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Fulltext Preliminary study shows novel variant detected in the screening of RET gene in Malaysian patients with Hirschsprung’s disease

Nor Azian Abdul Murad, Sue-Mian, Then, Mohd Ridhwan Abdul Razak, Conjeevaram, Rajendrarao Thambidorai, Sri Noraima Othman, Rosniza Mohamad Hussain, et al.

Asia-Pacific Journal of Molecular Medicine, 2017;7(1):1-6.
MyJurnal

Hirschsprung’s disease (HSCR) is a disorder associated with congenital absence of ganglion cells in the
gastrointestinal tract. Molecular analyses have identified variants in various genes including RET, GDNF,
EDN3 and EDNRB that are involved in the development, migration and survival of neural cells. Variants
in the receptor tyrosine kinase (RET) are most common and have been identified in 10-20% of sporadic
HSCR patients. The objective of this study was to screen for RET gene variants in Malaysian patients with
HSCR. Thirty-two patients with HSCR and 30 normal controls were recruited for this study. Mutations
were screened using the Polymerase Chain Reaction – Denaturing High Performance Liquid
Chromatography (PCR-dHPLC) approach. Mutations identified were then confirmed using Sanger
sequencing. We identified one novel rare variant in exon 4 (A268A c807 G>C) in one patient. We also
identified the common coding sequence variantsA45A (c135G>A), A432A (c1296A>G), L769L (c2307 T>G)
and the G691S in our cohort of patients. In conclusion, our Malaysian patients with HSCR diseases showed
the presence of similar RET gene common variants which have been described in other populations. We
have also identified a novel variant in exon 4 (A268A).
Fulltext Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum

Mohd Abd Razak MR, Afzan A, Ali R, Amir Jalaluddin NF, Wasiman MI, Shiekh Zahari SH, et al.

BMC Complement Altern Med, 2014;14:492.
PMID: 25510573 DOI: 10.1186/1472-6882-14-492

The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties.
Fulltext Repair of segmental load-bearing bone defect by autologous mesenchymal stem cells and plasma-derived fibrin impregnated ceramic block results in early recovery of limb function

Ng MH, Duski S, Tan KK, Yusof MR, Low KC, Rose IM, et al.

Biomed Res Int, 2014;2014:345910.
PMID: 25165699 DOI: 10.1155/2014/345910

Calcium phosphate-based bone substitutes have not been used to repair load-bearing bone defects due to their weak mechanical property. In this study, we reevaluated the functional outcomes of combining ceramic block with osteogenic-induced mesenchymal stem cells and platelet-rich plasma (TEB) to repair critical-sized segmental tibial defect. Comparisons were made with fresh marrow-impregnated ceramic block (MIC) and partially demineralized allogeneic bone block (ALLO). Six New Zealand White female rabbits were used in each study group and three rabbits with no implants were used as negative controls. By Day 90, 4/6 rabbits in TEB group and 2/6 in ALLO and MIC groups resumed normal gait pattern. Union was achieved significantly faster in TEB group with a radiological score of 4.50 ± 0.78 versus ALLO (1.06 ± 0.32), MIC (1.28 ± 0.24), and negative controls (0). Histologically, TEB group scored the highest percentage of new bone (82% ± 5.1%) compared to ALLO (5% ± 2.5%) and MIC (26% ± 5.2%). Biomechanically, TEB-treated tibiae achieved the highest compressive strength (43.50 ± 12.72 MPa) compared to those treated with ALLO (15.15 ± 3.57 MPa) and MIC (23.28 ± 6.14 MPa). In conclusion, TEB can repair critical-sized segmental load-bearing bone defects and restore limb function.
Fulltext Population genetic structure of peninsular Malaysia Malay sub-ethnic groups

Hatin WI, Nur-Shafawati AR, Zahri MK, Xu S, Jin L, Tan SG, et al.

