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Fulltext Comparative mitogenomics of the Decapoda reveals evolutionary heterogeneity in architecture and composition

Tan MH, Gan HM, Lee YP, Bracken-Grissom H, Chan TY, Miller AD, et al.

Sci Rep, 2019 Jul 24;9(1):10756.
PMID: 31341205 DOI: 10.1038/s41598-019-47145-0

The emergence of cost-effective and rapid sequencing approaches has resulted in an exponential rise in the number of mitogenomes on public databases in recent years, providing greater opportunity for undertaking large-scale comparative genomic and systematic research. Nonetheless, current datasets predominately come from small and disconnected studies on a limited number of related species, introducing sampling biases and impeding research of broad taxonomic relevance. This study contributes 21 crustacean mitogenomes from several under-represented decapod infraorders including Polychelida and Stenopodidea, which are used in combination with 225 mitogenomes available on NCBI to investigate decapod mitogenome diversity and phylogeny. An overview of mitochondrial gene orders (MGOs) reveals a high level of genomic variability within the Decapoda, with a large number of MGOs deviating from the ancestral arthropod ground pattern and unevenly distributed among infraorders. Despite the substantial morphological and ecological variation among decapods, there was limited evidence for correlations between gene rearrangement events and species ecology or lineage specific nucleotide substitution rates. Within a phylogenetic context, predicted scenarios of rearrangements show some MGOs to be informative synapomorphies for some taxonomic groups providing strong independent support for phylogenetic relationships. Additional comparisons for a range of mitogenomic features including nucleotide composition, strand asymmetry, unassigned regions and codon usage indicate several clade-specific trends that are of evolutionary and ecological interest.
Immune responses against enterovirus A71 infection: Implications for vaccine success

Aw-Yong KL, NikNadia NMN, Tan CW, Sam IC, Chan YF

Rev Med Virol, 2019 09;29(5):e2073.
PMID: 31369184 DOI: 10.1002/rmv.2073

Enterovirus A71 (EV-A71) from the Picornaviridae family is an important emerging pathogen causing hand, foot, and mouth disease (HFMD) outbreaks worldwide. EV-A71 also caused fatal neurological complications in young children especially in Asia. On the basis of seroepidemiological studies from many Asian countries, EV-A71 infection is very common. Children of very young age are particularly vulnerable. Large-scale epidemics that occur every 3 to 4 years are associated with accumulation of an immunologically naive younger population. Capsid proteins especially VP1 with the presence of major B- and T-cell epitopes are the most antigenic proteins. The nonstructural proteins mainly contribute to T-cell epitopes that induce cross-reactive immune responses against other enteroviruses. Dominant epitopes and their neutralization magnitudes differ in mice, rabbits, and humans. Neutralizing antibody is sufficient for immune protection, but poorer cellular immunity may lead to severe neurological complications and deaths. Some chemokines/cytokines are consistently found in severely ill patients, for example, IL-6, IL-10, IL-17A, MCP-1, IL-8, MIG, IP-10, IFN-γ, and G-CSF. An increase in white cell counts is a risk factor for severe HFMD. Recent clinical trials on EV-A71 inactivated vaccine showed >90% efficacy and a robust neutralization response that was protective, indicating neutralizing antibody correlates for protection. No protection against other enteroviruses was observed. A comprehensive understanding of the immune responses to EV-A71 infection will benefit the development of diagnostic tools, potential therapeutics, and subunit vaccine candidates. Future development of a multivalent enterovirus vaccine will require knowledge of correlates of protection, understanding of cross-protection and memory T-cell responses among enteroviruses.
Adherence to Alternative Healthy Eating Index (AHEI-2010) is not associated with risk of stroke in Iranian adults: A case-control study

Mousavi SM, Milajerdi A, Pouraram H, Saadatnia M, Shakeri F, Keshteli AH, et al.

