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Extremes of foetal birthweight for gestation in infants of diabetic mothers

Kek LP, Ng CS, Chng KP, Ratnam SS, Cheah JS, Yeo PB, et al.

Ann Acad Med Singap, 1985 Apr;14(2):303-6.
PMID: 4037690

100 patients were registered at the Diabetic Clinic in 1981, where they were managed by a team of physician, obstetrician and paediatrician, based on a preset protocol. Only 92 patients were eventually analysed. The study showed a 1.3% incidence of pregnancies complicated by diabetes mellitus. The mean birthweights of infants of both gestational and established diabetics were heavier than that of the general population by race and gestation. 25% of the 92 infants of diabetic mothers have birthweight exceeding the 90th centile of population. Further division of the 92 patients into the "true gestational" diabetics, as shown by an oral glucose tolerance test performed 6 weeks post-natally, also showed a 25% incidence of macrosomia. Late antenatal booking, delayed detection of abnormal glucose tolerance and treatment attributed to the high incidence of macrosomia. Only one infant had birthweight below the tenth centile. There were no perinatal mortality in the 92 patients studied. Macrosomia is a common complication in infants of diabetic mothers despite a physician-obstetrician joint-care system. Also, the risk of having macrosomia amongst gestational diabetics is high.
Diagnosis of retinal health in digital fundus images using continuous wavelet transform (CWT) and entropies

Koh JEW, Acharya UR, Hagiwara Y, Raghavendra U, Tan JH, Sree SV, et al.

Comput Biol Med, 2017 05 01;84:89-97.
PMID: 28351716 DOI: 10.1016/j.compbiomed.2017.03.008

Vision is paramount to humans to lead an active personal and professional life. The prevalence of ocular diseases is rising, and diseases such as glaucoma, Diabetic Retinopathy (DR) and Age-related Macular Degeneration (AMD) are the leading causes of blindness in developed countries. Identifying these diseases in mass screening programmes is time-consuming, labor-intensive and the diagnosis can be subjective. The use of an automated computer aided diagnosis system will reduce the time taken for analysis and will also reduce the inter-observer subjective variabilities in image interpretation. In this work, we propose one such system for the automatic classification of normal from abnormal (DR, AMD, glaucoma) images. We had a total of 404 normal and 1082 abnormal fundus images in our database. As the first step, 2D-Continuous Wavelet Transform (CWT) decomposition on the fundus images of two classes was performed. Subsequently, energy features and various entropies namely Yager, Renyi, Kapoor, Shannon, and Fuzzy were extracted from the decomposed images. Then, adaptive synthetic sampling approach was applied to balance the normal and abnormal datasets. Next, the extracted features were ranked according to the significances using Particle Swarm Optimization (PSO). Thereupon, the ranked and selected features were used to train the random forest classifier using stratified 10-fold cross validation. Overall, the proposed system presented a performance rate of 92.48%, and a sensitivity and specificity of 89.37% and 95.58% respectively using 15 features. This novel system shows promise in detecting abnormal fundus images, and hence, could be a valuable adjunct eye health screening tool that could be employed in polyclinics, and thereby reduce the workload of specialists at hospitals.
Fulltext Is universal HLA-B*15:02 screening a cost-effective option in an ethnically diverse population? A case study of Malaysia

Chong HY, Mohamed Z, Tan LL, Wu DBC, Shabaruddin FH, Dahlui M, et al.

