Browse publications by year: 2018

  1. Yee A, Loh HS, Danaee M, Riahi S, Ng CG, Sulaiman AH
    J Sex Med, 2018 02;15(2):159-166.
    PMID: 29275046 DOI: 10.1016/j.jsxm.2017.12.004
    BACKGROUND: Methadone has been recognized as an effective maintenance treatment for opioid dependence. However, its use is associated with several complications, including sexual dysfunction in men.

    AIM: To assess plasma testosterone and sexual function in Southeast Asian men on methadone maintenance treatment (MMT) or buprenorphine maintenance treatment (BMT).

    METHODS: 76 sexually active men on MMT (mean age = 43.30 ± 10.32 years) and 31 men on BMT (mean age = 41.87 ± 9.76 years) from a Southeast Asian community were evaluated using plasma total testosterone (TT) and prolactin levels, body mass index, social demographics, substance use measures, and depression severity scale.

    OUTCOMES: Prevalence and associated factors of TT level lower than the reference range in men on MMT or BMT.

    RESULTS: More than 1 third of men (40.8%, n = 31) on MMT had TT levels lower than the reference range, whereas 1 fourth of men (22.6%, n = 7) on BMT did. At univariate analysis, MMT vs BMT (β = 0.298, adjusted R2 = 0.08, P = .02) and body mass index (β = -0.23, adjusted R2 = 0.12, P = .02) were associated with changes in TT after stepwise regression. There were no significant associations with age; Opiate Treatment Index Q scores for alcohol, heroin, stimulant, tobacco, or cannabis use and social functioning domain; education levels; hepatitis C status; and severity of depression. Prolactin level did not differ between the MMT and BMT groups.

    CLINICAL IMPLICATIONS: The sex hormonal assay should be used regularly to check men on MMT.

    STRENGTHS AND LIMITATIONS: This is the first study conducted in the Southeast Asian community. Our study was limited by the lack of a healthy group as the reference for serum levels of testosterone and prolactin.

    CONCLUSIONS: The findings showed that plasma testosterone levels are lower in MMT than in BMT users. Hence, men who are receiving MMT should be screened for hypogonadism routinely in the clinical setting. Yee A, Loh HS, Danaee M, et al. Plasma Testosterone and Sexual Function in Southeast Asian Men Receiving Methadone and Buprenorphine Maintenance Treatment. J Sex Med 2018;15:159-166.