Int J Vitam Nutr Res, 2021 Jan;91(1-2):48-55.
PMID: 31259666 DOI: 10.1024/0300-9831/a000603

Background: Stroke is a major global health problem that contributes to a significant burden of morbidity and mortality. The association of several foods and nutrients with stroke has been well-established. However, the effect of the whole diet on stroke is poorly understood. In this work, we aimed to examine the association between the quality of whole diet, as measured using Alternate Healthy Eating Index-2010 (AHEI-2010), and risk of stroke in Iranian adults. Methods: In this hospital-based case-control study, 193 stroke patients (diagnosed based on clinical and brain CT findings) and 193 controls with no history of cerebrovascular diseases or neurologic disorders were included. The participants' dietary intakes were examined using a validated 168-item semi-quantitative food frequency questionnaire. AHEI-2010 was constructed based on earlier studies. Participants were classified according to tertiles of AHEI-2010 scores and multivariate logistic regression was used to evaluate the association between whole diet quality and risk of stroke. Results: Individuals with greater adherence to AHEI-2010 had a higher intake of fruits, vegetables, nuts and legumes, whole grains and carbohydrate, and a lower intake of trans-fatty acids, sugar-sweetened beverages, total energy and fat (P
Purified ingredient-based high-fat diet is superior to chow-based equivalent in the induction of metabolic syndrome

Cheng HS, Phang SCW, Ton SH, Abdul Kadir K, Tan JBL

J Food Biochem, 2019 02;43(2):e12717.
PMID: 31353646 DOI: 10.1111/jfbc.12717

The present study aimed to outline the physiological and metabolic disparity between chow- and purified ingredient-based high-fat diets and their efficacy in the induction of metabolic syndrome (MetS). Male, 3-week-old Sprague Dawley rats were randomly assigned to chow-based control diet, chow-based high-fat diet, purified control diet, and purified high-fat diet for 12 weeks. Physical and biochemical changes were documented. Chow-based diets, irrespective of the lipid content, resulted in significantly lower weight gain and organ weight compared to purified ingredient-based diets. Circulating insulin, total proteins, albumin, and certain lipid components like the triglycerides, total cholesterol, and high-density lipoprotein-cholesterol were also lower in the chow-based diet groups. Both chow- and purified high-fat diets induced central obesity, hypertension, and hyperglycaemia, but the latter was associated with earlier onset of the metabolic aberrations and additionally, dyslipidaemia. In conclusion, purified high-fat diet is a better diet for MetS induction in rats. PRACTICAL APPLICATIONS: Modeling metabolic syndrome is commonly accomplished with the use of chow- or purified ingredient diets enriched with carbohydrates and/or lipids, but the differences and associated drawbacks are unclear. This study highlights that chow- or modified chow-based diets have a tendency to introduce unwanted metabolic changes which are inconsistent with the progression of metabolic syndrome. Thus, the use of these diets in metabolic disease study should be avoided. On the other hand, purified high-fat diet which can effectively induce the features of metabolic syndrome is highly recommended.
Early growth and home environment are associated with cognitive development in the first year of life of Malaysian infants

Nurliyana AR, Mohd Shariff Z, Mohd Taib MN, Gan WY, Tan KA

Early Hum Dev, 2020 Jan;140:104890.
PMID: 31655334 DOI: 10.1016/j.earlhumdev.2019.104890

BACKGROUND: Undernutrition and poor home environment in the first 2 years of life may have long-term effects on cognitive development.
AIMS: To determine the influence of linear growth and home environment towards cognitive development in the first year of life of Malaysian infants.
STUDY DESIGN: Cross-sectional findings at 12-13 months from a prospective cohort study of infants in Malaysia.
SUBJECTS: One hundred fifty-one infants recruited at 2-5 months were visited at home at 12-13 months (M = 12.95, SD = 0.98).
OUTCOME MEASURES: Maternal and infant measures during pregnancy and at birth were obtained from patient health clinic cards. Weight and length of infants were measured at 12-13 months. Home environment and cognitive development were assessed using HOME inventory and Bayley-III, respectively.
RESULTS: About 22.5% of infants experienced stunting and 14.6% had low home environment quality. The mean cognitive score was 94.54 (SD = 12.00). Stunted infants had 7.59 lower cognitive scores than non-stunted infants, while infants with low home environment quality had 12.09 lower cognitive scores than those with high home environment quality. Cognitive scores increased with better home environment quality in both stunted and non-stunted infants, but stunted infants scored lower than non-stunted infants in all conditions.
CONCLUSION: Stunting, a form of chronic undernutrition, and poor home environment may significantly influence cognitive development of infants. Interventions to prevent undernutrition should start as early as during pregnancy and caregivers should be informed on their roles in providing cognitive stimulation within the home environment for their children.
Fulltext Identification of Antidiabetic Metabolites from Paederia foetida L. Twigs by Gas Chromatography-Mass Spectrometry-Based Metabolomics and Molecular Docking Study

