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The interaction of green zinc oxide nanoparticles (ZnO NPs) with bacterial strains are still scarcely reported. This work was conducted to study the green-one-pot-synthesized ZnO NPs from the Aloe Vulgarize (AV) leaf peel extract assisted with different sonication techniques followed by the physicochemical, biological activities and molecular docking studies. The NPs structure was analyzed using FTIR, UV-vis and EDX. The morphology, particle size and crystallinity of ZnO NPs were identified using FESEM and XRD. It was found that the formed flower-like structure with sharp edge and fine size of particulates in ZnO NPs/AV could enhance the bacterial inhibition. The minimum inhibitory concentration (MIC) for all the tested bacterial strains is at 3.125 µg/ml and the bacterial growth curve are dependent on the ZnO NPs dosage. The results of disc diffusion revealed that the ZnO NPs/AV possess better antibacterial effect with bigger ZOI due to the presence of AV active ingredient. The molecular docking between active ingredients of AV in the NPs with the protein of IFCM and 1MWU revealed that low binding energy (E bind  = -6.56 kcal/mol and -8.99 kcal/mol, respectively) attributes to the excessive hydrogen bond from AV that highly influenced their interaction with the amino acid of the selected proteins. Finally, the cytotoxicity test on the biosynthesized ZnO NPs with concentration below 20 µg/ml are found nontoxic on the HDF cell. Overall, ZnO NPs/20 % AV (probe sonication) is considered as the best synthesis option due to its efficient one-pot method, short sonication time but own the best antibacterial effect., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Many studies have investigated the coronary risk factors (CRFs) among premature coronary artery disease (PCAD) patients. However, reports on the proportion and CRFs of PCAD according to different age cut-offs for PCAD is globally under-reported. This study aimed to determine the proportion of PCAD patients and analyse the significant CRFs according to different age cut-offs among percutaneous coronary intervention (PCI)-treated patients. Patients who underwent PCI between 2007 and 2018 in two cardiology centres were included (n = 29,241) and were grouped into four age cut-off groups that defines PCAD: (A) Males/females: < 45, (B) Males: < 50; Females: < 55, (C) Males: < 55; Females: < 60 and (D) Males: < 55; Females: < 65 years old. The average proportion of PCAD was 28%; 9.2% for group (A), 21.5% for group (B), 38.6% and 41.9% for group (C) and (D), respectively. The top three CRFs of PCAD were LDL-c level, TC level and hypertension (HTN). Malay ethnicity, smoking, obesity, family history of PCAD, TC level and history of MI were the independent predictors of PCAD across all age groups. The proportion of PCAD in Malaysia is higher compared to other studies. The most significant risk factors of PCAD are LDL-c, TC levels and HTN. Early prevention, detection and management of the modifiable risk factors are highly warranted to prevent PCAD., (© 2024. The Author(s).)

Baeckea frutescens L. has been traditionally used for treating snakebites and is known to possess antifebrile and hemostatic properties. These properties are closely related to wound healing. This study aimed to evaluate the wound healing properties of B. frutescens leaves extract (BFLE) in vitro and in vivo. The in vitro study focused on proliferation, migration, and expression of TGF-β, IL-1β, VEGF, and MMP-2 genes and proteins. The in vivo study included excisional wound healing, histology, and tensile strength studies. The ethanolic extract of B. frutescens (BFLE) was tested for its effects on proliferation and migration using keratinocytes (HaCaT) and fibroblasts (BJ) cells. Gene and protein expression related to wound healing were analyzed using real-time PCR and Western blot assays. The wound healing properties of BFLE were evaluated in vivo using Wistar albino rats, focusing on excisional wound healing, histology, and tensile strength studies. The BFLE displayed significant proliferative and migratory effects on keratinocytes and fibroblasts cells, while upregulating the expression of TGF-β, IL-1β, VEGF, and MMP-2 genes and proteins. BFLE also exhibited significant wound healing effects on Wistar albino rats' excisional wounds and improved the overall tensile strength. The results suggest that BFLE has strong wound healing properties, as demonstrated by its ability to increase keratinocytes and fibroblasts proliferation and migration, upregulate genes and proteins involved in the wound healing process, and improve wound healing rates and tensile strength. The findings of this study provide important insights into the potential use of B. frutescens as a natural wound healing agent., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Antimicrobial resistance (AMR) is a growing and concerning threat to global public health, necessitating innovative strategies to combat this crisis. Amidine-containing compounds have emerged as promising agents in the battle against AMR. This review gives a summary of recent advances from the past decade in studies of antimicrobial amidine-containing compounds with the aim to feature their structural diversity and the pharmacological relevance of the moiety to antimicrobial activity and their potential use in combating antimicrobial resistance, to the greatest extent possible. Highlighting is put on chemical structure of such compounds in relation to antimicrobial activities such as antibacterial, antifungal, and antiparasitic activities. Researchers commonly modify molecules containing amidine or incorporate amidine into existing antimicrobial agents to enhance their pharmacological attributes and combat antimicrobial resistance. This comprehensive review consolidates the current knowledge on amidine-containing compounds, elucidating their antimicrobial mechanisms and highlighting their promise in addressing the global AMR crisis. By offering a multidisciplinary perspective, we aim to inspire further research and innovation in this critical area of antimicrobial research., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Dr. Noor Aisyah Ahmad Shah reports financial support was provided by 10.13039/501100012322National Defence University of Malaysia. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Previous research has shown that natural medications pose health risks, especially in subjects with comorbidities. This study aimed to evaluate the safety of saffron ethanolic extract (SEE) administration in early and established atherosclerotic rabbits. Rabbits were given a high-cholesterol diet (HCD) for 4 and 8 weeks to induce early and established atherosclerosis respectively, and then they were treated with 50 and 100 mg/kg/day SEE. The body weight of the animals was recorded. Blood samples were collected at baseline, pre-treatment, and post-treatment for hematological studies, lipid profiles, and biochemical profiles. Tissue specimens of the vital organs were subjected to histological examination. The above parameters were significantly altered post-intervention with 4 and 8 weeks of HCD. No significant differences in body weight were observed in all the groups post-treatment with 50 and 100mg/kg of SEE compared to pre-treatment. However, low-density lipoprotein cholesterol, total cholesterol, serum urea, and glucose significantly decreased post-treatment with 50 and 100mg/kg/day SEE compared to pre-treatment in early and established atherosclerosis groups. Hematological parameters that were affected post-intervention with HCD returned to their baseline values post-treatment with 50 and 100mg/kg/day SEE. There was a significant improvement in the vital organs post-treatment with 50 and 100mg/kg SEE. SEE can safely be administered without causing harmful effects on the hematological, biochemical profiles, and vital organs. Notably, SEE exerts hypolipidemic and hypoglycemic effects on atherosclerotic conditions. Further clinical trials are warranted to ensure the safety of saffron administration in patients with atherosclerosis-related diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Abd Rahim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Aims: Patients with familial hypercholesterolemia (FH) are known to have higher exposure to coronary risk than those without FH with similar low-density lipoprotein cholesterol (LDL-C) level. Lipid-lowering medications (LLMs) are the mainstay treatments to lower the risk of premature coronary artery disease in patients with hypercholesterolemia. However, the LLM prescription pattern and its effectiveness among Malaysian patients with FH are not yet reported. The aim of this study was to report the LLM prescribing pattern and its effectiveness in lowering LDL-C level among Malaysian patients with FH treated in specialist hospitals., Methods: Subjects were recruited from lipid and cardiac specialist hospitals. FH was clinically diagnosed using the Dutch Lipid Clinic Network Criteria. Patients' medical history was recorded using a standardized questionnaire. LLM prescription history and baseline LDL-C were acquired from the hospitals' database. Blood samples were acquired for the latest lipid profile assay., Results: A total of 206 patients with FH were recruited. Almost all of them were on LLMs (97.6%). Only 2.9% and 7.8% of the patients achieved the target LDL-C of ＜1.4 and ＜1.8 mmol/L, respectively. The majority of patients who achieved the target LDL-C were prescribed with statin-ezetimibe combination medications and high-intensity or moderate-intensity statins. All patients who were prescribed with ezetimibe monotherapy did not achieve the target LDL-C., Conclusion: The majority of Malaysian patients with FH received LLMs, but only a small fraction achieved the therapeutic target LDL-C level. Further investigation has to be conducted to identify the cause of the suboptimal treatment target attainment, be it the factors of patients or the prescription practice.

