Browse publications by year: 2017

  1. Lawrence RJ, Gatzweiler FW
    J Urban Health, 2017 08;94(4):592-596.
    PMID: 28695402 DOI: 10.1007/s11524-017-0182-x
    The current disconnection between access to increasing amounts of data about urbanization, health, and other global changes and the conflicting meanings and values of that data has created uncertainty and reduced the ability of people to act upon available information which they do not necessarily understand. We see a disconnection between increasing data availability and data processing capability and capacity. In response to this disconnection, modeling has been attributed an important role in international and national research programs in order to predict the future based on past and recent trends. Predictive models are often data heavy and founded on assumptions which are difficult to verify, especially regarding urban health issues in specific contexts. Producing large volumes of data warrants debate about what data are prerequisites for better understanding human health in changing urban environments. Another concern is how data and information can be used to apply knowledge. Making sense of empirical knowledge requires a new transdisciplinary knowledge domain created by a commitment to convergence between researchers in multiple academic disciplines and other actors and institutions in cities. Disciplinary-based researchers are no longer the sole producers of empirical knowledge. Today, diverse kinds of knowledge are becoming an emergent product of multiple societal stakeholders acting collectively to address challenges that impact on their habitat, their livelihood, and their health. Insights from complexity science also require a fundamental rethinking of the role and responsibility of human agency while admitting rather than denying complexity and radical uncertainty.
    MeSH terms: Humans; Urban Health*; Urbanization*; Interdisciplinary Communication*
  2. Chin KY
    Postgrad Med, 2017 Sep;129(7):734-746.
    PMID: 28695762 DOI: 10.1080/00325481.2017.1353394
    The prevalence of osteoporosis in Asian countries is growing. An effective screening method will enable patients at risk for osteoporosis to receive early diagnosis and treatment, and avoid overcrowding the limited dual-energy x-ray absorptiometry (DXA) machines available in Asian countries. Many simple osteoporosis screening algorithms have been developed but they are not validated for use in Asian populations. osteoporosis self-assessment tools for Asians (OSTA), established using a multinational Asian cohort, is the first screening algorithm that caters for the Asian populations. It considers only body weight and age in the algorithm. It shows consistently high performance and sensitivity in identifying postmenopausal women at risk for osteoporosis in many Asian countries. Its usage has been expanded for identifying osteoporosis in men, as well as determining fracture risk for both sexes. However, the performance of OSTA is influenced by age, sex, ethnicity and site of BMD measurement to define osteoporosis. Its usage is also limited in individuals without apparent risk factors. These limitations should be noted by physicians considering the use of OSTA in clinical setting. As a conclusion, OSTA is a cost-effective measure for osteoporosis screening in primary healthcare setting.
    MeSH terms: Adult; Age Factors; Aged; Aged, 80 and over; Algorithms*; Female; Humans; Male; Mass Screening/methods*; Middle Aged; Osteoporosis/diagnosis*; Osteoporosis/epidemiology; Self-Assessment; Sensitivity and Specificity; Sex Factors; Prevalence; Postmenopause; Risk Assessment; Asian Continental Ancestry Group*; Fractures, Bone/diagnosis*
  3. Ng CJ, Teo CH, Ho CCK, Tan HM
    Nat Rev Urol, 2017 Oct;14(10):630-636.
    PMID: 28695921 DOI: 10.1038/nrurol.2017.93
    Men have shorter life expectancy and higher mortality than women; however, only a few countries have dedicated men's health policies. Men's health reports can support the development of men's health policies. The 2013 Asian Men's Health Report (AMHR) systematically documents and compares the status of men's health across countries in Asia. The AMHR can be used as an exemplar to guide future men's health reports. The main challenges during creation of the AMHR were the lack of comprehensive health databases and the variety of data quality between countries. The AMHR revealed variations in mortality and morbidity across diseases, regions, and income groups, prompting a Delphi survey among men's health stakeholders to determine whether any dedicated men's health policies in Asia existed and to reach a consensus on the recommendations of men's health policies. The AMHR helped to promote men's health in Asia and across the world, generated research questions and collaborations, provided evidence to support development of men's health policies, identified the need to improve existing health databases, and developed a framework for the creation of other men's health reports.
    MeSH terms: Asia; Health Policy*; Humans; Male; Asian Continental Ancestry Group/statistics & numerical data*; Men's Health/statistics & numerical data*
  4. Bauer R, Conell J, Glenn T, Alda M, Ardau R, Baune BT, et al.
    Nord J Psychiatry, 2017 Aug;71(6):473-476.