Br J Dermatol, 2017 Oct;177(4):1102-1112.
PMID: 28346659 DOI: 10.1111/bjd.15498

BACKGROUND: A strong association has been documented between HLA-B*15:02 and carbamazepine-induced severe cutaneous adverse reactions (SCARs) in Asians. Human leucocyte antigen testing is potentially valuable in many countries to facilitate early recognition of patient susceptibility to SCARs.
OBJECTIVES: To determine the cost-effectiveness of universal HLA-B*15:02 screening in preventing carbamazepine-induced Stevens-Johnson syndrome/toxic epidermal necrolysis in an ethnically diverse Malaysian population.
METHODS: A hybrid model of a decision tree and Markov model was developed to evaluate three strategies for treating newly diagnosed epilepsy among adults: (i) carbamazepine initiation without HLA-B*15:02 screening (current practice); (ii) universal HLA-B*15:02 screening prior to carbamazepine initiation; and (iii) alternative treatment [sodium valproate (VPA)] prescribing without HLA-B*15:02 screening. Base-case analysis and sensitivity analyses were performed over a lifetime time horizon. Incremental cost-effectiveness ratios were calculated.
RESULTS: Both universal HLA-B*15:02 screening and VPA prescribing were dominated by current practice. Compared with current practice, universal HLA-B*15:02 screening resulted in a loss of 0·0255 quality-adjusted life years (QALYs) at an additional cost of 707 U.S. dollars (USD); VPA prescribing resulted in a loss of 0·2622 QALYs at an additional cost of USD 4127, owing to estimated differences in antiepileptic treatment efficacy.
CONCLUSIONS: Universal HLA-B*15:02 screening is unlikely to be a cost-effective intervention in Malaysia. However, with the emergence of an ethnically diverse population in many other countries, this may render HLA-B*15:02 screening a viable intervention when an increasing proportion of the population is at risk and an equally effective yet safer antiepileptic drug is available.
Metabolomic-guided discovery of Alzheimer's disease biomarkers from body fluid

Enche Ady CNA, Lim SM, Teh LK, Salleh MZ, Chin AV, Tan MP, et al.

J Neurosci Res, 2017 Oct;95(10):2005-2024.
PMID: 28301062 DOI: 10.1002/jnr.24048

The rapid increase in the older population has made age-related diseases like Alzheimer's disease (AD) a global concern. Given that there is still no cure for this neurodegenerative disease, the drastic growth in the number of susceptible individuals represents a major emerging threat to public health. The poor understanding of the mechanisms underlying AD is deemed the greatest stumbling block against progress in definitive diagnosis and management of this disease. There is a dire need for biomarkers that can facilitate early diagnosis, classification, prognosis, and treatment response. Efforts have been directed toward discovery of reliable and distinctive AD biomarkers but with very little success. With the recent emergence of high-throughput technology that is able to collect and catalogue vast datasets of small metabolites, metabolomics offers hope for a better understanding of AD and subsequent identification of biomarkers. This review article highlights the potential of using multiple metabolomics platforms as useful means in uncovering AD biomarkers from body fluids. © 2017 Wiley Periodicals, Inc.
Genoproteomics-assisted improvement of Andrographis paniculata: toward a promising molecular and conventional breeding platform for autogamous plants affecting the pharmaceutical industry

Valdiani A, Talei D, Lattoo SK, Ortiz R, Rasmussen SK, Batley J, et al.

Crit Rev Biotechnol, 2017 Sep;37(6):803-816.
PMID: 28049346 DOI: 10.1080/07388551.2016.1260525

Andrographis paniculata (Burm. f.) Wall. ex Nees. (AP) is a hermaphroditic, self-compatible, and habitual inbreeding plant. Its main bioactive component is andrographolide, which is capable of inducing autophagic cell death in some human cancer cells and helps fight HIV/AIDS. Increasing the andrographolide content by investigating the genetic mechanisms controlling its biosynthesis in order to improve and develop high-yielding cultivars are the main breeding targets for AP. However, there might exist some limitations or barriers for crossability within AP accessions. Recently, this problem was addressed in AP by using a combination of crossbreeding and biotechnology-aided genetic methods. This review emphasizes that development of a breeding platform in a hard-to-breed plant, such as AP, requires the involvement of a broad range of methods from classical genetics to molecular breeding. To this end, a phenological stage (for example, flowering and stigma development) can be simplified to a quantitative morphological trait (for example, bud or stigma length) to be used as an index to express the highest level of receptivity in order to manage outcrossing. The outcomes of the basic crossability research can be then employed in diallel mating and crossbreeding. This review explains how genomic data could produce useful information regarding genetic distance and its influence on the crossability of AP accessions. Our review indicates that co-dominant DNA markers, such as microsatellites, are also capable of resolving the evolutionary pathway and cryptic features of plant populations and such information can be used to select the best breeding strategy. This review also highlights the importance of proteomic analysis as a breeding tool. In this regard, protein diversification, as well as the impact of normal and stress-responsive proteins on morphometric and physiological behaviors, could be used in breeding programs. These findings have immense potential for improving plant production and, therefore, can be regarded as prospective breeding platforms for medicinal plants that have an autogamous mode of reproduction. Finally, this review suggests that novel site-directed genome editing approaches such as TALENs (Transcription Activator-Like Effector Nucleases) and CRISPR (clustered regularly interspaced short palindromic repeats)/Cas9 (CRISPR-associated protein-9 nuclease) systems together with other new plant breeding technologies (NPBT) should simultaneously be taken into consideration for improvement of pharmaceutical plants.
Fulltext Clinical Profile and Visual Outcome of Ocular Bartonellosis in Malaysia

