Browse publications by year: 2018

Functional Analysis of Circular RNAs

Shanmugapriya, Huda HA, Vijayarathna S, Oon CE, Chen Y, Kanwar JR, et al.

Adv Exp Med Biol, 2018 9 28;1087:95-105.
PMID: 30259360 DOI: 10.1007/978-981-13-1426-1_8

Circular RNAs characterize a class of widespread and diverse endogenous RNAs which are non-coding RNAs that are made by back-splicing events and have covalently closed loops with no polyadenylated tails. Various indications specify that circular RNAs (circRNAs) are plentiful in the human transcriptome. However, their participation in biological processes remains mostly undescribed. To date thousands of circRNAs have been revealed in organisms ranging from Drosophila melanogaster to Homo sapiens. Functional studies specify that these transcripts control expression of protein-coding linear transcripts and thus encompass a key component of gene expression regulation. This chapter provide a comprehensive overview on functional validation of circRNAs. Furthermore, we discuss the recent modern methodologies for the functional validation of circRNAs such as RNA interference (RNAi) gene silencing assay, luciferase reporter assays, circRNA gain-of-function investigation via overexpression of circular transcript assay, RT-q-PCR quantification, and other latest applicable assays. The methods described in this chapter are demonstrated on the cellular model.

MeSH terms: Animals; Gene Expression Regulation/genetics*; Humans; RNA/analysis; RNA/biosynthesis; RNA/genetics*; Software; Alternative Splicing; In Situ Hybridization/methods; Genes, Reporter; Computational Biology; Reverse Transcriptase Polymerase Chain Reaction/methods; Databases, Genetic; RNA, Long Noncoding/analysis; RNA, Long Noncoding/genetics
Prospective Advances in Circular RNA Investigation

Sulaiman SA, Abdul Murad NA, Mohamad Hanif EA, Abu N, Jamal R

Adv Exp Med Biol, 2018 9 28;1087:357-370.
PMID: 30259380 DOI: 10.1007/978-981-13-1426-1_28

circRNAs have emerged as one of the key regulators in many cellular mechanisms and pathogenesis of diseases. However, with the limited knowledge and current technologies for circRNA investigations, there are several challenges that need to be addressed for. These include challenges in understanding the regulation of circRNA biogenesis, experimental designs, and sample preparations to characterize the circRNAs in diseases as well as the bioinformatics pipelines and algorithms. In this chapter, we discussed the above challenges and possible strategies to overcome those limitations. We also addressed the differences between the existing applications and technologies to study the circRNAs in diseases. By addressing these challenges, further understanding of circRNAs roles and regulations as well as the discovery of novel circRNAs could be achieved.

MeSH terms: Agriculture/methods; Forecasting; Gene Expression Regulation/genetics; Humans; Research/trends*; RNA/analysis; RNA/genetics*; Genetic Therapy; Biomarkers; Computational Biology; Databases, Genetic
Sera of patients with systemic lupus erythematosus cross-neutralizes dengue viruses

Zainal N, Tan KK, Johari J, Hussein H, Wan Musa WR, Hassan J, et al.

Microbiol. Immunol., 2018 Oct;62(10):659-672.
PMID: 30259549 DOI: 10.1111/1348-0421.12652

Dengue is the most prevalent mosquito-borne disease in Southeast Asia, where the incidence of systemic lupus erythematosus (SLE) is approximately 30 to 53 per 100,000. Severe dengue, however, is rarely reported among individuals with SLE. Here, whether sera of patients with SLE cross-neutralize dengue virus (DENV) was investigated. Serum samples were obtained from individuals with SLE who were dengue IgG and IgM serology negative. Neutralization assays were performed against the three major DENV serotypes. Of the dengue serology negative sera of individuals with SLE, 60%, 61% and 52% of the sera at 1/320 dilution showed more than 50% inhibition against dengue type-1 virus (DENV-1), DENV-2 and DENV-3, respectively. The neutralizing capacity of the sera was significantly greater against DENV-1 (P

MeSH terms: Adult; Animals; Antibodies, Viral/blood; Antibodies, Viral/immunology*; Epitopes/immunology; Cercopithecus aethiops; Cross Reactions/immunology; Dengue/immunology*; Dengue/prevention & control; Dengue Virus/immunology*; Female; Humans; Immunoglobulin G/blood; Immunoglobulin M/blood; Lupus Erythematosus, Systemic/blood*; Lupus Erythematosus, Systemic/immunology*; Malaysia; Male; Middle Aged; Neutralization Tests; Vero Cells; Antibodies, Neutralizing/blood; Antibodies, Neutralizing/immunology*; Immunity, Heterologous*; Serogroup
Fulltext Effects of clinoptilolite zeolite on phosphorus dynamics and yield of Zea Mays L. cultivated on an acid soil