Tan DC, Kassim NK, Ismail IS, Hamid M, Ahamad Bustamam MS

Biomed Res Int, 2019;2019:7603125.
PMID: 31275982 DOI: 10.1155/2019/7603125

Paederia foetida L. (Rubiaceae) is a climber which is widely distributed in Asian countries including Malaysia. The plant is traditionally used to treat various diseases including diabetes. This study is to evaluate the enzymatic inhibition activity of Paederia foetida twigs extracts and to identify the metabolites responsible for the bioactivity by gas chromatography-mass spectrometry (GC-MS) metabolomics profiling. Three different twig extracts, namely, hexane (PFH), chloroform (PFC), and methanol (PFM), were submerged for their α-amylase and α-glucosidase inhibition potential in 5 replicates for each. Results obtained from the loading column scatter plot of orthogonal partial least square (OPLS) model revealed the presence of 12 bioactive compounds, namely, dl-α-tocopherol, n-hexadecanoic acid, 2-hexyl-1-decanol, stigmastanol, 2-nonadecanone, cholest-8(14)-en-3-ol, 4,4-dimethyl-, (3β,5α)-, stigmast-4-en-3-one, stigmasterol, 1-ethyl-1-tetradecyloxy-1-silacyclohexane, ɣ-sitosterol, stigmast-7-en-3-ol, (3β,5α,24S)-, and α-monostearin. In silico molecular docking was carried out using the crystal structure α-amylase (PDB ID: 4W93) and α-glucosidase (PDB ID: 3WY1). α-Amylase-n-hexadecanoic acid exhibited the lowest binding energy of -2.28 kcal/mol with two hydrogen bonds residue, namely, LYS178 and TYR174, along with hydrophobic interactions involving PRO140, TRP134, SER132, ASP135, and LYS172. The binding interactions of α-glucosidase-n-hexadecanoic acid complex ligand also showed the lowest binding energy among 5 major compounds with the energy value of -4.04 kcal/mol. The complex consists of one hydrogen bond interacting residue, ARG437, and hydrophobic interactions with ALA444, ASP141, GLN438, GLU432, GLY374, LEU373, LEU433, LYS352, PRO347, THR445, HIS348, and PRO351. The study provides informative data on the potential antidiabetic inhibitors identified in Paederia foetida twigs, indicating the plant has the therapeutic effect properties to manage diabetes.
Fulltext Study on bioaccessibility of betacyanins from red dragon fruit (Hylocereus polyrhizus)

Choo KY, Ong YY, Lim RLH, Tan CP, Ho CW

Food Sci Biotechnol, 2019 Aug;28(4):1163-1169.
PMID: 31275716 DOI: 10.1007/s10068-018-00550-z

Betacyanins are bioactive dietary phytochemicals which can be found in red dragon fruit (RDF). Therefore, the bioaccessibility of betacyanins that present in fermented red dragon fruit drink (RDFD) and pressed red dragon fruit juice (RDFJ) was accessed in simulated gastric and intestinal digestion. Results disclosed that betacyanins from RDFD and RDFJ suffered minor loss (
Fulltext Health and saliva microbiomes of a semi-urbanized indigenous tribe in Peninsular Malaysia