PLoS One, 2011;6(4):e18312.
PMID: 21483678 DOI: 10.1371/journal.pone.0018312

Patterns of modern human population structure are helpful in understanding the history of human migration and admixture. We conducted a study on genetic structure of the Malay population in Malaysia, using 54,794 genome-wide single nucleotide polymorphism genotype data generated in four Malay sub-ethnic groups in peninsular Malaysia (Melayu Kelantan, Melayu Minang, Melayu Jawa and Melayu Bugis). To the best of our knowledge this is the first study conducted on these four Malay sub-ethnic groups and the analysis of genotype data of these four groups were compiled together with 11 other populations' genotype data from Indonesia, China, India, Africa and indigenous populations in Peninsular Malaysia obtained from the Pan-Asian SNP database. The phylogeny of populations showed that all of the four Malay sub-ethnic groups are separated into at least three different clusters. The Melayu Jawa, Melayu Bugis and Melayu Minang have a very close genetic relationship with Indonesian populations indicating a common ancestral history, while the Melayu Kelantan formed a distinct group on the tree indicating that they are genetically different from the other Malay sub-ethnic groups. We have detected genetic structuring among the Malay populations and this could possibly be accounted for by their different historical origins. Our results provide information of the genetic differentiation between these populations and a valuable insight into the origins of the Malay sub-ethnic groups in Peninsular Malaysia.
In vitro evaluation of cytochrome P450 induction and the inhibition potential of mitragynine, a stimulant alkaloid

Lim EL, Seah TC, Koe XF, Wahab HA, Adenan MI, Jamil MF, et al.

Toxicol In Vitro, 2013 Mar;27(2):812-24.
PMID: 23274770 DOI: 10.1016/j.tiv.2012.12.014

CYP450 enzymes are key determinants in drug toxicities, reduced pharmacological effect and adverse drug reactions. Mitragynine, an euphoric compound was evaluated for its effects on the expression of mRNAs encoding CYP1A2, CYP2D6 and CYP3A4 and protein expression and resultant enzymatic activity. The mRNA and protein expression of CYP450 isoforms were carried out using an optimized multiplex qRT-PCR assay and Western blot analysis. CYP1A2 and CYP3A4 enzyme activities were evaluated using P450-Glo™ assays. The effects of mitragynine on human CYP3A4 protein expression were determined using an optimized hCYP3A4-HepG2 cell-based assay. An in silico computational method to predict the binding conformation of mitragynine to the active site of the CYP3A4 enzyme was performed and further validated using in vitro CYP3A4 inhibition assays. Mitragynine was found to induce mRNA and protein expression of CYP1A2. For the highest concentration of 25 μM, induction of mRNA was approximately 70% that of the positive control and was consistent with the increased CYP1A2 enzymatic activity. Thus, mitragynine is a significant in vitro CYP1A2 inducer. However, it appeared to be a weak CYP3A4 inducer at the transcriptional level and a weak CYP3A4 enzyme inhibitor. It is therefore, unlikely to have any significant clinical effects on CYP3A4 activity.
Comparison of bioengineered human bone construct from four sources of osteogenic cells

Ng AM, Saim AB, Tan KK, Tan GH, Mokhtar SA, Rose IM, et al.

