Browse publications by year: 2016

  1. Deshmukh R, Sharma L, Tekade M, Kesharwani P, Trivedi P, Tekade RK
    J Biomed Res, 2016 Mar;30(2):149-161.
    PMID: 28276670 DOI: 10.7555/JBR.30.20150074
    In this investigation, sensitive and reproducible methods are described for quantitative determination of deflazacort in the presence of its degradation product. The method was based on high performance liquid chromatography of the drug from its degradation product on reverse phase using Acquity UPLC BEH C18 columns (1.7 µm, 2.1 mm × 150 mm) using acetonitrile and water (40:60 V/V) at a flow rate of 0.2 mL/minute in UPLC. UV detection was performed at 240.1 nm. Deflazacort was subjected to oxidative, acid, base, hydrolytic, thermal and photolytic degradation. The drug was found to be stable in water and thermal stress, as well as under neutral stress conditions. However, forced-degradation study performed on deflazacort showed that the drug degraded under alkaline, acid and photolytic stress. The degradation products were well resolved from the main peak, which proved the stability-indicating power of the method. The developed method was validated as per ICH guidelines with respect to accuracy, linearity, limit of detection, limit of quantification, accuracy, precision and robustness, selectivity and specificity. Apart from the aforementioned, the results of the present study also emphasize the importance of isolation characterization and identification of degradant. Hence, an attempt was made to identify the degradants in deflazacort. One of the degradation products of deflazacort was isolated and identified by the FTIR, NMR and LC-MS study.
  2. Zain RB, Kallarakkal TG, Ramanathan A, Kim J, Tilakaratne WM, Takata T, et al.
    Asian Pac J Cancer Prev, 2016 01 09;17(9):4491.
    PMID: 27865210 DOI: 10.7314/APJCP.2016.17.(9).4491
    Verruco-papillary lesions (VPLs) of the oral cavity described in the literature involve a spectrum of conditions
    including squamous papilloma, verruca vulgaris, focal epithelial hyperplasia, condyloma, proliferative verrucous
    leukoplakia and verrucous carcinoma. A majority of the VPLs are slow growing, benign in nature and have a
    viral aetiology. Virus associated benign mucosal outgrowths are not too difficult to diagnose either clinically or
    by microscopy. Apart from virus-associated lesions, VPLs harboring malignant potential or behaviour such as
    verrucous carcinoma, proliferative verrucous leukoplakia, oral verrucous hyperplasia (OVH), oral papillary
    squamous cell carcinoma (PSCC) and oral conventional squamous cell carcinoma with papillary features (CSCC)
    need to be further clarified for better understanding of their predictable biologic behavior and appropriate
    treatment. Current understanding of potentially malignant VPLs is perplexing and is primarily attributed to
    the use of confusing and unsatisfactory terminology. In particular, the condition referred to as oral verrucous
    hyperplasia (OVH) poses a major diagnostic challenge. OVH represents a histopathological entity whose clinical
    features are not well recognised and is usually clinically indistinguishable from a verrucous carcinoma and a
    PSCC or a CSCC. A consensus report published by an expert working group from South Asia as an outcome of
    the ‘First Asian Regional Meeting on the Terminology and Criteria for Verruco-papillary Lesions of the Oral
    Cavity’ held in Kuala Lumpur, Malaysia, recognised the clinical description of these OVH as a new entity named
    ‘Exophytic Verrucous Hyperplasia’. Previously described clinical features of OVH such as the ‘blunt’ or ‘sharp’
    variants; and the ‘mass’ or ‘plaque’ variants can now collectively fall under this newly described entity. This paper
    discusses in detail the application of the standardized criteria guidelines of ‘Exophytic Verrucous Hyperplasia’
    as published by the expert group which will enable clinicians and pathologists to uniformly interpret their pool
    of OVH cases and facilitate a better understanding of OVH malignant potential.
    MeSH terms: Asia; Biological Products; Carcinoma, Squamous Cell; Hyperplasia; Leukoplakia, Oral; Malaysia; Microscopy; Warts; Focal Epithelial Hyperplasia; Carcinoma, Verrucous; Consensus; Pathologists
  3. Al-Naggar RA, Anil Sh
    Asian Pac J Cancer Prev, 2016 10 01;17(10):4661-4664.
