Browse publications by year: 2018

  1. Arifin SA, Paternoster S, Carlessi R, Casari I, Ekberg JH, Maffucci T, et al.
    Biochim Biophys Acta Mol Cell Biol Lipids, 2018 09;1863(9):1132-1141.
    PMID: 29883799 DOI: 10.1016/j.bbalip.2018.06.007
    The gastrointestinal tract is increasingly viewed as critical in controlling glucose metabolism, because of its role in secreting multiple glucoregulatory hormones, such as glucagon like peptide-1 (GLP-1). Here we investigate the molecular pathways behind the GLP-1- and insulin-secreting capabilities of a novel GPR119 agonist, Oleoyl-lysophosphatidylinositol (Oleoyl-LPI). Oleoyl-LPI is the only LPI species able to potently stimulate the release of GLP-1 in vitro, from murine and human L-cells, and ex-vivo from murine colonic primary cell preparations. Here we show that Oleoyl-LPI mediates GLP-1 secretion through GPR119 as this activity is ablated in cells lacking GPR119 and in colonic primary cell preparation from GPR119-/- mice. Similarly, Oleoyl-LPI-mediated insulin secretion is impaired in islets isolated from GPR119-/- mice. On the other hand, GLP-1 secretion is not impaired in cells lacking GPR55 in vitro or in colonic primary cell preparation from GPR55-/- mice. We therefore conclude that GPR119 is the Oleoyl-LPI receptor, upstream of ERK1/2 and cAMP/PKA/CREB pathways, where primarily ERK1/2 is required for GLP-1 secretion, while CREB activation appears dispensable.
    MeSH terms: Cyclic AMP/metabolism; Animals; Cell Line; Epithelial Cells/cytology; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Gene Expression Regulation; Humans; Insulin/metabolism*; Islets of Langerhans/drug effects; Islets of Langerhans/metabolism; Lysophospholipids/pharmacology*; Mice, Inbred C57BL; Oleic Acids/pharmacology*; Signal Transduction; Cyclic AMP Response Element-Binding Protein/genetics; Cyclic AMP Response Element-Binding Protein/metabolism; Cyclic AMP-Dependent Protein Kinases/genetics; Cyclic AMP-Dependent Protein Kinases/metabolism; Enteroendocrine Cells/cytology; Enteroendocrine Cells/drug effects*; Enteroendocrine Cells/metabolism; Mitogen-Activated Protein Kinase 1/genetics; Mitogen-Activated Protein Kinase 1/metabolism; Receptors, G-Protein-Coupled/deficiency; Receptors, G-Protein-Coupled/genetics*; Receptors, Cannabinoid/deficiency; Receptors, Cannabinoid/genetics; Cell Line, Tumor; Mitogen-Activated Protein Kinase 3/genetics; Mitogen-Activated Protein Kinase 3/metabolism; Mice; Glucagon-Like Peptide 1/genetics*; Glucagon-Like Peptide 1/metabolism; Primary Cell Culture
  2. Mukhtar NH, Mamat NA, See HH
    J Pharm Biomed Anal, 2018 Sep 05;158:184-188.
    PMID: 29883881 DOI: 10.1016/j.jpba.2018.05.044
    A sample pre-treatment method based on a dynamic mixed matrix membrane tip extraction followed by capillary electrophoresis with contactless conductivity detection (CE-C4D) was evaluated for the determination of tobramycin in human plasma. The extraction tip device consisted of a cellulose triacetate membrane tip wall immobilised with 15% (w/w) of hydrophilic lipophilic balance (HLB) nanoparticles as adsorbent. The extraction was performed dynamically by withdrawing/dispensing the plasma sample through the tip device followed by desorption into 20 μL of acidified aqueous solution at pH 3 prior to the CE-C4D analysis. Under the optimum conditions, the detection limit of the method for tobramycin was 10 ng/mL, with intraday and interday repeatability RSDs of 3.5% and 4.5%, respectively. Relative recoveries in spiked human plasma were 99.6%-99.9%. The developed approach was successfully demonstrated for the quantification of tobramycin in human plasma samples.
    MeSH terms: Anti-Bacterial Agents/blood*; Anti-Bacterial Agents/therapeutic use; Bacterial Infections/blood; Bacterial Infections/drug therapy*; Electric Conductivity; Chemical Fractionation/methods*; Humans; Membranes, Artificial; Tobramycin/blood*; Tobramycin/therapeutic use; Drug Monitoring/methods*; Electrophoresis, Capillary/methods; Limit of Detection
  3. Ei Thu H, Hussain Z, Shuid AN
    Curr Drug Targets, 2018;19(8):865-876.
    PMID: 27894237 DOI: 10.2174/1389450117666161125174625
    Psychotic disorders are recognized as severe mental disorders that rigorously affect patient's personality, critical thinking, and perceptional ability. High prevalence, global dissemination and limitations of conventional pharmacological approaches compel a significant burden to the patient, medical professionals and the healthcare system. To date, numerous orally administered therapies are available for the management of depressive disorders, schizophrenia, anxiety, bipolar disorders and autism spectrum problems. However, poor water solubility, erratic oral absorption, extensive first-pass metabolism, low oral bioavailability and short half-lives are the major factors which limit the pharmaceutical significance and therapeutic feasibility of these agents. In recent decades, nanotechnology-based delivery systems have gained remarkable attention of the researchers to mitigate the pharmaceutical issues related to the antipsychotic therapies and to optimize their oral drug delivery, therapeutic outcomes, and patient compliance. Therefore, the present review was aimed to summarize the available in vitro and in vivo evidences signifying the pharmaceutical importance of the advanced delivery systems in improving the aqueous solubility, transmembrane permeability, oral bioavailability and therapeutic outcome of the antipsychotic agents.