Introduction: A 1-year-old Malay girl presented with pallor, failure to thrive and hepatosplenomegaly. Her blood was sent for thalassaemia screening and it was incidentally found that her blood appeared lipaemic., Case Report: Primary and secondary causes of hyperlipidaemia were investigated. Her blood was sent for fasting lipid profile, thyroid function test (TFT), fasting plasma glucose (FPG), liver function test (LFT), renal profile (RP) and HIV screening. Lipaemic interference was removed by high-speed centrifugation. She is a product of non-consanguineous marriage. She is staying together with her stepfather who is HIV positive. Her mother's infective status was negative with no dyslipidaemic features and a normal lipid profile. Lipid profile of her biological father was not known. No other lipid stigmata such as eruptive xanthoma or lipaemia retinalis was seen in the patient. Haemoglobin analysis showed Hb E-Beta thalassaemia major. Her triglycerides was 9.05 mmol/L with normal total cholesterol, 2.85 mmol/L and high-density lipoprotein cholesterol (HDL-c), 0.26 mmol/L. Calculated low-density lipoprotein cholesterol (LDL-c) was invalid as triglycerides was >4.5 mmol/L. TFT, RP, FPG, LFT were normal and HIV status was negative. She was transfused with 10 ml/kg packed cell and her blood post transfusion appeared non lipaemic., Conclusion: Primary hypertriglyceridaemia was excluded based on insignificant family history of dyslipidaemia. Secondary causes of hypertriglyceridaemia were ruled out based on unremarkable laboratory investigations. Thus, we conclude that this patient is having hypertriglyceridaemia thalassaemia syndrome (HTS) which is a rare disorder with unknown pathogenesis. Further research may be required to explore this unknown association.

