Displaying publications 61 - 80 of 104 in total

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  1. Lai PS, Mohd Mudri S, Chinna K, Othman S
    BMC Med Ethics, 2016 10 18;17(1):61.
    PMID: 27756366
    BACKGROUND: Advance care planning is a voluntary process whereby individual preferences, values and beliefs are used to aid a person in planning for end-of-life care. Currently, there is no local instrument to assess an individual's awareness and attitude towards advance care planning. This study aimed to develop an Advance Care Planning Questionnaire and to determine its validity and reliability among older people in Malaysia.

    METHODS: The Advance Care Planning Questionnaire was developed based on literature review. Face and content validity was verified by an expert panel, and piloted among 15 participants. Our study was conducted from October 2013 to February 2014, at an urban primary care clinic in Malaysia. Included were those aged >50 years, who could understand English. A retest was conducted 2 weeks after the first administration.

    RESULTS: Participants from the pilot study did not encounter any problems in answering the Advance Care Planning Questionnaire. Hence, no further modifications were made. Flesch reading ease was 71. The final version of the Advance Care Planning Questionnaire consists of 66 items: 30 items were measured on a nominal scale, whilst 36 items were measured on a Likert-like scale; of which we were only able to validate 22 items, as the remaining 14 items were descriptive in nature. A total of 245 eligible participants were approached; of which 230 agreed to participate (response rate = 93.9 %). Factor analysis on the 22 items measured on a Likert-scale revealed four domains: "feelings regarding advance care planning", "justifications for advance care planning", "justifications for not having advance care planning: fate and religion", and "justifications for not having advance care planning: avoid thinking about death". The Cronbach's alpha values for items each domain ranged from 0.637-0.915. In test-retest, kappa values ranged from 0.738-0.947.

