Browse publications by year: 2017

  1. Zin NM, Baba MS, Zainal-Abidin AH, Latip J, Mazlan NW, Edrada-Ebel R
    Drug Des Devel Ther, 2017;11:351-363.
    PMID: 28223778 DOI: 10.2147/DDDT.S121283
    Endophytic Streptomyces strains are potential sources for novel bioactive molecules. In this study, the diketopiperazine gancidin W (GW) was isolated from the endophytic actinobacterial genus Streptomyces, SUK10, obtained from the bark of Shorea ovalis tree, and it was tested in vivo against Plasmodium berghei PZZ1/100. GW exhibited an inhibition rate of nearly 80% at 6.25 and 3.125 μg kg-1 body weight on day four using the 4-day suppression test method on male ICR strain mice. Comparing GW at both concentrations with quinine hydrochloride and normal saline as positive and negative controls, respectively, 50% of the mice treated with 3.125 μg kg-1 body weight managed to survive for more than 11 months after infection, which almost reached the life span of normal mice. Biochemical tests of selected enzymes and proteins in blood samples of mice treated with GW were also within normal levels; in addition, no abnormalities or injuries were found on internal vital organs. These findings indicated that this isolated bioactive compound from Streptomyces SUK10 exhibits very low toxicity and is a good candidate for potential use as an antimalarial agent in an animal model.
    MeSH terms: Animals; Antimalarials/isolation & purification; Antimalarials/pharmacology*; Antimalarials/chemistry; Disease Models, Animal; Dose-Response Relationship, Drug; Malaria/drug therapy*; Malaria/parasitology*; Male; Mice, Inbred ICR; Molecular Conformation; Piperazines/isolation & purification; Piperazines/pharmacology*; Piperazines/chemistry; Plasmodium berghei/drug effects*; Streptomyces/chemistry*; Parasitic Sensitivity Tests; Mice
  2. Won H, Abdul MZ, Mat Ludin AF, Omar MA, Razali R, Shahar S
    Clin Interv Aging, 2017;12:275-282.
    PMID: 28223785 DOI: 10.2147/CIA.S118942
    PURPOSE: Older adults are at risk of mild cognitive impairment (MCI), and simple anthropometric measurements can be used to screen for this condition. Thus, the aim of this study was to explore the cut-off values of body mass index (BMI) and waist circumference (WC) for predicting the risk of MCI in older Malaysian adults.

    METHODS: A total of 2,240 Malaysian older adults aged ≥60 years were recruited using multistage random sampling in a population based cross-sectional study. Receiver operating characteristic (ROC) curve was used to determine the cut-off values of BMI and WC with optimum sensitivity and specificity for the detection of MCI. Age, gender, years of education, smoking habit, alcohol consumption, depression, and medical conditions were used as confounding factors in this analysis.

    RESULTS: A BMI cut-off value of 26 kg/m(2) (area under the receiver operating characteristic curve [AUC] 0.725; sensitivity 90.5%; specificity 38.8%) was appropriate in identifying the risk of getting MCI in both men and women. The optimum WC cut-offs for likelihood of MCI were 90 cm (AUC 0.745; sensitivity 78.0%; specificity 59.8%) for men and 82 cm (AUC 0.714; sensitivity 84.3%; specificity 49.7%) for women. The optimum calf circumference (CC) cut-off values for identifying MCI were 29 cm (AUC 0.731; sensitivity 72.6%; specificity 61.1%) for men and 26 cm (AUC 0.598; sensitivity 79.1%; specificity 45.3%) for women.

    CONCLUSION: The cut-off values could be advocated and used as part of the screening of MCI among older Malaysian adults. There is a need to further determine the predictive values of these cut-off points on outcomes through longitudinal study design.