Yeo LF, Aghakhanian FF, Tan JSY, Gan HM, Phipps ME

F1000Res, 2019;8:175.
PMID: 31275564 DOI: 10.12688/f1000research.17706.3

Background: The indigenous people of Peninsular Malaysia, also known as Orang Asli, have gradually been urbanized. A shift towards non-communicable diseases commonly associated with sedentary lifestyles have been reported in many tribes. This study engaged with a semi-urbanized Temiar tribe from Kampong Pos Piah, Perak, who are experiencing an epidemiological transition. Methods: Weight, height, waist circumference, blood pressure, HbA1C and lipid levels were measured as indicators of cardio-metabolic health. DNA was extracted from saliva using salting-out method followed by PCR amplification of the V3-V4 region of the 16S rRNA gene and sequencing on Illumina MiSeq. Microbiome analysis was conducted on Qiime v1.9. Statistical analysis was conducted using Qiime v1.9 and R. Results: The study revealed that 60.4% of the Temiar community were overweight/obese, with a higher prevalence among women. HbA1C levels showed that 45% of Temiar had pre-diabetes. Insulin resistance was identified in 21% of Temiar by using a surrogate marker, TG/HDL. In total, 56.5% of Temiar were pre-hypertensive, and the condition was prevalent across all age-groups. The saliva microbiome profiles of Temiar revealed significant differences by gender, BMI, abdominal obesity as well as smoking status. The relative abundance of the genus Bifidobacterium was increased in men whereas the genera Prevotella, Capnocytophaga, Leptotrichia, Neisseria and Streptococcus were increased in women. Proteobacteria was significantly depleted in smokers. Conclusions: Temiar from Pos Piah had a high prevalence of cardio-metabolic risks, including general and abdominal obesity, pre-diabetes, prehypertension and hypertension. This phenomenon has not been previously reported in this tribe. The saliva microbiome profiles were significantly different for individuals of different gender, BMI, abdominal obesity and smoking status.
Storage stability and degradation kinetics of bioactive compounds in red palm oil microcapsules produced with solution-enhanced dispersion by supercritical carbon dioxide: A comparison with the spray-drying method

Lee WJ, Tan CP, Sulaiman R, Hee YY, Chong GH

Food Chem, 2020 Jan 30;304:125427.
PMID: 31494501 DOI: 10.1016/j.foodchem.2019.125427

Solution-enhanced dispersion by supercritical carbon dioxide (SEDS) and spray drying (SD) were used to microencapsulate red palm oil (RPO) to prolong the functionality of carotenes and vitamin E. The protective effects provided by SEDS and SD were evaluated in terms of the oxidative stability (65 °C for 35 days), fatty acid compositions, color change and degradation kinetics of carotenes and vitamin E (25 °C, 45 °C, 65 °C, and 85 °C for up to 198 days). SEDS microcapsules (SEDS-M) were the most oxidatively stable (total oxidation (Totox): 26.5), followed by SD microcapsules (SD-M) (34.9) and RPO (56.7). Degradation of carotenes and vitamin E fitted well a first-order kinetic model (average absolute relative deviation = 2-16%). SEDS-M offered better protection to vitamin E (Ea = 36 kJ/mol), whereas SD-M provided better protection for α + β carotene (Ea = 29 kJ/mol). Overall, encapsulation protected RPO during storage, with SEDS-microencapsulated RPO performing better than SD-microencapsulated RPO.
Fulltext Gravid oviposition sticky trap and dengue non-structural 1 antigen test for early surveillance of dengue in multi-storey dwellings: study protocol of a cluster randomized controlled trial

Liew JWK, Selvarajoo S, Tan W, Ahmad Zaki R, Vythilingam I

Infect Dis Poverty, 2019 Sep 03;8(1):71.
PMID: 31477185 DOI: 10.1186/s40249-019-0584-y

BACKGROUND: Dengue is a global disease, transmitted by the Aedes vectors. In 2018, there were 80 615 dengue cases with 147 deaths in Malaysia. Currently, the nationwide surveillance programs are dependent on Aedes larval surveys and notifications of lab-confirmed human infections. The existing, reactive programs appear to lack sensitivity and proactivity. More efficient dengue vector surveillance/control methods are needed.
METHODS: A parallel, cluster, randomized controlled, interventional trial is being conducted for 18 months in Damansara Damai, Selangor, Malaysia, to determine the efficacy of using gravid oviposition sticky (GOS) trap and dengue non-structural 1 (NS1) antigen test for early surveillance of dengue among Aedes mosquitoes to reduce dengue outbreaks. Eight residential apartments were randomly assigned into intervention and control arms. GOS traps are set at the apartments to collect Aedes weekly, following which dengue NS1 antigen is detected in these mosquitoes. When a dengue-positive mosquito is detected, the community will be advised to execute vector search-and-destroy and protective measures. The primary outcome concerns the the percentage change in the (i) number of dengue cases and (ii) durations of dengue outbreaks. Whereas other outcome measures include the change in density threshold of Aedes and changes in dengue-related knowledge, attitude and practice among cluster inhabitants.
DISCUSSION: This is a proactive and early dengue surveillance in the mosquito vector that does not rely on notification of dengue cases. Surveillance using the GOS traps should be able to efficiently provide sufficient coverage for multistorey dwellings where population per unit area is likely to be higher. Furthermore, trapping dengue-infected mosquitoes using the GOS trap, helps to halt the dengue transmission carried by the mosquito. It is envisaged that the results of this randomized controlled trial will provide a new proactive, cheap and targeted surveillance tool for the prevention and control of dengue outbreaks.
TRIAL REGISTRATION: This is a parallel-cluster, randomized controlled, interventional trial, registered at ClinicalTrials.gov (ID: NCT03799237), on 8th January 2019 (retrospectively registered).
Fulltext Counseling interactions between patients living with persistent pain and pharmacists in Australia: are we on the same page?

