positive influence of G6PDH on algal growth and lipid accumulation in P. tricornutum. The improvement of algal growth, lipid content as well as polyunsaturated fatty acids in high-CO2 cultivated G6PDH overexpressed P. tricornutum suggested this G6PDH overexpression-high CO2 cultivation pattern provides an efficient and economical route for algal strain improvement to develop algal-based biodiesel production.

    MeSH terms: Carbon Dioxide; Fatty Acids; Fatty Acids, Unsaturated; Genetic Engineering; Glucosephosphate Dehydrogenase; NADP; Pentose Phosphate Pathway; Photosynthesis; Eicosapentaenoic Acid; Diatoms; Oxidative Stress; Biofuels; Microalgae
  13. Lin Y, Lin Z, He F, Hu Z, Zimet GD, Alias H, et al.
    Vaccine, 2019 Oct 16;37(44):6714-6723.
    PMID: 31548016 DOI: 10.1016/j.vaccine.2019.09.026
    BACKGROUND: Little research has been conducted on the intention to obtain HPV vaccine now that the vaccine is approved for use in China. Acceptance of the three HPV vaccines, which differ in valency and price, has never been investigated.

    METHODS: An online cross-sectional survey assessing female undergraduate students' intention to obtain the HPV vaccine and their acceptability of 2-, 4- and 9-valent HPV vaccines (2vHPV, 4vHPV, and 9vHPV, respectively).

    RESULTS: Of a total of 997 complete responses, 55.2% reported intent to obtain the HPV vaccine. Some of the significant factors exerting influence on intent to obtain HPV vaccination were high knowledge score (OR = 1.469, 95% CI:1.087-1.987), perceived high risk of HPV infection (OR = 1.466, 95%CI:1.017-2.114), perception of no serious side effects (OR = 1.562, 95%CI:1.150-2.121), and mass media exposure to HPV vaccination information (OR = 2.196, 95%CI: 1.625-2.966). Socioeconomic status indicators did not significantly influence intent to obtain the HPV vaccine. A higher proportion of respondents were willing to pay for 2vHPV (78.6%) and 4vHPV (68.0%) compared with 9vHPV (49.3%). Socioeconomic status indicators were the strongest correlates of acceptability for all the three vaccines. Exposure to mass media reporting about HPV vaccination is the factor which exerts the most influence on acceptance of 9vHPV after socioeconomic status indicators.

    CONCLUSIONS: It is important to improve knowledge and health beliefs, and to establish a mass media marketing strategy to promote HPV vaccination in order to enhance HPV vaccine uptake. Undergraduate female students should be provided with detailed information about the different valency vaccine choices to help them make informed decisions about immunization.