    CONCLUSIONS: The final Advance Care Planning Questionnaire consisted of 63 items and 4 domains. It was found to be a valid and reliable instrument to assess the awareness and attitude of older people in Malaysia towards advance care planning.
  2. Kapitonova MY, Kuznetsov SL, Salim N, Othman S, Kamauzaman TM, Ali AM, et al.
    Bull. Exp. Biol. Med., 2014 Jan;156(3):393-8.
    PMID: 24771384 DOI: 10.1007/s10517-014-2357-8
    Morphological and phenotypical signs of cultured readaptation osteoblasts were studied after a short-term space mission. The ultrastructure and phenotype of human osteoblasts after Soyuz TMA-11 space flight (2007) were evaluated by scanning electron microscopy, laser confocal microscopy, and ELISA. The morphofunctional changes in cell cultures persisted after 12 passages. Osteoblasts retained the drastic changes in their shape and size, contour deformation, disorganization of the microtubular network, redistribution of organelles and specialized structures of the plasmalemma in comparison with the ground control cells. On the other hand, the expression of osteoprotegerin and osteocalcin (bone metabolism markers) increased; the expression of bone resorption markers ICAM-1 and IL-6 also increased, while the expression of VCAM-1 decreased. Hence, space flight led to the development of persistent shifts in cultured osteoblasts indicating injuries to the cytoskeleton and the phenotype changes, indicating modulation of bone metabolism biomarkers.
  3. Kapitonova MY, Salim N, Othman S, Muhd Kamauzaman TM, Ali AM, Nawawi HM, et al.
    Malays J Pathol, 2013 Dec;35(2):153-63.
    PMID: 24362479 MyJurnal
    Experiments involving short-term space flight have shown an adverse effect on the physiology, morphology and functions of cells investigated. The causes for this effect on cells are: microgravity, temperature fluctuations, mechanical stress, hypergravity, nutrient restriction and others. However, the extent to which these adverse effects can be repaired by short-term space flown cells when recultured in conditions of normal gravity remains unclear. Therefore this study aimed to investigate the effect of short-term spaceflight on cytoskeleton distribution and recovery of cell functions of normal human osteoblast cells. The ultrastructure was evaluated using ESEM. Fluorescent staining was done using Hoechst, Mito Tracker CMXRos and Tubulin Tracker Green for cytoskeleton. Gene expression of cell functions was quantified using qPCR. As a result, recovered cells did not show any apoptotic markers when compared with control. Tubulin volume density (p<0.001) was decreased significantly when compared to control, while mitochondria volume density was insignificantly elevated. Gene expression for IL-6 (p<0.05) and sVCAM-1 (p<0.001) was significantly decreased while alkaline phosphatase (p<0.001), osteocalcin and sICAM (p<0.05) were significantly increased in the recovered cells compared to the control ones. The changes in gene and protein expression of collagen 1A, osteonectin, osteoprotegerin and beta-actin, caused by short-term spaceflight, were statistically not significant. These data indicate that short term space flight causes morphological changes in osteoblast cells which are consistent with hypertrophy, reduced cell differentiation and increased release of monocyte attracting proteins. The long-term effect of these changes on bone density and remodeling requires more detailed studies.
  4. Kapitonova MY, Muid S, Froemming GR, Yusoff WN, Othman S, Ali AM, et al.
    Malays J Pathol, 2012 Dec;34(2):103-13.
    PMID: 23424772 MyJurnal
    Microgravity, hypergravity, vibration, ionizing radiation and temperature fluctuations are major factors of outer space flight affecting human organs and tissues. There are several reports on the effect of space flight on different human cell types of mesenchymal origin while information regarding changes to vascular endothelial cells is scarce. Ultrastructural and cytophysiological features of macrovascular endothelial cells in outer space flight and their persistence during subsequent culturing were demonstrated in the present investigation. At the end of the space flight, endothelial cells displayed profound changes indicating cytoskeletal lesions and increased cell membrane permeability. Readapted cells of subsequent passages exhibited persisting cytoskeletal changes, decreased metabolism and cell growth indicating cellular senescence.
  5. Kamal NM, Zamri-Saad M, Masarudin MJ, Othman S
    BMC Vet Res, 2017 Jun 19;13(1):186.
    PMID: 28629460 DOI: 10.1186/s12917-017-1109-1
    BACKGROUND: Pasteurella multocida B:2 causes bovine haemorrhagic septicaemia (HS), leading to rapid fatalities in cattle and buffaloes. An attenuated derivative of P. multocida B:2 GDH7, was previously constructed through mutation of the gdhA gene and proved to be an effective live attenuated vaccine for HS. Currently, only two potential live attenuated vaccine candidates for HS are being reported; P. multocida B:2 GDH7 and P. multocida B:2 JRMT12. This study primarily aims to investigate the potential of P. multocida B:2 GDH7 strain as a delivery vehicle for DNA vaccine for future multivalent applications.

    RESULTS: An investigation on the adherence, invasion and intracellular survival of bacterial strains within the bovine aortic endothelial cell line (BAEC) were carried out. The potential vaccine strain, P. multocida B:2 GDH7, was significantly better (p ≤ 0.05) at adhering to and invading BAEC compared to its parent strain and to P. multocida B:2 JRMT12 and survived intracellularly 7 h post treatment, with a steady decline over time. A dual reporter plasmid, pSRGM, which enabled tracking of bacterial movement from the extracellular environment into the intracellular compartment of the mammalian cells, was subsequently transformed into P. multocida B:2 GDH7. Intracellular trafficking of the vaccine strain, P. multocida B:2 GDH7 was subsequently visualized by tracking the reporter proteins via confocal laser scanning microscopy (CLSM).

    CONCLUSIONS: The ability of P. multocida B:2 GDH7 to model bactofection represents a possibility for this vaccine strain to be used as a delivery vehicle for DNA vaccine for future multivalent protection in cattle and buffaloes.

  6. Kadir MFA, Othman S, Nellore K
    Curr Pharm Biotechnol, 2020;21(15):1654-1665.
    PMID: 32525770 DOI: 10.2174/1389201021666200611113734
    BACKGROUND: The re-emerging of targeting Dihydroorotate Dehydrogenase (DHODH) in cancer treatment particularly Acute Myelogenous Leukemia (AML) has corroborated the substantial role of DHODH in cancer and received the attention of many pharmaceutical industries.

    OBJECTIVE: The effects of Brequinar Sodium (BQR) and 4SC-101 on lymphoblastoid cell lines were investigated.

