Browse publications by year: 2018

Sepsis in tropical regions: Report from the task force on tropical diseases by the World Federation of Societies of Intensive and Critical Care Medicine

McGloughlin S, Richards GA, Nor MBM, Prayag S, Baker T, Amin P

J Crit Care, 2018 08;46:115-118.
PMID: 29310974 DOI: 10.1016/j.jcrc.2017.12.018

Sepsis and septic shock in the tropics are caused by a wide array of organisms. These infections are encountered mainly in low and middle-income countries (LMIC) where a lack of infrastructure and medical facilities contribute to the high morbidity and mortality. Published sepsis guidelines are based on studies primarily performed in high income countries and as such recommendations may or may not be relevant to practice in the tropics. Failure to adhere to guidelines, particularly among non-intensive care specialists even in high-income countries, is an area of concern for sepsis management. Additionally, inappropriate use of antimicrobials has led to significant antimicrobial resistance. Access to rapid, low-cost, and accurate diagnostic tests is critical in countries where tropical diseases are prevalent to facilitate early diagnosis and treatment. Implementation of performance improvement programs may improve outcomes for patients with sepsis and the addition of resuscitation and treatment bundles may further reduce mortality. Associated co-morbidities such as malnutrition and HIV influence outcomes and must be considered.

MeSH terms: Anti-Infective Agents/therapeutic use; Critical Care/methods; Critical Care/organization & administration*; Humans; Poverty; Resuscitation; Risk; Shock, Septic/mortality; Shock, Septic/epidemiology*; Societies, Medical; Tropical Medicine/organization & administration; Global Health; Comorbidity; Sepsis/epidemiology*; Sepsis/therapy; Advisory Committees; Early Diagnosis
Ultrasound guided interscalene brachial plexus block with low dose sedation - Technique of choice for reducing shoulder dislocation

Beh ZY, Osman A, Fathil S, Karmakar MK

Am J Emerg Med, 2018 04;36(4):717-718.
PMID: 29310985 DOI: 10.1016/j.ajem.2018.01.013
Fulltext Phylogeny and putative virulence gene analysis of Bartonella bovis

Tay ST, Kho KL, Lye SF, Ngeow YF

J Vet Med Sci, 2018 Apr 18;80(4):653-661.
PMID: 29311425 DOI: 10.1292/jvms.17-0448

Bartonella bovis is a small Gram-negative bacterium recognized as an etiological agent for bacteremia and endocarditis in cattle. As few reports are available on the taxonomic position of B. bovis and its mechanism of virulence, this study aims to resolve the phylogeny of B. bovis and investigate putative virulence genes based on whole genome sequence analysis. Genome-wide comparisons based on single nucleotide polymorphisms (SNP) and orthologous genes were performed in this study for phylogenetic inference of 27 Bartonella species. Rapid Annotation using Subsystem Technology (RAST) analysis was used for annotation of putative virulence genes. The phylogenetic tree generated from the genome-wide comparison of orthologous genes exhibited a topology almost similar to that of the tree generated from SNP-based comparison, indicating a high concordance in the nucleotide and amino acid sequences of Bartonella spp. The analyses show consistent grouping of B. bovis in a cluster related to ruminant-associated species, including Bartonella australis, Bartonella melophagi and Bartonella schoenbuchensis. RAST analysis revealed genes encoding flagellar components, in corroboration with the observation of flagella-like structure of BbUM strain under negative straining. Genes associated with virulence, disease and defence, prophages, membrane transport, iron acquisition, motility and chemotaxis are annotated in B. bovis genome. The flagellin (flaA) gene of B. bovis is closely related to Bartonella bacilliformis and Bartonella clarridgeiae but distinct from other Gram-negative bacteria. The absence of type IV secretion systems, the bona fide pathogenicity factors of bartonellae, in B. bovis suggests that it may have a different mechanism of pathogenicity.