Tan CL, Fhun LC, Tai EL, Abdul Gani NH, Muhammed J, Tuan Jaafar TN, et al.

J Trop Med, 2017;2017:7946123.
PMID: 28265290 DOI: 10.1155/2017/7946123

Background. Ocular bartonellosis can present in various ways, with variable visual outcome. There is limited data on ocular bartonellosis in Malaysia. Objective. We aim to describe the clinical presentation and visual outcome of ocular bartonellosis in Malaysia. Materials and Methods. This was a retrospective review of patients treated for ocular bartonellosis in two ophthalmology centers in Malaysia between January 2013 and December 2015. The diagnosis was based on clinical features, supported by a positive Bartonella spp. serology. Results. Of the 19 patients in our series, females were predominant (63.2%). The mean age was 29.3 years. The majority (63.2%) had unilateral involvement. Five patients (26.3%) had a history of contact with cats. Neuroretinitis was the most common presentation (62.5%). Azithromycin was the antibiotic of choice (42.1%). Concurrent systemic corticosteroids were used in approximately 60% of cases. The presenting visual acuity was worse than 6/18 in approximately 60% of eyes; on final review, 76.9% of eyes had a visual acuity better than 6/18. Conclusion. Ocular bartonellosis tends to present with neuroretinitis. Azithromycin is a viable option for treatment. Systemic corticosteroids may be considered in those with poor visual acuity on presentation.
Mycoplasma hominis, Ureaplasma urealyticum and Chlamydia trachomatis Respiratory Colonization in Malaysian Preterm Infants

Ng KF, Kee Tan K, Chok MC, Zamil Mohd Muzzamil N, Choo P, Paramasivam U, et al.

J Trop Pediatr, 2017 Dec 01;63(6):447-453.
PMID: 28334949 DOI: 10.1093/tropej/fmx011

This prospective observational study aims to determine the incidence, predictors and clinical features of Mycoplasma hominis (MH), Ureaplasma urealyticum (UU) and Chlamydia trachomatis (CT) respiratory colonization in infants <37 weeks of gestation. A total of 200 preterm newborns admitted to a tertiary center in Malaysia between 2013 and 2015 for increased breathing effort had their respiratory secretions tested for these bacteria by polymerase chain reaction. Fifteen of the 200 (7.5%) infants were detected to have these organisms in their respiratory tracts. Preterm prelabor rupture of membrane was associated with positive detection (odds ratio: 3.7; 95% confidence interval: 1.2-11.3). Seventy-three of the 200 (36.5%) infants were given macrolide for presumed infection but only 4.1% (3 of 73) were positive for these organisms. The incidence of UU respiratory colonization among preterm infants in our center is lower than other published reports, while the frequency of MH and CT isolation is comparable with many studies. There should be judicious use of empirical antibiotics for presumed UU, MH and CT infection in preterm infants.
Zebrafish phenotypic screen identifies novel Notch antagonists

Velaithan V, Okuda KS, Ng MF, Samat N, Leong SW, Faudzi SM, et al.