Background: Familial hypercholesterolemia (FH) is predominantly caused by mutations in the 4 FH candidate genes (FHCGs), namely, low-density lipoprotein receptor (LDLR), apolipoprotein B-100 (APOB-100), proprotein convertase subtilisin/kexin type 9 (PCSK9), and the LDL receptor adaptor protein 1 (LDLRAP1). It is characterized by elevated low-density lipoprotein cholesterol (LDL-c) levels leading to premature coronary artery disease. FH can be clinically diagnosed using established clinical criteria, namely, Simon Broome (SB) and Dutch Lipid Clinic Criteria (DLCC), and can be identified using the Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT), a primary care screening tool., Objective: This study aims to (1) compare the detection rate of genetically confirmed FH and diagnostic accuracy between the FAMCAT, SB, and DLCC in the Malaysian primary care setting; (2) identify the genetic mutation profiles, including novel variants, in individuals with suspected FH in primary care; (3) explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing in primary care; and (4) evaluate the clinical utility of a web-based FH Identification Tool that includes the FAMCAT, SB, and DLCC in the Malaysian primary care setting., Methods: This is a mixed methods evaluation study conducted in 11 Ministry of Health primary care clinics located at the central administrative region of Malaysia. In Work stream 1, the diagnostic accuracy study design is used to compare the detection rate and diagnostic accuracy of the FAMCAT, SB, and DLCC against molecular diagnosis as the gold standard. In Work stream 2, the targeted next-generation sequencing of the 4 FHCGs is used to identify the genetic mutation profiles among individuals with suspected FH. In Work stream 3a, a qualitative semistructured interview methodology is used to explore the experience, concern, and expectation of individuals with suspected FH who have undergone genetic testing. Lastly, in Work stream 3b, a qualitative real-time observation of primary care physicians using the "think-aloud" methodology is applied to evaluate the clinical utility of a web-based FH Identification Tool., Results: The recruitment for Work stream 1, and blood sampling and genetic analysis for Work stream 2 were completed in February 2023. Data collection for Work stream 3 was completed in March 2023. Data analysis for Work streams 1, 2, 3a, and 3b is projected to be completed by June 2023, with the results of this study anticipated to be published by December 2023., Conclusions: This study will provide evidence on which clinical diagnostic criterion is the best to detect FH in the Malaysian primary care setting. The full spectrum of genetic mutations in the FHCGs including novel pathogenic variants will be identified. Patients' perspectives while undergoing genetic testing and the primary care physicians experience in utilizing the web-based tool will be established. These findings will have tremendous impact on the management of patients with FH in primary care and subsequently reduce their risk of premature coronary artery disease., International Registered Report Identifier (irrid): DERR1-10.2196/47911., (©Anis Safura Ramli, Nadeem Qureshi, Hasidah Abdul-Hamid, Aisyah Kamal, Johanes Dedi Kanchau, Nur Syahirah Shahuri, Ralph Kwame Akyea, Luisa Silva, Laura Condon, Suraya Abdul-Razak, Alyaa Al-Khateeb, Yung-An Chua, Mohamed-Syarif Mohamed-Yassin, Noorhida Baharudin, Siti Fatimah Badlishah-Sham, Aznida Firzah Abdul Aziz, Noor Alicezah Mohd Kasim, Siti Hamimah Sheikh Abdul Kadir, Joe Kai, Jo Leonardi-Bee, Hapizah Nawawi. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 02.06.2023.)

BACKGROUND In Malaysia, the prevalence of genetically confirmed heterozygous familial hypercholesterolemia (FH) was reported as 1 in 427. Despite this, FH remains largely underdiagnosed and undertreated in primary care. CASE REPORT In this case series, we report 3 FH cases detected in primary care due to mutations in the low-density lipoprotein receptor (LDLR), apolipoprotein-B (APOB), and proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The mutations in case 1 (frameshift c.660del pathogenic variant in LDLR gene) and case 2 (missense c.10579C>T pathogenic variant in APOB gene) were confirmed as pathogenic, while the mutation in case 3 (missense c.277C>T mutation in PCSK9 gene) may have been benign. In case 1, the patient had the highest LDL-c level, 8.6 mmol/L, and prominent tendon xanthomas. In case 2, the patient had an LDL-c level of 5.7 mmol/L and premature corneal arcus. In case 3, the patient had an LDL-c level of 5.4 mmol/L but had neither of the classical physical findings. Genetic counseling and diagnosis were delivered by primary care physicians. These index cases were initially managed in primary care with statins and therapeutic lifestyle modifications. They were referred to the lipid specialists for up-titration of lipid lowering medications. First-degree relatives were identified and referred for cascade testing. CONCLUSIONS This case series highlights different phenotypical expressions in patients with 3 different FH genetic mutations. Primary care physicians should play a pivotal role in the detection of FH index cases, genetic testing, management, and cascade screening of family members, in partnership with lipid specialists.

Background: Various methods were used to induce atherosclerosis in rabbits. One of the most common methods used is high-cholesterol diet (HCD) feeding. However, the exact amount and duration of HCD feeding to induce early and established atherosclerosis in New Zealand white rabbits (NZWR) continue to be debated among researchers. Therefore, this study aims to evaluate the effectiveness of 1% HCD feeding in inducing early and established atherosclerosis lesions in NZWR., Methods: A total of 50 g/kg/day of 1% HCD was fed to three to four months old male rabbits weighing 1.8 to 2.0 kg for four and eight weeks to induce early and established atherosclerosis respectively. The body weight and lipid profile were measured at baseline and post-HCD intervention. Following euthanasia, the aorta was excised and prepared for histology and immunohistochemical analysis to confirm the stages of atherosclerosis., Results: The mean body weight of the rabbits in early and established atherosclerosis groups increased significantly up to 17.5% ( p = 0.026) and 19.75% ( p = 0.019) respectively compared to baseline. The total cholesterol level dramatically elevated up to 13-fold ( p = 0.005) and 38-fold ( p = 0.013) compared to baseline, after four and eight weeks of 1% HCD feeding respectively. The low-density lipoprotein level significantly increased up to 42-fold ( p = 0.006) and 128-fold ( p = 0.011) compared to baseline, after four and eight weeks of 1% HCD feeding respectively. Rabbits fed with four and eight weeks 1% HCD significantly developed 5.79% ( p = 0.008) and 21.52% ( p = 0.008) aortic lesion areas compared to the control group. Histological evaluation in the aorta showed accumulation of foam cells in early atherosclerosis group and formation of fibrous plaque and lipid core in the established atherosclerosis group. Rabbits fed with eight weeks HCD showed higher tissue expressions of ICAM-1, VCAM-1, e-selectin, IL-6, IL-8, NF-κBp65, and MMP-12 compared to four weeks of HCD intervention., Conclusions: A total of 50 g/kg/day of 1% HCD for four and eight weeks is sufficient to induce early and established atherosclerosis in NZWR respectively. The consistent results through this method could facilitate researchers in inducing early and established atherosclerosis in NZWR., Competing Interests: The authors declare no conflict of interest., (© 2023 The Author(s). Published by IMR Press.)