    MeSH terms: China/epidemiology; Cross-Sectional Studies; Female; Health Personnel*; Humans; Patient Acceptance of Health Care*; Socioeconomic Factors; Students*; Vaccination; Papillomavirus Infections/epidemiology*; Papillomavirus Infections/prevention & control*; Intention*
  14. Mudgil P, Baby B, Ngoh YY, Vijayan R, Gan CY, Maqsood S
    J Dairy Sci, 2019 Dec;102(12):10748-10759.
    PMID: 31548068 DOI: 10.3168/jds.2019-16520
    Novel bioactive peptides from camel milk protein hydrolysates (CMPH) were identified and tested for inhibition of cholesterol esterase (CEase), and their possible binding mechanisms were elucidated by molecular docking. Papain-generated CMPH showed the highest degree of hydrolysis. All CMPH produced upon enzymatic degradation demonstrated a dramatic enhancement of CEase inhibition compared with intact camel milk proteins, with papain-generated hydrolysate P9 displaying the highest inhibition. Peptide identification and their modeling through PepSite 2 revealed that among 20 potential bioactive peptides in alcalase-generated hydrolysate A9, only 3 peptides, with sequences KFQWGY, SQDWSFY, and YWYPPQ, showed the highest binding toward CEase catalytic sites. Among 43 peptides in 9-h papain-generated hydrolysate P9, 4 peptides were found to be potent CEase inhibitors. Molecular docking revealed that WPMLQPKVM, CLSPLQMR, MYQQWKFL, and CLSPLQFR from P9 hydrolysates were able to bind to the active site of CEase with good docking scores and molecular mechanics-generalized born surface area binding energies. Overall, this is the first study reporting CEase inhibitory potential of peptides generated from milk proteins.
    MeSH terms: Animals; Sterol Esterase/antagonists & inhibitors*; Enzyme Inhibitors/isolation & purification*; Enzyme Inhibitors/chemistry; Female; Milk/chemistry; Milk Proteins/chemistry*; Papain/chemistry; Peptides/isolation & purification; Peptides/chemistry*; Protein Hydrolysates/chemistry; Subtilisins/chemistry; Molecular Docking Simulation
  15. Constable PD, Megahed AA, Hiew MWH
    J Dairy Sci, 2019 Dec;102(12):11370-11383.
    PMID: 31548071 DOI: 10.3168/jds.2019-16805
    Urine pH (UpH) and net acid excretion (NAE) are used to monitor the degree of systemic acidification and predict the magnitude of resultant hypercalciuria when feeding an acidogenic ration to control periparturient hypocalcemia in dairy cattle. The objectives of this study were to evaluate the diagnostic performance of urine dipstick and pH paper for measuring UpH, and to characterize the UpH-NAE relationship and the association of urine Ca concentration ([Ca]) with UpH and NAE. Urine samples (n = 1,116) were collected daily from 106 periparturient Holstein-Friesian cows fed an acidogenic ration during late gestation. Net acid excretion was measured by titration, and UpH was measured by a glass-electrode pH meter (reference method), Multistix-SG urine dipsticks (Siemens Medical Solutions Inc., Ann Arbor, MI), and Hydrion pH paper (Micro Essential Laboratory Inc., Brooklyn, NY). Diagnostic performance was evaluated using Spearman correlation coefficient (rs), Bland-Altman plots, and logistic regression. Urine pH measured by urine dipstick (rs = 0.94) and pH paper (rs = 0.96) were strongly associated with UpH. Method-comparison studies indicated that the urine dipstick measured an average of 0.28 pH units higher, and pH paper 0.10 pH units lower, than UpH. Urine [Ca] was more strongly associated with UpH (rs = -0.65) than NAE (rs = 0.52). Goals for controlling periparturient hypocalcemia under the study conditions were UpH <6.22 and <6.11, based on achieving urine [Ca] ≥5 mmol/L and estimated urinary Ca excretion ≥4 g/d, respectively. Urine pH was as accurate at predicting urine [Ca] as NAE when UpH >6.11. We conclude that pH paper is an accurate, practical, and low-cost cow-side test for measuring UpH and provides a clinically useful estimate of urine [Ca].
    MeSH terms: Acids; Animals; Cattle; Diagnostic Tests, Routine; Electrodes; Female; Goals; Homeostasis; Hypocalcemia; Monitoring, Physiologic; Pregnancy; Logistic Models; Hypercalciuria
  16. Aziz ZAA, Nasir HM, Ahmad A, Setapar SHM, Ahmad H, Noor MHM, et al.
    Sci Rep, 2019 Sep 23;9(1):13678.
    PMID: 31548590 DOI: 10.1038/s41598-019-50134-y