Nur Aainaa H, Haruna Ahmed O, Ab Majid NM

PLoS One, 2018;13(9):e0204401.
PMID: 30261005 DOI: 10.1371/journal.pone.0204401

Efficient management of P fertilizers ensures good yield of crops and adequate food supply. In the acid soil of the tropics, soluble P is fixed by Al and Fe. Exploitation of the high CEC and pH of Clinoptilolite zeolite (CZ) could mitigate low soil pH and P fixation in acid soils. This study was undertaken to determine the effects of amending a weathered acid soil with CZ on: (i) soil P availability and other related soil chemical properties, and (ii) nutrient concentration, nutrient uptake, above-ground biomass, agronomic efficiency, and yield of Zea mays L. on a tropical acidic soil. Triple superphosphate (TSP), Egypt Rock phosphate (ERP), and Christmas Island Rock phosphate (CIRP) were used as P sources. The treatments evaluated were: (i) soil alone, (ii) 100% recommended fertilizer rate (NPK), and (iii) 75% fertilizer rate + Clinoptilolite zeolite. Selected soil chemical properties and P availability were determined before and after field trials. Zea mays L. above-ground biomass, nutrient concentration, nutrient uptake, agronomic efficiency, and fresh cob yield were also determined. Results revealed that the effects of treatments with and without CZ treatments on soil pH, P fractions, soil acidity, dry matter production, yield of maize, nutrient uptake, and agronomic efficiency were similar. Hence, suggesting CZ inclusion in the fertilization program of Zea mays L is beneficial in terms of reducing excessive or unbalanced use of chemical fertilizers due to reduction of fertilizers usage by 25%.

MeSH terms: Agriculture/methods*; Zea mays/growth & development*; Zea mays/metabolism*; Fertilizers; Hydrogen-Ion Concentration; Phosphorus/analysis; Phosphorus/metabolism*; Soil/chemistry*; Tropical Climate; Zeolites*; Biomass; Crops, Agricultural/growth & development; Crops, Agricultural/metabolism
Fulltext The effectiveness of Realistic Mathematics Education approach: The role of mathematical representation as mediator between mathematical belief and problem solving

Yuanita P, Zulnaidi H, Zakaria E

PLoS One, 2018;13(9):e0204847.
PMID: 30261056 DOI: 10.1371/journal.pone.0204847

This study aims to identify the role of mathematical representation as a mediator between mathematical belief and problem solving. A quasi-experimental design was developed that included 426 Form 1 secondary school students. Respondents comprised 209 and 217 students in the treatment and control groups, respectively. SPSS 23.0, ANATES 4 and Amos 18 were used for data analysis. Findings indicated that mathematical representation plays a significant role as mediator between mathematical belief and arithmetic problem solving. The Realistic Mathematics Education (RME) approach successfully increased the arithmetic problem-solving ability of students.

MeSH terms: Achievement; Mathematics; Problem Solving; Surveys and Questionnaires; Research Design; Students; Control Groups
Fulltext Antifungal activity of Boesenbergia Rotunda (temukunci) extract against filamentous spoilage fungi from vegetables

Zakuan, Z., Mustapa, S.A., Sukor, R., Rukayadi, Y.

International Food Research Journal, 2018;25(1):433-438.
MyJurnal

The filamentous spoilage fungi in vegetables can lead to significant impact in food and economic loss. In order to overcome this problem, chemical fungicide has been implemented in vegetable farming and processing but it causes problems towards environment and food safety. Thus, the utilization of natural products such as plants extracts, which exhibit antimicrobial and antifungal activity, is more acceptable to solve this problem. The aim of this study is to investigate the antifungal activity of Boesenbergia rotunda extract against ten filamentous spoilage fungi isolated from five vegetables. The extract was used to treat fungal isolates from vegetables; CRb 002 (Penicillium sp.), CHa 009 (Aspergillus sp.), TMa 001 (Geotrichum sp.), TMa 002 (Aspergillus sp), ONb 001 (Aspergillus sp.), WBb 003 and WBb 004 (Fusarium sp.) WBb 007 (unidentified), WBb 008 (Aureobasidium sp.) and WBb 010 (Penicillium sp.). The results showed that the yield of the extract of B. rotunda using ethanol (95%) was 11.42% (w/v). The 10% of B. rotunda extract exhibited antifungal activities against ten filamentous fungi after 5 days treatment with growth reduction of 41.56%, 30.68%, 86.20%, 50.62%, 26.67%, 47.44%, 50.74%, 36.39%, 42.86%, and 39.39% for WBb 008, WBb 004, WBb 007, WBb 003, CRb 002, WBb 010, CHa 009, TMa 001, ONb 001, and TMa 002, respectively. B. rotunda extract showed highest antifungal activity against fungi isolated from winged bean (WBb 007) with percentage reduction in growth was 86.20%, while the lowest activity was against fungi isolated from the carrot (CRb 002) with 26.67% reduction in growth. Generally, the TPC of fungi in the vegetable samples were reduced after treatment with 5% of B. rotunda extract at 5 min and 10 min of exposure time. The results suggested that B. rotunda extract has high potential to become natural food preservative which can reduce the fungi spoilage of vegetables.

