Browse publications by year: 2019

  1. Serrano O, Lovelock CE, B Atwood T, Macreadie PI, Canto R, Phinn S, et al.
    Nat Commun, 2019 10 02;10(1):4313.
    PMID: 31575872 DOI: 10.1038/s41467-019-12176-8
    Policies aiming to preserve vegetated coastal ecosystems (VCE; tidal marshes, mangroves and seagrasses) to mitigate greenhouse gas emissions require national assessments of blue carbon resources. Here, we present organic carbon (C) storage in VCE across Australian climate regions and estimate potential annual CO2 emission benefits of VCE conservation and restoration. Australia contributes 5-11% of the C stored in VCE globally (70-185 Tg C in aboveground biomass, and 1,055-1,540 Tg C in the upper 1 m of soils). Potential CO2 emissions from current VCE losses are estimated at 2.1-3.1 Tg CO2-e yr-1, increasing annual CO2 emissions from land use change in Australia by 12-21%. This assessment, the most comprehensive for any nation to-date, demonstrates the potential of conservation and restoration of VCE to underpin national policy development for reducing greenhouse gas emissions.
    MeSH terms: Australia; Carbon/analysis*; Conservation of Natural Resources*; Ecosystem; Wetlands*; Climate Change*
  2. Alzoubi MM, Hayati KS, Rosliza AM, Ahmad AA, Al-Hamdan ZM
    Risk Manag Healthc Policy, 2019;12:167-177.
    PMID: 31576185 DOI: 10.2147/RMHP.S197038
    Background: Synergistic integration of predictors and elements that determine the success of total quality management (TQM) implementations in hospitals has been the bane of theoretical development in the TQM research area. Thus, this paper aims to offer a systematic literature review to provide a foundation on which research on TQM can be built and to identify the predictors of successful TQM in the health-care context.

    Materials and methods: A systematic literature survey was adopted in this paper, involving the review of 25 relevant researched articles found in the databases Science Direct, EBSCO, MEDLINE, CINAHL and PubMed.

    Result: The systematic literature survey reveals five variables to be core predictors of TQM, signifying how important these variables are in the successful implementation of TQM in the health-care context. Also, it is revealed that the identified core predictors have positive effects on an improved health-care system. However, the systematic survey of the literature reveals a dearth of studies on TQM in the health-care context.

    Conclusion: As TQM has become an important management approach for advancing effectiveness in the health-care sector, this kind of research is of value to researchers and managers. Stakeholders in the health sectors should introduce and implement TQM in hospitals and clinics. Nevertheless, this study has limitations, including that the databases and search engines adopted for the literature search are not exhaustive.