MeSH terms: Bacterial Proteins/genetics; Bacterial Proteins/metabolism; Bartonella/genetics*; Bartonella/pathogenicity*; Base Sequence; DNA, Bacterial/genetics; Phylogeny*; Virulence; Gene Expression Regulation, Bacterial/physiology; Sequence Analysis, DNA; Virulence Factors/genetics*
Fulltext Severe visceral pentastomiasis in an oriental small-clawed otter with functional thyroid carcinoma

Hsu CD, Mathura Y

J Vet Med Sci, 2018 Feb 20;80(2):320-322.
PMID: 29311490 DOI: 10.1292/jvms.17-0383

In January 2016, a 20-year-old female oriental small-clawed otter (Aonyx cinereus) from Night Safari in Singapore was euthanized and diagnosed with a thyroid gland carcinoma. Postmortem examination and histology also revealed metastasis to the regional lymph nodes and severe visceral pentastomiasis. Grossly, the lymph nodes were infested, and encapsulation was observed on the visceral serosal surface. Histopathologically, the lymph nodes were encysted by a thick fibrous connective capsule with minimal inflammatory response. Pentastomiasis has been previously reported in the smooth-coated otter (Lutrogale perspicillata) in Malaysia. This report is the first case of severe visceral pentastomiasis in an oriental small-clawed otter with functional thyroid carcinoma.

MeSH terms: Animals; Female; Otters/parasitology*; Parasitic Diseases, Animal/complications*; Parasitic Diseases, Animal/pathology; Thyroid Neoplasms/complications; Thyroid Neoplasms/pathology; Thyroid Neoplasms/veterinary*; Pentastomida*
Fulltext Characterization and toxicity of citral incorporated with nanostructured lipid carrier

Nordin N, Yeap SK, Zamberi NR, Abu N, Mohamad NE, Rahman HS, et al.

PeerJ, 2018;6:e3916.
PMID: 29312812 DOI: 10.7717/peerj.3916

The nanoparticle as a cancer drug delivery vehicle is rapidly under investigation due to its promising applicability as a novel drug delivery system for anticancer agents. This study describes the development, characterization and toxicity studies of a nanostructured lipid carrier (NLC) system for citral. Citral was loaded into the NLC using high pressure homogenization methods. The characterizations of NLC-citral were then determined through various methods. Based on Transmission Electron Microscope (TEM) analysis, NLC-Citral showed a spherical shape with an average diameter size of 54.12 ± 0.30 nm and a polydipersity index of 0.224 ± 0.005. The zeta potential of NLC-Citral was -12.73 ± 0.34 mV with an entrapment efficiency of 98.9 ± 0.124%, and drug loading of 9.84 ± 0.041%. Safety profile of the formulation was examined via in vitro and in vivo routes to study its effects toward normal cells. NLC-Citral exhibited no toxic effects towards the proliferation of mice splenocytes. Moreover, no mortality and toxic signs were observed in the treated groups after 28 days of treatment. There were also no significant alterations in serum biochemical analysis for all treatments. Increase in immunomodulatory effects of treated NLC-Citral and Citral groups was verified from the increase in CD4/CD3 and CD8/CD3 T cell population in both NLC-citral and citral treated splenocytes. This study suggests that NLC is a promising drug delivery system for citral as it has the potential in sustaining drug release without inducing any toxicity.

MeSH terms: Animals; Antineoplastic Agents; Delayed-Action Preparations; Lipids; Spleen; T-Lymphocytes; CD8-Positive T-Lymphocytes; Monoterpenes; Microscopy, Electron, Transmission; Cell Proliferation; Mice; Nanoparticles; Drug Liberation
Leaking in silence: women with stress urinary incontinence who do not have access to or refuse surgery

Lim R, Liong ML, Yuen KH

Int Urogynecol J, 2018 04;29(4):457-458.
PMID: 29313087 DOI: 10.1007/s00192-017-3550-x
MeSH terms: Developing Countries*; Female; Humans; Urinary Incontinence, Stress/therapy*
Dietary supplementation of defatted kenaf (Hibiscus cannabinus L.) seed meal and its phenolics-saponins rich extract effectively attenuates diet-induced hypercholesterolemia in rats