MeSH terms: Agriculture; Ethanol; Anti-Infective Agents; Antifungal Agents; Aspergillus; Biological Products; Food Preservatives; Fungi; Fungicides, Industrial; Fusarium; Geotrichum; Penicillium; Vegetables; Daucus carota; Zingiberaceae; Food Safety
Fulltext Factors affecting pineapple market supply in Johor, Malaysia

Jaji, K., Nawi, N.M., Man, N.

International Food Research Journal, 2018;25(1):366-375.
MyJurnal

Pineapple (Ananas comosus L. Merr.) is a tropical and economic fruit with encouraging market potential in the global market. It is the first crop grown as a commodity crop in Malaysia and raised the country’s position to a very significant level in the world between the late 60 s and early 70 s. However, Malaysian pineapple’s contribution to the global market in the recent time has been experiencing downward trend, resulting to a set-back in its competitiveness. This study aimed to determine factors influencing pineapple market supply in Johor, Malaysia, with objectives of identifying factors affecting pineapple market supply and quantity supplied of pineapple to the market in the study area. Data were collected using a well-structured close ended questionnaire via face-to- face from 170 randomly selected pineapple farmers. The obtained data were analysed using descriptive analysis, exploratory factor analysis, and regression analysis. Six factors identi¬fied by exploratory factor analysis as the factors affecting pineapple supply are credit access, pineapple varieties, distance to the market, cost of input, price of pineapples and extension services. The result of regression analysis revealed that, quantity of pineapple supplied to the market was found affected by farming experience, farm size, credit access, pineapple varieties, cost of inputs, price of pineapples, and extension services at 5%, 1%, 1%, 5%, 1%, 5% and 5% significant level respectively. The study recommends the need for designing appropriate intervention mechanisms focusing on the aforementioned factors to improve industry’s performance in the global market and uplift the status of smallholder pineapple farmers.
Fulltext Malay language translation and validation of the oldenburg burnout inventory measuring burnout

Nur Farhanie Mahadi, Chin, Ri Wei Andrew, Chua, Yun Yuan, Chu, Min Ning, Wong, Mung Seong, Muhamad Saiful Bahri Yusof, et al.

Education in Medicine Journal, 2018;10(2):27-40.
MyJurnal

This study aimed to translate Oldenburg Burnout Inventory (OLBI) into Malay language, and test its
response process (face validity) and internal structure (factor structure and internal consistency). To
the author’s knowledge, OLBI is not yet validated in Malay language, thus this study aimed to produce
a validated Malay version of OLBI (OLBI-M) in order to measure burnout among the healthcare
learner population in Malaysia. OLBI has great potentials mainly due to its accessibility and free of
any cost to use it, thus might promote more researchers to conduct burnout research in Malaysia. The
forward-backward translation was performed as per standard guideline. The OLBI-M was distributed
to 32 medical students to assess face validity and later to 452 medical students to assess construct
validity. Data analysis was performed by Microsoft Excel, Statistical Package for the Social Sciences
(SPSS), and Analysis of Moment Structures (AMOS). The face validity index of OLBI-M was more
than 0.70. The two factors of CBI-M achieved good level of goodness of fit indices (Cmin/df = 3.585,
RMSEA = 0.076, GFI = 0.958, CFI = 0.934, NFI = 0.912, TLI = 0.905) after removal of several
items. The composite reliability values of the two factors ranged from 0.71 to 0.73. The Cronbach’s
alpha values of the three factors ranged from 0.70 to 0.74. This study shows OLBI-M is a reliable
and valid tool to measure burnout in medical students. Future burnout studies in Malaysia are highly
recommended to utilise OLBI-M. However, it is crucial for further validity to be carried out to verify
the credential of OLBI-M.
Fulltext Students’ feedback on effectiveness of combined flipped classroom and high fidelity simulated teaching on airway and ventilation during accident and emergency posting

