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Antifungal susceptibility profile and biofilm-producing capability of Candida tropicalis isolates in a tertiary medical centre

Navarathinam SD, Neoh HM, Tan TL, Wahab AA, Mohd Nizam Tzar MN, Ding CH

Malays J Pathol, 2023 Dec;45(3):417-424.
PMID: 38155383

BACKGROUND: Candida tropicalis is a globally distributed yeast that has been popping up in the medical literature lately, albeit for unenviable reasons. C. tropicalis is associated with substantial morbidity, mortality as well as drug resistance. The aims of this study were to ascertain the antifungal susceptibility profile and the biofilm-producing capability of this notorious yeast in our centre.
METHODS: C. tropicalis isolates from sterile specimens were collected over a 12-month period. Conclusive identification was achieved biochemically with the ID 32 C kit. Susceptibility to nine antifungal agents was carried out using the colourimetric broth microdilution kit Sensititre YeastOne YO10. Biofilm-producing capability was evaluated by quantifying biomass formation spectrophotometrically following staining with crystal violet.
RESULTS: Twenty-four non-repetitive isolates of C. tropicalis were collected. The resistance rates to the triazole agents were 29.2% for fluconazole, 16.7% for itraconazole, 20.8% for voriconazole and 8.3% for posaconazole-the pan-azole resistance rate was identical to that of posaconazole. No resistance was recorded for amphotericin B, flucysosine or any of the echinocandins tested. A total of 16/24 (66.7%) isolates were categorized as high biomass producers and 8/24 (33.3%) were moderate biomass producers. None of our isolates were low biomass producers.
CONCLUSION: The C. tropicalis isolates from our centre were resistant only to triazole agents, with the highest resistance rate being recorded for fluconazole and the lowest for posaconazole. While this is not by itself alarming, the fact that our isolates were prolific biofilm producers means that even azole-susceptible isolates can be paradoxically refractory to antifungal therapy.
MicroRNA profiling in complete and partial hydatidiform moles

Chia WK, Yeoh HXY, Mustangin M, Khong TY, Wong YP, Tan GC

Malays J Pathol, 2023 Dec;45(3):353-362.
PMID: 38155377

INTRODUCTION: Hydatidiform mole is one of the gestational trophoblastic disease and comprises complete (CM) and partial moles (PM), which carries a risk of developing persistence disease, invasive mole or choriocarcinoma. MicroRNAs (miRNAs) have been discovered in various tissues, including neoplastic tissues. Its role in the pathogenesis of molar pregnancy or as biomarkers are still largely uncertain. The aim of this study is to identify the differentially expressed miRNAs in CM and PM.
MATERIALS AND METHODS: Using next-generation sequencing, the miRNAs profiles of CM (n=3) and PM (n=3) moles, including placenta of non-molar abortus (n=3) as control were determined. The differentially expressed miRNAs between each group were analysed. Subsequently, bioinformatics analysis using miRDB and Targetscan was utilised to predict target genes.
RESULTS: We found 10 differentially expressed miRNAs in CMs and PMs, compared to NMAs, namely miR- 518a-5p, miR-423-3p, miR-503-5p, miR-302a-3p, and miR-1323. The other 5 miRNAs were novel, not listed in the known database. The 3 differentially expressed miRNAs in CMs were predicted to commonly target ZTBT46 and FAM73B mRNAs.
DISCUSSION: miR-518 was consistently observed to be downregulated in CM versus PM, and CM versus NMA. Further bioinformatic analysis to provide insight into the possible role of these miRNAs in the pathogenesis of HMs, progression of disease and as potential diagnostic biomarkers as well as therapeutic targets for HMs is needed.
Fulltext Preventative and therapeutic potential of tocotrienols on musculoskeletal diseases in ageing