    PMID: 27892680
    Background: Artificial light at night (ALAN) has been linked to increased risk of cancers in body sites like the breast
    and colorectum. However exposure of ALAN as an environmental risk factor and its relation to cancers in humans has
    never been studied in detail. Objective: To explore the association of ALAN with all forms of cancers in 158 countries.
    Materials and Methods: An ecological study encompassing global data was conducted from January to June 2015,
    with age-standardized rates (ASR) of cancers as the outcome measure. ALAN, in the protected areas, as the exposure
    variable, was measured with reference to the Protected Area Light Pollution Indicator (PALI) and the Protected Area
    Human Influence Indicator (PAHI). Pearson’s correlations were calculated for PALI and PAHI with ASR of cancers for
    158 countries, adjusted for country populations, electricity consumption, air pollution, and total area covered by forest.
    Stratified analysis was conducted according to the country income levels. Linear regression was applied to measure the
    variation in cancers explained by PALI and PAHI. Results: PALI and PAHI were positively associated with ASR of all
    forms of cancer, and also the four most common cancers (p < 0.05). These positive correlations remained statistically
    significant for PAHI with all forms of cancer, lung, breast, and colorectal cancer after adjusting for confounders. Positive
    associations of PALI and PAHI with cancers varied with income level of the individual countries. Variation in all forms
    of cancers, and the four most common cancers explained by PALI and PAHI, ranged from 3.3 – 35.5%. Conclusion:
    Artificial light at night is significantly correlated for all forms of cancer as well as lung, breast, colorectal, and prostate
    cancers individually. Immediate measures should be taken to limit artificial light at night in the main cities around the
    world and also inside houses.
    MeSH terms: Air Pollution; Cities; Colonic Neoplasms; Electricity; Environmental Pollution; Humans; Lung Neoplasms; Male; Prostate; Risk Factors; Colorectal Neoplasms; Linear Models; Forests
  4. Zamani A, Mat Jusoh SA, Al-Jamal HA, Sul'ain MD, Johan MF
    Asian Pac J Cancer Prev, 2016 11 01;17(11):4857-4861.
    PMID: 28030911
    Background: Imatinib mesylate, a tyrosine kinase inhibitor specifically targeting the BCR/ABL fusion protein, induces hematological remission in patients with chronic myeloid leukemia (CML). However, the majority of CML patients treated with imatinib develop resistance with prolonged therapy. Dendrophthoe pentandra (L.) Miq. is a Malaysian mistletoe species that has been used as a traditional treatment for several ailments such as smallpox, ulcers, and cancers. Methods: We developed a resistant cell line (designated as K562R) by long-term co-culture of a BCR/ ABL positive CML cell line, K562, with imatinib mesylate. We then investigated the anti-proliferative effects of D. pentandra methanol extract on parental K562 and resistant K562R cells. Trypan blue exclusion assays were performed to determine the IC50 concentration; apoptosis and cell cycle analysis were conducted by flow cytometry. Results: D. pentandra extract had greater anti-proliferative effects towards K562R (IC50= 192 μg/mL) compared to K562 (500 μg/ mL) cells. Upon treatment with D. pentandra extract at the IC50. concentration: K562 but not K562R demonstrated increase in apoptosis and cell cycle arrest in the G2/M phase. Conclusion: D. pentandra methanol extract exerts potent anti-proliferative effect on BCR/ABL positive K562 cells.
    MeSH terms: Imatinib Mesylate; Methanol; Flow Cytometry; Humans; Smallpox; Variola virus; Trypan Blue; Ulcer; Mistletoe; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Fusion Proteins, bcr-abl; Coculture Techniques; K562 Cells; Inhibitory Concentration 50; Protein Kinase Inhibitors; Cell Cycle Checkpoints
  5. Chan HK, Lim YM
    Asian Pac J Cancer Prev, 2016 11 01;17(11):4951-4957.