    MeSH terms: Adult; Analgesics, Opioid/administration & dosage; Buprenorphine/administration & dosage*; Depression/epidemiology; Female; Humans; Hypogonadism/epidemiology; Male; Methadone/administration & dosage*; Middle Aged; Opioid-Related Disorders/drug therapy; Prolactin/blood; Sexual Dysfunction, Physiological/epidemiology; Testosterone/blood*; Prevalence; Opiate Substitution Treatment/methods*
  2. Lau YY, Wong YS, Ang TZ, Ong SA, Lutpi NA, Ho LN
    Environ Sci Pollut Res Int, 2018 Mar;25(7):7067-7075.
    PMID: 29275478 DOI: 10.1007/s11356-017-1069-9
    The theme of present research demonstrates performance of copper (II) sulfate (CuSO4) as catalyst in thermolysis process to treat reactive black 5 (RB 5) dye. During thermolysis without presence of catalyst, heat was converted to thermal energy to break the enthalpy of chemical structure bonding and only 31.62% of color removal. With CuSO4 support as auxiliary agent, the thermally cleaved molecular structure was further destabilized and reacted with CuSO4. Copper ions functioned to delocalize the coordination of π of the lone paired electron in azo bond, C=C bond of the sp2 carbon to form C-C of the sp3 amorphous carbon in benzene and naphthalene. Further, the radicals of unpaired electrons were stabilized and RB 5 was thermally decomposed to methyl group. Zeta potential measurement was carried out to analyze the mechanism of RB 5 degradation and measurement at 0 mV verified the critical chemical concentration (CCC) (0.7 g/L copper (II) sulfate), as the maximum 92.30% color removal. The presence of copper (II) sulfate catalyst has remarkably increase the RB 5 dye degradation as the degradation rate constant without catalyst, k1 is 6.5224 whereas the degradation rate constant with catalyst, k2 is 25.6810. This revealed the correlation of conversion of thermal energy from heat to break the chemical bond strength, subsequent fragmentation of RB 5 dye molecular mediated by copper (II) sulfate catalyst. The novel framework on thermolysis degradation of molecular structure of RB 5 with respect to the bond enthalpy and interfacial intermediates decomposition with catalyst reaction were determined.
    MeSH terms: Azo Compounds/analysis*; Catalysis; Coloring Agents/analysis*; Hot Temperature; Kinetics; Naphthalenesulfonates/analysis*; Water Pollutants, Chemical/analysis*; Water Purification/methods*; Copper Sulfate/chemistry*
  3. Chen C, Chong NS, Smith R
    Math Biosci, 2018 02;296:98-112.
    PMID: 29273381 DOI: 10.1016/j.mbs.2017.12.002
    Mass-media reports on an epidemic or pandemic have the potential to modify human behaviour and affect social attitudes. Here we construct a Filippov model to evaluate the effects of media coverage and quarantine on the transmission dynamics of influenza. We first choose a piecewise smooth incidence rate to represent media reports being triggered once the number of infected individuals exceeds a certain critical level [Formula: see text] . Further, if the number of infected cases increases and exceeds another larger threshold value [Formula: see text] ( [Formula: see text] ), we consider that the incidence rate tends to a saturation level due to the protection measures taken by individuals; meanwhile, we begin to quarantine susceptible individuals when the number of susceptible individuals is larger than a threshold value Sc. Then, for each susceptible threshold value Sc, the global properties of the Filippov model with regard to the existence and stability of all possible equilibria and sliding-mode dynamics are examined, as we vary the infected threshold values [Formula: see text] and [Formula: see text] . We show generically that the Filippov system stabilizes at either the endemic equilibrium of the subsystem or the pseudoequilibrium on the switching surface or the endemic equilibrium [Formula: see text] depending on the choice of the threshold values. The findings suggest that proper combinations of infected and susceptible threshold values can maintain the number of infected individuals either below a certain threshold level or at a previously given level.