  3. Ganesan P, Arulselvan P, Choi DK
    Int J Nanomedicine, 2017;12:1097-1111.
    PMID: 28223801 DOI: 10.2147/IJN.S124601
    Type 2 diabetes mellitus (T2DM) is a major chronic disease that is prevalent worldwide, and it is characterized by an increase in blood glucose, disturbances in the metabolism, and alteration in insulin secretion. Nowadays, food-based therapy has become an important treatment mode for type 2 diabetes, and phytobioactive compounds have gained an increasing amount of attention to this end because they have an effect on multiple biological functions, including the sustained secretion of insulin and regeneration of pancreatic islets cells. However, the poor solubility and lower permeability of these phyto products results in a loss of bioactivity during processing and oral delivery, leading to a significant reduction in the bioavailability of phytobioactive compounds to treat T2DM. Recently, nanotechnological systems have been developed for use as various types of carrier systems to improve the delivery of bioactive compounds and thus obtain a greater bioavailability. Furthermore, carrier systems in most nanodelivery systems are highly biocompatible, with nonimmunologic behavior, a high degree of biodegradability, and greater mucoadhesive strength. Therefore, this review focuses on the various types of nanodelivery systems that can be used for phytobioactive compounds in treating T2DM with greater antidiabetic effects. There is also additional focus on improving the effects of various phytobioactive compounds through nanotechnological delivery to ensure a highly efficient treatment of type 2 diabetes.
    MeSH terms: Animals; Diabetes Mellitus, Type 2/drug therapy*; Humans; Hypoglycemic Agents/therapeutic use*; Plant Extracts/therapeutic use*; Drug Delivery Systems*; Nanoparticles/administration & dosage*; Nanoparticles/chemistry
  4. Saperi BS, Ramli R, Ahmed Z, Muhd Nur A, Ibrahim MI, Rashdi MF, et al.
    Clinicoecon Outcomes Res, 2017;9:107-113.
    PMID: 28223831 DOI: 10.2147/CEOR.S119910
    OBJECTIVE: Facial injury (FI) may occur in isolation or in association with injuries to other parts of the body (facial and other injury [FOI]). The objective of this study was to determine the direct treatment costs incurred during the management of facial trauma.

    MATERIALS AND METHODS: A prospective cohort study on treatment cost for FIs and FOIs due to road-traffic crashes in two university hospitals in Malaysia was conducted from July 2010 to June 2011. The patients were recruited from emergency departments and reviewed after 6 months from the date of initial treatment. Direct cost analysis, comparison of cost and length of hospital stay, and Injury Severity Score (ISS) were performed.

    RESULTS: A total of 190 patients were enrolled in the study, of whom 83 (43.7%) had FI only, and 107 (56.3%) had FOI. The mean ISS was 5.4. The mean length of stay and costs for patients with FI only were 5.8 days with a total cost of US$1,261.96, whereas patients with FOI were admitted for 7.8 days with a total cost of US$1,716.47. Costs doubled if the treatment was performed under general anesthesia compared to local anesthesia.

    CONCLUSION: Treatment of FI and FOI imposes a financial burden on the health care system in Malaysia.