    MeSH terms: Surveys and Questionnaires; Research; Research Personnel; MEDLINE; Total Quality Management; Health Care Sector; PubMed; Search Engine
  3. Lee HM, Okuda KS, González FE, Patel V
    Adv Exp Med Biol, 2019;1164:11-34.
    PMID: 31576537 DOI: 10.1007/978-3-030-22254-3_2
    Of the ~129,079 new cases of nasopharyngeal carcinoma (NPC) and 72,987 associated deaths estimated for 2018, the majority will be geographically localized to South East Asia, and likely to show an upward trend annually. It is thought that disparities in dietary habits, lifestyle, and exposures to harmful environmental factors are likely the root cause of NPC incidence rates to differ geographically. Genetic differences due to ethnicity and the Epstein Barr virus (EBV) are likely contributing factors. Pertinently, NPC is associated with poor prognosis which is largely attributed to lack of awareness of the salient symptoms of NPC. These include nose hemorrhage and headaches and coupled with detection and the limited therapeutic options. Treatment options include radiotherapy or chemotherapy or combination of both. Surgical excision is generally the last option considered for advanced and metastatic disease, given the close proximity of nasopharynx to brain stem cell area, major blood vessels, and nerves. To improve outcome of NPC patients, novel cellular and in vivo systems are needed to allow an understanding of the underling molecular events causal for NPC pathogenesis and for identifying novel therapeutic targets and effective therapies. While challenges and gaps in current NPC research are noted, some advances in targeted therapies and immunotherapies targeting EBV NPCs are discussed in this chapter, which may offer improvements in outcome of NPC patients.
    MeSH terms: Asia, Southeastern/epidemiology; Humans; Risk Factors; Epstein-Barr Virus Infections/complications
  4. Ngo TA, Dinh H, Nguyen TM, Liew FF, Nakata E, Morii T
    Chem Commun (Camb), 2019 Oct 15;55(83):12428-12446.
    PMID: 31576822 DOI: 10.1039/c9cc04661e
    DNA is an attractive molecular building block to construct nanoscale structures for a variety of applications. In addition to their structure and function, modification the DNA nanostructures by other molecules opens almost unlimited possibilities for producing functional DNA-based architectures. Among the molecules to functionalize DNA nanostructures, proteins are one of the most attractive candidates due to their vast functional variations. DNA nanostructures loaded with various types of proteins hold promise for applications in the life and material sciences. When loading proteins of interest on DNA nanostructures, the nanostructures by themselves act as scaffolds to specifically control the location and number of protein molecules. The methods to arrange proteins of interest on DNA scaffolds at high yields while retaining their activity are still the most demanding task in constructing usable protein-modified DNA nanostructures. Here, we provide an overview of the existing methods applied for assembling proteins of interest on DNA scaffolds. The assembling methods were categorized into two main classes, noncovalent and covalent conjugation, with both showing pros and cons. The recent advance of DNA-binding adaptor mediated assembly of proteins on the DNA scaffolds is highlighted and discussed in connection with the future perspectives of protein assembled DNA nanoarchitectures.
    MeSH terms: DNA/metabolism*; DNA/chemistry; Proteins/metabolism*; Proteins/chemistry; Nanostructures/chemistry
  5. Gulzari UA, Khan S, Sajid M, Anjum S, Torres FS, Sarjoughian H, et al.
    PLoS One, 2019;14(10):e0222759.
    PMID: 31577809 DOI: 10.1371/journal.pone.0222759
    This paper presents the Hybrid Scalable-Minimized-Butterfly-Fat-Tree (H-SMBFT) topology for on-chip communication. Main aspects of this work are the description of the architectural design and the characteristics as well as a comparative analysis against two established indirect topologies namely Butterfly-Fat-Tree (BFT) and Scalable-Minimized-Butterfly-Fat-Tree (SMBFT). Simulation results demonstrate that the proposed topology outperforms its predecessors in terms of performance, area and power dissipation. Specifically, it improves the link interconnectivity between routing levels, such that the number of required links isreduced. This results into reduced router complexity and shortened routing paths between any pair of communicating nodes in the network. Moreover, simulation results under synthetic as well as real-world embedded applications workloads reveal that H-SMBFT can reduce the average latency by up-to35.63% and 17.36% compared to BFT and SMBFT, respectively. In addition, the power dissipation of the network can be reduced by up-to33.82% and 19.45%, while energy consumption can be improved byup-to32.91% and 16.83% compared to BFT and SMBFT, respectively.
    MeSH terms: Algorithms*; Computer Communication Networks*; Computer Simulation; Electric Power Supplies*
  6. Wong KS, Lee L, Hung YM, Yeo LY, Tan MK
    Anal Chem, 2019 10 01;91(19):12358-12368.
    PMID: 31500406 DOI: 10.1021/acs.analchem.9b02850