    MeSH terms: Humans; Influenza, Human/transmission*; Mass Media*; Models, Theoretical*; Quarantine*
  4. Marcus AJ, Iezhitsa I, Agarwal R, Vassiliev P, Spasov A, Zhukovskaya O, et al.
    Eur J Pharm Sci, 2018 Mar 01;114:245-254.
    PMID: 29274441 DOI: 10.1016/j.ejps.2017.12.015
    In an effort to find new ocular hypotensive drug candidates, a total of 27 condensed benzimidazoles based compounds were screened. This study was done in normotensive rats and rebound tonometry was used to estimate IOP. All compounds were topically applied as a single drop, unilaterally, at 3 different concentrations (0.1%, 0.2% and 0.4%). The contralateral eye was instilled with vehicle and served as control. The IOP reduction was measured up to 6h. It was observed that with a single topical instillation, compounds RU 551, RU 555, RU839 (pyrimido[1,2-a]benzimidazole derivatives), and RU 615 (imidazo[1,2-a]benzimidazole derivative) showed significant IOP lowering activities in ocular normotensive rats. All other compounds showed none, weak and inconsistent IOP lowering effect. The relationship between ability of IOP lowering and hypotensive activities was studied. According to the pharmacophore analysis, the class of pyrimido[1,2-a]benzimidazole is more promising than the class of imidazo[1,2-a]benzimidazole as a source of compounds with high IOP lowering activity. Pharmacophore analysis also showed that the critical features of high IOP lowering activity are methoxyphenyl and [phenyl]alkyl fragments, and non-conjugated six-membered heterocyclic ring.
    MeSH terms: Animals; Antihypertensive Agents/administration & dosage*; Antihypertensive Agents/chemistry*; Benzimidazoles/administration & dosage*; Benzimidazoles/chemistry*; Intraocular Pressure/drug effects*; Intraocular Pressure/physiology; Structure-Activity Relationship; Treatment Outcome; Rats, Sprague-Dawley; Rats; Administration, Ophthalmic
  5. Ghawanmeh AA, Chong KF, Sarkar SM, Bakar MA, Othaman R, Khalid RM
    Eur J Med Chem, 2018 Jan 20;144:229-242.
    PMID: 29274490 DOI: 10.1016/j.ejmech.2017.12.029
    Antimitotic colchicine possesses low therapeutic index due to high toxicity effects in non-target cell. However, diverse colchicine analogs have been derivatized as intentions for toxicity reduction and structure-activity relationship (SAR) studying. Hybrid system of colchicine structure with nontoxic biofunctional compounds modified further affords a new entity in chemical structure with enhanced activity and selectivity. Moreover, nanocarrier formulation strategies have been used for colchicine delivery. This review paper focuses on colchicine nanoformulation, chemical synthesis of colchicine prodrugs and codrugs with different linkers, highlights linker chemical nature and biological activity of synthesized compounds. Additionally, classification of colchicine prodrugs based on type of conjugates is discussed, as biopolymers prodrugs, fluorescent prodrug, metal complexes prodrug, metal-labile prodrug and bioconjugate prodrug. Finally, we briefly summarized the biological importance of colchicine nanoformulation, colchicine prodrugs and codrugs.
    MeSH terms: Animals; Colchicine/analogs & derivatives*; Colchicine/pharmacology*; Humans; Mitosis/drug effects; Prodrugs/pharmacology*; Prodrugs/chemistry*; Structure-Activity Relationship; Drug Design; Tubulin Modulators/pharmacology*; Tubulin Modulators/chemistry*
  6. Chong YS, Mai CW, Leong CO, Wong LC
    Cutan Ocul Toxicol, 2018 Mar;37(1):52-60.
    PMID: 28554225 DOI: 10.1080/15569527.2017.1335748
    PURPOSE: Dysfunction of the microRNA (miRNA)-processing enzyme DICER1 and Alu RNA accumulation are linked to the pathogenesis of age-related macular degeneration (AMD). This study determined the optimal dose of lutein (LUT) and zeaxanthin (ZEA) to protect human retinal pigment epithelium (RPE) cells against hydrogen peroxide (H2O2). The effect of the optimal dose of LUT and ZEA as DICER1 and Alu RNA modulators in cultured human RPE cells challenged with H2O2 was investigated.