Dyslipidaemia is a major cause of morbidity and mortality. The aims of this study are to determine the prevalence of dyslipidaemia subtypes, the proportions of lipid-lowering therapy (LLT) use, and the achievement of low-density lipoprotein cholesterol (LDL-C) treatment targets for high-risk (HR) and very high-risk (VHR) Malaysians. This cross-sectional study involves 5279 participants across 11 states in Malaysia. The data were obtained through a standardised questionnaire, anthropometric measurements, venous glucose and lipid profile. The participants with existing cardiovascular disease (CVD) or diabetes with at least one of the other major risk factors (smoking, hypertension or dyslipidaemia) were grouped into the VHR category. Other participants were risk-categorised using the Framingham General CVD Risk Score (FRS-CVD). The prevalence of elevated LDL-C, LLT use and LDL-C target were set according to respective risk categories. Pearson's chi-squared test was used to test the difference in the proportions. The mean ± standard deviation (SD) age was 41.1 ± 14.8 years, and 62.2% (3283/5279) of the group were females. Within the participant group, 51.5% were found to have elevated total cholesterol, 28.8% had low HDL-C, and 33.8% had high triglyceride. As for elevated LDL-C, 9.8% were in VHR, 8.6% in HR, 5.8% in MR and 34.9% in LR categories. Among the VHR group, 75.8% were not on LLT, and only 15.9% achieved the LDL-C target. As for the HR category, 87.7% were not on LLT, and only 16.1% achieved the LDL-C target. Dyslipidaemia is highly prevalent among Malaysians. The majority of VHR and HR participants were not on LLT and did not achieve LDL-C treatment targets. Proactive programs are warranted to combat dyslipidaemia-associated CVD events in these groups.

Homozygous familial hypercholesterolaemia (FH) is a rare genetic disorder with aberrantly high level of low-density lipoprotein cholesterol (LDL-C) requiring multiple combined aggressive lipidlowering therapy to reduce the progression of atherosclerotic cardiovascular disease. Alirocumab, a proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) has been approved for treatment of FH, which requires further lowering of LDL-C in addition to diet modification and maximally tolerated statin therapy. We report the response of short-term alirocumab treatment on a young patient with clinically and genetically confirmed FH, who suffered from acute coronary syndrome, and in particular, discussed the hypothesised legacy effect of PCSK9i. The patient was initially treated with a combination of high-intensity statin and ezetimibe for 12 weeks. Subsequently, alirocumab was added to the patient's lipid-lowering regime and he managed to attain guideline recommended LDL-C target within 10 weeks. However, alirocumab was stopped at week 54 due to financial constraint. Interestingly, despite cessation of PCSK9i therapy for a period of 30 weeks, the patient's LDL-C level rose slightly not returning to his baseline level.

Familial hypercholesterolaemia (FH) is caused by mutations in lipid metabolism genes, predominantly in low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), proprotein convertase subtilisin/kexin-type 9 (PCSK9) and LDL receptor adaptor protein 1 (LDLRAP1). The prevalence of genetically confirmed FH and the detection rate of pathogenic variants (PV) amongst clinically diagnosed patients is not well established. Targeted next-generation sequencing of LDLR, APOB, PCSK9 and LDLRAP1 was performed on 372 clinically diagnosed Malaysian FH subjects. Out of 361 variants identified, 40 of them were PV (18 = LDLR, 15 = APOB, 5 = PCSK9 and 2 = LDLRAP1). The majority of the PV were LDLR and APOB, where the frequency of both PV were almost similar. About 39% of clinically diagnosed FH have PV in PCSK9 alone and two novel variants of PCSK9 were identified in this study, which have not been described in Malaysia and globally. The prevalence of genetically confirmed potential FH in the community was 1:427, with a detection rate of PV at 0.2% (12/5130). About one-fourth of clinically diagnosed FH in the Malaysian community can be genetically confirmed. The detection rate of genetic confirmation is similar between potential and possible FH groups, suggesting a need for genetic confirmation in index cases from both groups. Clinical and genetic confirmation of FH index cases in the community may enhance the early detection of affected family members through family cascade screening.

The reputation of nanofluids as a convenient heat transfer media has grown in recent years. The synthesis of nanofluids is often challenging, particularly carbon-based nanofluids, due to the rapid agglomeration of the nanoparticles and the instability of the nanofluids. In this regard, surface modification and surfactant addition are potential approaches to improve the physical and thermal properties of carbon-based nanofluids that have been studied and the structural, morphological, and thermal characteristics of surface-oxidised carbon nanofibre (CNF)-based nanofluids has been characterised. Commercial CNF was first subjected to three different acid treatments to introduce surface oxygen functional groups on the CNF surface. Following the physical and thermal characterisation of the three surface-oxidised CNFs (CNF-MA, CNF-MB, and CNF-MC), including Raman spectroscopy, Fourier transform infrared (FTIR), thermogravimetric analysis (TGA), and field emission scanning electron microscopy (FESEM), the CNF-MB was selected as the best method to synthesise the surface-oxidised CNF-based nanofluid. A total of 40 mL of ultrapure water was used as a pure base fluid and mixed with the surface-oxidised CNF at a concentration range of 0.1-1.0 wt.%, with a fixed of 10 wt.% amount of polyvinylpyrrolidone (PVP). The thermal conductivity of CNF-based nanofluid was then characterised at different temperatures (6, 25, and 40 °C). Based on the results, surface oxidation via Method B significantly affected the extent of surface defects and effectively enhanced the group functionality on the CNF surface. Aside from the partially defective and rough surface of CNF-MB surfaces from the FESEM analysis, the presence of surface oxygen functional groups on the CNF wall was confirmed via the Raman analysis, TGA curve, and FTIR analysis. The visual sedimentation observation also showed that the surface-oxidised CNF particles remained dispersed in the nanofluid due to the weakened van der Waals interaction. The dispersion of CNF particles was improved by the presence of PVP, which further stabilised the CNF-based nanofluids. Ultimately, the thermal conductivity of the surface-oxidised CNF-based nanofluid with PVP was significantly improved with the highest enhancement percentage of 18.50, 16.84, and 19.83% at 6, 25, and 40 °C, respectively, at an optimum CNF concentration of 0.7 wt.%.

