Browse publications by year: 2018

  1. Chen Z, Ding G, Wang Y, Xu J, Lin Z
    J Genet, 2018 Nov 14;97(5):e147-e151.
    PMID: 30574879
    The tiger frog Hoplobatrachus rugulosus (Wiegmann 1834) is a large robust dicroglossid frog widely distributed in southern China, Malaysia, Myanmar, Vietnam and Thailand. The escaped bred tiger frog introduced from Thailand hybridized with Chinese native population may have affected the genetic diversity of local Chinese tiger frogs. However, previous microsatellite loci of this species do not offer enough information to construct the genetic map. Here, we reported 33 new microsatellite loci from transcriptome sequencing for H. rugulosus. Alleles ranged between 1 and 10 per locus and only one locus (HRT001) was monomorphic. The polymorphic information content, observed and expected heterozygosity were 0-0.794, 0-0.969 and 0-0.831, respectively. None of the loci was observed in linkage disequilibrium and two loci (HRT023 and HRT068) deviated from Hardy-Weinberg equilibrium after Bonferroni correction for multiple tests. These transcriptome-derived microsatellite markers will be usedto study the genetic divergence and construct the genetic map in H. rugulosus.
    MeSH terms: Alleles; Animals; Myanmar; China; Malaysia; Ranidae; Thailand; Genetic Variation; Vietnam; Linkage Disequilibrium; Microsatellite Repeats; Genetic Drift; Transcriptome
  2. Willmott AGB, Hayes M, James CA, Dekerle J, Gibson OR, Maxwell NS
    Physiol Rep, 2018 Dec;6(24):e13936.
    PMID: 30575321 DOI: 10.14814/phy2.13936
    This experiment aimed to investigate the efficacy of twice-daily, nonconsecutive heat acclimation (TDHA) in comparison to once-daily heat acclimation (ODHA) and work matched once- or twice-daily temperate exercise (ODTEMP, TDTEMP) for inducing heat adaptations, improved exercise tolerance, and cytokine (immune) responses. Forty males, matched biophysically and for aerobic capacity, were assigned to ODHA, TDHA, ODTEMP, or TDTEMP. Participants completed a cycling-graded exercise test, heat acclimation state test, and a time to task failure (TTTF) at 80% peak power output in temperate (TTTFTEMP : 22°C/40% RH) and hot conditions (TTTFHOT : 38°C/20% RH), before and after 10-sessions (60 min of cycling at ~2 W·kg-1 ) in 45°C/20% RH (ODHA and TDHA) or 22°C/40% RH (ODTEMP or TDTEMP). Plasma IL-6, TNF-α, and cortisol were measured pre- and postsessions 1, 5, and 10. ODHA and TDHA induced equivalent heat adaptations (P  0.05) following ODHA (+14 ± 4%), TDHA (14 ± 8%), ODTEMP (9 ± 10%) or TDTEMP (8 ± 13%). Acute (P  0.05) increases were observed in IL-6, TNF-α, or cortisol during ODHA and TDHA, or ODTEMP and TDTEMP. Once- and twice-daily heat acclimation conferred similar magnitudes of heat adaptation and exercise tolerance improvements, without differentially altering immune function, thus nonconsecutive TDHA provides an effective, logistically flexible method of HA, benefitting individuals preparing for exercise-heat stress.
    MeSH terms: Adolescent; Adult; Body Temperature Regulation; Humans; Hydrocortisone/blood; Male; Plasma Volume; Random Allocation; Cytokines/blood*; Exercise Tolerance*; Physical Conditioning, Human/methods*; Thermotolerance*
  3. Fulsom BG, Pedlar TK, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Dec 07;121(23):232001.
    PMID: 30576207 DOI: 10.1103/PhysRevLett.121.232001
