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Assessing Complex Left Ventricular Adaptations in Aortic Stenosis Using Personalized 3D + time Cardiac MRI Modeling

Chuah SH, Md Sari NA, Tan LK, Chiam YK, Chan BT, Abdul Aziz YF, et al.

J Cardiovasc Transl Res, 2023 Oct;16(5):1110-1122.
PMID: 37022611 DOI: 10.1007/s12265-023-10375-9

Left ventricular adaptations can be a complex process under the influence of aortic stenosis (AS) and comorbidities. This study proposed and assessed the feasibility of using a motion-corrected personalized 3D + time LV modeling technique to evaluate the adaptive and maladaptive LV response to aid treatment decision-making. A total of 22 AS patients were analyzed and compared against 10 healthy subjects. The 3D + time analysis showed a highly distinct and personalized pattern of remodeling in individual AS patients which is associated with comorbidities and fibrosis. Patients with AS alone showed better wall thickening and synchrony than those comorbid with hypertension. Ischemic heart disease in AS caused impaired wall thickening and synchrony and systolic function. Apart from showing significant correlations to echocardiography and clinical MRI measurements (r: 0.70-0.95; p
Fulltext Prognostic capabilities of coronary computed tomographic angiography before non-cardiac surgery: prospective cohort study

Sheth T, Chan M, Butler C, Chow B, Tandon V, Nagele P, et al.

BMJ, 2015;350:h1907.
PMID: 25902738 DOI: 10.1136/bmj.h1907

To determine if coronary computed tomographic angiography enhances prediction of perioperative risk in patients before non-cardiac surgery and to assess the preoperative coronary anatomy in patients who experience a myocardial infarction after non-cardiac surgery.
Fulltext Combination of the chemokine receptor type 2 (CCR2) antagonist DMX-200 and candesartan for COVID-19: a randomised controlled trial

O'Hara DV, Bassi A, Wilcox A, Jha V, Rathore V, D'Cruz S, et al.

BMJ Open, 2024 Oct 22;14(10):e081790.
PMID: 39438096 DOI: 10.1136/bmjopen-2023-081790

OBJECTIVE: To determine whether a chemokine receptor type 2 antagonist, DMX-200 (repagermanium), in combination with an angiotensin receptor blocker, candesartan, improves clinical outcomes in people with COVID-19.
DESIGN: Prospective, multicentre, double-blind, placebo-controlled trial.
SETTING: Ten acute care hospitals in India.
PARTICIPANTS: Adults <65 years old intended for hospital admission with moderate/severe COVID-19 disease (respiratory rate ≥24 breaths per minute or oxygen saturation ≤93% on room air).
INTERVENTION: DMX-200 120 mg two times per day, or placebo, on background of titratable candesartan commencing at 4 mg two times per day, for 28 days.
MAIN OUTCOME MEASURES: The primary endpoint was COVID-19 disease severity on a modified WHO Clinical Progression Scale (WHO scale) on day 14. Secondary outcomes included the WHO scale at days 28, 60, 90 and 180; intensive care unit (ICU) admission, respiratory failure or death within 28 days; length of hospitalisation; and requirement for ventilatory support or dialysis.
RESULTS: Between December 2021 and August 2022, 518 people were screened, with 49 randomised to DMX-200 or placebo on a background of candesartan. The study was terminated early due to recruitment barriers, including an external requirement to restrict enrolment to adults <65 years old, contributing to a 91% screen failure rate. The median WHO Clinical Progression Scale (WHO scale) score at day 14 for both groups was 1 (IQR 1-1), indicating most participants were discharged with no limitations on activities by this time. Formal comparison was not performed due to the small sample size. One participant receiving DMX-200 died of COVID-19 disease progression. No participants required ICU admission, ventilation or dialysis. Median length of hospitalisation in both groups was 6 days (IQR 6-7 days). WHO scale scores were similar at 28, 60, 90 and 180 days.
CONCLUSION: Due to recruitment barriers, the study was unable to determine whether DMX-200 improves clinical outcomes in people with COVID-19.
TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT05122182.
Assessment of sarcopenia in virally suppressed HIV-infected Asians receiving treatment

Abdul Aziz SA, Mcstea M, Ahmad Bashah NS, Chong ML, Ponnampalavanar S, Syed Omar SF, et al.