    METHODS: DHODH expression and cell proliferation inhibition of lymphoblastoid and lymphoma cell lines were analyzed using Western blot analysis and XTT assay, respectively. JC-1 probe and ATP biochemiluminescence kit were used to evaluate the mitochondrial membrane potential and ATP generation in these cell lines. Furthermore, we explored the cell cycle progression using Muse™ Cell Cycle Kit.

    RESULTS: Ramos, SUDHL-1 and RPMI-1788 cells are fast-growing cells with equal expression of DHODH enzyme and sensitivity to DHODH inhibitors that showed that the inhibition of DHODH was not cancer-specific. In ATP depletion assay, the non-cancerous RPMI-1788 cells showed only a minor ATP reduction compared to Ramos and SUDHL-1 (cancer) cells. In the mechanistic impact of DHODH inhibitors on non-cancerous vs cancerous cells, the mitochondrial membrane potential assay revealed that significant depolarization and cytochrome c release occurred with DHODH inhibitors treatment in Ramos but not in the RPMI-1788 cells, indicating a different mechanism of proliferation inhibition in normal cells.

    CONCLUSION: The findings of this study provide evidence that DHODH inhibitors perturb the proliferation of non-cancerous cells via a distinct mechanism compared to cancerous cells. These results may lead to strategies for overcoming the impact on non-cancerous cells during treatment with DHODH inhibitors, leading to a better therapeutic window in patients.

  7. K C B, Binti Mohd Yusoff Z, Alrasheedy AA, Othman S
    J Clin Diagn Res, 2013 Jul;7(7):1408-13.
    PMID: 23998077 DOI: 10.7860/JCDR/2013/5450.3148
    CONTEXT: Pain is a major health care problem for the patients with cancer and one of the most frequent and disturbing cancer related symptoms.

    AIM: To study the characteristics of pain in cancer patients and its pharmacological management by using a subjective self-assessment questionnaire and the World Health Organization (WHO)analgesic ladder for pain management.

    SETTINGS AND DESIGNS: This study was conducted in the Oncology Wards of Penang Hospital, Penang, Malaysia. A questionnaire was developed to assess the pain characteristics and their effect on the patients' daily life activities and the information on the pharmacological management of the cancer pain. The cancer pain intensity was noted from the patients' medical database.

    METHOD AND MATERIAL: By using the validated questionnaire, an observational, cross sectional study was conducted on the cancer patientswho were admitted in the oncology wards of Penang Hospital, Malaysia, for a period of 1 month.

    STATISTICAL ANALYSIS: Descriptive statistics like mean, frequency and percentages were used for this study.

    RESULTS AND CONCLUSION: A total of 42 patients out of 143, who fulfilled the criteria, were interviewed. The results showed mild pain in 66.7% (28) of the patients, moderate pain in 7.1% (3) and severe painin 26.2% (11). The normal daily life activities were affected by the pain in almost all the patients. Among the interviewed patients, sleep was affected in 88% (37) of the patients and the normal physical activity was affected in 92.9% (39) of the patients. Similarly, the pain decreased the appetite in 78.6% (33) of the patients, it affected the personal relationship in 35.7% (15), it affected the emotion in 71.5% (30) and it affected the visual activity in 33.6% (13) of the patients. Mild pain with distressing symptoms was not treated with any analgesic or adjuvant medications in 40.5% (17) of the patients. In contrast, all the patients with moderate and severe pain were treated with medications. Among them, 66.7% (2) of the patients with moderate pain and 90.9% (10) of the patients with severe pain were treated with analgesics as per the WHO analgesic ladder. The WHO analgesic ladder guide for pain management was followed in a majority of the cases, when analgesics were prescribed. However, there was inadequate treatment of the cancer pain in many patients with mild pain and, consequently, their quality of life was largely affected.

  8. Juvarajah T, Wan-Ibrahim WI, Ashrafzadeh A, Othman S, Hashim OH, Fung SY, et al.
    Breastfeed Med, 2018 11;13(9):631-637.
    PMID: 30362820 DOI: 10.1089/bfm.2018.0057
    BACKGROUND: Bioactive proteins from milk fat globule membrane (MFGM) play extensive roles in cellular processes and defense mechanisms in infants. The aims of this study were to identify differences in protein compositions in human and caprine MFGM using proteomics and evaluate possible nutritional benefits of caprine milk toward an infant's growth, as an alternative when breastfeeding or human milk administration is not possible or inadequate.