Saud Gany SL, Chin KY, Tan JK, Aminuddin A, Makpol S

Front Pharmacol, 2023;14:1290721.
PMID: 38146461 DOI: 10.3389/fphar.2023.1290721

Musculoskeletal health is paramount in an ageing population susceptible to conditions such as osteoporosis, arthritis and fractures. Age-related changes in bone, muscle, and joint function result in declining musculoskeletal health, reduced mobility, increased risk of falls, and persistent discomfort. Preserving musculoskeletal wellbeing is essential for maintaining independence and enhancing the overall quality of life for the elderly. The global burden of musculoskeletal disorders is significant, impacting 1.71 billion individuals worldwide, with age-related muscle atrophy being a well-established phenomenon. Tocotrienols, a unique type of vitamin E found in various sources, demonstrate exceptional antioxidant capabilities compared to tocopherols. This characteristic positions them as promising candidates for addressing musculoskeletal challenges, particularly in mitigating inflammation and oxidative stress underlying musculoskeletal disorders. This review paper comprehensively examines existing research into the preventive and therapeutic potential of tocotrienols in addressing age-related musculoskeletal issues. It sheds light on the promising role of tocotrienols in enhancing musculoskeletal health and overall wellbeing, emphasizing their significance within the broader context of age-related health concerns.
Fulltext A systemic review and recommendation for an autopsy approach to death followed the COVID 19 vaccination

Tan LJ, Koh CP, Lai SK, Poh WC, Othman MS, Hussin H

Forensic Sci Int, 2022 Nov;340:111469.
PMID: 36162300 DOI: 10.1016/j.forsciint.2022.111469

The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started in December 2019. An immediate prevention approach for the outbreak is the development of a vaccination program. Despite a growing number of publications showing the effectiveness of vaccination in preventing SARS-CoV-2 outbreak and reducing the mortality rate, substantial fatal adverse effects were reported after vaccination. Confirmation of the causal relationship of death is required to reimburse under the national vaccination program and could provide a reference for the selection of vaccination. However, a lack of guidelines in the laboratory study and autopsy approach hampered the investigation of post-vaccination death. In this paper, we performed a systematic electronic search on scientific articles related to severe Covid-19 vaccination adverse effects and approaches in identifying the severe side effects using PubMed and Cochrane libraries. A summary on the onset, biochemistry changes and histopathological analyzes of major lethally side effects post-vaccination were discussed. Ultimately, a checklist is suggested to improve the quality of investigation.
Fulltext Transtubular Transoral Approach for Irreducible Ventral Craniovertebral Junction Compressive Pathologies: Surgical Technique and Outcome

Ariffin MH, Mohd-Mahdi SN, Baharudin A, M Tamil A, Abdul-Rhani S, Ibrahim K, et al.

Malays Orthop J, 2023 Jul;17(2):35-42.
PMID: 37583520 DOI: 10.5704/MOJ.2307.006

INTRODUCTION: To investigate the use of a tubular retractor to provide access to the craniovertebral junction (CVJ) sparing the soft palate with the aim of reducing complications associated with traditional transoral approach but yet allowing adequate decompression of the CVJ.
MATERIALS AND METHODS: Twelve consecutive patients with severe myelopathy (JOA-score less than 11) from ventral CVJ compression were operated between 2014-2020 using a tubular retractor assisted transoral decompression.
RESULTS: All patients improved neurologically statistically (p=0.02). There were no posterior pharynx wound infections or rhinolalia. There was one case with incomplete removal of the lateral wall of odontoid and one incidental durotomy.
CONCLUSIONS: A Tubular retractor provides adequate access for decompression of the ventral compression of CVJ. As the tubular retractor pushed away the uvula, soft palate and pillars of the tonsils as it docked on the posterior pharyngeal wall, the traditional complications associated with traditional transoral procedures is completely avoided.
A Deep Learning Framework for Soft Robots with Synthetic Data