Cardiovascular disease (CVD) has been a burden to many developing countries for decades, including Malaysia. Although various steps have been taken to prevent and manage CVD, it remains the leading cause of morbidity and mortality. The rising prevalence of CVD risk factors such as hypertension, hypercholesterolaemia, diabetes, overweight and obesity is the main driving force behind the CVD epidemic. Therefore, a nationwide health study coined as the Malaysian Health and Wellbeing Assessment (MyHEBAT) was designed. It aimed to investigate the prevalence of CVD and the associated risk factors in the community across Malaysia. The MyHEBAT study recruited participants (18-75 years old) through community health screening programmes from 11 states in Malaysia. The MyHEBAT study was further divided into two sub-studies, namely, the Cardiovascular Risk Epidemiological Study (MyHEBAT-CRES) and the MyHEBAT Familial Hypercholesterolaemia Study (MyHEBAT-FH). These studies assessed the prevalence of CVD risk factors and the prevalence of FH in the community, respectively. The data garnered from the MyHEBAT study will provide information for healthcare providers to devise better prevention and clinical practice guidelines for managing CVD in Malaysia.

Background: Familial hypercholesterolaemia (FH) patients have elevated levels of low-density lipoprotein cholesterol, rendering them at high risk of premature coronary artery disease (PCAD). However, the FH prevalence among angiogram-proven PCAD (AP-PCAD) patients and their status of coronary risk factors (CRFs) have not been reported in the Asian population., Objectives: This study aimed to (1) determine the prevalence of clinically diagnosed FH among AP-PCAD patients, (2) compare CRFs between AP-PCAD patients with control groups, and (3) identify the independent predictors of PCAD., Methods: AP-PCAD patients and FH patients without PCAD were recruited from Cardiology and Specialist Lipid Clinics. Subjects were divided into AP-PCAD with FH (G1), AP-PCAD without FH (G2), FH without PCAD (G3) and normal controls (G4). Medical records were collected from the clinic database and standardised questionnaires. FH was clinically diagnosed using Dutch Lipid Clinic Network Criteria., Results: A total of 572 subjects were recruited (males:86.4%; mean±SD age: 55.6±8.5years). The prevalence of Definite, Potential and All FH among AP-PCAD patients were 6%(19/319), 16% (51/319) and 45.5% (145/319) respectively. G1 had higher central obesity, family history of PCAD and family history of hypercholesterolaemia compared to other groups. Among all subjects, diabetes [OR(95% CI): 4.7(2.9,7.7)], hypertension [OR(95% CI): 14.1(7.8,25.6)], FH [OR(95% CI): 2.9(1.5,5.5)] and Potential (Definite and Probable) FH [OR(95% CI): 4.5(2.1,9.6)] were independent predictors for PCAD. Among FH patients, family history of PCAD [OR(95% CI): 3.0(1.4,6.3)] and Definite FH [OR(95% CI): 7.1(1.9,27.4)] were independent predictors for PCAD., Conclusion: Potential FH is common among AP-PCAD patients and contributes greatly to the AP-PCAD. FH-PCAD subjects have greater proportions of various risk factors compared to other groups. Presence of FH, diabetes, hypertension, obesity and family history of PCAD are independent predictors of PCAD. FH with PCAD is in very-high-risk category, hence, early management of modifiable CRFs in these patients are warranted., Competing Interests: The authors have declared that no competing interests exist.

Saffron is widely used in traditional medicine to treat various medical disorders, including hyperlipidaemia. This study aims to systematically review the effects of saffron extract (SE) on lipid profile in in vivo studies. A strategic literature search was done following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The Scopus, PubMed (MEDLINE) and Web of Science databases and hand-searching methods were utilised to identify studies published up to January 2020 that reported the effects of SE on lipid profile in a hyperlipidaemic experimental animal model. A total of six articles met the inclusion criteria. The methods of extraction were aqueous ( n = 4), ethanolic ( n = 1) and hydroalcoholic ( n = 1) extracts. Five doses of SE ranging from 10 mg/kg to 100 mg/kg were administered to rats and hamsters, with a duration ranging from 10 days to 8 weeks. SE at doses of 40 mg/kg/day and 80 mg/kg/day significantly decreased the levels of total cholesterol (21.4%-35.4%), low-density lipoproteins (38.7%-50.0%) and triglycerides (TGs) (29.1%-45.0%) and markedly increased the level of high-density lipoproteins (36.6%-65%) in the treated group compared to the untreated group with a minimum 3-week intervention duration ( P < 0.05). This systematic review demonstrated that SE exhibits hypolipidaemic effects compared to a placebo. SE has almost the same ability to reduce cholesterol levels as the standard therapy., Competing Interests: Conflict of Interest None., (© Penerbit Universiti Sains Malaysia, 2022.)

Aim: Familial hypercholesterolaemia (FH) is the most common autosomal dominant lipid disorder, leading to severe hypercholesterolaemia. Early detection and treatment with lipid-lowering medications may reduce the risk of premature coronary artery disease in FH patients. However, there is scarcity of data on FH prevalence, detection rate, treatment and control with lipid-lowering therapy in the Malaysian community., Methods: Community participants (n=5130) were recruited from all states in Malaysia. Blood samples were collected for lipid profiles and glucose analyses. Personal and family medical histories were collected by means of assisted questionnaire. Physical examination for tendon xanthomata and premature corneal arcus were conducted on-site. FH were clinically screened using Dutch Lipid Clinic Network Criteria., Results: Out of 5130 recruited community participants, 55 patients were clinically categorised as potential (Definite and Probable) FH, making the prevalence FH among the community as 1:100. Based on current total population of Malaysia (32 million), the estimated number of FH patients in Malaysia is 320,000, while the detection rates are estimated as 0.5%. Lipid-lowering medications were prescribed to 54.5% and 30.5% of potential and possible FH patients, respectively, but none of them achieved the therapeutic LDL-c target., Conclusion: Clinically diagnosed FH prevalence in Malaysian population is much higher than most of the populations in the world. At community level, FH patients are clinically under-detected, with majority of them not achieving target LDL-c level for high-risk patients. Therefore, public health measures are warranted for early detection and treatment, to enhance opportunities for premature CAD prevention.