    MATERIALS AND METHODS: Human and caprine MFGM proteins were isolated and analyzed, initially by polyacrylamide gel electrophoresis, and subsequently by quadrupole time-of-flight liquid chromatography-mass spectrometry. This was then followed by database search and gene ontology analysis. In general, this method selectively analyzed the abundantly expressed proteins in milk MFGM.

    RESULTS: Human MFGM contains relatively more abundant bioactive proteins compared with caprine. While a total of 128 abundant proteins were detected in the human MFGM, only 42 were found in that of the caprine. Seven of the bioactive proteins were apparently found to coexist in both human and caprine MFGM.

    RESULTS/DISCUSSION: Among the commonly detected MFGM proteins, lactotransferrin, beta-casein, lipoprotein lipase, fatty acid synthase, and butyrophilin subfamily 1 member A1 were highly expressed in human MFGM. On the other hand, alpha-S1-casein and EGF factor 8 protein, which are also nutritionally beneficial, were found in abundance in caprine MFGM. The large number of human MFGM abundant proteins that were generally lacking in caprine appeared to mainly support human metabolic and developmental processes.

    CONCLUSION: Our data demonstrated superiority of human MFGM by having more than one hundred nutritionally beneficial and abundantly expressed proteins, which are clearly lacking in caprine MFGM. The minor similarity in the abundantly expressed bioactive proteins in caprine MFGM, which was detected further, suggests that it is still nutritionally beneficial, and therefore should be included when caprine milk-based formula is used as an alternative.

  9. Jiwa M, Othman S, Hanafi NS, Ng CJ, Khoo EM, Chia YC
    Qual Prim Care, 2012;20(5):317-20.
    PMID: 23113999
    Malaysia has achieved reasonable health outcomes even though the country spends a modest amount of Gross Domestic Product on healthcare. However, the country is now experiencing a rising incidence of both infectious diseases and chronic lifestyle conditions that reflect growing wealth in a vibrant and successful economy. With an eye on an ageing population, reform of the health sector is a government priority. As in other many parts of the world, general practitioners are the first healthcare professional consulted by patients. The Malaysian health system is served by public and private care providers. The integration of the two sectors is a key target for reform. However, the future health of the nation will depend on leadership in the primary care sector. This leadership will need to be informed by research to integrate care providers, empower patients, bridge cultural gaps and ensure equitable access to scarce health resources.
  10. Jatuponwiphat T, Chumnanpuen P, Othman S, E-Kobon T, Vongsangnak W
    Microb Pathog, 2019 Feb;127:257-266.
    PMID: 30550841 DOI: 10.1016/j.micpath.2018.12.013
    Pasteurella multocida causes respiratory infectious diseases in a multitude of birds and mammals. A number of virulence-associated genes were reported across different strains of P. multocida, including those involved in the iron transport and metabolism. Comparative iron-associated genes of P. multocida among different animal hosts towards their interaction networks have not been fully revealed. Therefore, this study aimed to identify the iron-associated genes from core- and pan-genomes of fourteen P. multocida strains and to construct iron-associated protein interaction networks using genome-scale network analysis which might be associated with the virulence. Results showed that these fourteen strains had 1587 genes in the core-genome and 3400 genes constituting their pan-genome. Out of these, 2651 genes associated with iron transport and metabolism were selected to construct the protein interaction networks and 361 genes were incorporated into the iron-associated protein interaction network (iPIN) consisting of nine different iron-associated functional modules. After comparing with the virulence factor database (VFDB), 21 virulence-associated proteins were determined and 11 of these belonged to the heme biosynthesis module. From this study, the core heme biosynthesis module and the core outer membrane hemoglobin receptor HgbA were proposed as candidate targets to design novel antibiotics and vaccines for preventing pasteurellosis across the serotypes or animal hosts for enhanced precision agriculture to ensure sustainability in food security.
  11. Jackson AA, Lai PSM, Alias AM, Atiya N, Ramdzan SN, Abdul Malik TF, et al.
    J Infect Dev Ctries, 2019 03 31;13(3):219-226.
    PMID: 32040451 DOI: 10.3855/jidc.11089
    INTRODUCTION: Diagnosis and management of urinary tract infection (UTI) are complex, and do not always follow guidelines. The aim of this study was to determine adherence to the 2014 Malaysian Ministry of Health guidelines for managing suspected UTI in a Malaysian primary care setting.