Subramaniam T, Valuyeetham PS, Tay JS

Education in Medicine Journal, 2018;10(2):5-13.
MyJurnal DOI: 10.21315/eimj2018.10.2.2

Simulation-based medical education enables knowledge, skills and attitudes to be taught in a safe,
realistic manner. Flipped classroom teaching encourages self-learning. Emergency medicine exposes
students to diverse group of patients and physicians’ decision making. This study aims to determine
students’ perception on knowledge, skills and confidence after combined flipped classroom and
simulated teaching. Two cohorts of Semester 7 students Group 1 (n = 120) and Group 2 (n = 78)
completed a 5-point Likert scale questionnaire. Group 1 completed the questionnaire after a lapse
of six months while Group 2 at the end the posting. Responses from both cohorts were compared
using the Mann-Whitney U test. Of 198 (Groups 1 and 2) students, 91.41% (n = 181) felt the
simulated sessions helped better understand care of emergency patients. The sessions helped identify
knowledge gaps (89.90%; n = 178), improve knowledge and understanding of oxygen therapy devices
(85.35%; n = 169), and airway equipment (90.91%; n = 180). They prepared better for the flipped
classroom teaching than traditional sessions (80.81%; n = 160). They felt that their communication
skills (82.32%; n = 163) and confidence (63.64%; n = 126) improved. Significant differences noted
to questions (p = 0.006, p = 0.005, p = 0.041 respectively) targeting knowledge on oxygen therapy
devices, confidence, and identification of gaps in knowledge respectively. Combined simulation and
flipped classroom teaching was well received by students though this requires more preparation.

MeSH terms: Education, Medical; Humans; Malaysia; Students, Medical; Universities; Knowledge; Young Adult; Airway Management
Fulltext Integrated cumulative grade point average (iCGPA): benefits and challenges of implementation for the medical faculty

Suhaila Sanip, Nur Faraheen Abdul Rahman

Education in Medicine Journal, 2018;10(1):69-80.
MyJurnal

The Ministry of Higher Education introduced the integrated cumulative grade point average (iCGPA)
system in 2016 as an aspiration to produce holistic and well-balanced graduates based on Malaysian
Qualification Agency’s (MQA) learning domains. In this article, we provide a comparison of iCGPA
with other established medical competency frameworks and share our experience in implementing
iCGPA in the medical faculty. Throughout the process, it was noted that medical educators require
several core competencies in order to successfully implement iCGPA in their courses. Two of the most
important core competencies are understanding the pedagogies of the 21st century (heutagogies,
paragogies, and cybergogies) and apprehending the concept of outcome-based education. On top of
the requirement of core competencies, there were also challenges in tailoring teaching and learning to
meet the requirement of the Industrial Revolution 4.0. We also describe in detail the benefits and other
challenges of iCGPA implementation in our faculty. We conclude this article with our recommendation
for successful iCGPA implementation in the future for the medical faculty.
Fulltext The structural framework, implementation strategies and students’ perception of team-based learning in undergraduate medical Education of a medical school in Malaysia

Shahid Hassan, Mohd Salami Ibrahim, Hassan, Nabiha Gul

Education in Medicine Journal, 2018;10(1):55-68.
MyJurnal

Delivery and implementation strategies are key to curriculum success. There is growing evidence
that team-based learning (TBL) is an effective way of interactive teaching. TBL is a method that uses
learning teams to enhance student engagement and quality of learning. Individual accountability for
out-of-class reading is followed by individual and group assessment. In-class application exercises,
which is the hallmark of team-based learning promotes both learning and team development. TBL
uses educational principles of transforming traditional content into application of knowledge
and problem solving skills in an interactive learning environment. To experience the structural
framework and to determine the students’ perception about TBL in clinical setting of MBBS
program in a Malaysian medical school. A total of 120 students assigned to 22 small subgroups of
5–6 per group underwent a number of TBL sessions delivered in three phases. In Phase I, students
were assigned reading material. In Phase II, students were assessed through One Best Answer
(OBA) items for individual and group readiness assessment test as individual readiness assessment
test (IRAT) and group readiness assurance test (GRAT) respectively followed by a mini-lecture.
In Phase III, in-class application of learning activity was performed. Finally, peer assessment
evaluated the contribution of peer in TBL. A TBL Classroom Evaluation Inventory (TBLCEI)
developed to probe student’s perception of TBL, comprised of 40 items composite scale with
Cronbach’s alpha at 0.881. In addition, students were asked to provide their estimated grade in
end of the posting assessment. Grades were categorised into excellent pass >85%, high pass 70%–
84%; average to good pass 50%–69% and fail
Fulltext Which personality traits have favourable impact on psychological health during stressful condition?