    Rayleigh surface acoustic waves (SAWs) have been demonstrated as a powerful and effective means for driving a wide range of microfluidic actuation processes. Traditionally, SAWs have been generated on piezoelectric substrates, although the cost of the material and the electrode deposition process makes them less amenable as low-cost and disposable components. As such, a "razor-and-blades" model that couples the acoustic energy of the SAW on the piezoelectric substrate through a fluid coupling layer and into a low-cost and, hence, disposable silicon superstrate on which various microfluidic processes can be conducted has been proposed. Nevertheless, it was shown that only bulk vibration in the form of Lamb waves can be excited in the superstrate, which is considerably less efficient and flexible in terms of microfluidic functionality compared to its surface counterpart, that is, the SAW. Here, we reveal an extremely simple way that quite unexpectedly and rather nonintuitively allows SAWs to be generated on the superstrate-by coating the superstrate with a thin gold layer. In addition to verifying the existence of the SAW on the coated superstrate, we carry out finite-difference time domain numerical simulations that not only confirm the experimental observations but also facilitate an understanding of the surprising difference that the coating makes. Finally, we elucidate the various power-dependent particle concentration phenomena that can be carried out in a sessile droplet atop the superstrate and show the possibility for simply carrying out rapid and effective microcentrifugation-a process that is considerably more difficult with Lamb wave excitation on the superstrate.
    MeSH terms: Acoustics; Automobile Driving; Electrodes; Gold; Silicon; Sound; Vibration; Microfluidics
  7. Diez Roux AV, Slesinski SC, Alazraqui M, Caiaffa WT, Frenz P, Jordán Fuchs R, et al.
    Glob Chall, 2019 Apr;3(4):1800013.
    PMID: 31565372 DOI: 10.1002/gch2.201800013
    This article describes the origins and characteristics of an interdisciplinary multinational collaboration aimed at promoting and disseminating actionable evidence on the drivers of health in cities in Latin America and the Caribbean: The Network for Urban Health in Latin America and the Caribbean and the Wellcome Trust funded SALURBAL (Salud Urbana en América Latina, or Urban Health in Latin America) Project. Both initiatives have the goals of supporting urban policies that promote health and health equity in cities of the region while at the same time generating generalizable knowledge for urban areas across the globe. The processes, challenges, as well as the lessons learned to date in launching and implementing these collaborations, are described. By leveraging the unique features of the Latin American region (one of the most urbanized areas of the world with some of the most innovative urban policies), the aim is to produce generalizable knowledge about the links between urbanization, health, and environments and to identify effective ways to organize, design, and govern cities to improve health, reduce health inequalities, and maximize environmental sustainability in cities all over the world.
    MeSH terms: Health Equity; Americas; Cities; Goals; Hispanic Americans; Latin America; Socioeconomic Factors; United States; Urban Health; Urbanization; West Indies; Caribbean Region; Health Status Disparities
  8. Makaremi M, Yousefi H, Cavallaro G, Lazzara G, Goh CBS, Lee SM, et al.
    Polymers (Basel), 2019 Sep 29;11(10).
    PMID: 31569482 DOI: 10.3390/polym11101594
    Extensive usage of long-lasting petroleum based plastics for short-lived application such as packaging has raised concerns regarding their role in environmental pollution. In this research, we have developed active, healable, and safely dissolvable alginate-pectin based biocomposites that have potential applications in food packaging. The morphological study revealed the rough surface of these biocomposite films. Tensile properties indicated that the fabricated samples have mechanical properties in the range of commercially available packaging films while possessing excellent healing efficiency. Biocomposite films exhibited higher hydrophobicity properties compared to neat alginate films. Thermal analysis indicated that crosslinked biocomposite samples possess higher thermal stability in temperatures below 120 °C, while antibacterial analysis against E. coli and S. aureus revealed the antibacterial properties of the prepared samples against different bacteria. The fabricated biodegradable multi-functional biocomposite films possess various imperative properties, making them ideal for utilization as packaging material.
    MeSH terms: Alginates; Anti-Bacterial Agents; Drug Packaging; Environmental Pollution; Escherichia coli; Hexuronic Acids; Pectins; Petroleum; Plastics; Staphylococcus aureus; Temperature; Food Packaging; Glucuronic Acid; Hydrophobic and Hydrophilic Interactions
  9. Aziz SB, Abdulwahid RT, Hamsan MH, Brza MA, Abdullah RM, Kadir MFZ, et al.
    Molecules, 2019 Sep 27;24(19).
    PMID: 31569650 DOI: 10.3390/molecules24193508