    METHODOLOGY: We retrospectively reviewed computerized medical records of adults with suspected UTI between July-December 2016. Excluded were consultations misclassified by the search engine, duplicated records of the same patient, consultations for follow-up of suspected UTI, patients who were pregnant, catheterised, or who had a renal transplant. Records were reviewed by two primary care physicians and a clinical microbiologist.

    RESULTS: From 852 records, 366 consultations were a fresh episode of possible UTI. Most subjects were female (78.2%) with median age of 61.5 years. The major co-morbidities were hypertension (37.1%), prostatic enlargement in males (35.5%) and impaired renal function (31.1%). Symptoms were reported in 349 (95.4%) consultations. Antibiotics were prescribed in 307 (83.9%) consultations, which was appropriate in 227/307 (73.9%), where the subject had at least one symptom, and leucocytes were raised in urine full examination and microscopic examination (UFEME). In 73 (23.8%) consultations antibiotics were prescribed inappropriately, as the subjects were asymptomatic (14,4.6%), urine was clear (17,5.5%), or UFEME did not show raised leucocytes (42,13.7%). In 7 (2.3%) consultations appropriateness of antibiotics could not be determined as UFEME was not available.

    CONCLUSION: Several pitfalls contributed to suboptimal adherence to guidelines for diagnosis and management of suspected UTI. This illustrates the complexity of managing suspected UTI in older subjects with multiple co-morbidities.

  12. Ishak IH, Low WY, Othman S
    J Sex Med, 2010 Sep;7(9):3080-7.
    PMID: 20584130 DOI: 10.1111/j.1743-6109.2010.01848.x
    INTRODUCTION: Female sexual dysfunction (FSD) is a highly prevalent sexual health problem but poorly investigated at the primary care level.
    AIM: This article examines the prevalence of sexual dysfunction and its possible risk factors associated with women at high risk of FSD in a hospital-based primary practice.
    METHODS: A validated Malay version of the Female Sexual Function Index (MVFSFI) was utilized to determine FSD in a cross-sectional study design, involving 163 married women, aged 18-65 years, in a tertiary hospital-based primary care clinic in Kuala Lumpur, Malaysia. Sociodemographic, marital profile, health, and lifestyle for women at high risk of FSD and those who were not at high risk were compared and their risk factors were determined.
    MAIN OUTCOME MEASURES: Prevalence of FSD in Malaysian women based on the MVFSFI, and its risk factors for developing FSD.
    RESULTS: Some 42 (25.8%) out of 163 women had sexual dysfunction. Prevalence of sexual dysfunction increased significantly with age. Sexual dysfunctions were detected as desire problem (39.3%), arousal problem (25.8%), lubrication problem (21.5%), orgasm problem (16.6%), satisfaction problem (21.5%) and pain problems (16.6%). Women at high risk of FSD were significantly associated with age (OR 4.1, 95% CI 1.9 to 9.0), husband's age (OR 4.3 95% C.I 1.9 to 9.3), duration of marriage (OR 3.3, 95% CI 1.6 to 6.8), medical problems (OR 8.5, 95% CI 3.3 to 21.7), menopausal status (OR 6.6, 95% CI 3.1 to 14.3), and frequency of sexual intercourse (OR 10.7, 95% CI 3.6 to 31.7). Multivariate analysis showed that medical problem (adjusted OR 4.6, 95% CI 1.6 to 14.0) and frequency of sexual intercourse (adjusted OR 7.2, 95% CI 2.1 to 24.0) were associated with increased risk of having FSD. Those who practiced contraception were less likely to have FSD.
    CONCLUSION: Sexual health problems are prevalent in women attending primary care clinic where one in four women were at high risk of FSD. Thus, primary care physician should be trained and prepared to address this issue.
    Study site: Primary Care Clinic, University Malaya Medical Centre (UMMC), Kuala Lumpur, Malaysia
  13. Ibrahim NH, Kassim N, Othman S, Omar A, Shaari N, Awiskarni AA, et al.
    J Health Popul Nutr, 2023 Nov 20;42(1):129.
    PMID: 37986125 DOI: 10.1186/s41043-023-00464-5
    BACKGROUND: This study aims to validate two predictive formulas of weight estimating strategies in children with special needs, namely the Cattermole formula and the Mercy formula.