The wide availability and diversity of dangerous microbes poses a considerable problem for health professionals and in the development of new healthcare products. Numerous studies have been conducted to develop membrane filters that have antibacterial properties to solve this problem. Without proper protective filter equipment, healthcare providers, essential workers, and the general public are exposed to the risk of infection. A combination of nanotechnology and biosorption is expected to offer a new and greener approach to improve the usefulness of polysaccharides as an advanced membrane filtration material. Nanocellulose is among the emerging materials of this century and several studies have proven its use in filtering microbes. Its high specific surface area enables the adsorption of various microbial species, and its innate porosity can separate various molecules and retain microbial objects. Besides this, the presence of an abundant OH groups in nanocellulose grants its unique surface modification, which can increase its filtration efficiency through the formation of affinity interactions toward microbes. In this review, an update of the most relevant uses of nanocellulose as a new class of membrane filters against microbes is outlined. Key advancements in surface modifications of nanocellulose to enhance its rejection mechanism are also critically discussed. To the best of our knowledge, this is the first review focusing on the development of nanocellulose as a membrane filter against microbes.

Conducting polymers have been widely used in electrochemical sensors as receptors of the sensing signal's analytes and transducers. Polypyrrole (PPy) conducting polymers are highlighted due to their good electrical conductive properties, ease in preparation, and flexibility of surface characteristics. The objective of this review paper is to discuss the theoretical background of the two main types of electrochemical detection: impedimetric and voltammetric analysis. It also reviews the application and results obtained from these two electrochemical detections when utilizing PPy as a based sensing material in electrochemical sensor. Finally, related aspects in electrochemical sensor construction using PPy will also be discussed. It is anticipated that this review will provide researchers, especially those without an electrochemical analysis background, with an easy-to-understand summary of the concepts and technologies used in electrochemical sensor research, particularly those interested in utilizing PPy as a based sensing material.

Acephate (Ac) is an organophosphate (OP) compound, which is able to inhibit the activity of acetylcholinesterase. Thus, the aim of this study was to optimize the detection of Ac using a thiolated acephate binding aptamer-citrate capped gold nanoparticle (TABA-Cit-AuNP) sensor that also incorporated an image processing technique. The effects of independent variables, such as the incubation period of TABA-Cit-AuNPs (3-24 h) for binding TABA to Cit-AuNPs, the concentration of phosphate buffer saline (PBS) (0.001-0.01 M), the concentration of thiolated acephate binding aptamer (TABA) (50-200 nM), and the concentration of magnesium sulphate (MgSO 4 ) (1-300 mM) were investigated. A quadratic model was developed using a central composite design (CCD) from response surface methodology (RSM) to predict the sensing response to Ac. The optimum conditions such as the concentration of PBS (0.01 M), the concentration of TABA (200 nM), the incubation period of TABA-Cit-AuNPs (3 h), and the concentration of MgSO 4 (1 mM) were used to produce a TABA-Cit-AuNPs sensor for the detection of Ac. Under optimal conditions, this sensor showed a detection ranging from 0.01 to 2.73 μM and a limit of detection (LOD) of 0.06 μM. Real sample analysis demonstrated this aptasensor as a good analytical method to detect Ac., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Homozygous familial hypercholesterolaemia (HoFH) is a rare genetic disorder of lipoprotein metabolism mainly due to mutation of the low-density lipoprotein (LDL)-receptor gene (LDLR). It is a life-threatening disease that causes accelerated, multi-vessel atherosclerosis presented in early childhood. Pregnancy in HoFH may pose early coronary morbidity and mortality to both the foetus and mother. The combination of HoFH and pregnancy can be a fatal condition. While statins are very effective in lowering low-density lipoprotein cholesterol (LDL-C) levels, they are generally contraindicated during pregnancy, thus their use during pregnancy is uncommon. On the other hand, lipid apheresis (LA) has turned into an effective treatment to control cholesterol level amid pregnancy. However, the procedure is not widely available in our region. To date, there are scarcely documented case reports of HoFH in pregnancy in which the majority of them underwent LA to keep LDL-C at a low level. We report a rare case of successful pregnancy outcome of HoFH patient treated with lipid-lowering drugs including statin without LA therapy. Apart from that, we also discussed the genetic findings of the proband and all screened family members in which to the best of our knowledge, the first study using the whole-exome sequencing technique to identify the causative gene mutations for familial hypercholesterolaemia among the Malaysian population.

Chemical contaminants such as heavy metals, dyes, and organic oils seriously affect the environment and threaten human health. About 2 million tons of waste is released every day into the water system. Heavy metals are the largest contributor which cover about 31% of the total composition of water contaminants. Every day, approximately 14 000 people die due to environmental exposure to selected chemicals. Removal of these contaminants down to safe levels is expensive, high energy and unsustainable by current approaches such as oxidation, biodegradation, photocatalysis, precipitation, reverse osmosis and adsorption. A combination of biosorption and nanotechnology offers a new way to remediate these chemical contaminants. Nanostructured materials are proven to have higher adsorption capacities than the same material in its larger-scale form. Nanocellulose is very promising as a high-performance bioadsorbent due to its interesting characteristics of high adsorption capacity, high mechanical strength, hydrophilic surface chemistry, renewability and biodegradability. It has been proven to have higher adsorption capacity and better binding affinity than other similar materials at the macroscale. The high specific surface area and abundance of hydroxyl groups within lead to the possible functionalization of this material for decontamination purposes. Several research papers have shown the effectiveness of nanocellulose in the remediation of chemical contaminants. This review aims to provide an overview of the most recent developments regarding nanocellulose as an adsorbent for chemical contamination remediation. Recent advancements regarding the modification of nanocellulose to enhance its adsorption efficiency towards heavy metals, dyes and organic oils were highlighted. Moreover, the desorption capability and environmental issue related to every developed nanocellulose-based adsorbent were also tackled., Competing Interests: There are no conflicts of interest to declare., (This journal is © The Royal Society of Chemistry.)