Lau ET, Tan SH, Antwertinger YJ, Hall T, Nissen LM

J Pain Res, 2019;12:2441-2455.
PMID: 31496787 DOI: 10.2147/JPR.S199017

Background: People living with persistent pain in Australia often cannot access adequate care to manage their pain. Therefore, as the most accessible healthcare professionals, community pharmacists have an important role to play in helping to improve patient outcomes. Hence, it is important to investigate patient needs and expectations in terms of counseling interactions with pharmacists, along with pharmacists' approach to counseling interactions with these patients.
Method: The nature of patient-pharmacist counseling interactions was explored with seven patients (one focus group), and 10 practicing pharmacists (two focus groups, three semi-structured interviews). The themes identified informed the development of an online survey that was advertised online to patients and pharmacists across Australia.
Results: A total of 95 patients and 208 pharmacists completed the survey. Overall, more than half of patients (77/95) were satisfied with the care provided by their pharmacist, but only a third (71/205) of pharmacists were satisfied with the care they provided to patients. The majority of patients (67/94) reported that pharmacists provided good information about medications. This aligned with pharmacists' responses, as most reported focusing on medication side effects (118/188) and instructions for taking pain medication (93/183) during patient interactions. However, when asked about empathy and rapport from pharmacists, only half to two-thirds (48-61/95) of patients expressed positive views. Overall, half of the patients (39/75) wanted a caring, empathetic, respectful, and private conversation with the pharmacist, and nearly half (40/89) perceived the pharmacist's role as providing (new) information on alternative pharmacological and non-pharmacological therapies, including general advice on pain management.
Conclusion: There was a disparity in the nature of the interaction and information that patients wanted from pharmacists, compared to what was provided by pharmacists. Training and education may help pharmacists to better engage in patient-centered care when interacting with people living with persistent pain, thereby improving health outcomes for these patients.
Role of Composite Glycemic Indices: A Comparison of the Comprehensive Glucose Pentagon Across Diabetes Types and HbA1c Levels

Rama Chandran S, A Vigersky R, Thomas A, Lim LL, Ratnasingam J, Tan A, et al.

Diabetes Technol Ther, 2020 02;22(2):103-111.
PMID: 31502876 DOI: 10.1089/dia.2019.0277

Background:
Complex changes of glycemia that occur in diabetes are not fully captured by any single measure. The Comprehensive Glucose Pentagon (CGP) measures multiple aspects of glycemia to generate the prognostic glycemic risk (PGR), which constitutes the relative risk of hypoglycemia combined with long-term complications. We compare the components of CGP and PGR across type 1 and type 2 diabetes.
Methods:
Participants: n = 60 type 1 and n = 100 type 2 who underwent continuous glucose monitoring (CGM). Mean glucose, coefficient of variation (%CV), intensity of hypoglycemia (INThypo), intensity of hyperglycemia (INThyper), time out-of-range (TOR <3.9 and >10 mmol/L), and PGR were calculated. PGR (median, interquartile ranges [IQR]) for diabetes types, and HbA1c classes were compared.
Results:
While HbA1c was lower in type 1 (type 1 vs. type 2: 8.0 ± 1.6 vs. 8.6 ± 1.7, P = 0.02), CGM-derived mean glucoses were similar across both groups (P > 0.05). TOR, %CV, INThypo, and INThyper were all higher in type 1 [type 1 vs. type 2: 665 (500, 863) vs. 535 (284, 823) min/day; 39% (33, 46) vs. 29% (24, 34); 905 (205, 2951) vs. 18 (0, 349) mg/dL × min2; 42,906 (23,482, 82,120) vs. 30,166 (10,276, 57,183) mg/dL × min2, respectively, all P
Influence of bariatric surgery on weight reduction and control of chronic disease among obese patients in Malaysia

