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  1. Fulltext Assessing the efficacy of machine learning algorithms for syncope classification: A systematic review
    Goh CH, Ferdowsi M, Gan MH, Kwan BH, Lim WY, Tee YK, et al.
    MethodsX, 2024 Jun;12:102508.
    PMID: 38162148 DOI: 10.1016/j.mex.2023.102508
    Syncope is a transient loss of consciousness with rapid onset. The aims of the study were to systematically evaluate available machine learning (ML) algorithm for supporting syncope diagnosis to determine their performance compared to existing point scoring protocols. We systematically searched IEEE Xplore, Web of Science, and Elsevier for English articles (Jan 2011 - Sep 2021) on individuals aged five and above, employing ML algorithms in syncope detection with Head-up titl table test (HUTT)-monitored hemodynamic parameters and reported metrics. Extracted data encompassed subject count, age range, syncope protocols, ML type, hemodynamic parameters, and performance metrics. Of the 6301 studies initially identified, 10 studies, involving 1205 participants aged 5 to 82 years, met the inclusion criteria, and formed the basis for it. Selected studies must use ML algorithms in syncope detection with hemodynamic parameters recorded throughout HUTT. The overall ML algorithm performance achieved a sensitivity of 88.8% (95% CI: 79.4-96.1%), specificity of 81.5% (95% CI: 69.8-92.8%) and accuracy of 85.8% (95% CI: 78.6-92.8%). Machine learning improves syncope diagnosis compared to traditional scoring, requiring fewer parameters. Future enhancements with larger databases are anticipated. Integrating ML can curb needless admissions, refine diagnostics, and enhance the quality of life for syncope patients.
  2. Association of psychological distress with arm morbidity symptoms in breast cancer survivors: outcomes from the use of PHQ-9 and GAD-7 questionnaires
    Yusof KM, Mohd Sidik S, Mahmud R, Abdullah M, Avery-Kiejda KA, Rosli R
    Breast Cancer, 2023 Sep;30(5):810-819.
    PMID: 37306933 DOI: 10.1007/s12282-023-01475-0
    BACKGROUND: Although higher survival rates of breast cancer are achieved these days, breast cancer survivors are challenged with unwanted side effects from treatment or management that affect physical, functional, and psychological well-being of an individual. This study aimed to assess psychological distress status in Malaysian breast cancer survivors and factors that affected the condition.

    METHODS: A cross-sectional study design was conducted on 162 breast cancer survivors from various breast cancer support groups in Malaysia. Psychological distress status was assessed based on depression and anxiety scores by applying the Malay version of Patient Health Questionnaire (PHQ-9) and General Anxiety Disorder (GAD-7). Both instruments were self-administered along with a set of questionnaires comprising demographic, medical history, quality of life, and upper extremity function assessment. Outcomes from the PHQ-9 and GAD-7 were analyzed for severity level of psychological distress, and its association with relevant variables, arm morbidity symptoms, as well as the duration of cancer survivorship.

    RESULTS: The univariate analysis showed that breast cancer survivors with arm morbidities after breast surgery had a higher score of depression (5.0 vs 4.0, p = 0.011) and anxiety (3.0 vs 1.0, p = 0.026) than those who did not. Besides that, receiving fewer post-rehabilitation treatments (p = 0.049) and having a family history of cancer (p = 0.022) were correlated with higher anxiety level. The level of depression and anxiety was inversely proportionate with quality of life and positively correlated with greater disability of the arm function (p 

  3. Integrated consensus genetic map and genomic scaffold re-ordering of oil palm (Elaeis guineensis) genome
    Mohd Sanusi NSN, Rosli R, Chan KL, Halim MAA, Ting NC, Singh R, et al.
    Comput Biol Chem, 2023 Feb;102:107801.
    PMID: 36528019 DOI: 10.1016/j.compbiolchem.2022.107801
    A high-quality reference genome is an important resource that can help decipher the genetic basis of traits in combination with linkage or association analyses. The publicly available oil palm draft genome sequence of AVROS pisifera (EG5) accounts for 1.535 Gb of the 1.8 Gb oil palm genome. However, the assemblies are fragmented, and the earlier assembly only had 43% of the sequences placed on pseudo-chromosomes. By integrating a number of SNP and SSR-based genetic maps, a consensus map (AM_EG5.1), comprising of 828.243 Mb genomic scaffolds anchored to 16 pseudo-chromosomes, was generated. This accounted for 54% of the genome assembly, which is a significant improvement to the original assembly. The total length of N50 scaffolds anchored to the pseudo-chromosomes increased by ∼18% compared to the previous assembly. A total of 139 quantitative trait loci for agronomically important quantitative traits, sourced from literature, were successfully mapped on the new pseudo-chromosomes. The improved assembly could also be used as a reference to identify potential errors in placement of specific markers in the linkage groups of the genetic maps used to assemble the consensus map. The 3422 unique markers from five genetic maps, anchored to the pseudo-chromosomes of AM_EG5.1, are an important resource that can be used preferentially to either construct new maps or fill gaps in existing genetic maps. Synteny analysis further revealed that the AM_EG5.1 had high collinearity with the date palm genome cultivar 'Barhee BC4' and shared most of its segmental duplications. This improved chromosomal-level genome is a valuable resource for genetic research in oil palm.