    PMID: 28696841 DOI: 10.1080/08039488.2017.1334819
    BACKGROUND: Peer support is an established component of recovery from bipolar disorder, and online support groups may offer opportunities to expand the use of peer support at the patient's convenience. Prior research in bipolar disorder has reported value from online support groups.

    AIMS: To understand the use of online support groups by patients with bipolar disorder as part of a larger project about information seeking.

    METHODS: The results are based on a one-time, paper-based anonymous survey about information seeking by patients with bipolar disorder, which was translated into 12 languages. The survey was completed between March 2014 and January 2016 and included questions on the use of online support groups. All patients were diagnosed by a psychiatrist. Analysis included descriptive statistics and general estimating equations to account for correlated data.

    RESULTS AND CONCLUSIONS: The survey was completed by 1222 patients in 17 countries. The patients used the Internet at a percentage similar to the general public. Of the Internet users who looked online for information about bipolar disorder, only 21.0% read or participated in support groups, chats, or forums for bipolar disorder (12.8% of the total sample). Given the benefits reported in prior research, clarification of the role of online support groups in bipolar disorder is needed. With only a minority of patients using online support groups, there are analytical challenges for future studies.

    MeSH terms: Adult; Bipolar Disorder/epidemiology; Bipolar Disorder/psychology*; Bipolar Disorder/therapy*; Female; Humans; Male; Middle Aged; Surveys and Questionnaires*; Self-Help Groups/utilization*; Internet/utilization*; Internationality*
  5. Kesharwani P, Gothwal A, Iyer AK, Jain K, Chourasia MK, Gupta U
    Drug Discov Today, 2017 Jul 08.
    PMID: 28697371 DOI: 10.1016/j.drudis.2017.06.009
    Highly controllable dendritic structural design means dendrimers are a leading carrier in drug delivery applications. Dendrimer- and other nanocarrier-based hybrid systems are an emerging platform in the field of drug delivery. This review is a compilation of increasing reports of dendrimer interactions, such as dendrimer-liposome, dendrimer-carbon-nanotube, among others, known as hybrid carriers. This should prompt entirely new research with promising results for these hybrid carriers. It is assumed that such emerging hybrid nanosystems - from combining two already-established drug delivery platforms - could lead the way for the development of newer delivery systems with multiple applicability for latent theranostic applications in the future.
    MeSH terms: Theranostic Nanomedicine; Drug Carriers; Liposomes; Drug Delivery Systems; Nanotubes, Carbon; Dendrimers
  6. Teah YF, Abduraman MA, Amanah A, Adenan MI, Sulaiman SF, Tan ML
    Food Chem Toxicol, 2017 Sep;107(Pt A):293-301.
    PMID: 28689918 DOI: 10.1016/j.fct.2017.07.011
    Elephantopus scaber Linn and its major bioactive component, deoxyelephantopin are known for their medicinal properties and are often reported to have various cytotoxic and antitumor activities. This plant is widely used as folk medicine for a plethora of indications although its safety profile remains unknown. Human ether-a-go-go-related gene (hERG) encodes the cardiac IKr current which is a determinant of the duration of ventricular action potentials and QT interval. The hERG potassium channel is an important antitarget in cardiotoxicity evaluation. This study investigated the effects of deoxyelephantopin on the current, mRNA and protein expression of hERG channel in hERG-transfected HEK293 cells. The hERG tail currents following depolarization pulses were insignificantly affected by deoxyelephantopin in the transfected cell line. Current reduction was less than 40% as compared with baseline at the highest concentration of 50 μM. The results were consistent with the molecular docking simulation and hERG surface protein expression. Interestingly, it does not affect the hERG expression at both transcriptional and translational level at most concentrations, although higher concentration at 10 μM caused protein accumulation. In conclusion, deoxyelephantopin is unlikely a clinically significant hERG channel and Ikr blocker.
    MeSH terms: Heart/drug effects; Humans; Lactones/pharmacology*; Myocardium/metabolism*; Plant Extracts/pharmacology*; Potassium/metabolism*; Sesquiterpenes/pharmacology*; Asteraceae/chemistry*; Ether-A-Go-Go Potassium Channels/genetics*; Ether-A-Go-Go Potassium Channels/metabolism; Delayed Rectifier Potassium Channels/genetics*; Delayed Rectifier Potassium Channels/metabolism; HEK293 Cells
  7. Chung PY, Khanum R
    J Microbiol Immunol Infect, 2017 Aug;50(4):405-410.