    PMID: 28032722
    Background: Apart from reducing occupational exposure to cytotoxic hazards, the PhaSeal® closed-system transfer device (CSTD) can extend the beyond-use dates (BUDs) of unfinished vials of antineoplastic drugs for up to 168 hours (seven days). In this study, the total material cost incurred by its use in a Malaysian government-funded hospital was calculated. Methods: A list of vial stability following initial needle punctures of 29 commonly-used antineoplastic drugs was compiled. The amount of the materials used, including drugs, infusion bottles, the PhaSeal® CSTD and other consumables, was recorded on a daily basis for three months in 2015. The total cost was calculated based on the actual acquisition costs, and was compared with that of a hypothetical scenario, whereby conventional syringe-needle sets were used for the same amounts of preparations. Results: The use of the PhaSeal® CSTD incurred a cost of MYR 383,634.52 (USD 92,072.28) in three months, representing an average of MYR 170.5 (USD 40.92) per preparation or an estimated annual cost of MYR 1,534,538.08 (USD 368,289.14). Compared with conventional syringe-needle approach, it is estimated to lead to an additional spending of MYR 148,627.68 (USD 35,670.64) yearly. Conclusion: Although there was a reduction of drug wastage achieved by extending BUDs of unfinished vials using the PhaSeal® CSTD, cost saving was not observed, likely attributable to the wide use of lower-priced generic drugs in Malaysia. Future studies should further evaluate the possibility of cost saving, especially in health settings where branded and high-cost antineoplastic drugs are more commonly used.
    MeSH terms: Antineoplastic Agents; Cachexia; Government; Malaysia; Protective Devices; Punctures; Syringes; Occupational Exposure; Drugs, Generic; Cost Savings
  6. Nyam KL, Chang CY, Tan CS, Ng ST
    Int J Med Mushrooms, 2016;18(12):1093-1104.
    PMID: 28094747 DOI: 10.1615/IntJMedMushrooms.v18.i12.40
    The aim of this study was to determine the antiulcer activity of Lignosus rhinocerotis in rats. A total of 48 Sprague-Dawley rats were used in ethanol-induced, aspirin-induced, and water immersion-restraint stress-induced ulcer models. Rats were equally divided into 4 groups for each model and orally administered 5 mL/kg distilled water, 20 mg/kg omeprazole, as well as 250 and 500 mg/kg of L. rhinocerotis powder. L. rhinocerotis powder at both 250 and 500 mg/kg doses demonstrated significant (P < 0.05) protection against gastric ulceration in all the induced ulcer models. Histological studies revealed severe damage and hemorrhage of gastric mucosa in the negative control group for all ulcer-induced models. The study suggests that L. rhinocerotis powder possesses dose-dependent antiulcer activity in the gastric mucosa, as ascertained grossly and histologically, compared with the negative control groups.
    MeSH terms: Administration, Oral; Animals; Anti-Ulcer Agents/administration & dosage*; Diet/methods*; Male; Polyporaceae*; Stomach Ulcer/prevention & control*; Treatment Outcome; Rats, Sprague-Dawley
  7. Makmor, T, Raja Noriza, RA, NurulHuda, MS, Sook-Lu, Y, Soo-Kun, L, Kok-Peng, N, et al.
    JUMMEC, 2016;19(1):1-6.
    MyJurnal
    Introduction:
    Living donation is an important source for organs transplantation in Malaysia. This study aims to investigate
    the Malaysian living donors’ follow-up attendance, their preferences on medical-institutional facilities, and
    the financial circumstances pertaining to the follow-up costs
    Materials and Methods:
    Primary data were collected through a survey of 80 living donors who made their donation at the University
    of Malaya Medical Center (UMMC) between 1991 and 2012.
    Results:
    Out total of 178 donors, only 111 were reachable and 80 of them participated in the survey (72%). The findings
    revealed that most of the donors (71.2%) attend the follow-up regularly. Nevertheless, donors seem to neglect
    the importance of follow-up as they consider themselves healthy (28.9%) or consider the follow-up as being
    troublesome (28.9%). Most donors (67.5%) are not in favour of being treated as patients, but prefer to be
    monitored under donor registry (88.8%) and getting their health service in special clinics for donors (80%).
