Browse publications by year: 2016

  1. Voorhoeve A, Edejer TTT, Kapiriri L, Norheim OF, Snowden J, Basenya O, et al.
    Health Hum Rights, 2016 Dec;18(2):11-22.
    PMID: 28559673
    The goal of achieving Universal Health Coverage (UHC) can generally be realized only in stages. Moreover, resource, capacity, and political constraints mean governments often face difficult trade-offs on the path to UHC. In a 2014 report, Making fair choices on the path to UHC, the WHO Consultative Group on Equity and Universal Health Coverage articulated principles for making such trade-offs in an equitable manner. We present three case studies which illustrate how these principles can guide practical decision-making. These case studies show how progressive realization of the right to health can be effectively guided by priority-setting principles, including generating the greatest total health gain, priority for those who are worse off in a number of dimensions (including health, access to health services, and social and economic status), and financial risk protection. They also demonstrate the value of a fair and accountable process of priority setting.
    MeSH terms: Decision Making*; Health Services; Humans; Human Rights*; Socioeconomic Factors; Universal Coverage*
  2. Hafizudin Mohamad Nor, Amirah Rahman, Ahmad Izani Md. Ismail, Ahmad Abd. Majid
    MATEMATIKA, 2016;32(1):53-67.
    MyJurnal
    Homotopy continuation methods (HCMs) can be used to find the solutions
    of polynomial equations. The advantages of HCMs over classical methods such as the
    Newton and bisection methods are that HCMs are able to resolve divergence and starting
    value problems. In this paper, we develop Super Ostrowski-HCM as a technique to
    overcome the starting value problem. We compare the performance of this proposed
    method with Ostrowski-HCM. The results provide evidence of the superiority of Super
    Ostrowski-HCM.
  3. Zangrillo A, Alvaro G, Pisano A, Guarracino F, Lobreglio R, Bradic N, et al.
    Am Heart J, 2016 Jul;177:66-73.
    PMID: 27297851 DOI: 10.1016/j.ahj.2016.03.021
    OBJECTIVE: Patients undergoing cardiac surgery are at risk of perioperative low cardiac output syndrome due to postoperative myocardial dysfunction. Myocardial dysfunction in patients undergoing cardiac surgery is a potential indication for the use of levosimendan, a calcium sensitizer with 3 beneficial cardiovascular effects (inotropic, vasodilatory, and anti-inflammatory), which appears effective in improving clinically relevant outcomes.

    DESIGN: Double-blind, placebo-controlled, multicenter randomized trial.

    SETTING: Tertiary care hospitals.

    INTERVENTIONS: Cardiac surgery patients (n = 1,000) with postoperative myocardial dysfunction (defined as patients with intraaortic balloon pump and/or high-dose standard inotropic support) will be randomized to receive a continuous infusion of either levosimendan (0.05-0.2 μg/[kg min]) or placebo for 24-48 hours.

    MEASUREMENTS AND MAIN RESULTS: The primary end point will be 30-day mortality. Secondary end points will be mortality at 1 year, time on mechanical ventilation, acute kidney injury, decision to stop the study drug due to adverse events or to start open-label levosimendan, and length of intensive care unit and hospital stay. We will test the hypothesis that levosimendan reduces 30-day mortality in cardiac surgery patients with postoperative myocardial dysfunction.

    CONCLUSIONS: This trial is planned to determine whether levosimendan could improve survival in patients with postoperative low cardiac output syndrome. The results of this double-blind, placebo-controlled randomized trial may provide important insights into the management of low cardiac output in cardiac surgery.