  4. Fulltext Centella asiatica (L.) Urban. Attenuates Cell Damage in Hydrogen Peroxide-Induced Oxidative Stress in Transgenic Murine Embryonic Stem Cell Line-Derived Neural-Like Cells: A Preliminary Study for Potential Treatment of Alzheimer's Disease
    Mansor NI, Ling KH, Rosli R, Hassan Z, Adenan MI, Nordin N
    J Alzheimers Dis, 2023;94(s1):S21-S44.
    PMID: 37334592 DOI: 10.3233/JAD-221233
    BACKGROUND: Centella asiatica (L.) (C. asiatica) is commonly known in South East and South East Asia communities for its nutritional and medicinal benefits. Besides being traditionally used to enhance memory and accelerate wound healing, its phytochemicals have been extensively documented for their neuroprotective, neuroregenerative, and antioxidant properties.

    OBJECTIVE: The present study aims to investigate the effects of a standardized raw extract of C. asiatica (RECA) on hydrogen peroxide (H2O2)-induced oxidative stress and apoptotic death in neural-like cells derived from mouse embryonic stem (ES) cell line.

    METHODS: A transgenic mouse ES cell (46C) was differentiated into neural-like cells using 4-/4+ protocol with addition of all-trans retinoic acid. These cells were then exposed to H2O2 for 24 h. The effects of RECA on H2O2-induced neural-like cells were assessed through cell viability, apoptosis, and reactive oxygen species (ROS) assays, as well as neurite length measurement. The gene expression levels of neuronal-specific and antioxidant markers were assessed by RT-qPCR analysis.

    RESULTS: Pre-treatment with H2O2 for 24 hours, in a dose-dependent manner, damaged neural-like cells as marked by a decrease in cell viability, substantial increase in intracellular ROS accumulation, and increase in apoptotic rate compared to untreated cells. These cells were used to treat with RECA. Treatment with RECA for 48 h remarkably restored cell survival and promoted neurite outgrowth in the H2O2- damaged neurons by increasing cell viability and decreasing ROS activity. RT-qPCR analysis revealed that RECA upregulated the level of antioxidant genes such as thioredoxin-1 (Trx-1) and heme oxygenase-1 (HO-1) of treated cells, as well as the expression level of neuronal-specific markers such as Tuj1 and MAP2 genes, suggesting their contribution in neuritogenic effect.

    CONCLUSION: Our findings indicate that RECA promotes neuroregenerative effects and exhibits antioxidant properties, suggesting a valuable synergistic activity of its phytochemical constituents, thus, making the extract a promising candidate in preventing or treating oxidative stress-associated Alzheimer's disease.

  5. Fulltext Evaluation of Circulating MicroRNAs and Adipokines in Breast Cancer Survivors with Arm Lymphedema
    Yusof KM, Groen K, Rosli R, Abdullah M, Mahmud R, Avery-Kiejda KA
    Int J Mol Sci, 2022 Sep 26;23(19).
    PMID: 36232660 DOI: 10.3390/ijms231911359
    Breast cancer-related lymphedema (BCRL) is a form of secondary lymphedema that is characterized by abnormal swelling of one or both arms due to the accumulation of lymph fluid in the interstitial tissue spaces, resulting from obstruction of the lymphatic vessels due to surgery insults, radiotherapy, or chemotherapy. Due to the multifactorial nature of this condition, the pathogenesis of secondary lymphedema remains unclear and the search for molecular factors associated with the condition is ongoing. This study aimed to identify serum microRNAs and adipokines associated with BCRL. Blood was collected from 113 breast cancer survivors and processed to obtain serum for small RNA-sequencing (BCRL vs. non-BCRL, n = 7 per group). MicroRNAs that were differentially expressed (fold change >1.5, p < 0.05) between lymphedema cases and those without lymphedema were further quantified in a validation cohort through quantitative reverse transcription PCR (BCRL n = 16, non-BCRL, n = 83). Leptin and adiponectin levels were measured in a combined cohort (BCRL n = 23, non-BCRL n = 90) using enzyme-linked immunosorbent assays. Two of the most significantly upregulated microRNAs, miR-199a-3p and miR-151a-3p, were strongly correlated with the onset of lymphedema and diabetes mellitus in the BCRL group. Leptin levels were higher in the BCRL cohort compared to the non-BCRL cohort (p < 0.05). A metabolic syndrome biomarker, the adiponectin/leptin ratio, was found to be lower in the BCRL group than in the non-BCRL group (median: 0.28 vs. 0.41, p < 0.05). Extensive studies on the mechanisms of the identified microRNAs and association of leptin with arm lymphedema may provide new insights on the potential biomarkers for lymphedema that should be followed up in a prospective cohort study.