    METHODOLOGY: A cross-sectional study with a universal sampling of children and adolescents with special needs aged 2-18 years old, diagnosed with cerebral palsy, down syndrome, autism and attention-deficit/hyperactivity disorder was conducted at Community-Based Rehabilitation in Central Zone Malaysia. Socio-demographic data were obtained from files, and medical reports and anthropometric measurements (body weight, height, humeral length, and mid-upper arm circumference) were collected using standard procedures. Data were analysed using IBM SPSS version 26. The accuracy of the formula was determined by intraclass correlation, prediction at 20% of actual body weight, residual error (RE) and root mean square error (RMSE).

    RESULT: A total of 502 children with a median age of 7 (6) years were enrolled in this study. The results showed that the Mercy formula demonstrated a smaller degree of bias than the Cattermole formula (PE = 1.97 ± 15.99% and 21.13 ± 27.76%, respectively). The Mercy formula showed the highest intraclass correlation coefficient (0.936 vs. 0.858) and predicted weight within 20% of the actual value in the largest proportion of participants (84% vs. 48%). The Mercy formula also demonstrated lower RE (0.3 vs. 3.6) and RMSE (3.84 vs. 6.56) compared to the Cattermole formula. Mercy offered the best option for weight estimation in children with special needs in our study population.

  14. Hisham R, Ng CJ, Liew SM, Lai PSM, Chia YC, Khoo EM, et al.
    BMC Fam Pract, 2018 06 23;19(1):98.
    PMID: 29935527 DOI: 10.1186/s12875-018-0779-5
    BACKGROUND: Evidence-Based Medicine (EBM) integrates best available evidence from literature and patients' values, which then informs clinical decision making. However, there is a lack of validated instruments to assess the knowledge, practice and barriers of primary care physicians in the implementation of EBM. This study aimed to develop and validate an Evidence-Based Medicine Questionnaire (EBMQ) in Malaysia.

    METHODS: The EBMQ was developed based on a qualitative study, literature review and an expert panel. Face and content validity was verified by the expert panel and piloted among 10 participants. Primary care physicians with or without EBM training who could understand English were recruited from December 2015 to January 2016. The EBMQ was administered at baseline and two weeks later. A higher score indicates better knowledge, better practice of EBM and less barriers towards the implementation of EBM. We hypothesized that the EBMQ would have three domains: knowledge, practice and barriers.

    RESULTS: The final version of the EBMQ consists of 80 items: 62 items were measured on a nominal scale, 22 items were measured on a 5 point Likert-scale. Flesch reading ease was 61.2. A total of 343 participants were approached; of whom 320 agreed to participate (response rate = 93.2%). Factor analysis revealed that the EBMQ had eight domains after 13 items were removed: "EBM websites", "evidence-based journals", "types of studies", "terms related to EBM", "practice", "access", "patient preferences" and "support". Cronbach alpha for the overall EBMQ was 0.909, whilst the Cronbach alpha for the individual domain ranged from 0.657-0.940. The EBMQ was able to discriminate between doctors with and without EBM training for 24 out of 42 items. At test-retest, kappa values ranged from 0.155 to 0.620.

    CONCLUSIONS: The EBMQ was found to be a valid and reliable instrument to assess the knowledge, practice and barriers towards the implementation of EBM among primary care physicians in Malaysia.

  15. Hassan BA, Yusoff ZB, Hassali MA, Bin Othman S
    Asian Pac J Cancer Prev, 2011;12(11):2841-5.
    PMID: 22393951
    INTRODUCTION: Thrombocytopenia denotes abnormal decreases in platelet numbers and is a major detrimental side effect of the chemotherapy or cancer disease itself which cal lead to hemorrhage from vital organ. This is particularly a problem for the brain specifically within solid cancer patients and has a great negative effect on cancer patients quality of life (QOL). It ranges from mild bleeding from small blood vessels to severe bleeding from large blood vessels. The present study was conducted to evaluate the effectiveness of treatment guidelines for thrombocytopenia among solid cancer patients in Penang hospital and to find associations between these treatments and thrombocytopenia onset and severity and to suggest changes in the guidelines.

