Browse publications by year: 2017

  1. Usman MM, Ismail S, Teoh TC
    Cent Eur J Immunol, 2017;42(2):196-204.
    PMID: 28867962 DOI: 10.5114/ceji.2017.69362
    One of the aims of the World Health Organisation (WHO) Millennium Development Goals (MDG) is to reduce the number of cases of tuberculosis (TB) infection by the year 2015. However, 9 million new cases were reported in 2013, with an estimated 480,000 new cases of multi-drug resistant tuberculosis (MDR-TB) globally. Bacille Calmette-Guérin (BCG) is the most available and currently used candidate vaccine against tuberculosis; it prevents childhood TB, but its effectiveness against pulmonary TB in adults and adolescents is disputed. To achieve the goal of the WHO MDG, the need for a new improved vaccine is of primary importance. This review highlights several articles that have reported vaccine development. There are about 16 TB vaccines in different phases of clinical trials at the time of writing, which include recombinant peptide/protein, live-attenuated and recombinant live-attenuated, protein/adjuvant, viral-vectored, and immunotherapeutic vaccine. Further studies in reverse vaccinology and massive campaigns on vaccination are needed in order to achieve the target for TB eradication by 2050.
  2. Mandala S, Di TC
    J Med Biol Eng, 2017;37(4):441-453.
    PMID: 28867990 DOI: 10.1007/s40846-017-0281-x
    Many studies showed electrocardiogram (ECG) parameters are useful for predicting fatal ventricular arrhythmias (VAs). However, the studies have several shortcomings. Firstly, all studies lack of effective way to present behavior of various ECG parameters prior to the occurrence of the VAs. Secondly, they also lack of discussion on how to consider the parameters as abnormal. Thirdly, the reports do not include approaches to increase the detection accuracy for the abnormal patterns. The purpose of this study is to address the aforementioned issues. It identifies ten ECG parameters from various sources and then presents a review based on the identified parameters. From the review, it has been found that the increased risk of VAs can be represented by presence and certain abnormal range of the parameters. The variation of parameters range could be influenced by either gender or age. This study also has discovered the facts that averaging, outliers elimination and morphology detection algorithms can contribute to the detection accuracy.
    MeSH terms: Algorithms; Arrhythmias, Cardiac; Electrocardiography
  3. Hassan Z, Bosch OG, Singh D, Narayanan S, Kasinather BV, Seifritz E, et al.
    Front Psychiatry, 2017;8:152.
    PMID: 28868040 DOI: 10.3389/fpsyt.2017.00152
    A feature of human culture is that we can learn to consume chemical compounds, derived from natural plants or synthetic fabrication, for their psychoactive effects. These drugs change the mental state and/or the behavioral performance of an individual and can be instrumentalized for various purposes. After the emergence of a novel psychoactive substance (NPS) and a period of experimental consumption, personal and medical benefits and harm potential of the NPS can be estimated on evidence base. This may lead to a legal classification of the NPS, which may range from limited medical use, controlled availability up to a complete ban of the drug form publically accepted use. With these measures, however, a drug does not disappear, but frequently continues to be used, which eventually allows an even better estimate of the drug's properties. Thus, only in rare cases, there is a final verdict that is no more questioned. Instead, the view on a drug can change from tolerable to harmful but may also involve the new establishment of a desired medical application to a previously harmful drug. Here, we provide a summary review on a number of NPS for which the neuropharmacological evaluation has made important progress in recent years. They include mitragynine ("Kratom"), synthetic cannabinoids (e.g., "Spice"), dimethyltryptamine and novel serotonergic hallucinogens, the cathinones mephedrone and methylone, ketamine and novel dissociative drugs, γ-hydroxybutyrate, γ-butyrolactone, and 1,4-butanediol. This review shows not only emerging harm potentials but also some potential medical applications.
    MeSH terms: Butylene Glycols; Cannabinoids; N,N-Dimethyltryptamine; Hallucinogens; Humans; Ketamine; Methamphetamine; Sodium Oxybate; 4-Butyrolactone; Mitragyna; Secologanin Tryptamine Alkaloids
  4. Tiong KI, Mohd Zahidin AZ, Sumugam SKA, Uchang J, Mohd Isa HD
    Asia Pac J Ophthalmol (Phila), 2017;6(5):403-406.