    MATERIALS AND METHODS: ARPE-19 cells were pre-treated with LUT, ZEA, or both for 24 h before 200 μM H2O2 challenge. Cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. DICER1 and Alu RNA were quantified by western blotting and real-time polymerase chain reaction, respectively.

    RESULTS: H2O2 increased cell Alu RNA expression and decreased cell viability of ARPE-19, but had no significant impact on the DICER1 protein level. LUT, alone and in combination with ZEA pre-treatment, prior to H2O2 challenge significantly improved cell viability of ARPE-19 and reduced the level of Alu RNA compared to the negative control.

    CONCLUSIONS: These results support the use of LUT alone, and in combination with ZEA, in AMD prevention and treatment. This study is also the first to report LUT modulating effects on Alu RNA.

    MeSH terms: Cell Line; Cell Survival/drug effects; Drug Therapy, Combination; Epithelial Cells/drug effects*; Epithelial Cells/metabolism; Humans; Hydrogen Peroxide/toxicity*; Macular Degeneration/prevention & control*; RNA/metabolism*; Lutein/pharmacology*; Alu Elements/genetics*; Ribonuclease III/metabolism; DEAD-box RNA Helicases/metabolism; Retinal Pigment Epithelium/cytology*; Zeaxanthins/pharmacology
  7. Sankari M, Rao PR, Hemachandran H, Pullela PK, Doss C GP, Tayubi IA, et al.
    J Biotechnol, 2018 Jan 20;266:89-101.
    PMID: 29247672 DOI: 10.1016/j.jbiotec.2017.12.010
    Carotenoids are isoprenoid pigments synthesized exclusively by plants and microorganisms and play critical roles in light harvesting, photoprotection, attracting pollinators and phytohormone production. In recent years, carotenoids have been used for their health benefits due to their high antioxidant activity and are extensively utilized in food, pharmaceutical, and nutraceutical industries. Regulation of carotenoid biosynthesis occurs throughout the life cycle of plants, with vibrant changes in composition based on developmental needs and responses to external environmental stimuli. With advancements in metabolic engineering techniques, there has been tremendous progress in the production of industrially valuable secondary metabolites such as carotenoids. Application of metabolic engineering and synthetic biology has become essential for the successful and improved production of carotenoids. Synthetic biology is an emerging discipline; metabolic engineering approaches may provide insights into novel ideas for biosynthetic pathways. In this review, we discuss the current knowledge on carotenoid biosynthetic pathways and genetic engineering of carotenoids to improve their nutritional value. In addition, we investigated synthetic biological approaches for the production of carotenoids. Theoretical biology approaches that may aid in understanding the biological sciences are discussed in this review. A combination of theoretical knowledge and experimental strategies may improve the production of industrially relevant secondary metabolites.
    MeSH terms: Carotenoids/biosynthesis*; Carotenoids/genetics*; Computer Simulation*; Synthetic Biology/methods*; Metabolic Engineering/methods*
  8. Law FL, Zulkifli I, Soleimani AF, Liang JB, Awad EA
    Asian-Australas J Anim Sci, 2018 Aug;31(8):1291-1300.
    PMID: 29268592 DOI: 10.5713/ajas.17.0581
    OBJECTIVE: This experiment was conducted to investigate the effects of dietary crude protein (CP) level and exogenous protease supplementation on growth performance, serum metabolites, carcass traits, small intestinal morphology and endogenous protease activity in broiler chickens reared under a tropical climate.

    METHODS: A total of 480 day-old male broiler chicks were randomly assigned to eight dietary treatments in a 4×2 factorial arrangement. The main effects were CP level (21.0%, 19.7%, 18.5%, or 17.2% from 1 to 21 days and 19.0%, 17.9%, 16.7%, or 15.6% from 22 to 35 days) and protease enzyme supplementation (0 ppm or 500 ppm). All experimental diets were fortified with synthetic feed-grade lysine, methionine, threonine and tryptophan to provide the minimum amino acid recommended levels for Cobb 500.

    RESULTS: Reducing dietary CP linearly reduced (p<0.05) growth performance, serum albumin, total protein, and carcass traits and increased (p<0.05) serum triglycerides and abdominal fat. There was no consistent effect of reducing dietary CP on morphological parameters of the intestine and on the pancreatic and intestinal endogenous protease activity (p>0.05). Protease supplementation improved (p<0.05) feed conversion ratio, body weight gain, carcass yield and intestinal absorptive surface area.

    CONCLUSION: Protease supplementation, as measured by growth performance, intestinal morphology and carcass yield, may alleviate the detrimental effects of low protein diets in broiler chickens.