    We report the observation of ϒ(2S)→γη_{b}(1S) decay based on an analysis of the inclusive photon spectrum of 24.7  fb^{-1} of e^{+}e^{-} collisions at the ϒ(2S) center-of-mass energy collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We measure a branching fraction of B[ϒ(2S)→γη_{b}(1S)]=(6.1_{-0.7-0.6}^{+0.6+0.9})×10^{-4} and derive an η_{b}(1S) mass of 9394.8_{-3.1-2.7}^{+2.7+4.5}  MeV/c^{2}, where the uncertainties are statistical and systematic, respectively. The significance of our measurement is greater than 7 standard deviations, constituting the first observation of this decay mode.
    MeSH terms: Biometry; Photons; Uncertainty; Physical Phenomena
  4. Loke MF, Chua EG, Gan HM, Thulasi K, Wanyiri JW, Thevambiga I, et al.
    PLoS One, 2018;13(12):e0208584.
    PMID: 30576312 DOI: 10.1371/journal.pone.0208584
    Colorectal cancer (CRC) is ranked the third most common cancer in human worldwide. However, the exact mechanisms of CRC are not well established. Furthermore, there may be differences between mechanisms of CRC in the Asian and in the Western populations. In the present study, we utilized a liquid chromatography-mass spectrometry (LC-MS) metabolomic approach supported by the 16S rRNA next-generation sequencing to investigate the functional and taxonomical differences between paired tumor and unaffected (normal) surgical biopsy tissues from 17 Malaysian patients. Metabolomic differences associated with steroid biosynthesis, terpenoid biosynthesis and bile metabolism could be attributed to microbiome differences between normal and tumor sites. The relative abundances of Anaerotruncus, Intestinimonas and Oscillibacter displayed significant relationships with both steroid biosynthesis and terpenoid and triterpenoid biosynthesis pathways. Metabolites involved in serotonergic synapse/ tryptophan metabolism (Serotonin and 5-Hydroxy-3-indoleacetic acid [5-HIAA]) were only detected in normal tissue samples. On the other hand, S-Adenosyl-L-homocysteine (SAH), a metabolite involves in methionine metabolism and methylation, was frequently increased in tumor relative to normal tissues. In conclusion, this study suggests that local microbiome dysbiosis may contribute to functional changes at the cancer sites. Results from the current study also contributed to the list of metabolites that are found to differ between normal and tumor sites in CRC and supported our quest for understanding the mechanisms of carcinogenesis.
    MeSH terms: Adult; Aged; Bacteria/classification; Bacteria/genetics*; Bacteria/isolation & purification; Chromatography, High Pressure Liquid; Female; Humans; Intestinal Mucosa/microbiology*; Male; Middle Aged; RNA, Ribosomal, 16S/genetics; RNA, Ribosomal, 16S/metabolism*; RNA, Ribosomal, 16S/chemistry; S-Adenosylhomocysteine/metabolism; Steroids/biosynthesis; Terpenes/metabolism; Terpenes/chemistry; Colorectal Neoplasms/microbiology; Colorectal Neoplasms/pathology*; Sequence Analysis, DNA; Principal Component Analysis; Tandem Mass Spectrometry; Metabolomics*; High-Throughput Nucleotide Sequencing; Microbiota*
  5. Muhamad NA, Buang SN, Jaafar S, Jais R, Tan PS, Mustapha N, et al.
    BMC Public Health, 2018 Dec 22;18(1):1402.
    PMID: 30577816 DOI: 10.1186/s12889-018-6316-6
    BACKGROUND: In 2006, 4 years of planning was started by the Ministry of Health, Malaysia (MOH), to implement the HPV (human papillomavirus) vaccination programme. An inter-agency and multi-sectoral collaborations were developed for Malaysia's HPV school-based immunisation programme. It was approved for nationwide school base implementation for 13-year-old girls or first year secondary students in 2010. This paper examines how the various strategies used in the implementation over the last 7 years (2010-2016) that unique to Malaysia were successful in achieving optimal coverage of the target population.