    METHODS: This retrospective observational study, conducted in a government hospital on Penang island included 341 cancer patients with thrombocytopenia who were admitted in the period between 2003 to 2009. The main statistical tests used were Chi-square test and Logistic regression test. The level of significance was set at P < 0.05.

    RESULTS: Of the total of 341, 21 (6.2%) showed thrombocytopenia before receiving chemotherapy and the remaining 320 (93.8%) after chemotherapy. The majority suffered from moderate thrombocytopenia (n=172; 53.8%), followed by mild a (n=97; 30.3%) and finally severe (n=51; 15.9%). For treatment, chemotherapy was delayed/ reduced (n=223; 65.4%) or platelets were transfused (n=51; 34.6%). However, thrombocytopenia problems were only temporarily solved.

    CONCLUSION: Effectiveness of thrombocytopenia treatment guidelines was found to be insufficient. It is advisable that thrombopoietin be used as a cornerstone even for patients who suffer from moderate thrombocytopenia and platelets transfusion should be used just for emergency cases when thrombocytopenia leads to a critical situation.

  16. Hassan R, Sharis Othman S, Ahmad Mukari SA, Abu Bakar A
    Med J Malaysia, 2013 Jun;68(3):264-6.
    PMID: 23749020 MyJurnal
    Pituitary apoplexy is a well-known complication of a pituitary adenoma. However, an ischaemic event caused by pituitary apoplexy is rare. We reported a case of pituitary apoplexy with middle cerebral artery infarction in a 44-year old man who presented with a sudden onset of altered sensorium. Vasospasm is the most likely underlying cause of the infarction in this case secondary to transdiaphragmatic rupture of the sella tumour into the subarachnoid space.
  17. Harith AA, Ahmad NA, Sahril N, Wahab NA, Kassim NA, Othman S, et al.
    Geriatr Gerontol Int, 2020 Dec;20 Suppl 2:43-48.
    PMID: 33370862 DOI: 10.1111/ggi.14039
    AIM: An aging population is a potential burden for unprepared developing countries. Malaysia is foreseen to be an aging country by 2035. Thus, this study aimed to determine the prevalence and factors associated with hearing disability among older persons in Malaysia.

    METHODS: Data from a nationwide survey implemented using a stratified cluster sampling design were analyzed. This study was carried out through face-to-face interviews and guided questionnaires. The questions were based on the Washington Group of Disability (WG) questionnaires, which produce multiple disability identifiers. Hearing disability is defined as at least one domain or question out of four questions coded as "A lot of difficulty" or "Cannot hear at all".

    RESULTS: The prevalence of hearing disability among older persons aged ≥60 years was 6.4% (95% CI 5.0-8.3), whereas 1.5% (95% CI 0.90, 2.50) older persons were reported to be using a hearing aid. The determinants of hearing disability are being male (aOR 2.67, 95% CI 1.94-3.66), being unemployed (retired, homemaker, unemployed; aOR 1.86, 95% CI 1.86-4.14) and had no formal education (aOR 18.25, 95% CI 4.18-79.55).

    CONCLUSIONS: Promoting healthy aging is important and crucial for Malaysia, in preparation toward an aging nation, as it could reduce the country's financial burden in the long term. Health-related agencies should promote health awareness and treatment centers in relation to hearing disability among older persons, as they should be educated and informed about healthcare choices availability, which is aligned with the Global Disability Action Plan 2014-2021. Geriatr Gerontol Int 2020; 20: 43-48.