  5. Othman K, Liza-Sharmini AT, Ibrahim M, Tharakan J, Yanai R, Zunaina E
    Int Med Case Rep J, 2017;10:35-40.
    PMID: 28223848 DOI: 10.2147/IMCRJ.S121863
    Behçet's disease (BD) is a multisystemic disease that is very rare in Malaysia. About 5% of patients develop central nervous system involvement, termed neuro-Behçet's. Neuro-Behçet's is one of the most serious causes of long-term morbidity and mortality. We report two cases of neuro-Behçet's associated with uveitis (ocular BD) highlighting the clinical presentation, diagnostic measurement, and therapeutic management of these cases.
  6. Choi JR, Yong KW, Wan Safwani WKZ
    Cell Mol Life Sci, 2017 07;74(14):2587-2600.
    PMID: 28224204 DOI: 10.1007/s00018-017-2484-2
    Human adipose-derived mesenchymal stem cells (hASCs) are an ideal cell source for regenerative medicine due to their capabilities of multipotency and the readily accessibility of adipose tissue. They have been found residing in a relatively low oxygen tension microenvironment in the body, but the physiological condition has been overlooked in most studies. In light of the escalating need for culturing hASCs under their physiological condition, this review summarizes the most recent advances in the hypoxia effect on hASCs. We first highlight the advantages of using hASCs in regenerative medicine and discuss the influence of hypoxia on the phenotype and functionality of hASCs in terms of viability, stemness, proliferation, differentiation, soluble factor secretion, and biosafety. We provide a glimpse of the possible cellular mechanism that involved under hypoxia and discuss the potential clinical applications. We then highlight the existing challenges and discuss the future perspective on the use of hypoxic-treated hASCs.
    MeSH terms: Adipose Tissue/cytology*; Clinical Trials as Topic*; Humans; Models, Biological; Cell Hypoxia; Mesenchymal Stromal Cells/cytology*
  7. Mohd Sukri SA, Heng LY, Abd Karim NH
    J Fluoresc, 2017 May;27(3):1009-1023.
    PMID: 28224358 DOI: 10.1007/s10895-017-2035-0
    The platinum(II) salphen complex N,N'-Bis-4-(hydroxysalicylidene)-phenylenediamine-platinum(II); (1) and its two derivatives containing hydroxyl functionalized side chains N,N'-bis-[4-[[1-(2-hydroxyethoxy)] salicylidene] phenylenediamine-platinum(II); (2) and N,N'-bis-[4-[[1-(3-hydroxypropoxy)] salicylidene] phenylenediamine-platinum(II); (3) were synthesized and characterized. The structures of the complexes were confirmed by 1H and 13C NMR spectroscopy, FTIR, ESI-MS and CHN elemental analyses. The effects of the hydroxyl substituent on the spectral properties and the DNA binding behaviors of the Pt(II) complexes were explored. The binding mode and interactions of these complexes with duplex DNA (calf thymus DNA and porcine DNA) and also single-stranded DNA were studied by UV-Vis and emission DNA titration. The complexes interact with DNA by intercalation binding mode with the binding constants in the order of magnitude (Kb = 104 M-1, CT-DNA) and (Kb = 105 M-1, porcine DNA). The intercalation of the complex in the DNA structure was proposed to happen by π-π stacking due to its square-planar geometry and aromatic rings structure. The phosphorescence emission spectral characteristics of Pt(II) complexes when interacted with DNA have been studied. Also, the application of the chosen hydroxypropoxy side chains complex (3) as an optical DNA biosensor, specifically for porcine DNA was investigated. These findings will be valuable for the potential use of the platinum(II) salphen complex as an optical DNA biosensor for the detection of porcine DNA in food products.
    MeSH terms: Animals; DNA/analysis*; DNA/metabolism*; Phenylenediamines/chemistry*; Platinum/chemistry*; Swine; Biosensing Techniques/methods*; Coordination Complexes/chemistry*