    MeSH terms: Animals; Mental Disorders/drug therapy*; Mental Disorders/physiopathology; Biological Availability; Half-Life; Humans; Permeability; Solubility; Antipsychotic Agents/administration & dosage*; Antipsychotic Agents/pharmacokinetics; Antipsychotic Agents/chemistry; Drug Delivery Systems*; Nanotechnology
  4. Yusof F, Sidi H, Das S, Midin M, Kumar J, Hatta MH
    Curr Drug Targets, 2018;19(8):856-864.
    PMID: 27993112 DOI: 10.2174/1389450117666161215161108
    Premature ejaculation (PE) is one of the commonest male sexual dysfunctions. It is characterized by ejaculation which occurs before or soon after vaginal penetration, which causes significant psychological distress to the individual, and his partner. The exact cause of PE is still unknown but several mechanisms are proposed, and these involve complex interactions of neurophysiological, psychosocial, and cognitive factors. We discuss the role of serotonin, nitric oxide, phosphodiesterase enzymes and other neurotransmitters. Treatment of PE tends to co-occur with other sexual difficulties, especially erectile dysfunction (ED). Treatment with selective serotonin reuptake inhibitors (SSRIs) and Dapoxitene are also discussed in detail. The treatment strategy requires a comprehensive holistic approach incorporating both combination of psychopharmacological agent and cognitive-behavioral therapy (CBT). The present review highlights the integration of the hypothalamic-neural and reverberating emotional circuit and discusses the etiology and treatment for patients with PE.
    MeSH terms: Combined Modality Therapy; Ejaculation/drug effects*; Humans; Male; Psychotropic Drugs/administration & dosage*; Psychotropic Drugs/pharmacology; Cognitive Therapy/methods; Serotonin Uptake Inhibitors/administration & dosage; Serotonin Uptake Inhibitors/pharmacology; Neurotransmitter Agents/metabolism; Premature Ejaculation/drug therapy*; Premature Ejaculation/physiopathology; Premature Ejaculation/psychology
  5. Rappek NAM, Sidi H, Kumar J, Kamarazaman S, Das S, Masiran R, et al.
    Curr Drug Targets, 2018;19(12):1352-1358.
    PMID: 28025939 DOI: 10.2174/1389450117666161227142947
    Sexual dysfunctions are commonly seen in women on selective serotonin reuptake inhibitors (SSRIs). The complexities of female sexual functioning are reflected through modulation of inter- playing factors like the neuropsychophysiological factors, inter-personal and relationship issue, psychiatric co-morbidities and physical disorder. The incidence of SSRIs-induced FSD is difficult to estimate because of the potential confounding effects of SSRIs, presence of polypharmacy, marital effect, socio-cultural factors and due to the design and assessment problems in majority of the studies. The exact mechanism of FSD-induced SSRIs is unknown. It has been postulated that although SSRIs may modulate other neurotransmitter system such as nitric oxide (NO), noradrenergic and dopamine in inducing FSD. In the present review, we highlight current evidence regarding potential mechanism of SSRIs in causing FSD, which include low sexual desire (low libido), arousal difficulties (lack of lubrication), and anorgasmia. The specific association of FSD to SSRI use, has not been ellucidated. The relationship is dose-dependent, and may vary among the groups with respect to mechanism of serotonin and dopamine reuptake, induction of release of prolactin from the pituitary gland, anticholinergic side-effects, inhibition of NO synthesis and emotional-memory circuit encryption for sexual experiences. Various interventional strategies exist regarding the treatment of SSRI-induced FSD and this includes tolerance, titration dosage, substitution to another antidepressant drug and psychotherapy. There is a need of better understanding of SSRIs-induced FSD for better treatment outcome.
    MeSH terms: Dopamine/metabolism; Female; Humans; Norepinephrine/metabolism; Serotonin/metabolism; Serotonin Antagonists/pharmacology; Serotonin Antagonists/therapeutic use; Sexual Dysfunction, Physiological/chemically induced*; Sexual Dysfunction, Physiological/drug therapy*; Serotonin Uptake Inhibitors/adverse effects*
  6. Hsiao YH, Chen C, Han HS, Kano R
    J Vet Med Sci, 2018 Jun 06;80(6):898-900.
    PMID: 29657238 DOI: 10.1292/jvms.17-0680
    A 2-year-old, exotic shorthair cat presented with baldness and mild scaling on trunk that was confirmed as Microsporum canis (M. canis) infection by the following methods. Wood's lamp and trichogram were used to demonstrate fungal elements suggestive of dermatophytosis consistent with M. canis. Dermatophyte test medium (DTM) and polymerase chain reaction (PCR) were used for identification. E-test and broth microdilution test were then utilized to estimate antifungal minimal inhibitory concentrations (MICs) towards ITZ and TRF respectively. The strain was isolated from the patient and revealed TRF MIC >32 µg/ml and ITZ MIC 0.023 µg/ml. Patient was cured of dermatophytosis with systemic ITZ.
