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Fulltext Proteomic Analysis on Anti-Proliferative and Apoptosis Effects of Curcumin Analog, 1,5-bis(4-Hydroxy-3-Methyoxyphenyl)-1,4-Pentadiene-3-One-Treated Human Glioblastoma and Neuroblastoma Cells

Lee YQ, Rajadurai P, Abas F, Othman I, Naidu R

Front Mol Biosci, 2021;8:645856.
PMID: 33996900 DOI: 10.3389/fmolb.2021.645856

Curcumin analogs with excellent biological properties have been synthesized to address and overcome the poor pharmacokinetic profiles of curcumin. This study aims to investigate the cytotoxicity, anti-proliferative, and apoptosis-inducing ability of curcumin analog, MS13 on human glioblastoma U-87 MG, and neuroblastoma SH-SY5Y cells, and to examine the global proteome changes in these cells following treatment. Our current findings showed that MS13 induced potent cytotoxicity and anti-proliferative effects on both cells. Increased caspase-3 activity and decreased bcl-2 concentration upon treatment indicate that MS13 induces apoptosis in these cells in a dose- and time-dependent manner. The label-free shotgun proteomic analysis has defined the protein profiles in both glioblastoma and neuroblastoma cells, whereby a total of nine common DEPs, inclusive of glyceraldehyde 3-phosphate dehydrogenase (GAPDH), alpha-enolase (ENO1), heat shock protein HSP 90-alpha (HSP90AA1), Heat shock protein HSP 90-beta (HSP90AB1), Eukaryotic translation initiation factor 5A-1 (EFI5A), heterogenous nuclear ribonucleoprotein K (HNRNPK), tubulin beta chain (TUBB), histone H2AX (H2AFX), and Protein SET were identified. Pathway analysis further elucidated that MS13 may induce its anti-tumor effects in both cells via the common enriched pathways, "Glycolysis" and "Post-translational protein modification." Conclusively, MS13 demonstrates an anti-cancer effect that may indicate its potential use in the management of brain malignancies.
Comparison of Malaysia's Bachelor of Dental Technology curriculum with three other countries: Proposing a basic curriculum framework

Lin GSS, Lee YQ, Ng YM, Cheah YY

Eur J Dent Educ, 2023 Aug;27(3):614-621.
PMID: 35997544 DOI: 10.1111/eje.12848

INTRODUCTION: A dental technologist is one of the most essential allied dental health professionals and the dental technology curriculum should be comprehensively reviewed on a regular basis. This study aims to compare the only existing Bachelor of Dental Technology (BDT) curriculum in Malaysia with BDT programmes offered by other well-established universities, and map out the similarities and differences, as well as to explore future recommendations and propose a new curriculum framework.
MATERIALS AND METHODS: A descriptive analysis was carried out using Laurie Brady's four-stage strategy. First, available curriculum materials were collected from four different institutions' electronic webpage: AIMST (Malaysia), GU (Australia), UO (New Zealand) and CMU (United Kingdom), and then compared based on three key domains: curriculum contents, teaching and learning strategies and assessments. Following that, the similarities and differences between various curricula were identified. Future recommendations and a curriculum framework were then proposed.
RESULTS: The core BDT curriculum content is concurred upon by all four universities, with an emphasis on basic sciences, laboratory materials, practical sessions and research projects. However, the credit weightage for each course or module varied across the four institutions, with some offering unique subjects and implementing different teaching methods and assessments. A simple BDT curriculum framework with a proposed syllabus was designed based on the three key domains and future recommendations for curriculum improvement were explored.
CONCLUSION: The present study identified several areas for Malaysian BDT curriculum development and improvement. The proposed framework can be a guide for Malaysian dental schools in designing a comprehensive dental technology programme.
Fulltext Clonal relatedness in the acquisition of intestinal carriage and transmission of multidrug resistant (MDR) Klebsiella pneumoniae and Escherichia coli and its risk factors among preterm infants admitted to the neonatal intensive care unit (NICU)

Lee YQ, Ahmad Kamar A, Velayuthan RD, Chong CW, Teh CSJ

Pediatr Neonatol, 2021 03;62(2):129-137.
PMID: 33218933 DOI: 10.1016/j.pedneo.2020.10.002

BACKGROUND: Gastrointestinal carriage of multidrug resistant (MDR) Gram-negative bacilli, especially Klebsiella pneumoniae and Escherichia coli, was highly associated with severe nosocomial infections. The main objectives of this study were to determine the clonal relatedness of intestinal carriage and transmission risk factors of MDR E. coli and K. pneumoniae amongst preterm infants admitted to the neonatal intensive care unit (NICU).
METHODS: A prospective cohort study of preterm infants with gestational age
Methicillin-resistant Staphylococcus aureus bacteraemia, 2003-2015: Comparative evaluation of changing trends in molecular epidemiology and clinical outcomes of infections

Niek WK, Teh CSJ, Idris N, Sit PS, Lee YQ, Thong KL, et al.