  9. Baiee FH, Wahid H, Rosnina Y, Ariff O, Yimer N, Jeber Z, et al.
    Cryobiology, 2018 02;80:43-50.
    PMID: 29269043 DOI: 10.1016/j.cryobiol.2017.12.006
    This study aims to assess the effect of Eurycoma longifolia aqueous extract on chilled and cryopreserved quality of bull sperm. Semen samples were obtained from four Simmental-Brangus. Each sample was divided into two fractions: the first fraction was used for chilling the semen, and the second fraction was used for the freezing process. Both fractions were extended with Tris-egg yolk extender supplemented with 0.0, 0.25, 0.5, 1.0, 2.5, 5.0, and 7.5 mg/ml Eurycoma longifolia aqueous extract. The diluted chilled fraction was chilled at 5 °C for 6 days, whereas the frozen-thawed fraction was frozen in liquid nitrogen. Data revealed that 1 mg/ml E. longifolia aqueous extract yielded significantly (p 
    MeSH terms: Animals; Cattle; Cryoprotective Agents/pharmacology*; DNA/drug effects; Egg Yolk; Freezing; Male; Plant Extracts/pharmacology*; Semen Preservation/methods*; Semen Preservation/veterinary; Sperm Motility/drug effects; Spermatozoa/drug effects; Spermatozoa/physiology; Tromethamine; Lipid Peroxidation/drug effects; Cryopreservation/methods*; Cryopreservation/veterinary; Eurycoma*
  10. Oo A, Rausalu K, Merits A, Higgs S, Vanlandingham D, Bakar SA, et al.
    Antiviral Res, 2018 02;150:101-111.
    PMID: 29269135 DOI: 10.1016/j.antiviral.2017.12.012
    The past decade has seen the re-emergence of Chikungunya virus (CHIKV) as a major global health threat, affecting millions around the world. Although fatal infections are rare among infected patients, the occurrence of long-lasting polyarthralgia has a significant impact on patients' quality of lives and ability to work. These issues were the stimuli for this study to determine the potential of baicalin, a bioflavonoid, as the novel antiviral compound against CHIKV. It was found that baicalin was well tolerated by Vero, BHK-21 and HEK 293T cells with maximal nontoxic doses >600 μM, ≈ 350 μM and ≈110 μM, respectively. Antiviral assays indicated that baicalin was the most effective inhibitor when tested for its direct virucidal activity with EC50 ≈ 7 μM, followed by inhibition of virus entry into the host cell, attachment of virus particle to cellular receptors and finally intracellular replication of viral RNA genome. In silico analysis using molecular docking demonstrated close interactions between baicalin and CHIKV envelope protein with considerably strong binding affinity of -9.7 kcal/mol. qRT-PCR analysis revealed that baicalin had the greatest effect on the synthesis of viral negative stand RNA with EC50 ≈ 0.4 μM followed by the inhibition of synthesis of positive-strand genomic (EC50 ≈ 13 μM) and subgenomic RNAs (EC50 ≈ 14 μM). These readings indicate that the compound efficiently inhibits replicase complexes formation but is a less potent inhibitor of existing replicase complexes. Coherent with this hypothesis, the use of recombinant CHIKV replicons harboring Renilla luciferase marker showed that replication of corresponding replicon RNAs was only slightly downregulated at higher doses of baicalin, with EC50 > 100 μM. Immunofluorescence and western blotting experiments demonstrated dose-dependent inhibition of expression of different viral proteins. It was also observed that levels of important protein markers for cellular autophagy (LC3) and apoptosis (Bax) were reduced in baicalin treatment groups as compared with untreated virus infected controls. In summary, given its low toxicity and high efficacy against CHIKV, baicalin has great potential to be developed as the novel antiviral compound for CHIKV. In vivo studies to evaluate its activity in a more complexed system represent a necessary step for future analysis.
    MeSH terms: Animals; Antiviral Agents/pharmacology*; Antiviral Agents/chemistry; Cercopithecus aethiops; Chikungunya virus/drug effects*; Dogs; Dose-Response Relationship, Drug; Flavonoids/pharmacology*; Flavonoids/chemistry; Humans; Vero Cells; Virus Replication/drug effects; Genes, Reporter; Virus Attachment/drug effects; Virus Internalization/drug effects; Chikungunya Fever/drug therapy; Chikungunya Fever/virology*
  11. Mohmmed AO, Nasif MS, Al-Kayiem HH
    Data Brief, 2018 Feb;16:527-530.
    PMID: 29270452 DOI: 10.1016/j.dib.2017.11.026
    The data presented in this article were the basis for the study reported in the research articles entitled "Statistical assessment of experimental observation on the slug body length and slug translational velocity in a horizontal pipe" (Al-Kayiem et al., 2017) [1] which presents an experimental investigation of the slug velocity and slug body length for air-water tow phase flow in horizontal pipe. Here, in this article, the experimental set-up and the major instruments used for obtaining the computed data were explained in details. This data will be presented in the form of tables and videos.
    MeSH terms: Animals; Biometry; Interior Design and Furnishings; Protein Processing, Post-Translational; Gastropoda; Physical Phenomena
  12. Mosavat M, Omar SZ, Tan PC, Razif MFM, Sthaneshwar P
    Arch Gynecol Obstet, 2018 03;297(3):797-803.
    PMID: 29270728 DOI: 10.1007/s00404-017-4617-0
    PURPOSE: To assess the association of serum leptin and its receptor (SLeptinR) with the risk of gestational diabetes mellitus (GDM) and to evaluate the longitudinal circulation of these peptides in pregnancy.