AIDS, 2018 05 15;32(8):1025-1034.
PMID: 29547442 DOI: 10.1097/QAD.0000000000001798

OBJECTIVES: In a clinic-based, treated HIV-infected cohort, we identified individuals with sarcopenia and compared with age, sex and ethnically matched controls; and investigated associated risk factors and health outcomes.
DESIGN: Sarcopenia (age-related muscle loss) causes significant morbidity to the elderly, leading to frequent hospitalizations, disability and death. Few have characterized sarcopenia in the HIV-infected who experience accelerated aging.
METHODS: Sarcopenia was defined as low muscle mass with weak grip strength and/or slow gait speed using lower 20th percentiles of controls. Multivariate logistic and linear regression analyses were used to explore risk factors and health-related outcomes associated with sarcopenia among HIV-infected individuals.
RESULTS: We recruited 315 HIV-infected individuals aged at least 25 years with at least 1-year history of undetectable viral load on treatment (HIV RNA <50 copies/ml). Percentage of sarcopenia in 315 HIV-infected was 8%. Subsequently, 153 of the 315 were paired with age, sex and ethnically matched HIV-uninfected. The percentage of sarcopenia in the HIV-infected (n = 153) compared with uninfected (n = 153) were 10 vs. 6% (P = 0.193) respectively, whereas of those at least 50 years of age among them were 17% vs. 4% (P = 0.049), respectively. Associated risk factors among the HIV-infected include education level, employment status, BMI, baseline CD4 cell count, duration on NRTIs and GGT levels. Identified negative outcomes include mortality risk scores [5.42; 95% CI 1.46-9.37; P = 0.007) and functional disability (3.95; 95% CI 1.57-9.97; P = 0.004).
CONCLUSION: Sarcopenia is more prevalent in HIV-infected at least 50 years old compared with matched controls. Our findings highlight associations between sarcopenia with loss of independence and greater healthcare burden among treated HIV-infected individuals necessitating early recognition and intervention.
Fulltext Utility of Using the Montreal Cognitive Assessment (MoCA) as a Screening Tool for HIV-Associated Neurocognitive Disorders (HAND) In Multi-Ethnic Malaysia

Mukherjee T, Sakthivel R, Fong HY, McStea M, Chong ML, Omar SF, et al.

AIDS Behav, 2018 Oct;22(10):3226-3233.
PMID: 29508103 DOI: 10.1007/s10461-018-2073-x

This study determines the optimal cut-off scores for the Montreal Cognitive Assessment (MoCA) to detect HIV-associated neurocognitive disorders (HAND) in a multi-ethnic Malaysian HIV-positive cohort by developing demographically corrected normative standards among 283 HIV-negative community-based controls with overlapping demographic characteristics. The norms (corrected for age, sex, education, ethnicity) were applied to 342 HIV-positive virally suppressed individuals on cART. Impairment rates were classified using the Global Deficit Score (GDS ≥ .5) method. The MoCA was also scored according to the recommended cut-off of ≤ 26, and functional decline was applied to both impairment definitions to classify HAND per the Frascati criteria. The ≤ 26 cut-off considerably overestimated cognitive impairment in both samples (59.4% HIV-negative; 69.3% HIV-positive). In contrast, corrected scores yielded impairment rates consistent with what has been reported internationally in virally suppressed cohorts (23.4% with 83.3% mild impairment, 16.7% moderate impairment). A supplemental file allowing the computation of corrected MoCA scores and impairment status is included.
1 H-NMR metabolomics for evaluating the protective effect of Clinacanthus nutans (Burm. f) Lindau water extract against nitric oxide production in LPS-IFN-γ activated RAW 264.7 macrophages

Khoo LW, Kow ASF, Maulidiani M, Ang MY, Chew WY, Lee MT, et al.

Phytochem Anal, 2019 Jan;30(1):46-61.
PMID: 30183131 DOI: 10.1002/pca.2789

INTRODUCTION: Clinacanthus nutans, a small shrub that is native to Southeast Asia, is commonly used in traditional herbal medicine and as a food source. Its anti-inflammation properties is influenced by the metabolites composition, which can be determined by different binary extraction solvent ratio and extraction methods used during plant post-harvesting stage.
OBJECTIVE: Evaluate the relationship between the chemical composition of C. nutans and its anti-inflammatory properties using nuclear magnetic resonance (NMR) metabolomics approach.
METHODOLOGY: The anti-inflammatory effect of C. nutans air-dried leaves extracted using five different binary extraction solvent ratio and two extraction methods was determined based on their nitric oxide (NO) inhibition effect in lipopolysaccharide-interferon-gamma (LPS-IFN-γ) activated RAW 264.7 macrophages. The relationship between extract bioactivity and metabolite profiles and quantifications were established using 1 H-NMR metabolomics and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The possible metabolite biosynthesis pathway was constructed to further strengthen the findings.
RESULTS: Water and sonication prepared air-dried leaves possessed the highest NO inhibition activity (IC50 = 190.43 ± 12.26 μg/mL, P
Fulltext Classification of Raw Stingless Bee Honeys by Bee Species Origins Using the NMR- and LC-MS-Based Metabolomics Approach

Razali MTA, Zainal ZA, Maulidiani M, Shaari K, Zamri Z, Mohd Idrus MZ, et al.