    In this report, a facile solution casting technique was used to fabricate polymer blend electrolytes of chitosan (CS):poly (ethylene oxide) (PEO):NH4SCN with high electrochemical stability (2.43V). Fourier transform infrared (FTIR) spectroscopy was used to investigate the polymer electrolyte formation. For the electrochemical property analysis, cyclic voltammetry (CV), linear sweep voltammetry (LSV), and electrochemical impedance spectroscopy (EIS) techniques were carried out. Referring to the FTIR spectra, a complex formation between the added salt and CS:PEO was deduced by considering the decreasing and shifting of FTIR bands intensity in terms of functional groups. The CS:PEO:NH4SCN electrolyte was found to be electrochemically stable as the applied voltage linearly swept up to 2.43V. The cyclic voltammogram has presented a wide potential window without showing any sign of redox peaks on the electrode surface. The proved mechanisms of charge storage in these fabricated systems were found to be double layer charging. The EIS analysis showed the existence of bulk resistance, wherein the semicircle diameter decreased with increasing salt concentration. The calculated maximum DC conductivity value was observed to be 2.11 × 10-4 S/cm for CS:PEO incorporated with 40 wt% of NH4SCN salt. The charged species in CS:PEO:NH4SCN electrolytes were considered to be predominantly ionic in nature. This was verified from transference number analysis (TNM), in which ion and electron transference numbers were found to be tion = 0.954 and tel = 0.045, respectively. The results obtained for both ion transference number and DC conductivity implied the possibility of fabricating electrolytes for electrochemical double layer capacitor (EDLC) device application. The specific capacitance of the fabricated EDLC was obtained from the area under the curve of the CV plot.
    MeSH terms: Electrochemistry*; Electrolytes/chemistry*; Polymers/chemistry*; Protons*; Electric Impedance; Spectroscopy, Fourier Transform Infrared; Electric Capacitance*; Chitosan/chemistry*
  10. Chen Y, Tang WY, Tong X, Ji H
    Cancer Commun (Lond), 2019 10 01;39(1):53.
    PMID: 31570104 DOI: 10.1186/s40880-019-0402-8
    Despite the tremendous efforts for improving therapeutics of lung cancer patients, its prognosis remains disappointing. This can be largely attributed to the lack of comprehensive understanding of drug resistance leading to insufficient development of effective therapeutics in clinic. Based on the current progresses of lung cancer research, we classify drug resistance mechanisms into three different levels: molecular, cellular and pathological level. All these three levels have significantly contributed to the acquisition and evolution of drug resistance in clinic. Our understanding on drug resistance mechanisms has begun to change the way of clinical practice and improve patient prognosis. In this review, we focus on discussing the pathological changes linking to drug resistance as this has been largely overlooked in the past decades.
    MeSH terms: Animals; Carcinoma, Squamous Cell/drug therapy; Carcinoma, Squamous Cell/pathology; Humans; Lung Neoplasms/drug therapy*; Lung Neoplasms/pathology*; Carcinoma, Adenosquamous/drug therapy; Carcinoma, Adenosquamous/pathology; Drug Resistance, Neoplasm*; Small Cell Lung Carcinoma/drug therapy; Small Cell Lung Carcinoma/pathology
  11. Mohamed Amin Z, Che Ani MA, Tan SW, Yeap SK, Alitheen NB, Syed Najmuddin SUF, et al.
    Sci Rep, 2019 Sep 30;9(1):13999.
    PMID: 31570732 DOI: 10.1038/s41598-019-50222-z
    The Newcastle disease virus (NDV) strain AF2240 is an avian avulavirus that has been demonstrated to possess oncolytic activity against cancer cells. However, to illicit a greater anti-cancer immune response, it is believed that the incorporation of immunostimulatory genes such as IL12 into a recombinant NDV backbone will enhance its oncolytic effect. In this study, a newly developed recombinant NDV that expresses IL12 (rAF-IL12) was tested for its safety, stability and cytotoxicity. The stability of rAF-IL12 was maintained when passaged in specific pathogen free (SPF) chicken eggs from passage 1 to passage 10; with an HA titer of 29. Based on the results obtained from the MTT cytotoxic assay, rAF-IL12 was determined to be safe as it only induced cytotoxic effects against normal chicken cell lines and human breast cancer cells while sparing normal cells. Significant tumor growth inhibition (52%) was observed in the rAF-IL12-treated mice. The in vivo safety profile of rAF-IL12 was confirmed through histological observation and viral load titer assay. The concentration and presence of the expressed IL12 was quantified and verified via ELISA assay. In summary, rAF-IL12 was proven to be safe, selectively replicating in chicken and cancer cells and was able to maintain its stability throughout several passages; thus enhancing its potential as an anti-breast cancer vaccine.
    MeSH terms: Animals; Breast Neoplasms/therapy*; Female; Genetic Engineering/methods; Humans; Mice, Inbred BALB C; Newcastle disease virus/genetics*; Newcastle disease virus/metabolism; Interleukin-12/metabolism*; Cell Line, Tumor; Oncolytic Virotherapy/methods*; Mice; Real-Time Polymerase Chain Reaction
  12. Zakaria Z, Zulkifle MF, Wan Hasan WAN, Azhari AK, Abdul Raub SH, Eswaran J, et al.
    Onco Targets Ther, 2019;12:7749-7756.
    PMID: 31571924 DOI: 10.2147/OTT.S214611
    Background: Epidermal growth factor receptor (EGFR) is a member of the ErbB family of tyrosine kinase receptor proteins that plays important roles in tumour cell survival and proliferation. EGFR has been reported to be overexpressed in up to 78% of triple-negative breast cancer (TNBC) cases suggesting it as a potential therapeutic target. The clinical trials of anti-EGFR agents in breast cancer showed low response rates. However, a subgroup of patients demonstrated response to EGFR inhibitors highlighting the necessity to stratify patients, who might benefit from effective combination therapy that could include anti EGFR-agents. Population variability in EGFR expression warrants systematic evaluation in specific populations.