J Orthop Sci, 2005;10(2):192-9.
PMID: 15815868

Osteoprogenitor cells have been reported to be present in periosteum, cancellous and cortical bone, and bone marrow; but no attempt to identify the best cell source for bone tissue engineering has yet been reported. In this study, we aimed to investigate the growth and differentiation pattern of cells derived from these four sources in terms of cell doubling time and expression of osteoblast-specific markers in both monolayer cells and three-dimensional cell constructs in vitro. In parallel, human plasma derived-fibrin was evaluated for use as biomaterial when forming three-dimensional bone constructs. Our findings showed osteoprogenitor cells derived from periosteum to be most proliferative followed by cortical bone, cancellous bone, and then bone marrow aspirate. Bone-forming activity was observed in constructs formed with cells derived from periosteum, whereas calcium deposition was seen throughout the constructs formed with cells derived from cancellous and cortical bones. Although no mineralization activity was seen in constructs formed with osteoprogenitor cells derived from bone marrow, well-organized lacunae as would appear in the early phase of bone reconstruction were noted. Scanning electron microscopy evaluation showed cell proliferation throughout the fibrin matrix, suggesting the possible application of human fibrin as the bioengineered tissue scaffold at non-load-bearing sites.
Fulltext The association between bone health indicated by calcaneal quantitative ultrasound and metabolic syndrome in Malaysian men

Chin KY, Ima-Nirwana S, Mohamed IN, Ahmad F, Mohd Ramli ES, Aminuddin A, et al.

J Diabetes Metab Disord, 2015;14:9.
PMID: 25789255 DOI: 10.1186/s40200-015-0136-3

BACKGROUND: Previous studies on the relationship between bone health and metabolic syndrome (MS) have revealed heterogeneous results. There are limited studies employing bone quantitative ultrasonometry in evaluating this relationship. This study aimed to determine the relationship between MS and bone health in a group of Malaysian middle-aged and elderly men using bone quantitative ultrasonometry.
METHODS: This cross-sectional study recruited 309 free living Chinese and Malay men aged 40 years and above residing in Klang Valley, Malaysia. Their demographic and anthropometric data were collected. Their calcaneal speed of sound (SOS) was measured using a CM-200 bone ultrasonometer. Their blood was collected for the evaluation of lipid profile, total testosterone and sex hormone-binding globulin. The joint interim MS definition was used for the classification of subjects. Multiple linear regression analysis was used to assess the association between SOS and indicators of MS and the presence of MS, with suitable adjustment for confounders.
RESULTS: There was no significant difference in SOS value between MS and non-MS subjects (p > 0.05). The SOS values among subjects with different MS scores did not differ significantly (p > 0.05). There were no significant associations between SOS values and indicators of MS or the presence of MS (p > 0.05).
CONCLUSIONS: The relationship between bone health and MS is not significant in Malaysian middle-aged and elderly men. A longitudinal study should be conducted to evaluate the association between bone loss and MS to confirm this finding.
Fulltext Alcohol Use Disorder, Neurodegeneration, Alzheimer's and Parkinson's Disease: Interplay Between Oxidative Stress, Neuroimmune Response and Excitotoxicity

Kamal H, Tan GC, Ibrahim SF, Shaikh MF, Mohamed IN, Mohamed RMP, et al.

Front Cell Neurosci, 2020;14:282.
PMID: 33061892 DOI: 10.3389/fncel.2020.00282

Alcohol use disorder (AUD) has been associated with neurodegenerative diseases such as Alzheimer's and Parkinson's disease. Prolonged excessive alcohol intake contributes to increased production of reactive oxygen species that triggers neuroimmune response and cellular apoptosis and necrosis via lipid peroxidation, mitochondrial, protein or DNA damage. Long term binge alcohol consumption also upregulates glutamate receptors, glucocorticoids and reduces reuptake of glutamate in the central nervous system, resulting in glutamate excitotoxicity, and eventually mitochondrial injury and cell death. In this review, we delineate the following principles in alcohol-induced neurodegeneration: (1) alcohol-induced oxidative stress, (2) neuroimmune response toward increased oxidants and lipopolysaccharide, (3) glutamate excitotoxicity and cell injury, and (4) interplay between oxidative stress, neuroimmune response and excitotoxicity leading to neurodegeneration and (5) potential chronic alcohol intake-induced development of neurodegenerative diseases, including Alzheimer's and Parkinson's disease.
Fulltext Evaluation of types of poisoning exposure calls managed by the Malaysia National Poison Centre (2006-2015): A retrospective review

Tangiisuran B, Jiva M, Ariff AM, Abdul Rani NA, Misnan A, Rashid SM, et al.