Chan KW, Ismail M, Mohd Esa N, Imam MU, Ooi J, Khong NMH

Food Funct, 2018 Feb 21;9(2):925-936.
PMID: 29313544 DOI: 10.1039/c7fo01109a

Kenaf is one of the important commercial fiber crops worldwide and defatted kenaf seed meal (DKSM) is a secondary by-product from the kenaf industry. Thus, efforts to turn this low-cost agricultural waste into value-added functional food ingredients will definitely bring advantageous impacts to the community health, environment and economy. The present study was aimed to investigate the cardioprotective properties of DKSM and its phenolics-saponins rich extract (PSRE) in diet-induced hypercholesterolemic rat model. Hypercholesterolemia was induced in Sprague-Dawley rats via atherogenic diet feeding and dietary interventions were conducted by incorporating DKSM (15% and 30%) and equivalent levels of PSRE (2.3% and 4.6%, respectively, equivalent to the total content of phenolics and saponins in DKSM groups) into the atherogenic diets. After 10 weeks of DKSM and PSRE supplementation, the hepatosomatic index, hepatosteatosis, serum lipid profile, Castelli risk indexes as well as hepatic and renal functions of hypercholesterolemic rats were significantly improved (p < 0.05). Besides, the levels of hepatic Hmgcr and serum Pcsk9 were lowered, along with transcriptional upregulations of hepatic Cyp7a1, Abca1, Lcat, ApoA2 and ApoE (p < 0.05). The gene expression of hepatic Ldlr was marginally enhanced by DKSM supplementation (p > 0.05), but superiorly upregulated by PSRE (p < 0.05). The combined results showed that hypercholesterolemia and the atherogenic risk in rats were effectively attenuated by DKSM and PSRE supplementation, possibly via modulations of multiple vital processes in hepatic cholesterol metabolism. Furthermore, phenolics and saponins may be the bioactives conferring DKSM and PSRE with their anti-hypercholesterolemic properties. In conclusion, DKSM and PSRE are prospective cardioprotective functional food ingredients for hypercholesterolemic individuals.

MeSH terms: Animals; Anticholesteremic Agents/administration & dosage*; Anticholesteremic Agents/analysis; Diet, Atherogenic/adverse effects; Humans; Hypercholesterolemia/drug therapy*; Hypercholesterolemia/genetics*; Hypercholesterolemia/metabolism; Cholesterol, LDL/metabolism; Liver/drug effects; Liver/metabolism; Male; Phenols/administration & dosage*; Phenols/analysis; Saponins/administration & dosage*; Saponins/analysis; Seeds/chemistry; Apolipoprotein A-II/genetics; Apolipoprotein A-II/metabolism; Rats, Sprague-Dawley; Dietary Supplements/analysis; Hibiscus/chemistry*; Rats; Proprotein Convertase 9/genetics; Proprotein Convertase 9/metabolism
Are strict organ allocation systems fanning the illegal trade?

Khoo EJ

Pediatr Transplant, 2018 03;22(2).
PMID: 29314481 DOI: 10.1111/petr.13122
Clinical and economic implications of upper gastrointestinal adverse events in Asian rheumatological patients on long-term non-steroidal anti-inflammatory drugs

Pok LSL, Shabaruddin FH, Dahlui M, Sockalingam S, Mohamed Said MS, Rosman A, et al.

Int J Rheum Dis, 2018 May;21(5):943-951.
PMID: 29314744 DOI: 10.1111/1756-185X.13256

AIM: To determine the incidence and direct costs of NSAID-induced upper GI adverse events in Malaysian rheumatology patients.
METHODS: A retrospective, multi-centre, cohort study of rheumatology patients on long-term NSAIDs was conducted. Clinical data of patients treated between 2010 and 2013 were collected for a 24-month follow-up period. The costs of managing upper GI adverse events were based on patient level resource use data.
RESULTS: Six hundred and thirty-four patients met the inclusion criteria: mean age 53.4 years, 89.9% female, diagnosis of rheumatoid arthritis (RA; 59.3%), osteoarthritis (OA; 10.3%) and both RA and OA (30.3%). Three hundred and seventy-one (58.5%) patients were prescribed non-selective NSAIDs and 263 (41.5%) had cyclo-oxygenase-2 inhibitors. Eighty-four upper GI adverse events occurred, translating into a risk of 13.2% and an incidence rate of 66.2 per 1000 person-years. GI adverse events comprised: dyspepsia n = 78 (12.3%), peptic ulcer disease (PUD) n = 5 (0.79%) and upper GI bleeding (UGIB) n = 1 (0.16%). The total direct healthcare cost of managing adverse events was Malaysian Ringgit (MR) 37 352 (US dollars [USD] 11 419) with a mean cost of MR 446.81 ± 534.56 (USD 136.60 ± 163.42) per patient, consisting mainly of GI pharmacotherapy (33.8%), oesophagoduodenoscopies (23.1%) and outpatient clinic visits (18.2%). Mean cost per patient by GI events were: dyspepsia, MR 408.98 ± 513.29 (USD125.03 ± 156.92); PUD, MR 805.93 ± 578.80 (USD 246.39 ± 176.95); UGIB, MR 1601.94 (USD 489.74, n = 1).
CONCLUSION: The economic burden of GI adverse events due to long-term NSAIDs use in Malaysian patients with chronic rheumatic diseases is modest.
Study site: Rheumatology clinics, Hospital Putrajaya, Hospital Selayang, Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM), University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia

MeSH terms: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal/administration & dosage; Anti-Inflammatory Agents, Non-Steroidal/adverse effects*; Anti-Inflammatory Agents, Non-Steroidal/economics*; Arthritis, Rheumatoid; Female; Gastrointestinal Diseases/chemically induced*; Gastrointestinal Diseases/economics*; Gastrointestinal Diseases/ethnology; Gastrointestinal Diseases/therapy; Hospitals, University; Humans; Malaysia; Malaysia/epidemiology; Male; Middle Aged; Outpatient Clinics, Hospital; Retrospective Studies; Rheumatic Diseases/diagnosis; Rheumatic Diseases/drug therapy*; Rheumatic Diseases/economics*; Rheumatic Diseases/ethnology; Risk Factors; Time Factors; Incidence; Drug Costs; Treatment Outcome; Health Care Costs*; Asian Continental Ancestry Group
Validity and reliability of a Malay version of the Lawton instrumental activities of daily living scale among the Malay speaking elderly in Malaysia

Kadar M, Ibrahim S, Razaob NA, Chai SC, Harun D

Aust Occup Ther J, 2018 02;65(1):63-68.
PMID: 29315609 DOI: 10.1111/1440-1630.12441

BACKGROUND/AIM: The Lawton Instrumental Activities of Daily Living Scale is a tool often used to assess independence among elderly at home. Its suitability to be used with the elderly population in Malaysia has not been validated. This current study aimed to assess the validity and reliability of the Lawton Instrumental Activities of Daily Living Scale - Malay Version to Malay speaking elderly in Malaysia.
METHODS: This study was divided into three phases: (1) translation and linguistic validity involving both forward and backward translations; (2) establishment of face validity and content validity; and (3) establishment of reliability involving inter-rater, test-retest and internal consistency analyses. Data used for these analyses were obtained by interviewing 65 elderly respondents.
RESULTS: Percentages of Content Validity Index for 4 criteria were from 88.89 to 100.0. The Cronbach α coefficient for internal consistency was 0.838. Intra-class Correlation Coefficient of inter-rater reliability and test-retest reliability was 0.957 and 0.950 respectively.
CONCLUSIONS: The result shows that the Lawton Instrumental Activities of Daily Living Scale - Malay Version has excellent reliability and validity for use with the Malay speaking elderly people in Malaysia. This scale could be used by professionals to assess functional ability of elderly who live independently in community.

MeSH terms: Activities of Daily Living*; Aged; Aged, 80 and over; Female; Humans; Malaysia; Male; Middle Aged; Occupational Therapy/methods*; Occupational Therapy/standards; Psychometrics; Quality of Life; Socioeconomic Factors; Translations*; Reproducibility of Results; Geriatric Assessment/methods*
Fulltext Biosynthesis of bioactive diterpenoids in the medicinal plant Vitex agnus-castus

Heskes AM, Sundram TCM, Boughton BA, Jensen NB, Hansen NL, Crocoll C, et al.