  6. Fulltext Chemo-Sensitization of CD133+ Cancer Stem Cell Enhances the Effect of Mesenchymal Stem Cell Expressing TRAIL in Non-Small Cell Lung Cancer Cell Lines
    Fakiruddin KS, Lim MN, Nordin N, Rosli R, Abdullah S
    Biology (Basel), 2021 Oct 26;10(11).
    PMID: 34827096 DOI: 10.3390/biology10111103
    Pre-clinical studies have demonstrated the efficacy of mesenchymal stem cells (MSCs) expressing tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) or MSC-TRAIL against several tumors. However, due to the existence of cancer stem cells (CSCs), some tumors, including non-small cell lung cancer (NSCLC), exhibit TRAIL resistance. This study was designed to evaluate the capacity of using first-line chemotherapies including cisplatin, 5-fluorouracil (5-FU) and vinorelbine to act as a chemo-sensitizer on CD133+ (prominin-1 positive) CSCs derived from NSCLC cell lines (A549, H460 and H2170) for the purpose of MSC-TRAIL-induced inhibition. We showed that MSC-TRAIL was resistant to all three chemotherapies compared to the NSCLC cell lines, suggesting that the chemotherapies had little effect on MSC-TRAIL viability. Pre-treatment using either cisplatin or 5-FU, but not with vinorelbine, was able to increase the efficacy of MSC-TRAIL to kill the TRAIL-resistant A549-derived CSCs. The study also demonstrated that both 5-FU and vinorelbine were an effective chemo-sensitizer, used to increase the anti-tumor effect of MSC-TRAIL against H460- and H2170-derived CSCs. Furthermore, pre-treatment using cisplatin was noted to enhance the effect of MSC-TRAIL in H460-derived CSCs; however, this effect was not detected in the H2170-derived CSCs. These findings suggest that a pre-treatment using certain chemotherapies in NSCLC could enhance the anti-tumor effect of MSC-TRAIL to target the CSCs, and therefore the combination of chemotherapies and MSC-TRAIL may serve as a novel approach for the treatment of NSCLC.
  7. Fulltext Challenges and Research Priorities for Dementia Care in Malaysia from the Perspective of Health and Allied Health Professionals
    Rosli R, Goodson M, Tan MP, Mohan D, Reidpath D, Allotey P, et al.
    Int J Environ Res Public Health, 2021 10 20;18(21).
    PMID: 34769530 DOI: 10.3390/ijerph182111010
    Few studies to date have evaluated dementia care in Malaysia, and the focus of studies has primarily been on epidemiological and laboratory research. In this study, we aimed to identify potential challenges for the delivery of dementia care in Malaysia and priorities for research and enhancing existing dementia care. This study used thematic analysis to evaluate the open and focus group workshop discussions guided by semi-structured questions. Triangulation of the collected data (sticky notes, collated field notes, and transcripts of discussions) was achieved through stakeholder consensus agreement during a workshop held in 2017. Five main themes as priorities for dementia care were identified: (1) availability of a valued multi-disciplinary care service, (2) accessibility of training to provide awareness, (3) the functionality of the governance in establishing regulation and policy to empower care services, (4) perceived availability and accessibility of research data, and (5) influence of cultural uniqueness. The findings of this study seek to enhance existing dementia care in Malaysia but have potential application for other low and middle-income countries with a similar social and health care set up. The constructed relationship between themes also tries to tackle the challenges in a more efficient and effective manner, as none of these aforementioned issues are standalone challenges. In addition, we demonstrated how a carefully constructed workshop with defined aims and objectives can provide a useful analysis tool to evaluate health and social care challenges in a multidisciplinary forum.
  8. Fulltext Assessment of Potential Risk Factors and Skin Ultrasound Presentation Associated with Breast Cancer-Related Lymphedema in Long-Term Breast Cancer Survivors
    Yusof KM, Avery-Kiejda KA, Ahmad Suhaimi S, Ahmad Zamri N, Rusli MEF, Mahmud R, et al.
    Diagnostics (Basel), 2021 Jul 21;11(8).