    The majority of the donors fund the follow-up costs themselves (32.4%), while 25% of the donors’ follow-up
    costs were funded by family members. Among those donors without income and those of low-income (84.8%
    of respondents), 60.3% believe that the follow-up costs should be borne by the government.
    Conclusions:
    Based on the findings, it is therefore suggested that the government provides all living donors with proper
    free health service through donor registry and donor clinics. Adequate care has to be given to the donors to
    pre-empt any unforeseen health complications due to the organ donation surgical procedures.
    MeSH terms: Financial Management; Follow-Up Studies; Government; Humans; Malaysia; Tissue and Organ Procurement; Surveys and Questionnaires; Registries; Universities; Living Donors
  8. Kamal, M., Amini, F., Ramasamy, TS
    JUMMEC, 2016;19(1):23-32.
    MyJurnal
    Glaucoma is a common eye disease that can cause irreversible damage if left undiagnosed and untreated. It is one of the most common neurodegenerative diseases causing blindness. Pre-clinical studies have been carried out on animal models of glaucoma for stem cell therapy. We carried out a systematic review to determine whether stem cell therapy had the potential to treat glaucoma. Nine studies were selected based on the predetermined inclusion and exclusion criteria. Of these nine studies, eight focused on neuroprotection conferred by stem cells, and the remaining one on neuroregeneration. Results from these studies showed that there was a potential in stem cell based therapy in treating glaucoma, especially regarding neuroprotection via neurotrophic factors. The studies revealed that a brain-derived neurotrophic factor expressed by stem cells promoted the survival of retinal ganglion cells in murine glaucoma models. The transplanted cells survived without any side effects. While these studies proved that stem cells provided neuroprotection in glaucoma, improvement of vision could not be determined. Clinical studies would be required to determine whether the protection of RGC correlated with improvement in visual function. Furthermore, these murine studies could not be translated into clinical therapy due to the heterogeneity of the experimental methods and the
    use of different cell lines. In conclusion, the use of stem cells in the clinical therapy of glaucoma will be an important step in the future as it will transform present-day treatment with the hope of restoring sight to patients with glaucoma.
    MeSH terms: Neuroprotection; Animals; Blindness; Cell Line; Glaucoma; Humans; Nerve Regeneration; Retinal Ganglion Cells; Tetrahymenina; Brain-Derived Neurotrophic Factor; Neurodegenerative Diseases; Models, Animal; Stem Cell Transplantation; Mice; Cell- and Tissue-Based Therapy
  9. Sudheer S, Ali A, Manickam S
    Int J Med Mushrooms, 2016;18(10):935-943.
    PMID: 27910761
    Rigorous research has been carried out regarding the cultivation of Ganoderma lucidum using different agricultural residues. Nevertheless, large-scale cultivation and the separation of active compounds of G. lucidum are still challenges for local farmers. The objective of this study was to evaluate the use of oil palm waste fibers such as empty fruit bunch fibers and mesocarp fibers as effective substrates for the growth of G. lucidum mycelia to study the possibility of solid-state cultivation and to determine the optimum conditions necessary for the growth of mycelia of this mushroom on these waste fibers. Various parameters such as temperature, pH, humidity, and carbon and nitrogen compositions required for the optimum growth of mycelia have been determined. Oil palm fibers are a vivid source of lignocellulose, and their availability in Malaysia is high compared to that of sawdust. G. lucidum is a wood-rotting fungi that can easily decay and utilize this lignocellulose biomass, a major agricultural waste in Malaysia.
    MeSH terms: Carbon/metabolism*; Humidity; Hydrogen-Ion Concentration; Lignin/metabolism*; Malaysia; Nitrogen/metabolism*; Temperature; Biomass; Reishi/growth & development; Reishi/chemistry*; Mycelium/growth & development; Arecaceae/growth & development; Arecaceae/microbiology*; Arecaceae/ultrastructure
  10. Maddin N, Husin A, Gan SH, Aziz BA, Ankathil R
    Oncol Ther, 2016;4(2):303-314.