BMJ Open, 2018 12 31;8(12):e024162.
PMID: 30598487 DOI: 10.1136/bmjopen-2018-024162

OBJECTIVE: Accidental or intentional poisoning is a public health concern requiring intervention. The current study designs to evaluate the types of poisoning exposure calls received by the Malaysia National Poison Centre (NPC) over a 10-year period.
SETTINGS AND DATA SOURCES: The poisoning enquiries database (2006-2015) from the Malaysia NPC was used for the analysis.
PARTICIPANTS: The NPC records all telephone calls that it manages using a validated and standardised form. Demographics and types of the poisoning exposure calls were extracted and descriptive analysis was applied.
PRIMARY AND SECONDARY OUTCOMES: The primary outcome of this study is to evaluate NPC data for trends in the poisoning exposure calls based on the types and modes of poisoning over a 10-year period. The secondary outcome is to evaluate the characteristics of human exposure cases based on the calls received by the NPC.
RESULTS: There was a notable increase in the number of poisoning exposure calls noticed during the 10-year period but dropped significantly in 2012. The highest number of poisoning exposure calls came from Selangor (21.0%), Perak (18.0%) and Negeri Sembilan (9.8%). More than half of the exposure was intentional (53.8%) involving more women (50.3%) as compared with men (41.9%), and in the 20-29 years age group category (33.5%). Exposure mostly occurred at home (96%) through the ingestion route (94.1%). Pharmaceutical products (40.5%), pesticides (31.7%) and household products (20.1%) were the common agents implicated for intentional exposure.
CONCLUSIONS: There is an increasing trend in enquiries on poisoning exposure calls made to the NPC. Most of the intentional poisoning exposures occurred among younger women and involved pharmaceuticals, pesticides or household products. Poisoning safety education and other interventions are needed to curb poisoning incidents.
LBOS 02-06 HISTOPATHOLOGICAL-SPECIFIC MUTATION SPECTRUM OF ALDOSTERONE-PRODUCING ADENOMAS

Azizan E, Sukor N, Kamaruddin NA, Jamal AR, Ceral J, Solar M, et al.

J Hypertens, 2016 Sep;34 Suppl 1 - ISH 2016 Abstract Book:e550.
PMID: 27754305

Aldosterone-producing adenoma (APA) is a common curable cause of hypertension. Somatic mutations in five genes (KCNJ5, ATP1A1, ATP2B3, CACNA1D, and CTNNB1) have been found to cause the excess aldosterone production of two thirds of APAs [1-4]. KCNJ5 mutant APAs, the most common and largest, had explicit genotype-phenotype relationship - a low protein expression of KCNJ5 relative to their peritumoural zona glomerulosa (ZG) and a zona fasciculata-like composition [5-6]. Conversely for the other genes, controversy arises on whether they have the opposite cell phenotype [4,7-8]. This prospective study aim to to characterize the histopathological-specific mutation spectrum of APAs.
The state of psychiatric research in the Asia Pacific region

Roche GC, Fung P, Ransing R, Noor IM, Shalbafan M, El Hayek S, et al.

Asia Pac Psychiatry, 2021 Mar;13(1):e12432.
PMID: 33145988 DOI: 10.1111/appy.12432