  8. Zianor Azrina ZA, Beg MDH, Rosli MY, Ramli R, Junadi N, Alam AKMM
    Carbohydr Polym, 2017 Apr 15;162:115-120.
    PMID: 28224888 DOI: 10.1016/j.carbpol.2017.01.035
    Nanocrystalline cellulose (NCC) was isolated from oil palm empty fruit bunch pulp (EFBP) using ultrasound assisted acid hydrolysis. The obtained NCC was analysed using FESEM, XRD, FTIR, and TGA, and compared with raw empty fruit bunch fibre (REFB), empty fruit bunch pulp (EFBP), and treated empty fruit bunch pulp (TEFBP). Based on FESEM analysis, it was found that NCC has a spherical shaped after acid hydrolysis with the assistance of ultrasound. This situation was different compared to previous studies that obtained rod-like shaped of NCC. Furthermore, the crystallinity of NCC is higher compared to REFB and EFBP. According to thermal stability, the NCC obtained shows remarkable sign of high thermal stability compared to REFB and EFBP.
    MeSH terms: Cellulose/chemistry*; Fruit/chemistry*; Hydrolysis; Arecaceae/chemistry*
  9. See-Too WS, Ee R, Lim YL, Convey P, Pearce DA, Yin WF, et al.
    Sci Rep, 2017 02 22;7:42968.
    PMID: 28225085 DOI: 10.1038/srep42968
    Planococcus is a Gram-positive halotolerant bacterial genus in the phylum Firmicutes, commonly found in various habitats in Antarctica. Quorum quenching (QQ) is the disruption of bacterial cell-to-cell communication (known as quorum sensing), which has previously been described in mesophilic bacteria. This study demonstrated the QQ activity of a psychrotolerant strain, Planococcus versutus strain L10.15T, isolated from a soil sample obtained near an elephant seal wallow in Antarctica. Whole genome analysis of this bacterial strain revealed the presence of an N-acyl homoserine lactonase, an enzyme that hydrolyzes the ester bond of the homoserine lactone of N-acyl homoserine lactone (AHLs). Heterologous gene expression in E. coli confirmed its functions for hydrolysis of AHLs, and the gene was designated as aidP (autoinducer degrading gene from Planococcus sp.). The low temperature activity of this enzyme suggested that it is a novel and uncharacterized class of AHL lactonase. This study is the first report on QQ activity of bacteria isolated from the polar regions.
    MeSH terms: Amino Acid Sequence; Bacterial Proteins/classification; Bacterial Proteins/genetics*; Carboxylic Ester Hydrolases/classification; Carboxylic Ester Hydrolases/genetics*; Escherichia coli/metabolism; Phylogeny; 4-Butyrolactone/analogs & derivatives; 4-Butyrolactone/analysis; 4-Butyrolactone/metabolism; Sequence Alignment; Quorum Sensing; Planococcus Bacteria/enzymology*; Planococcus Bacteria/isolation & purification
  10. Khan NA, Ong TYY, Siddiqui R
    ACS Chem Neurosci, 2017 04 19;8(4):687-688.
    PMID: 28225265 DOI: 10.1021/acschemneuro.7b00049
    Brain infections due to Acanthamoeba spp., Balamuthia mandrillaris, and Naegleria fowleri often lead to death. Despite differences in the preferential sites of infection in the brain, the mode of delivery of drugs is often intravenous. Here, we discuss targeted therapeutic approach to affect parasite viability without affecting the host cells, with an eye to improve formulation of drugs and/or administration of drugs against brain-eating amoebae.
    MeSH terms: Antiprotozoal Agents/administration & dosage*; Humans; Central Nervous System Protozoal Infections/drug therapy*
  11. Javaid A, Hasan R, Zafar A, Chaudry MA, Qayyum S, Qadeer E, et al.
    Int J Tuberc Lung Dis, 2017 03 01;21(3):303-308.
    PMID: 28225340 DOI: 10.5588/ijtld.16.0444
    BACKGROUND: Drug resistance in general, and multidrug-resistant tuberculosis (MDR-TB) in particular, threatens global tuberculosis (TB) control efforts. Population-based estimates of drug resistance are needed to develop strategies for controlling drug-resistant TB in Pakistan.