    METHODS: Free vaccination was offered to school girls in secondary school (year seven) in Malaysia, which is usually at the age of 13 in the index year. All recipients of the HPV vaccine were identified through school enrolments obtained from education departments from each district in Malaysia. A total of 242,638 girls aged between 12 to 13 years studying in year seven were approached during the launch of the program in 2010. Approximately 230,000 girls in secondary schools were offered HPV vaccine per year by 646 school health teams throughout the country from 2010 to 2016.

    RESULTS: Parental consent for their daughters to receive HPV vaccination at school was very high at 96-98% per year of the programme. Of those who provided consent, over 99% received the first dose each year and 98-99% completed the course per year. Estimated population coverage for the full vaccine course, considering also those not in school, is estimated at 83 to 91% per year. Rates of adverse events reports following HPV vaccination were low at around 2 per 100,000 and the majority was injection site reactions.

    CONCLUSION: A multisectoral and integrated collaborative structure and process ensured that the Malaysia school-based HPV immunisation programme was successful and sustained through the programme design, planning, implementation and monitoring and evaluation. This is a critical factor contributing to the success and sustainability of the school-based HPV immunisation programme with very high coverage.

    MeSH terms: Adolescent; Child; Female; Humans; Malaysia; School Health Services*; Vaccination/statistics & numerical data*; Program Evaluation; Immunization Programs*; Papillomavirus Vaccines/administration & dosage*
  6. Ee Uli J, Yong CS, Yeap SK, Alitheen NB, Rovie-Ryan JJ, Mat Isa N, et al.
    BMC Res Notes, 2018 Dec 22;11(1):923.
    PMID: 30577850 DOI: 10.1186/s13104-018-4014-1
    OBJECTIVE: Using high-throughput RNA sequencing technology, this study aimed to sequence the transcriptome of kidney and liver tissues harvested from Peninsular Malaysia cynomolgus macaque (Macaca fascicularis). M. fascicularis are significant nonhuman primate models in the biomedical field, owing to the macaque's biological similarities with humans. The additional transcriptomic dataset will supplement the previously described Peninsular Malaysia M. fascicularis transcriptomes obtained in a past endeavour.

    RESULTS: A total of 75,350,240 sequence reads were obtained via Hi-seq 2500 sequencing technology. A total of 5473 significant differentially expressed genes were called. Gene ontology functional categorisation showed that cellular process, catalytic activity, and cell part categories had the highest number of expressed genes, while the metabolic pathways category possessed the highest number of expressed genes in the KEGG pathway analysis. The additional sequence dataset will further enrich existing M. fascicularis transcriptome assemblies, and provide a dataset for further downstream studies.

    MeSH terms: Animals; Humans; Kidney; Liver; Macaca fascicularis; Malaysia; Metabolic Networks and Pathways; High-Throughput Nucleotide Sequencing; Transcriptome; Gene Ontology
  7. Svane JK, Chiou ST, Groene O, Kalvachova M, Brkić MZ, Fukuba I, et al.
    Implement Sci, 2018 12 22;13(1):153.
    PMID: 30577871 DOI: 10.1186/s13012-018-0848-0
    BACKGROUND: Implementation of clinical health promotion (CHP) aiming at better health gain is slow despite its effect. CHP focuses on potentially modifiable lifestyle risks such as smoking, alcohol, diet, and physical inactivity. An operational program was created to improve implementation. It included patients, staff, and the organization, and it combined existing standards, indicators, documentation models, a performance recognition process, and a fast-track implementation model. The aim of this study was to evaluate if the operational program improved implementation of CHP in clinical hospital departments, as measured by health status of patients and staff, frequency of CHP service delivery, and standards compliance.

    METHODS: Forty-eight hospital departments were recruited via open call and stratified by country. Departments were assigned to the operational program (intervention) or usual routine (control group). Data for analyses included 36 of these departments and their 5285 patients (median 147 per department; range 29-201), 2529 staff members (70; 10-393), 1750 medical records (50; 50-50), and standards compliance assessments. Follow-up was measured after 1 year. The outcomes were health status, service delivery, and standards compliance.

    RESULTS: No health differences between groups were found, but the intervention group had higher identification of lifestyle risk (81% versus 60%, p 

    MeSH terms: Adolescent; Adult; Aged; Delivery of Health Care/standards; Female; Health Promotion/methods*; Health Status; Hospitals/statistics & numerical data*; Humans; Male; Middle Aged; Outcome Assessment (Health Care); Young Adult; Quality Improvement
  8. George D, Hassali MA, Hss AS
    JMIR Hum Factors, 2018 Dec 21;5(4):e12232.
    PMID: 30578216 DOI: 10.2196/12232
    BACKGROUND: Reporting of medication errors is one of the essential mechanisms to identify risky health care systems and practices that lead to medication errors. Unreported medication errors are a real issue; one of the identified causes is a burdensome medication error reporting system. An anonymous and user-friendly mobile app for reporting medication errors could be an alternative method of reporting medication error in busy health care settings.

    OBJECTIVE: The objective of this paper is to report usability testing of the Medication Error Reporting App (MERA), a mobile app for reporting medication errors anonymously.

    METHODS: Quantitative and qualitative methods were employed involving 45 different testers (pharmacists, doctors, and nurses) from a large tertiary hospital in Malaysia. Quantitative data was retrieved using task performance and rating of MERA and qualitative data were retrieved through focus group discussions. Three sessions, with 15 testers each session, were conducted from January to March 2018.

