Browse publications by year: 2015

Fulltext Fatty acid compositions of silver catfish, Pangasius sp. farmed in several rivers of Pahang, Malaysia

Hashim RB, Jamil EF, Zulkipli FH, Daud JM

J Oleo Sci, 2015;64(2):205-9.
PMID: 25748380 DOI: 10.5650/jos.ess14191

Pangasius micronemus (Black Pangasius sp.) and Pangasius nasutus (Fruit Pangasius sp.) are two species of silver catfish widely consumed in Malaysia. The present study evaluated fatty acid profiles of fish muscles in these two Pangasius sp. from different farms and locations to determine which species or location is better in term of lipid quality. The results showed MUFAs (Monounsaturated fatty acid) content was highest (35.0-44.4%) followed by SFA (Saturated fatty acid) [32.0-41.5%] and PUFAs (polyunsaturated fatty acids) [9.3-19.3%]. P. micronemus of Sg. Kanchong displayed higher palmitic acid (SFA; 29.0%) than P. nasutus from Peramu (23.5%). In contrast, oleic acid (MUFA) revealed highest in P. nasutus (38.1%) while lowest in P. micronemus of Sg. Kanchong (29.7%). Additionally, utmost PUFAs belonged to P. micronemus of Sg. Kanchong (19.3%) and lower most in P. nasutus from Peramu (9.3%). P. micronemus presented with a higher EPA (eicosapentaenoic acid) [1.0-1.4%], DHA (Docosahexaenoic acid) [1.7-2.8%] and LA (Linoleic acid) [11.8-12.0%] than P. nasutus (EPA; 0.3%, DHA; 1.0%, LA; 4.8%). However, P. nasutus established higher GLA (gamma-linolenic acid) [0.4%] than P. micronemus (0.04-0.06%). Both Pangasius sp. can be regarded as good supplies of omega-3 and omega-6. Overall, P. micronemus from Sg. Kanchong is the best choice among all for reason high in EPA and DHA.

MeSH terms: Animals; Catfishes/metabolism*; Docosahexaenoic Acids/analysis; Fatty Acids/analysis*; Fatty Acids, Monounsaturated/analysis*; Fatty Acids, Unsaturated/analysis*; Fisheries/methods*; Malaysia; Eicosapentaenoic Acid/analysis; Fatty Acids, Omega-3/analysis; Oleic Acid/analysis; Palmitic Acid/analysis; Linoleic Acid/analysis; Fatty Acids, Omega-6/analysis; Rivers*
Mouse fibroblast L929 cells are less permissive to infection by Nelson Bay orthoreovirus compared to other mammalian cell lines

Mok L, Wynne JW, Grimley S, Shiell B, Green D, Monaghan P, et al.

J Gen Virol, 2015 Jul;96(Pt 7):1787-94.
PMID: 25748429 DOI: 10.1099/vir.0.000112

In recent years, bats have been identified as a natural reservoir for a diverse range of viruses. Nelson Bay orthoreovirus (NBV) was first isolated from the heart blood of a fruit bat (Pteropus poliocephalus) in 1968. While the pathogenesis of NBV remains unknown, other related members of this group have caused acute respiratory disease in humans. Thus the potential for NBV to impact human health appears plausible. Here, to increase our knowledge of NBV, we examined the replication and infectivity of NBV using different mammalian cell lines derived from bat, human, mouse and monkey. All cell lines supported the replication of NBV; however, L929 cells showed a greater than 2 log reduction in virus titre compared with the other cell lines. Furthermore, NBV did not induce major cytopathic effects in the L929 cells, as was observed in other cell lines. Interestingly, the related Pteropine orthoreoviruses, Pulau virus (PulV) and Melaka virus (MelV) were able to replicate to high titres in L929 cells but infection resulted in reduced cytopathic effect. Our study demonstrates a unique virus-host interaction between NBV and L929 cells, where cells effectively control viral infection/replication and limit the formation of syncytia. By elucidating the molecular mechanisms that control this unique relationship, important insights will be made into the biology of this fusogenic virus.