    METHODS: This study consisted of 53 subjects diagnosed with GDM and 43 normal glucose tolerance (NGT) pregnant women. Serum leptin and SLeptinR were measured at 24-28 weeks, prior and after delivery, and post-puerperium.

    RESULTS: Lower levels of leptin and SLeptinR were observed in GDM compared to NGT. Leptin [OR 0.97 (95% CI 0.94-1.0)] and SLeptinR [OR 0.86 (95% CI 0.79-0.93]) were inversely associated with GDM. Participants in the lowest tertile for leptin and SLeptinR had a 2.8-fold (95% CI 1.0-7.6) and a 5.7-fold (95% CI 1.9-17.3) higher risk of developing GDM compared with the highest tertile, respectively. These relationships were attenuated after adjustment for covariates. In both the groups, peak leptin was observed at 24-28 weeks, decreasing continuously during pregnancy (p > 0.05) and after delivery (p 

    MeSH terms: Adult; Female; Glucose/analysis; Humans; Middle Aged; Pregnancy; Prospective Studies; Case-Control Studies; Diabetes, Gestational/blood*; Leptin/blood*; Postpartum Period; Receptors, Leptin/blood*
  13. Kamishima M, Hattori T, Suzuki G, Matsukami H, Komine C, Horii Y, et al.
    J Appl Toxicol, 2018 05;38(5):649-655.
    PMID: 29271492 DOI: 10.1002/jat.3569
    Exposure to endocrine-disrupting chemicals may adversely affect animals, particularly during development. Tris(1,3-dichloroisopropyl) phosphate (TDCIPP) is an organophosphate with anti-androgen function in vitro that is present in indoor dust at relatively high concentrations. In male rats, androgens are necessary for the development of reproductive organs, as well as the endocrine and central nervous systems. However, we currently do not know the exact effects of TDCIPP exposure through suckling on subsequent reproductive behavior in males. Here, we show that TDCIPP exposure (25-250 mg kg-1 via oral administration over 28 consecutive days post-birth) suppressed male sexual behavior and reduced testes size. These changes were dose-dependent and appeared first in adults rather than in juveniles. These results demonstrate that TDCIPP exposure led to normal body growth and appearance in juveniles, but disrupted the endocrine system and physiology in adults. Therefore, assays should be performed using adult animals to ensure accuracy, and to confirm the influence of chemical substances given during early mammalian life.
    MeSH terms: Animals; Dose-Response Relationship, Drug; Male; Sexual Behavior, Animal/drug effects*; Testosterone/blood; Rats, Wistar; Rats; Endocrine Disruptors/toxicity*
  14. Abdullah WZW, Mackey BM, Karatzas KAG
    J Food Prot, 2018 Jan;81(1):93-104.
    PMID: 29271685 DOI: 10.4315/0362-028X.JFP-17-190
    Salmonella is an important foodborne pathogen, whose ability to resist stress and survive can vary among strains. This variability is normally not taken into account when predictions are made about survival in foods with negative consequences. Therefore, we examined the contribution of variable phenotypic properties to survival under stress in 10 Salmonella serovars. One strain (Typhimurium 10) was intentionally RpoS-negative; however, another strain (Heidelberg) showed an rpoS mutation, rendering it inactive. We assessed an array of characteristics (motility, biofilm formation, bile resistance, acid resistance, and colony morphology) that show major variability among strains associated with a 10- to 19-fold difference between the highest and the lowest strain for most characteristics. The RpoS status of isolates did not affect variability in the characteristics, with the exception of resistance to NaCl, acetic acid, lactic acid, and the combination of acetic acid and salt, where the variability between the highest and the lowest strain was reduced to 3.1-fold, 1.7-fold, 2-fold, and 1.7-fold, respectively, showing that variability was significant among RpoS-positive strains. Furthermore, we also found a good correlation between acid resistance and lysine decarboxylase activity, showing its importance for acid resistance, and demonstrated a possible role of RpoS in the lysine decarboxylase activity in Salmonella.
    MeSH terms: Acids/chemistry*; Animals; Bacterial Proteins/genetics*; Bacterial Proteins/chemistry; Salmonella; Salmonella Infections, Animal/microbiology*; Salmonella enterica/genetics*; Salmonella enterica/chemistry; Food Safety; Serogroup
  15. Yahya F, Gaffney K, Hamilton L, Lonsdale E, Leeder J, Brooksby A, et al.
    Rheumatology (Oxford), 2018 Apr 01;57(4):619-624.
    PMID: 29272541 DOI: 10.1093/rheumatology/kex457
    Objectives: To analyse long-term survival and efficacy of TNFi, reasons for switching or discontinuing, baseline predictors of response and remission in axial spondyloarthritis (axSpA) patients in a UK cohort.