Background: Primary care physicians (PCP) play an important role in detecting Familial Hypercholesterolaemia (FH) early. However, knowledge, awareness and practice (KAP) regarding FH among Malaysian PCP are not well established, and there was no validated tool to assess their FH KAP. Thus, the aim of this study was to adapt an FH KAP questionnaire and determine its validity and reliability among Malaysian PCP., Methods: This cross-sectional validation study involved Malaysian PCP with ≥ 1-year work experience in the primary care settings. In Phase 1, the original 19-item FH KAP questionnaire underwent content validation and adaptation by 7 experts. The questionnaire was then converted into an online survey instrument and was face validated by 10 PCP. In Phase 2, the adapted questionnaire was disseminated through e-mail to 1500 PCP. Data were collected on their KAP, demography, qualification and work experience. The construct validity was tested using known-groups validation method. The hypothesis was PCP holding postgraduate qualification (PCP-PG-Qual) would have better FH KAP compared with PCP without postgraduate qualification (PCP-noPG-Qual). Internal consistency reliability was calculated using Kuder Richardson formula-20 (KR-20) and test-retest reliability was tested on 26 PCP using kappa statistics., Results: During content validation and adaptation, 10 items remained unchanged, 8 items were modified, 1 item was moved to demography and 7 items were added. The adapted questionnaire consisted of 25 items (11 knowledge, 5 awareness and 9 practice items). A total of 130 out of 1500 PCP (response rate: 8.7%) completed the questionnaire. The mean percentage knowledge score was found to be significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (53.5, SD ± 13.9 vs. 35.9, SD ± 11.79), t(128) = 6.90, p < 0.001. The median percentage awareness score was found to be significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (15.4, IqR ± 23.08 vs. 7.7, IqR ± 15.38), p = 0.030. The mean percentage practice score was significantly higher in PCP-PG-Qual compared with PCP-noPG-Qual (69.2, SD ± 17.62 vs. 54.4, SD ± 19.28), t(128) = 3.79, p < 0.001. KR-20 value was 0.79 (moderate reliability) and average Kappa was 0.796 (substantial agreement)., Conclusion: This study has proven that the 25-item adapted FH KAP questionnaire is valid and reliable. It can be used to measure and establish FH KAP among PCP in Malaysia.

Introduction: Homicide is the act of killing one human being by another, encompassing death as a result of criminal act including justifiable homicide such as judicial killing and self-defence. This study aimed to ascertain the epidemiology and patterns of injury of homicide victims., Materials and Methods: We reviewed records of medico-legal autopsy cases performed at the Department of Forensic Medicine, Hospital Sungai Buloh, for a period of five years, from January 2012 until December 2016. Subjects' demographic data such as age, gender, nationality, ethnicity and cause of death were recorded., Results: A total of 122 homicide cases were documented. 90% of the victims were 18 to 65 years old. Males contributed 80% of the subjects. An alarming 42% of the subjects comprised of non-Malaysians. Indonesian subjects contributed one-third of the non-citizen category, followed by Bangladeshis at 20.4%. Other nationalities were Burmese, Nepalese, Pakistani, Vietnamese and unspecified. Among Malaysians, 50% of the subjects were Indians, followed by Malay (31.5%) and Chinese (17.8%). Sharp and blunt force traumas were the most common injuries found, contributing 33% and 32% respectively. Asphyxiation and firearm injuries recorded an almost similar frequency, contributing 25% in combination. Other patterns included combined sharp and blunt objects (4.9%) and burns (3%)., Conclusions: A large number of immigrants in the country have significantly increased the forensic casework. Sharp and blunt objects continue to be the weapon of choice due to its easy accessibility. As domestic violence including fatal spousal and child abuse continue to rise, in-depth study in the area is warranted.

Background: Ficus deltoidea (FD) has been shown to have antidiabetic, anti-inflammatory, antinociceptive and antioxidant properties. However, its effects on key events in the pathogenesis of atherosclerosis are unknown., Aim: To investigate the endothelial activation, inflammation, monocyte-endothelial cell binding and oxidative stress effects of four FD varieties., Methods: Human coronary artery endothelial cells (HCAEC) were incubated with different concentrations of aqueous ethanolic extracts of FD var. trengganuensis (FDT), var. kunstleri (FDK), var. deltoidea (FDD) and var. intermedia (FDI), together with LPS. Protein and gene expression of vascular cell adhesion molecule-1 (VCAM-1), intercellular cell adhesion molecule-1 (ICAM-1), endothelial-leukocyte adhesion molecule-1 (E-selectin), interleukin-6 (IL-6), Nuclear factor-κB (NF-κB) p50 and p65 and endothelial nitric oxide synthase (eNOS) were measured using ELISA and QuantiGene plex, respectively. Adhesion of monocyte to HCAEC and formation of reactive oxygen species (ROS) were detected by Rose Bengal staining and 2'-7'-dichlorofluorescein diacetate (DCFH-DA) assay., Results: FDK exhibited the highest inhibition of biomarkers in relation to endothelial activation and inflammation, second in reducing monocyte binding (17.3%) compared to other varieties. FDK (25.6%) was also the most potent at decreasing ROS production., Conclusion: FD has anti-atherogenic effects, possibly mediated by NF-κB and eNOS pathways; with FDK being the most potent variety. It is potentially beneficial in mitigating atherogenesis.