  18. Hariono M, Choi SB, Roslim RF, Nawi MS, Tan ML, Kamarulzaman EE, et al.
    PLoS One, 2019;14(1):e0210869.
    PMID: 30677071 DOI: 10.1371/journal.pone.0210869
    Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC50 = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC50 of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.
  19. Gandhi S, Nor Rashid N, Mohamad Razif MF, Othman S
    Mol Biol Rep, 2021 Jun;48(6):5121-5133.
    PMID: 34169395 DOI: 10.1007/s11033-021-06509-4
    The High-Risk Human Papillomaviruses (HR-HPVs) 16 and 18 are known to cause cervical cancer, which is primarily attributed to E6 and E7 oncoproteins. In addition, recent studies have focused on the vital role of the p130 pocket protein as an oncosuppressor to limit the expression of E2F transcription factors required for cell cycle progression. In view of this, the current study was conducted to investigate the mechanism by which transfection with HPV16/18 E7 leads to the deregulation of the host cell cycle, altering the localisation of p130, and expression of differentiation genes in Human Keratinocytes (HaCaT) cells. Co-immunoprecipitation, Western blot analysis, immunofluorescence microscopy, flow cytometry, quantitative-Polymerase Chain Reaction (qPCR), and the inhibition of p130 by MG132 inhibitor were employed to investigate the loss of p130 and its disruption in HPV 16/18 E7-transfected HaCaT cells. The HPV16- and HPV18-transformed cells, known as CaSki and HeLa, respectively, were also used to complement the ectopic expressions of E7 in HaCaT cells. Normal keratinocytes displayed higher level of p130 expression than HPV-transformed cells. In addition, the immunofluorescence analysis revealed that both HPV 16/18 E7-transfected HaCaT and HPV-transformed cells exhibited higher level of cytoplasmic p130 compared to nuclear p130. A significant increase in the number of S/G2 phase cells in HPV-transformed cells was also recorded since E7 has been shown to stimulate proliferation through the deactivation of Retinoblastoma Protein (pRB)-dependent G1/S checkpoint. Furthermore, the findings recorded the down-regulation of keratinocyte differentiation markers, namely p130, keratin10, and involucrin. The proteasomal degradation of the exported p130 confirmed the cellular localisation pattern of p130, which was commonly observed in cancerous cells. The findings provide strong evidence that the localisation of nuclear p130 nuclear was disrupted by HPV16/18 E7 led to the deregulation of the cell cycle and the impairment of cellular differentiation ultimately lead to cellular transformation.
  20. Gandhi S, Mohamad Razif MF, Othman S, Chakraborty S, Nor Rashid N
    Mol Med Rep, 2023 Feb;27(2).
    PMID: 36633133 DOI: 10.3892/mmr.2023.12933
    The lack of specific and accurate therapeutic targets poses a challenge in the treatment of cervical cancer (CC). Global proteomics has the potential to characterize the underlying and intricate molecular mechanisms that drive the identification of therapeutic candidates for CC in an unbiased manner. The present study assessed human papillomavirus (HPV)‑induced proteomic alterations to identify key cancer hallmark pathways and protein‑protein interaction (PPI) networks, which offered the opportunity to evaluate the possibility of using these for targeted therapy in CC. Comparative proteomic profiling of HPV‑transfected (HPV16/18 E7), HPV‑transformed (CaSki and HeLa) and normal human keratinocyte (HaCaT) cells was performed using the liquid chromatography‑tandem mass spectrometry (LC‑MS/MS) technique. Both label‑free quantification and differential expression analysis were performed to assess differentially regulated proteins in HPV‑transformed and ‑transfected cells. The present study demonstrated that protein expression was upregulated in HPV‑transfected cells compared with in HPV‑transformed cells. This was probably due to the ectopic expression of E7 protein in the former cell type, in contrast to its constitutive expression in the latter cell type. Subsequent pathway visualization and network construction demonstrated that the upregulated proteins in HPV16/18 E7‑transfected cells were predominantly associated with a diverse array of cancer hallmarks, including the mTORC1 signaling pathway, MYC targets V1, hypoxia and glycolysis. Among the various proteins present in the cancer hallmark enrichment pathways, phosphoglycerate kinase 1 (PGK1) was present across all pathways. Therefore, PGK1 may be considered as a potential biomarker. PPI analysis demonstrated a direct interaction between p130 and polyubiquitin B, which may lead to the degradation of p130 via the ubiquitin‑proteasome proteolytic pathway. In summary, elucidation of the key signaling pathways in HPV16/18‑transfected and ‑transformed cells may aid in the design of novel therapeutic strategies for clinical application such as targeted therapy and immunotherapy against cervical cancer.
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