    PMID: 28690026 DOI: 10.1016/j.jmii.2016.12.005
    Bacterial resistance to commonly used drugs has become a global health problem, causing increased infection cases and mortality rate. One of the main virulence determinants in many bacterial infections is biofilm formation, which significantly increases bacterial resistance to antibiotics and innate host defence. In the search to address the chronic infections caused by biofilms, antimicrobial peptides (AMP) have been considered as potential alternative agents to conventional antibiotics. Although AMPs are commonly considered as the primitive mechanism of immunity and has been extensively studied in insects and non-vertebrate organisms, there is now increasing evidence that AMPs also play a crucial role in human immunity. AMPs have exhibited broad-spectrum activity against many strains of Gram-positive and Gram-negative bacteria, including drug-resistant strains, and fungi. In addition, AMPs also showed synergy with classical antibiotics, neutralize toxins and are active in animal models. In this review, the important mechanisms of action and potential of AMPs in the eradication of biofilm formation in multidrug-resistant pathogen, with the goal of designing novel antimicrobial therapeutics, are discussed.
    MeSH terms: Animals; Anti-Infective Agents/pharmacology*; Bacteria/drug effects*; Humans; Bacterial Physiological Phenomena*; Biofilms/drug effects*; Antimicrobial Cationic Peptides/pharmacology*
  8. Habiba U, Joo TC, Siddique TA, Salleh A, Ang BC, Afifi AM
    Int J Biol Macromol, 2017 Nov;104(Pt A):1133-1142.
    PMID: 28690164 DOI: 10.1016/j.ijbiomac.2017.07.007
    The chitosan/polyvinyl alcohol/TiO2 composite was synthesized. Two different degrees of deacetylation of chitosan were prepared by hydrolysis to compare the effectiveness of them. The composite was analyzed via field emission scanning electron microscopy, Fourier transform infrared, X-ray diffraction, thermal gravimetric analysis, weight loss test and adsorption study. The FTIR and XRD results proved the interaction among chitosan, PVA and TiO2 without any chemical reaction. It was found that, chitosan with higher degree of deacetylation has better stability. Furthermore, it also showed that higher DD of chitosan required less time to reach equilibrium for methyl orange. The adsorption followed the pseudo-second-order kinetic model. The Langmuir and Freundlich isotherm models were fitted well for isotherm study. Adsorption capacity was higher for the composite containing chitosan with higher DD. The dye removal rate was independent of the dye's initial concentration. The adsorption capacity was increased with temperature and it was found from reusability test that the composite containing chitosan with higher DD is more reusable. It was notable that adsorption capacity was even after 15 runs. Therefore, chitosan/PVA/TiO2 composite can be a very useful material for dye removal.
    MeSH terms: Adsorption; Azo Compounds; Coloring Agents; Fourier Analysis; Hydrolysis; Microscopy, Electron, Scanning; Polyvinyl Alcohol; Temperature; Titanium; X-Ray Diffraction; Weight Loss; Spectroscopy, Fourier Transform Infrared; Chitosan
  9. Kua KP, Lee SWH
    Front Pharmacol, 2017;8:396.
    PMID: 28690542 DOI: 10.3389/fphar.2017.00396
    Objective: To evaluate the effectiveness of combined epinephrine and corticosteroid therapy for acute bronchiolitis in infants. Methods: Four electronic databases (MEDLINE, EMBASE, CINAHL, and CENTRAL) were searched from their inception to February 28, 2017 for studies involving infants aged less than 24 months with bronchiolitis which assessed the use of epinephrine and corticosteroid combination therapy. The methodological quality of the included studies was assessed using the Cochrane Collaboration's Risk of Bias Tool. A random-effects meta-analysis was used to pool the effect estimates. The primary outcomes were hospital admission rate and length of hospital stay. Results: Of 1,489 citations identified, 5 randomized controlled trials involving 1,157 patients were included. All studies were of high quality and low risk of bias. Results of the meta-analysis showed no significant differences in the primary outcomes. Hospitalization rate was reduced by combinatorial therapy of epinephrine and corticosteroid in only one out of five studies, whereas pooled data indicated no benefit over epinephrine plus placebo. Clinical severity scores were significantly improved in all five RCTs when assessed individually, but no benefit was observed compared to epinephrine monotherapy when the data were pooled together. Pooled data showed that combination therapy was more effective at improving oxygen saturation level (mean difference: -0.70; 95% confidence interval: -1.17 to -0.22, p = 0.004). There was no difference in the risk of serious adverse events in infants treated with the combined epinephrine and corticosteroid therapy. Conclusions: Combination treatment of epinephrine and dexamethasone was ineffective in reducing hospital admission and length of stay among infants with bronchiolitis.