INTRODUCTION: This study aims to review recent scientific publications and research output in the field of psychiatry, from a series of countries in the Asia-Pacific region (Australia, India, Indonesia, Iran, Lebanon, Malaysia, and Nepal), with a view to identify themes and similarities across regions, as well as to examine the barriers and challenges in mental health research faced by countries in the region.
METHODS: Seven psychiatrists from seven countries reviewed recent published and ongoing research in psychiatry in their respective nations, with respect to themes, as well as any barriers or challenges faced by mental health researchers.
RESULTS: While the seven nations included in this review vary in terms of research capabilities and economic development level, they share many similarities both in terms of research direction, and with regards to challenges faced. Limitations in the form of sociocultural differences from the West, and a lack of funding were some of the barriers identified.
DISCUSSION: Mental health research in the region has been progressing well. However, more varied research in the form of qualitative or economic studies are lacking, as are multi-center studies. The similar issues that nations face with regards to research could perhaps benefit from collaborative efforts and initiatives for the furtherance of research in the region.
Missense mutations in MLH1, MSH2, KRAS, and APC genes in colorectal cancer patients in Malaysia

Abdul Murad NA, Othman Z, Khalid M, Abdul Razak Z, Hussain R, Nadesan S, et al.

Dig Dis Sci, 2012 Nov;57(11):2863-72.
PMID: 22669205 DOI: 10.1007/s10620-012-2240-2

BACKGROUND: Colorectal cancer (CRC) is the third most common cancer worldwide with approximately 1 million cases diagnosed annually. In Malaysia, CRC is the second most common cancer in women and ranked first in men. The underlying cause of CRC remains unknown.
AIMS: The aim of this study was to analyze the mutations in genes involved in CRC including MLH1, MSH2, KRAS, and APC genes.
METHODS: A total of 76 patients were recruited. We used the polymerase chain reaction-denaturing high-performance liquid chromatography for the detection of mutations in the mismatch repair (MMR) and APC genes and the PCR single-strand conformation polymorphism for screening of the KRAS gene mutations.
RESULTS: We identified 17 types of missense mutations in 38 out of 76 patients in our patients. Nine mutations were identified in the APC gene, five mutations were detected in the KRAS gene, and two mutations were identified in the MSH2 gene. Only one mutation was identified in MLH1. Out of these 17 mutations, eight mutations (47 %) were predicted to be pathogenic. Seven patients were identified with multiple mutations (3: MSH2 and KRAS, 1: KRAS and APC, 1: MLH1 and APC, 2: APC and APC).
CONCLUSIONS: We have established the PCR-DHPLC and PCR-SSCP for screening of mutations in CRC patients. This study has given a snapshot of the spectrum of mutations in the four genes that were analyzed. Mutation screening in patients and their family members will help in the early detection of CRC and hence will reduce mortality due to CRC.
Fulltext Optimal set of microsatellite markers required to detect illegitimate progenies in selected oil palm (Elaeis guineensis Jacq.) breeding crosses

Zolkafli SH, Ithnin M, Chan KL, Zainol Abidin MI, Ismail I, Ting NC, et al.

Breed Sci, 2021 Apr;71(2):253-260.
PMID: 34377073 DOI: 10.1270/jsbbs.19022

Oil palm is continually being improved via controlled crossing of selected palms to ensure sustainable yields and productivity. As such, correct parental assignment is important as the presence of illegitimates will compromise the progress of improvement. In the present study, we determined the optimal number of microsatellite (SSR) markers for detection of illegitimates in selected oil palm crosses with high confidence. Determining the optimal number of markers to assign parentage will ensure that the DNA fingerprinting will be cost effective for routine use as a quality control tool in oil palm improvement programs. Here, we evaluated a wide range of crosses that included a cross derived from wild germplasm palm. The results revealed that markers with high PIC are informative and detect most of the alleles present in a cross, including those exhibited by the illegitimates. A larger number of optimum sets of markers are needed to detect all illegitimates for crosses with higher levels of genetic diversity. The optimal number of polymorphic SSR markers determined in the present study can ensure that appropriate quality control is implemented for oil palm improvement programs.
Fulltext Epidemiology and risk factors of pesticide poisoning in Malaysia: a retrospective analysis by the National Poison Centre (NPC) from 2006 to 2015

Kamaruzaman NA, Leong YH, Jaafar MH, Mohamed Khan HR, Abdul Rani NA, Razali MF, et al.