    OBJECTIVE: To obtain population-based data on Mycobacterium tuberculosis drug resistance in Pakistan.

    METHODS: To obtain drug resistance data, we conducted a population-based study of TB cases in all provinces of Pakistan. We performed culture and drug susceptibility testing on M. tuberculosis isolates from patients with a prior history of anti-tuberculosis treatment (retreatment cases) from all over the country.

    RESULTS: Of 544 isolates from previously treated cases, 289 (53.1%) were susceptible to all first-line drugs, 255 (46.9%) were resistant to at least one anti-tuberculosis drug and 132 (24.3%) were MDR-TB. Among MDR-TB isolates, 47.0% were ofloxacin (OFX) resistant. Extensively drug-resistant TB was found in two (0.4%) isolates.

    CONCLUSION: Prevalence of drug resistance in retreatment isolates was high. The alarmingly high prevalence of OFX resistance among MDR-TB isolates may threaten the success of efforts to control and treat MDR-TB.

    MeSH terms: Adolescent; Adult; Antitubercular Agents/administration & dosage; Antitubercular Agents/pharmacology*; Cross-Sectional Studies; Female; Humans; Male; Microbial Sensitivity Tests; Mycobacterium tuberculosis/drug effects*; Mycobacterium tuberculosis/isolation & purification; Pakistan/epidemiology; Tuberculosis, Pulmonary/drug therapy*; Tuberculosis, Pulmonary/microbiology; Tuberculosis, Pulmonary/epidemiology; Ofloxacin/pharmacology; Prevalence; Tuberculosis, Multidrug-Resistant/drug therapy; Tuberculosis, Multidrug-Resistant/microbiology; Tuberculosis, Multidrug-Resistant/epidemiology; Retreatment; Extensively Drug-Resistant Tuberculosis/drug therapy*; Extensively Drug-Resistant Tuberculosis/microbiology; Extensively Drug-Resistant Tuberculosis/epidemiology; Young Adult
  12. Yavari S, Malakahmad A, Sapari NB, Yavari S
    J Environ Manage, 2017 Feb 18;193:201-210.
    PMID: 28226259 DOI: 10.1016/j.jenvman.2017.02.035
    Imidazolinones are a family of herbicides that are used to control a broad range of weeds. Their high persistence and leaching potential make them probable risk to the ecosystems. In this study, biochar, the biomass-derived solid material, was produced from oil palm empty fruit bunches (EFB) and rice husk (RH) through pyrolysis process. Feedstock and pyrolysis variables can control biochar sorption capacity. Therefore, the present study attempts to evaluate effects of three pyrolysis variables (temperature, heating rate and retention time) on abilities of biochars for removal of imazapic and imazapyr herbicides from soil. Response surface methodology (RSM) was used for optimizing the variables to achieve maximum sorption performance of the biochars. Experimental data were interpreted accurately by quadratic models. Based on the results, sorption capacities of both biochars raised when temperature decreased to 300 °C, mainly because of increased biochars effective functionality in sorption of polar molecules. Heating rate of 3°C/min provided optimum conditions to maximize the sorption capacities of both biochars. Retention time of about 1 h and 3 h were found to be the best for EFB and RH biochars, respectively. EFB biochar was more efficient in removal of the herbicides, especially imazapyr due to its chemical composition and higher polarity index (0.42) rather than RH biochar (0.39). Besides, higher cation exchange capacity (CEC) values of EFB biochar (83.90 cmolc/kg) in comparison with RH biochar (70.73 cmolc/kg) represented its higher surface polarity effective in sorption of the polar herbicides.
    MeSH terms: Charcoal; Fruit; Heating; Herbicides; Imidazoles; Oryza; Soil; Temperature; Ecosystem; Biomass
  13. Lim JC, Thevarajoo S, Selvaratnam C, Goh KM, Shamsir MS, Ibrahim Z, et al.
    J Basic Microbiol, 2017 Feb;57(2):151-161.
    PMID: 27859397 DOI: 10.1002/jobm.201600494
    Anoxybacillus sp. SK 3-4 is a Gram-positive, rod-shaped bacterium and a member of family Bacillaceae. We had previously reported that the strain is an aluminum resistant thermophilic bacterium. This is the first report to provide a detailed analysis of the global transcriptional response of Anoxybacillus when the cells were exposed to 600 mg L(-1) of aluminum. The transcriptome was sequenced using Illumina MiSeq sequencer. Total of 708 genes were differentially expressed (fold change >2.00) with 316 genes were up-regulated while 347 genes were down-regulated, in comparing to control with no aluminum added in the culture. Based on Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, the majority of genes encoding for cell metabolism such as glycolysis, sulfur metabolism, cysteine and methionine metabolism were up-regulated; while most of the gene associated with tricarboxylic acid cycle (TCA cycle) and valine, leucine and isoleucine metabolism were down-regulated. In addition, a significant number of the genes encoding ABC transporters, metal ions transporters, and some stress response proteins were also differentially expressed following aluminum exposure. The findings provide further insight and help us to understand on the resistance of Anoxybacillus sp. SK 3-4 toward aluminium.
    MeSH terms: Aluminum/metabolism*; Stress, Physiological*; Sequence Analysis, DNA; Gene Expression Profiling*; Metabolic Networks and Pathways/genetics; Anoxybacillus/drug effects*; Anoxybacillus/genetics*; High-Throughput Nucleotide Sequencing
  14. Raftari M, Ghafourian S, Abu Bakar F
    J Appl Microbiol, 2017 Apr;122(4):1009-1019.
    PMID: 28028882 DOI: 10.1111/jam.13388
    AIMS: This study was an attempt to create a novel milk clotting procedure using a recombinant bacterium capable of milk coagulation.

    METHODS AND RESULTS: The Rhizomucor pusillus proteinase (RPP) gene was sub-cloned into a pALF expression vector. The recombinant pALF-RPP vector was then electro-transferred into Lactococcus lactis. Finally, the milk coagulation ability of recombinant L. lactis carrying a RPP gene was evaluated. Nucleotide sequencing of DNA insertion from the clone revealed that the RPP activity corresponded to an open reading frame consisting of 1218 bp coding for a 43·45 kDa RPP protein. The RPP protein assay results indicated that the highest RPP enzyme expression with 870 Soxhlet units (SU) per ml and 7914 SU/OD were obtained for cultures which were incubated at pH 5·5 and 30°C. Interestingly, milk coagulation was observed after 205 min of inoculating milk with recombinant L. lactis carrying the RPP gene.

    CONCLUSION: The recombinant L. lactis carrying RPP gene has the ability to function as a starter culture for acidifying and subsequently coagulating milk by producing RPP as a milk coagulant agent.

    SIGNIFICANCE AND IMPACT OF THE STUDY: Creating a recombinant starter culture bacterium that is able to coagulate milk. It is significant because the recombinant L. lactis has the ability to work as a starter culture and milk coagulation agent.