MeSH terms: Animals; Haplorhini; Cell Line/virology*; Chiroptera; Fibroblasts/virology*; Humans; Virus Cultivation; Virus Replication; Orthoreovirus/growth & development; Orthoreovirus/physiology*; Viral Load; Mice; Viral Tropism*
A step ahead of PPARγ full agonists to PPARγ partial agonists: therapeutic perspectives in the management of diabetic insulin resistance

Chigurupati S, Dhanaraj SA, Balakumar P

Eur J Pharmacol, 2015 May 15;755:50-7.
PMID: 25748601 DOI: 10.1016/j.ejphar.2015.02.043

Described since long as a member of the nuclear receptor superfamily, peroxisome proliferator-activated receptors (PPARs) regulate the gene expression of proteins involved in glucose and lipid metabolism. PPARs indeed regulate several physiologic processes, including lipid homeostasis, adipogenesis, inflammation, and wound healing. PPARs bind natural or synthetic PPAR ligands can function as cellular sensors to regulate the gene transcription. Dyslipidemia, and type 2 diabetes mellitus (T2DM) with insulin resistance are treated using agonists of PPARα and PPARγ, respectively. The PPARγ is a key regulator of insulin sensitization and glucose metabolism, and therefore is considered as an imperative pharmacological target to combat diabetic metabolic disease and insulin resistance. Of note, currently available PPARγ full agonists like rosiglitazone display serious adverse effects such as fluid retention/oedema, weight gain, and increased incidence of cardiovascular events. On the other hand, PPARγ partial agonists are being suggested to devoid or having less incidence of these undesirable events, and are under developmental stages. Current research is on the way for the development of novel PPARγ partial agonists with enhanced therapeutic efficacy and reduced adverse effects. This review sheds lights on the current status of development of PPARγ partial agonists, for the management of T2DM, having comparatively less or no adverse effects to that of PPARγ full agonists.

MeSH terms: Animals; Diabetes Mellitus, Type 2/drug therapy*; Humans; Hypoglycemic Agents/therapeutic use*; Insulin Resistance*; PPAR gamma/agonists*
Fulltext Seropositivity and serointensity of Toxoplasma gondii antibodies and DNA among patients with schizophrenia

Omar A, Bakar OC, Adam NF, Osman H, Osman A, Suleiman AH, et al.

Korean J Parasitol, 2015 Feb;53(1):29-34.
PMID: 25748706 DOI: 10.3347/kjp.2015.53.1.29

The aim of this cross sectional case control study was to examine the serofrequency and serointensity of Toxoplasma gondii (Tg) IgG, IgM, and DNA among patients with schizophrenia. A total of 101 patients with schizophrenia and 55 healthy controls from Sungai Buloh Hospital, Selangor, Malaysia and University Malaya Medical Center (UMMC) were included in this study. The diagnosis of schizophrenia was made based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). The presence of Tg infection was examined using both indirect (ELISA) and direct (quantitative real-time PCR) detection methods by measuring Tg IgG and IgM and DNA, respectively. The serofrequency of Tg IgG antibodies (51.5%, 52/101) and DNA (32.67%, 33/101) among patients with schizophrenia was significantly higher than IgG (18.2%, 10/55) and DNA (3.64%, 2/55) of the controls (IgG, P=0.000, OD=4.8, CI=2.2-10.5; DNA, P=0.000, OD=12.9, CI=2.17-10.51). However, the Tg IgM antibody between patients with schizophrenia and controls was not significant (P>0.005). There was no significant difference (P>0.005) in both serointensity of Tg IgG and DNA between patients with schizophrenia and controls. These findings have further demonstrated the strong association between the active Tg infection and schizophrenia.

MeSH terms: Adolescent; Adult; Aged; Antibodies, Protozoan/blood*; Cross-Sectional Studies; Enzyme-Linked Immunosorbent Assay; Female; Humans; Immunoglobulin G/blood; Immunoglobulin M/blood; Malaysia; Male; Middle Aged; Schizophrenia/complications*; Toxoplasma/classification; Toxoplasma/genetics; Toxoplasma/immunology; Toxoplasma/isolation & purification*; Toxoplasmosis/immunology; Toxoplasmosis/epidemiology*; Toxoplasmosis/parasitology*; Case-Control Studies; Seroepidemiologic Studies; DNA, Protozoan/blood*; Young Adult; Real-Time Polymerase Chain Reaction
A novel polymer inclusion membranes based optode for sensitive determination of Al³⁺ ions

Suah FB, Ahmad M, Heng LY

Spectrochim Acta A Mol Biomol Spectrosc, 2015 Jun 5;144:81-7.
PMID: 25748985 DOI: 10.1016/j.saa.2015.02.068