Invest New Drugs, 2017 04;35(2):166-179.
PMID: 28058624 DOI: 10.1007/s10637-016-0423-y

Zebrafish represents a powerful in vivo model for phenotype-based drug discovery to identify clinically relevant small molecules. By utilizing this model, we evaluated natural product derived compounds that could potentially modulate Notch signaling that is important in both zebrafish embryogenesis and pathogenic in human cancers. A total of 234 compounds were screened using zebrafish embryos and 3 were identified to be conferring phenotypic alterations similar to embryos treated with known Notch inhibitors. Subsequent secondary screens using HEK293T cells overexpressing truncated Notch1 (HEK293TΔE) identified 2 compounds, EDD3 and 3H4MB, to be potential Notch antagonists. Both compounds reduced protein expression of NOTCH1, Notch intracellular domain (NICD) and hairy and enhancer of split-1 (HES1) in HEK293TΔE and downregulated Notch target genes. Importantly, EDD3 treatment of human oral cancer cell lines demonstrated reduction of Notch target proteins and genes. EDD3 also inhibited proliferation and induced G0/G1 cell cycle arrest of ORL-150 cells through inducing p27KIP1. Our data demonstrates the utility of the zebrafish phenotypic screen and identifying EDD3 as a promising Notch antagonist for further development as a novel therapeutic agent.
Fulltext Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus

Yeow TP, Pacini G, Tura A, Hor CP, Lim SL, Tan FH, et al.

BMJ Open Diabetes Res Care, 2017;5(1):e000352.
PMID: 28321312 DOI: 10.1136/bmjdrc-2016-000352

OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM.

RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS) in OGTT and surrogate index of SI from the minimal model (calculated SI, CSI). Acute insulin response (AIR) was obtained from IVGTT. Total BC was computed as incremental area under the curve of insulin/incremental area under the curve of glucose, during OGTT (BCOG) and IVGTT (BCIV), respectively. Disposition index (DI) was calculated using the product of insulin sensitivity and insulin secretion. GLP-1 response to oral glucose was calculated as incremental area under the curve of GLP-1 (ΔAUCGLP-1). Per cent incretin effect was estimated as 100×(BCOG-BCIV)/BCOG).

RESULTS: The YT2DM had marked impairment in BC (>80% reduction in AIR and BCOG, p<0.001) and lower QUICKI (p<0.001), OGIS (p<0.001) and CSI (p=0.015) compared with controls. There was no difference in GLP-1 at all time points and ΔAUCGLP-1 but the per cent incretin effect was reduced in the YT2DM compared with controls (12.1±8.93 vs 70.0±4.03, p<0.001).

CONCLUSIONS: Asian YT2DM showed similar GLP-1 response to oral glucose as controls but reduced incretin effect, BC and insulin sensitivity. The lack of compensatory mechanisms, as shown by the DI may be partly ascribed to the impaired incretin effect, similar to that of adult T2DM.

TRIAL REGISTRATION NUMBER: NMRR-12-1042-13254.
Management of rheumatoid arthritis in clinical practice using treat-to-target strategy: Where do we stand in the multi-ethnic Malaysia population?

Tan BE, Lim AL, Kan SL, Lim CH, Ng YF, Tng SLC, et al.

Rheumatol Int, 2017 Jun;37(6):905-913.
PMID: 28389855 DOI: 10.1007/s00296-017-3705-6

To evaluate the achievement of treat-to-target (T2T) strategy in rheumatoid arthritis (RA) and identify factors associated with failed treatment target in a public rheumatology center. A cross-sectional study was conducted from June 2015 to February 2016. RA patients with disease duration greater than 2 years and under T2T for over a year were invited to the study. Demographic, clinical data, disease activity score of 28 joints (DAS28), and clinical disease activity index (CDAI) were collected in a single routine clinic visit. Treatment target was defined as DAS28 <3.2 or CDAI ≤10. Retrospective chart review was performed to determine reasons of failed treatment target. A total of 371 patients were recruited and 87.1% were female. Mean age and duration of RA were 53.5 years (SD 10.3) and 9.1 years (SD 6.6), respectively. Ethnic distribution was 49% Chinese, 27% Malay, and 24% Indian. T2T was achieved in 81.7% of the cohort. Non-Chinese ethnicity, positive rheumatoid factor, and treatment with three disease modifying anti-rheumatic drugs (DMARDs) were associated with failed treatment target. After controlling for covariates, Malay ethnicity (OR 2.96; 95% CI 1.47-5.96) and treatment with three DMARDs (OR 2.14; 95% CI 1.06-4.35) were associated with failed treatment target. There was no association between age, gender, duration of RA, BMI, smoking status, anti-citrulinated cyclic peptide, and achievement of T2T. The most common reasons of failed treatment target were inability to escalate DMARDs due to side effects (18.8%), lack of biologics fund (15.6%), and persistent disease despite optimum treatment (14.1%). T2T was successfully implemented. Malay patients need aggressive treatment adaptation to achieve optimal outcome.
Paediatric rheumatology clinic population in Southeast Asia: are we different?