    MeSH terms: Animals; Milk*; Peptide Hydrolases/genetics*; Peptide Hydrolases/metabolism; Recombinant Proteins/metabolism; Lactococcus lactis/genetics*; Lactococcus lactis/metabolism; Lactic Acid/metabolism; Rhizomucor/enzymology; Rhizomucor/genetics
  15. Liu J, Lan Y, Yu Z, Tan CS, Parker RM, Abell C, et al.
    Acc Chem Res, 2017 Feb 21;50(2):208-217.
    PMID: 28075551 DOI: 10.1021/acs.accounts.6b00429
    Microencapsulation is a fundamental concept behind a wide range of daily applications ranging from paints, adhesives, and pesticides to targeted drug delivery, transport of vaccines, and self-healing concretes. The beauty of microfluidics to generate microcapsules arises from the capability of fabricating monodisperse and micrometer-scale droplets, which can lead to microcapsules/particles with fine-tuned control over size, shape, and hierarchical structure, as well as high reproducibility, efficient material usage, and high-throughput manipulation. The introduction of supramolecular chemistry, such as host-guest interactions, endows the resultant microcapsules with stimuli-responsiveness and self-adjusting capabilities, and facilitates hierarchical microstructures with tunable stability and porosity, leading to the maturity of current microencapsulation industry. Supramolecular architectures and materials have attracted immense attention over the past decade, as they open the possibility to obtain a large variety of aesthetically pleasing structures, with myriad applications in biomedicine, energy, sensing, catalysis, and biomimicry, on account of the inherent reversible and adaptive nature of supramolecular interactions. As a subset of supramolecular interactions, host-guest molecular recognition involves the formation of inclusion complexes between two or more moieties, with specific three-dimensional structures and spatial arrangements, in a highly controllable and cooperative manner. Such highly selective, strong yet dynamic interactions could be exploited as an alternative methodology for programmable and controllable engineering of supramolecular architectures and materials, exploiting reversible interactions between complementary components. Through the engineering of molecular structures, assemblies can be readily functionalized based on host-guest interactions, with desirable physicochemical characteristics. In this Account, we summarize the current state of development in the field of monodisperse supramolecular microcapsules, fabricated through the integration of traditional microfluidic techniques and interfacial host-guest chemistry, specifically cucurbit[n]uril (CB[n])-mediated host-guest interactions. Three different strategies, colloidal particle-driven assembly, interfacial condensation-driven assembly and electrostatic interaction-driven assembly, are classified and discussed in detail, presenting the methodology involved in each microcapsule formation process. We highlight the state-of-the-art in design and control over structural complexity with desirable functionality, as well as promising applications, such as cargo delivery stemming from the assembled microcapsules. On account of its dynamic nature, the CB[n]-mediated host-guest complexation has demonstrated efficient response toward various external stimuli such as UV light, pH change, redox chemistry, and competitive guests. Herein, we also demonstrate different microcapsule modalities, which are engineered with CB[n] host-guest chemistry and also can be disrupted with the aid of external stimuli, for triggered release of payloads. In addition to the overview of recent achievements and current limitations of these microcapsules, we finally summarize several perspectives on tunable cargo loading and triggered release, directions, and challenges for this technology, as well as possible strategies for further improvement, which will lead to substainitial progress of host-guest chemistry in supramolecular architectures and materials.
  16. Kamal MA, Smith PF, Chaiyakunapruk N, Wu DBC, Pratoomsoot C, Lee KKC, et al.
    Br J Clin Pharmacol, 2017 07;83(7):1580-1594.
    PMID: 28176362 DOI: 10.1111/bcp.13229
    AIMS: A modular interdisciplinary platform was developed to investigate the economic impact of oseltamivir treatment by dosage regimen under simulated influenza pandemic scenarios.

    METHODS: The pharmacology module consisted of a pharmacokinetic distribution of oseltamivir carboxylate daily area under the concentration-time curve at steady state (simulated for 75 mg and 150 mg twice daily regimens for 5 days) and a pharmacodynamic distribution of viral shedding duration obtained from phase II influenza inoculation data. The epidemiological module comprised a susceptible, exposed, infected, recovered (SEIR) model to which drug effect on the basic reproductive number (R0 ), a measure of transmissibility, was linked by reduction of viral shedding duration. The number of infected patients per population of 100 000 susceptible individuals was simulated for a series of pandemic scenarios, varying oseltamivir dose, R0 (1.9 vs. 2.7), and drug uptake (25%, 50%, and 80%). The number of infected patients for each scenario was entered into the health economics module, a decision analytic model populated with branch probabilities, disease utility, costs of hospitalized patients developing complications, and case-fatality rates. Change in quality-adjusted life years was determined relative to base case.