A novel approach for the determination of Al(3+) from aqueous samples was developed using an optode membrane produced by physical inclusion of Al(3+) selective reagent, which is morin into a plasticized poly(vinyl chloride). The inclusion of Triton X-100 was found to be valuable and useful for enhancing the sorption of Al(3+) ions from liquid phase into the membrane phase, thus increasing the intensity of optode's absorption. The optode showed a linear increase in the absorbance at λ(max)=425 nm over the concentration range of 1.85×10(-6)-1.1×10(-4) mol L(-1) (0.05-3 μg mL(-1)) of Al(3+) ions in aqueous solution after 5 min. The limit of detection was determined to be 1.04×10(-6) mol L(-1) (0.028 μg mL(-1)). The optode developed in the present work was easily prepared and found to be stable, has good mechanical strength, sensitive and reusable. In addition, the optode was tested for Al(3+) determination in lake water, river water and pharmaceutical samples, which the result was satisfactory.

MeSH terms: Aluminum/analysis*; Pharmaceutical Preparations/chemistry; Flavonoids; Hydrogen-Ion Concentration; Ions; Kinetics; Membranes, Artificial*; Polymers/chemistry*; Solutions; Spectrum Analysis; Time Factors; Water Pollutants, Chemical/analysis; Reproducibility of Results; Optics and Photonics*; Recycling
Synthesis, X-ray, NMR, FT-IR, UV/vis, DFT and TD-DFT studies of N-(4-chlorobutanoyl)-N'-(2-, 3- and 4-methylphenyl)thiourea derivatives

Abosadiya HM, Anouar el H, Hasbullah SA, Yamin BM

Spectrochim Acta A Mol Biomol Spectrosc, 2015 Jun 5;144:115-24.
PMID: 25748989 DOI: 10.1016/j.saa.2015.01.092

A new isomers of thiourea derivatives, namely N-(4-chlorobutanoyl)-N'-(2-methylphenyl)-thiourea (1a), N-(4-chlorobutanoyl)-N'-(3-methylphenyl)thiourea (1b) and N-(4-chlorobutanoyl)-N'-(4-methylphenyl)thiourea (1c) have been synthesized by refluxing mixture of equimolar amounts of 4-chlorobutanoylisothiocyanate with 2, 3 or 4-toluidine, respectively. The three isomers were characterized by spectroscopic (UV/vis, FT-IR and NMR) and X-ray crystallography techniques. To investigate the isomerization effect on spectroscopic data, DFT and TD-DFT calculations have been carried out using five hybrid functionals (B3LYP, B3P86, CAM-B3LYP, M06-2X and PBE0) to predict UV/vis absorption bands (n→π∗ and π→π∗), (1)H and (13)C NMR chemical shifts, FT-IR vibration modes and X-ray parameters (bonds, bond angles and torsion angles) for 1a, 1b and 1c isomers. The results showed that the isomerization effect is significant on λ(MAX) absorption bands, while for IR and NMR the effect is negligible. In accordance with previous studies, B3LYP, B3P86 and PBE0 gave the most reliable to predict the excitation energies of thiourea derivatives.

MeSH terms: Isomerism; Models, Molecular*; Molecular Conformation; Magnetic Resonance Spectroscopy*; Phenylthiourea/analogs & derivatives*; Phenylthiourea/chemical synthesis; Phenylthiourea/chemistry; Quantum Theory*; Spectrophotometry, Ultraviolet; Thiourea/chemical synthesis*; Thiourea/chemistry*; Vibration; X-Rays; Spectroscopy, Fourier Transform Infrared; Crystallography, X-Ray; Carbon-13 Magnetic Resonance Spectroscopy; Proton Magnetic Resonance Spectroscopy
A radiographic measurement technique for crest bone changes related to dental implants

Patil PG, Nimbalkar-Patil S

J Prosthet Dent, 2015 Apr;113(4):350-1.
PMID: 25749086 DOI: 10.1016/j.prosdent.2014.11.002
Determination of para-arsanilic acid with improved diazotization reaction using differential pulse cathodic stripping voltammetry in aqueous system

Misni M, Sathishkumar P, Ahamad R, MohdYusoff AR

Environ Technol, 2015;36(17):2249-54.
PMID: 25749108 DOI: 10.1080/09593330.2015.1025105