    MeSH terms: Animals; Antifungal Agents/pharmacology*; Cat Diseases/drug therapy; Cat Diseases/microbiology*; Cats; Dermatomycoses/drug therapy; Dermatomycoses/microbiology; Dermatomycoses/veterinary*; Female; Microsporum/drug effects*; Microsporum/isolation & purification; Naphthalenes/pharmacology*; Drug Resistance, Fungal*
  7. Sherlala AIA, Raman AAA, Bello MM, Asghar A
    Chemosphere, 2018 Feb;193:1004-1017.
    PMID: 29874727 DOI: 10.1016/j.chemosphere.2017.11.093
    Graphene-based adsorbents have attracted wide interests as effective adsorbents for heavy metals removal from the environment. Due to their excellent electrical, mechanical, optical and transport properties, graphene and its derivatives such as graphene oxide (GO) have found various applications. However, in many applications, surface modification is necessary as pristine graphene/GO may be ineffective in some specific applications such as adsorption of heavy metal ions. Consequently, the modification of graphene/GO using various metals and non-metals is an ongoing research effort in the carbon-material realm. The use of organic materials represents an economical and environmentally friendly approach in modifying GO for environmental applications such as heavy metal adsorption. This review discusses the applications of organo-functionalized GO composites for the adsorption of heavy metals. The aspects reviewed include the commonly used organic materials for modifying GO, the performance of the modified composites in heavy metals adsorption, effects of operational parameters, adsorption mechanisms and kinetic, as well as the stability of the adsorbents. Despite the significant research efforts on GO modification, many aspects such as the interaction between the functional groups and the heavy metal ions, and the quantitative effect of the functional groups are yet to be fully understood. The review, therefore, offers some perspectives on the future research needs.
    MeSH terms: Adsorption; Graphite/chemistry*; Metals, Heavy/chemistry*; Nanocomposites/chemistry*
  8. Sim TY, Harith HH, Tham CL, Md Hashim NF, Shaari K, Sulaiman MR, et al.
    Molecules, 2018 Jun 05;23(6).
    PMID: 29874809 DOI: 10.3390/molecules23061355
    Alveolar epithelial barrier dysfunction contributes to lung edema and can lead to acute lung injury (ALI). The features include increased epithelial permeability, upregulation of inflammatory mediators and downregulation of junctional complex molecules; these changes are often induced by inflammation. tHGA is an acetophenone analogue with therapeutic potential in asthma. Its therapeutic potential in ALI is presently unknown. Herein, the effects of tHGA on epithelial barrier dysfunction were determined in TNF-α-induced human alveolar epithelial cells. The anti-inflammatory properties of tHGA were assessed by monocyte adhesion assay and analysis of MCP-1 and ICAM-1 expression. The epithelial barrier function was assessed by paracellular permeability and transepithelial electrical resistance (TEER) assays, and analysis of junctional complex molecules expression. To elucidate the mechanism of action, the effects of tHGA on the NF-κB and MAPK pathways were determined. Gene and protein expression were analyzed by RT-PCR and Western blotting or ELISA, respectively. tHGA suppressed leukocyte adhesion to TNF-α-induced epithelium and reduced MCP-1 and ICAM-1 gene expression and secretion. tHGA also increased TEER readings, reduced epithelial permeability and enhanced expression of junctional complex molecules (zona occludens-1, occludin and E-cadherin) in TNF-α-induced cells. Correspondingly, the NF-κB, ERK and p38 MAPK pathways were also inhibited by tHGA. These findings suggest that tHGA is able to preserve alveolar epithelial barrier function in response to acute inflammation, via its anti-inflammatory activity and stabilization of epithelial barrier integrity, mediated by NF-κB, ERK and p38 MAPK signaling.
    MeSH terms: Acetophenones/pharmacology*; Acetophenones/chemistry; Anti-Inflammatory Agents/pharmacology*; Cell Membrane Permeability/drug effects*; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; Epithelial Cells/drug effects; Epithelial Cells/metabolism; Humans; Models, Biological*; Pulmonary Alveoli/cytology; Pulmonary Alveoli/drug effects*; Pulmonary Alveoli/metabolism; Tumor Necrosis Factor-alpha/pharmacology*; Blotting, Western; Down-Regulation; Up-Regulation; NF-kappa B/metabolism; Intercellular Adhesion Molecule-1/metabolism; Inflammation Mediators/pharmacology*; Chemokine CCL2/metabolism; U937 Cells; MAP Kinase Signaling System/drug effects; Membrane Transport Proteins/metabolism
  9. Landais E, Moskal A, Mullee A, Nicolas G, Gunter MJ, Huybrechts I, et al.
    Nutrients, 2018 Jun 05;10(6).
    PMID: 29874819 DOI: 10.3390/nu10060725
    BACKGROUND: Coffee and tea are among the most commonly consumed nonalcoholic beverages worldwide, but methodological differences in assessing intake often hamper comparisons across populations. We aimed to (i) describe coffee and tea intakes and (ii) assess their contribution to intakes of selected nutrients in adults across 10 European countries.