    Purpose: To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population.

    Patients and methods: In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively.

    Results: EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification.

    Conclusion: This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.

    MeSH terms: Cell Survival; Fluorescence; Gene Amplification; Humans; Immunohistochemistry; Malaysia; Receptor, Epidermal Growth Factor; Cohort Studies; In Situ Hybridization, Fluorescence; Gene Dosage; Genes, erbB-1; Receptor Protein-Tyrosine Kinases; Cell Proliferation; Triple Negative Breast Neoplasms
  13. Setia S, Tay JC, Chia YC, Subramaniam K
    Adv Med Educ Pract, 2019;10:805-812.
    PMID: 31572042 DOI: 10.2147/AMEP.S219104
    Continuing medical education (CME) is meant to not only improve clinicians' knowledge and skills but also lead to better patient care processes and outcomes. The delivery of CME should be able to encourage the health providers to accept new evidence-based practices, and discard or discontinue less effective care. However, continuing use of expensive yet least effective and inappropriate tools and techniques predominates for CME delivery. Hence, the evidence shows a disconnect between evidence-based recommendations and real-world practice - borne out by less than optimal patient outcomes or treatment targets not being met especially in low- to middle-income countries. There is an ethical and professional obligation on CME-providers and decision-makers to safeguard that CME interventions are appraised not only for their quality and effectiveness but also for cost-effectiveness. The process of learning needs to be engaging, convenient, user-friendly and of minimal cost, especially where it is most needed. Today's technology permits these characteristics to be integrated, along with further enhancement of the engagement process. We review the literature on the mechanics of CME learning that utilizes today's technology tools and propose a framework for more engaging, efficient and cost-effective approach that implements massive open online courses for CME, adapted for the twenty-first century.
    MeSH terms: Cost-Benefit Analysis; Education, Medical, Continuing; Patient Care; Humans; Learning; Morals; Knowledge
  14. Nazir MA, Izhar F, Akhtar K, Almas K
    J Family Community Med, 2019 10 2;26(3):206-212.
    PMID: 31572052 DOI: 10.4103/jfcm.JFCM_55_19
    BACKGROUND: Oral health is integral to systemic health. There is a growing body of evidence of an association between periodontal and systemic diseases. The aim of the study was to evaluate the awareness of dentists regarding link between oral and systemic health.