Para-arsanilic acid (p-ASA) has been widely used in the poultry industry to promote growth and prevent dysentery. It is excreted unchanged in the manure and released into non-target sites causing organoarsenic pollution risk to the environment and living system. Therefore, simple and effective analytical strategies are demanded for determining the samples that contain p-ASA. However, direct determination of both p-ASA and ortho-arsanilic acid (o-ASA) using differential pulse cathodic stripping voltammetry (DPCSV) gives the similar voltammograms that directly hamper the analysis used by the DPCSV technique. In this study, a method to determine and differentiate p-ASA from o-ASA via diazotization and coupling reaction of the amine groups followed by the direct DPCSV determination of diazo compounds is presented. The diazotization reaction carried out at pH 1.5 and 0 ± 1°C for 10 min showed two reduction peaks in DPCSV at-70 mV and -440 mV vs. Ag/AgCl (KCl 3 M). However, when the diazotization reaction was performed at pH 12.5 and 0 ± 1°C for 40 min, a coloured azo compound was produced and the DPCSV showed only one reduction peak that appeared at -600 mV vs. Ag/AgCl (3 M of KCl). The results of this study show that only p-ASA compound gave a reduction peak, whereas o-ASA compound did not give any peak. The detection limit of p-ASA was found to be 4 × 10(-8 )M. As a result, the proposed electro-analytical technique might be a good candidate to determine and differentiate the p-ASA present in the poultry and environmental samples.

MeSH terms: Animal Feed/analysis; Arsanilic Acid/analysis*; Azo Compounds/analysis; Electrodes; Water/analysis*; Water Pollutants, Chemical/analysis*; Electrochemical Techniques/methods*; Limit of Detection
Mathematical model of the effect of ischemia-reperfusion on brain capillary collapse and tissue swelling

Mohamed Mokhtarudin MJ, Payne SJ

Math Biosci, 2015 May;263:111-20.
PMID: 25749185 DOI: 10.1016/j.mbs.2015.02.011

Restoration of an adequate cerebral blood supply after an ischemic attack is a primary clinical goal. However, the blood-brain barrier may break down after a prolonged ischemia causing the fluid in the blood plasma to filtrate and accumulate into the cerebral tissue interstitial space. Accumulation of this filtration fluid causes the cerebral tissue to swell, a condition known as vasogenic oedema. Tissue swelling causes the cerebral microvessels to be compressed, which may further obstruct the blood flow into the tissue, thus leading to the no-reflow phenomenon or a secondary ischemic stroke. The actual mechanism of this however is still not fully understood. A new model is developed here to study the effect of reperfusion on the formation of vasogenic oedema and cerebral microvessel collapse. The formation of vasogenic oedema is modelled using the capillary filtration equation while vessel collapse is modelled using the tube law of microvessel. Tissue swelling is quantified in terms of displacement, which is modelled using poroelastic theory. The results show that there is an increase in tissue displacement and interstitial pressure after reperfusion. In addition, the results also show that vessel collapse can occur at high value of reperfusion pressure, low blood osmotic pressure, high cerebral capillary permeability and low cerebral capillary stiffness. This model provides insight on the formation of ischemia-reperfusion injury by tissue swelling and vessel collapse.
Fulltext Glucose uptake during contraction in isolated skeletal muscles from neuronal nitric oxide synthase μ knockout mice

Hong YH, Frugier T, Zhang X, Murphy RM, Lynch GS, Betik AC, et al.

J Appl Physiol (1985), 2015 May 1;118(9):1113-21.
PMID: 25749441 DOI: 10.1152/japplphysiol.00056.2015