    PMID: 28868833 DOI: 10.22608/APO.2017134
    PURPOSE: To compare the interleukin-17 (IL-17) and interleukin-23 (IL-23) positive cell counts between pterygium and normal conjunctiva.

    DESIGN: A case-control study.

    METHODS: This study received ethical approval (NMRR Research ID 23957) and informed consent was obtained from all participants. It involved 20 participants with 20 samples of pterygium and 20 samples of normal conjunctiva that were obtained from the same eye of each participant. All the participants underwent history taking, slit lamp examination, and pterygium excision surgery. Both samples underwent immunohistochemistry procedure. Pretreatment procedure was conducted using heat-induced epitope retrieval with PT link, subsequently followed by EnVision FLEX staining procedure and incubation with anti‒IL-17 antibody and anti‒IL-23 antibody. Slides were examined in high-power fields (400x) for both samples in 3 different fields. Total positive stained cell counts in all 3 fields with IL-17 and IL-23 between pterygium and normal conjunctiva were analyzed by using Wilcoxon signed rank test.

    RESULTS: IL-17 positive cell counts for normal conjunctiva showed mean 196.10 ± 80.487 but for pterygium was 331.10 ± 108.416. As for IL-23, the mean for positive cell counts for normal conjunctiva was 62.10 ± 33.462 and IL-23 positive cell counts for pterygium showed mean 102.95 ± 41.378. Both IL-17 and IL-23 were significantly increased in pterygium compared with normal conjunctiva (P < 0.001).

    CONCLUSIONS: Both IL-17 and IL-23 were found to be significantly higher in the pterygium group than in the normal conjunctiva group with P < 0.001 by Wilcoxon signed rank test.

    MeSH terms: Adult; Aged; Conjunctiva/metabolism*; Female; Humans; Immunohistochemistry; Male; Middle Aged; Pterygium/metabolism*; Biomarkers/metabolism; Case-Control Studies; Interleukin-17/metabolism*; Interleukin-23/metabolism*
  5. Higuchi A, Ku NJ, Tseng YC, Pan CH, Li HF, Kumar SS, et al.
    Lab Invest, 2017 Oct;97(10):1167-1179.
    PMID: 28869589 DOI: 10.1038/labinvest.2017.100
    Cardiovascular disease remains the leading cause of death and disability in advanced countries. Stem cell transplantation has emerged as a promising therapeutic strategy for acute and chronic ischemic cardiomyopathy. The current status of stem cell therapies for patients with myocardial infarction is discussed from a bioengineering and biomaterial perspective in this review. We describe (a) the current status of clinical trials of human pluripotent stem cells (hPSCs) compared with clinical trials of human adult or fetal stem cells, (b) the gap between fundamental research and application of human stem cells, (c) the use of biomaterials in clinical and pre-clinical studies of stem cells, and finally (d) trends in bioengineering to promote stem cell therapies for patients with myocardial infarction. We explain why the number of clinical trials using hPSCs is so limited compared with clinical trials using human adult and fetal stem cells such as bone marrow-derived stem cells.
    MeSH terms: Animals; Biocompatible Materials; Clinical Trials as Topic*; Humans; Myocardial Infarction/therapy*; Stem Cell Transplantation*; Pluripotent Stem Cells/cytology; Pluripotent Stem Cells/transplantation; Mice; Stem Cell Research
  6. Mawang CI, Lim YY, Ong KS, Muhamad A, Lee SM
    J Appl Microbiol, 2017 Nov;123(5):1148-1159.
    PMID: 28869803 DOI: 10.1111/jam.13578
    AIMS: The potential of Dicranopteris linearis leaves' extract and its bioactive components were investigated for the first time for its disrupting ability against Staphylococcus aureus biofilms.

    METHODS AND RESULTS: The leaves of D. linearis were subjected to sonication-assisted extraction using hexane (HEX), dichloromethane, ethyl acetate and methanol (MeOH). It was found that only the MeOH fraction exhibited antimicrobial activity using broth microdilution assay; while all four fractions do not exhibit biofilm inhibition activity against S. aureusATCC 6538P, S. aureusATCC 43300, S. aureusATCC 33591 and S. aureusATCC 29213 using crystal violet assay. Among the four fractions tested, only the HEX fraction showed biofilm disrupting ability, with 60-90% disruption activity at 5 mg ml-1against all four S. aureus strains tested. Bioassay-guided purification of the active fraction has led to the isolation of α-tocopherol. α-Tocopherol does not affect the cells within the biofilms but instead affects the biofilm matrix in order to disrupt S. aureus biofilms.