    PMID: 28261657 DOI: 10.1007/s40487-016-0035-x
    INTRODUCTION: Imatinib mesylate (IM), a selective inhibitor of the BCR-ABL tyrosine kinase, is a well-established first-line treatment for chronic myeloid leukemia (CML). IM is metabolized mainly by cytochrome P450 (CYP) in the liver, specifically the CYP3A4 and CYP3A5 enzymes. Polymorphisms in these genes can alter the enzyme activity of IM and may affect its response. In this study, the impact of two single-nucleotide polymorphisms (SNPs), CYP3A5*3 (6986A>G) and CYP3A4*18 (878T>C), on IM treatment response in CML patients (n = 270; 139 IM resistant and 131 IM good responders) was investigated.

    METHODS: Genotyping of CYP3A4*18 and CYP3A5*3 was performed using the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) technique. The association between allelic variants and treatment response was assessed by means of odds ratio (OR) with 95% confidence intervals calculated by logistic regression.

    RESULTS: Our results indicated that CML patients carrying the heterozygous (AG) and homozygous variant (GG) genotype of CYP3A5*3 were associated with a significantly lower risk of acquiring resistance with OR 0.171; 95% CI: 0.090-0.324, p 

  11. Al-Khateeb, A, Al-Talib, H
    JUMMEC, 2016;19(2):1-11.
    MyJurnal
    Background:
    Familial hypercholesterolaemia (FH) is one of the most frequent inherited metabolic disorders that can lead
    to a risk of premature cardiovascular disease. Publications on FH are mainly from western patients as there is
    little research on Asians, including Malaysians. The aim of this review is to provide an up-to- date information
    on Malaysian studies on FH genotyping and its relation to the phenotype of the affected patients.
    Method:
    A search was conducted for data from online databases on FH in Malaysia.
    Results:
    The mutation spectrum for FH among Malaysian patients was extremely broad. The gene variants were located
    mainly in the low-density lipoprotein receptor (LDLR) and apolipoprotein B-100 (APOB-100) genes rather than
    in the proprotein convertase subtilisin kexin type 9 (PCSK9) gene. The exon 9 and 14 were the hotspots in the
    LDLR gene. The most frequent mutation was p.Cys255Ser, at 12.5%, followed by p.Arg471Gly, at 11%, and the
    most common single nucleotide polymorphism (SNP) was c.1060+7 T>C at 11.7%. The LDLR gene variants were
    more common compared to the APOB-100 gene variants, while variants in the PCSK9 gene were very few.
    Phenotype-genotype associations were identified. Subjects with LDLR and APOB-100 genes mutations had a
    higher frequency of cardiovascular disease, a family history of hyperlipidaemia and tendon xanthoma and a
    higher low-density lipoprotein cholesterol (LDL-C) level than non-carriers.
    Conclusion:
    Research on Malaysian familial hypercholesterolaemic patients by individual groups is encouraging. However,
    more extensive molecular studies on FH on a national scale, with a screening of the disease-causing mutations
    together with a comprehensive genotype-phenotype association study, can lead to a better outcome for
    patients with the disease.
    MeSH terms: Cardiovascular Diseases; Cholesterol; Exons; Genotype; Humans; Hyperlipoproteinemia Type II; Lipoproteins, LDL; Malaysia; Mutation; Phenotype; Receptors, LDL; Subtilisins; Tendons; Xanthomatosis; Polymorphism, Single Nucleotide; Proprotein Convertases; Apolipoprotein B-100; Genetic Association Studies
  12. Cheong, CS, Gan, GG, Chen, TM, Lim, CC, Nadarajan, VS, Bee, PC
    JUMMEC, 2016;19(2):12-16.
    MyJurnal
    Haemophagocytic lymphohistiocytosis (HLH) is a clinico-pathologic entity caused by increased proliferation
    and activation of benign macrophages with haemophagocytosis throughout the reticulo-endothelial system.