    MeSH terms: Adrenal Cortex Hormones; Bronchiolitis; Child, Preschool; Combined Modality Therapy; Dexamethasone; Epinephrine; Hospitalization; Humans; Infant; Length of Stay; Oxygen; Confidence Intervals; Randomized Controlled Trials as Topic; MEDLINE
  10. Hassali MA, Arief M, Saleem F, Khan MU, Ahmad A, Mariam W, et al.
    Pharm Pract (Granada), 2017 Apr-Jun;15(2):929.
    PMID: 28690695 DOI: 10.18549/PharmPract.2017.02.929
    OBJECTIVE: The present study was aimed to evaluate the practices and attitudes of young Malaysian adults towards the use of antibiotics, and to determine the socioeconomic factors associated with the antibiotic use.

    METHODS: A survey was carried in Cheras community by approaching a conveniently selected sample of 480 participants. A pre-tested questionnaire was used for data collection.

    RESULT: Of 480 participants approached, 400 agreed to participate in this study, giving a response rate of 83.3%. The study results showed that 42.75% of the participants exhibited poor attitudes towards antibiotic usage. Chinese race and high income were significantly associated with the positive attitudes towards antibiotic usage. It is shown that the practice of the participants towards antibiotics was relatively poor. The majority of participants agreed that they do not consult a doctor for minor illnesses (64%). The main reason for not consulting a doctor was the high fees of consultation (34.25%) and the inconvenience of visit (29.25%). However, a large proportion of respondents (77.5%) agreed that there is a need to enhance antibiotic education among public.

    CONCLUSION: The study results identified some crucial gaps in the attitudes and practices of Cheras community about the use of antibiotics. Thus, improving the public knowledge and changing their attitude towards antibiotic use along with proper interventions to regulate the ease of their availability would play a significant role for the effective use of antibiotics in the community.
    MeSH terms: Adult; Anti-Bacterial Agents; Attitude; Humans; Income; Surveys and Questionnaires; Referral and Consultation; Socioeconomic Factors
  11. Kho BP, Hassali MA, Lim CJ, Saleem F
    Pharm Pract (Granada), 2017 Apr-Jun;15(2):933.
    PMID: 28690697 DOI: 10.18549/PharmPract.2017.02.933
    BACKGROUND: The provision of professional pharmacy services by community pharmacists continues to be limited, particularly in low and middle income countries. It was postulated that multiple management challenges faced by community pharmacists contribute to this situation.

    OBJECTIVE: The primary aim of the research was to determine the challenges faced in the management of community pharmacies in Sarawak (the largest state in Malaysia), and practical strategies to cope and overcome the challenges.

    METHODS: Semi-structured interviews were carried out with community pharmacists practising in Sarawak. Purposive and snowball sampling were employed to ensure a diverse group of informants. The interviews were audio-recorded and transcribed verbatim, with the resultant data analysed using thematic analysis. Data collection, coding, interpretation were carried out iteratively until theoretical saturation.

    RESULTS: Twenty respondents from different demographic characteristics were recruited. Six major themes were identified. Management challenges faced by community pharmacists traverse five major domains: market competition, legislative issues, customers' knowledge and expectations, macroeconomic impacts and operational challenges. Most of these challenges require government intervention to be resolved. In the meantime, improving customer service and expanding the range of professional services were seen as the most viable strategies to cope with existing challenges. The main concern is that current legislative and economic landscape may hinder these strategies. Enactment of dispensing separation and more protective measures against market competition were suggested to alleviate the challenges faced.

    CONCLUSION: Numerous management challenges faced by community pharmacists that distract them from delivering professional pharmacy services have been highlighted. Urgent affirmative actions by the government are warranted in supporting community pharmacists to realise and maximise their potentials.
    MeSH terms: Community Pharmacy Services; Demography; Employment; Government; Humans; Income; Malaysia; Pharmacies; Pharmacists; Surveys and Questionnaires
  12. Murshid MA, Mohaidin Z
    Pharm Pract (Granada), 2017 Apr-Jun;15(2):990.