    METHOD: Between 1995 and 2000, a standardized 24-h dietary recall was conducted among 36,018 men and women from 27 European Prospective Investigation into Cancer and Nutrition (EPIC) study centres. Adjusted arithmetic means of intakes were estimated in grams (=volume) per day by sex and centre. Means of intake across centres were compared by sociodemographic characteristics and lifestyle factors.

    RESULTS: In women, the mean daily intake of coffee ranged from 94 g/day (~0.6 cups) in Greece to 781 g/day (~4.4 cups) in Aarhus (Denmark), and tea from 14 g/day (~0.1 cups) in Navarra (Spain) to 788 g/day (~4.3 cups) in the UK general population. Similar geographical patterns for mean daily intakes of both coffee and tea were observed in men. Current smokers as compared with those who reported never smoking tended to drink on average up to 500 g/day more coffee and tea combined, but with substantial variation across centres. Other individuals' characteristics such as educational attainment or age were less predictive. In all centres, coffee and tea contributed to less than 10% of the energy intake. The greatest contribution to total sugar intakes was observed in Southern European centres (up to ~20%).

    CONCLUSION: Coffee and tea intake and their contribution to energy and sugar intake differed greatly among European adults. Variation in consumption was mostly driven by geographical region.

    MeSH terms: Adult; Aged; Energy Intake*; Coffee*; Europe/epidemiology; Feeding Behavior*; Female; Humans; Life Style; Male; Middle Aged; Nutrition Surveys; Nutritional Status*; Nutritive Value*; Prospective Studies; Smoking/epidemiology; Socioeconomic Factors; Tea*; Time Factors; Benchmarking*; Recommended Dietary Allowances*
  10. Lyn Heng JJ, Teng JH, Saravanan M, Pushpamalar J
    Sci Pharm, 2018 Jun 05;86(2).
    PMID: 29874858 DOI: 10.3390/scipharm86020024
    The purpose behind the work was to fabricate alginate beads with better drug loading and extended drug release. Ispaghula was used to enhance the drug loading while zein was employed to extend the drug release. Ibuprofen was employed as a model drug in this study. Ibuprofen-loaded alginate beads with and without ispaghula were prepared using vibration technology and coated with zein. The beads prepared with alginate alone were shown to have loading and entrapment efficiencies of 35% and 70% w/w, respectively. Addition of ispaghula in alginate showed a significant increase (p < 0.05) in the drug loading (42% w/w) and entrapment efficiency (84% w/w). Fourier-transform infrared spectroscopy confirmed the presence of ispaghula and zein coating in the alginate beads as well as the ibuprofen loading. Scanning electron microscopy revealed better spherical geometry in the beads with ispaghula. The surface morphology of the uncoated beads was rough due to crystalline and surface drug. The zein coating has produced a smoother surface and particle adhesion. Differential scanning calorimetry has shown a reduction in drug crystallinity. Alginate beads extended the drug release for 4 h and the presence of zein extended the release for 6 h.
    MeSH terms: Alginates; Calorimetry, Differential Scanning; Hexuronic Acids; Ibuprofen; Microscopy, Electron, Scanning; Psyllium; Vibration; Zein; Spectroscopy, Fourier Transform Infrared; Glucuronic Acid; Drug Liberation
  11. Abohabib AM, Fayed MM, Labib AH
    J Orthod, 2018 09;45(3):149-156.
    PMID: 29874972 DOI: 10.1080/14653125.2018.1481710
    OBJECTIVE: To investigate the effect of low-intensity laser therapy on mini-implant stability using resonance frequency analysis during canine retraction with fixed appliances.