    MeSH terms: Cardiac Output, Low/mortality; Cardiac Output, Low/therapy*; Cardiotonic Agents/therapeutic use*; Double-Blind Method; Cardiac Surgical Procedures/mortality; Humans; Hydrazones/therapeutic use*; Infusions, Intravenous; Intensive Care Units; Intra-Aortic Balloon Pumping*; Length of Stay/statistics & numerical data; Postoperative Complications/mortality; Postoperative Complications/therapy*; Pyridazines/therapeutic use*; Respiration, Artificial; Acute Kidney Injury/epidemiology
  4. Leong KH, Abdul-Rahman H, Wang C, Onn CC, Loo SC
    PLoS One, 2016;11(12):e0166064.
    PMID: 27930659 DOI: 10.1371/journal.pone.0166064
    Railway and metro transport systems (RS) are becoming one of the popular choices of transportation among people, especially those who live in urban cities. Urbanization and increasing population due to rapid development of economy in many cities are leading to a bigger demand for urban rail transit. Despite being a popular variant of Traveling Salesman Problem (TSP), it appears that the universal formula or techniques to solve the problem are yet to be found. This paper aims to develop an optimization algorithm for optimum route selection to multiple destinations in RS before returning to the starting point. Bee foraging behaviour is examined to generate a reliable algorithm in railway TSP. The algorithm is then verified by comparing the results with the exact solutions in 10 test cases, and a numerical case study is designed to demonstrate the application with large size sample. It is tested to be efficient and effective in railway route planning as the tour can be completed within a certain period of time by using minimal resources. The findings further support the reliability of the algorithm and capability to solve the problems with different complexity. This algorithm can be used as a method to assist business practitioners making better decision in route planning.
    MeSH terms: Algorithms; Animals; Bees*; Humans; Indonesia; Models, Theoretical*; Problem Solving; Railroads/methods*
  5. Misnan R, Salahudin Abd Aziz N, Mohamad Yadzir ZH, Bakhtiar F, Abdullah N, Murad S
    Iran J Allergy Asthma Immunol, 2016 Aug;15(4):309-316.
    PMID: 27921412
    Snail is one of the worst causes of food allergy. Thus, the aim of this study was to identify the major and minor allergens of the local marine snail (Cerithidea obtusa) and subsequently to investigate the impacts of heat treatment on the IgE-binding activity of snail allergens. Proteins from raw and heat-treated snails (boiled, roasted and fried) were extracted and then resolved by sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Immunoblotting of all extracts were then performed using sera from patients with snail allergy. The results showed that the raw extract contains numerous protein bands between 12 to>250 kDa. Some thermostable proteins, predominantly the 33 and 42 kDa bands, remained detected in all cooked extracts with decreasing intensities from boiled to roasted to fried extracts, while the majority of thermolabile bands denatured after heating. Boiled snail had more protein bands compared to roasted and fried snails. Immunoblotting of raw extract demostrated 19 IgE-binding bands ranging from 15 to 240 kDa. The thermostable bands of 33 and 42 kDa and a thermolabile of 30 kDa band were identified as the major allergens of this snail. The cooked extracts yielded less allergenic bands. The boiled extract yielded approximately 14 IgE-binding bands with some smeared bands at high molecular weight regions. The roasted extract had lesser IgE-binding bands and the majority appeared as smears, while the IgE-reactivity in the fried extract was less visible and appeared as weak smears. This study indicated that both raw and cooked snails played a crucial role in snail allergenicity, as this species of snail contains both thermostable and thermolabile major allergens. The degree of snail allergenicity was revealed in the order: raw> boiled > roasted> fried. Thus, the results would facilitate in the development of effective diagnosis and management strategies of snail allergy in this country.
    MeSH terms: Shellfish Hypersensitivity/immunology*; Animals; Cooking*; Female; Hot Temperature*; Humans; Immunoglobulin E/immunology*; Male; Shellfish/adverse effects*; Shellfish/analysis*; Snails*
  6. Fadilah N, Hanafiah A, Razlan H, Wong ZQ, Mohamed Rose I, Rahman MM
    Br J Biomed Sci, 2016 Oct;73(4):180-187.
    PMID: 27922429
    BACKGROUND: No gold standard has yet been established for the diagnosis of H. pylori infection. A multiplex polymerase chain reaction (mPCR) was developed in this study for rapid, sensitive and specific detection of H. pylori from gastric biopsies.

    METHODS: H. pylori infections were determined by in-house rapid urease test (iRUT), culture, histology and multiplex PCR.

    RESULTS: A total of 140 (60.9%) from 230 patients were positive for H. pylori infection. H. pylori were detected in 9.6% (22/230), 17% (39/230), 12.6% (29/230) and 60% (138/230) of biopsy specimens by culture, iRUT, histology and mPCR, respectively. mPCR identified H. pylori infection in 100% of biopsies with positive histology and culture. All biopsies with positive iRUT yielded positive PCR except two cases. mPCR also detected H. pylori in additional 116, 101 and 109 biopsies that were negative by culture, iRUT and histology, respectively. Positive samples by mPCR showed lower average in H. pylori density, activity and inflammation scores. The Indians showed the highest prevalence of H. pylori infection compared to the Chinese and the Malays. In addition, Chinese patients with older age were significantly infected compared to other ethnicities.