Yusoff MSB

Education in Medicine Journal, 2018;10(1):35-42.
MyJurnal

Personality researchers have proposed five dimensions of personality that are extroversion,
conscientiousness, agreeableness, neuroticism, and openness. The five-factor model offers a theoretical basis for medical educators to understand the impact of personality traits on medical students’ psychological health during stressful medical training. This study attempted to investigate on which personality traits have favour impact on psychological health of medical students during a stressful period – the final examination of first year. A cross-sectional study was conducted on medical students in a public medical school. Personality traits were measured by USM Personality Inventory and psychological health parameters were measured by 21-item Depression Anxiety Stress Scale. Pearson correlation test was performed by SPSS to determine correlation between personality trait and psychological health parameters. A total of 174 medical students participated in this study. Extroversion (rstress = –0.44, ranxiety = -0.41, rdepression = –0.56), conscientiousness (rstress= –0.38, ranxiety =–0.36, rdepression= –0.51), agreeableness (rstress = –0.28, ranxiety = –0.25, rdepression = –0.47) and openness
(rstress = –0.34, ranxiety = –0.31, rdepression = –0.47) negatively correlated with stress, anxiety and depression. Neuroticism (rstress = 0.53, ranxiety = 0.47, rdepression = 0.60) positively correlated with stress, anxiety and depression. Extroversion, conscientiousness, agreeableness and openness demonstrated favourable impact and neuroticism demonstrated unfavourable impact on stress, anxiety and depression of the medical students during a stressful period.
Fulltext Students perceptions about the immediate feedback assessment technique (If-At) in team based learning using pre-test versus post-test evaluation

Hassan, Shahid, Begum, Imtiaz, Hassan, Nabiha Gul

Education in Medicine Journal, 2018;10(1):25-34.
MyJurnal

Immediate feedback assessment technique (IF-AT) are self-scoring answer sheets, based on the
concepts of immediate feedback for choosing the correct answer in multiple choice questions (MCQs)
during group readiness assurance tests (GRATs) in team-based learning (TBL). IF-AT scratch card
system rewards a student with partial credit for proximate knowledge. This technique motivates
students to pursue learning with just-in-time feedback and gives them the opportunity for collaborative
learning and analytic reasoning among group members. A rubric for partial credit is decided pre-hand
depending upon the number of options used in MCQs. In this study, we assessed students’ perception
about immediate feedback assessment technique before and after the training. To determine students’
perception of the IF-AT scratch card system in instruction and assessment. Students perceptions
about the IF-AT system has been explored using a 25-item questionnaire administered to 60 students
assigned randomly to control and training groups using pre-test and post-test analysis. Paired-sample
t-test and independent-sample t-test statistics were employed and the data was analysed. Descriptive
statistics observed for mean (SD) was found greater in trained group = 58.48 (4.87) vs. control group
= 66.43 (5.81) with t-statistics significant at p = < 0.001. A significant difference in mean (SD) of
pre-test minus post-test scores (5.16) of control and trained group = 5.37 (4.85) and 10.53 (8.36)
respectively was also found with independent t-test analysis. It was found highly significant with
t = –2.92, p < 0.05 and the effect size of 78.1%, established by Cohen’s d criteria. The IF-AT system
provides an individualised and instantaneous instruction as feedback in an assessment, which is
marked with collaborative learning as in team-based learning. The IF-AT system promotes analytic
reasoning with problem solving skills through partial credit for proximate knowledge. Students’
perceive the concept of immediate feedback and partial credit for proximate knowledge as the most
important features of the IF-AT scratch card system.
Fulltext The application of learning taxonomy in anatomy assessment in medical school