    CONCLUSIONS: α-Tocopherol was identified to be the bioactive component of D. linearis with disruption activity against S. aureus biofilm matrix.

    SIGNIFICANCE AND IMPACT OF THE STUDY: The use of α-tocopherol as a biofilm disruptive agent might potentially be useful to treat biofilm-associated infections in the future.

    MeSH terms: Anti-Bacterial Agents/isolation & purification; Anti-Bacterial Agents/pharmacology*; Anti-Bacterial Agents/chemistry; Humans; Plant Extracts/isolation & purification; Plant Extracts/pharmacology*; Plant Extracts/chemistry; Staphylococcal Infections/microbiology; Staphylococcus aureus/drug effects*; Staphylococcus aureus/physiology; Biofilms/drug effects*; Plant Leaves/chemistry; alpha-Tocopherol/isolation & purification; alpha-Tocopherol/pharmacology*; alpha-Tocopherol/chemistry; Ferns/chemistry*
  7. Man F, Choo CY
    PMID: 28869873 DOI: 10.1016/j.jchromb.2017.08.037
    Bruceines D and E are quassinoids from seeds of Brucea javanica (L.) Merr. exhibiting hypoglycemia effect. The crude drug is used as a traditional medicine by diabetes patients. The aim of this study is to understand the bioavailability and pharmacokinetics of both the bruceines D & E. A rapid and sensitive HPLC-MS/MS method was developed and validated for the quantification of both quassinoids, bruceines D & E in rat plasma. Both the bruceines D & E were separated with the Zorbax SBC-18 column with gradient elution and mobile phase system of acetonitrile and deionized water with 0.1% formic acid at a flow rate of 0.5mL/min. Analytes were detected in multiple reaction monitoring (MRM) mode with electrospray positive ionization. The quassinoids, namely bruceines D & E were detected with transitions of m/z 411.2→393.2 and m/z 395.2→377.2, respectively. Another quassinoid, eurycomanone was used as the internal standard with transition of m/z 409.2→391.2. The method was validated and conformed to the regulatory requirements. The validated method was applied to pharmacokinetic and bioavailability studies in rats. The pharmacokinetic study indicated both bruceine D and E were rapidly absorbed into the circulation system and reached its peak concentration at 0.54±0.34h and 0.66±0.30h, respectively. Bruceine E was eliminated slower than Bruceine D with t1/2 value almost increased two-fold compared to Bruceine D. In conclusion, a rapid, selective and sensitive HPLC-MS/MS method was developed for the simultaneous determination of both the bruceines D and E in rat plasma. Both bruceines D and E displayed poor oral bioavailability.
    MeSH terms: Animals; Chromatography, High Pressure Liquid/methods*; Drug Stability; Male; Sensitivity and Specificity; Reproducibility of Results; Linear Models; Rats, Sprague-Dawley; Quassins/administration & dosage; Quassins/blood*; Quassins/pharmacokinetics*; Quassins/chemistry; Rats; Tandem Mass Spectrometry/methods*
  8. Acharya UR, Oh SL, Hagiwara Y, Tan JH, Adam M, Gertych A, et al.
    Comput Biol Med, 2017 10 01;89:389-396.