    PMID: 28690701 DOI: 10.18549/PharmPract.2017.02.990
    To date, research on the prescribing decisions of physician lacks sound theoretical foundations. In fact, drug prescribing by doctors is a complex phenomenon influenced by various factors. Most of the existing studies in the area of drug prescription explain the process of decision-making by physicians via the exploratory approach rather than theoretical. Therefore, this review is an attempt to suggest a value conceptual model that explains the theoretical linkages existing between marketing efforts, patient and pharmacist and physician decision to prescribe the drugs. The paper follows an inclusive review approach and applies the previous theoretical models of prescribing behaviour to identify the relational factors. More specifically, the report identifies and uses several valuable perspectives such as the 'persuasion theory - elaboration likelihood model', the stimuli-response marketing model', the 'agency theory', the theory of planned behaviour,' and 'social power theory,' in developing an innovative conceptual paradigm. Based on the combination of existing methods and previous models, this paper suggests a new conceptual model of the physician decision-making process. This unique model has the potential for use in further research.
    MeSH terms: Decision Making; Humans; Persuasive Communication; Pharmacists; Physicians; Drug Prescriptions; Likelihood Functions; Marketing
  13. Chen G, Zhou W, Guan D, Sunarso J, Zhu Y, Hu X, et al.
    Sci Adv, 2017 06;3(6):e1603206.
    PMID: 28691090 DOI: 10.1126/sciadv.1603206
    Perovskite oxides exhibit potential for use as electrocatalysts in the oxygen evolution reaction (OER). However, their low specific surface area is the main obstacle to realizing a high mass-specific activity that is required to be competitive against the state-of-the-art precious metal-based catalysts. We report the enhanced performance of Ba0.5Sr0.5Co0.8Fe0.2O3-δ (BSCF) for the OER with intrinsic activity that is significantly higher than that of the benchmark IrO2, and this result was achieved via fabrication of an amorphous BSCF nanofilm on a surface-oxidized nickel substrate by magnetron sputtering. The surface nickel oxide layer of the Ni substrate and the thickness of the BSCF film were further used to tune the intrinsic OER activity and stability of the BSCF catalyst by optimizing the electronic configuration of the transition metal cations in BSCF via the interaction between the nanofilm and the surface nickel oxide, which enables up to 315-fold enhanced mass-specific activity compared to the crystalline BSCF bulk phase. Moreover, the amorphous BSCF-Ni foam anode coupled with the Pt-Ni foam cathode demonstrated an attractive small overpotential of 0.34 V at 10 mA cm-2 for water electrolysis, with a BSCF loading as low as 154.8 μg cm-2.
  14. Simoneau G, Levis B, Cuijpers P, Ioannidis JPA, Patten SB, Shrier I, et al.
    Biom J, 2017 Nov;59(6):1317-1338.
    PMID: 28692782 DOI: 10.1002/bimj.201600184
    Individual patient data (IPD) meta-analyses are increasingly common in the literature. In the context of estimating the diagnostic accuracy of ordinal or semi-continuous scale tests, sensitivity and specificity are often reported for a given threshold or a small set of thresholds, and a meta-analysis is conducted via a bivariate approach to account for their correlation. When IPD are available, sensitivity and specificity can be pooled for every possible threshold. Our objective was to compare the bivariate approach, which can be applied separately at every threshold, to two multivariate methods: the ordinal multivariate random-effects model and the Poisson correlated gamma-frailty model. Our comparison was empirical, using IPD from 13 studies that evaluated the diagnostic accuracy of the 9-item Patient Health Questionnaire depression screening tool, and included simulations. The empirical comparison showed that the implementation of the two multivariate methods is more laborious in terms of computational time and sensitivity to user-supplied values compared to the bivariate approach. Simulations showed that ignoring the within-study correlation of sensitivity and specificity across thresholds did not worsen inferences with the bivariate approach compared to the Poisson model. The ordinal approach was not suitable for simulations because the model was highly sensitive to user-supplied starting values. We tentatively recommend the bivariate approach rather than more complex multivariate methods for IPD diagnostic accuracy meta-analyses of ordinal scale tests, although the limited type of diagnostic data considered in the simulation study restricts the generalization of our findings.
    MeSH terms: Biometry/methods*; Health Surveys; Humans; Meta-Analysis as Topic*; Models, Statistical*; Multivariate Analysis; Poisson Distribution; Diagnostic Techniques and Procedures*
  15. Dalu T, Wasserman RJ, Tonkin JD, Mwedzi T, Magoro ML, Weyl OLF
    Sci Total Environ, 2017 Dec 31;607-608:317-325.