    RESULTS: The majority of testers were pharmacists (23/45, 51%), female (35/45, 78%), and the mean age was 36 (SD 9) years. A total of 135 complete reports were successfully submitted by the testers (three reports per tester) and 79.2% (107/135) of the reports were correct. There was significant improvement in mean System Usability Scale scores in each session of the development process (P

  9. Ramli ZAC, Kamarudin SK
    Nanoscale Res Lett, 2018 Dec 22;13(1):410.
    PMID: 30578446 DOI: 10.1186/s11671-018-2799-4
    Platinum (Pt)-based nanoparticle metals have received a substantial amount of attention and are the most popular catalysts for direct methanol fuel cell (DMFC). However, the high cost of Pt catalysts, slow kinetic oxidation, and the formation of CO intermediate molecules during the methanol oxidation reaction (MOR) are major challenges associate with single-metal Pt catalysts. Recent studies are focusing on using either Pt alloys, such as Fe, Ni, Co, Rh, Ru, Co, and Sn metals, or carbon support materials to enhance the catalytic performance of Pt. In recent years, Pt and Pt alloy catalysts supported on great potential of carbon materials such as MWCNT, CNF, CNT, CNC, CMS, CNT, CB, and graphene have received remarkable interests due to their significant properties that can contribute to the excellent MOR and DMFC performance. This review paper summaries the development of the above alloys and support materials related to reduce the usage of Pt, improve stability, and better electrocatalytic performance of Pt in DMFC. Finally, discussion of each catalyst and support in terms of morphology, electrocatalytic activity, structural characteristics, and its fuel cell performance are presented.
  10. See KF, Yen SH
    Health Econ Rev, 2018 Dec 21;8(1):33.
    PMID: 30578526 DOI: 10.1186/s13561-018-0214-6
    BACKGROUND: The main objective of this study is to assess the performance of the global health system, emphasising the contribution of people's happiness to health system efficiency across countries. Technical efficiency (TE) scores are estimated using the output-oriented variable returns to scale (VRS) data envelopment analysis (DEA) model based on the input measures: health expenditure, labour, hospital beds and education, and the output measures: healthy life expectancy and inverse mortality index. The efficiency scores are regressed against three explanatory variables: happiness index, population density, and healthcare share of gross domestic product (GDP). The analysis involved 121 selected countries using double bootstrap DEA as proposed by Simar, L., Wilson, P.W J Econ 136:1‑34, 2007.

    RESULTS: The bootstrap truncated regression indicates that happiness is one of the factors that contributes significantly to health system efficiency. The study also revealed that the selected health systems perform well, on average, in terms of population density and healthcare share of GDP.

    CONCLUSIONS: In addition to improving the economic standard of living, policy-makers should also consider ways to increase the happiness and well-being of society. Policies focusing on well-being and happiness can lead to improved well-being and improved health outcomes, which may ultimately reduce the healthcare burden and enhance healthcare performance.

  11. Idris I, Tohid H, Muhammad NA, A Rashid MR, Mohd Ahad A, Ali N, et al.
    BMJ Open, 2018 12 22;8(12):e025125.
    PMID: 30580276 DOI: 10.1136/bmjopen-2018-025125
    OBJECTIVES: This study aimed to determine the prevalence of anaemia among patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) at primary care settings and its associated factors.
    DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study involved 808 adult patients with T2DM and CKD who were recruited via systematic sampling from 20 public primary care clinics in Peninsular Malaysia. Their sociodemographic, clinical and biomedical profiles were collected through interviews, examination of medical records and blood testing.
    RESULTS: The prevalence of anaemia was 31.7% (256/808). The anaemia was mainly mild (61.5%) and normocytic normochromic (58.7%). About 88.7% of the patients with anaemia were not known to have anaemia prior to the study. Among 36 patients with documented history of anaemia, 80.6% were still anaemic, and only a half received iron therapy. Multivariate regression analysis showed that women (adjusted odd ratio (AOR): 1.57, 95% CI: 1.12 to 2.21, p=0.009) and those with older age (AOR: 1.04, 95% CI: 1.01 to 1.06, p<0.001), CKD stage 3a (AOR: 2.47; 95% CI: 1.25 to 4.87, p=0.009), CKD stage 3b (AOR: 4.36; 95% CI: 2.14 to 8.85, p<0.001), CKD stage 4 (AOR: 10.12; 95% CI: 4.36 to 23.47, p<0.001), CKD stage 5 (AOR: 10.80; 95% CI: 3.32 to 35.11, p<0.001) and foot complication (AOR 3.12, 95% CI: 1.51 to 6.46, p=0.002) were more likely to have anaemia. Having higher body mass index (AOR 0.95, 95% CI: 0.92 to 0.99, p=0.012) and higher diastolic blood pressure (AOR 0.97, 95% CI: 0.95 to 0.99, p<0.001) were associated with lower odds to have anaemia.
    CONCLUSION: Anaemia among patients with T2DM and CKD in primary care was common, and the majority was unrecognised. Inadequate treatment of anaemia was also prevalent. Therefore, screening of anaemia should be incorporated into the routine assessment of diabetic complications particularly for those with significant associated factors. It is hoped that such strategy could lead to early treatment and hence improve their overall care.