Sapai S, Loo JY, Ding ZY, Tan CP, Baskaran VM, Nurzaman SG

Soft Robot, 2023 Dec;10(6):1224-1240.
PMID: 37590485 DOI: 10.1089/soro.2022.0188

Data-driven methods with deep neural networks demonstrate promising results for accurate modeling in soft robots. However, deep neural network models rely on voluminous data in discovering the complex and nonlinear representations inherent in soft robots. Consequently, while it is not always possible, a substantial amount of effort is required for data acquisition, labeling, and annotation. This article introduces a data-driven learning framework based on synthetic data to circumvent the exhaustive data collection process. More specifically, we propose a novel time series generative adversarial network with a self-attention mechanism, Transformer TimeGAN (TTGAN) to precisely learn the complex dynamics of a soft robot. On top of that, the TTGAN is incorporated with a conditioning network that enables it to produce synthetic data for specific soft robot behaviors. The proposed framework is verified on a widely used pneumatic-based soft gripper as an exemplary experimental setup. Experimental results demonstrate that the TTGAN generates synthetic time series data with realistic soft robot dynamics. Critically, a combination of the synthetic and only partially available original data produces a data-driven model with estimation accuracy comparable to models obtained from using complete original data.
Machine Learning-Based Early Prediction of Sepsis Using Electronic Health Records: A Systematic Review

Islam KR, Prithula J, Kumar J, Tan TL, Reaz MBI, Sumon MSI, et al.

J Clin Med, 2023 Aug 30;12(17).
PMID: 37685724 DOI: 10.3390/jcm12175658

BACKGROUND: Sepsis, a life-threatening infection-induced inflammatory condition, has significant global health impacts. Timely detection is crucial for improving patient outcomes as sepsis can rapidly progress to severe forms. The application of machine learning (ML) and deep learning (DL) to predict sepsis using electronic health records (EHRs) has gained considerable attention for timely intervention.
METHODS: PubMed, IEEE Xplore, Google Scholar, and Scopus were searched for relevant studies. All studies that used ML/DL to detect or early-predict the onset of sepsis in the adult population using EHRs were considered. Data were extracted and analyzed from all studies that met the criteria and were also evaluated for their quality.
RESULTS: This systematic review examined 1942 articles, selecting 42 studies while adhering to strict criteria. The chosen studies were predominantly retrospective (n = 38) and spanned diverse geographic settings, with a focus on the United States. Different datasets, sepsis definitions, and prevalence rates were employed, necessitating data augmentation. Heterogeneous parameter utilization, diverse model distribution, and varying quality assessments were observed. Longitudinal data enabled early sepsis prediction, and quality criteria fulfillment varied, with inconsistent funding-article quality correlation.
CONCLUSIONS: This systematic review underscores the significance of ML/DL methods for sepsis detection and early prediction through EHR data.
Fulltext Novel cationic cryptides in Penaeus vannamei demonstrate antimicrobial and anti-cancer activities

Abd El-Aal AAA, Jayakumar FA, Lahiri C, Tan KO, Reginald K

Sci Rep, 2023 Sep 06;13(1):14673.
PMID: 37673929 DOI: 10.1038/s41598-023-41581-9

Cryptides are a subfamily of bioactive peptides that exist in all living organisms. They are latently encrypted in their parent sequences and exhibit a wide range of biological activities when decrypted via in vivo or in vitro proteases. Cationic cryptides tend to be drawn to the negatively charged membranes of microbial and cancer cells, causing cell death through various mechanisms. This makes them promising candidates for alternative antimicrobial and anti-cancer therapies, as their mechanism of action is independent of gene mutations. In the current study, we employed an in silico approach to identify novel cationic cryptides with potential antimicrobial and anti-cancer activities in atypical and systematic strategy by reanalysis of a publicly available RNA-seq dataset of Pacific white shrimp (Penaus vannamei) in response to bacterial infection. Out of 12 cryptides identified, five were selected based on their net charges and potential for cell penetration. Following chemical synthesis, the cryptides were assayed in vitro to test for their biological activities. All five cryptides demonstrated a wide range of selective activity against the tested microbial and cancer cells, their anti-biofilm activities against mature biofilms, and their ability to interact with Gram-positive and negative bacterial membranes. Our research provides a framework for a comprehensive analysis of transcriptomes in various organisms to uncover novel bioactive cationic cryptides. This represents a significant step forward in combating the crisis of multi-drug-resistant microbial and cancer cells, as these cryptides neither induce mutations nor are influenced by mutations in the cells they target.
Effects of high stocking density on growth performance and expression of MyD88, and its temporal expression under the challenge of Vibrio parahaemolyticus in the noble scallop Chlamys nobilis

Feng M, Tan K, Zhang H, Duan X, Li S, Ma H, et al.