BMJ Open, 2020 06 01;10(6):e036048.
PMID: 32487578 DOI: 10.1136/bmjopen-2019-036048

OBJECTIVE: Pesticide poisoning is a global health problem, and its progressive deterioration is a major cause of concern. The objective of this study is to assess epidemiological characteristics and identify risk factors of pesticide poisoning in Malaysia.
SETTING: Pesticide poisoning database of Malaysia National Poison Centre (NPC) from 2006 to 2015.
PARTICIPANTS: Telephone enquiries regarding pesticide poisoning were made by healthcare professionals. Information received by the NPC was entered into a retrievable database of standardised Poison Case Report Form, as adapted from the World Health Organization (WHO).
OUTCOMES: The outcome of the study is to provide an overview of national epidemiological profile of pesticide poisoning. High-risk groups of people and their circumstances were also identified to ensure that appropriate measures are strategised.
RESULTS: Within the study period, a total of 11 087 pesticide poisoning cases were recorded. Sixty per cent of these cases were intentional in nature and most were found among male individuals (57%) of the Indian race (36.4%) aged between 20 and 29 years (25.5%), which occurred at home (90%) through the route of ingestion (94%). The highest number of poisoning was due to herbicides (44%) followed by agricultural insecticides (34%), rodenticides (9.9%), household insecticides (9.5%) and fungicides (0.5%). In addition, 93.6% of intentional pesticide poisoning cases were caused by suicide attempts. The results of this study show that there was an increasing trend in pesticide poisoning incidents over the 10-year duration. This indicates that pesticide poisoning is a prevalent public health problem in Malaysia, resulting in an average incidence rate of 3.8 per 100 000 population.
CONCLUSIONS: Deliberate pesticide ingestion as a method of suicide has become a disturbing trend among Malaysians. Therefore, regulation of highly hazardous pesticides must be enforced to ensure controlled and limited access to these chemicals by the public.
Preparation and characterization of cockle shell aragonite nanocomposite porous 3D scaffolds for bone repair

Mahmood SK, Zakaria MZAB, Razak ISBA, Yusof LM, Jaji AZ, Tijani I, et al.

Biochem Biophys Rep, 2017 Jul;10:237-251.
PMID: 28955752 DOI: 10.1016/j.bbrep.2017.04.008

The demands for applicable tissue-engineered scaffolds that can be used to repair load-bearing segmental bone defects (SBDs) is vital and in increasing demand. In this study, seven different combinations of 3 dimensional (3D) novel nanocomposite porous structured scaffolds were fabricated to rebuild SBDs using an extraordinary blend of cockle shells (CaCo3) nanoparticles (CCN), gelatin, dextran and dextrin to structure an ideal bone scaffold with adequate degradation rate using the Freeze Drying Method (FDM) and labeled as 5211, 5400, 6211, 6300, 7101, 7200 and 8100. The micron sized cockle shells powder obtained (75 µm) was made into nanoparticles using mechano-chemical, top-down method of nanoparticles synthesis with the presence of the surfactant BS-12 (dodecyl dimethyl bataine). The phase purity and crystallographic structures, the chemical functionality and the thermal characterization of the scaffolds' powder were recognized using X-Ray Diffractometer (XRD), Fourier transform infrared (FTIR) spectrophotometer and Differential Scanning Calorimetry (DSC) respectively. Characterizations of the scaffolds were assessed by Scanning Electron Microscopy (SEM), Degradation Manner, Water Absorption Test, Swelling Test, Mechanical Test and Porosity Test. Top-down method produced cockle shell nanoparticles having averagely range 37.8±3-55.2±9 nm in size, which were determined using Transmission Electron Microscope (TEM). A mainly aragonite form of calcium carbonate was identified in both XRD and FTIR for all scaffolds, while the melting (Tm) and transition (Tg) temperatures were identified using DSC with the range of Tm 62.4-75.5 °C and of Tg 230.6-232.5 °C. The newly prepared scaffolds were with the following characteristics: (i) good biocompatibility and biodegradability, (ii) appropriate surface chemistry and (iii) highly porous, with interconnected pore network. Engineering analyses showed that scaffold 5211 possessed 3D interconnected homogenous porous structure with a porosity of about 49%, pore sizes ranging from 8.97 to 337 µm, mechanical strength 20.3 MPa, Young's Modulus 271±63 MPa and enzymatic degradation rate 22.7 within 14 days.
Fulltext Review of Dendritic Cells, Their Role in Clinical Immunology, and Distribution in Various Animal Species