Inhibition of nitric oxide synthase (NOS) significantly attenuates the increase in skeletal muscle glucose uptake during contraction/exercise, and a greater attenuation is observed in individuals with Type 2 diabetes compared with healthy individuals. Therefore, NO appears to play an important role in mediating muscle glucose uptake during contraction. In this study, we investigated the involvement of neuronal NOSμ (nNOSμ), the main NOS isoform activated during contraction, on skeletal muscle glucose uptake during ex vivo contraction. Extensor digitorum longus muscles were isolated from nNOSμ(-/-) and nNOSμ(+/+) mice. Muscles were contracted ex vivo in a temperature-controlled (30°C) organ bath with or without the presence of the NOS inhibitor N(G)-monomethyl-l-arginine (L-NMMA) and the NOS substrate L-arginine. Glucose uptake was determined by radioactive tracers. Skeletal muscle glucose uptake increased approximately fourfold during contraction in muscles from both nNOSμ(-/-) and nNOSμ(+/+) mice. L-NMMA significantly attenuated the increase in muscle glucose uptake during contraction in both genotypes. This attenuation was reversed by L-arginine, suggesting that L-NMMA attenuated the increase in muscle glucose uptake during contraction by inhibiting NOS and not via a nonspecific effect of the inhibitor. Low levels of NOS activity (~4%) were detected in muscles from nNOSμ(-/-) mice, and there was no evidence of compensation from other NOS isoform or AMP-activated protein kinase which is also involved in mediating muscle glucose uptake during contraction. These results indicate that NO regulates skeletal muscle glucose uptake during ex vivo contraction independently of nNOSμ.

MeSH terms: Animals; Arginine/metabolism; Biological Transport/drug effects; Biological Transport/physiology; Enzyme Inhibitors/pharmacology; Female; Glucose/metabolism*; Male; Mice, Inbred C57BL; Muscle Contraction/drug effects; Muscle Contraction/physiology*; Nitric Oxide/metabolism; Physical Conditioning, Animal/physiology; Mice, Knockout; Muscle, Skeletal/drug effects; Muscle, Skeletal/metabolism*; Muscle, Skeletal/physiology*; omega-N-Methylarginine/pharmacology; Mice; Nitric Oxide Synthase Type I/metabolism*; AMP-Activated Protein Kinases/metabolism
Socioeconomic and gender group differences in early literacy skills: a multiple-group confirmatory factor analysis approach

Lee JA, Otaiba SA

Educational research and evaluation : an international journal on theory and practice, 2015 3 10;21(1):40-59.
PMID: 25750582

Socioeconomic status and gender are important demographic variables that strongly relate to academic achievement. This study examined the early literacy skills differences between 4 sociodemographic groups, namely, boys ineligible for free or reduced-price lunch (FRL), girls ineligible for FRL, boys eligible for FRL, and girls eligible for FRL. Data on kindergarteners (N = 462) were analysed using multiple-group confirmatory factory analysis. Early literacy skill differences between boys and girls are more nuanced than previously reported; subsidy status and gender interact. Both boys and girls from high-poverty households performed significantly lower than the girls from low-poverty households in alphabet knowledge, phonological awareness, and spelling. There were gender gaps, with a female advantage, among children from high-poverty households in alphabet knowledge and spelling and among children from low-poverty households in alphabet knowledge. These results highlight the importance of employing methodologically sound techniques to ascertain group differences in componential early literacy skills.

MeSH terms: Literacy; Child; Family Characteristics; Female; Humans; Language; Male; Men; Poverty; Sex Factors; Social Class; Lunch
Impact of Haemodialysis on Insulin Kinetics of Acute Kidney Injury Patients in Critical Care

Jamaludin UK, Docherty PD, Geoffrey Chase J, Shaw GM

J Med Biol Eng, 2015 02 03;35(1):125-133.
PMID: 25750607

Critically ill patients are occasionally associated with an abrupt decline in renal function secondary to their primary diagnosis. The effect and impact of haemodialysis (HD) on insulin kinetics and endogenous insulin secretion in critically ill patients remains unclear. This study investigates the insulin kinetics of patients with severe acute kidney injury (AKI) who required HD treatment and glycaemic control (GC). Evidence shows that tight GC benefits the onset and progression of renal involvement in precocious phases of diabetic nephropathy for type 2 diabetes. The main objective of GC is to reduce hyperglycaemia while determining insulin sensitivity. Insulin sensitivity (S
I
) is defined as the body response to the effects of insulin by lowering blood glucose levels. Particularly, this study used S
I
to track changes in insulin levels during HD therapy. Model-based insulin sensitivity profiles were identified for 51 critically ill patients with severe AKI on specialized relative insulin nutrition titration GC during intervals on HD (OFF/ON) and after HD (ON/OFF). The metabolic effects of HD were observed through changes in S
I
over the ON/OFF and OFF/ON transitions. Changes in model-based S
I
at the OFF/ON and ON/OFF transitions indicate changes in endogenous insulin secretion and/or changes in effective insulin clearance. Patients exhibited a median reduction of -29 % (interquartile range (IQR): [-58, 6 %], p = 0.02) in measured S
I
after the OFF/ON dialysis transition, and a median increase of +9 % (IQR -15 to 28 %, p = 0.7) after the ON/OFF transition. Almost 90 % of patients exhibited decreased S
I
at the OFF/ON transition, and 55 % exhibited increased S
I
at the ON/OFF transition. Results indicate that HD commencement has a significant effect on insulin pharmacokinetics at a cohort and per-patient level. These changes in metabolic behaviour are most likely caused by changes in insulin clearance or/and endogenous insulin secretion.