    TRIAL REGISTRATION NUMBER: NMRR-15-660-24324.
    MeSH terms: Adult; Ambulatory Care Facilities; Anemia*; Cross-Sectional Studies; Diabetes Mellitus, Type 2*; Humans; Malaysia; Prevalence; Renal Insufficiency*
  12. Wong YP, Tan GC, Wong KK, Anushia S, Cheah FC
    Malays J Pathol, 2018 Dec;40(3):267-286.
    PMID: 30580358
    Gardnerella vaginalis (GV) is a facultatively anaerobic gram-variable bacillus and is the major organism involved in bacterial vaginosis. GV-associated bacterial vaginosis has been associated with adverse pregnancy outcomes include preterm parturition and subclinical chorioamnionitis. Inflammatory response induced by GV presents paediatric problems as well. Studies had shown that increased levels of proinflammatory cytokines include TNF-α, IL-1β and IL-6 following fetal inflammatory response syndrome secondary to GV-induced intrauterine infection may result in the development of periventricular leukomalacia and bronchopulmonary dysplasia in the infected fetus. There is increasing evidence that GV-associated BV infection serves as a risk factor for long-term neurological complications, such as cerebral palsy and learning disability. GV is fastidious and could elude conventional detection methods such as bacterial cultures. With current more sophisticated molecular biology detection methods, its role and pathogenic effects have been shown to have a greater impact on intrauterine inflammation and fetal/neonatal infection. This review gives an overview on the characteristics of GV and its virulence properties. Its detrimental role in causing unfavourable GV-related perinatal outcomes, with emphasis on the possible mechanistic pathways is discussed. The discovery of disease mechanisms allows the building of a strong platform where further research on innovative therapies can be based on, for instance, an anti-TLR monoclonal antibody as therapeutic agent to halt inflammation-precipitate adverse perinatal outcomes.
    MeSH terms: Female; Gardnerella vaginalis*; Humans; Infant, Newborn; Pregnancy; Vaginosis, Bacterial/pathology*; Gram-Positive Bacterial Infections/pathology*
  13. Thambiah SC, Wong TH, Das Gupta E, Radhakrishnan AK, Gun SC, Chembalingam G, et al.
    Malays J Pathol, 2018 Dec;40(3):287-294.
    PMID: 30580359
    INTRODUCTION: Low 25-hydroxyvitamin D [25(OH)D] levels have not been consistently associated with bone mineral density (BMD). It has been suggested that calculation of the free/bioavailable 25(OH)D may correlate better with BMD. We examined this hypothesis in a cohort of Malaysian women.

    MATERIALS AND METHODS: A cross-sectional study of 77 patients with rheumatoid arthritis (RA) and 29 controls was performed. Serum 25(OH)D was measured using the Roche Cobas E170 immunoassay. Serum vitamin D binding protein (VDBP) was measured using a monoclonal enzyme-linked immunosorbent assay (ELISA). Free/bioavailable 25(OH)D were calculated using both the modified Vermuelen and Bikle formulae.

    RESULTS: Since there were no significant differences between RA patients and controls for VDBP and 25(OH)D, the dataset was analysed as a whole. Calculated free 25(OH)D by Vermeulen was strongly correlated with Bikle (r = 1.00, p < 0.001). A significant positive correlation was noted between measured total 25(OH)D with free/bioavailable 25(OH)D (r = 0.607, r = 0.637, respectively, p < 0.001). Median free/bioavailable 25(OH)D values were significantly higher in Chinese compared with Malays and Indians, consistent with their median total 25(OH)D. Similar to total 25(OH)D, the free/bioavailable 25(OH)D did not correlate with BMD.