    PMID: 28869899 DOI: 10.1016/j.compbiomed.2017.08.022
    The electrocardiogram (ECG) is a standard test used to monitor the activity of the heart. Many cardiac abnormalities will be manifested in the ECG including arrhythmia which is a general term that refers to an abnormal heart rhythm. The basis of arrhythmia diagnosis is the identification of normal versus abnormal individual heart beats, and their correct classification into different diagnoses, based on ECG morphology. Heartbeats can be sub-divided into five categories namely non-ectopic, supraventricular ectopic, ventricular ectopic, fusion, and unknown beats. It is challenging and time-consuming to distinguish these heartbeats on ECG as these signals are typically corrupted by noise. We developed a 9-layer deep convolutional neural network (CNN) to automatically identify 5 different categories of heartbeats in ECG signals. Our experiment was conducted in original and noise attenuated sets of ECG signals derived from a publicly available database. This set was artificially augmented to even out the number of instances the 5 classes of heartbeats and filtered to remove high-frequency noise. The CNN was trained using the augmented data and achieved an accuracy of 94.03% and 93.47% in the diagnostic classification of heartbeats in original and noise free ECGs, respectively. When the CNN was trained with highly imbalanced data (original dataset), the accuracy of the CNN reduced to 89.07%% and 89.3% in noisy and noise-free ECGs. When properly trained, the proposed CNN model can serve as a tool for screening of ECG to quickly identify different types and frequency of arrhythmic heartbeats.
    MeSH terms: Arrhythmias, Cardiac/diagnosis; Arrhythmias, Cardiac/physiopathology*; Electrocardiography*; Female; Heart Rate*; Humans; Male; Models, Cardiovascular*; Myocardial Contraction*; Signal Processing, Computer-Assisted*; Databases, Factual*; Neural Networks (Computer)*
  9. Jasni MJF, Arulkumar M, Sathishkumar P, Mohd Yusoff AR, Buang NA, Gu FL
    J Colloid Interface Sci, 2017 Dec 15;508:591-602.
    PMID: 28869916 DOI: 10.1016/j.jcis.2017.08.075
    Bisphenol A (BPA) is highly considered as an emerging contaminants (ECs) due to their endocrine disrupting and reproductive toxicant nature. It has been detected in drinking water sources in many countries. This study deals with the adsorptive removal of BPA using nylon 6,6 nanofibrous membrane (NNM) fabricated by electrospinning technique. Langmuir and Freundlich isotherm models (R2=0.99) were obeyed for BPA adsorption, which indicates the monolayer adsorption of BPA and also surface heterogeneity of NNM. The adsorption kinetics of BPA was followed pseudo second order rate (R2=0.89-0.99), which suggests the occurrence of rapid adsorption rate through interaction of surface functional groups present in NNM. The maximum adsorption of BPA (91.3mgg-1) was attained at 30°C. The hydroxyl groups of BPA form hydrogen bonding with carbonyl groups of NNM during the adsorptive removal process. Reusability study confirmed a much better stability of NNM in the recyclic application. Finally, this study suggests that NNM might be an outstanding nano-adsorbent for the emerging contaminants removal, including BPA from drinking water sources.
  10. Roohinejad S, Koubaa M, Barba FJ, Saljoughian S, Amid M, Greiner R
    Food Res Int, 2017 09;99(Pt 3):1066-1083.
    PMID: 28865618 DOI: 10.1016/j.foodres.2016.08.016
    Edible seaweeds are a good source of antioxidants, dietary fibers, essential amino acids, vitamins, phytochemicals, polyunsaturated fatty acids, and minerals. Many studies have evaluated the gelling, thickening and therapeutic properties of seaweeds when they are used individually. This review gives an overview on the nutritional, textural, sensorial, and health-related properties of food products enriched with seaweeds and seaweed extracts. The effect of seaweed incorporation on properties of meat, fish, bakery, and other food products were highlighted in depth. Moreover, the positive effects of foods enriched with seaweeds and seaweed extracts on different lifestyle diseases such as obesity, dyslipidemia, hypertension, and diabetes were also discussed. The results of the studies demonstrated that the addition of seaweeds, in powder or extract form, can improve the nutritional and textural properties of food products. Additionally, low-fat products with less calories and less saturated fatty acids can be prepared using seaweeds. Moreover, the addition of seaweeds also affected the health properties of food products. The results of these studies demonstrated that the health value, shelf-life and overall quality of foods can be improved through the addition of either seaweeds or seaweed extracts.
    MeSH terms: Animals; Anti-Infective Agents/isolation & purification; Anti-Infective Agents/pharmacology; Antioxidants/isolation & purification; Antioxidants/pharmacology; Colloids/isolation & purification; Colloids/pharmacology; Food Preservation/methods*; Food Preservatives/isolation & purification; Food Preservatives/pharmacology*; Humans; Nutritive Value; Seaweed/chemistry*; Time Factors; Diet, Fat-Restricted; Dietary Supplements*; Plant Preparations/isolation & purification; Plant Preparations/pharmacology*; Caloric Restriction; Food Storage/methods*; Healthy Diet*
  11. Shang X, Peng Z, Ye Y, Asan, Zhang X, Chen Y, et al.
    EBioMedicine, 2017 Sep;23:150-159.