MeSH terms: Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Renal Dialysis; Humans; Hyperglycemia; Insulin; Insulin Resistance; Kidney; Kinetics; Cohort Studies; Critical Illness; Disease Progression; Acute Kidney Injury; Insulin, Regular, Human
Fulltext Genetic diversity of geographically distinct Streptococcus dysgalactiae isolates from fish

Abdelsalam M, Eissa AE, Chen SC

J Adv Res, 2015 Mar;6(2):233-8.
PMID: 25750757 DOI: 10.1016/j.jare.2013.12.003

Streptococcus dysgalactiae is an emerging pathogen of fish. Clinically, infection is characterized by the development of necrotic lesions at the caudal peduncle of infected fishes. The pathogen has been recently isolated from different fish species in many countries. Twenty S. dysgalactiae isolates collected from Japan, Taiwan, Malaysia and Indonesia were molecularly characterized by biased sinusoidal field gel electrophoresis (BSFGE) using SmaI enzyme, and tuf gene sequencing analysis. DNA sequencing of ten S. dysgalactiae revealed no genetic variation in the tuf amplicons, except for three strains. The restriction patterns of chromosomal DNA measured by BSFGE were differentiated into six distinct types and one subtype among collected strains. To our knowledge, this report gives the first snapshot of S. dysgalactiae isolates collected from different countries that are localized geographically and differed on a multinational level. This genetic unrelatedness among different isolates might suggest a high recombination rate and low genetic stability.

MeSH terms: Animals; Base Sequence; DNA; Electrophoresis; Fishes; Indonesia; Japan; Malaysia; Recombination, Genetic; Streptococcus; Taiwan; Sequence Analysis, DNA
Fulltext A portable automatic endpoint detection system for amplicons of loop mediated isothermal amplification on microfluidic compact disk platform

Uddin SM, Ibrahim F, Sayad AA, Thiha A, Pei KX, Mohktar MS, et al.

Sensors (Basel), 2015 Mar 05;15(3):5376-89.
PMID: 25751077 DOI: 10.3390/s150305376

In recent years, many improvements have been made in foodborne pathogen detection methods to reduce the impact of food contamination. Several rapid methods have been developed with biosensor devices to improve the way of performing pathogen detection. This paper presents an automated endpoint detection system for amplicons generated by loop mediated isothermal amplification (LAMP) on a microfluidic compact disk platform. The developed detection system utilizes a monochromatic ultraviolet (UV) emitter for excitation of fluorescent labeled LAMP amplicons and a color sensor to detect the emitted florescence from target. Then it processes the sensor output and displays the detection results on liquid crystal display (LCD). The sensitivity test has been performed with detection limit up to 2.5 × 10(-3) ng/µL with different DNA concentrations of Salmonella bacteria. This system allows a rapid and automatic endpoint detection which could lead to the development of a point-of-care diagnosis device for foodborne pathogens detection in a resource-limited environment.

MeSH terms: DNA, Bacterial/isolation & purification*; DNA, Bacterial/chemistry; Food Microbiology*; Humans; Salmonella/isolation & purification*; Salmonella/pathogenicity; Compact Disks; Microfluidic Analytical Techniques/methods*
Country perspective on medical tourism: the Malaysian experience

Abd Manaf NH, Hussin H, Jahn Kassim PN, Alavi R, Dahari Z

Leadersh Health Serv (Bradf Engl), 2015;28(1):43-56.
PMID: 25751248 DOI: 10.1108/LHS-11-2013-0038

The study seeks to explore the perception of international patients on Malaysia as a medical tourism destination country, as well as overall patient satisfaction, perceived value and future intention for repeat treatment and services.
Fulltext Genome-wide association analysis of more than 120,000 individuals identifies 15 new susceptibility loci for breast cancer

Michailidou K, Beesley J, Lindstrom S, Canisius S, Dennis J, Lush MJ, et al.