    DESIGN: A split-mouth randomised clinical trial.

    SETTING: Subjects were recruited and treated in the outpatient clinic, Department of Orthodontics, Faculty of Dentistry, Cairo University.

    PARTICIPANTS: Fifteen subjects with mean age 20.9 (±3.4) years who required extraction of maxillary first premolar teeth and mini-implant-supported canine retraction.

    METHODS: Thirty orthodontic mini-implants were inserted bilaterally in the maxillary arches of recruited subjects following alignment and levelling. Mini-implants were immediately loaded with a force of 150 g using nickel titanium coil springs with split-mouth randomisation to a low-intensity laser-treated side and control side. The experimental sides were exposed to low-intensity laser therapy from a diode laser with a wavelength of 940 nm at (0, 7, 14, 21 days) after mini-implant placement. Mini-implant stability was measured using resonance frequency analysis at (0, 1, 2, 3, 4, 6, 8, 10 weeks) after implant placement.

    RESULTS: A total sample of 28 mini-implants were investigated with 14 in each group. Clinically, both mini-implant groups had the same overall success rate of 78.5%. There were no significant differences in resonance frequency scores between low-intensity laser and control sides from baseline to week 2. However, from week 3 to 10, the low-intensity laser sides showed significantly increased mean resonance frequency values compared to control (P > 0.05).

    CONCLUSIONS: Despite evidence of some significant differences in resonance frequency between mini-implants exposed to low-intensity laser light over a 10 weeks period there were no differences in mini-implant stability. Low-intensity laser light cannot be recommended as a clinically useful adjunct to promoting mini-implant stability during canine retraction.

    MeSH terms: Bicuspid; Humans; Maxilla; Orthodontics*; Dental Implants*; Orthodontic Anchorage Procedures*; Laser Therapy*
  12. Pandey M, Choudhury H, Yeun OC, Yin HM, Lynn TW, Tine CLY, et al.
    Curr Pharm Biotechnol, 2018;19(4):276-292.
    PMID: 29874994 DOI: 10.2174/1389201019666180605125234
    BACKGROUND: Targeting chemotherapeutic agents to the tumor tissues and achieving accumulation with ideal release behavior for desired therapy requires an ideal treatment strategy to inhibit division of rapid growing cancerous cells and as an outcome improve patient's quality of life. However, majority of the available anticancer therapies are well known for their systemic toxicities and multidrug resistance.

    METHODS: Application of nanotechnology in medicine have perceived a great evolution during past few decades. Nanoemulsion, submicron sized thermodynamically stable distribution of two immiscible liquids, has gained extensive importance as a nanocarrier to improve chemotherapies seeking to overcome the limitations of drug solubilization, improving systemic delivery of the chemotherapeutics to the site of action to achieve a promising inhibitory in tumor growth profile with reduced systemic toxicity.

    RESULTS AND CONCLUSION: This review has focused on potential application of nanoemulsion in the translational research and its role in chemotherapy using oral, parenteral and transdermal route to enhance systemic availability of poorly soluble drug. In summary, nanoemulsion is a multifunctional nanocarrier capable of enhancing drug delivery potential of cytotoxic agents, thereby, can improve the outcomes of cancer treatment by increasing the life-span of the patient and quality of life, however, further clinical research and characterization of interactive reactions should need to be explored.