    MATERIALS AND METHODS: Data was collected using a self-administered pilot-tested questionnaire. Dentists awareness about link between oral and systemic link was assessed on five point likert scale. Data was entered and analysed using SPSS.

    RESULTS: Of the 588 dentists, 500 completed the questionnaire (response rate 85.03%). About 93% of the participants (mean age 25.82 ± 4.21 years) agreed that oral health was associated with systemic health. Most dentists were aware of a connection between periodontal disease and diabetes (84.4%) and heart disease (70.2%). Similarly, 85.6% believed in the negative impact of oral disease on the quality of life of patients. More female than male dentists were aware of the relationship between periodontal disease and adverse pregnancy outcomes, diabetes, and rheumatoid arthritis (P < 0.001). Most dentists (97%) believed that more patients would seek oral care if they were aware of the oral-systemic link. After adjustments, private dentists were 4.65 times more likely than public dentists to believe in improving access to oral care with increased patient awareness of the oral-systemic connection (P = 0.011).

    CONCLUSIONS: Most dentists were aware of the oral-systemic link. They believed that patients' access to oral care would improve if they were aware of a connection between oral and systemic health. Therefore, patients should be informed of the oral-systemic link to improve their oral health.

    MeSH terms: Adult; Arthritis, Rheumatoid; Dentists; Diabetes Mellitus; Female; Gingival Diseases; Heart Diseases; Humans; Male; Mouth Diseases; Oral Health; Periodontal Diseases; Pregnancy; Pregnancy Outcome; Quality of Life; Surveys and Questionnaires; Young Adult; Pilots
  15. Kandasamy M, Mak KK, Devadoss T, Thanikachalam PV, Sakirolla R, Choudhury H, et al.
    BMC Chem, 2019 Dec;13(1):117.
    PMID: 31572984 DOI: 10.1186/s13065-019-0633-4
    Background: The transcription factor Nuclear factor erythroid-2-related factor 2 (NRF2) and its principal repressive regulator, Kelch-like ECH-associated protein 1 (KEAP1), are perilous in the regulation of inflammation, as well as maintenance of homeostasis. Thus, NRF2 activation is involved in cytoprotection against many inflammatory disorders. N'-Nicotinoylquinoxaline-2-carbohdyrazide (NQC) was structurally designed by the combination of important pharmacophoric features of bioactive compounds reported in the literature.

    Methods: NQC was synthesised and characterised using spectroscopic techniques. The compound was tested for its anti-inflammatory effect using Lipopolysaccharide from Escherichia coli (LPSEc) induced inflammation in mouse macrophages (RAW 264.7 cells). The effect of NQC on inflammatory cytokines was measured using enzyme-linked immune sorbent assay (ELISA). The Nrf2 activity of the compound NQC was determined using 'Keap1:Nrf2 Inhibitor Screening Assay Kit'. To obtain the insights on NQC's activity on Nrf2, molecular docking studies were performed using Schrödinger suite. The metabolic stability of NQC was determined using mouse, rat and human microsomes.