    CONCLUSION: PCR was able to detect the highest numbers of positive cases although the lowest average scores were recorded in the activity, inflammatory and H. pylori density.

    MeSH terms: Adolescent; Adult; Aged; Aged, 80 and over; Biopsy; DNA, Viral/analysis*; Feasibility Studies; Female; Humans; Male; Middle Aged; RNA, Ribosomal, 16S/genetics; Sensitivity and Specificity; Stomach/microbiology; Stomach/pathology; Urease/metabolism; Reproducibility of Results; Helicobacter pylori/genetics*; Helicobacter pylori/metabolism; Helicobacter pylori/physiology; Helicobacter Infections/diagnosis*; Helicobacter Infections/microbiology; Helicobacter Infections/pathology; Adhesins, Bacterial/genetics; Host-Pathogen Interactions; Young Adult; Multiplex Polymerase Chain Reaction/methods*
  7. Ripple WJ, Chapron G, López-Bao JV, Durant SM, Macdonald DW, Lindsey PA, et al.
    Bioscience, 2016 Oct 01;66(10):807-812.
    PMID: 28533560 DOI: 10.1093/biosci/biw092
  8. Kachuri L, Amos CI, McKay JD, Johansson M, Vineis P, Bueno-de-Mesquita HB, et al.
    Carcinogenesis, 2016 Jan;37(1):96-105.
    PMID: 26590902 DOI: 10.1093/carcin/bgv165
    Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(-9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(-6)), rs112290073 (OR = 1.85, P = 1.27×10(-5)), rs138895564 (OR = 2.16, P = 2.06×10(-5); among young cases, OR = 3.77, P = 8.41×10(-4)). In addition, we found that rs139852726 (P = 1.44×10(-3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(-7)) and lung cancer (P = 2.37×10(-5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism.
    MeSH terms: Chromosome Mapping/methods; Chromosomes, Human, Pair 5*; Female; Humans; Lung Neoplasms/genetics*; Male; Middle Aged; Case-Control Studies; Genetic Predisposition to Disease; Genetic Loci*; Genotyping Techniques/methods
  9. Vilhena-Franco T, Mecawi AS, Elias LL, Antunes-Rodrigues J
    J Endocrinol, 2016 Nov;231(2):167-180.
    PMID: 27613338
    Water deprivation (WD) induces changes in plasma volume and osmolality, which in turn activate several responses, including thirst, the activation of the renin-angiotensin system (RAS) and vasopressin (AVP) and oxytocin (OT) secretion. These systems seem to be influenced by oestradiol, as evidenced by the expression of its receptor in brain areas that control fluid balance. Thus, we investigated the effects of oestradiol treatment on behavioural and neuroendocrine changes of ovariectomized rats in response to WD. We observed that in response to WD, oestradiol treatment attenuated water intake, plasma osmolality and haematocrit but did not change urinary volume or osmolality. Moreover, oestradiol potentiated WD-induced AVP secretion, but did not alter the plasma OT or angiotensin II (Ang II) concentrations. Immunohistochemical data showed that oestradiol potentiated vasopressinergic neuronal activation in the lateral magnocellular PVN (PaLM) and supraoptic (SON) nuclei but did not induce further changes in Fos expression in the median preoptic nucleus (MnPO) or subfornical organ (SFO) or in oxytocinergic neuronal activation in the SON and PVN of WD rats. Regarding mRNA expression, oestradiol increased OT mRNA expression in the SON and PVN under basal conditions and after WD, but did not induce additional changes in the mRNA expression for AVP in the SON or PVN. It also did not affect the mRNA expression of RAS components in the PVN. In conclusion, our results show that oestradiol acts mainly on the vasopressinergic system in response to WD, potentiating vasopressinergic neuronal activation and AVP secretion without altering AVP mRNA expression.
    MeSH terms: Animals; Arginine Vasopressin/analysis; Arginine Vasopressin/secretion; Arginine Vasopressin/agonists; Behavior, Animal/drug effects; Dehydration/physiopathology*; Dehydration/therapy; Vestibular Nucleus, Lateral/drug effects; Vestibular Nucleus, Lateral/metabolism; Vestibular Nucleus, Lateral/pathology; Vestibular Nucleus, Lateral/secretion; Drinking/drug effects; Estradiol/therapeutic use*; Estrogens/therapeutic use*; Female; Fluid Therapy; Gene Expression Regulation/drug effects; Nerve Tissue Proteins/genetics; Nerve Tissue Proteins/metabolism; Nerve Tissue Proteins/secretion; Neurons/drug effects*; Neurons/metabolism; Neurons/pathology; Neurons/secretion; Ovariectomy/adverse effects; Paraventricular Hypothalamic Nucleus/drug effects*; Paraventricular Hypothalamic Nucleus/metabolism; Paraventricular Hypothalamic Nucleus/pathology; Paraventricular Hypothalamic Nucleus/secretion; Preoptic Area/drug effects; Preoptic Area/metabolism; Preoptic Area/pathology; Preoptic Area/secretion; Subfornical Organ/drug effects; Subfornical Organ/metabolism; Subfornical Organ/pathology; Subfornical Organ/secretion; Supraoptic Nucleus/drug effects*; Supraoptic Nucleus/metabolism; Supraoptic Nucleus/pathology; Supraoptic Nucleus/secretion; Water-Electrolyte Imbalance/blood; Water-Electrolyte Imbalance/etiology; Water-Electrolyte Imbalance/physiopathology; Water-Electrolyte Imbalance/prevention & control*; Estrogen Replacement Therapy; Rats, Wistar
  10. Swarna Nantha Y, Abd Patah NA, Ponnusamy Pillai M
    Clin Nutr ESPEN, 2016 Dec;16:42-47.
    PMID: 28531454 DOI: 10.1016/j.clnesp.2016.08.001
    BACKGROUND AND AIMS: Researchers suggest that the rise in obesity rates may be explained by the addictive properties of certain types of food. In view of the growing obesity epidemic in South-East Asia, there is a need for a psychometric tool to assess the concept of food addiction amongst high-risk populations. The objective of this study is to translate the Yale Food Addiction Scale (YFAS) into the Malay language and subsequently validate its use in an obese population.