Molecules, 2018 Aug 28;23(9).
PMID: 30154302 DOI: 10.3390/molecules23092160

The official standard for quality control of honey is currently based on physicochemical properties. However, this method is time-consuming, cost intensive, and does not lead to information on the originality of honey. This study aims to classify raw stingless bee honeys by bee species origins as a potential classifier using the NMR-LCMS-based metabolomics approach. Raw stingless bee honeys were analysed and classified by bee species origins using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and an ultra-high performance liquid chromatography-quadrupole time of flight mass spectrometry (UHPLC-QTOF MS) in combination with chemometrics tools. The honey samples were able to be classified into three different groups based on the bee species origins of Heterotrigona itama, Geniotrigona thoracica, and Tetrigona apicalis. d-Fructofuranose (H. itama honey), β-d-Glucose, d-Xylose, α-d-Glucose (G. thoracica honey), and l-Lactic acid, Acetic acid, l-Alanine (T. apicalis honey) ident d-Fructofuranose identified via ¹H-NMR data and the diagnostic ions of UHPLC-QTOF MS were characterized as the discriminant metabolites or putative chemical markers. It could be suggested that the quality of honey in terms of originality and purity can be rapidly determined using the classification technique by bee species origins via the ¹H-NMR- and UHPLC-QTOF MS-based metabolomics approach.
Fulltext Development and Validation of Positive Smoker Identity Questionnaire (PSmoQi): A New Instrument for Smoking Cessation Correlates

Ahmad MH, Ibrahim MI, Ab Rahman A, Musa KI, Mohd Zin F, Mohd Zain R, et al.

Int J Environ Res Public Health, 2019 01 26;16(3).
PMID: 30691181 DOI: 10.3390/ijerph16030351

Background: The positive smoker identity construct, which was based on West's PRIME Theory, affected the smoking prevalence, quit attempts and cessation success. A validated questionnaire which could measure this rich and complex construct may facilitate prediction models of successful cessation. We aimed to develop and validate a questionnaire that assesses positive smoker identity based on West's PRIME Theory. Method: The initial item pool was developed based on a theoretical framework, empirical literature, existing scales and expert review. The questionnaire was conveniently distributed to 100 smokers. Exploratory factor analysis was utilized to explore domains in the questionnaire. Construct and criterion validity, internal consistency and reliability of the domains were analyzed. Results: The final positive smoker identity questionnaire (PSmoQi) has 26 items under four internally-consistent and reliable domains: Contributory factors, contextual and temporal patterning, identity related to smoking, and behaviour in relation to smoking. The full scale demonstrated good internal consistency (∝ = 0.78), acceptable convergent and divergent validity, and good concurrent validity with the smoker self-concept scale. Conclusion: The current study provides fundamental evidence for the PSmoQi as a valid instrument in research related to smoking cessation and interventional strategy. The PSmoQi contained validated domains which could measure almost a full spectrum of smoking cessation components.
Novel 2-Benzoyl-6-(2,3-Dimethoxybenzylidene)-Cyclohexenol Confers Selectivity toward Human MLH1 Defective Cancer Cells through Synthetic Lethality

Song DSS, Leong SW, Ng KW, Abas F, Shaari K, Leong CO, et al.

SLAS Discov, 2019 06;24(5):548-562.
PMID: 30897027 DOI: 10.1177/2472555219831405

DNA mismatch repair (MMR) deficiency has been associated with a higher risk of developing colorectal, endometrial, and ovarian cancer, and confers resistance in conventional chemotherapy. In addition to the lack of treatment options that work efficaciously on these MMR-deficient cancer patients, there is a great need to discover new drug leads for this purpose. In this study, we screened through a library of commercial and semisynthetic natural compounds to identify potential synthetic lethal drugs that may selectively target MLH1 mutants using MLH1 isogenic colorectal cancer cell lines and various cancer cell lines with known MLH1 status. We identified a novel diarylpentanoid analogue, 2-benzoyl-6-(2,3-dimethoxybenzylidene)-cyclohexenol, coded as AS13, that demonstrated selective toxicity toward MLH1-deficient cancer cells. Subsequent analysis suggested AS13 induced elevated levels of oxidative stress, resulting in DNA damage where only the proficient MLH1 cells were able to be repaired and hence escaping cellular death. While AS13 is modest in potency and selectivity, this discovery has the potential to lead to further drug development that may offer better treatment options for cancer patients with MLH1 deficiency.
Fulltext Anti-Edematogenic and Anti-Granuloma Activity of a Synthetic Curcuminoid Analog, 5-(3,4-Dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one, in Mouse Models of Inflammation

Hisamuddin N, Shaik Mossadeq WM, Sulaiman MR, Abas F, Leong SW, Kamarudin N, et al.