    Virus-associated HLH is a well-recognised entity. Although majority of parvovirus B19 associated HLH does not
    require any specific treatment and carries good prognosis, outcome of children is worse than adults. We report
    here a case of HLH associated with acute parvovirus B19 infection in a young healthy patient with underlying
    hereditary spherocytosis, with bone marrow findings typical of parvovirus infection. Although this patient
    had spontaneous recovery of cell counts, he succumbed due to complication from prolonged ventilation.
    Unexpectedly, his immunoglobulin levels were inappropriately normal despite on-going ventilator associated
    pneumonia, which reflects inadequate humoral immune response towards infection.
    MeSH terms: Adult; Bone Marrow; Cell Count; Child; Humans; Immunoglobulins; Macrophages; Male; Parvoviridae Infections; Pneumonia; Prognosis; Spherocytosis, Hereditary; Erythema Infectiosum; Parvovirus B19, Human; Parvovirus; Immunity, Humoral
  13. Lumbanraja, SN
    JUMMEC, 2016;19(2):17-25.
    MyJurnal
    Background: Kangaroo mother care (KMC) in low birth weight newborns has been found to be beneficial, but
    studies have shown that maternal factors might be of concern in the successful application of KMC.
    Aim: To study the influence of maternal factors on growth parameters in low-birth-weight babies with KMC.
    Methods: This is a prospective cohort study of 40 low birth weight newborns in our institutions. We randomly
    assigned the newborns to the group which received KMC and to the group which received conventional care.
    Maternal factors were recorded. We measured weight, length, and head circumferences of newborns daily
    for thirty days. Data was processed by SPSS x22.0.
    Results: A total of 40 newborns were recruited into the study. Weight parameters were significantly higher
    in the KMC group than in the conventional group except for the Z scores. Regarding maternal characteristics,
    only gestational age was found to influence the initial and the last head circumference (p=0.035). There were
    no differences in maternal age, parity, maternal education, mode of delivery, fetal sex, and initial Apgar score
    with any of the growth parameters.
    Conclusion: There were no maternal and fetal differences in the growth parameters of the groups, except in
    the delayed growth of head circumferences in preterm infants.
    Keywords: Growth parameters, KMC method, low birth weight
    MeSH terms: Apgar Score; Child; Female; Gestational Age; Humans; Infant; Infant, Low Birth Weight; Infant, Newborn; Infant, Premature; Maternal Age; Parity; Pregnancy; Prospective Studies; Parturition; Delivery, Obstetric; Kangaroo-Mother Care Method; Mating Factor
  14. Musa AS
    J Transcult Nurs, 2016 Mar;27(2):117-25.
    PMID: 24867886 DOI: 10.1177/1043659614537305
    This study reported the differences in factor structure of the Spiritual Well-Being Scale (SWBS) among Jordanian Arab and Malaysian Muslim participants and further examined its validity and reliability. A convenience sample of 553 Jordanian Arab and 183 Malaysian Malay Muslim university students was recruited from governmental universities in northern Jordan. The findings of this study revealed that this scale consists of two factors for the Jordanian Arab group, representing the "Religious Well-Being" and the "Existential Well-Being" subscales, and consists of three factors for the Malaysian group, representing the "Affiliation/Meaning and Purpose," "Positive Existential Well-Being/God Caring and Love," and "Alienation/Despair" subscales. In conclusion, the factor structure of the SWBS for both groups in this study was psychometrically sound with evidence of acceptable to good validity and reliability. Furthermore, this study supported the multidimensional nature of the SWBS and the earlier notion that ethnicity shapes responses to this scale.
    MeSH terms: Adolescent; Cultural Characteristics; Factor Analysis, Statistical; Humans; Islam*; Jordan; Malaysia/ethnology; Male; Psychometrics; Surveys and Questionnaires*; Students*; Universities; Transcultural Nursing; Spirituality*; Young Adult
  15. Syafawati WU, Zefarina Z, Zafarina Z, Hassan MN, Norazmi MN, Panneerchelvam S, et al.
    Immunohematology, 2016 Dec;32(4):143-160.