    PMID: 28865746 DOI: 10.1016/j.ebiom.2017.08.015
    Hemoglobinopathies are among the most common autosomal-recessive disorders worldwide. A comprehensive next-generation sequencing (NGS) test would greatly facilitate screening and diagnosis of these disorders. An NGS panel targeting the coding regions of hemoglobin genes and four modifier genes was designed. We validated the assay by using 2522 subjects affected with hemoglobinopathies and applied it to carrier testing in a cohort of 10,111 couples who were also screened through traditional methods. In the clinical genotyping analysis of 1182 β-thalassemia subjects, we identified a group of additional variants that can be used for accurate diagnosis. In the molecular screening analysis of the 10,111 couples, we detected 4180 individuals in total who carried 4840 mutant alleles, and identified 186 couples at risk of having affected offspring. 12.1% of the pathogenic or likely pathogenic variants identified by our NGS assay, which were undetectable by traditional methods. Compared with the traditional methods, our assay identified an additional at-risk 35 couples. We describe a comprehensive NGS-based test that offers advantages over the traditional screening/molecular testing methods. To our knowledge, this is among the first large-scale population study to systematically evaluate the application of an NGS technique in carrier screening and molecular diagnosis of hemoglobinopathies.
    MeSH terms: Adolescent; Adult; China/epidemiology; Erythrocyte Indices; Genotype; Hemoglobinopathies/diagnosis*; Hemoglobinopathies/genetics*; Hemoglobinopathies/epidemiology; Hemoglobins, Abnormal/genetics; Heterozygote Detection; Humans; Middle Aged; Phenotype; Population Surveillance; Sensitivity and Specificity; Severity of Illness Index; Genetic Variation; Reproducibility of Results; Prevalence; Case-Control Studies; Genetic Predisposition to Disease*; Polymorphism, Single Nucleotide; Young Adult; Genotyping Techniques*; Geography, Medical
  12. Vignesh R, Shankar EM
    EBioMedicine, 2017 Oct;24:20-21.
    PMID: 28865747 DOI: 10.1016/j.ebiom.2017.08.025
    MeSH terms: Humans; Immunosuppressive Agents/pharmacology*; Thalidomide/pharmacology*; Virus Activation/drug effects*; Virus Activation/immunology; CD4-Positive T-Lymphocytes/drug effects; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/metabolism; CD4-Positive T-Lymphocytes/virology; HIV-1/drug effects*; HIV-1/physiology*; HIV Infections/immunology; HIV Infections/metabolism; HIV Infections/virology*; Virus Latency/drug effects*; Virus Latency/immunology; Immunomodulation/drug effects
  13. Adiana G, Juahir H, Joseph B, Shazili NAM
    Mar Pollut Bull, 2017 Oct 15;123(1-2):232-240.
    PMID: 28865793 DOI: 10.1016/j.marpolbul.2017.08.055
    The present study aims to define the possible sources that contribute to the level of Pb into the Brunei Bay, Borneo. The cluster analysis has classified the bay into the northern part with heavy and agriculture-related industries; the southern area with a moderate rural human settlement as well as the southwestern area with a more pristine environment and a low level of human settlement. The score plot of spatial discriminant analysis verified a significant influence of the river system toward the estuary, whereas the temporal discriminant analysis has discriminated the seasonal changes. In comparison to elsewhere, the stable Pb isotopic ratios in Brunei Bay showed a fingerprint similar to coal-related sources and of aerosol input. Briefly, even though Pb in the Brunei Bay ecosystem proved to be at a low level, the stable Pb isotopic ratios showed that human and industrial activities are slowly contributing Pb into the bay ecosystem.
    MeSH terms: Borneo; Environmental Monitoring/methods; Industry; Isotopes/analysis; Lead/analysis*; Mass Spectrometry/methods; Water Pollutants, Chemical/analysis*; Geologic Sediments/chemistry; Rivers; Bays/chemistry; Estuaries
  14. Dieng H, Satho T, Suradi NFB, Hakim H, Abang F, Aliasan NE, et al.
    Acta Trop, 2017 Dec;176:446-454.