Nat Genet, 2015 Apr;47(4):373-80.
PMID: 25751625 DOI: 10.1038/ng.3242

Genome-wide association studies (GWAS) and large-scale replication studies have identified common variants in 79 loci associated with breast cancer, explaining ∼14% of the familial risk of the disease. To identify new susceptibility loci, we performed a meta-analysis of 11 GWAS, comprising 15,748 breast cancer cases and 18,084 controls together with 46,785 cases and 42,892 controls from 41 studies genotyped on a 211,155-marker custom array (iCOGS). Analyses were restricted to women of European ancestry. We generated genotypes for more than 11 million SNPs by imputation using the 1000 Genomes Project reference panel, and we identified 15 new loci associated with breast cancer at P < 5 × 10(-8). Combining association analysis with ChIP-seq chromatin binding data in mammary cell lines and ChIA-PET chromatin interaction data from ENCODE, we identified likely target genes in two regions: SETBP1 at 18q12.3 and RNF115 and PDZK1 at 1q21.1. One association appears to be driven by an amino acid substitution encoded in EXO1.

MeSH terms: Female; Humans; Cohort Studies; Case-Control Studies; Genetic Predisposition to Disease*; Polymorphism, Single Nucleotide; Microarray Analysis; Genome-Wide Association Study; Genetic Loci*
Comparing NAL-NL1 and DSL v5 in Hearing Aids Fit to Children with Severe or Profound Hearing Loss: Goodness of Fit-to-Targets, Impacts on Predicted Loudness and Speech Intelligibility

Ching TY, Quar TK, Johnson EE, Newall P, Sharma M

J Am Acad Audiol, 2015 Mar;26(3):260-74.
PMID: 25751694 DOI: 10.3766/jaaa.26.3.6

BACKGROUND: An important goal of providing amplification to children with hearing loss is to ensure that hearing aids are adjusted to match targets of prescriptive procedures as closely as possible. The Desired Sensation Level (DSL) v5 and the National Acoustic Laboratories' prescription for nonlinear hearing aids, version 1 (NAL-NL1) procedures are widely used in fitting hearing aids to children. Little is known about hearing aid fitting outcomes for children with severe or profound hearing loss.
PURPOSE: The purpose of this study was to investigate the prescribed and measured gain of hearing aids fit according to the NAL-NL1 and the DSL v5 procedure for children with moderately severe to profound hearing loss; and to examine the impact of choice of prescription on predicted speech intelligibility and loudness.
RESEARCH DESIGN: Participants were fit with Phonak Naida V SP hearing aids according to the NAL-NL1 and DSL v5 procedures. The Speech Intelligibility Index (SII) and estimated loudness were calculated using published models.
STUDY SAMPLE: The sample consisted of 16 children (30 ears) aged between 7 and 17 yr old.
DATA COLLECTION AND ANALYSIS: The measured hearing aid gains were compared with the prescribed gains at 50 (low), 65 (medium), and 80 dB SPL (high) input levels. The goodness of fit-to-targets was quantified by calculating the average root-mean-square (RMS) error of the measured gain compared with prescriptive gain targets for 0.5, 1, 2, and 4 kHz. The significance of difference between prescriptions for hearing aid gains, SII, and loudness was examined by performing analyses of variance. Correlation analyses were used to examine the relationship between measures.
RESULTS: The DSL v5 prescribed significantly higher overall gain than the NAL-NL1 procedure for the same audiograms. For low and medium input levels, the hearing aids of all children fit with NAL-NL1 were within 5 dB RMS of prescribed targets, but 33% (10 ears) deviated from the DSL v5 targets by more than 5 dB RMS on average. For high input level, the hearing aid fittings of 60% and 43% of ears deviated by more than 5 dB RMS from targets of NAL-NL1 and DSL v5, respectively. Greater deviations from targets were associated with more severe hearing loss. On average, the SII was higher for DSL v5 than for NAL-NL1 at low input level. No significant difference in SII was found between prescriptions at medium or high input level, despite greater loudness for DSL v5 than for NAL-NL1.
CONCLUSIONS: Although targets between 0.25 and 2 kHz were well matched for both prescriptions in commercial hearing aids, gain targets at 4 kHz were matched for NAL-NL1 only. Although the two prescriptions differ markedly in estimated loudness, they resulted in comparable predicted speech intelligibility for medium and high input levels.