    PMID: 34441238 DOI: 10.3390/diagnostics11081303
    Breast cancer has been reported to have the highest survival rate among various cancers. However, breast cancer survivors face several challenges following breast cancer treatment including breast cancer-related lymphedema (BCRL), sexual dysfunction, and psychological distress. This study aimed to investigate the potential risk factors of BCRL in long term breast cancer survivors. A total of 160 female breast cancer subjects were recruited on a voluntary basis and arm lymphedema was assessed through self-reporting of diagnosis, arm circumference measurement, and ultrasound examination. A total of 33/160 or 20.5% of the women developed BCRL with significantly higher scores for upper extremity disability (37.14 ± 18.90 vs. 20.08 ± 15.29, p < 0.001) and a lower score for quality of life (103.91 ± 21.80 vs. 115.49 ± 16.80, p = 0.009) as compared to non-lymphedema cases. Univariate analysis revealed that multiple surgeries (OR = 5.70, 95% CI: 1.21-26.8, p < 0.001), axillary lymph nodes excision (>10) (OR = 2.83, 95% CI: 0.94-8.11, p = 0.047), being overweight (≥25 kg/m2) (OR = 2.57, 95% CI: 1.04 - 6.38, p = 0.036), received fewer post-surgery rehabilitation treatment (OR = 2.37, 95% CI: 1.05-5.39, p = 0.036) and hypertension (OR = 2.38, 95% CI: 1.01-5.62, p = 0.043) were associated with an increased risk of BCRL. Meanwhile, multivariate analysis showed that multiple surgeries remained significant and elevated the likelihood of BCRL (OR = 5.83, 95% CI: 1.14-29.78, p = 0.034). Arm swelling was more prominent in the forearm area demonstrated by the highest difference of arm circumference measurement when compared to the upper arm (2.07 ± 2.48 vs. 1.34 ± 1.91 cm, p < 0.001). The total of skinfold thickness of the affected forearm was also significantly higher than the unaffected arms (p < 0.05) as evidenced by the ultrasound examination. The continuous search for risk factors in specific populations may facilitate the development of a standardized method to reduce the occurrence of BCRL and provide better management for breast cancer patients.
  9. Fulltext Oxidative stress cytotoxicity induced by platinum-doped magnesia nanoparticles in cancer cells
    Al-Fahdawi MQ, Al-Doghachi FAJ, Abdullah QK, Hammad RT, Rasedee A, Ibrahim WN, et al.
    Biomed Pharmacother, 2021 Jun;138:111483.
    PMID: 33744756 DOI: 10.1016/j.biopha.2021.111483
    The aim of this study was to prepare, characterize, and determine the in vitro anticancer effects of platinum-doped magnesia (Pt/MgO) nanoparticles. The chemical compositions, functional groups, and size of nanoparticles were determined using X-ray diffraction, Fourier transform infrared spectroscopy, energy dispersive X-ray spectroscopy, transmission electron microscopy, and scanning electron microscopy. Pt/MgO nanoparticles were cuboid and in the nanosize range of 30-50 nm. The cytotoxicity of Pt/MgO nanoparticles was determined via the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay on the human lung and colonic cancer cells (A549 and HT29 respectively) and normal human lung and colonic fibroblasts cells (MRC-5 and CCD-18Co repectively). The Pt/MgO nanoparticles were relatively innocuous to normal cells. Pt/MgO nanoparticles downregulated Bcl-2 and upregulated Bax and p53 tumor suppressor proteins in the cancer cells. Pt/MgO nanoparticles also induced production of reactive oxygen species, decreased cellular glutathione level, and increased lipid peroxidation. Thus, the anticancer effects of Pt/MgO nanoparticles were attributed to the induction of oxidative stress and apoptosis. The study showed the potential of Pt/MgO nanoparticles as an anti-cancer compound.
  10. BsmI-ApaI-TaqI TAC (BAt) Haplotype of Vitamin D Receptor Gene Is Associated with Increased Risk of Major Depressive Disorder
    Lye MS, Tor YS, Tey YY, Shahabudin A, Loh SP, Ibrahim N, et al.
    J Mol Neurosci, 2021 May;71(5):981-990.