    PMID: 28257229
    MeSH terms: Alleles; Genotype; Humans; Malaysia; Genetic Variation; Polymerase Chain Reaction; Antigens, Human Platelet/genetics*
  16. Rebbeck TR, Friebel TM, Mitra N, Wan F, Chen S, Andrulis IL, et al.
    Breast Cancer Res, 2016 11 11;18(1):112.
    PMID: 27836010
    BACKGROUND: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood.

    METHODS: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2.

    RESULTS: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p 

    MeSH terms: Alleles; Breast Neoplasms/genetics; Breast Neoplasms/pathology; Exons; Female; Heterozygote; Humans; Phenotype; Population Surveillance*; Promoter Regions, Genetic; Germ-Line Mutation*; Genes, BRCA1*; Loss of Heterozygosity; Genes, BRCA2*
  17. Liu J, Lončar I, Collée JM, Bolla MK, Dennis J, Michailidou K, et al.
    Sci Rep, 2016 Nov 15;6:36874.
    PMID: 27845421 DOI: 10.1038/srep36874
    NBS1, also known as NBN, plays an important role in maintaining genomic stability. Interestingly, rs2735383 G > C, located in a microRNA binding site in the 3'-untranslated region (UTR) of NBS1, was shown to be associated with increased susceptibility to lung and colorectal cancer. However, the relation between rs2735383 and susceptibility to breast cancer is not yet clear. Therefore, we genotyped rs2735383 in 1,170 familial non-BRCA1/2 breast cancer cases and 1,077 controls using PCR-based restriction fragment length polymorphism (RFLP-PCR) analysis, but found no association between rs2735383CC and breast cancer risk (OR = 1.214, 95% CI = 0.936-1.574, P = 0.144). Because we could not exclude a small effect size due to a limited sample size, we further analyzed imputed rs2735383 genotypes (r2 > 0.999) of 47,640 breast cancer cases and 46,656 controls from the Breast Cancer Association Consortium (BCAC). However, rs2735383CC was not associated with overall breast cancer risk in European (OR = 1.014, 95% CI = 0.969-1.060, P = 0.556) nor in Asian women (OR = 0.998, 95% CI = 0.905-1.100, P = 0.961). Subgroup analyses by age, age at menarche, age at menopause, menopausal status, number of pregnancies, breast feeding, family history and receptor status also did not reveal a significant association. This study therefore does not support the involvement of the genotype at NBS1 rs2735383 in breast cancer susceptibility.
    MeSH terms: Alleles; Binding Sites; Breast Neoplasms/genetics*; Breast Neoplasms/pathology; Female; Genotype; Humans; Nuclear Proteins/genetics*; Risk Factors; Odds Ratio; Cell Cycle Proteins/genetics*; BRCA1 Protein/genetics; Genetic Predisposition to Disease; 3' Untranslated Regions; Polymorphism, Single Nucleotide; BRCA2 Protein/genetics; MicroRNAs/metabolism*
  18. Cobley JN, Ab Malik Z, Morton JP, Close GL, Edwards BJ, Burniston JG
    Proteomes, 2016 Apr 08;4(2).
    PMID: 28248225 DOI: 10.3390/proteomes4020015
    Traditional methods for phenotyping skeletal muscle (e.g., immunohistochemistry) are labor-intensive and ill-suited to multixplex analysis, i.e., assays must be performed in a series. Addressing these concerns represents a largely unmet research need but more comprehensive parallel analysis of myofibrillar proteins could advance knowledge regarding age- and activity-dependent changes in human muscle. We report a label-free, semi-automated and time efficient LC-MS proteomic workflow for phenotyping the myofibrillar proteome. Application of this workflow in old and young as well as trained and untrained human skeletal muscle yielded several novel observations that were subsequently verified by multiple reaction monitoring (MRM). We report novel data demonstrating that human ageing is associated with lesser myosin light chain 1 content and greater myosin light chain 3 content, consistent with an age-related reduction in type II muscle fibers. We also disambiguate conflicting data regarding myosin regulatory light chain, revealing that age-related changes in this protein more closely reflect physical activity status than ageing per se. This finding reinforces the need to control for physical activity levels when investigating the natural process of ageing. Taken together, our data confirm and extend knowledge regarding age- and activity-related phenotypes. In addition, the MRM transitions described here provide a methodological platform that can be fine-tuned to suite multiple research needs and thus advance myofibrillar phenotyping.