Plant J, 2018 03;93(5):943-958.
PMID: 29315936 DOI: 10.1111/tpj.13822

Vitex agnus-castus L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of V. agnus-castus show that it contains an enormous array of structurally related diterpenoids and, as such, holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in V. agnus-castus. With the assistance of matrix-assisted laser desorption ionisation-mass spectrometry imaging (MALDI-MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome-specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs); three class I diTPSs; and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in V. agnus-castus. The identified CYP, VacCYP76BK1, was found to catalyse 16-hydroxylation of the diol-diterpene, peregrinol, to labd-13Z-ene-9,15,16-triol when expressed in Saccharomyces cerevisiae. Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan- and lactone-containing diterpenoids that are present in this species.

MeSH terms: Cytochrome P-450 Enzyme System/genetics; Cytochrome P-450 Enzyme System/metabolism; Diterpenes/analysis; Diterpenes/metabolism*; Oxidation-Reduction; Phylogeny; Plant Proteins/genetics; Plant Proteins/metabolism*; Plants, Medicinal/metabolism; Plant Leaves/genetics; Plant Leaves/metabolism; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Gene Expression Profiling; Vitex/genetics; Vitex/metabolism*; Trichomes/metabolism
Fully automated segmentation of the left ventricle in cine cardiac MRI using neural network regression

Tan LK, McLaughlin RA, Lim E, Abdul Aziz YF, Liew YM

J Magn Reson Imaging, 2018 07;48(1):140-152.
PMID: 29316024 DOI: 10.1002/jmri.25932

BACKGROUND: Left ventricle (LV) structure and functions are the primary assessment performed in most clinical cardiac MRI protocols. Fully automated LV segmentation might improve the efficiency and reproducibility of clinical assessment.
PURPOSE: To develop and validate a fully automated neural network regression-based algorithm for segmentation of the LV in cardiac MRI, with full coverage from apex to base across all cardiac phases, utilizing both short axis (SA) and long axis (LA) scans.
STUDY TYPE: Cross-sectional survey; diagnostic accuracy.
SUBJECTS: In all, 200 subjects with coronary artery diseases and regional wall motion abnormalities from the public 2011 Left Ventricle Segmentation Challenge (LVSC) database; 1140 subjects with a mix of normal and abnormal cardiac functions from the public Kaggle Second Annual Data Science Bowl database.
FIELD STRENGTH/SEQUENCE: 1.5T, steady-state free precession.
ASSESSMENT: Reference standard data generated by experienced cardiac radiologists. Quantitative measurement and comparison via Jaccard and Dice index, modified Hausdorff distance (MHD), and blood volume.
STATISTICAL TESTS: Paired t-tests compared to previous work.
RESULTS: Tested against the LVSC database, we obtained 0.77 ± 0.11 (Jaccard index) and 1.33 ± 0.71 mm (MHD), both metrics demonstrating statistically significant improvement (P < 0.001) compared to previous work. Tested against the Kaggle database, the signed difference in evaluated blood volume was +7.2 ± 13.0 mL and -19.8 ± 18.8 mL for the end-systolic (ES) and end-diastolic (ED) phases, respectively, with a statistically significant improvement (P < 0.001) for the ED phase.
DATA CONCLUSION: A fully automated LV segmentation algorithm was developed and validated against a diverse set of cardiac cine MRI data sourced from multiple imaging centers and scanner types. The strong performance overall is suggestive of practical clinical utility.
LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018.
Diversity of pollination ecology in the Schismatoglottis Calyptrata Complex Clade (Araceae)

Hoe YC, Gibernau M, Wong SY

Plant Biol (Stuttg), 2018 May;20(3):563-578.
PMID: 29316090 DOI: 10.1111/plb.12687