    PMID: 33034825 DOI: 10.1007/s12031-020-01719-0
    Heritability of major depressive disorder (MDD) is between 36 and 44%, suggesting that up to nearly half of the phenotypic variability is attributable to genes. A number of genetic polymorphisms have been shown to predispose certain individuals to depression. Of particular interest are the polymorphisms of the vitamin D receptor (VDR) gene. Although the VDR gene has been well characterized and a vast number of polymorphisms have been identified, the association between BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) single-nucleotide polymorphisms (SNPs), together with their haplotypes, and MDD risk have yet to be established. We conducted a matched case-control study with a total of 600 participants comprising 300 major depressive disorder (MDD) cases and 300 controls matched by age, gender and ethnicity in a 1:1 ratio, in four public hospitals in Kuala Lumpur and Selangor. Three adjacent SNPs of the VDR gene-BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236)-were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Odds ratios and 95% confidence intervals (CIs) were obtained from conditional logistic regression using Stata 16. Linkage disequilibrium and haplotype association with MDD were analyzed using the online SNPStats program. None of the genotypes of the three SNPs was significantly associated with risk of developing MDD after adjusting for confounding factors. However, the TAC (BAt) haplotype was associated with increased odds of MDD (adjusted OR = 2.17, 95% CI = 1.30-3.61, p = 0.003) using CCT (baT) as reference haplotype. The findings suggest that the BsmI-ApaI-TaqI TAC (BAt) haplotype of the VDR gene increases susceptibility to MDD.
  11. Fulltext Cross-Cultural Adaptation of the Functional Assessment of Cancer Therapy-Breast (FACT-B) in Malaysian Breast Cancer Survivors
    Md Yusof K, Mahmud R, Abdullah M, Avery-Kiejda KA, Rosli R
    Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1055-1061.
    PMID: 33906296 DOI: 10.31557/APJCP.2021.22.4.1055
    INTRODUCTION: The survival rate of female breast cancer survivors has been reported to be higher than other types of cancer in Malaysia. Nonetheless, breast cancer survivors face new challenges from unwanted side effects of treatment or management such as fatigue, psychological disturbance, or arm swelling, which can lead to the decline of quality of life (QOL). This study aims to adapt the Malay version of the Functional Assessment of Cancer Therapy-Breast (FACT-B) to evaluate the QOL and to test its reliability and validity in Malaysian breast cancer survivors.

    METHODS: The Malay version of the FACT-B, with Disabilities of Arms, Shoulders and Hands (DASH), and Patient Health Questionnaire Anxiety-Depression Scale (PHQ-ADS) were distributed to female breast cancer survivors which were recruited on a voluntary basis, from cancer support groups based in selected states in Malaysia. Reliability was assessed based on internal consistency (Cronbach's α), whereas concurrent validity was examined by comparing domains in FACT-B with DASH and PHQ-ADS. Finally, total scores of each domain were analysed between lymphedema and without lymphedema groups for known-group validity.

    RESULTS: A total of 113 breast cancer survivors agreed to participate (response rate = 100%) in the study. Our results showed that the Cronbach's α value for Malay FACT-B is 0.88, and each domain ranged from 0.62 to 0.88. A strong correlation was found between the physical well-being domain of FACT-B with DASH. Meanwhile, the breast cancer scale (BCS) displayed significant correlation with the instrument, Patient Health Questionnaire- Anxiety Depression Scale (PHQ-ADS), indicating that multiple factors including psychological distress were measured in the BCS domain. Furthermore, the instrument was able to detect differences in physical, functional and QOL between participants from lymphedema and without lymphedema groups.

    CONCLUSION: The Malay version of the FACT-B demonstrated reliable properties and is effective in assessing QOL and can be applied in Malaysian breast cancer survivors.

  12. Fulltext Asymptomatic neurotoxicity of amyloid β-peptides (Aβ1-42 and Aβ25-35) on mouse embryonic stem cell-derived neural cells
    Mansor NI, Ntimi CM, Abdul-Aziz NM, Ling KH, Adam A, Rosli R, et al.
    Bosn J Basic Med Sci, 2021 Feb 01;21(1):98-110.
    PMID: 32156249 DOI: 10.17305/bjbms.2020.4639
    One of the strategies in the establishment of in vitro oxidative stress models for neurodegenerative diseases, such as Alzheimer's disease (AD), is to induce neurotoxicity by amyloid beta (Aβ) peptides in suitable neural cells. Presently, data on the neurotoxicity of Aβ in neural cells differentiated from stem cells are limited. In this study, we attempted to induce oxidative stress in transgenic 46C mouse embryonic stem cell-derived neurons via treatment with Aβ peptides (Aβ1-42 and Aβ25-35). 46C neural cells were generated by promoting the formation of multicellular aggregates, embryoid bodies in the absence of leukemia inhibitory factor, followed by the addition of all-trans retinoic acid as the neural inducer. Mature neuronal cells were exposed to different concentrations of Aβ1-42 and Aβ25-35 for 24 h. Morphological changes, cell viability, and intracellular reactive oxygen species (ROS) production were assessed. We found that 100 µM Aβ1-42 and 50 µM Aβ25-35 only promoted 40% and 10%, respectively, of cell injury and death in the 46C-derived neuronal cells. Interestingly, treatment with each of the Aβ peptides resulted in a significant increase of intracellular ROS activity, as compared to untreated neurons. These findings indicate the potential of using neurons derived from stem cells and Aβ peptides in generating oxidative stress for the establishment of an in vitro AD model that could be useful for drug screening and natural product studies.