    CONCLUSION: In this first study of a multiethnic female Malaysian population, free/bioavailable 25(OH)D were found to reflect total 25(OH)D, and was not superior to total 25(OH)D in its correlation with BMD. Should they need to be calculated, the Bikle formula is easier to use but only calculates free 25(OH)D. The Vermuelen formula calculates both free/bioavailable 25(OH)D but is more complex to use.
    MeSH terms: Adult; Aged; Aged, 80 and over; Arthritis, Rheumatoid; Arthritis, Rheumatoid/blood*; China/ethnology; Cross-Sectional Studies; Female; Humans; India/ethnology; Malaysia; Malaysia/ethnology; Middle Aged; Vitamin D/analogs & derivatives*; Vitamin D/blood; Vitamin D-Binding Protein/blood*; Absorptiometry, Photon; Bone Density/physiology*
  14. Othman SN, Zainol Rashid Z, Abdul Wahab A, Abdul Samat MN, Ding CH, Ali UK
    Malays J Pathol, 2018 Dec;40(3):295-302.
    PMID: 30580360
    INTRODUCTION: Infant hepatitis B vaccination was introduced into the Expanded Programme on Immunisation (EPI) in Malaysia in 1989. This study aimed to investigate seroprevalence of hepatitis B among UKM pre-clinical medical students, born between 1991 and 1995, and had their infant vaccination more than 20 years ago.

    MATERIALS AND METHODS: A prospective, cross-sectional study involving 352 students, comprising 109 (31.0%) males and 243 (69.0%) females. Blood specimens were tested for anti-HBs, where levels of ≥10 mIU/mL was considered reactive and protective. Students with non-reactive levels were given a 20 μg HBV vaccine booster. Anti-HBs levels were tested six weeks after the first booster dose. Those with anti-HBs <10 mIU/mL were then given another two booster doses, at least one month apart. Anti-HBs levels were tested six weeks after the third dose.

    RESULTS: Ninety-seven students (27.6%) had anti-HBs ranging from 10 to >1000 mIU/mL while 255 (72.4%) had anti-HBs <10 mIU/mL. After one booster dose, 208 (59.1%) mounted anti-HBs ≥10 mIU/mL. Among the remaining 47 (13.3%), all except two students (0.6%) responded following completion of three vaccination doses. They were negative for HBsAg and anti-HBcore antibody, thus regarded as non-responders.

    CONCLUSIONS: Anti-HBs levels waned after 20 years post-vaccination, where more than 70% were within non-reactive levels. For healthcare workers, a booster dose followed by documenting anti-HBs levels of ≥10 mIU/mL may be recommended, to guide the management of post-exposure prophylaxis. Pre-booster anti-HBs testing may not be indicated. Serological surveillance is important in long-term assessment of HBV vaccination programs. No HBV carrier was detected.

    MeSH terms: Adult; Cross-Sectional Studies; Female; Hepatitis B Antibodies/blood*; Humans; Malaysia; Male; Prospective Studies; Students, Medical*; Universities; Vaccination*; Viral Hepatitis Vaccines*; Seroepidemiologic Studies
  15. Tengku Din TADAA, Abdul Jalal MI, Seeni A, Shamsuddin S, Jaafar H
    Malays J Pathol, 2018 Dec;40(3):303-312.
    PMID: 30580361
    INTRODUCTION: This study focused on PF4 effects on caspase-3,-6, -7, -8 and -9 which regulate the apopotosis process in breast cancer.

    MATERIALS AND METHODS: Breast tumours were induced in forty 21-day-old female Sprague Dawley rats (SDRs) using MNU until tumour size reached 14.5 mm (SD: 0.5 mm). The rats were then divided into two groups: Group 1 (control injected with 0.9% saline; n = 20), and Group 2 (platelet factor 4 (PF4); n = 20). PF4 was administered through focal intralesional injection at 20 μg/lesion dose. Following 5-day treatment, the SDRs were sacrificed. Subsequently, representative sections from the tumour were obtained for haematoxylin and eosin (H&E) staining. The expressions of caspase-3, -6, -7, -8 and -9 were evaluated using immunohistochemistry (IHC) staining.

    RESULTS: The majority of breast tumour specimens were of aggressive types [ncontrol = 13 (65%); nPF4 = 12 (60%)]. Invasive ductal carcinoma not otherwise specified (IDC-NOS) was the most commonly observed breast tumour histology for control and PF4 groups (n = 8 (40%) in respective groups). PF4-treated group exhibited significant differences in the caspase-3, -6 and -8 expression levels compared to the control group (all p < 0.001). There were no significant differences in caspase-7 (p = 0.347) and caspase-9 (p = 0.373) expression levels between both groups.