    PMID: 28865898 DOI: 10.1016/j.actatropica.2017.08.033
    In dengue vector control, attempts to minimize or replace the use of pesticides have mostly involved use of predators, but success has been severely impeded by difficulties associated with financial and environmental costs, predator mass production, and persistence in target habitats. Visual deterrents have been used successfully to control animal pests, in some cases in an effort to replace pesticide use. Despite evidence that visual signals are crucial in site choice for egg deposition by dengue vectors, and that female mosquitoes respond to artificial predation, the role of predator intimidation as it affects the oviposition behavior of dengue vectors remains largely unexplored. Here, we examined the oviposition responses of Aedes aegypti exposed to various mosquito predator pictures. Gravid females were presented with equal opportunities to oviposit in two cups with predator images [Toxorhynchites splendens-TXI, Goldfish (Carassius auratus)-small (SFI) and large (LFI) and Tx. splendens+Goldfish-TXFI] and two others without pictures. Differences in egg deposition were examined between sites with and without these images. When given a chance to oviposit in cups with and without TXI, Ae. aegypti females were similarly attracted to both sites. When provided an opportunity to oviposit in cups displaying pictures of fish (SFI or LFI) and blank cups, egg deposition rates were much lower in the fish picture sites. Females showed a preference for blank cups over TXFI for egg deposition. They also equally avoided cups with pictures of fish, regardless of the size of the picture. Our results indicate that the presence of images of goldfish and their association with Tx. larvae significantly reduced egg deposition by Ae. aegypti, and this was not the case with the predatory larvae alone. The observations that the images of natural predators can repel gravid females of a dengue vector provide novel possibilities to develop effective and inexpensive alternative tools to harmful insecticides.
    MeSH terms: Aedes/physiology*; Animals; Behavior, Animal; Breeding; Dengue/prevention & control*; Dengue/transmission; Female; Goldfish; Larva; Oviposition*; Photic Stimulation; Visual Perception*; Ecosystem; Mosquito Vectors/physiology*
  15. Benelli G, Maggi F, Romano D, Stefanini C, Vaseeharan B, Kumar S, et al.
    Ticks Tick Borne Dis, 2017 10;8(6):821-826.
    PMID: 28865955 DOI: 10.1016/j.ttbdis.2017.08.004
    Ticks serve as vectors of a wide range of infectious agents deleterious to humans and animals. Tick bite prevention is based to a large extent on the use of chemical repellents and acaricides. However, development of resistance in targeted ticks, environmental pollution, and contamination of livestock meat and milk are major concerns. Recently, metal, metal oxide and carbon nanoparticles, particularly those obtained through green fabrication routes, were found to be highly effective against a wide array of arthropod pests and vectors. We summarize current knowledge on the toxicity of nanoparticles against tick vectors of medical and veterinary importance. We also discuss the toxicity of products from botanical- and bacterial-based as well as classic chemical nanosynthesis routes, showing differences in bioactivity against ticks based on the products used for the fabrication of nanoparticles. Further research is needed, to validate the efficacy of nanoparticle-based acaricides in the field and clarify mechanisms of action of nanoparticles against ticks. From a technical point of view, the literature analyzed here showed little standardization of size and weight of tested ticks, a lack of uniform methods to assess toxicity and concerns related to data analysis. Finally, an important challenge for future research is the need for ecotoxicology studies to evaluate potential negative effects on non-target organisms and site contamination arising from nanoparticle-based treatments in close proximity of livestock and farmers.
    MeSH terms: Animals; Arachnid Vectors/drug effects*; Oxides/pharmacology; Tick Control/instrumentation; Tick Control/methods*; Ixodidae/drug effects*; Metal Nanoparticles*; Acaricides/pharmacology*
  16. Taha A, Akram M, Jawad Z, Alshemary AZ, Hussain R
    Mater Sci Eng C Mater Biol Appl, 2017 Nov 01;80:93-101.