  13. Fulltext A Qualitative Study on Formal and Informal Carers' Perceptions of Dementia Care Provision and Management in Malaysia
    Goodson M, McLellan E, Rosli R, Tan MP, Kamaruzzaman S, Robinson L, et al.
    Front Public Health, 2021;9:637484.
    PMID: 34368037 DOI: 10.3389/fpubh.2021.637484
    Background: The number of people living with dementia worldwide is increasing, particularly in low- and middle-income countries (LMICs) where little is known about existing post-diagnostic care and support. This study aimed to better understand healthcare provision for people living with dementia in Malaysia, and to identify priorities for providing timely, quality, and accessible care and support to all. Methods: This is a qualitative interview study on care providers and facilitators (health and community care professionals, paid carers, traditional medicine practitioners, faith healers, community leaders, non-governmental organisations). A topic guide, piloted in Malaysia and peer reviewed by all LMIC partners, elicited the understanding of dementia and dementia care and barriers and facilitators to care for people living with dementia and carers, and perceptions of key priorities for developing efficient, feasible, and sustainable dementia care pathways. Verbatim transcription of audio-recorded interviews was followed by iterative, thematic data analysis. Results: Twenty interviews were conducted (11 healthcare professionals, 4 traditional medicine practitioners, and 5 social support providers). The findings indicate that dementia care and support services exist in Malaysia, but that they are not fully utilised because of variations in infrastructure and facilities across the country. Despite a locally recognised pathway of care being available in an urban area, people with dementia still present to the healthcare system with advanced disease. The interviewees linked this to a public perception that symptoms of dementia, in particular, are normal sequelae of ageing. Earlier detection of dementia is commonly opportunistic when patients present to GPs, government clinic staff, and general physicians with other ailments. Dementia may only be identified by practitioners who have some specialist interest or expertise in it. Workforce factors that hindered early identification and management of dementia included lack of specialists, overburdened clinics, and limited knowledge of dementia and training in guideline use. Post-diagnostic social care was reported to be largely the domain of families, but additional community-based support was reported to be available in some areas. Raising awareness for both the public and medical professionals, prevention, and more support from the government are seen as key priorities to improve dementia management. Conclusions: This qualitative study provides novel insight into the availability, delivery, and use of post-diagnostic care and support in Malaysia from the perspective of care providers. The respondents in this study perceived that while there was a provision for dementia care in the hospital and community settings, the different care sectors are largely unaware of the services each provides. Future work should explore how care provision across different service sectors and providers can be supported to better facilitate patient access and referral between primary, secondary, and social care. The importance of supporting families to understand dementia and its progression, and strategies to help them care for relatives was emphasised. There is also a need for broad workforce training and development, at both the postgraduate and undergraduate levels, as well as improved general awareness in the community to encourage earlier help-seeking for symptoms of dementia. This will enable the use of preventive strategies and access to specialist services to optimise care and quality of life for people living with dementia in Malaysia.
  14. Fulltext Crosstalk Between microRNAs and the Pathological Features of Secondary Lymphedema
    Yusof KM, Groen K, Rosli R, Avery-Kiejda KA
    Front Cell Dev Biol, 2021;9:732415.
    PMID: 34733847 DOI: 10.3389/fcell.2021.732415
    Secondary lymphedema is characterized by lymphatic fluid retention and subsequent tissue swelling in one or both limbs that can lead to decreased quality of life. It often arises after loss, obstruction, or blockage of lymphatic vessels due to multifactorial modalities, such as lymphatic insults after surgery, immune system dysfunction, deposition of fat that compresses the lymphatic capillaries, fibrosis, and inflammation. Although secondary lymphedema is often associated with breast cancer, the condition can occur in patients with any type of cancer that requires lymphadenectomy such as gynecological, genitourinary, or head and neck cancers. MicroRNAs demonstrate pivotal roles in regulating gene expression in biological processes such as lymphangiogenesis, angiogenesis, modulation of the immune system, and oxidative stress. MicroRNA profiling has led to the discovery of the molecular mechanisms involved in the pathophysiology of auto-immune, inflammation-related, and metabolic diseases. Although the role of microRNAs in regulating secondary lymphedema is yet to be elucidated, the crosstalk between microRNAs and molecular factors involved in the pathological features of lymphedema, such as skin fibrosis, inflammation, immune dysregulation, and aberrant lipid metabolism have been demonstrated in several studies. MicroRNAs have the potential to serve as biomarkers for diseases and elucidation of their roles in lymphedema can provide a better understanding or new insights of the mechanisms underlying this debilitating condition.