    Eucalyptus globulus is an aromatic medicinal plant which known for its 1,8-cineole main pharmacological constituent exhibits as natural analgesic agent. Eucalyptus globulus-loaded micellar nanoparticle was developed via spontaneous emulsification technique and further evaluation for its analgesic efficacy study, in vivo analgesic activity assay in rats. The nanoemulsion system containing Eucalyptus-micelles was optimized at different surfactant types (Tween 40, 60 and 80) and concentrations (3.0, 6.0, 9.0, 12.0, 15.0, and 18.0 wt. %). These formulations were characterized by thermodynamically stability, viscosity, micelles particle size, pH, and morphology structure. The spontaneous emulsification technique offered a greener micelles formation in nanoemulsion system by slowly titrated of organic phase, containing Eucalyptus globulus (active compound), grape seed oil (carrier oil) and hydrophilic surfactant into aqueous phase, and continuously stirred for 30 min to form a homogeneity solution. The characterizations evaluation revealed an optimized formulation with Tween 40 surfactant type at 9.0 wt. % of surfactant concentration promoted the most thermodynamic stability, smaller micelles particle size (d = 17.13 ± 0.035 nm) formed with spherical shape morphological structure, and suitable in viscosity (≈2.3 cP) and pH value (6.57) for transdermal purpose. The in vivo analgesic activity assay of optimized emulsion showed that the transdermal administration of micellar nanoparticle of Eucalyptus globulus on fore and hind limb of rats, possessed the central and peripheral analgesic effects by prolonged the rats pain responses towards the heat stimulus after being put on top of hot plate (55 °C), with longest time responses, 40.75 s at 60 min after treatment administration. Thus, this study demonstrated that micellar nanoparticle of Eucalyptus globulus formed in nanoemulsion system could be promising as an efficient transdermal nanocarrier for the analgesic therapy alternative.
    MeSH terms: Animals; Emulsions/pharmacology*; Emulsions/therapeutic use; Emulsions/chemistry; Hot Temperature; Male; Micelles; Pain/drug therapy*; Rats, Sprague-Dawley; Pain Threshold/drug effects*; Nanotechnology; Rats
  17. Edvall NK, Gunan E, Genitsaridi E, Lazar A, Mehraei G, Billing M, et al.
    Front Neurosci, 2019;13:879.
    PMID: 31548840 DOI: 10.3389/fnins.2019.00879
    There is increasing evidence of associations between the presence of temporomandibular joint (TMJ) disorders and tinnitus. It has been recently proposed that tinnitus patients with TMJ complaints could constitute a subtype, meaning a subgroup of tinnitus patients responsive to specific treatments. Tinnitus patients with TMJ complaints are often young women with somatosensory features of their tinnitus. Here, we investigate the socio-economic factors, phenotypic characteristics and psychological variables of tinnitus subjects from the Swedish Tinnitus Outreach Project, with (n = 486) or without (n = 1,996) TMJ complaints. The prevalence of TMJ complaints was greater in tinnitus subjects with severe tinnitus (36%) when compared to those with any tinnitus (19%), strongly indicating the contribution of TMJ problems to the severity of tinnitus. Comparing subgroups with or without TMJ complaints in the whole sample, differences were found regarding a large number of socioeconomic, phenotypic, and psychological characteristics. Subjects with TMJ complaints were more often women, more often reported stress as the cause of tinnitus, were more severely affected by tinnitus, scored worse in measures of psychological well-being and life quality, and were more often affected by problems tolerating sounds, headache, vertigo/dizziness, and neck pain. In addition, they more often reported pulsating and tonal tinnitus, somatic modulation of tinnitus, and aggravation of tinnitus by loud sounds and stress. When focusing the analysis in subjects with tinnitus as a big problem using the Tinnitus Functional Index cut-off ≥ 48, or with severe tinnitus according to the Tinnitus Handicap Inventory cut-off ≥ 58, the impact of somatosensory modulations and stress on tinnitus were greater in subjects with TMJ complaints in comparison to those without. In light of these results, we hypothesize that stress could contribute to the co-occurrence of TMJ problems and tinnitus and also to the development of severe tinnitus. Our study supports the need of involving dental care and stress management in the holistic treatment of patients with severe tinnitus.
    MeSH terms: Dental Care; Dizziness; Female; Headache; Humans; Psychotherapy; Quality of Life; Sweden; Temporomandibular Joint; Temporomandibular Joint Disorders; Tinnitus; Vertigo; Prevalence; Neck Pain
  18. Darrat M, Flaherty GT
    PMID: 31548898 DOI: 10.1186/s40794-019-0094-8
    Background: Older people represent a significant proportion of overseas travellers. The epidemiology of older international travellers is not well described in the literature. This study aims to identify demographics, travel characteristics and the medical profile of older travellers seeking pre-travel health advice in a specialist travel medicine clinic.