  19. Viswanathan S, Botross N, Rusli BN, Riad A
    Mult Scler Relat Disord, 2016 Nov;10:112-115.
    PMID: 27919476 DOI: 10.1016/j.msard.2016.10.001
    Acute disseminated encephalomyelitis (ADEM) complicating dengue infection is still exceedingly rare even in endemic countries such as Malaysia. Here we report two such cases, the first in an elderly female patient and the second in a young man. Both presented with encephalopathy, brainstem involvement and worsening upper and lower limb weakness. Initial magnetic resonance imaging (MRI) of the brain was normal in the first case. Serum for dengue Ig M and NS-1 was positive in both cases. Cerebrospinal fluid (CSF) showed pleocytosis in both with Dengue IgM and NS-1 positive in the second case but not done in the first. MRI brain showed changes of perpendicular subcortical palisading white matter, callosal and brainstem disease mimicking multiple sclerosis (MS) in both patients though in the former case there was a lag between the onset of clinical symptoms and MRI changes which was only clarified on reimaging. The temporal evolution and duration of the clinical symptoms, CSF changes and neuroimaging were more suggestive of Dengue ADEM rather than an encephalitis though initially the first case began as dengue encephalitis. Furthermore in dengue encephalitis neuroimaging is usually normal or rarely edema, haemorrhage, brainstem, thalamic or focal lesions are seen. Therefore, early recognition of ADEM as a sequelae of dengue infection with neuroimaging mimicking MS and repeat imaging helped in identifying these two cases. Treatment with intravenous steroids followed by maintenance oral steroids produced good outcome in both patients.
    MeSH terms: Adult; Dengue/cerebrospinal fluid; Dengue/complications*; Dengue/drug therapy; Diagnosis, Differential; Encephalomyelitis, Acute Disseminated/cerebrospinal fluid; Encephalomyelitis, Acute Disseminated/complications*; Encephalomyelitis, Acute Disseminated/drug therapy; Female; Humans; Male; Middle Aged; Multiple Sclerosis/cerebrospinal fluid
  20. Yew YC, Hor JY, Lim TT, Kanesalingam R, Ching YM, Arip M, et al.
    Mult Scler Relat Disord, 2016 Nov;10:22-25.
    PMID: 27919493 DOI: 10.1016/j.msard.2016.08.009
    It is difficult to predict whether a particular attack of neuromyelitis optica spectrum disorder (NMOSD) will affect the optic nerve [optic neuritis (ON): unilateral or bilateral], spinal cord (myelitis), brain or brainstem, or a combination of the above. We report an interesting case of recurrent ON of the same eye for a total of 11 episodes in a Chinese woman. Over a period of 22 years, the attacks only involved the left eye, and never the right eye and also no myelitis. For a prolonged duration, she was diagnosed as recurrent idiopathic ON. Only until she was tested positive for aquaporin 4 antibody that her diagnosis was revised to NMOSD. Optical coherence tomography revealed thinning of the retinal nerve fibre layer (RNFL) for the affected left eye, while the RNFL thickness was within normal range for the unaffected right eye. The disability accrual in NMOSD is generally considered to be attack-related - without a clinical attack of ON, there shall be no visual impairment, and no significant subclinical thinning of RNFL. Our case is in agreement with this notion. This is in contrast to multiple sclerosis where subclinical RNFL thinning does occur. This case highlights the importance of revisiting and questioning a diagnosis of recurrent idiopathic ON particularly when new diagnostic tools are available.
    MeSH terms: Autoantibodies/blood; Diagnosis, Differential; Evoked Potentials, Visual; Eye/physiopathology*; Female; Humans; Functional Laterality; Middle Aged; Neuromyelitis Optica/drug therapy; Neuromyelitis Optica/physiopathology*; Recurrence; Tomography, Optical Coherence; Aquaporin 4/immunology
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