  15. Fulltext The Roles of Non-Coding RNAs in Tumor-Associated Lymphangiogenesis
    Md Yusof K, Rosli R, Abdullah M, A Avery-Kiejda K
    Cancers (Basel), 2020 Nov 06;12(11).
    PMID: 33172072 DOI: 10.3390/cancers12113290
    Lymphatic vessels are regarded as the "forgotten" circulation. Despite this, growing evidence has shown significant roles for the lymphatic circulation in normal and pathological conditions in humans, including cancers. The dissemination of tumor cells to other organs is often mediated by lymphatic vessels that serve as a conduit and is often referred to as tumor-associated lymphangiogenesis. Some of the most well-studied lymphangiogenic factors that govern tumor lymphangiogenesis are the vascular endothelial growth factor (VEGF-C/D and VEGFR-2/3), neuroplilin-2 (NRP2), fibroblast growth factor (FGF), and hepatocyte growth factor (HGF), to name a few. However, recent findings have illustrated that non-coding RNAs are significantly involved in regulating gene expression in most biological processes, including lymphangiogenesis. In this review, we focus on the regulation of growth factors and non-coding RNAs (ncRNAs) in the lymphatic development in normal and cancer physiology. Then, we discuss the lymphangiogenic factors that necessitate tumor-associated lymphangiogenesis, with regards to ncRNAs in various types of cancer. Understanding the different roles of ncRNAs in regulating lymphatic vasculature in normal and cancer conditions may pave the way towards the development of ncRNA-based anti-lymphangiogenic therapy.
  16. Characterization of Oil Palm Acyl-CoA-Binding Proteins and Correlation of Their Gene Expression with Oil Synthesis
    Amiruddin N, Chan PL, Azizi N, Morris PE, Chan KL, Ong PW, et al.
    Plant Cell Physiol, 2020 Apr 01;61(4):735-747.
    PMID: 31883014 DOI: 10.1093/pcp/pcz237
    Acyl-CoA-binding proteins (ACBPs) are involved in binding and trafficking acyl-CoA esters in eukaryotic cells. ACBPs contain a well-conserved acyl-CoA-binding domain. Their various functions have been characterized in the model plant Arabidopsis and, to a lesser extent, in rice. In this study, genome-wide detection and expression analysis of ACBPs were performed on Elaeis guineensis (oil palm), the most important oil crop in the world. Seven E. guineensis ACBPs were identified and classified into four groups according to their deduced amino acid domain organization. Phylogenetic analysis showed conservation of this family with other higher plants. All seven EgACBPs were expressed in most tissues while their differential expression suggests various functions in specific tissues. For example, EgACBP3 had high expression in inflorescences and stalks while EgACBP1 showed strong expression in leaves. Because of the importance of E. guineensis as an oil crop, expression of EgACBPs was specifically examined during fruit development. EgACBP3 showed high expression throughout mesocarp development, while EgACBP1 had enhanced expression during rapid oil synthesis. In endosperm, both EgACBP1 and EgACBP3 exhibited increased expression during seed development. These results provide important information for further investigations on the biological functions of EgACBPs in various tissues and, in particular, their roles in oil synthesis.
  17. Anticancer palladium-doped magnesia nanoparticles: synthesis, characterization, and in vitro study
    Al-Fahdawi MQ, Rasedee A, Al-Doghachi FA, Rosli R, Taufiq-Yap YH, Al-Qubaisi MS
    Nanomedicine (Lond), 2020 03;15(6):547-561.
    PMID: 32063101 DOI: 10.2217/nnm-2019-0178
    Aim: To prepare, physicochemically characterize and determine the anticancer effects of palladium-doped magnesia (Pd/MgO) nanoparticles. Materials & methods: Pd/MgO nanoparticles were prepared by the co-precipitation method from the aqueous solution of Mg(NO3)2.6H2O using K2CO3 and the impregnation of MgO into palladium acetylacetonate. Results: Pd/MgO nanoparticles were between 47 and 70 nm in size, cuboid in shape, and tended to form aggregates. Nanoparticles were more antiproliferative toward cancer than the normal cells. In cancer cells, Pd/MgO nanoparticles induced apoptosis by increasing caspase activities and stimulating cytochrome C release. The anticancer effects of Pd/MgO nanoparticles were accentuated by the upregulation of Bax and p53 and downregulation of Bcl-2 protein expressions. Conclusion: Pd/MgO nanoparticles have potential to be developed as an anticancer compound.