Infect Genet Evol, 2020 11;85:104567.
PMID: 32980576 DOI: 10.1016/j.meegid.2020.104567

Methicillin-resistant Staphylococcus aureus (MRSA) is a prominent pathogen causing invasive infections such as bacteraemia. The continued excessive use of antibiotics to treat MRSA infections has resulted in the evolution of antimicrobial resistant of S. aureus. This study aims to perform a comparative evaluation of changing trends in molecular epidemiology of MRSA and clinical characteristics of patients. This study shows that ST22-MRSA-IV has gradually replaced ST239-MRSA-III as the predominant MRSA clone in the tertiary teaching hospital studied. Independent predictors of mortality among patients included devices in situ at the time of infection, pre-exposure to macrolides, catheter-related bloodstream infection and mono-microbial infection. Hence, our study affirmed community-associated MRSA, which was previously identified from individuals without any exposure to healthcare settings, has now emerged in healthcare settings, causing healthcare-associated MRSA infections.
Fulltext Characterisation of Non-Carbapenemase-Producing Carbapenem-Resistant Klebsiella pneumoniae Based on Their Clinical and Molecular Profile in Malaysia

Lee YQ, Sri La Sri Ponnampalavanar S, Chong CW, Karunakaran R, Vellasamy KM, Abdul Jabar K, et al.

Antibiotics (Basel), 2022 Nov 21;11(11).
PMID: 36421313 DOI: 10.3390/antibiotics11111670

Non-carbapenemase-producing carbapenem-resistant Klebsiella pneumoniae (NC-CRKP) confers carbapenem resistance through a combination of chromosomal mutations and acquired non-carbapenemase resistance mechanisms. In this study, we aimed to evaluate the clinical and molecular profiles of NC-CRKP isolated from patients in a tertiary teaching hospital in Malaysia from January 2013 to October 2019. During the study period, 54 NC-CRKP-infected/colonised patients' isolates were obtained. Clinical parameters were assessed in 52 patients. The all-cause in-hospital mortality rate among NC-CRKP patients was 46.2% (24/52). Twenty-three (44.2%) patients were infected, while others were colonised. Based on the Charlson Comorbidity Index (CCI) score, 92.3% (48/52) of the infected/colonised patients had a score of ≥ 1. Resistance genes found among the 54 NC-CRKP isolates were blaTEM, blaSHV, blaCTX-M, blaOXA, and blaDHA. Porin loss was detected in 25/54 (46.3%) strains. None of the isolated strains conferred carbapenem resistance through the efflux pumps system. In conclusion, only 25/54 (46.3%) NC-CRKP conferred carbapenem resistance through a combination of porin loss and the acquisition of non-carbapenemase resistance mechanisms. The carbapenem resistance mechanisms for the remaining strains (53.7%) should be further investigated as rapid identification and distinction of the NC-CRKP mechanisms enable optimal treatment and infection control efforts.
Impact of BRCA1/2 cascade testing on anxiety, depression, and cancer worry levels among unaffected relatives in a multiethnic Asian cohort

Padmanabhan H, Mariapun S, Lee SY, Hassan NT, Lee DS, Meiser B, et al.

J Genet Couns, 2023 Feb;32(1):43-56.
PMID: 35913122 DOI: 10.1002/jgc4.1619

Cascade testing for families with BRCA pathogenic variants is important to identify relatives who are carriers. These relatives can benefit from appropriate risk management and preventative strategies arising from an inherited increased risk of breast, ovarian, prostate, melanoma, and pancreatic cancers. Cascade testing has the potential to enable cost-effective cancer control even in low- and middle-income settings, but few studies have hitherto evaluated the psychosocial impact of cascade testing in an Asian population, where the cultural and religious beliefs around inheritance and destiny have previously been shown to influence perception and attitudes toward screening. In this study, we evaluated the short- and long-term psychosocial impact of genetic testing among unaffected relatives of probands identified through the Malaysian Breast Cancer Genetics Study and the Malaysian Ovarian Cancer Study, using validated questionnaires (Hospital Anxiety and Depression Scale and Cancer Worry Scale) administered at baseline, and 1-month and 2-year post-disclosure of results. Of the 305 unaffected relatives from 98 independent families who were offered cascade testing, 256 (84%) completed predictive testing and family history of cancers was the only factor significantly associated with uptake of predictive testing. We found that the levels of anxiety, depression, and cancer worry among unaffected relatives decreased significantly after result disclosure and remained low 2-year post-result disclosure. Younger relatives and relatives of Malay descent had higher cancer worry at both baseline and after result disclosure compared to those of Chinese and Indian descent, whereas relatives of Indian descent and those with family history of cancers had higher anxiety and depression levels post-result disclosure. Taken together, the results from this Asian cohort highlight the differences in psychosocial needs in different communities and inform the development of culture-specific genetic counseling strategies.
Fulltext Psychosocial outcome and health behaviour intent of breast cancer patients with BRCA1/2 and PALB2 pathogenic variants unselected by a priori risk