    METHODS: Between the year 2014 and 2015, a total of 250 obese adults were assessed for food addiction utilizing the Malay version of the YFAS at a primary care clinic. An assessment of the psychometric properties of the scale was performed to determine the factor structure, item statistics and internal consistency of the scale.

    RESULTS: A one factorial structure of YFAS was confirmed in this study through factor analysis. All items except 4 (items 19, 22, 24 and 25) had factor loadings >0.42. The internal reliability (KR-20) coefficient of the one-factor solution was α = 0.76. The mean YFAS symptom count was M = 2.74 (SD = 1.57) with 10.4% (N = 26) of the participants received the diagnosis of food addiction.

    CONCLUSIONS: The determination of construct validity and the identification of other latent variables in the Malay food addiction model is necessary prior to the formal utilization of the scale as a tool to detect addictive eating patterns in the community.
    MeSH terms: Adolescent; Adult; Aged; Ambulatory Care Facilities; Feeding and Eating Disorders/etiology; Feeding and Eating Disorders/psychology; Cross-Sectional Studies; Factor Analysis, Statistical; Feeding Behavior/psychology*; Female; Humans; Malaysia; Male; Middle Aged; Obesity/etiology*; Obesity/psychology; Pilot Projects; Psychiatric Status Rating Scales*; Surveys and Questionnaires; Risk Factors; Translating; Reproducibility of Results; Body Mass Index; Young Adult
  11. Chu WL, Phang SM
    Mar Drugs, 2016 Dec 07;14(12).
    PMID: 27941599 DOI: 10.3390/md14120222
    Obesity is a major epidemic that poses a worldwide threat to human health, as it is also associated with metabolic syndrome, type 2 diabetes and cardiovascular disease. Therapeutic intervention through weight loss drugs, accompanied by diet and exercise, is one of the options for the treatment and management of obesity. However, the only approved anti-obesity drug currently available in the market is orlistat, a synthetic inhibitor of pancreatic lipase. Other anti-obesity drugs are still being evaluated at different stages of clinical trials, while some have been withdrawn due to their severe adverse effects. Thus, there is a need to look for new anti-obesity agents, especially from biological sources. Marine algae, especially seaweeds are a promising source of anti-obesity agents. Four major bioactive compounds from seaweeds which have the potential as anti-obesity agents are fucoxanthin, alginates, fucoidans and phlorotannins. The anti-obesity effects of such compounds are due to several mechanisms, which include the inhibition of lipid absorption and metabolism (e.g., fucoxanthin and fucoidans), effect on satiety feeling (e.g., alginates), and inhibition of adipocyte differentiation (e.g., fucoxanthin). Further studies, especially testing bioactive compounds in long-term human trials are required before any new anti-obesity drugs based on algal products can be developed.
    MeSH terms: Alginates/pharmacology; Alginates/chemistry; Animals; Humans; Obesity/drug therapy*; Polysaccharides/pharmacology; Polysaccharides/chemistry; Seaweed/chemistry*; Anti-Obesity Agents/pharmacology; Anti-Obesity Agents/therapeutic use*; Anti-Obesity Agents/chemistry; Xanthophylls/pharmacology; Xanthophylls/chemistry; Aquatic Organisms/chemistry*
  12. Boo NY
    Malays J Pathol, 2016 Dec;38(3):223-227.
    PMID: 28028291 MyJurnal
    Necrotising enterocolitis (NEC) is the most commonly acquired gastrointestinal disease of neonates, particularly the very preterm (gestation <32 weeks) and/or very low birth weight (<1500g). It is associated with high morbidity and mortality. Despite improvement in neonatal care and increased use of expressed breast milk (EBM), the incidence remains high in many neonatal intensive care units (NICU), and even shows increasing trend in some countries. Numerous studies have pointed to the infective nature of NEC. Some investigators have reported an increase in the incidence of NEC in their NICU