Siti Nurma Hanim Hadie

Education in Medicine Journal, 2018;10(1):13-23.
MyJurnal

It is generally accepted that assessment is a single powerful tool that drives students’ learning.
However, assessment of anatomy subject in medical curriculum is disputable as it focusses more on
testing the low order thinking skills. In medical education context, it is of paramount importance to
align the assessment with the curriculum (i.e., learning outcomes) and teaching methods as to enhance
learning through a meaningful learning experience. Hence, the use of learning taxonomy should be
emphasised in designing a proper and suitable assessment for anatomy subject. Among the most
commonly used taxonomies in higher education, are the Bloom’s taxonomy, Miller’s pyramid, SOLO
taxonomy, Krathwohl’s taxonomy of affective domain, and Simpson’s psychomotor domain. However,
being a core basic medical subject with high cognitive input, it is often difficult to achieve contextual
learning in anatomy through application of these taxonomies. Therefore, with raising concern of lack
in the evaluation of higher order thinking skills, affective and psychomotor domains, the anatomy
assessment in modern medical curriculum have been improvised to address the aforementioned
issues. The modern form of assessment in anatomy facilitates the contextual learning with beneficial
attributes gained by students including better understanding of anatomy knowledge, synthesis of
anatomical concept, appreciation of the clinical importance of anatomy, increases communication
skills, and increase in the confidence level.
Parkinson's disease: Cause factors, measurable indicators, and early diagnosis

Bhat S, Acharya UR, Hagiwara Y, Dadmehr N, Adeli H

Comput Biol Med, 2018 11 01;102:234-241.
PMID: 30253869 DOI: 10.1016/j.compbiomed.2018.09.008

Parkinson's disease (PD) is a neurodegenerative disease of the central nervous system caused due to the loss of dopaminergic neurons. It is classified under movement disorder as patients with PD present with tremor, rigidity, postural changes, and a decrease in spontaneous movements. Comorbidities including anxiety, depression, fatigue, and sleep disorders are observed prior to the diagnosis of PD. Gene mutations, exposure to toxic substances, and aging are considered as the causative factors of PD even though its genesis is unknown. This paper reviews PD etiologies, progression, and in particular measurable indicators of PD such as neuroimaging and electrophysiology modalities. In addition to gene therapy, neuroprotective, pharmacological, and neural transplantation treatments, researchers are actively aiming at identifying biological markers of PD with the goal of early diagnosis. Neuroimaging modalities used together with advanced machine learning techniques offer a promising path for the early detection and intervention in PD patients.

MeSH terms: Machine Learning; Anxiety; Anxiety Disorders; Depression; Electrophysiology; Goals; Humans; Muscle Rigidity; Mutation; Parkinson Disease; Sleep Wake Disorders; Tremor; Genetic Therapy; Biomarkers; Comorbidity; Early Diagnosis; Dopaminergic Neurons; Neuroimaging
Fulltext S-acylation regulates the trafficking and stability of the unconventional Q-SNARE STX19

Ampah KK, Greaves J, Shun-Shion AS, Asnawi AW, Lidster JA, Chamberlain LH, et al.

J Cell Sci, 2018 10 22;131(20).
PMID: 30254024 DOI: 10.1242/jcs.212498

STX19 is an unusual Qa-SNARE as it lacks a C-terminal transmembrane domain. However, it is efficiently targeted to post-Golgi membranes. Here, we set out to determine the intracellular localisation of endogenous STX19 and elucidate the mechanism by which it is targeted to membranes. We have found that a pool of STX19 is localised to tubular recycling endosomes where it colocalises with MICAL-L1 and Rab8 (which has Rab8a and Rab8b forms). Using a combination of genetic, biochemical and cell-based approaches, we have identified that STX19 is S-acylated at its C-terminus and is a substrate for several Golgi-localised S-acyltransferases, suggesting that STX19 is initially S-acylated at the Golgi before trafficking to the plasma membrane and endosomes. Surprisingly, we have found that S-acylation is a key determinant in targeting STX19 to tubular recycling endosomes, suggesting that S-acylation may play a general role in directing proteins to this compartment. In addition, S-acylation also protects STX19 from proteosomal degradation, indicating that S-acylation regulates the function of STX19 at multiple levels.This article has an associated First Person interview with the first author of the paper.

MeSH terms: Acylation/genetics*; Humans; Protein Transport/genetics*; Q-SNARE Proteins/metabolism*
Fulltext In vitro molecular study of wound healing using biosynthesized bacteria nanocellulose/silver nanocomposite assisted by bioinformatics databases

Moniri M, Boroumand Moghaddam A, Azizi S, Abdul Rahim R, Zuhainis SW, Navaderi M, et al.