Fish Shellfish Immunol, 2023 Oct;141:109059.
PMID: 37678479 DOI: 10.1016/j.fsi.2023.109059

High stocking density has been regarded as an adverse factor in bivalve aquaculture. However, its subsequent molecular response to pathogenic bacteria has been little studied. In order to study the question, a novel MyD88 was first cloned using adult noble scallops Chlamys nobilis (CnMyD88), and its tissue distribution was investigated. Then, 1860 juvenile scallops were divided into two groups with two initial densities of high density (200 individuals/layer, HD) and normal density (110 individuals/layer, ND) and in-situ cultured for three months, in which their growth, survival, and the differential expression of CnMyD88 were examined, respectively. Finally, scallops were injected with the Vibrio parahaemolyticus to assess the temporal expression of CnMyD88. As the results show, CnMyD88 cDNA has a full length of 2241 bp and contains an 1107 bp ORF that encodes a 368-derived protein. It was widely expressed in examined tissues with a significantly higher level in hemolymph, intestine, mantle, and gonad than others. Besides, the HD group showed lower growth (0.39 ± 0.05 mm/day) and survival (37.00 ± 8.49%) than the ND group (0.55 ± 0.02 mm/day and 76.82 ± 5.78%). More importantly, the HD group exhibited significantly lower expression levels of CnMyD88 in their examined tissues than the ND group. After V. parahaemolyticus challenging, CnMyD88 had significantly lower expression levels in the scallops from the HD group than that of the scallops from the ND group at 6th, 24th, and 36th. The present results indicated that high stocking density not only made adverse impacts on growth and survival but also may induce immunosuppression in the noble scallop. Therefore, appropriate low stocking density may be worth considering to adopt in scallop aquaculture.
Clinicopathological correlation of oral candidiasis - Our experience in a tertiary centre over two decades

Tan CC, Lim D, Mohd Hisham NQ, Elias NA, Azli AS, Goh YC

Malays J Pathol, 2023 Aug;45(2):237-246.
PMID: 37658533

INTRODUCTION: Oral candidiasis is one of the most common fungal infections that has been widely reported around the world. In Malaysia, the available studies for this infection are scarce.
MATERIALS AND METHODS: This is a 20-year retrospective study aimed to investigate the prevalence, demographic characteristics, clinical presentations, and the association of oral candidiasis with clinical parameters in oral candidiasis cases reported in the Faculty of Dentistry, Universiti Malaya from 1999 until 2019. A total of 12,964 histopathological records from the Oral Pathology Diagnostic and Research Laboratory (OPDRL) between 1999 to 2019 were retrieved. Oral candidiasis cases were selected according to the inclusion and exclusion criteria. Information of interest was obtained and analysed.
RESULTS: From the total records retrieved, 378 oral candidiasis cases were recorded and 82.8% were diagnosed from smear test. This study showed that oral candidiasis was predominantly reported in female (64.2%) and Indian population (64.2%). The peak incidence was in the sixth decades of life (27.0%). The most commonly affected site was tongue and coated tongue was the most common clinical presentation. More than 50% of the cases had comorbidity and 10.6% were associated with dentures. Ethnicity and site of occurrence were significantly associated (p<0.05) with oral candidiasis.
CONCLUSION: This is the first large-scale study of oral candidiasis cases in Malaysia. The findings of this study are useful for clinical assessment of patients suspected of oral candidiasis.
Fulltext Parasitic egg recognition using convolution and attention network