    Methods: All patients with a physician-verified diagnosis of axSpA attending two specialist centres who fulfilled the eligibility criteria for TNFi were included. Routinely recorded patient data were reviewed retrospectively. Initial TNFi was recorded as the index drug.

    Results: Six hundred and fifty-one patients (94% AS) were included; adalimumab (n = 332), etanercept (n = 205), infliximab (n = 51), golimumab (n = 40) and certolizumab pegol (n = 23) were index TNFi. The mean (s.d.) duration from symptom onset to time of diagnosis was 8.6 (8.7) years and mean (s.d.) duration from diagnosis to TNFi initiation was 12.6 (11.5) years. A total of 224 (34.4%) stopped index TNFi, and 105/224 switched to a second TNFi. Median drug survival for index and second TNFi were 10.2 years (95% CI: 8.8, 11.6 years) and 5.5 years (95% CI: 2.7, 8.3 years), respectively (P < 0.05). Survival rates were not influenced by choice of TNFi. HLA-B27 predicted BASDAI50 and/or two or more point reduction within 6 months and long-term drug survival (P < 0.05). Low disease activity was predicted by non-smoking and low baseline BASDAI (P < 0.05).

    Conclusion: We have observed good TNFi survival rates in axSpA patients treated in a real-life setting. This is best for first TNFi and not influenced by drug choice.