Field studies integrating pollination investigations with an assessment of floral scent composition and thermogenesis in tropical aroids are rather few. Thus, this study aimed to investigate the pollination biology of nine species belonging to Schismatoglottis Calyptrata Complex Clade. The flowering mechanism, visiting insect activities, reproductive system, thermogenesis and floral scent composition were examined. Anthesis for all species started at dawn and lasted 25-29 h. Colocasiomyia (Diptera, Drosophilidae) are considered the main pollinators for all the investigated species. Cycreon (Coleoptera, Hydrophilidae) are considered secondary pollinators as they are only present in seven of the nine host plants, despite the fact that they are the most effective pollen carrier, carrying up to 15 times more pollen grains than Colocasiomyia flies. However, the number of Colocasiomyia individuals was six times higher than Cycreon beetles. Chaloenus (Chrysomelidae, Galeuricinae) appeared to be an inadvertent pollinator. Atheta (Coleoptera, Staphylinidae) is considered a floral visitor in most investigated species of the Calyptrata Complex Clade in Sarawak, but a possible pollinator in S. muluensis. Chironomidae midges and pteromalid wasps are considered visitors in S. calyptrata. Thermogenesis in a biphasic pattern was observed in inflorescences of S. adducta, S. calyptrata, S. giamensis, S. pseudoniahensis and S. roh. The first peak occurred during pistillate anthesis; the second peak during staminate anthesis. Inflorescences of all investigated species of Calyptrata Complex Clade emitted four types of ester compound, with methyl ester-3-methyl-3-butenoic acid as a single major VOC (volatile organic compound). The appendix, pistillate zone, staminate zone and spathe emitted all these compounds. A mixed fly-beetle pollination system is considered an ancestral trait in the Calyptrata Complex Clade, persisting in Sarawak taxa, whereas the marked reduction of interpistillar staminodes in taxa from Peninsular Malaysia and especially, Ambon, Indonesia, is probably linked to a shift in these taxa to a fly-pollinated system.

MeSH terms: Animals; Beetles/physiology; Diptera/physiology; Ecology; Insects/physiology; Pollen/physiology; Thermogenesis/physiology; Araceae/physiology*; Flowers/anatomy & histology; Flowers/physiology; Biodiversity; Pollination/physiology*
Proteome Heterogeneity in Colorectal Cancer

Lim LC, Lim YM

Proteomics, 2018 02;18(3-4).
PMID: 29316255 DOI: 10.1002/pmic.201700169

Tumor heterogeneity is an important feature of colorectal cancer (CRC) manifested by dynamic changes in gene expression, protein expression, and availability of different tumor subtypes. Recent publications in the past 10 years have revealed proteome heterogeneity between different colorectal tumors and within the same tumor site. This paper reviews recent research works on the proteome heterogeneity in CRC, which includes the heterogeneity within a single tumor (intratumor heterogeneity), between different anatomical sites at the same organ, and between primary and metastatic sites (intertumor heterogeneity). The potential use of proteome heterogeneity in precision medicine and its implications in biomarker discovery and therapeutic outcomes will be discussed. Identification of the unique proteome landscape between and within individual tumors is imperative for understanding cancer biology and the management of CRC patients.

MeSH terms: Colonic Neoplasms; Humans; Colorectal Neoplasms; Biomarkers; Proteome; Proteomics; Precision Medicine
Estimating radiotherapy demands in South East Asia countries in 2025 and 2035 using evidence-based optimal radiotherapy fractions

Yahya N, Roslan N

Asia Pac J Clin Oncol, 2018 Oct;14(5):e543-e547.
PMID: 29316293 DOI: 10.1111/ajco.12831

BACKGROUND AND PURPOSE: As about 50% of cancer patients may require radiotherapy, the demand of radiotherapy as the main treatment to treat cancer is likely to rise due to rising cancer incidence. This study aims to quantify the radiotherapy demand in countries in Southeast Asia (SEA) in 2025 and 2035 using evidence-based optimal radiotherapy fractions.
MATERIALS AND METHODS: SEA country-specific cancer incidence by tumor site for 2015, 2025 and 2035 was extracted from the GLOBOCAN database. We utilized the optimal radiotherapy utilization rate model by Wong et al. (2016) to calculate the optimal number of fractions for all tumor sites in each SEA country. The available machines (LINAC & Co-60) were extracted from the IAEA's Directory of Radiotherapy Centres (DIRAC) from which the number of available fractions was calculated.
RESULTS: The incidence of cancers in SEA countries are expected to be 1.1 mil cases (2025) and 1.4 mil (2035) compared to 0.9 mil (2015). The number of radiotherapy fractions needed in 2025 and 2035 are 11.1 and 14.1 mil, respectively, compared to 7.6 mil in 2015. In 2015, the radiotherapy fulfillment rate (RFR; required fractions/available fractions) varied between countries with Brunei, Singapore and Malaysia are highest (RFR > 1.0 - available fractions > required fractions), whereas Cambodia, Indonesia, Laos, Myanmar, Philippines, Timor-Leste and Vietnam have RFR