Tan KC, Chang CT, Cheah WK, Vinayak CR, Chan HK

Med J Malaysia, 2019 Jun;74(3):215-218.
PMID: 31256176

INTRODUCTION: This study was designed to determine the influence of bariatric surgery on changes in the body mass index (BMI), and the control of diabetes, hypertension and dyslipidaemia among obese patients in Malaysia.
MATERIALS AND METHODS: This was a retrospective cohort study undertaken at a public tertiary care centre in the state of Perak, Malaysia. Information of obese patients who underwent bariatric surgery was obtained from their medical records. The changes in the BMI, HbA1C, systolic and diastolic blood pressure (SBP and DBP), and lipid levels between three months before and after the surgery were assessed.
RESULTS: The patients (n=106) were mostly Malay (66.0%), had at least one comorbidity (61.3%), and had a mean age of 40.38±11.75 years. Following surgery, the BMI of the patients was found to reduce by 9.78±5.82kg/m2. For the patients who had diabetes (n=24) and hypertension (n=47), their mean HbA1C, SBP and DBP were also shown to reduce significantly by 2.02±2.13%, 17.19±16.97mmHg, and 11.45±12.63mmHg, respectively. Meanwhile, the mean total cholesterol, triglyceride and low-density lipoprotein levels of those who had dyslipidaemia (n=21) were, respectively, lowered by 0.91±1.18mmol/L, 0.69±1.11mmol/L and 0.47±0.52mmol/L.
CONCLUSION: The findings suggest that in addition to weight reduction, bariatric surgery is helpful in improving the diabetes, hypertension and dyslipidaemia control among obese patients. However, a large-scale trial with a control group is required to verify our findings.
Fulltext Extracellular matrix from decellularized mesenchymal stem cells improves cardiac gene expressions and oxidative resistance in cardiac C-kit cells

Ng WH, Ramasamy R, Yong YK, Ngalim SH, Lim V, Shaharuddin B, et al.

Regen Ther, 2019 Dec;11:8-16.
PMID: 31193142 DOI: 10.1016/j.reth.2019.03.006

OBJECTIVE: Myocardial infarction remains the number one killer disease worldwide. Cellular therapy using cardiac c-kit cells (CCs) are capable of regenerating injured heart. Previous studies showed mesenchymal stem cell-derived (MSC) extracellular matrices can provide structural support and are capable of regulating stem cell functions and differentiation. This study aimed to evaluate the effects of human MSC-derived matrices for CC growth and differentiation.
METHODS: Human Wharton's Jelly-derived MSCs were cultured in ascorbic acid supplemented medium for 14 days prior to decellularisation using two methods. 1% SDS/Triton X-100 (ST) or 20 mM ammonia/Triton X-100 (AT). CCs isolated from 4-week-old C57/BL6N mice were cultured on the decellularised MSC matrices, and induced to differentiate into cardiomyocytes in cardiogenic medium for 21 days. Cardiac differentiation was assessed by immunocytochemistry and qPCR. All data were analysed using ANOVA.
RESULTS: In vitro decellularisation using ST method caused matrix delamination from the wells. In contrast, decellularisation using AT improved the matrix retention up to 30% (p
Fulltext Nobiletin and Derivatives: Functional Compounds from Citrus Fruit Peel for Colon Cancer Chemoprevention

Goh JXH, Tan LT, Goh JK, Chan KG, Pusparajah P, Lee LH, et al.