when the percentage of infants with pathogens isolated from their gut increased, and decreased when gut colonisation rate was low. Both bacteria and viruses have been reported to be associated with outbreaks of NEC. The majority (>90%) of the NEC cases occurred in neonates on enteral feeding. Studies have shown that milk (whether EBM or formula) fed to neonates was not sterile and were further contaminated during collection, transport, storage and/or feeding. Other investigators have reported a reduction in the incidence of NEC when they improved infection control measures and hygienic procedures in handling milk. It is, therefore, hypothesised that the most common cause of NEC is due to the feeding of neonates, particularly the vulnerable very preterm small neonates, with milk heavily contaminated during collection at source, transport, storage and/or feeding. Because of the immaturity of the immune system of the neonates, excessive inflammatory response to the pathogen load in the gut leads to the pathogenesis of NEC.
    MeSH terms: Animals; Female; Food Contamination; Humans; Infant, Low Birth Weight; Infant, Newborn; Male; Milk, Human/microbiology*; Enterocolitis, Necrotizing/microbiology*; Infant Formula/microbiology*
  13. Pour AM, Masir N, Rose IM
    Malays J Pathol, 2016 Dec;38(3):229-233.
    PMID: 28028292 MyJurnal
    To assess the diagnostic utility of glypican-3 (GPC-3) in comparison to Hep Par 1 in the diagnosis of liver tumours, a cross-sectional study involving 66 resected liver tumours were tested for the protein expression of these markers by immunohistochemistry using monoclonal antibodies. Of the 66 cases, 26 (39.4%) were hepatocellular carcinoma (HCC), 4 (6.1%) were intrahepatic cholangiocarcinoma and 36 (54.5%) were metastatic tumours. Hep Par 1 and GPC-3 expressions in HCC were 24/26 (92.3%) and 19/26 (73.1%) respectively. In contrast, of non-HCC cases, only 2/40 cases (5.0%) expressed Hep Par 1, including a metastatic colorectal adenocarcinoma and a metastatic gastric adenocarcinoma. GPC-3 was expressed in 3/40 cases (7.5%), i.e. a metastatic adenocarcinoma of unknown origin, a metastatic gastric adenocarcinoma and an intrahepatic cholangiocarcinoma. The sensitivity and specificity for Hep Par 1 were 92.3% and 95% respectively while that of GPC-3 was 73.1% and 92.5% respectively. GPC-3 is a useful marker in the diagnosis of HCC. However it is not superior to Hep Par 1 in its sensitivity and specificity. We recommend that it is utilized together with Hep Par 1 as a panel in the diagnosis of HCC.
    MeSH terms: Adenocarcinoma/diagnosis; Adult; Aged; Antigens, Neoplasm/analysis; Antigens, Neoplasm/biosynthesis*; Cross-Sectional Studies; Diagnosis, Differential; Female; Carcinoma, Hepatocellular/diagnosis*; Humans; Immunohistochemistry; Liver Neoplasms/diagnosis*; Male; Middle Aged; Sensitivity and Specificity; Biomarkers, Tumor/analysis; Cholangiocarcinoma/diagnosis; Tissue Array Analysis; Glypicans/analysis; Glypicans/biosynthesis*
  14. Wan Mohd Saman WA, Hassan R, Mohd Yusoff S, Che Yaakob CA, Abdullah NA, Ghazali S, et al.
    Malays J Pathol, 2016 Dec;38(3):235-239.
    PMID: 28028293 MyJurnal
    BACKGROUND: Thalassemia and hemoglobinopathies are inherited red blood cell disorders found worldwide. Hemoglobin (Hb) E disorder is one of the hemoglobinopathies known to have the high prevalence in South East Asia. Most of transfusion-dependent thalassemias were genotypically compound heterozygous Hb E/ β-thalassemia. In Malaysia, the national screening program for thalassemia was implemented for early pregnancy or secondary school girls; however many participants do not turn-up and missed the screening test. Screening for thalassemia using samples from cord blood is an alternative choice as it is a readily available source of blood and hence early detection of the disease. The purpose of this study was to determine the potential use of cord blood for the screening of HbE hemoglobinopathy by using capillary electrophoresis (CE).