Arkachaisri T, Tang SP, Daengsuwan T, Phongsamart G, Vilaiyuk S, Charuvanij S, et al.

Rheumatology (Oxford), 2017 03 01;56(3):390-398.
PMID: 27994096 DOI: 10.1093/rheumatology/kew446

Objectives: To examine the descriptive epidemiology of the patient population referred to paediatric rheumatology centres (PRCs) in Southeast Asia (SEA) and to compare the frequency of conditions encountered with other PRC populations.

Methods: A web-based Registry for Childhood Onset Paediatric Rheumatic Diseases was established in 2009 and seven PRCs in four SEA countries, where paediatric rheumatologists are available, participated in a prospective 24 month data collection (43 months for Singapore).

Results: The number of patients analysed was 4038 (788 from Malaysia, 711 from the Philippines, 1943 from Singapore and 596 from Thailand). Over 70% of patients evaluated in PRCs in Malaysia, the Philippines and Thailand had rheumatic diseases (RDs), as compared with one-half of the proportion seen in Singaporean PRCs, which was similar to the Western PRC experience. Among RDs diagnosed (n = 2602), JIA was the most common disease encountered in Malaysia (41%) and Thailand (61%) as compared with systemic vasculitides in the Philippines (37%) and Singapore (35%) among which Henoch-Schönlein purpura was the most prevalent. SLE and related diseases were more common, but idiopathic pain syndrome and abnormal immunological laboratory tests were rarer than those seen in the West. JIA subtype distributions were different among countries. Among non-RDs (n = 1436), orthopaedic and related conditions predominated (21.7-59.4%).

Conclusion: The frequencies of RDs seen by SEA PRCs were different from those in the West. Systemic vasculitides and SLE were common in addition to JIA. Paediatric rheumatologist availability and healthcare accessibility partially explain these observed discrepancies.

Study site: multination + Selayang Hospital, Malaysia
Validation of the CancerMath prognostic tool for breast cancer in Southeast Asia

Miao H, Hartman M, Verkooijen HM, Taib NA, Wong HS, Subramaniam S, et al.

BMC Cancer, 2016 10 21;16(1):820.
PMID: 27769212

BACKGROUND: CancerMath is a set of web-based prognostic tools which predict nodal status and survival up to 15 years after diagnosis of breast cancer. This study validated its performance in a Southeast Asian setting.
METHODS: Using Singapore Malaysia Hospital-Based Breast Cancer Registry, clinical information was retrieved from 7064 stage I to III breast cancer patients who were diagnosed between 1990 and 2011 and underwent surgery. Predicted and observed probabilities of positive nodes and survival were compared for each subgroup. Calibration was assessed by plotting observed value against predicted value for each decile of the predicted value. Discrimination was evaluated by area under a receiver operating characteristic curve (AUC) with 95 % confidence interval (CI).
RESULTS: The median predicted probability of positive lymph nodes is 40.6 % which was lower than the observed 43.6 % (95 % CI, 42.5 %-44.8 %). The calibration plot showed underestimation for most of the groups. The AUC was 0.71 (95 % CI, 0.70-0.72). Cancermath predicted and observed overall survival probabilities were 87.3 % vs 83.4 % at 5 years after diagnosis and 75.3 % vs 70.4 % at 10 years after diagnosis. The difference was smaller for patients from Singapore, patients diagnosed more recently and patients with favorable tumor characteristics. Calibration plot also illustrated overprediction of survival for patients with poor prognosis. The AUC for 5-year and 10-year overall survival was 0.77 (95 % CI: 0.75-0.79) and 0.74 (95 % CI: 0.71-0.76).
CONCLUSIONS: The discrimination and calibration of CancerMath were modest. The results suggest that clinical application of CancerMath should be limited to patients with better prognostic profile.
An anomaly detection approach for the identification of DME patients using spectral domain optical coherence tomography images

Sidibé D, Sankar S, Lemaître G, Rastgoo M, Massich J, Cheung CY, et al.