    Methods: Records of travellers aged 60 years and older attending the Tropical Medical Bureau clinic in Galway, Ireland between 2014 and 2018 were examined. Descriptive and inferential.analysis of data was performed.

    Results: A total of 337 older travellers sought pre-travel health advice during the study period. The mean age of the cohort was 65.42 (±10) years. Most of the travellers (n = 267, 80%) had at least one travelling companion. Nearly half of older travellers (n = 155, 46.8%) were travelling with a single companion. Tourism was the main reason for travel for the majority (n = 260, 77.6%), followed by visiting friends and relatives (VFR) (n = 23, 6.9%) travellers. The mean interval remaining before the planned trip was 4.36 (±2) weeks, and the mean duration of travel was 3.16 (±1) weeks. The most popular single country of destination was India with 33 (9.8%) visitors, and South East Asia was the most popular region with 132 (39.2%) older travellers. The majority of travellers (n = 267, 79.2%) had a documented pre-existing medical condition. The most commonly reported medical conditions were hypertension (n = 26, 7.7%), dyslipidaemia (n = 18, 5.3%), diabetes mellitus (n = 12, 3.5%), insect bite sensitivity (n = 11, 3.3%), and hypothyroidism (n = 9, 2.6%). Antihypertensive agents (n = 32, 9.4%) and statins (n = 24, 7.1%) were the most frequently used medications. Typhoid (n = 112, 33.2%) and hepatitis A (n = 84, 24.9%) were the most common vaccinations administered to older travellers at the clinic.

    Conclusions: This study provides an insight into the demographics, travel characteristics, and medical profile of elderly travellers seeking advice at a large travel clinic in Ireland. A wide range of travel destinations, diseases and medication use was reported among this group of travellers, which may enable travel medicine physicians to provide more tailored advice and to more appropriately counsel older travellers.

    MeSH terms: Aged; Antihypertensive Agents; Demography; Diabetes Mellitus; Hepatitis A; Humans; Hypertension; Hypothyroidism; India; Insect Bites and Stings; Ireland; Middle Aged; Travel; Typhoid Fever; Vaccination; Cohort Studies; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Friends; Dyslipidemias; Travel Medicine
  19. Takeshita RSC, Mendonça RS, Bercovitch FB, Huffman MA
    PMID: 31549180 DOI: 10.1007/s00360-019-01235-7
    Non-invasive measures of stress are crucial for captive and conservation management programs. The adrenal hormone dehydroepiandrosterone-sulfate (DHEAS) has recently been adopted as a stress marker, but there is little investigation of its relationship to glucocorticoids (GC), well-known indicators of stress. This study examined the influence of age, reproductive state and environment on GC and DHEAS levels in orangutans, to test whether the GC/DHEAS ratio can provide an index of stress response in primates. We measured fecal GC (fGC) and fecal DHEAS (fDHEAS) concentrations in 7 captive orangutans from zoological parks in Japan and 22 wild orangutans from Danum Valley Conservation Area, Malaysia. We found that in a stressful condition (transportation), fDHEAS levels increased 2 days after the fGC response, which occurred 1 day after the stressor. One pregnant female had elevated levels of both hormones, and a higher fGC/fDHEAS ratio than baseline. Females in the first year of lactation had fGC levels and the fGC/fDHEAS ratio significantly higher than both baseline and females in the second and subsequent years of lactation. There was no effect of age on fGC levels, but the fGC/fDHEAS ratio was higher in infants than adults and adolescents. fDHEAS concentrations were lower in infants than juveniles, adolescents and adults, a phenomenon known as adrenarche, shared with humans and other great apes. We suggest that changes in DHEAS during orangutan life history are associated with changes in the dynamics of maintaining homeostasis that vary with age and reproductive state. The GC/DHEAS ratio index is useful to evaluate age-related abilities of responding to stressful challenges.
    MeSH terms: Age Factors; Animals; Animals, Wild; Animals, Zoo; Dehydroepiandrosterone/analogs & derivatives; Dehydroepiandrosterone/analysis; Dehydroepiandrosterone/metabolism*; Dehydroepiandrosterone/chemistry; Feces/chemistry; Female; Glucocorticoids/analysis; Glucocorticoids/metabolism*; Glucocorticoids/chemistry; Lactation/metabolism; Male; Pongo pygmaeus/growth & development*; Pongo pygmaeus/physiology; Pregnancy; Stress, Physiological*
  20. Chandramouli C, Tay WT, Bamadhaj NS, Tromp J, Teng TK, Yap JJL, et al.
    PLoS Med, 2019 09;16(9):e1002916.
    PMID: 31550265 DOI: 10.1371/journal.pmed.1002916
    BACKGROUND: Asians are predisposed to a lean heart failure (HF) phenotype. Data on the 'obesity paradox', reported in Western populations, are scarce in Asia and have only utilised the traditional classification of body mass index (BMI). We aimed to investigate the association between obesity (defined by BMI and abdominal measures) and HF outcomes in Asia.