    METHODS: Cord blood samples were collected from 300 newborns of healthy mothers. Hematological parameters were determined and hemoglobin quantitation for all cord blood samples were performed using capillary electrophoresis system (CES) and high performance liquid chromatography (HPLC).

    RESULTS: Majority of cord blood samples (63%) revealed Hb AF followed by Hb AFA2 (20%). Hb AFE was detected in 10.7% with the mean value of Hb E ranging from 2.3%-11.1%.

    CONCLUSION: Hemoglobin E was detected in cord blood using capillary electrophoresis system. It can be recommended in areas where Hb E/β is prevalent. Implementation of a screening strategy using CE on cord blood sampling will identify the disease early. With regular follow-up on these patients, the status of their disease can be determined earlier and appropriate management implemented.

    MeSH terms: Chromatography, High Pressure Liquid; Cross-Sectional Studies; Female; Fetal Blood*; Hemoglobinopathies/diagnosis*; Humans; Infant, Newborn; Malaysia; Male; Mass Screening/methods*; Electrophoresis, Capillary
  15. Muhammad Shazwan S, Muhammad Aliff M, Asral Wirda AA, Hayati AR, Maizatul Azma M, Nur Syahrina AR, et al.
    Malays J Pathol, 2016 Dec;38(3):273-283.
    PMID: 28028298 MyJurnal
    INTRODUCTION: Antiphospholipid antibodies (aPL) are autoantibodies that attack phospholipid through anti-beta 2-glycoprotein 1. The actions of aPL are associated with events leading to thrombosis and morbidity in pregnancy. Antiphospholipid syndrome (APS) is diagnosed when a patient is persistently positive for aPL and also has recognised clinical manifestations such as recurrent pregnancy losses, arterial or venous thrombosis and in a catastrophic case, can result in death. Unfortunately, the pathogenesis of APS is still not well established. Recently, microRNA expressed in many types of diseased tissues were claimed to be involved in the pathological progression of diseases and has become a useful biomarker to indicate diseases, including APS.

    OBJECTIVE: This systematic review aims to search for research papers that are focussing on microRNA expression profiles in APS.

    METHOD: Three search engines (Ebcohost, ProQuest and Ovid) were used to identify papers related to expression of specific microRNA in antiphospholipid syndrome.

    RESULTS AND DISCUSSION: A total of 357 papers were found and screened, out of which only one study fulfilled the requirement. In this particular study blood samples from APS patients were tested. The microRNAs found to be related to APS were miR-19b and miR-20a. No data was found on specific microRNA being expressed in obstetric antiphospholipid syndrome. Analysis on the microRNA target genes revealed that most genes targeted by miR-19b and miR-20a involve in TGF-Beta Signalling and VEGF, hypoxia and angiogenesis pathways.