Padmanabhan H, Hassan NT, Wong SW, Lee YQ, Lim J, Hasan SN, et al.

PLoS One, 2022;17(2):e0263675.
PMID: 35167615 DOI: 10.1371/journal.pone.0263675

There is an increasing number of cancer patients undertaking treatment-focused genetic testing despite not having a strong family history or high a priori risk of being carriers because of the decreasing cost of genetic testing and development of new therapies. There are limited studies on the psychosocial outcome of a positive result among breast cancer patients who are at low a priori risk, particularly in women of Asian descent. Breast cancer patients enrolled under the Malaysian Breast Cancer Genetic Study between October 2002 and February 2018 were tested for BRCA1, BRCA2 and PALB2 genes. All 104 carriers identified were invited by a research genetic counsellor for result disclosure. Of the 104 carriers, 64% (N = 66) had low a priori risk as determined by PENN II scores. Psychosocial, risk perception and health behaviour measures survey were conducted at baseline (pre-result disclosure), and at two to six weeks after result disclosure. At baseline, younger carriers with high a priori risk had higher Cancer Worry Scale scores than those with low a priori risk but all scores were within acceptable range. Around 75% and 55% of high a priori risk carriers as well as 80% and 67% of low a priori risk carriers had problems in the "living with cancer" and "children" psychosocial domains respectively. All carriers regardless of their a priori risk demonstrated an improved risk perception that also positively influenced their intent to undergo risk management procedures. This study has shown that with sufficient counselling and support, low a priori risk carriers are able to cope psychologically, have improved perceived risk and increased intent for positive health behaviour despite having less anticipation from a family history prior to knowing their germline carrier status.
Fulltext A multicentre study to determine the in vitro efficacy of flomoxef against extended-spectrum beta-lactamase producing Escherichia coli in Malaysia

Yap PSX, Chong CW, Ponnampalavanar S, Ramli R, Harun A, Tengku Jamaluddin TZM, et al.

PeerJ, 2023;11:e16393.
PMID: 38047021 DOI: 10.7717/peerj.16393

BACKGROUND: The high burden of extended-spectrum beta-lactamase-producing (ESBL)-producing Enterobacterales worldwide, especially in the densely populated South East Asia poses a significant threat to the global transmission of antibiotic resistance. Molecular surveillance of ESBL-producing pathogens in this region is vital for understanding the local epidemiology, informing treatment choices, and addressing the regional and global implications of antibiotic resistance.
METHODS: Therefore, an inventory surveillance of the ESBL-Escherichia coli (ESBL-EC) isolates responsible for infections in Malaysian hospitals was conducted. Additionally, the in vitro efficacy of flomoxef and other established antibiotics against ESBL-EC was evaluated.
RESULTS: A total of 127 non-repetitive ESBL-EC strains isolated from clinical samples were collected during a multicentre study performed in five representative Malaysian hospitals. Of all the isolates, 33.9% were isolated from surgical site infections and 85.8% were hospital-acquired infections. High rates of resistance to cefotaxime (100%), cefepime (100%), aztreonam (100%) and trimethoprim-sulfamethoxazole (100%) were observed based on the broth microdilution test. Carbapenems remained the most effective antibiotics against the ESBL-EC, followed by flomoxef. Antibiotic resistance genes were identified by PCR. The blaCTX-M-1 was the most prevalent ESBL gene, with 28 isolates (22%) harbouring blaCTX-M-1 only, 27 isolates (21.3%) co-harbouring blaCTX-M-1 and blaTEM, and ten isolates (7.9%) co-harbouring blaCTX-M-1, blaTEM and blaSHV. A generalised linear model showed significant antibacterial activity of imipenem against different types of infection. Besides carbapenems, this study also demonstrated a satisfactory antibacterial activity of flomoxef (81.9%) on ESBL-EC, regardless of the types of ESBL genes.