AlDahoul N, Karim HA, Momo MA, Escobar FIF, Magallanes VA, Tan MJT

Sci Rep, 2023 Sep 02;13(1):14475.
PMID: 37660120 DOI: 10.1038/s41598-023-41711-3

Intestinal parasitic infections (IPIs) caused by protozoan and helminth parasites are among the most common infections in humans in low-and-middle-income countries. IPIs affect not only the health status of a country, but also the economic sector. Over the last decade, pattern recognition and image processing techniques have been developed to automatically identify parasitic eggs in microscopic images. Existing identification techniques are still suffering from diagnosis errors and low sensitivity. Therefore, more accurate and faster solution is still required to recognize parasitic eggs and classify them into several categories. A novel Chula-ParasiteEgg dataset including 11,000 microscopic images proposed in ICIP2022 was utilized to train various methods such as convolutional neural network (CNN) based models and convolution and attention (CoAtNet) based models. The experiments conducted show high recognition performance of the proposed CoAtNet that was tuned with microscopic images of parasitic eggs. The CoAtNet produced an average accuracy of 93%, and an average F1 score of 93%. The finding opens door to integrate the proposed solution in automated parasitological diagnosis.
Fulltext A New Association Of Guillain Barre Syndrome In A Patient With Central Nervous System Melioidosis

Koh EJ, Tan KN, Chan ZW, Candice Wong HY, Chin ML, Lee TC

J Ayub Med Coll Abbottabad, 2023;35(2):334-336.
PMID: 37422834 DOI: 10.55519/JAMC-02-11470

Burkholderia pseudomallei affecting the central nervous system has been extensively reported in the literature. However, combined central nervous system and peripheral nervous system involvement in melioidosis has never been reported. We report a 66-year-old man with diabetes mellitus who was diagnosed to have central nervous system melioidosis and developed acute flaccid quadriplegia. Nerve conduction studies and anti-ganglioside antibodies were consistent with Guillain-Barre syndrome. This case report highlights the importance to recognise the possibility of Guillain Barre syndrome complicating central nervous system melioidosis and stresses the urgency of early consideration of this complication, as early immunomodulatory therapy may hasten neurological recovery.
Fulltext Breast cancer and breast cancer screening use-beliefs and behaviours in a nationwide study in Malaysia

Tan MM, Jamil ASA, Ismail R, Donnelly M, Su TT

BMC Public Health, 2023 Jul 10;23(1):1319.
PMID: 37430228 DOI: 10.1186/s12889-023-16227-0

BACKGROUND: Many upper-middle-income countries (UMICs), including Malaysia, continue to face low breast cancer (BC) screening rates and patients with delayed presentation of BC. This study investigated the role of beliefs about BC and use of screening (e.g. beliefs about whether or not screening reduced the possibility of dying from BC).
METHODS: A nationwide cross-sectional study was conducted in which a total of 813 women (aged ≥ 40 years old) were randomly selected and surveyed using the validated Awareness and Beliefs about Cancer (ABC) measure. The association between BC screening use, sociodemographic characteristics, and negative beliefs about BC screening were analysed using stepwise Poisson regressions.
RESULTS: Seven out of ten Malaysian women believed that BC screening was necessary only when experiencing cancer symptoms. Women > 50 years and from households with more than one car or motorcycle were 1.6 times more likely to attend a mammogram or a clinical breast examination (mammogram: Prevalence Ratio (PR) = 1.60, 95% Confidence Interval (CI) = 1.19-2.14, Clinical Breast Examination (CBE): PR = 1.61, 95% CI = 1.29-1.99). About 23% of women expected to feel anxious about attending BC screening, leading them to avoid the procedure. Women who held negative beliefs about BC screening were 37% less likely to attend a mammogram (PR = 0.63, 95% CI = 0.42-0.94) and 24% less likely to seek a CBE (PR = 0.75, 95% CI = 0.60-0.95).
CONCLUSIONS: Public health strategies or behaviour interventions targeting negative beliefs about BC screening among Malaysian women may increase uptake and reduce late presentation and advanced-stage cancer. Insights from the study suggest that women under 50 years, in the lower income group without a car or motorcycle ownership, and of Malay or Indian ethnicity (compared to Chinese-Malay) are more likely to hold beliefs inhibiting BC screening.
Detection of Sarcopenia in a Community-Dwelling Older Population in China