    RESULTS: Oseltamivir 75 mg relative to no treatment reduced the median number of infected patients, increased change in quality-adjusted life years by deaths averted, and was cost-saving under all scenarios; 150 mg relative to 75 mg was not cost effective in low transmissibility scenarios but was cost saving in high transmissibility scenarios.

    CONCLUSION: This methodological study demonstrates proof of concept that the disciplines of pharmacology, disease epidemiology and health economics can be linked in a single quantitative framework.

    MeSH terms: Antiviral Agents/economics; Antiviral Agents/pharmacology; Antiviral Agents/therapeutic use*; Cost-Benefit Analysis/methods*; Humans; Influenza, Human/drug therapy*; Influenza, Human/economics; Influenza, Human/mortality; Influenza, Human/epidemiology; Methods; Models, Theoretical; Interdisciplinary Communication; Oseltamivir/economics; Oseltamivir/pharmacology; Oseltamivir/therapeutic use*; Pandemics/economics*
  17. Ng WC, Lim TL, Yoon TL
    J Chem Inf Model, 2017 03 27;57(3):517-528.
    PMID: 28178783 DOI: 10.1021/acs.jcim.6b00553
    Melting dynamics of hafnium clusters are investigated using a novel approach based on the idea of the chemical similarity index. Ground state configurations of small hafnium clusters are first derived using Basin-Hopping and Genetic Algorithm in the parallel tempering mode, employing the COMB potential in the energy calculator. These assumed ground state structures are verified by using the Low Lying Structures (LLS) method. The melting process is carried out either by using the direct heating method or prolonged simulated annealing. The melting point is identified by a caloric curve. However, it is found that the global similarity index is much more superior in locating premelting and total melting points of hafnium clusters.
    MeSH terms: Hafnium/chemistry*; Models, Molecular*; Transition Temperature; Phase Transition*
  18. Miswan MF, Saman MS, Hui TS, Al-Fayyadh MZ, Ali MR, Min NW
    J Orthop Surg (Hong Kong), 2017 01;25(1):2309499017690317.
    PMID: 28215115 DOI: 10.1177/2309499017690317
    INTRODUCTION: We conducted a study to elucidate the correlation between the anatomy of the shoulder joint with the development of rotator cuff tear (RCT) and glenohumeral osteoarthritis (GHOA) by using acromioglenoid angle (AGA).

    MATERIALS AND METHODS: The AGA is a new measured angle formed between the line from midglenoid to lateral end of the acromion with the line parallel to the glenoid surface. The AGA was measured in a group of 85 shoulders with RCT, 49 with GHOA and 103 non-RCT/GHOA control shoulders. The AGA was compared with other radiological parameters, such as, the critical shoulder angle (CSA), the acromion index (AI) and the acromiohumeral interval (AHI). Correlational and regression analysis were performed using SPSS 20.

    RESULTS: The mean AGA was 50.9° (45.2-56.5°) in the control group, 53.3° (47.6-59.1°) in RCT group and 45.5° (37.7-53.2°) in OA group. Among patients with AGA > 51.5°, 61% were in the RCT group and among patients with AGA < 44.5°, 56% were in OA group. Pearson correlation analysis had shown significant correlation between AGA and CSA ( r = 0.925, p < 0.001). It was also significant of AHI in RCT group with mean 6.6 mm (4.7-8.5 mm) and significant AI in OA group with mean 0.68 (0.57-0.78) with p value < 0.001 respectively.

    CONCLUSION: The AGA method of measurement is an excellent predictive parameter for diagnosing RCT and GHOA.

    MeSH terms: Adult; Aged; Female; Humans; Male; Middle Aged; Osteoarthritis/epidemiology*; Prospective Studies; Radiography; Sensitivity and Specificity; Shoulder Joint*; Incidence; Case-Control Studies; Rotator Cuff Injuries/epidemiology*; Rotator Cuff Injuries/diagnostic imaging
  19. Lo Vecchio A, Liguoro I, Dias JA, Berkley JA, Boey C, Cohen MB, et al.
    Vaccine, 2017 Mar 14;35(12):1637-1644.
    PMID: 28216189 DOI: 10.1016/j.vaccine.2017.01.082
    BACKGROUND: Rotavirus (RV) is a major agent of gastroenteritis and an important cause of child death worldwide. Immunization (RVI) has been available since 2006, and the Federation of International Societies of Gastroenterology Hepatology and Nutrition (FISPGHAN) identified RVI as a top priority for the control of diarrheal illness. A FISPGHAN working group on acute diarrhea aimed at estimating the current RVI coverage worldwide and identifying barriers to implementation at local level.