    MeSH terms: Administration, Cutaneous; Administration, Oral; Antineoplastic Agents/administration & dosage*; Antineoplastic Agents/therapeutic use*; Emulsions; Humans; Infusions, Parenteral; Drug Delivery Systems; Nanotechnology*
  13. Kalra K, Chandrabose ST, Ramasamy TS, Kasim NHBA
    Curr Drug Targets, 2018;19(13):1463-1477.
    PMID: 29874998 DOI: 10.2174/1389450119666180605112917
    Diabetes mellitus is one of the leading causes of death worldwide. Loss and functional failure of pancreatic β-cells, the parenchyma cells in the islets of Langerhans, progress diabetes mellitus. The increasing incidence of this metabolic disorder necessitates efficient strategies to produce functional β-cells for treating diabetes mellitus. Human induced Pluripotent Stem Cells (hiPSC), hold potential for treating diabetes ownig to their self-renewal capacity and the ability to differentiate into β- cells. iPSC technology also provides unlimited starting material to generate differentiated cells for regenerative applications. Progress has also been made in establishing in-vitro culture protocols to yield definitive endoderm, pancreatic endoderm progenitor cells and β-cells via different reprogramming strategies and growth factor supplementation. However, these generated β-cells are still immature, lack functional characteristics and exhibit lower capability in reversing the diseases conditions. Current methods employed to generate mature and functional β-cells include; use of small and large molecules to enhance the reprogramming and differentiation efficiency, 3D culture systems to improve the functional properties and heterogeneity of differentiated cells. This review details recent advancements in the generation of mature β-cells by reprogramming stem cells into iPSCs that are further programmed to β-cells. It also provides deeper insight into current reprogramming protocols and their efficacy, focusing on the underlying mechanism of chemical-based approach to generate iPSCs. Furthermore, we have highlighted the recent differentiation strategies both in-vitro and in-vivo to date and the future prospects in the generation of mature β-cells.
    MeSH terms: Animals; Cell Differentiation; Cells, Cultured; Diabetes Mellitus/metabolism; Diabetes Mellitus/therapy*; Humans; Insulin/metabolism*; Signal Transduction; Regenerative Medicine; Insulin-Secreting Cells/cytology; Insulin-Secreting Cells/drug effects; Insulin-Secreting Cells/metabolism; Insulin-Secreting Cells/transplantation*; Small Molecule Libraries/pharmacology; Induced Pluripotent Stem Cells/cytology*; Cellular Reprogramming/drug effects
  14. Andiesta NS, Hamid MA, Lee K, Pau A
    JMIR Res Protoc, 2018 Jun 06;7(6):e10053.
    PMID: 29875086 DOI: 10.2196/10053
    BACKGROUND: In 2012, nearly 4000 children in Malaysia were referred to hospital pediatric dental services due to dental caries. Recent research has reported the effectiveness of dental home visits in preventing caries development in young children. Dental home visits (DHVs) are described as an ongoing relationship between the dentist and their patients, providing all aspects of a preventive oral health care program in the presence of the parents at home.

    OBJECTIVE: The objective of this study is to evaluate the cost-effectiveness of dental home visits and oral health information, in the form of educational leaflets, in preventing new caries development in young children, compared to those receiving only educational leaflets over a period of two years. Cost-effectiveness analysis will be used to evaluate the cost-effectiveness of dental home visits.

    METHODS: This is a collaborative project with the Oral Health Division of the Ministry of Health Malaysia. The Oral Health Division will provide access to a subsample from the National Oral Health of Preschoolers Survey which was carried out in 2015. The population of interest is children aged 5 and 6 years from kindergartens in the Selangor state of Malaysia. The study adopted a societal perspective for cost-effectiveness analysis and all types of resources that are of value to society will be included in analyzing the costs; such as cost to the patient, cost to the provider or institution, and indirect costs because of loss of productivity.

    RESULTS: The trial has been approved by the International Medical University Malaysia's Joint Research and Ethics Committee (Project ID: IMU R157-2014 [File III - 2016]). This trial is currently recruiting participants.

    CONCLUSIONS: The number of young children in Malaysia who have been referred to the hospital children's dentistry service for severe caries is disturbing. The cost of dental treatment in young children is high due to the severity of the caries which require an aggressive treatment, and the need for general anesthesia or sedation. This study will provide information on the cost and effectiveness of DHVs in caries prevention of young children in Malaysia.

    REGISTERED REPORT IDENTIFIER: RR1-10.2196/10053.