Int J Nanomedicine, 2018;13:5097-5112.
PMID: 30254435 DOI: 10.2147/IJN.S164573

Background: In recent years, bacterial nanocellulose (BNC) based nanocomposites have been developed to promote healing property and antibacterial activity of BNC wound dressing. Molecular study can help to better understanding about interaction of genes and pathways involved in healing progression.
Objectives: The aim of this study was to prepare bacterial nanocellulose/silver (BNC/Ag) nanocomposite films as ecofriendly wound dressing in order to assess their physical, cytotoxicity and antimicrobial properties. The in vitro molecular study was performed to evaluate expression of genes involved in healing of wounds after treatment with BNC/Ag biofilms.
Study design materials and methods: Silver nanoparticles were formed by using Citrullus colocynthis extract within new isolated bacterial nanocellulose (BNC) RM1. The nanocomposites were characterized using X-ray diffraction, Fourier transform infrared, and field emission scanning electron microscopy. Besides, swelling property and Ag release profile of the nanocomposites were studied. The ability of nanocomposites to promote wound healing of human dermal fibroblast cells in vitro was studied. Bioinformatics databases were used to identify genes with important healing effect. Key genes which interfered with healing were studied by quantitative real time PCR.
Results: Spherical silver nanoparticles with particle size ranging from 20 to 50 nm were synthesized and impregnated within the structure of BNC. The resulting nanocomposites showed significant antibacterial activities with inhibition zones ranging from 7±0.25 to 16.24±0.09 mm against skin pathogenic bacteria. Moreover, it was compatible with human fibroblast cells (HDF) and could promote in vitro wound healing after 48h. Based on bioinformatics databases, the genes of TGF-β1, MMP2, MMP9, CTNNB1, Wnt4, hsa-miR-29b-3p and hsa-miR-29c-3p played important role in wound healing. The nanocomposites had an effect in expression of the genes in healing. Thus, the BNC/Ag nanocomposite can be used to heal wound in a short period and simple manner.
Conclusion: This eco-friendly nanocomposite with excellent antibacterial activities and healing property confirming its utility as potential wound dressings.

MeSH terms: Anti-Bacterial Agents/pharmacology; Bacteria/drug effects; Bacteria/chemistry*; Bandages; Cell Line; Cellulose/pharmacology*; Cellulose/ultrastructure; Fibroblasts/drug effects; Fibroblasts/metabolism; Gene Expression Regulation/drug effects; Humans; Microbial Sensitivity Tests; Silver/pharmacology*; Silver/chemistry; Wound Healing/drug effects; Wound Healing/genetics*; X-Ray Diffraction; Cell Death/drug effects; Spectroscopy, Fourier Transform Infrared; Computational Biology*; Nanocomposites/ultrastructure; Nanocomposites/chemistry*; Metal Nanoparticles/ultrastructure; Drug Liberation
Fulltext A retrospective study on atrial fibrillation after coronary artery bypass grafting surgery at The National Heart Institute, Kuala Lumpur

Farouk Musa A, Quan CZ, Xin LZ, Soni T, Dillon J, Hay YK, et al.

F1000Res, 2018;7:164.
PMID: 30254739 DOI: 10.12688/f1000research.13244.2

Background: Atrial fibrillation (AF) is common after cardiac surgery and has been associated with poor outcome and increased resource utilization. The main objective of this study is to determine the incidence of POAF in Malaysia and identify the predictors of developing POAF. The secondary outcome of this study would be to investigate the difference in mortality and morbidity rates and the duration of intensive care unit (ICU), high dependency unit (HDU) and hospital stay between the two. Methods: This is a retrospective single-center, cross sectional study conducted at the National Heart Institute, Malaysia. Medical records of 637 who underwent coronary artery bypass grafting (CABG) surgery in 2015 were accrued. Pre-operative, operative and post-operative information were subsequently collected on a pre-formulated data collection sheet. Data were then analyzed using IBM SPSS v23. Results: The incidence of POAF in our study stands at 28.7% with a mean onset of 45±33 hours post operatively. Variables with independent association with POAF include advancing age, Indian population, history of chronic kidney disease, left ventricular ejection fraction and beta-blocker treatment. The mortality rate is significantly higher statistically ( p < 0.05), and similarly the incidence of stroke. The incidence of other post-operative complications was also significantly higher statistically. The duration of ICU, HDU and hospital stays were statistically longer ( p < 0.001) with higher rates of ICU readmissions and reintubations seen. Conclusion: We conclude that the incidence of POAF in Malaysia is comparable to the figures in Western countries, making POAF one of the most commonly encountered condition after CABG with similar higher rates of mortality, poor outcomes and longer duration of stay, and therefore increased cost of care. Strategies to reduce the incidence of AF after cardiac surgery should favorably affect surgical outcomes and reduce utilization of resources and thus lower cost of care.