    Results: NQC was found to be non-toxic at the dose of 50 µM on RAW 264.7 cells. NQC showed potent anti-inflammatory effect in an in vitro model of LPSEc stimulated murine macrophages (RAW 264.7 cells) with an IC50 value 26.13 ± 1.17 µM. NQC dose-dependently down-regulated the pro-inflammatory cytokines [interleukin (IL)-1β (13.27 ± 2.37 μM), IL-6 (10.13 ± 0.58 μM) and tumor necrosis factor (TNF)-α] (14.41 ± 1.83 μM); and inflammatory mediator, prostaglandin E2 (PGE2) with IC50 values, 15.23 ± 0.91 µM. Molecular docking studies confirmed the favourable binding of NQC at Kelch domain of Keap-1. It disrupts the Nrf2 interaction with kelch domain of keap 1 and its IC50 value was 4.21 ± 0.89 µM. The metabolic stability studies of NQC in human, rat and mouse liver microsomes revealed that it is quite stable with half-life values; 63.30 ± 1.73, 52.23 ± 0.81, 24.55 ± 1.13 min; microsomal intrinsic clearance values; 1.14 ± 0.31, 1.39 ± 0.87 and 2.96 ± 0.34 µL/min/g liver; respectively. It is observed that rat has comparable metabolic profile with human, thus, rat could be used as an in vivo model for prediction of pharmacokinetics and metabolism profiles of NQC in human.

    Conclusion: NQC is a new class of NRF2 activator with potent in vitro anti-inflammatory activity and good metabolic stability.

    MeSH terms: RAW 264.7 Cells; Animals; Anti-Inflammatory Agents; Escherichia coli; Half-Life; Homeostasis; Humans; Inflammation; Lipopolysaccharides; Liver; Macrophages; Microsomes, Liver; Dinoprostone; Interleukin-6; Cytokines; Cytoprotection; Inhibitory Concentration 50; Tumor Necrosis Factors; NF-E2-Related Factor 2; Mice; Rats; Interleukin-1beta; Metabolome; Molecular Docking Simulation; Kelch Repeat; Kelch-Like ECH-Associated Protein 1
  16. Nagai K, Kuwabara T, Ahmad MF, Nakano M, Karakawa M, Taima T, et al.
    Chem Commun (Camb), 2019 Oct 15;55(83):12491-12494.
    PMID: 31573004 DOI: 10.1039/c9cc04759j
    Photoelectrochemical oxidation of thiols was enhanced with a threshold potential of -0.35 V vs. Ag/AgCl by the use of a ZnPc/PCBM:P3HT/ZnO electode, which was prepared by removing the PEDOT:PSS/Au electrode of an inverted OPV device and coating it with ZnPc. A co-photocatalysis property of ZnPc was observed in the photoelectrochemistry and scanning Kelvin probe microscopy.
    MeSH terms: Electrodes; Indoles; Microscopy; Organometallic Compounds; Sulfhydryl Compounds; Zinc Oxide
  17. Conlon B, Hamilton C, Hughes S, Meade E, Hall DA, Vanneste S, et al.
    JMIR Res Protoc, 2019 Sep 27;8(9):e13176.
    PMID: 31573942 DOI: 10.2196/13176
    BACKGROUND: There is increasing evidence from animal and human studies that bimodal neuromodulation combining sound and electrical somatosensory stimulation of the tongue can induce extensive brain changes and treat tinnitus.

    OBJECTIVE: The main objectives of the proposed clinical study are to confirm the efficacy, safety, and tolerability of treatment demonstrated in a previous large-scale study of bimodal auditory and trigeminal nerve (tongue) stimulation (Treatment Evaluation of Neuromodulation for Tinnitus - Stage A1); evaluate the therapeutic effects of adjusting stimulation parameters over time; and determine the contribution of different features of bimodal stimulation in improving tinnitus outcomes.