MeSH terms: Asia, Southeastern; Developing Countries; Health Services Needs and Demand*; Humans; Neoplasms/epidemiology*; Neoplasms/radiotherapy*; Radiotherapy*; Incidence; Evidence-Based Medicine; Dose Fractionation
Selective binding of pyrene in subdomain IB of human serum albumin: Combining energy transfer spectroscopy and molecular modelling to understand protein binding flexibility

Ling I, Taha M, Al-Sharji NA, Abou-Zied OK

Spectrochim Acta A Mol Biomol Spectrosc, 2018 Apr 05;194:36-44.
PMID: 29316482 DOI: 10.1016/j.saa.2018.01.005

The ability of human serum albumin (HSA) to bind medium-sized hydrophobic molecules is important for the distribution, metabolism, and efficacy of many drugs. Herein, the interaction between pyrene, a hydrophobic fluorescent probe, and HSA was thoroughly investigated using steady-state and time-resolved fluorescence techniques, ligand docking, and molecular dynamics (MD) simulations. A slight quenching of the fluorescence signal from Trp214 (the sole tryptophan residue in the protein) in the presence of pyrene was used to determine the ligand binding site in the protein, using Förster's resonance energy transfer (FRET) theory. The estimated FRET apparent distance between pyrene and Trp214 was 27Å, which was closely reproduced by the docking analysis (29Å) and MD simulation (32Å). The highest affinity site for pyrene was found to be in subdomain IB from the docking results. The calculated equilibrium structure of the complex using MD simulation shows that the ligand is largely stabilized by hydrophobic interaction with Phe165, Phe127, and the nonpolar moieties of Tyr138 and Tyr161. The fluorescence vibronic peak ratio I1/I3 of bound pyrene inside HSA indicates the presence of polar effect in the local environment of pyrene which is less than that of free pyrene in buffer. This was clarified by the MD simulation results in which an average of 5.7 water molecules were found within 0.5nm of pyrene in the binding site. Comparing the fluorescence signals and lifetimes of pyrene inside HSA to that free in buffer, the high tendency of pyrene to form dimer was almost completely suppressed inside HSA, indicating a high selectivity of the binding pocket toward pyrene monomer. The current results emphasize the ability of HSA, as a major carrier of several drugs and ligands in blood, to bind hydrophobic molecules in cavities other than subdomain IIA which is known to bind most hydrophobic drugs. This ability stems from the nature of the amino acids forming the binding sites of the protein that can easily adapt their shape to accommodate a variety of molecular structures.

MeSH terms: Binding Sites; Humans; Models, Molecular*; Protein Binding; Pyrenes/metabolism*; Pyrenes/chemistry*; Fluorescence Resonance Energy Transfer/methods*; Molecular Dynamics Simulation; Protein Domains
The recurrent intertriginous rash

How KN, Bhullar A

Eur J Intern Med, 2018 07;53:e4-e5.
PMID: 29307504 DOI: 10.1016/j.ejim.2017.12.016
MeSH terms: Calcium-Transporting ATPases/genetics; Exanthema/etiology*; Female; Humans; Middle Aged; Pemphigus, Benign Familial/diagnosis*; Pemphigus, Benign Familial/genetics; Pemphigus, Benign Familial/pathology*
A Case of Posterior Tibial Nerve Injury After Arthroscopic Calcaneoplasty

Retrouvey H, Silvanathan J, Bleakney RR, Anastakis DJ

J Foot Ankle Surg, 2018 01 05;57(3):587-592.
PMID: 29307741 DOI: 10.1053/j.jfas.2017.10.004

We report the first case of distal posterior tibial nerve injury after arthroscopic calcaneoplasty. A 59-year-old male had undergone right arthroscopic calcaneoplasty to treat retrocalcaneal bursitis secondary to a Haglund's deformity. The patient complained of numbness in his right foot immediately after the procedure. Two years later and after numerous assessments and investigations, a lateral plantar nerve and medial calcaneal nerve lesion was diagnosed. In the operating room, the presence of an iatrogenic lesion to the distal right lateral plantar nerve (neuroma incontinuity involving 20% of the nerve) and the medial calcaneal nerve (complete avulsion) was confirmed. The tarsal tunnel was decompressed, and both the medial and the lateral plantar nerve were neurolyzed under magnification. To the best of our knowledge, our case report is the first to describe iatrogenic posterior tibial nerve injury after arthroscopic calcaneoplasty. It is significant because this complication can hopefully be avoided in the future with careful planning and creation of arthroscopic ports and treated appropriately with early referral to a nerve specialist if the patient's symptoms do not improve within 3 months.