Comput Methods Programs Biomed, 2017 Feb;139:109-117.
PMID: 28187882 DOI: 10.1016/j.cmpb.2016.11.001

This paper proposes a method for automatic classification of spectral domain OCT data for the identification of patients with retinal diseases such as Diabetic Macular Edema (DME). We address this issue as an anomaly detection problem and propose a method that not only allows the classification of the OCT volume, but also allows the identification of the individual diseased B-scans inside the volume. Our approach is based on modeling the appearance of normal OCT images with a Gaussian Mixture Model (GMM) and detecting abnormal OCT images as outliers. The classification of an OCT volume is based on the number of detected outliers. Experimental results with two different datasets show that the proposed method achieves a sensitivity and a specificity of 80% and 93% on the first dataset, and 100% and 80% on the second one. Moreover, the experiments show that the proposed method achieves better classification performance than other recently published works.
Erratum to: Zebrafish phenotypic screen identifies novel Notch antagonists

Velaithan V, Okuda KS, Ng MF, Samat N, Leong SW, Faudzi SM, et al.

Invest New Drugs, 2017 04;35(2):250.
PMID: 28185040 DOI: 10.1007/s10637-017-0437-0
Fulltext Genomic insight into pathogenicity of dematiaceous fungus Corynespora cassiicola

Looi HK, Toh YF, Yew SM, Na SL, Tan YC, Chong PS, et al.

PeerJ, 2017;5:e2841.
PMID: 28149676 DOI: 10.7717/peerj.2841

Corynespora cassiicola is a common plant pathogen that causes leaf spot disease in a broad range of crop, and it heavily affect rubber trees in Malaysia (Hsueh, 2011; Nghia et al., 2008). The isolation of UM 591 from a patient's contact lens indicates the pathogenic potential of this dematiaceous fungus in human. However, the underlying factors that contribute to the opportunistic cross-infection have not been fully studied. We employed genome sequencing and gene homology annotations in attempt to identify these factors in UM 591 using data obtained from publicly available bioinformatics databases. The assembly size of UM 591 genome is 41.8 Mbp, and a total of 13,531 (≥99 bp) genes have been predicted. UM 591 is enriched with genes that encode for glycoside hydrolases, carbohydrate esterases, auxiliary activity enzymes and cell wall degrading enzymes. Virulent genes comprising of CAZymes, peptidases, and hypervirulence-associated cutinases were found to be present in the fungal genome. Comparative analysis result shows that UM 591 possesses higher number of carbohydrate esterases family 10 (CE10) CAZymes compared to other species of fungi in this study, and these enzymes hydrolyses wide range of carbohydrate and non-carbohydrate substrates. Putative melanin, siderophore, ent-kaurene, and lycopene biosynthesis gene clusters are predicted, and these gene clusters denote that UM 591 are capable of protecting itself from the UV and chemical stresses, allowing it to adapt to different environment. Putative sterigmatocystin, HC-toxin, cercosporin, and gliotoxin biosynthesis gene cluster are predicted. This finding have highlighted the necrotrophic and invasive nature of UM 591.
Fulltext Synthetic curcumin derivative DK1 possessed G2/M arrest and induced apoptosis through accumulation of intracellular ROS in MCF-7 breast cancer cells

Ali NM, Yeap SK, Abu N, Lim KL, Ky H, Pauzi AZM, et al.