    MeSH terms: Certolizumab Pegol; Etanercept; Adalimumab; Infliximab; Antibodies, Monoclonal; Humans; Retrospective Studies; Cohort Studies; HLA-B27 Antigen; Survival Rate; Spondylarthritis
  16. Humphries D, Jaques R, Dijkstra HP, International Syllabus in Sport and Exercise Medicine Group (ISSEMG)
    Br J Sports Med, 2018 Apr;52(8):490-492.
    PMID: 29263024 DOI: 10.1136/bjsports-2017-098477
    Training in the medical specialty of sport and exercise medicine is now available in many, but not all countries. Lack of resources may be a barrier to the development of this important specialty field and the International Syllabus in Sport and Exercise Medicine Group was convened to reduce one potential barrier, the need to develop a syllabus. The group is composed of 17 sport and exercise medicine specialists residing in 12 countries (Australia, Canada, India, Ireland, Malaysia, the Netherlands, Qatar, South Africa, Sweden, Switzerland, the UK and USA). This paper presents the first phase of this project covering the domains and general learning areas of a specialist training syllabus in sport and exercise medicine.
    MeSH terms: Curriculum*; Delphi Technique*; Education, Medical, Graduate*; Humans; International Cooperation; Sports Medicine*
  17. Wan Nur Ismah WAK, Takebayashi Y, Findlay J, Heesom KJ, Jiménez-Castellanos JC, Zhang J, et al.
    PMID: 29263066 DOI: 10.1128/AAC.01814-17
    Fluoroquinolone resistance in Gram-negative bacteria is multifactorial, involving target site mutations, reductions in fluoroquinolone entry due to reduced porin production, increased fluoroquinolone efflux, enzymes that modify fluoroquinolones, and Qnr, a DNA mimic that protects the drug target from fluoroquinolone binding. Here we report a comprehensive analysis, using transformation and in vitro mutant selection, of the relative importance of each of these mechanisms for fluoroquinolone nonsusceptibility using Klebsiella pneumoniae as a model system. Our improved biological understanding was then used to generate 47 rules that can predict fluoroquinolone susceptibility in K. pneumoniae clinical isolates. Key to the success of this predictive process was the use of liquid chromatography-tandem mass spectrometry to measure the abundance of proteins in extracts of cultured bacteria, identifying which sequence variants seen in the whole-genome sequence data were functionally important in the context of fluoroquinolone susceptibility.
    MeSH terms: Anti-Bacterial Agents/pharmacology; Chromatography, Liquid/methods*; Genotype; Klebsiella pneumoniae/drug effects; Klebsiella pneumoniae/genetics; Microbial Sensitivity Tests; Fluoroquinolones/pharmacology*; Tandem Mass Spectrometry/methods*
  18. Yogarajah T, Ong KC, Perera D, Wong KT
    J Virol, 2018 03 15;92(6).
    PMID: 29263272 DOI: 10.1128/JVI.01914-17
    Coxsackievirus A16 (CV-A16) and enterovirus A71 (EV-A71) are closely related enteroviruses that cause the same hand, foot, and mouth disease (HFMD), but neurological complications occur only very rarely in CV-A16 compared to EV-A71 infections. To elucidate host responses that may be able to explain these differences, we performed transcriptomic analysis and real-time quantitative PCR (RT-qPCR) in CV-A16-infected neuroblastoma cells (SK-N-SH), and the results showed that the radical S-adenosylmethionine domain containing 2 (RSAD2) was the highest upregulated gene in the antimicrobial pathway. Increased RSAD2 expression was correlated with reduced viral replication, while RSAD2 knockdown cells were correlated with increased replication. EV-A71 replication showed no apparent correlation to RSAD2 expressions. Absent in melanoma 2 (AIM2), which is associated with pyroptotic cell death, was upregulated in EV-A71-infected neurons but not in CV-A16 infection, suggesting that the AIM2 inflammasome played a significant role in suppressing EV-A71 replication. Chimeric viruses derived from CV-A16 and EV-A71 but containing swapped 5' nontranslated regions (5' NTRs) showed that RSAD2 expression/viral replication and AIM2 expression/viral replication patterns may be linked to the 5' NTRs of parental viruses. Differences in secondary structure of internal ribosomal entry sites within the 5' NTR may be responsible for these findings. Overall, our results suggest that CV-A16 and EV-A71 elicit different host responses to infection, which may help explain the apparent lower incidence of CV-A16-associated neurovirulence in HFMD outbreaks compared to EV-A71 infection.IMPORTANCE Although coxsackievirus A16 (CV-A16) and enterovirus A17 (EV-A71) both cause hand, foot, and mouth disease, EV-A71 has emerged as a leading cause of nonpolio, enteroviral fatal encephalomyelitis among young children. The significance of our research is in the identification of the possible differing and novel mechanisms of CV-A16 and EV-A71 inhibition in neuronal cells that may impact viral neuropathogenesis. We further showed that viral 5' NTRs may play significant roles in eliciting different host response mechanisms.
    MeSH terms: DNA-Binding Proteins/genetics; DNA-Binding Proteins/metabolism*; Humans; Neurons/metabolism*; Neurons/pathology; Neurons/virology; Proteins/genetics; Proteins/metabolism*; Virus Replication/physiology*; 5' Untranslated Regions*; Enterovirus A, Human/physiology*; Enterovirus C, Human/physiology*; Cell Line, Tumor; Gene Knockdown Techniques
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