    PMID: 28692901 DOI: 10.1016/j.scitotenv.2017.06.267
    Water pollution is a critical management issue, with many rivers and streams draining urban areas being polluted by the disposal of untreated solid waste and wastewater discharge, storm water and agricultural runoff. This has implications for biodiversity, and many rivers in the developing world are now considered compromised. We investigated benthic macroinvertebrate community structure and composition in relation to physico-chemical conditions of the water column and sediments. The study was conducted in an Austral catchment subject to both urban and agricultural pollutants in two different seasons. We assessed whether sediment characteristics were more important drivers of macroinvertebrate community composition than water column characteristics. We expected clear differences in macroinvertebrate community composition and in the associated community metrics due to distinct flow conditions between the two seasons. A combination of multivariate analyses (canonical correspondence analysis (CCA)) and biological indicator analysis were used to examine these patterns. Chironomidae was the most abundant family (>60%) in the upper mainstem river and stream sites. Stream sites were positively associated with CCA axis 2, being characterised by high turbidity and lower pH, salinity, phosphate concentration, channel width and canopy cover. Canopy cover, channel width, substrate embeddedness, phosphate concentration, pH, salinity and turbidity all had a significant effect on macroinvertebrate community composition. Using CCA variation partitioning, water quality was, however, a better predictor of benthic macroinvertebrate composition than sediment chemical conditions. Furthermore, our results suggest that seasonality had little effect on structuring benthic macroinvertebrate communities in this south-eastern zone of South Africa, despite clear changes in sediment chemistry. This likely reflects the relative lack of major variability in water chemistry compared to sediment chemistry between seasons and the relatively muted variability in precipitation between seasons than the more classic Austral temperate climates.
    MeSH terms: Agriculture; Animals; Chironomidae; Phosphates; Seasons; South Africa; Water; Water Pollution; Multivariate Analysis; Geologic Sediments; Biodiversity; Rivers; Salinity; Water Quality; Waste Water; Solid Waste
  16. Tan CH, Wong KY, Tan KY, Tan NH
    J Proteomics, 2017 08 23;166:48-58.
    PMID: 28688916 DOI: 10.1016/j.jprot.2017.07.002
    The venom proteome of Laticauda colubrina (Bali, Indonesia) was elucidated by nano-ESI-LCMS/MS of the venom reverse-phase HPLC fractions. Altogether 31 distinct forms of proteins were identified and clustered into three toxin families: three-finger toxin (3FTX, 66.12% of total venom proteins), phospholipase A2 (PLA2, 33.26%) and cysteine-rich secretory protein (CRiSP, 0.05%). The 3FTX were α-neurotoxins (five long neurotoxins, LNTX, 48.87%; two short neurotoxins, SNTX, 16.94%) and a trace amount of two cytotoxins (CTX, 0.31%). PLA2 were present with a large diversity of homologues (≥20 forms), however none was annotated to the lethal proteoform reported previously. The venom is highly lethal in mice (LD50=0.10μg/g) and this is driven primarily by the SNTX and LNTX (LD50=0.05-0.13μg/g), since the PLA2 proteins were non-lethal up to 2μg/g (20-time the venom LD50). The SNTX and LNTX were effectively cross-neutralized by the heterologous Sea Snake Antivenom (SSAV, Australian product) (potency=0.27mg toxin per ml antivenom, and 0.40mg/ml, respectively), corroborating the cross-neutralization of the whole venom (potency=1.09mg/ml) and its antigenic immunoreactivity toward SSAV. Furthermore, compared with earlier studies, the present work reveals geographical variation of venom composition for L. colubrina which may have implication for the evolution and conservation of the species.

    BIOLOGICAL SIGNIFICANCE: Laticauda colubrina (yellow-lipped sea krait) is a widely distributed, semi-aquatic venomous snake species. The venom proteome at the level of protein family is unsophisticated and consistent with its restricted prey selection. Nonetheless, the subproteomic findings revealed geographical variability of the venom for this widely distributed species. In contrast to two previous reports, the results for the Balinese L. colubrina venom showed that LNTX Neurotoxin a and Neurotoxin b were co-existent while the PLA2 lethal subtype (PLA-II) was undetected by means of LCMS/MS and by in vivo assay. This is an observable trait of L. colubrina considered divergent from specimens previously studied for the Philippines and the Solomon Islands. The stark geographical variation might be reflective of trophic adaptation following evolutionary arms race between the snake and the prey (eels) in different localities. The preferred trait would likely propagate and remain significant within the geographical population, since the strong behaviour of site fidelity in the species would have minimized gene flow between distant populations. Meanwhile, the in vivo neutralization study verified that the efficacy of the heterologous Sea Snake Antivenom (Australian product) is attributable to the cross-neutralization of SNTX and LNTX, two principal lethal toxins that made up the bulk of L. colubrina venom proteins. The findings also implied that L. colubrina, though could be evolutionarily more related to the terrestrial elapids, has evolved a much streamlined, neurotoxin- and PLA2-predominated venom arsenal, with major antigenicity shared among the true sea snakes and the Australo-Papuan elapids. The findings enrich our current understanding of the complexity of L. colubrina venom and the neutralizing spectrum of antivenom against the principal toxins from this unique elapid lineage.