    CONCLUSION: This study found that PF4 acts via the caspase-mediated extrinsic apoptosis pathway without the involvement of the intrinsic pathway.
    MeSH terms: Animals; Female; Mammary Glands, Animal/drug effects; Mammary Glands, Animal/metabolism*; Mammary Glands, Animal/pathology; Mammary Neoplasms, Experimental/metabolism*; Mammary Neoplasms, Experimental/pathology; Platelet Factor 4/pharmacology*; Signal Transduction/drug effects; Rats, Sprague-Dawley; Apoptosis/drug effects*; Apoptosis/physiology; Caspases/metabolism*; Rats
  16. Mohtarrudin N, Ghazali R, Md Roduan MR
    Malays J Pathol, 2018 Dec;40(3):313-318.
    PMID: 30580362
    INTRODUCTION: Cyclooxygenase-2 (COX-2) promotes carcinogenesis by inducing proliferation and angiogenesis while decreasing apoptosis and immunosuppressive activity. It is overexpressed in many malignancies including renal cell carcinoma (RCC). The aim of this study was to investigate COX-2 expression in clear cell RCC and its association with tumour grades and demographic parameters.

    MATERIALS AND METHODS: Thirty-six clear cell RCC cases were selected. There were 21 (58.3%) men and 15 (41.7%) women with median age of 56.6 years (range: 16-74 years). Chinese constituted 16 (44.4%) of the cases; Malays 14 (38.9%) cases and Indian 6 (16.7%) cases. There were 6 (16.7%) grade 1, 20 (55.6%) grade 2, 10 (27.8%) grade 3 and none was grade 4. The paraffin embedded tissues were cut at 4 μm thick and stained with COX-2 monoclonal antibody.

    RESULTS: Eighteen (50%) of the RCC cases were immunopositive, of which all showed strong positivity. The immunopositive cases showed cytoplasmic membrane positivity.

    CONCLUSION: There was no significant association between COX-2 expression with grade, age, sex and ethnicity (p=0.457, p=0.054, p=0.389 and p=0.568 respectively). Strong positivity of COX-2 suggest that COX-2 may play a role in cell proliferation and in carcinogenesis.

    MeSH terms: Adolescent; Adult; Aged; Carcinoma, Renal Cell/metabolism*; Carcinoma, Renal Cell/pathology; Female; Humans; Immunohistochemistry; Kidney/metabolism*; Kidney/pathology; Kidney Neoplasms/metabolism*; Kidney Neoplasms/pathology; Male; Middle Aged; Biomarkers, Tumor/metabolism; Cyclooxygenase 2/metabolism*; Young Adult
  17. Naicker MS, Tan GC
    Malays J Pathol, 2018 Dec;40(3):319-323.
    PMID: 30580363
    INTRODUCTION: Clinical decision making becomes difficult when clinical and methodological heterogeneity does not permit synthesis of results of multiple small studies.

    AIM: For studies done in Malaysia, to identity the sample sizes and heterogeneity present in the various studies which used p16 in evaluating lesions of the cervix. To evaluate if it would be possible for a single study to answer the various questions posed by the original authors. To highlight areas where the design features of future studies can be optimised.

    MATERIALS AND METHODS: Various databases were searched using synonyms for p16 AND cervix AND Malaysia. These were assessed for broad conformity to a Diagnostic Test Accuracy format. Methodological and clinical heterogeneity indicators were extracted into standardised fields.

    RESULTS: There were 5 studies eligible for inclusion. Each sought to study different aspects of the disease such as diagnostic grade stratification and pathogenesis. The study type broadly conformed to a Diagnostic Test Accuracy format. The study design used was either consecutive or non-consecutive. Sample size ranged from 75 to 201. Clinical heterogeneity was present in the choice of controls with some using normal and some using inflamed tissue. Methodological heterogeneity in applying the reference test, index test and different antibody clones were present.

    CONCLUSION: There was both clinical and methodological heterogeneity making synthesis of studies difficult. It is possible to design a study which would be able to answer all the questions posed by the original authors with internal validity while at the same time increasing sample size.

    MeSH terms: Uterine Cervical Neoplasms/metabolism; Uterine Cervical Neoplasms/pathology*; Female; Humans; Malaysia; Sensitivity and Specificity; Biomarkers, Tumor/analysis; Reproducibility of Results; Cyclin-Dependent Kinase Inhibitor p16/analysis*
  18. Tai L, Teoh HK, Cheong SK
    Malays J Pathol, 2018 Dec;40(3):325-329.
    PMID: 30580364
    INTRODUCTION: Induced pluripotent stem cells (iPSC) that exhibit embryonic stem cell-like properties with unlimited self-renewal and multilineage differentiation properties, are a potential cell source in regenerative medicine and cell-based therapy. Although retroviral and lentiviral transduction methods to generate iPSC are well established, the risk of mutagenesis limits the use of these products for therapeutic applications.