Zhang HY, Chong MC, Tan MP, Chua YP, Zhang JH

J Geriatr Phys Ther, 2023 Jul 13.
PMID: 37439875 DOI: 10.1519/JPT.0000000000000388

BACKGROUND AND PURPOSE: Sarcopenia is a common muscle disease among the older population, posing an increased risk for functional decline and intervention for loss of independence in daily living. Early detection of sarcopenia among older people before functional decline would be beneficial in enhancing their quality of life. The Asian Working Group for Sarcopenia (AWGS) 2019 recommends the use of 3 screening methods for community-based sarcopenia detection: calf circumference (CC), or the Strength, Assistance in walking, Rise from a chair, Climb stairs, and Falls (SARC-F) questionnaire, or the SARC-F in combination with CC (SARC-CalF) questionnaire. This study aims to compare the relative performance of these 3 methods as screening tools for sarcopenia within a community-dwelling older population.
METHODS: A total number of 700 community-dwelling older adults participated in the current study. Muscle mass, muscle strength, and physical performance were measured with bioelectrical impedance analysis, handgrip strength, and gait speed, respectively. The AWGS 2019 criteria were considered the criterion standard The sensitivity/specificity, receiver operating characteristic (ROC) curve, and area under the receiver operating characteristic curve (AUROC) analyses were determined for CC, SARC-F, and SARC-CalF to determine their relative diagnostic performance.
RESULTS: Sarcopenia was identified in 21.4% of participants according to the AWGS2019 criteria. The overall prevalence of sarcopenia was 56.6%, 14.7%, and 22.9% according to CC, SARC-F, and SARC-CalF, respectively. Calf circumference showed the highest sensitivity but lowest specificity based on AWGS 2019 as the criterion standard regardless of age, gender, and body mass index. The SARC-CalF showed better sensitivity but similar specificity than the SARC-F. The AUROC of CC was significantly better than that of SARC-F and SARC-CalF. The AUROCs of CC, SARC-F, and SARC-CalF were statistically significant in all populations, as well as in the categories of age, gender, and body mass index ( P < .05).
CONCLUSIONS: Calf circumference is useful in ruling out the presence of sarcopenia while the SARC-F is more effective in ruling in sarcopenia, especially in the context of population-based screening. Future studies should be carried out to investigate the value of population-based sarcopenia detection using these screening tools.
A simple and high efficiency purification of His-tagged turnip yellow mosaic virus-like particle (TYMV-VLP) by nickel ion affinity precipitation

Tan FH, Ng JF, Mohamed Alitheen NB, Muhamad A, Yong CY, Lee KW

J Virol Methods, 2023 Sep;319:114771.
PMID: 37437780 DOI: 10.1016/j.jviromet.2023.114771