    MeSH terms: Animals; Antigens; Antivenins/immunology*; Cross Reactions; Elapid Venoms/immunology*; Biological Evolution; Neurotoxins/analysis; Proteome/analysis; Phospholipases A2/analysis; Antibodies, Neutralizing
  17. Bera H, Nadimpalli J, Kumar S, Vengala P
    Int J Biol Macromol, 2017 Nov;104(Pt A):1229-1237.
    PMID: 28688948 DOI: 10.1016/j.ijbiomac.2017.07.027
    Flurbiprofen (FLU), a non-steroidal anti-inflammatory drug, exhibits limited clinical response due to its poor physicochemical properties. This study aimed at developing reliable drug carriers for intrgastric FLU delivery with a view to improve biopharmaceutical characteristics of drug and modulate its release in a controlled manner. In this context, FLU-loaded kondogogu gum (KG)-Zn(+2)-low methoxyl (LM) pectinate emulgel matrices reinforced with calcium silicate (CS) were accomplished by ionotropic gelation technique employing zinc acetate as cross-linker and characterized for their in vitro performances. All the formulations demonstrated excellent drug encapsulation efficiency (DEE, 46-87%) and sustained drug release behavior (Q7h, 70-91%). These quality attributes were remarkably influenced by polymer-blend (LM pectin:KG) ratios, low-density oil types and CS inclusion. The drug release profile of the FLU-loaded optimized matrices (F-7) was best fitted in Korsmeyer-Peppas model with Fickian diffusion driven mechanism. It also conferred excellent in vitro gastroretention capabilities. Moreover, the drug-excipient compatibility, alteration of crystallinity and thermal behavior of drug and surface morphology of matrices were evidenced with the results of FTIR, XRD, DSC and SEM analyses, respectively. Thus, the newly developed matrices are appropriate for sustained intragastric FLU delivery and simultaneous zinc supplementation for effective inflammation and arthritis management.
    MeSH terms: Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Delayed-Action Preparations; Drug Carriers; Excipients; Flurbiprofen; Inflammation; Pectins; Polymers; Spectroscopy, Fourier Transform Infrared; Calcium Compounds; Silicates; Zinc Acetate; Drug Liberation
  18. Johdi NA, Mazlan L, Sagap I, Jamal R
    Cytokine, 2017 11;99:35-42.
    PMID: 28689023 DOI: 10.1016/j.cyto.2017.06.015
    Soluble proteins including cytokines, chemokines and growth factors are small proteins that mediate and regulate immunity. They involved in the pathogenesis of many diseases including cancers. The concentration of these proteins in biological fluids (serum or plasma) and tissues in diseases may suggest pathway activation that leads to inflammatory response or disease progression. Therefore, these soluble proteins may be useful as a tool for screening, diagnosis classification between stages of disease or surveillance for therapy. Enzyme-linked immunosorbent assays (ELISA) and bioassay have been used as a gold standard in cytokine level measurements in clinical practice. However, these methods allow only single cytokine detection at a time and ineffective for screening purposes. Hence, the innovation of multiplexing technology allows measurement of many these soluble proteins simultaneously, thus allowing rapid, cost effective and better efficiency by using a minute amount of sample. In this study, we explored the profiles of key inflammatory cytokines, chemokines and other soluble proteins from the serum derived from colorectal carcinoma (CRC, n=20), colorectal polyps (P, n=20) and healthy volunteers (N, n=20) using multiplexed bead-based immunoassays. We aimed to evaluate if the levels of these soluble proteins can classify these groups of populations and explore the possible application of the soluble proteins as biomarkers in early stage screening and/or surveillance. We observed significant high IL-4, MIP-1β, FasL and TGF-β1 levels but lower levels for RANTES in P-derived serum as compared to N-derived serum. Significant high IL-8, VEGF, MIP-1β, Eotaxin and G-CSF observed in CRC-derived serum when compared to N-derived serum. Between CRC- and P-derived serum, significantly higher levels of IL-8, Eotaxin and G-CSF but lower levels for TGF-β1 were detected in CRC-derived serum. These preliminary results were obtained from small sample size and could be further validated with larger sample size cohort to produce a panel of biomarkers for CRC and P patients. Our findings might be useful in developing a disease-specific panel for biomarker screening assay. This could be used for early diagnosis and/or treatment surveillance.