    METHODS: This study will be a prospective, randomized, double-blind, parallel-arm, comparative clinical trial of a 12-week treatment for tinnitus using a Conformité Européenne (CE)-marked device with a pre-post and 12-month follow-up design. Four treatment arms will be investigated, in which each arm consists of two different stimulation settings, with the first setting presented during the first 6 weeks and the second setting presented during the next 6 weeks of treatment. The study will enroll 192 participants, split in a ratio of 80:80:16:16 across the four arms. Participants will be randomized to one of four arms and stratified to minimize baseline variability in four categories: two separate strata for sound level tolerance (using loudness discomfort level as indicators for hyperacusis severity), high tinnitus symptom severity based on the Tinnitus Handicap Inventory (THI), and tinnitus laterality. The primary efficacy endpoints are within-arm changes in THI and Tinnitus Functional Index as well as between-arm changes in THI after 6 weeks of treatment for the full cohort and two subgroups of tinnitus participants (ie, one hyperacusis subgroup and a high tinnitus symptom severity subgroup). Additional efficacy endpoints include within-arm or between-arm changes in THI after 6 or 12 weeks of treatment and in different subgroups of tinnitus participants as well as at posttreatment assessments at 6 weeks, 6 months, and 12 months. Treatment safety, attrition rates, and compliance rates will also be assessed and reported.

    RESULTS: This study protocol was approved by the Tallaght University Hospital/St. James's Hospital Joint Research Ethics Committee in Dublin, Ireland. The first participant was enrolled on March 20, 2018. The data collection and database lock are expected to be completed by February 2020, and the data analysis and manuscript submission are expected to be conducted in autumn of 2020.

    CONCLUSIONS: The findings of this study will be disseminated to relevant research, clinical, and health services and patient communities through publications in peer-reviewed journals and presentations at scientific and clinical conferences.

    TRIAL REGISTRATION: ClinicalTrials.gov NCT03530306; https://clinicaltrials.gov/ct2/show/NCT03530306.

    INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/13176.

  18. Paudel YN, Angelopoulou E, Jones NC, O'Brien TJ, Kwan P, Piperi C, et al.
    ACS Chem Neurosci, 2019 10 16;10(10):4199-4212.
    PMID: 31532186 DOI: 10.1021/acschemneuro.9b00460
    Emerging findings point toward an important interconnection between epilepsy and Alzheimer's disease (AD) pathogenesis. Patients with epilepsy (PWE) commonly exhibit cognitive impairment similar to AD patients, who in turn are at a higher risk of developing epilepsy compared to age-matched controls. To date, no disease-modifying treatment strategy is available for either epilepsy or AD, reflecting an immediate need for exploring common molecular targets, which can delineate a possible mechanistic link between epilepsy and AD. This review attempts to disentangle the interconnectivity between epilepsy and AD pathogenesis via the crucial contribution of Tau protein. Tau protein is a microtubule-associated protein (MAP) that has been implicated in the pathophysiology of both epilepsy and AD. Hyperphosphorylation of Tau contributes to the different forms of human epilepsy and inhibition of the same exerted seizure inhibitions and altered disease progression in a range of animal models. Moreover, Tau-protein-mediated therapy has demonstrated promising outcomes in experimental models of AD. In this review, we discuss how Tau-related mechanisms might present a link between the cause of seizures in epilepsy and cognitive disruption in AD. Untangling this interconnection might be instrumental in designing novel therapies that can minimize epileptic seizures and cognitive deficits in patients with epilepsy and AD.
    MeSH terms: Alzheimer Disease/complications; Alzheimer Disease/metabolism*; Brain/metabolism*; Epilepsy/complications; Epilepsy/metabolism*; Humans; tau Proteins/metabolism*; Mild Cognitive Impairment/complications; Mild Cognitive Impairment/metabolism*
  19. Lou Y, Fan L, Hou X, Dominiczak AF, Wang JG, Staessen JA, et al.
    Hypertension, 2019 11;74(5):1068-1074.
    PMID: 31564165 DOI: 10.1161/HYPERTENSIONAHA.119.13140
    MeSH terms: Adult; Biopsy, Needle; Urinary Bladder Neoplasms/pathology; Urinary Bladder Neoplasms/surgery*; Female; Humans; Hypertension/complications; Hypertension/diagnosis*; Hypertension/drug therapy; Immunohistochemistry; Male; Middle Aged; Paraganglioma/pathology; Paraganglioma/surgery*; Prognosis; Sampling Studies; Urination/physiology; Cystectomy/methods; Treatment Outcome; Rare Diseases; Positron Emission Tomography Computed Tomography/methods*
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