    METHODS: A survey was distributed to national experts in infectious diseases and health-care authorities (March 2015-April 2016), collecting information on local recommendations, costs and perception of barriers for implementation.

    RESULTS: Forty-nine of the 79 contacted countries (62% response rate) provided a complete analyzable data. RVI was recommended in 27/49 countries (55%). Although five countries have recommended RVI since 2006, a large number (16, 33%) included RVI in a National Immunization Schedule between 2012 and 2014. The costs of vaccination are covered by the government (39%), by the GAVI Alliance (10%) or public and private insurance (8%) in some countries. However, in most cases, immunization is paid by families (43%). Elevated cost of vaccine (49%) is the main barrier for implementation of RVI. High costs of vaccination (rs=-0.39, p=0.02) and coverage of expenses by families (rs=0.5, p=0.002) significantly correlate with a lower immunization rate. Limited perception of RV illness severity by the families (47%), public-health authorities (37%) or physicians (24%) and the timing of administration (16%) are further major barriers to large- scale RVI programs.

    CONCLUSIONS: After 10years since its introduction, the implementation of RVI is still unacceptably low and should remain a major target for global public health. Barriers to implementation vary according to setting. Nevertheless, public health authorities should promote education for caregivers and health-care providers and interact with local health authorities in order to implement RVI.

    MeSH terms: Gastroenteritis/epidemiology; Gastroenteritis/prevention & control; Humans; Surveys and Questionnaires; Rotavirus Infections/epidemiology*; Rotavirus Infections/prevention & control*; Global Health; Rotavirus Vaccines/administration & dosage*; Rotavirus Vaccines/immunology*
  20. Zainal N, Chang CP, Cheng YL, Wu YW, Anderson R, Wan SW, et al.
    Sci Rep, 2017 02 20;7:42998.
    PMID: 28216632 DOI: 10.1038/srep42998
    Dengue is one of the most significant mosquito-borne virus diseases worldwide, particularly in tropical and subtropical regions. This study sought to examine the antiviral activity of resveratrol (RESV), a phytoalexin secreted naturally by plants, against dengue virus (DENV) infection. Our data showed that RESV inhibits the translocation of high mobility group box 1 (HMGB1), a DNA binding protein that normally resides in the nucleus, into the cytoplasm and extracellular milieu. HMGB1 migrates out of the nucleus during DENV infection. This migration is inhibited by RESV treatment and is mediated by induction of Sirt1 which leads to the retention of HMGB1 in the nucleus and consequently helps in the increased production of interferon-stimulated genes (ISGs). Nuclear HMGB1 was found to bind to the promoter region of the ISG and positively regulated the expression of ISG. The enhanced transcription of ISGs by nuclear HMGB1 thus contributes to the antiviral activity of RESV against DENV. To the best of our knowledge, this is the first report to demonstrate that RESV antagonizes DENV replication and that nuclear HMGB1 plays a role in regulating ISG production.
    MeSH terms: Antiviral Agents/pharmacology*; Antiviral Agents/therapeutic use; Cell Nucleus/metabolism; Dengue/drug therapy; Dengue/pathology; Dengue/virology; Dengue Virus/isolation & purification; Dengue Virus/physiology; Humans; Interferon Type I/genetics; Interferon Type I/metabolism*; Promoter Regions, Genetic; Protein Binding; Stilbenes/pharmacology*; Stilbenes/therapeutic use; Virus Replication/drug effects*; Interferon-beta/genetics; Interferon-beta/metabolism; HMGB1 Protein/antagonists & inhibitors; HMGB1 Protein/genetics; HMGB1 Protein/metabolism*; RNA Interference; RNA, Small Interfering/metabolism; Cell Line, Tumor; Sirtuin 1/antagonists & inhibitors; Sirtuin 1/genetics; Sirtuin 1/metabolism; Myxovirus Resistance Proteins/genetics; Myxovirus Resistance Proteins/metabolism
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