  18. Fulltext Effect of fetal bovine serum on erythropoietin receptor expression and viability of breast cancer cells
    Teo GY, Rasedee A, Al-Haj NA, Beh CY, How CW, Rahman HS, et al.
    Saudi J Biol Sci, 2020 Feb;27(2):653-658.
    PMID: 32210684 DOI: 10.1016/j.sjbs.2019.11.032
    Erythropoietin receptors (EPORs) are present not only in erythrocyte precursors but also in non-hematopoietic cells including cancer cells. In this study, we determined the effect of fetal bovine serum (FBS) in culture medium on the EPOR expression and viability of the estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. Using flow cytometry, we showed that the inclusion of 10% FBS in the medium increased the EPOR expressions and viabilities of MDA-MB-231 and MCF-7 cells. The MDA-MB-231 showed greater EPOR expression than MCF-7 cells, suggesting that the presence of ERs on cells is associated with poor expression of EPOR. Culture medium containing 10% FBS also caused increased number of breast cancer cells entering the synthesis phase of the cell cycle. The study also showed that rHuEPO treatment did not affect viability of breast cancer cells. In conclusion, it was shown that the inclusion of FBS in culture medium increased expression of EPOR in breast cancer cells and rHuEPO treatment had no effect on the proliferation of these cancer cells.
  19. Fulltext Matrix Metallopeptidase 3 Polymorphisms: Emerging genetic Markers in Human Breast Cancer Metastasis
    Suhaimi SA, Chan SC, Rosli R
    J Breast Cancer, 2020 Feb;23(1):1-9.
    PMID: 32140265 DOI: 10.4048/jbc.2020.23.e17
    Matrix metallopeptidase 3 or MMP3, is a zinc-dependent proteolytic enzyme that is involved in various physiological processes via modification of the extracellular matrix. In particular, its over-expression has been associated with cancer metastasis and tumor growth in various cancers including breast cancer. MMP3 gene expression is regulated by several factors such as DNA polymorphisms which also serve as risk factors for breast cancer. As such, DNA polymorphisms of MMP3 have the potential to be utilized as genetic biomarkers for prediction and prognosis of metastatic breast cancer. Presently, genome-wide association studies of MMP3 gene polymorphisms which are associated with breast cancer risk and patient survival in a variety of populations are reviewed. In order to understand the potential role of MMP3 polymorphisms as genetic markers for breast cancer metastasis, the domain structure of MMP3, the regulation of its expression and its role in breast cancer metastasis are also briefly discussed in this review. The emergence of MMP3 gene polymorphisms as prognostic biomarker candidates for breast cancer metastasis may contribute towards improving targeted therapies and categorization of breast cancer cases in order to provide a better and more accurate prognosis.
  20. Fulltext Predictors of recurrence of major depressive disorder
    Lye MS, Tey YY, Tor YS, Shahabudin AF, Ibrahim N, Ling KH, et al.
    PLoS One, 2020;15(3):e0230363.
    PMID: 32191745 DOI: 10.1371/journal.pone.0230363
    A total of 201 patients with major depressive disorder from four hospitals in Malaysia were followed up for 5 years to determine the prognostic factors of recurrent major depressive disorder that could potentially contribute to improving the management of MDD patients. For each individual patient, at the time of recruitment as part of a case-control study, information was collected on recent threatening life events, personality and social and occupational functioning, while blood samples were collected to genotype single nucleotide polymorphisms of vitamin D receptor (VDR), zinc transporter-3 (ZnT3), dopamine transporter-1 (DAT1), brain-derived neurotropic factor (BDNF), serotonin receptor 1A (HT1A) and 2A (HT2A) genes. Kaplan-Meier and Cox-regression were used to estimate hazard functions for recurrence of major depressive disorder. Individuals with severe MDD in previous major depressive episodes had five and a half times higher hazard of developing recurrence compared to mild and moderate MDD (HR = 5.565, 95% CI = 1.631-18.994, p = 0.006). Individuals who scored higher on social avoidance had three and a half times higher hazard of recurrence of MDD (HR = 3.525, 95% CI = 1.349-9.209; p = 0.010). There was significant interaction between ApaI +64978C>A single nucleotide polymorphism and severity. The hazard ratio increased by 6.4 times from mild and moderate to severe MDD for A/A genotype while that for C/A genotype increased by 11.3 times. Social avoidance and severity of depression at first episode were prognostic of recurrence. Screening for personality factors at first encounter with MDD patients needs to be considered as part of the clinical practice. For those at risk of recurrence in relation to social avoidance, the psychological intervention prescribed should be customized to focus on this modifiable factor. Prompt and appropriate management of severe MDD is recommended to reduce risk of recurrence.
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