MeSH terms: Arthroscopy/adverse effects*; Arthroscopy/methods; Bursitis/surgery*; Calcaneus/surgery*; Follow-Up Studies; Foot Deformities/surgery*; Humans; Iatrogenic Disease; Magnetic Resonance Imaging/methods; Male; Middle Aged; Treatment Outcome; Risk Assessment; Neurosurgical Procedures/methods*; Recovery of Function; Tibial Neuropathy/etiology*; Tibial Neuropathy/physiopathology; Tibial Neuropathy/surgery
Fulltext Towards precision medicine: from quantitative imaging to radiomics

Acharya UR, Hagiwara Y, Sudarshan VK, Chan WY, Ng KH

J Zhejiang Univ Sci B, 2018 1 9;19(1):6-24.
PMID: 29308604 DOI: 10.1631/jzus.B1700260

Radiology (imaging) and imaging-guided interventions, which provide multi-parametric morphologic and functional information, are playing an increasingly significant role in precision medicine. Radiologists are trained to understand the imaging phenotypes, transcribe those observations (phenotypes) to correlate with underlying diseases and to characterize the images. However, in order to understand and characterize the molecular phenotype (to obtain genomic information) of solid heterogeneous tumours, the advanced sequencing of those tissues using biopsy is required. Thus, radiologists image the tissues from various views and angles in order to have the complete image phenotypes, thereby acquiring a huge amount of data. Deriving meaningful details from all these radiological data becomes challenging and raises the big data issues. Therefore, interest in the application of radiomics has been growing in recent years as it has the potential to provide significant interpretive and predictive information for decision support. Radiomics is a combination of conventional computer-aided diagnosis, deep learning methods, and human skills, and thus can be used for quantitative characterization of tumour phenotypes. This paper discusses the overview of radiomics workflow, the results of various radiomics-based studies conducted using various radiological images such as computed tomography (CT), magnetic resonance imaging (MRI), and positron-emission tomography (PET), the challenges we are facing, and the potential contribution of radiomics towards precision medicine.

MeSH terms: Diagnosis, Computer-Assisted; Humans; Magnetic Resonance Imaging; Neoplasms/therapy; Phenotype; Radiology/methods*; Tomography, X-Ray Computed; Biomarkers, Tumor; Radiology, Interventional/methods*; Genome; Genomics; Positron-Emission Tomography; Workflow; Precision Medicine/methods*
Using multi-attribute decision-making approaches in the selection of a hospital management system

Arasteh MA, Shamshirband S, Yee PL

Technol Health Care, 2018;26(2):279-295.
PMID: 29309042 DOI: 10.3233/THC-170947

The most appropriate organizational software is always a real challenge for managers, especially, the IT directors. The illustration of the term "enterprise software selection", is to purchase, create, or order a software that; first, is best adapted to require of the organization; and second, has suitable price and technical support. Specifying selection criteria and ranking them, is the primary prerequisite for this action. This article provides a method to evaluate, rank, and compare the available enterprise software for choosing the apt one. The prior mentioned method is constituted of three-stage processes. First, the method identifies the organizational requires and assesses them. Second, it selects the best method throughout three possibilities; indoor-production, buying software, and ordering special software for the native use. Third, the method evaluates, compares and ranks the alternative software. The third process uses different methods of multi attribute decision making (MADM), and compares the consequent results. Based on different characteristics of the problem; several methods had been tested, namely, Analytic Hierarchy Process (AHP), Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS), Elimination and Choice Expressing Reality (ELECTURE), and easy weight method. After all, we propose the most practical method for same problems.

MeSH terms: Algorithms; Decision Making*; Hospital Administration*; Hospital Information Systems/organization & administration*; Humans; Software*; Needs Assessment

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