    METHODS AND FINDINGS: Utilising the Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry (11 Asian regions including Taiwan, Hong Kong, China, India, Malaysia, Thailand, Singapore, Indonesia, Philippines, Japan, and Korea; 46 centres with enrolment between 1 October 2012 and 6 October 2016), we prospectively examined 5,964 patients with symptomatic HF (mean age 61.3 ± 13.3 years, 26% women, mean BMI 25.3 ± 5.3 kg/m2, 16% with HF with preserved ejection fraction [HFpEF; ejection fraction ≥ 50%]), among whom 2,051 also had waist-to-height ratio (WHtR) measurements (mean age 60.8 ± 12.9 years, 24% women, mean BMI 25.0 ± 5.2 kg/m2, 7% HFpEF). Patients were categorised by BMI quartiles or WHtR quartiles or 4 combined groups of BMI (low, <24.5 kg/m2 [lean], or high, ≥24.5 kg/m2 [obese]) and WHtR (low, <0.55 [thin], or high, ≥0.55 [fat]). Cox proportional hazards models were used to examine a 1-year composite outcome (HF hospitalisation or mortality). Across BMI quartiles, higher BMI was associated with lower risk of the composite outcome (ptrend < 0.001). Contrastingly, higher WHtR was associated with higher risk of the composite outcome. Individuals in the lean-fat group, with low BMI and high WHtR (13.9%), were more likely to be women (35.4%) and to be from low-income countries (47.7%) (predominantly in South/Southeast Asia), and had higher prevalence of diabetes (46%), worse quality of life scores (63.3 ± 24.2), and a higher rate of the composite outcome (51/232; 22%), compared to the other groups (p < 0.05 for all). Following multivariable adjustment, the lean-fat group had higher adjusted risk of the composite outcome (hazard ratio 1.93, 95% CI 1.17-3.18, p = 0.01), compared to the obese-thin group, with high BMI and low WHtR. Results were consistent across both HF subtypes (HFpEF and HF with reduced ejection fraction [HFrEF]; pinteraction = 0.355). Selection bias and residual confounding are potential limitations of such multinational observational registries.

    CONCLUSIONS: In this cohort of Asian patients with HF, the 'obesity paradox' is observed only when defined using BMI, with WHtR showing the opposite association with the composite outcome. Lean-fat patients, with high WHtR and low BMI, have the worst outcomes. A direct correlation between high WHtR and the composite outcome is apparent in both HFpEF and HFrEF.

    TRIAL REGISTRATION: Asian Sudden Cardiac Death in HF (ASIAN-HF) Registry ClinicalTrials.gov Identifier: NCT01633398.

    MeSH terms: Aged; Asia/epidemiology; Female; Heart Failure/diagnosis; Heart Failure/epidemiology*; Heart Failure/physiopathology; Humans; Male; Middle Aged; Obesity/diagnosis; Obesity/epidemiology*; Obesity/physiopathology; Prospective Studies; Registries; Risk Factors; Stroke Volume; Body Mass Index; Ventricular Function; Risk Assessment; Waist-Hip Ratio; Adiposity
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