    MeSH terms: Aged; Enzyme-Linked Immunosorbent Assay; Female; Humans; Male; Middle Aged; Neoplasm Proteins/blood*; Polyps/blood*; Solubility; Biomarkers, Tumor/blood*; Colorectal Neoplasms/blood*; Chemokines/blood*
  19. Ibau C, Md Arshad MK, Gopinath SCB
    Biosens Bioelectron, 2017 Dec 15;98:267-284.
    PMID: 28689113 DOI: 10.1016/j.bios.2017.06.049
    Early cancer diagnosis remains the holy-grail in the battle against cancers progression. Tainted with debates and medical challenges, current therapeutic approaches for prostate cancer (PCa) lack early preventive measures, rapid diagnostic capabilities, risk factors identification, and portability, i.e. the inherent attributes offered by the label-free biosensing devices. Electronic assisted immunosensing systems inherit the high sensitivity and specificity properties due to the predilection of the antigen-antibody affinity. Bioelectronic immunosensor for PCa has attracted much attentions among the researchers due to its high-performance, easy to prepare, rapid feedback, and possibility for miniaturization. This review explores the current advances on bioelectronic immunosensors for the detection of PCa biomarker revealed in the past decade. The research milestones and current trends of the immunosensors are reported to project the future visions in order to propel their "lab-to-market" realization.
    MeSH terms: Humans; Male; Prostatic Neoplasms/blood*; Biosensing Techniques*; Prostate-Specific Antigen/blood; Prostate-Specific Antigen/isolation & purification*; Early Detection of Cancer
  20. Kobayashi A, Tengku Ahmad TAF, Autsavapromporn N, Oikawa M, Homma-Takeda S, Furusawa Y, et al.
    Mutat Res, 2017 10;803-805:1-8.
    PMID: 28689138 DOI: 10.1016/j.mrfmmm.2017.06.006
    Understanding the mechanisms underlying the radiation-induced bystander effect (RIBE) and bi-directional signaling between irradiated carcinoma cells and their surrounding non-irradiated normal cells is relevant to cancer radiotherapy. The present study investigated propagation of RIBE signals between human lung carcinoma A549 cells and normal lung fibroblast WI38 cells in bystander cells, either directly or indirectly contacting irradiated A549 cells. We prepared A549-GFP/WI38 co-cultures and A549-GFP/A549 co-cultures, in which A549-GFP cells stably expressing H2BGFP were co-cultured with either A549 cells or WI38 cells, respectively. Using the SPICE-NIRS microbeam, only the A549-GFP cells were irradiated with 500 protons per cell. The level of γ-H2AX, a marker for DNA double-strand breaks (DSB), was subsequently measured for up to 24h post-irradiation in three categories of cells: (1) "targeted"/irradiated A549-GFP cells; (2) "neighboring"/non-irradiated cells directly contacting the "targeted" cells; and (3) "distant"/non-irradiated cells, which were not in direct contact with the "targeted" cells. We found that DSB repair in targeted A549-GFP cells was enhanced by co-cultured WI38 cells. The bystander response in A549-GFP/A549 cell co-cultures, as marked by γ-H2AX levels at 8h post-irradiation, showed a decrease to non-irradiated control level when approaching 24h, while the neighboring/distant bystander WI38 cells in A549-GFP/WI38 co-cultures was maintained at a similar level until 24h post-irradiation. Surprisingly, distant A549-GFP cells in A549-GFP/WI38 co-cultures showed time dependency similar to bystander WI38 cells, but not to distant cells in A549-GFP/A549 co-cultures. These observations indicate that γ-H2AX was induced in WI38 cells as a result of RIBE. WI38 cells were not only involved in rescue of targeted A549, but also in the modification of RIBE against distant A549-GFP cells. The present results demonstrate that radiation-induced bi-directional signaling had extended a profound influence on cellular sensitivity to radiation as well as the sensitivity to RIBE.
    MeSH terms: Cell Line; DNA Repair*; Fibroblasts/radiation effects*; Histones/metabolism; Humans; Lung Neoplasms/radiotherapy; Protons; Signal Transduction*; Coculture Techniques; Bystander Effect/radiation effects*; DNA Breaks, Double-Stranded*; A549 Cells
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