Cancers (Basel), 2019 Jun 21;11(6).
PMID: 31234411 DOI: 10.3390/cancers11060867

The search for effective methods of cancer treatment and prevention has been a continuous effort since the disease was discovered. Recently, there has been increasing interest in exploring plants and fruits for molecules that may have potential as either adjuvants or as chemopreventive agents against cancer. One of the promising compounds under extensive research is nobiletin (NOB), a polymethoxyflavone (PMF) extracted exclusively from citrus peel. Not only does nobiletin itself exhibit anti-cancer properties, but its derivatives are also promising chemopreventive agents; examples of derivatives with anti-cancer activity include 3'-demethylnobiletin (3'-DMN), 4'-demethylnobiletin (4'-DMN), 3',4'-didemethylnobiletin (3',4'-DMN) and 5-demethylnobiletin (5-DMN). In vitro studies have demonstrated differential efficacies and mechanisms of NOB and its derivatives in inhibiting and killing of colon cancer cells. The chemopreventive potential of NOB has also been well demonstrated in several in vivo colon carcinogenesis animal models. NOB and its derivatives target multiple pathways in cancer progression and inhibit several of the hallmark features of colorectal cancer (CRC) pathophysiology, including arresting the cell cycle, inhibiting cell proliferation, inducing apoptosis, preventing tumour formation, reducing inflammatory effects and limiting angiogenesis. However, these substances have low oral bioavailability that limits their clinical utility, hence there have been numerous efforts exploring better drug delivery strategies for NOB and these are part of this review. We also reviewed data related to patents involving NOB to illustrate the extensiveness of each research area and its direction of commercialisation. Furthermore, this review also provides suggested directions for future research to advance NOB as the next promising candidate in CRC chemoprevention.
Application of 18F-FDG PET-CT in the management of pulmonary nodule and mass - a pictorial review

Wong TH, Tan TH, George UR, Kow KS, Liam CK

Med J Malaysia, 2019 Jun;74(3):250-256.
PMID: 31256186

BACKGROUND: Lung cancer is one of the leading causes of cancer-related mortality worldwide. Pulmonary nodules are commonly encountered in clinical practice because of the recent implementation of low-dose CT lung screening programme, incidental finding on cardiac CT or CT for nonthoracic related disease. 18F-FDG PET-CT plays an important role in the management of pulmonary nodules.
METHODS: In this pictorial review, we present six different scenarios of using 18F-FDG PET-CT in the management of suspicious pulmonary nodule or mass. The advantages and limitations of 18F-FDG PET-CT and Herder model are discussed.
RESULTS: 18F-FDG PET-CT with risk assessment using Herder model provides added value in characterising indeterminate pulmonary nodules. Besides, 18F-FDG PET-CT is valuable to guide the site of biopsy and provide accurate staging of lung cancer.
CONCLUSION: To further improve its diagnostic accuracy, careful history taking, and CT morphological evaluation should be taken into consideration when interpreting 18FFDG PET-CT findings in patients with these nodules.
A web-based educational intervention module to improve knowledge and attitudes towards thalassaemia prevention in Malaysian young adults

Ngim CF, Ibrahim H, Abdullah N, Lai NM, Tan RKM, Ng CS, et al.

Med J Malaysia, 2019 Jun;74(3):219-225.
PMID: 31256177

BACKGROUND: Thalassaemia is a public health burden in Malaysia and its prevention faces many challenges. In this study, we aimed to assess the effectiveness of a web-based educational module in improving knowledge and attitudes about thalassaemia prevention amongst Malaysian young adults.
METHODS: We designed an interactive web-based educational module in the Malay language wherein videos were combined with text and pictorial visual cues. Malaysians aged 18-40 years old who underwent the module had their knowledge and attitudes assessed at baseline, post-intervention and at 6-month follow-up using a selfadministered validated questionnaire.
RESULTS: Sixty-five participants: 47 Malays (72.3%), 15 Chinese (23.1%), three Indians (4.6%) underwent the module. Questionnaires were completed at baseline (n=65), postintervention (n=65) and at 6-month follow-up (n=60). Out of a total knowledge score of 21, significant changes were recorded across three time-points- median scores were 12 at pre-intervention, 19 at post-intervention and 16 at 6-month follow-up (p<0.001). Post-hoc testing comparing preintervention and 6-month follow-up scores showed significant retention of knowledge (p<0.001). Compared to baseline, attitudes at 6-month follow-up showed an increased acceptance for "marriage avoidance between carriers" (pre-intervention 20%, 6-month follow-up 48.3%, p<0.001) and "prenatal diagnosis" (pre-intervention 73.8%, 6-month follow-up 86.2%, p=0.008). Acceptance for selective termination however, remained low without significant change (pre-intervention 6.2%, 6-month follow-up 16.7%, p=0.109).
CONCLUSION: A web-based educational module appears effective in improving knowledge and attitudes towards thalassaemia prevention and its incorporation in thalassaemia prevention programs is potentially useful in Malaysia and countries with a high internet penetration rate.
Fulltext Malaysian Tualang Honey Inhibits Hydrogen Peroxide-Induced Endothelial Hyperpermeability