Cancer Cell Int, 2017;17:30.
PMID: 28239299 DOI: 10.1186/s12935-017-0400-3

AIMS: Curcumin is a lead compound of the rhizomes of Curcuma longa and possess a broad range of pharmacological activities. Chemically, curcumin is 1,3-dicarbonyl class of compound, which exhibits keto-enol tautomerism. Despite of its strong biological properties, curcumin has yet been recommended as a therapeutic agent because of its poor bioavailability.
MAIN METHODS: A curcumin derivative (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1) was synthesized and its cytotoxicity was tested on breast cancer cell MCF-7 and normal cell MCF-10A using MTT assay. Meanwhile, cell cycle regulation and apoptosis on MCF-7 cell were evaluated using flow cytometry. Regulation of cell cycle and apoptosis related genes expression was investigated by quantitative real time polymerase chain reaction (qRT-PCR), western blot and caspases activity analyses. Activation of oxidative stress on MCF-7 were evaluated by measuring ROS and GSH levels.
KEY FINDINGS: DK1 was found to possess selective cytotoxicity on breast cancer MCF-7 cell than normal MCF-10A cell. Flow cytometry cell cycle and AnnexinV/PI analyses reported that DK1 effectively arrested MCF-7 at G2/M phase and induced apoptosis after 72 h of incubation than curcumin. Upregulation of p53, p21 and downregulation of PLK-1 subsequently promote phosphorylation of CDC2 which were found contributed to the arrest of G2/M phase. Moreover, increased of reactive oxygen species and reduced of antioxidant glutathione level correlate with apoptosis observed with raised of cytochrome c and active caspase 9.
SIGNIFICANCE: DK1 was found to be more effective in inducing cell cycle arrest and apoptosis against MCF-7 cell with much higher selectivity index of MCF-10A/MCF-7 than curcumin, which might be contributed by the overexpression of p53 protein.
Fulltext Consumption of ready-to-eat cereals (RTEC) among Malaysian children and association with socio-demographics and nutrient intakes - findings from the MyBreakfast study

Mohd Nasir MT, Nurliyana AR, Norimah AK, Jan Mohamed HJB, Tan SY, Appukutty M, et al.

Food Nutr Res, 2017;61(1):1304692.
PMID: 28469545 DOI: 10.1080/16546628.2017.1304692

Background: The association between different types of breakfast meals and nutrient intakes has been studied to a lesser extent. Objective: This study compared nutrient intakes at breakfast and throughout the day between Malaysian children who consumed ready-to-eat cereals (RTEC) and those who did not. Methods: Anthropometric and dietary data for 1955 children aged 6-12 years from the MyBreakfast study were used in the analysis. Results: Overall, 18% of the children consumed RTEC at breakfast on at least one of the recall days. RTEC consumption was associated with younger age, urban areas, higher income and education level of parents. Among consumers, RTEC contributed 10% and 15% to daily intakes of calcium and iron respectively and ≥20% to daily intakes of vitamin C, thiamin, riboflavin and niacin. RTEC consumers had significantly higher mean intakes of vitamin C, thiamin, riboflavin, niacin, calcium, iron and sugar but lower intakes of fat and sodium than non-RTEC consumers at breakfast and for the total day. Conclusion: Consumption of fortified RTEC at breakfast was associated with lower fat and sodium intakes and higher intakes of several micronutrients both at breakfast and for the total day. However, total sugar intakes appeared to be higher.
Fulltext Maintenance vitamin D3 dosage requirements in Chinese women with post menopausal osteoporosis living in the tropics

Venugopal Y, Hatta SFWM, Musa N, Rahman SA, Ratnasingam J, Paramasivam SS, et al.

Asia Pac J Clin Nutr, 2017 May;26(3):412-420.
PMID: 28429905 DOI: 10.6133/apjcn.042016.10

BACKGROUND AND OBJECTIVES: Vitamin D3 (cholecalciferol) dose required to maintain sufficiency in non- Caucasian women with postmenopausal osteoporosis (PMO) inthe tropics has not been well studied. Some guidelines mandate 800-1000 IU vitamin D/day but the Endocrine Society (US) advocates 1500-2000 IU/day to maintain 25-hydroxyvitamin-D (25(OH)D) concentration at >75 nmol/L. We aimed to establish oral cholecalciferol dose required to maintain 25(OH)D concentration at >75 nmol/L in PMO Chinese Malaysian women, postulating lower dose requirements amongst light-skinned subjects in the tropics.

METHODS AND STUDY DESIGN: 90 Chinese Malaysian PMO women in Kuala Lumpur, Malaysia (2°30'N) with baseline serum 25(OH)D levels >=50 nmol/L were recruited. Prior vitamin D supplements were discontinued and subjects randomized to oral cholecalciferol 25,000 IU/4-weekly (Group-A) or 50,000 IU/4-weekly (Group- B) for 16 weeks, administered under direct observation. Serum 25(OH)D, PTH, serum/urinary calcium were measured at baseline, 8 and 16 weeks.