    CONCLUSION: In view of the limited data on the expressions of microRNA in APS we recommend further research into this field. Characterization of microRNA profile in blood as well as in placenta tissue of patients with APS could be useful in identifying microRNAs involved in obstetric APS.
    MeSH terms: Humans; Antiphospholipid Syndrome/genetics*; MicroRNAs/biosynthesis*
  16. Muhammad Aliff M, Muhammad Shazwan S, Nur Fariha MM, Hayati AR, Nur Syahrina AR, Maizatul Azma M, et al.
    Malays J Pathol, 2016 Dec;38(3):285-294.
    PMID: 28028299 MyJurnal
    BACKGROUND: Antiphospholipid syndrome (APS) is a multisystem disease that may present as venous or arterial thrombosis and/or pregnancy complications with the presence of antiphospholipid antibodies. Until today, heterogeneity of pathogenic mechanism fits well with various clinical manifestations. Moreover, previous studies have indicated that genes are differentially expressed between normal and in the disease state. Hence, this study systematically searched the literature on human gene expression that was differentially expressed in Obstetric APS.

    METHODOLOGY: Electronic search was performed until 31st March 2015 through PubMed and Embase databases; where the following Medical Subject Heading (MeSH) terms were used and they had been specified as the primary focus of the articles; gene, antiphospholipid, obstetric, and pregnancy in the title or abstract. From 502 studies retrieved from the search, only original publications that had performed gene expression analyses of human placental tissue that reported on differentially expressed gene in pregnancies with Obstetric APS were included. Two reviewers independently scrutinized the titles and the abstracts before examining the eligibility of studies that met the inclusion criteria. For each study; diagnostic criteria for APS, method for analysis, and the gene signature were extracted independently by two reviewers. The genes listed were further analysed with the DAVID and the KEGG pathways.

    RESULTS: Three eligible gene expression studies involving obstetric APS, comprising the datasets on gene expression, were identified. All three studies showed a reduction in transcript expression on PRL, STAT5, TF, DAF, ABCA1, and HBEGF in Obstetric APS. The high enrichment score for functionality in DAVID had been positive regulation of cell proliferation. Meanwhile, pertaining to the KEGG pathway, two pathways were associated with some of the listed genes, which were ErBb signalling pathway and JAK-STAT signalling pathway.

    CONCLUSION: Ultimately, studies on a genetic level have the potential to provide new insights into the regulation and to widen the basis for identification of changes in the mechanism of Obstetric APS.
    MeSH terms: Female; Humans; Pregnancy; Pregnancy Complications/genetics*; Pregnancy Complications/immunology*; Antiphospholipid Syndrome/genetics*; Transcriptome/genetics*
  17. Habib A, Azize NA, Yakob Y, Md Yunus Z, Wee TK
    Malays J Pathol, 2016 Dec;38(3):305-310.
    PMID: 28028301 MyJurnal
    Lysinuric protein intolerance (LPI) is an inborn error of dibasic amino acid transport due to a defect in the dibasic amino acid transporter in the renal and intestine and has a heterogenous presentation. Three Malaysian patients with LPI were studied and their biochemical and molecular findings compared. There were differences and similarities in the biochemical and molecular findings. Molecular analysis of SLC7A7 gene revealed a novel mutation c.235G>A; p.(Gly79Arg) in exon three in Patient 1 and a mutation c.1417C>T; p.(Arg473*) in exon 10 in patient 2 and 3. The degree of concentration of dibasic amino acids may determine the type of disease of the cell membrane transport, however, a positive molecular confirmation will secure the diagnosis.
    MeSH terms: Amino Acid Metabolism, Inborn Errors/genetics*; Child, Preschool; DNA Mutational Analysis; Female; Humans; Infant; Malaysia; Male; Mutation; Polymerase Chain Reaction; Antigens, CD98 Light Chains/genetics*
  18. Tang YL, Chia WK, Yap EC, Julia MI, Leong CF, Salwati S, et al.
    Malays J Pathol, 2016 Dec;38(3):315-319.
    PMID: 28028303 MyJurnal
    INTRODUCTION: Individuals who are exposed to cytotoxic agents are at risk of developing therapyrelated myeloid neoplasms (t-MN). Cytogenetic findings of a neoplasm play an important role in stratifying patients into different risk groups and thus predict the response to treatment and overall survival.