    PMID: 28866230 DOI: 10.1016/j.msec.2017.05.117
    Microwave assisted wet precipitation method was used to synthesize calcium deficient strontium doped β-tricalcium phosphate (Sr-βTCP) with a chemical formula of Ca2.96-xSrx(PO4)2. Sr-βTCP was reacted with monocalcium phosphate monohydrate [Ca(H2PO4)2.H2O, MCPM] in presence of water to furnish corresponding Sr containing brushite cement (Sr-Brc). The samples were characterized by using X-ray diffractometry (XRD), Fourier transform infrared spectroscopy (FTIR) and field emission scanning electron microscopy (FESEM). Strontium content in the prepared samples was determined by using inductively coupled plasma optical emission spectrometry (ICP-OES). The effect of Sr2+ions on the structural, mechanical, setting properties and drug release of the cement is reported. Incorporation of Sr2+ions improved the injectability, setting time and mechanical properties of the Brc. The release profiles of antibiotics incorporated in Brc and Sr-Brc confirmed that the Sr incorporation into the Brc results in the efficient release of the antibiotics from the cement.
    MeSH terms: Bone Cements*; Calcium Phosphates; Strontium; X-Ray Diffraction
  17. Ali EZ, Yakob Y, Md Desa N, Ishak T, Zakaria Z, Ngu LK, et al.
    Malays J Pathol, 2017 08;39(2):99-106.
    PMID: 28866690 MyJurnal
    Fragile X syndrome (FXS) is a neurodevelopmental disorder commonly found worldwide, caused by the silencing of fragile X mental retardation 1 (FMR1) gene on the X-chromosome. Most of the patients lost FMR1 function due to an expansion of cytosine-guanine-guanine (CGG) repeat at the 5' untranslated region (5'UTR) of the gene. The purpose of this study is to identify the prevalence of FXS and characterize the FMR1 gene CGG repeats distribution among children with developmental disability in Malaysia. Genomic DNA of 2201 samples from different ethnicities (Malays, Chinese, Indian and others) of both genders were PCR-amplified from peripheral blood leukocytes based on specific primers at 5'UTR of FMR1 gene. Full mutations and mosaics were successfully identified by triple methylation specific PCR (ms-PCR) and subsequently verified with FragilEase kit. The findings revealed for the first time the prevalence of FXS full mutation in children with developmental disability in Malaysia was 3.5%, a slightly higher figure as compared to other countries. Molecular investigation also identified 0.2% and 0.4% probands have permutation and intermediate alleles, respectively. The CGG repeats length observation showed 95% of patients had normal alleles within 11 to 44 CGG repeats; with 29 repeats found most common among Malays and Indians while 28 repeats were most common among Chinese. In conclusion, this is the first report of prevalence and characterisation of CGG repeats that reflects genetic variability among Malaysian ethnic grouping.
    MeSH terms: Alleles; Child; Developmental Disabilities; Chromosomes; Cytosine; DNA; Fragile X Syndrome; Guanine; Humans; Leukocytes; Malaysia; Intellectual Disability; Methylation; Mutation; Prevalence; Polymerase Chain Reaction; DNA Primers; 5' Untranslated Regions; Genomics
  18. Yap E, Tumian NR, Azma RZ, Sharifah NA, Salwati S, Hamidah NH, et al.
    Malays J Pathol, 2017 Aug;39(2):107-113.
    PMID: 28866691 MyJurnal
    Clinical resistance to imatinib (IM) in chronic myeloid leukemia (CML) carries adverse consequences. We investigated 22 CML patients who developed IM-resistance for BCR-ABL kinase domain (KD) mutations. The median follow-up for this study was 101.9 months (range: 22.2 to 176.5 months) and the estimated mean overall survival was 150.87 months (95% CI: 130.0 to 171.0). Five out of 22 patients tested positive for BCR-ABL KD mutations: 2 had T315I, 2 had E255K and 1 had V289F mutations. Of the remaining 17 patients who did not harbor BCR-ABL KD mutations, 11 patients received nilotinib while the rest continued on IM. All 17 achieved haematological remission but only 5 patients achieved complete cytogenetic remission, 4 of whom did so after switching to nilotinib. Our study shows that most of our IM-resistant patients do not test positive for BCR-ABL KD mutations by available testing methods and the role of second generation tyrosine kinase inhibitors remains undetermined. A critical analysis of the BCR-ABL KD mutations and the underlying mechanisms/ pathways of BCR-ABL independent IM-resistance along with potential treatments in the horizon will be discussed.