    MeSH terms: Anesthesia, General; Child; Cost-Benefit Analysis; Dental Caries; Dental Service, Hospital; Dentists; House Calls; Humans; Malaysia; Oral Health; Parents; Surveys and Questionnaires; Universities; Ethics Committees; Dental Care for Children
  15. Rodrigues P, Patel SA, Harewood L, Olan I, Vojtasova E, Syafruddin SE, et al.
    Cancer Discov, 2018 Jul;8(7):850-865.
    PMID: 29875134 DOI: 10.1158/2159-8290.CD-17-1211
    Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states.Significance: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 850-65. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 781.
    MeSH terms: Animals; Enhancer Elements, Genetic*; Humans; Kidney Neoplasms/genetics; Kidney Neoplasms/metabolism*; Kidney Neoplasms/pathology; Lung Neoplasms/secondary; Male; Gene Expression Regulation, Neoplastic; NF-kappa B/metabolism*; Mice, SCID; Mice, Inbred NOD; Cell Line, Tumor; Mice; Basic Helix-Loop-Helix Transcription Factors/genetics*
  16. Rahman SA, Singh J, Muthusamy R, Alam MK
    Contemp Clin Dent, 2018 6 8;9(2):319-322.
    PMID: 29875581 DOI: 10.4103/ccd.ccd_870_17
    Eagle's syndrome (ES) refers to a group of various types and patterns of pain which spans over the head-and-neck region owing to an elongated styloid process or calcified stylohyoid ligament. These symptoms are often confused with those attributed to a wide variety of facial neuralgias. The diagnosis of ES is usually made through clinical exclusion which is then confirmed radiographically. Patients with ES are initially managed with nonsurgical therapy, but surgical resection seems to be the treatment of choice. The styloid process shortening can be achieved through an intraoral or extraoral approach. This clinical case report describes such a case of ES after sustaining neck trauma.
    MeSH terms: Facial Neuralgia; Humans; Ligaments; Ossification, Heterotopic; Pain; Temporal Bone
  17. Srisonchai R, Enghoff H, Likhitrakarn N, Panha S
    Zookeys, 2018.
    PMID: 29875597 DOI: 10.3897/zookeys.761.24214
    The dragon millipede genus Desmoxytes s.l. is split into five genera, based on morphological characters and preliminary molecular phylogenetic analyses. The present article includes a review of Desmoxytes s.s., while future articles will deal with Hylomus Cook and Loomis, 1924 and three new genera which preliminarily are referred to as the 'acantherpestes', 'gigas', and 'spiny' groups. Diagnostic morphological characters of each group are discussed. Hylomus is resurrected as a valid genus and the following 33 species are assigned to it: H. asper (Attems, 1937), comb. n., H. cattienensis (Nguyen, Golovatch & Anichkin, 2005), comb. n., H. cervarius (Attems, 1953), comb. n., H. cornutus (Zhang & Li, 1982), comb. n., H. draco Cook & Loomis, 1924, stat. rev., H. enghoffi (Nguyen, Golovatch & Anichkin, 2005), comb. n., H. eupterygotus (Golovatch, Li, Liu & Geoffroy, 2012), comb. n., H. getuhensis (Liu, Golovatch & Tian, 2014), comb. n., H. grandis (Golovatch, VandenSpiegel & Semenyuk, 2016), comb. n., H. hostilis (Golovatch & Enghoff, 1994), comb. n., H. jeekeli (Golovatch & Enghoff, 1994), comb. n., H. lingulatus (Liu, Golovatch & Tian, 2014), comb. n., H. laticollis (Liu, Golovatch & Tian, 2016), comb. n., H. longispinus (Loksa, 1960), comb. n., H. lui (Golovatch, Li, Liu & Geoffroy, 2012), comb. n., H. minutuberculus (Zhang, 1986), comb. n., H. nodulosus (Liu, Golovatch & Tian, 2014), comb. n., H. parvulus (Liu, Golovatch & Tian, 2014), comb. n., H. phasmoides (Liu, Golovatch & Tian, 2016), comb. n., H. pilosus (Attems, 1937), comb. n., H. proximus (Nguyen, Golovatch & Anichkin, 2005), comb. n., H. rhinoceros (Likhitrakarn, Golovatch & Panha, 2015), comb. n., H. rhinoparvus (Likhitrakarn, Golovatch & Panha, 2015), comb. n., H. scolopendroides (Golovatch, Geoffroy & Mauriès, 2010), comb. n., H. scutigeroides (Golovatch, Geoffroy & Mauriès, 2010), comb. n., H. similis (Liu, Golovatch & Tian, 2016), comb. n., H. simplex (Golovatch, VandenSpiegel & Semenyuk, 2016), comb. n., H. simplipodus (Liu, Golovatch & Tian, 2016), comb. n., H. specialis (Nguyen, Golovatch & Anichkin, 2005), comb. n., H. spectabilis (Attems, 1937), comb. n., H. spinitergus (Liu, Golovatch & Tian, 2016), comb. n., H. spinissimus (Golovatch, Li, Liu & Geoffroy, 2012), comb. n. and H. variabilis (Liu, Golovatch & Tian, 2016), comb. n.Desmoxytes s.s. includes the following species: D. breviverpa Srisonchai, Enghoff & Panha, 2016; D. cervina (Pocock,1895); D. delfae (Jeekel, 1964); D. des Srisonchai, Enghoff & Panha, 2016; D. pinnasquali Srisonchai, Enghoff & Panha, 2016; D. planata (Pocock, 1895); D. purpurosea Enghoff, Sutcharit & Panha, 2007; D. takensis Srisonchai, Enghoff & Panha, 2016; D. taurina (Pocock, 1895); D. terae (Jeekel, 1964), all of which are re-described based mainly on type material. Two new synonyms are proposed: Desmoxytes pterygota Golovatch & Enghoff, 1994, syn. n. (= Desmoxytes cervina (Pocock, 1895)), Desmoxytes rubra Golovatch & Enghoff, 1994, syn. n. (= Desmoxytes delfae (Jeekel, 1964)). Six new species are described from Thailand: D. aurata Srisonchai, Enghoff & Panha, sp. n., D. corythosaurus Srisonchai, Enghoff & Panha, sp. n., D. euros Srisonchai, Enghoff & Panha, sp. n., D. flabella Srisonchai, Enghoff & Panha, sp. n., D. golovatchi Srisonchai, Enghoff & Panha, sp. n., D. octoconigera Srisonchai, Enghoff & Panha, sp. n., as well as one from Malaysia: D. perakensis Srisonchai, Enghoff & Panha, sp. n., and one from Myanmar: D. waepyanensis Srisonchai, Enghoff & Panha, sp. n. The species can mostly be easily distinguished by gonopod structure in combination with other external characters; some cases of particularly similar congeners are discussed. All species of Desmoxytes s.s. seem to be endemic to continental Southeast Asia (except the 'tramp' species D. planata). Some biological observations (relationship with mites, moulting) are recorded for the first time. Complete illustrations of external morphological characters, an identification key, and distribution maps of all species are provided.
    MeSH terms: Animals; Arthropods; Myanmar; Malaysia; Mites; Perciformes; Phylogeny; Salicylates; Thailand; Molting
  18. Tham HW, Balasubramaniam V, Ooi MK, Chew MF
    Front Microbiol, 2018;9:1040.
    PMID: 29875751 DOI: 10.3389/fmicb.2018.01040
    Zika virus (ZIKV) has emerged as a new global health threat. Since its first discovery in Zika forest in Uganda, this virus has been isolated from several mosquito species, including Aedes aegypti and Aedes albopictus. The geographical distribution of these mosquito species across tropical and subtropical regions has led to several outbreaks, including the recent pandemic in Brazil, followed by the Pacific islands and other areas of North and South America. This has gained attention of the scientific community to elucidate the epidemiology and transmission of ZIKV. Despite its strong attention on clinical aspects for healthcare professionals, the relationships between ZIKV and its principal vectors, A. aegypti and A. albopictus, have not gained substantial interest in the scientific research community. As such, this review aims to summarize the current knowledge on ZIKV tropism and some important mechanisms which may be employed by the virus for effective strategies on viral survival in mosquitoes. In addition, this review identifies the areas of research that should be placed attention to, for which to be exploited for novel mosquito control strategies.
    MeSH terms: Zika Virus Infection; Zika Virus; Aedes; Animals; Attention; Brazil; Disease Outbreaks; Humans; Mosquito Control; Pacific Islands; Uganda; Global Health; Tropism; Pandemics; Forests
  19. Mesaik AM, Poh HW, Bin OY, Elawad I, Alsayed B
    Open Access Maced J Med Sci, 2018 May 20;6(5):757-766.
    PMID: 29875842 DOI: 10.3889/oamjms.2018.168
    BACKGROUND: Ziziphus jujuba belongs to family Rhamnaceae widely distributed in subtropical and tropical countries. It is used traditionally for several pharmacological purposes including anti-inflammation, antidiarrhoeal and antibacterial, as well as tonic and sometimes as hypnotic (sedative).