Virus-like particles (VLPs) is one of the most favourable subjects of study, especially in the field of nanobiotechnology and vaccine development because they possess good immunogenicity and self-adjuvant properties. Conventionally, VLPs can be tagged and purified using affinity chromatography or density gradient ultracentrifugation which is costly and time-consuming. Turnip yellow mosaic virus (TYMV) is a plant virus, where expression of the viral coat protein (TYMVc) in Escherichia coli (E. coli) has been shown to form VLP. In this study, we report a non-chromatographic method for VLP purification using C-terminally His-tagged TYMVc (TYMVcHis6) as a protein model. Firstly, the TYMVcHis6 was cloned and expressed in E. coli. Upon clarification of cell lysate, nickel (II) chloride [NiCl2; 15 µM or equivalent to 0.0000194% (w/v)] was added to precipitate TYMVcHis6. Following centrifugation, the pellet was resuspended in buffer containing 1 mM EDTA to chelate Ni2+, which is then removed via dialysis. A total of 50% of TYMVcHis6 was successfully recovered with purity above 0.90. Later, the purified TYMVcHis6 was analysed with sucrose density ultracentrifugation, dynamic light scattering (DLS), and transmission electron microscopy (TEM) to confirm VLP formation, which is comparable to TYMVcHis6 purified using the standard immobilized metal affinity chromatography (IMAC) column. As the current method omitted the need for IMAC column and beads while significantly reducing the time needed for column washing, nickel affinity precipitation represents a novel method for the purification of VLPs displaying poly-histidine tags (His-tags).
Malaysian burden of disease: years of life lost due to premature deaths

Khaw WF, Chan YM, Nasaruddin NH, Alias N, Tan L, Ganapathy SS

BMC Public Health, 2023 Jul 18;23(1):1383.
PMID: 37464344 DOI: 10.1186/s12889-023-16309-z

BACKGROUND: In Malaysia, the previous mortality burden has been a significant concern, particularly due to the high prevalence of noncommunicable diseases (NCDs) as the leading cause of death. Estimates of mortality are key indicators for monitoring population health and determining priorities in health policies and health planning. The aim of this study was to estimate the disease burden attributed to 113 major diseases and injuries in Malaysia in 2018 using years of life lost (YLL) method.
METHODS: This study included all deaths that occurred in Malaysia in 2018. The YLL was derived by adding the number of deaths from 113 specific diseases and multiplying it by the remaining life expectancy for that age and sex group. Data on life expectancy and mortality were collected from the Department of Statistics Malaysia.
RESULTS: In 2018, there were 3.5 million YLL in Malaysia. Group II (NCDs) caused 72.2% of total YLL. Ischaemic heart disease was the leading cause of premature mortality among Malaysians (17.7%), followed by lower respiratory infections (9.7%), road traffic injuries (8.7%), cerebrovascular disease (stroke) (8.0%), and diabetes mellitus (3.9%).
CONCLUSIONS: NCDs are a significant health concern in Malaysia and are the primary contributor to the overall burden of disease. These results are important in guiding the national health systems on how to design and implement effective interventions for NCDs, as well as how to prioritise and allocate healthcare resources. Key strategies to consider include implementing health promotion campaigns, adopting integrated care models, and implementing policy and regulatory measures. These approaches aim to enhance health outcomes and the managements of NCDs in Malaysia.
3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-Carbonyl]Amino]Propanoic Acid (THICAPA) Is Protective Against Aβ42-Induced Toxicity In Vitro and in an Alzheimer's Disease Drosophila

Tan FHP, Ting ACJ, Najimudin N, Watanabe N, Shamsuddin S, Zainuddin A, et al.

J Gerontol A Biol Sci Med Sci, 2023 Oct 28;78(11):1944-1952.
PMID: 37453137 DOI: 10.1093/gerona/glad169

Alzheimer's disease (AD) is the most prevalent type of dementia globally. The accumulation of amyloid-beta (Aβ) extracellular senile plaques in the brain is one of the hallmark mechanisms found in AD. Aβ42 is the most damaging and aggressively aggregating Aβ isomer produced in the brain. Although Aβ42 has been extensively researched as a crucial peptide connected to the development of the characteristic amyloid fibrils in AD, the specifics of its pathophysiology are still unknown. Therefore, the main objective was to identify novel compounds that could potentially mitigate the negative effects of Aβ42. 3-[[(3S)-1,2,3,4-Tetrahydroisoquinoline-3-carbonyl]amino]propanoic acid (THICAPA) was identified as a ligand for Aβ42 and for reducing fibrillary Aβ42 aggregation. THICAPA also improved cell viability when administered to PC12 neuronal cells that were exposed to Aβ42. Additionally, this compound diminished Aβ42 toxicity in the current AD Drosophila model by rescuing the rough eye phenotype, prolonging the life span, and enhancing motor functions. Through next-generation RNA-sequencing, immune response pathways were downregulated in response to THICAPA treatment. Thus, this study suggests THICAPA as a possible disease-modifying treatment for AD.
Fulltext Atypical Presentation of Lip Nodules in Clinically Diagnosed Juvenile Hyaline Fibromatosis