    CASE REPORT: A 59-year-old man was diagnosed with acute promyelocytic leukaemia. Following this, he underwent all-trans retinoic acid (ATRA) based chemotherapy and achieved remission. Four years later, the disease relapsed and he was given idarubicin, mitoxantrone and ATRA followed by maintenance chemotherapy (ATRA, mercaptopurine and methotrexate). He achieved a second remission for the next 11 years. During a follow-up later, his full blood picture showed leucocytosis, anaemia and leucoerythroblastic picture. Bone marrow examination showed hypercellular marrow with trilineage dysplasia, 3% blasts but no abnormal promyelocyte. Fluorescence in-situ hybridisation (FISH) study of the PML/RARA gene was negative. Karyotyping result revealed complex abnormalities and monosomal karyotype (MK). A diagnosis of therapy-related myelodysplastic syndrome/myeloproliferative neoplasm with unfavourable karyotypes and MK was made. The disease progressed rapidly and transformed into therapy-related acute myeloid leukaemia in less than four months, complicated with severe pneumonia. Despite aggressive treatment with antibiotics and chemotherapy, the patient succumbed to the illness two weeks after the diagnosis.

    DISCUSSION AND CONCLUSION: Diagnosis of t-MN should be suspected in patients with a history of receiving cytotoxic agents. Karyotyping analysis is crucial for risk stratification as MK in addition to complex aberrant karyotypes predicts unfavourable outcome. Further studies are required to address the optimal management for patients with t-MN.

    MeSH terms: Antineoplastic Combined Chemotherapy Protocols/adverse effects*; Humans; Karyotyping; Male; Methotrexate/administration & dosage; Methotrexate/adverse effects; Middle Aged; Mitoxantrone/administration & dosage; Mitoxantrone/adverse effects; Neoplasm Recurrence, Local/drug therapy; Tretinoin/administration & dosage; Tretinoin/adverse effects; 6-Mercaptopurine/administration & dosage; 6-Mercaptopurine/adverse effects; Idarubicin/administration & dosage; Idarubicin/adverse effects; Leukemia, Myeloid, Acute/genetics*; Leukemia, Promyelocytic, Acute/drug therapy*; Neoplasms, Second Primary/genetics*; In Situ Hybridization, Fluorescence; Abnormal Karyotype
  19. Mohd Nazri H, Suhair AA, Wan Suriana WA, Zefarina Z, Azlan H, Wan Zaidah A
    Malays J Pathol, 2016 Dec;38(3):327-331.
    PMID: 28028305 MyJurnal
    Factor X (FX) deficiency is a rare autosomal recessive congenital bleeding disorder. The clinical presentation is among the most severe among the rare coagulation defects. Thus, majority of diagnosed patients will receive factor replacement therapy before surgical manipulation. However, the diagnosis of FX deficiency may be overlooked because it is a rare entity. This is a case report of a 15-year-old male patient who was diagnosed with FX deficiency after developing post-operative complications. With regular fresh frozen plasma infusion given, the patient responded well and recovered. However, had he been diagnosed earlier pre-operatively, the post-operative complication could have been prevented. Therefore, pre-operative coagulation screening should be performed in patients with significant bleeding history in both emergency and elective situations to prevent surgical morbidity related to post-operative bleeding.
    MeSH terms: Adolescent; Appendectomy; Factor X Deficiency/complications*; Hemorrhage/etiology; Humans; Male; Postoperative Complications/blood*
  20. Isa, N. M., Mohamad Rushdi, R.A., A. Sadikin, Basharie, S.M.
    MyJurnal
    A method based on Computational Fluids Dynamics (CFD) was used to analyse the flow
    behaviour in the Biodiesel reactor with 6-blade at 45° pitch blade turbines. The study, which was based
    on the turbulent flow, had been associated with three sizes of the blades installed in the reactor by using
    the standard k-ε turbulence model. The study also included the pitch blade turbines that were installed
    at three clearances from the bottom in the reactor by using the standard k-ε turbulence model. The
    results showed that the flow behaviours differed for the three various locations, which were installed at
    C=T/4, C=T/2, and C=3T/4 for D=T/3. The results also showed that the flow behaviour had been
    different for the three impeller diameters installed at C=T/4. Besides, good quantitative agreement for
    velocity distribution was obtained. Good velocity distribution in the reactor was produced by D=T/3.
    Moreover, a comparison between the three impeller diameters in terms of velocity distribution
    suggested that the discharge flow from the smaller impeller had stronger axial flow during the mixing
    process.
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