    MATERIALS AND METHODS: In this study, reprogramming of human dermal fibroblasts (NHDF) into iPSC was carried out using non-integrative Sendai virus for transduction. The iPSC clones were characterised based on the morphological changes, gene expression of pluripotency markers, and spontaneous and directed differentiation abilities into cells of different germ layers.

    RESULTS: On day 18-25 post-transduction, colonies with embryonic stem cell-like morphology were obtained. The iPSC generated were free of Sendai genome and transgene after passage 10, as confirmed by RT-PCR. NHDF-derived iPSC expressed multiple pluripotency markers in qRT-PCR and immunofluorescence staining. When cultured in suspension for 8 days, iPSC successfully formed embryoid body-like spheres. NHDF-derived iPSC also demonstrated the ability to undergo directed differentiation into ectoderm and endoderm.

    CONCLUSION: NHDF were successfully reprogrammed into iPSC using non-integrating Sendai virus for transduction.

    MeSH terms: Fibroblasts/cytology*; Humans; Skin/cytology*; Sendai virus; Cell Proliferation/physiology; Induced Pluripotent Stem Cells/cytology*
  19. Sugawara T, Shindoh J, Hoshi D, Hashimoto M
    Malays J Pathol, 2018 Dec;40(3):331-335.
    PMID: 30580365
    INTRODUCTION: We report a case of intrahepatic cholangiocarcinoma and portal hypertension developing in a liver with biliary microhamartomas (von Meyenburg's complex).

    CASE REPORT: The patient was a 55-year-old man who had a past medical history of diffuse multiple liver abscesses. During follow-up examination, a hypovascular nodule measuring 2.1 cm in diameter was incidentally found in segment 8 of the liver. Surgical resection was performed based on a suspected diagnosis of hepatocellular carcinoma. A gastrofiberscopy examination detected characteristic findings of portal hypertensive gastropathy. During the laparotomy, multiple tiny cystic lesions were observed in a diffuse pattern across the liver surface. The liver parenchyma was slightly fibrotic and haemorrhagic. A histopathological examination revealed intrahepatic cholangiocarcinoma with vascular invasions in von Meyenburg's complex. Multiple biliary adenomas were also observed among the biliary microhamartomas adjacent to the main tumour, suggesting that the malignant transformation of the biliary adenomas might have been responsible for the development of the intrahepatic cholangiocarcinoma. The histopathologic examination also revealed sinusoidal dilation and abnormal spacing of the portal tracts and central veins as evidence of portal hypertension.

    MeSH terms: Bile Duct Neoplasms/complications; Bile Duct Neoplasms/pathology*; Bile Ducts, Intrahepatic/pathology; Hamartoma/complications; Hamartoma/pathology*; Humans; Hypertension, Portal/etiology; Hypertension, Portal/pathology*; Liver Neoplasms/etiology; Liver Neoplasms/pathology*; Male; Middle Aged; Cholangiocarcinoma/etiology; Cholangiocarcinoma/pathology*
  20. Samberkar PN, Chow TK, Samberkar SP
    Malays J Pathol, 2018 Dec;40(3):337-341.
    PMID: 30580366
    INTRODUCTION: Unforeseen emergency in late pregnancy can be catastrophic and cause unexpected maternal and foetal demise. Moreover, lack of awareness and failure of prompt treatment raise mortality rate. Such fatalities warrant a forensic autopsy as it may raise redundant medico-legal concerns.

    CASE REPORT: We report a case that revealed significant intra-abdominal haemorrhage at autopsy. The source of haemorrhage was at the spleen hilum and histology established rupture of splenic artery aneurysm. There was no associated obstetric cause found.

    CONCLUSION: Knowledge of spontaneous rupture of splenic artery aneurysm in late pregnancy is essential for monitoring maternal and foetal, morbidity and mortality. However, in the eventuality of death a comprehensive forensic autopsy is the only investigation to recognise such calamity and clear clinical confusion.

    MeSH terms: Adult; Female; Fetal Death; Humans; Pregnancy; Pregnancy Complications/pathology*; Pregnancy Trimester, Third; Rupture, Spontaneous/pathology; Splenic Artery/pathology*; Aneurysm, Ruptured/pathology*; Fatal Outcome
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