MeSH terms: Adult; Aged; Aged, 80 and over; Coronary Artery Bypass/adverse effects*; Atrial Fibrillation/surgery*; Cross-Sectional Studies; Female; Humans; Intensive Care Units/statistics & numerical data*; Length of Stay/statistics & numerical data*; Malaysia/epidemiology; Male; Middle Aged; Postoperative Complications/etiology; Postoperative Complications/mortality*; Postoperative Complications/epidemiology; Prognosis; Retrospective Studies; Risk Factors; Incidence; Survival Rate
Fulltext Vascular Protective Effects of Morinda citrifolia Leaf Extract on Postmenopausal Rats Fed with Thermoxidized Palm Oil Diet: Evidence at Microscopic Level

Chong CLG, Othman F, Hussan F

Int J Vasc Med, 2018;2018:6317434.
PMID: 30254765 DOI: 10.1155/2018/6317434

Atherosclerosis is now well understood as an inflammatory disease instead of lipid storage disorder; however, the conventional treatment is not targeted on treating the inflammation. Morinda citrifolia L. (Rubiaceae) leaf or noni leaf, which is a medicinal food (ulam) used in Traditional Malay Medicine to prevent chronic diseases, may have the potential to be formulated into a functional antiatherosclerotic agent. This study aimed to investigate the effectiveness of Morinda citrifolia leaf extract (MCLE) treatment at histological and ultrastructural level, comparing it with Simvastatin. Thirty-eight female Sprague Dawley rats were divided into five groups: Sham (Sham), ovariectomized (OVX), ovariectomized with Simvastatin 10 mg/kg (OVX+ST), ovariectomized with low dose MC 500 mg/kg (OVX+MCLD), and ovariectomized with high dose MC 1000 mg/kg (OVX+MCHD). Atherosclerosis was induced by producing oestrogen deficiency through ovariectomy and feeding with thermoxidized palm oil (TPO) diet for 12 weeks along with the treatment. The results revealed significantly (P<0.05) lower systolic blood pressure (SBP) in the group treated with MCHD compared to the untreated OVX, whereas the diastolic blood pressure (DBP) was significantly higher in the untreated OVX group compared to the Sham group. Treatment with MCHD also significantly lowered the total cholesterol (TC) level compared to the OVX. The OVX group showed significantly lower high-density lipoprotein (HDL) level compared to the Sham group. The untreated OVX group showed evident histological and ultrastructural features of vascular inflammation such as blood cells accumulation in the lumen, vacuolation of the endothelial cells, subendothelial space widening, elastic fibres disruption, increased intima media thickness (IMT), smooth muscle cells fragmentation, and perivascular adipose tissue (PVAT) deposition. All these pathological changes were less seen in the groups treated with MCLE. In conclusion, we reported the mechanism of antiatherosclerotic property of MCLE through lipids elimination and anti-inflammatory activity. In addition, we do not recommend the use of statin in the absence of dyslipidemia as it causes PVAT deposition.
Fulltext Comparative Study on Surgical Outcomes between Laparoscopic and Open Cornuotomy in Urban Tertiary Center of Malaysia

Ghazali WAHW, Abidin NHZ, Muda AM, Hamid HA

Gynecol Minim Invasive Ther, 2018;7(1):22-26.
PMID: 30254930 DOI: 10.4103/GMIT.GMIT_7_17

STUDY OBJECTIVE: The objective of the study was to evaluate the prevalence of interstitial ectopic pregnancy and to compare the surgical outcomes of laparoscopic cornuotomy (LC) and laparotomy (open) cornuotomy (OC) of cornual ectopic pregnancy and to analyze its associated factors.
MATERIALS AND METHODS: A cross-sectional study was conducted involving cases of interstitial ectopic in Hospital Putrajaya, Putrajaya, Malaysia, over a 10-year period (2005-2014). Data on sociodemographic, clinical profile, perioperative, and postoperative were obtained from the electronic medical records.
MEASUREMENT AND MAIN RESULTS: The prevalence of cornual pregnancy was 4.0% (n = 14) out of total 347 cases of all ectopic pregnancies in Putrajaya Hospital. The mean ± standard deviation age of patient in the LC group and OC group was 29.3 ± 5.9 years and 31.4 ± 7.3 years, respectively. The duration of hospitalization and mean operating time were both significantly shorter in the LC group than in the OC group (1.43 ± 0.54 versus 2.57 ± 0.79 and 61.4 ± 15.7 min versus 97.1 ± 38.2 min, respectively, P < 0.05).There were no statistically significant differences between both groups for the estimated blood loss, requirement of blood transfusion, complications, and future fertility.
CONCLUSION: Laparoscopic cornual resection (cornuotomy) is a safe and less invasive procedure with a comparable complication rate. It has shown that it is feasibility and should be considered as initial treatment in managing those cases in trained hand surgeons.

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