Zanna MY, Yasmin AR, Omar AR, Arshad SS, Mariatulqabtiah AR, Nur-Fazila SH, et al.

Int J Mol Sci, 2021 Jul 28;22(15).
PMID: 34360810 DOI: 10.3390/ijms22158044

Dendritic cells (DCs) are cells derived from the hematopoietic stem cells (HSCs) of the bone marrow and form a widely distributed cellular system throughout the body. They are the most efficient, potent, and professional antigen-presenting cells (APCs) of the immune system, inducing and dispersing a primary immune response by the activation of naïve T-cells, and playing an important role in the induction and maintenance of immune tolerance under homeostatic conditions. Thus, this review has elucidated the general aspects of DCs as well as the current dynamic perspectives and distribution of DCs in humans and in various species of animals that includes mouse, rat, birds, dog, cat, horse, cattle, sheep, pig, and non-human primates. Besides the role that DCs play in immune response, they also play a pathogenic role in many diseases, thus becoming a target in disease prevention and treatment. In addition, its roles in clinical immunology have also been addressed, which include its involvement in transplantation, autoimmune disease, viral infections, cancer, and as a vaccine target. Therefore, based on the current knowledge and understanding of the important roles they play, DCs can be used in the future as a powerful tool for manipulating the immune system.
Fulltext Activities of Daily Living and Determinant Factors among Older Adult Subjects with Lower Body Fracture after Discharge from Hospital: A Prospective Study

Ibrahim NI, Ahmad MS, Zulfarina MS, Zaris SNASM, Mohamed IN, Mohamed N, et al.

Int J Environ Res Public Health, 2018 05 16;15(5).
PMID: 29772744 DOI: 10.3390/ijerph15051002

Fracture is a type of musculoskeletal injury that contributes to an inability to perform daily activities. The objective of this study was to evaluate activities of daily living (ADL) of older adult patients with lower body fracture and to determine factors influencing ADL. Patient's ADL was assessed at pre-fracture, ward admission and post-discharge phases using the Katz ADL questionnaire. There were 129 subjects at pre-fracture and ward phases and 89 subjects at discharge phase. There were four independent variables; age, gender, type of fracture and ability to walk before fracture. Logistic regression models showed that 'age' and 'ability to walk before fracture' were the determinant factors of dependent for 'bathing', 'dressing' and 'toileting'. The 'ability to walk before fracture' was the determinant factor of dependent for 'transferring'. 'Age' and 'gender' were the determinant factors of dependent for 'continence', while 'age' was the determinant factor of dependent for 'feeding'. The ADL score changes were significant across the phases with a reduction in ADL score in the ward admission phase and partial increment during the post-discharge phase. There were improvements in the health outcomes of subjects aged more than 50 years old after 3 months of being discharged from the hospital. In conclusion, age, being female, having a hip fracture and using a walking aid before fracture were the determinants identified in this study.
Fulltext Demethylbelamcandaquinone B (Dmcq B) Is the Active Compound of Marantodes pumilum var. alata (Blume) Kuntze with Osteoanabolic Activities

Ahmad Hairi H, Jamal JA, Aladdin NA, Husain K, Mohd Sofi NS, Mohamed N, et al.