    MeSH terms: Imatinib Mesylate; Follow-Up Studies; Humans; Mutation; Pyrimidines; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Fusion Proteins, bcr-abl
  19. Mohd-Zain Z, Mohd-Nawi SFA, Adnan A, Kumar S
    Malays J Pathol, 2017 Aug;39(2):115-122.
    PMID: 28866692 MyJurnal
    BACKGROUND: HIV-infected patients pose a high risk of contracting skin and soft tissue infections caused by Staphylococcus aureus. Those who are colonized with methicillin-resistant S. aureus (MRSA) that carry Panton-Valentine leukocidin (PVL) are predisposed to severe infections that could lead to necrotic skin infections. However the association of S. aureus specifically methicillin sensitive S. aureus carrying PVL gene in HIV patients has not been widely reported. Here, we study the prevalence and the molecular epidemiology of PVL-producing S. aureus in HIV-infected patients.

    METHODS: Swabs from four body sites of 129 HIV-infected patients were cultured for S. aureus and identified by standard microbiological procedures. The isolates were subjected to antimicrobial susceptibility testing by disk diffusion against penicillin, erythromycin, clindamycin, and cotrimoxazole. PCR was used to detect the PVL gene and genetic relationship between the isolates was determined by using pulse field gel electrophoresis.

    RESULTS: A total of 51 isolates of S. aureus were obtained from 40 (31%) of the patients. The majority (43.1%) of the isolates were obtained from the anterior nares. Thirteen (25.5%) of all the isolates were resistant to more than one category of antibiotics, with one isolate identified as MRSA. Thirty-eight (74.5%) isolates (including the MRSA isolate) carried PVL gene where the majority (44.7%) of these isolates were from the anterior nares. A dendogram revealed that the isolates were genetically diverse with 37 distinct pulsotypes clustered in 11 groups.

    CONCLUSION: S. aureus obtained from multiple sites of the HIV patients were genetically diverse without any clonality observed.

    MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents; Bacterial Toxins; Clindamycin; Electrophoresis; Erythromycin; Exotoxins; Humans; Leukocidins; Methicillin; Penicillins; Staphylococcus aureus; HIV Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Prevalence; Methicillin Resistance; Polymerase Chain Reaction; Molecular Epidemiology; Soft Tissue Infections; Methicillin-Resistant Staphylococcus aureus
  20. Islam MA, Alam F, Gan SH, Sasongko TH, Wan Ghazali WS, Wong KK
    Malays J Pathol, 2017 08;39(2):123-133.
    PMID: 28866693 MyJurnal
    BACKGROUND: Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPLs) based on the Sydney criteria. We aimed to explore the clinico-laboratory features and treatment strategies of APS patients retrospectively.
    METHODOLOGY: The medical records of APS patients registered under Hospital Universiti Sains Malaysia (Kelantan state) between 2000 and 2015 were reviewed.
    RESULTS: A total of 17 APS subjects (age 40.7 ± 12.8 years) including 11 primary (64.7%) and six secondary APS (35.3%) patients were identified. The follow-up period was 9.5 ± 6.7 years with male:female ratio of 1.0:4.7. Pregnancy morbidity was the most common clinical manifestation (11/14; 78.6%) followed by recurrent venous thrombosis (10/17; 58.8%). For other clinical features, menorrhagia was the most frequently observed manifestation (4/14; 28.6%) followed by aPLs-associated thrombocytopenia (4/17; 23.5%) and ovarian cyst (3/14; 21.4%). LA and aCL were positive in 94.1% (16/17) and 81.8% (9/11) of the patients, respectively. APTT value (76.7 ± 17.0 sec) was significantly high (p < 0.05). Low intensity warfarin alone was successful to maintain target INR (2.0 - 3.0) and prevent recurrence of thrombosis.
    CONCLUSION: The tendency of pregnancy morbidity in this cohort of Malaysian Kelantanese APS patients was high compared to other previously reported APS cohorts. Low intensity warfarin was successful in preventing recurrence of thrombosis, however, APS women receiving long-term anticoagulants should be monitored for possible occurrence of menorrhagia and ovarian cysts.
    MeSH terms: Hospitals, University; Humans; Malaysia; Retrospective Studies; Antiphospholipid Syndrome*
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