Devasvaran K, Tan JJ, Ng CT, Fong LY, Yong YK

Oxid Med Cell Longev, 2019;2019:1202676.
PMID: 31531177 DOI: 10.1155/2019/1202676

Malaysian Tualang honey (TH) is a known therapeutic honey extracted from the honeycombs of the Tualang tree (Koompassia excelsa) and has been reported for its antioxidant, anti-inflammatory, antiproliferative, and wound healing properties. However, the possible vascular protective effect of TH against oxidative stress remains unclear. In this study, the effects of TH on hydrogen peroxide- (H2O2-) elicited vascular hyperpermeability in human umbilical vein endothelial cells (HUVECs) and Balb/c mice were evaluated. Our data showed that TH concentrations ranging from 0.01% to 1.00% showed no cytotoxic effect to HUVECs. Induction with 0.5 mM H2O2 was found to increase HUVEC permeability, but the effect was significantly reversed attenuated by TH (p < 0.05), of which the permeability with the highest inhibition peaked at 0.1%. In Balb/c mice, TH (0.5 g/kg-1.5 g/kg) significantly (p < 0.05) reduced H2O2 (0.3%)-induced albumin-bound Evans blue leak, in a dose-dependent manner. Immunofluorescence staining confirmed that TH reduced actin stress fiber formation while increasing cortical actin formation and colocalization of caveolin-1 and β-catenin in HUVECs. Signaling studies showed that HUVECs pretreated with TH significantly (p < 0.05) decreased intracellular calcium release, while sustaining the level of cAMP when challenged with H2O2. These results suggested that TH could inhibit H2O2-induced vascular hyperpermeability in vitro and in vivo by suppression of adherence junction protein redistribution via calcium and cAMP, which could have a therapeutic potential for diseases related to the increase of both oxidant and vascular permeability.
Fulltext Healthcare is not universal if undocumented migrants are excluded

Legido-Quigley H, Pocock N, Tan ST, Pajin L, Suphanchaimat R, Wickramage K, et al.

BMJ, 2019 Sep 16;366:l4160.
PMID: 31527060 DOI: 10.1136/bmj.l4160

Helena Legido-Quigley and colleagues examine the barriers that migrants face in accessing healthcare and argue they are counterproductive for host countries
Diabetes, arthritis, urinary incontinence, poor self-rated health, higher body mass index and lower handgrip strength are associated with falls among community-dwelling middle-aged and older adults: Pooled analyses from two cross-sectional Malaysian datasets

Singh DKA, Shahar S, Vanoh D, Kamaruzzaman SB, Tan MP

Geriatr Gerontol Int, 2019 Aug;19(8):798-803.
PMID: 31237103 DOI: 10.1111/ggi.13717

AIM: The identification of risk factors associated with comorbidities and physical fitness might provide pathways for planning therapeutic targets for future falls prevention. Results from large datasets that examined falls risk factors in Asia have been limited. The aim of the present study was to identify the risk factors for falls by pooling data consisting of medical history, physical performance and self-rated health from two large Malaysian epidemiological studies.
METHODS: Matching variables from the Towards Useful Aging and Malaysian Elders Longitudinal Research datasets related to falls, physical performance and determinants of falls were identified and pooled for analysis. The Timed Up and Go test and dominant handgrip strength tests were used as physical performance measures. Falls were self-reported, and functional status was assessed using activities of daily living.
RESULTS: Data of 3935 participants, mean age 68.9 ± 6.8 years, 2127 (54.0%) women and 1807 (46.0%) men were extracted for analyses. In an adjusted model, independent risk factors for falls from this cohort studies were diabetes (OR 1.258), arthritis (OR 1.366), urinary incontinence (OR 1.346), poor self-rated health (OR 1.293), higher body mass index (OR 1.029) and lower handgrip strength (OR 1.234).
CONCLUSIONS: Although the risk factors that emerged from our analyses were similar to available studies among older adults, the Timed Up and Go test did not appear as one of the risk factors in the present study that included middle-aged adults. Our findings will require confirmation in a prospective study. Geriatr Gerontol Int 2019; 19: 798-803.

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