Khoo ET, Tan JA, Al-Chalabi MMM, Mat Zain MA, Wan Sulaiman WA

Cureus, 2023 Jun;15(6):e40512.
PMID: 37461779 DOI: 10.7759/cureus.40512

Juvenile hyaline fibromatosis (JHF) is a rare, hereditary disease characterized by abnormal hyaline deposits within the skin, soft tissues, joints, and bones. The condition itself is often debilitating, with no curative treatment available. A definitive diagnosis is established by genetic testing. However, the hallmarks of gingival hypertrophy, subcutaneous scalp nodules, and joint contractures can be used as a clinical guide when genetic testing is unavailable. Here, we report an unusual case of a five-year-old child clinically diagnosed with juvenile hyaline fibromatosis with atypical nodules exclusively confined to the perioral region.
Fulltext Intestinal stem cells and gut microbiota therapeutics: hype or hope?

Ahmad Sophien AN, Jusop AS, Tye GJ, Tan YF, Wan Kamarul Zaman WS, Nordin F

Front Med (Lausanne), 2023;10:1195374.
PMID: 37547615 DOI: 10.3389/fmed.2023.1195374

The vital role of the intestines as the main site for the digestion and absorption of nutrients for the body continues subconsciously throughout one's lifetime, but underneath all the complex processes lie the intestinal stem cells and the gut microbiota that work together to maintain the intestinal epithelium. Intestinal stem cells (ISC) are multipotent stem cells from which all intestinal epithelial cells originate, and the gut microbiota refers to the abundant collection of various microorganisms that reside in the gastrointestinal tract. Both reside in the intestines and have many mechanisms and pathways in place with the ultimate goal of co-managing human gastrointestinal tract homeostasis. Based on the abundance of research that is focused on either of these two topics, this suggests that there are many methods by which both players affect one another. Therefore, this review aims to address the relationship between ISC and the gut microbiota in the context of regenerative medicine. Understanding the principles behind both aspects is therefore essential in further studies in the field of regenerative medicine by making use of the underlying designed mechanisms.
Cholesterol-linoleic acid liposomes induced extracellular vesicles secretion from immortalized adipose-derived mesenchymal stem cells for in vitro cell migration

Chen JW, Liew FF, Tan HW, Misran M, Chung I

Artif Cells Nanomed Biotechnol, 2023 Dec;51(1):346-360.
PMID: 37524112 DOI: 10.1080/21691401.2023.2237534

Extracellular vesicles (EVs) are small vesicles that are naturally released by cells and play a crucial role in cell-to-cell communication, tissue repair and regeneration. As naturally secreted EVs are limited, liposomes with different physicochemical properties, such as 1,2-dioleoyl-3-trimethylammonium propane (DOTAP) and linoleic acid (LA) with modifications have been formulated to improve EVs secretion for in vitro wound healing. Various analyses, including dynamic light scattering (DLS) and transmission electron microscopy (TEM) were performed to monitor the successful preparation of different types of liposomes. The results showed that cholesterol-LA liposomes significantly improved the secretion of EVs from immortalized adipose-derived mesenchymal stem cells (AD-MSCs) by 1.5-fold. Based on the cell migration effects obtained from scratch assay, both LA liposomal-induced EVs and cholesterol-LA liposomal-induced EVs significantly enhanced the migration of human keratinocytes (HaCaT) cell line. These findings suggested that LA and cholesterol-LA liposomes that enhance EVs secretion are potentially useful and can be extended for various tissue regeneration applications.

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