Organophosphorus (OP) compounds are highly toxic synthetic compounds which have been used as pesticides and developed as warfare nerve agents. They represent a threat to both military and civilian populations. OP pesticides affect the nervous system and are thought to have caused at least 5 million deaths since their discovery in the 1930s. At present the treatment of OP nerve agent poisoning commonly involves the use of parenteral oximes. However, the blood brain barrier (BBB) remains a challenge in the delivery of oximes to the central nervous system (CNS). This is because almost all macromolecule drugs (including oximes) fail to pass through the BBB to reach the CNS structures. The presence of a permanent cationic charge in oximes has made these compounds inefficient in crossing the BBB. Thus, oximes are unable to reactivate acetylcholinesterase (AChE) in the CNS. Using current structural and mechanistic understanding of the BBB under both physiological and pathological conditions, it becomes possible to design delivery systems for oximes and other drugs that are able to cross the BBB effectively. This review summarises the recent strategies in the development of oximes which are capable of crossing the BBB to treat OP poisoning. Several new developments using oximes are reviewed along with their advantages and disadvantages. This review could be beneficial for future directions in the development of oxime and other drug delivery systems into the CNS., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Background: Familial hypercholesterolaemia (FH) is the most common inherited metabolic disease with an autosomal dominant mode of inheritance. It is characterised by raised serum levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c), leading to premature coronary artery disease. Children with FH are subjected to early and enhanced atherosclerosis, leading to greater risk of coronary events, including premature coronary artery disease. To the best of our knowledge, this is the first report of a pair of monochorionic diamniotic identical twins with a diagnosis of heterozygous FH, resulting from mutations in both LDLR and ABCG8 genes., Case Presentation: This is a rare case of a pair of 8-year-old monochorionic diamniotic identical twin, who on family cascade screening were diagnosed as definite FH, according to the Dutch Lipid Clinic Criteria (DLCC) with a score of 10. There were no lipid stigmata noted. Baseline lipid profiles revealed severe hypercholesterolaemia, (TC = 10.5 mmol/L, 10.6 mmol/L; LDL-c = 8.8 mmol/L, 8.6 mmol/L respectively). Their father is the index case who initially presented with premature CAD, and subsequently diagnosed as FH. Family cascade screening identified clinical FH in other family members including their paternal grandfather who also had premature CAD, and another elder brother, aged 10 years. Genetic analysis by targeted next-generation sequencing using MiSeq platform (Illumina) was performed to detect mutations in LDLR, APOB100, PCSK9, ABCG5, ABCG8, APOE and LDLRAP1 genes. Results revealed that the twin, their elder brother, father and grandfather are heterozygous for a missense mutation (c.530C > T) in LDLR that was previously reported as a pathogenic mutation. In addition, the twin has heterozygous ABCG8 gene mutation (c.55G > C). Their eldest brother aged 12 years and their mother both had normal lipid profiles with absence of LDLR gene mutation., Conclusion: A rare case of Asian monochorionic diamniotic identical twin, with clinically diagnosed and molecularly confirmed heterozygous FH, due to LDLR and ABCG8 gene mutations have been reported. Childhood FH may not present with the classical physical manifestations including the pathognomonic lipid stigmata as in adults. Therefore, childhood FH can be diagnosed early using a combination of clinical criteria and molecular analyses.

Background and Aims: This study aimed to determine knowledge, awareness and practice (KAP) regarding familial hypercholesterolaemia (FH) among Malaysian primary care physicians (PCP), and to compare KAP between PCP with postgraduate qualification (PCP-PG-Qual) and PCP without PG qualification (PCP-noPG-Qual)., Methods: This was a cross-sectional study involving PCP with ≥1-year working experience in Malaysian primary care settings. An adapted and validated 25-item FH-KAP questionnaire was disseminated during primary care courses. Total score for each domain was calculated by summing-up the correct responses, converted into percentage scores. Normality distribution was examined and comparisons of mean/median percentage scores were made between the two groups of PCP., Results: A total of 372 PCP completed the questionnaire. Regarding knowledge, 77.7% correctly defined FH. However, only 8.3% correctly identified coronary artery disease risk in untreated FH. The mean percentage knowledge score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (48.9, SD ± 13.92 vs. 35.2, SD ± 14.13), t(370) = 8.66, p < 0.001. Regarding awareness, 39% were aware of the NICE FH guideline and only 27.2% were aware of FH diagnostic criteria. The median percentage awareness score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (15.4, IqR ± 23.08 vs. 7.7, IqR ± 11.54), p = 0.013. Regarding practice, only 19.1% stratified FH patients as high risk irrespective of other risk factors. The mean percentage practice score was significantly higher in PCP-PG-Qual compared to PCP-noPG-Qual (52.4, SD ± 12.92 vs. 42.7, SD ± 16.63), t(370) = 9.65, p < 0.001., Conclusions: Substantial gaps in FH-KAP among Malaysian PCP were identified, with PCP-PG-Qual having better knowledge, awareness and practice than PCP-noPG-Qual, emphasising the importance of professional training and certification., (Crown Copyright © 2018. Published by Elsevier B.V. All rights reserved.)

Introduction: Cardiac-related diseases contributed approximately 50-60% of sudden natural death cases. This study aimed to describe the cardiac troponin T (cTnT) findings in post mortem subjects irrespective of the cause and manner of death, and the possible use of post mortem serum cTnT as a modality in investigating sudden natural death., Methods: The study samples comprised 140 subjects aged 18 to 50 years old, natural and unnatural causes of sudden death brought to the Department of Forensic Medicine, Hospital Sungai Buloh (HSgB) and Hospital Sultanah Aminah Johor Bahru (HSAJB) for a period of 12 months. The subjects were categorised into 5 groups: cardiovascular disease (CVD), sudden unexplained death (SUD), thoracic trauma (TT), non-thoracic trauma (NTT) and other diseases (OD)., Results: Median troponin concentration in cases of CVD, SUD, TT, NTT, and OD were 0.51 μg/L, 0.17 μg/L, 0.62 μg/L, 0.90 μg/L and 0.51 μg/L respectively. We found no significant difference of troponin T level in different causes of death (p ≥ 0.05). NTT has the highest median troponin concentration with 0.90 μg/L, SUD possessed the lowest median concentration with 0.17 μg/L., Conclusion: Troponin T is neither specific nor useful as cardiac biomarker for post mortem sample. Therefore, it may not be a useful diagnostic tool at autopsy.