MeSH terms: Adolescent; Audiometry; Child; Equipment Design; Female; Hearing Aids*; Humans; Loudness Perception/physiology*; Male; Speech Perception/physiology*; Prosthesis Fitting; Hearing Loss/physiopathology; Hearing Loss/therapy*
Urban health in the post-2015 agenda

Talukder S, Capon A, Nath D, Kolb A, Jahan S, Boufford J

Lancet, 2015 Feb 28;385(9970):769.
PMID: 25752169 DOI: 10.1016/S0140-6736(15)60428-7
MeSH terms: Cities/statistics & numerical data; Conservation of Natural Resources; Humans; Population Growth*; Urban Health/trends*; Global Health/trends*
Exome sequencing and array-based comparative genomic hybridisation analysis of preferential 6-methylmercaptopurine producers

Chua EW, Cree S, Barclay ML, Doudney K, Lehnert K, Aitchison A, et al.

Pharmacogenomics J, 2015 Oct;15(5):414-21.
PMID: 25752523 DOI: 10.1038/tpj.2015.9

Preferential conversion of azathioprine or 6-mercaptopurine into methylated metabolites is a major cause of thiopurine resistance. To seek potentially Mendelian causes of thiopurine hypermethylation, we recruited 12 individuals who exhibited extreme therapeutic resistance while taking azathioprine or 6-mercaptopurine and performed whole-exome sequencing (WES) and copy-number variant analysis by array-based comparative genomic hybridisation (aCGH). Exome-wide variant filtering highlighted four genes potentially associated with thiopurine metabolism (ENOSF1 and NFS1), transport (SLC17A4) or therapeutic action (RCC2). However, variants of each gene were found only in two or three patients, and it is unclear whether these genes could influence thiopurine hypermethylation. Analysis by aCGH did not identify any unusual or pathogenic copy-number variants. This suggests that if causative mutations for the hypermethylation phenotype exist they may be heterogeneous, occurring in several different genes, or they may lie within regulatory regions not captured by WES. Alternatively, hypermethylation may arise from the involvement of multiple genes with small effects. To test this hypothesis would require recruitment of large patient samples and application of genome-wide association studies.

MeSH terms: Azathioprine; Humans; Mutation; Phenotype; Regulatory Sequences, Nucleic Acid; Drug Resistance, Neoplasm; Genomics; Comparative Genomic Hybridization; Genome-Wide Association Study; DNA Copy Number Variations; Exome
Optimisation of the continuum of supportive and palliative care for patients with breast cancer in low-income and middle-income countries: executive summary of the Breast Health Global Initiative, 2014

Distelhorst SR, Cleary JF, Ganz PA, Bese N, Camacho-Rodriguez R, Cardoso F, et al.

Lancet Oncol, 2015 Mar;16(3):e137-47.
PMID: 25752564 DOI: 10.1016/S1470-2045(14)70457-7

Supportive care and palliative care are now recognised as critical components of global cancer control programmes. Many aspects of supportive and palliative care services are already available in some low-income and middle-income countries. Full integration of supportive and palliative care into breast cancer programmes requires a systematic, resource-stratified approach. The Breast Health Global Initiative convened three expert panels to develop resource allocation recommendations for supportive and palliative care programmes in low-income and middle-income countries. Each panel focused on a specific phase of breast cancer care: during treatment, after treatment with curative intent (survivorship), and after diagnosis with metastatic disease. The panel consensus statements were published in October, 2013. This Executive Summary combines the three panels' recommendations into a single comprehensive document covering breast cancer care from diagnosis through curative treatment into survivorship, and metastatic disease and end-of-life care. The recommendations cover physical symptom management, pain management, monitoring and documentation, psychosocial and spiritual aspects of care, health professional education, and patient, family, and caregiver education.

MeSH terms: Breast Neoplasms/diagnosis; Breast Neoplasms/economics; Breast Neoplasms/psychology; Breast Neoplasms/therapy*; Developing Countries/economics*; Female; Health Services Accessibility/economics; Health Services Accessibility/standards*; Humans; Income*; Palliative Care/economics; Palliative Care/standards*; Patient Care Team/economics; Patient Care Team/standards; Poverty/economics*; Quality of Health Care/economics; Quality of Health Care/standards*; Delivery of Health Care, Integrated/economics; Delivery of Health Care, Integrated/standards*; Consensus

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