RESULTS: Baseline characteristics, including osteoporosis severity, sun exposure (~3 hours/week), and serum 25(OH)D did not differ between treatment arms. After 16 weeks, 91% of women sufficient at baseline, remained sufficient on 25,000 IU/4-weekly compared with 97% on 50,000 IU/4-weekly with mean serum 25(OH)D 108.1±20.4 and 114.7±18.4 SD nmol/L respectively (p=0.273). At trial's end, 39% and 80% of insufficient women at baseline attained sufficiency in Group A and Group B (p=0.057). Neither dose was associated with hyperparathyroidism or toxicity.

CONCLUSIONS: Despite pretrial vitamin D supplementation and adequate sun exposure, 25.6% Chinese Malaysian PMO women were vitamin D insufficient indicating sunshine alone cannot ensure sufficiency in the tropics. Both ~900 IU/day and ~1800 IU/day cholecalciferol can safely maintain vitamin D sufficiency in >90% of Chinese Malaysian PMO women. Higher doses are required with baseline concentration <75 nmol/L.
Ethnicity, obstructive sleep apnoea and ischaemic heart disease

Tan YK, Khoo KL, Low JA, Wong ZW, Theng CT, Ong TH, et al.

Ann Acad Med Singap, 1999 Mar;28(2):214-6.
PMID: 10497669

We studied the relationship between different ethnic groups, obstructive sleep apnoea (OSA) and ischaemic heart disease. Four hundred and thirty-two inpatients from the medical wards were interviewed. Limited overnight sleep studies were done in 129 of those who had habitual snoring, daytime sleepiness based on an Epworth sleepiness scale of 8 or more, or a large neck size of 40 cm or more. There were 315 Chinese (72.9%), 67 Malays (15.5%), 43 Indians (10%) and 3 from other races (1.4%). The prevalence of OSA was 19.7%, 30% and 12% among the Chinese, Malays and Indians, respectively. The prevalence ratio for OSA was 1.52 in Malays using Chinese patients as the baseline (P = 0.07). The median neck circumference was 37 cm in both racial groups. The median body mass index was 22.7 kg/m2 in Chinese compared to 23.6 kg/m2 in Malays. The median apnoea-hypopnoea index was 22.7, 19.0 and 26.9 events/hour among the Chinese, Malays and Indians, respectively. OSA was independently associated with the prevalence of IHD (adjusted prevalence ratio 1.68; 95% CI: 1.15, 2.46; P = 0.009). The prevalence of ischaemic heart disease (IHD) was 31%, 24% and 28% in Chinese, Malays and Indians, respectively. The prevalence ratio for IHD in Malays compared to Chinese was 0.77. After adjusting for OSA, there was an even greater reduction in the risk of IHD (adjusted prevalence ratio 0.70). This suggests that OSA is a confounder in the relationship between race and ischaemic heart disease.
Potential serum biomarkers associated with mild and severe leptospirosis infection: A cohort study in the Malaysian population

Tan XT, Amran FB, Thayan R, Ahmad N, Jaafar R, Haron R, et al.

Electrophoresis, 2017 09;38(17):2141-2149.
PMID: 28524240 DOI: 10.1002/elps.201600471

Leptospirosis is an emerging zoonotic infectious disease in Malaysia. The symptoms of leptospirosis vary from mild nonspecific flu-like illness to a severe condition which is usually associated with serious complication and fatality. To study the protein expression profile of mild and severe leptospirosis, 15 paired sera were collected from the patients who were mildly infected and following that progressed to severe stage. The proteome profiles of mild and severe cases were studied using 2DE analysis in combination with LC-MS/MS. The expression of proteins that were significantly different and had a fold difference of at least 2 had been identified and then validated using Western blot. Our study demonstrated apolipoprotein A-I (APOA-I), serum amyloid A (SAA), transferrin (TF), haptoglobin (HP) and transthyretin (TTR) have significantly different expression between mild and severe leptospirosis. The Ingenuity Pathway Analysis software suggested the expression of these five proteins were modulated by acute phase response signaling pathway. Besides that, a functional network of lipid metabolism, molecular transport and small molecule biochemistry that interconnects these five proteins with interactomes also had been predicted by this software. In conclusion, this finding supports the potential of these five proteins to be the biomarkers for mild and severe human leptospirosis.

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