Molecules, 2018 Jul 11;23(7).
PMID: 29997309 DOI: 10.3390/molecules23071686

Phytoestrogens have attracted considerable attention for their potential in the prevention of postmenopausal osteoporosis. Recently, a phytoestrogen-rich herbal plant, Marantodes pumilum var. alata (Blume) Kuntze was reported to protect against bone loss in ovariectomized rat. However, the bioactive compound responsible for these effects and the underlying mechanism were not known. Through bioassay-guided isolation, demethylbelamcandaquinone B (Dmcq B) was isolated and identified from Marantodes pumilum var. alata leaf extract. In terms of its bone anabolic effects, Dmcq B was at par with 17β-estradiol (E2), in promoting the proliferation, differentiation and mineralization of osteoblast cells. Dmcq-B increased early differentiation markers, collagen content and enzymatic ALP activity. It was demonstrated to regulate BMP2 signaling pathway which further activated the transcription factor, osterix. Subsequently, Dmcq B was able to increase the osteocalcin expression which promoted matrix mineralization as evidenced by the increase in calcium deposition. Dmcq B also reduced the protein level of receptor activator of NF-κβ ligand (RANKL) and promoted osteoprotegerin (OPG) protein expression by osteoblast cells, therefore hastening bone formation rate by decreasing RANKL/OPG ratio. Moreover, Dmcq B was able to increase ER expression, postulating its phytoestrogen property. As the conclusion, Dmcq B is the active compound isolated from Marantodes pumilum var. alata leaves, regulating osteoanabolic activities potentially through the BMP2 and ER signaling pathways.
A 19-Gene expression signature as a predictor of survival in colorectal cancer

Abdul Aziz NA, Mokhtar NM, Harun R, Mollah MM, Mohamed Rose I, Sagap I, et al.

BMC Med Genomics, 2016;9(1):58.
PMID: 27609023 DOI: 10.1186/s12920-016-0218-1

Histopathological assessment has a low potential to predict clinical outcome in patients with the same stage of colorectal cancer. More specific and sensitive biomarkers to determine patients' survival are needed. We aimed to determine gene expression signatures as reliable prognostic marker that could predict survival of colorectal cancer patients with Dukes' B and C.
Fulltext Modifiable factors associated with bone health in Malaysian adolescents utilising calcaneus quantitative ultrasound

Zulfarina MS, Sharif R, Syarifah-Noratiqah SB, Sharkawi AM, Aqilah-Sm ZS, Mokhtar SA, et al.

PLoS One, 2018;13(8):e0202321.
PMID: 30106982 DOI: 10.1371/journal.pone.0202321

Maximizing bone mineral accrual to attain an optimal peak bone mass (PBM), particularly during adolescence, appears to be an effective protective strategy in the prevention of osteoporosis. This study aimed to evaluate the influence of physical activity (PA), fat mass (FM), lean mass (LM), body mass index (BMI), calcium, or combination of vitamin D supplement intake, smoking and alcohol drinking status on bone health assessed by calcaneus quantitative ultrasound (QUS) in a healthy adolescent population. The participants comprised of 920 male and female secondary school adolescents aged 15-17 years old. Quantitative ultrasound measurements of the left heel were performed using Lunar Achilles EX II, which included results of broadband ultrasound attenuation (BUA), speed of sound (SOS), and a calculated stiffness index (SI). Multivariable linear regression analyses revealed that-PA was positively associated with all three QUS indices in both genders; BMI was positively associated with SI and SOS in females; LM was positively associated with BUA in both genders; and FM was negatively associated with SI in females. These variables accounted for 32.1%, 21.2% and 29.4% of females' SOS, BUA and SI variances (p<0.001), respectively and 23.6%, 15.4% and 17.2% of males' SOS, BUA and SI variances (p<0.001), respectively. Promoting health benefits from physical activity could influence bone status and consequently improve PBM, which is a potent protective determinant against osteoporosis in adulthood.

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