Molecules, 2019 Jul 18;24(14).
PMID: 31323775 DOI: 10.3390/molecules24142614

Curcumin, derived from the rhizome Curcuma longa, has been scientifically proven to possess anti-inflammatory activity but is of limited clinical and veterinary use owing to its low bioavailability and poor solubility. Hence, analogs of curcuminoids with improved biological properties have been synthesized to overcome these limitations. This study aims to provide the pharmacological basis for the use of 5-(3,4-dihydroxyphenyl)-3-hydroxy-1-(2-hydroxyphenyl)penta-2,4-dien-1-one (DHHPD), a synthetic curcuminoid analog, as an anti-edematogenic and anti-granuloma agent. The carrageenan-induced paw edema and the cotton pellet-induced granuloma assays were used to assess the anti-inflammatory activity of DHHPD in mice. The effects of DHHPD on the histaminergic, serotonergic, and bradykininergic systems were determined by the histamine-, serotonin-, and bradykinin-induced paw edema tests, respectively. DHHPD (0.1, 0.3, 1, and 3 mg/kg, intraperitoneal) evoked significant reductions (p < 0.05) in carrageenan-induced paw edema at different time intervals and granuloma formation (p < 0.0001) by 22.08, 32.57, 37.20, and 49.25%, respectively. Furthermore, DHHPD significantly reduced paw edema (p < 0.05) induced by histamine, serotonin, and bradykinin. The present study suggests that DHHPD exerts anti-edematogenic activity, possibly by inhibiting the synthesis or release of autacoid mediators of inflammation through the histaminergic, serotonergic, and bradykininergic systems. The anti-granuloma effect may be attributed to the suppression of transudative, exudative, and proliferative activities associated with inflammation.
Diffuse large B-cell lymphoma in Southeast Asian cohort: expression patterns of B-cell receptor (BCR) repertoire and its linkage with molecular subtypes and response to R-CHOP therapy

Masir N, Akhter A, Roshan TM, Florence CS, Abdul-Rahman F, Tumian NR, et al.

J Clin Pathol, 2019 Sep;72(9):630-635.
PMID: 31189540 DOI: 10.1136/jclinpath-2019-205837

AIMS: Heightened B-cell receptor (BCR) activity in diffuse large B-cell lymphoma (DLBCL) is well established, and a subset of patients with relapsed DLBCL can benefit from BCR-targeted therapies. Universal outreach of such emerging therapies mandates forming a global landscape of BCR molecular signalling in DLBCL, including Southeast Asia.
METHODS: 79 patients with DLBCL (nodal, 59% and extranodal, 41%) treated with rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy were selected. Expression levels of BCR and linked signalling pathway molecules were inter-related with Lymph2Cx-based cell of origin (COO) types and overall survival (OS).
RESULTS: Activated B-cell (ABC) type DLBCL constituted 49% (39/79) compared with germinal centre B-cell (GCB) type DLBCL (29/79; 37%) and revealed poor prognosis (p=0.013). In ABC-DLBCL, high BTK expression exerted poor response to R-CHOP, while OS in ABC-DLBCL with low BTK expression was similar to GCB-DLBCL subtype (p=0.004). High LYN expression coupled with a poor OS for ABC-DLBCL as well as GCB-DLBCL subtypes (p=0.001). Furthermore, high coexpression of BTK/LYN (BTKhigh/LYNhigh) showed poor OS (p=0.019), which linked with upregulation of several genes associated with BCR repertoire and nuclear factor-kappa B pathway (p<0.01). In multivariate analysis, high BTK and LYN expression retained prognostic significance against established clinical predictive factors such as age, International Prognostic Index and COO (p<0.05).
CONCLUSIONS: Our data provide a clear association between high BCR activity in DLBCL and response to therapy in a distinct population. Molecular data provided here will pave the pathway for the provision of promising novel-targeted therapies to patients with DLBCL in Southeast Asia.
Inhibition of nitric oxide and prostaglandin E2 production by pyrrolylated-chalcones: Synthesis, biological activity, crystal structure analysis, and molecular docking studies

Mohd Faudzi SM, Abdullah MA, Abdull Manap MR, Ismail AZ, Rullah K, Mohd Aluwi MFF, et al.