    AIM: To determine the in vivo antidiarrhoeal, antibacterial and anti-inflammatory activities of Z. jujuba fruit ethanolic extract.

    METHOD: The fruit was macerated and extracted by 95% (v/v) ethanol. The antidiarrhoeal activity was evaluated using castor oil and Escherichia coli induced diarrhoea mouse model. The antidiarrhoeal and antibacterial activity was investigated at graded doses (400-1200 mg/kg). The anti-inflammatory effects were tested using the carrageenan-induced paw oedema in female Wistar rats. Rat's treatment groups received tragacanth, 100 mg/kg diclofenac sodium, 800 mg/kg, 1200 mg/kg or 1600 mg/kg of an ethanolic extract of Z. jujuba (EEZJ). All treatment groups were fed with the compounds one hour before carrageenan injection at of rat's paw. Also, the EEZJ was further analysed by HPLC-PDA system for identification of the presence of betulinic acid and quercetin.

    RESULTS: EEZJ different doses did not show inhibitory activity against castor oil induced diarrhoea except for the higher (1200 mg/kg) dose. However, the frequency of defecation of stools and watery stool were reduced significantly when compared to control group (P ≤ 0.05 and P ≤ 0.01 respectively), resulted in overall 67% inhibition of diarrhoea. Our anti-inflammatory results demonstrated that EEZJ was able to inhibit the carrageenan-induced paw oedema in rats to a significant degree (p ≤ 0.05) and the paw volume and thickness of both left and right paw were affected compared to the negative control group.

    CONCLUSION: EEZJ possesses antidiarrhoeal and antibacterial activity in a dose depending manner and may provide a pharmacological basis for its clinical use in diarrheal diseases. The activity may partially be due to the presence of betulinic acid and quercetin.

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