Bioorg Chem, 2020 01;94:103376.
PMID: 31677861 DOI: 10.1016/j.bioorg.2019.103376

In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 - 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 264.7 macrophage cells. Results showed that none of the synthesized compounds were PAINS-associated molecules, with 3-(2,5-dimethoxyphenyl)-1-(1H-pyrrol-2-yl)-prop-2-en-1-one (compound 16) exhibiting remarkable inhibition activity towards PGE2 and NO production with IC50 values of 0.5 ± 1.5 µM and 12.1 ± 1.5 µM, respectively. Physicochemical and ADMET studies showed that majority of the compounds obey to Lipinski's rule of five (RO5) having high blood brain barrier (BBB) penetration, human intestinal absorption (HIA), P- glycoprotein (PgP) inhibition and plasma binding protein (PPB) inhibition. The obtained atomic coordinates for the single-crystal XRD of 16 were then applied in a molecular docking simulation, and compound 16 was found to participate in a number of important binding interactions in the binding sites of ERK and mPGES-1. Based on these results, we have observed the potential of compound 16 as a new hit anti-inflammatory agent, and these findings could serve as a basis for further studies on its mechanism of action.
Phenotyping of hypertensive heart disease and hypertrophic cardiomyopathy using personalized 3D modelling and cardiac cine MRI

Chuah SH, Md Sari NA, Chew BT, Tan LK, Chiam YK, Chan BT, et al.

Phys Med, 2020 Oct;78:137-149.
PMID: 33007738 DOI: 10.1016/j.ejmp.2020.08.022

Differential diagnosis of hypertensive heart disease (HHD) and hypertrophic cardiomyopathy (HCM) is clinically challenging but important for treatment management. This study aims to phenotype HHD and HCM in 3D + time domain by using a multiparametric motion-corrected personalized modeling algorithm and cardiac magnetic resonance (CMR). 44 CMR data, including 12 healthy, 16 HHD and 16 HCM cases, were examined. Multiple CMR phenotype data consisting of geometric and dynamic variables were extracted globally and regionally from the models over a full cardiac cycle for comparison against healthy models and clinical reports. Statistical classifications were used to identify the distinctive characteristics and disease subtypes with overlapping functional data, providing insights into the challenges for differential diagnosis of both types of disease. While HCM is characterized by localized extreme hypertrophy of the LV, wall thickening/contraction/strain was found to be normal and in sync, though it was occasionally exaggerated at normotrophic/less severely hypertrophic regions during systole to preserve the overall ejection fraction (EF) and systolic functionality. Additionally, we observed that hypertrophy in HHD could also be localized, although at less extreme conditions (i.e. more concentric). While fibrosis occurs mostly in those HCM cases with aortic obstruction, only minority of HHD patients were found affected by fibrosis. We demonstrate that subgroups of HHD (i.e. preserved and reduced EF: HHDpEF & HHDrEF) have different 3D + time CMR characteristics. While HHDpEF has cardiac functions in normal range, dilation and heart failure are indicated in HHDrEF as reflected by low LV wall thickening/contraction/strain and synchrony, as well as much reduced EF.
Fulltext A checklist of vascular plants and uses of some species for livelihood-making in Setiu Wetlands, Terengganu, Malaysia

Salim JM, Lee GE, Salam MR, Shahimi S, Pesiu E, Jani JM, et al.

PhytoKeys, 2020;160:7-43.
PMID: 32982549 DOI: 10.3897/phytokeys.160.52946

The Setiu Wetlands, a unique area with nine interconnected habitats, comprises a considerable fraction of the total Peninsular Malaysia's wetland flora. Although botanical collecting in the area has been active in the past 10 years, only a few studies dealing with the wetland flora have been published. Thus, a detailed checklist of this area is urgently needed to ensure the continuity of its inter-relating flora and fauna, as well as the livelihood of the local people. In this work we conducted a survey of the vascular plant flora of Setiu Wetlands and investigated the most important plants used by the local communities. Our checklist accounts for 406 taxa from 277 genera and 106 families, including 24 (6%) species of ferns and lycophytes, three gymnosperms, 257 (64%) dicotyledons and 122 (30%) monocotyledons. This comprehensive plant checklist will be a primary reference for the management of the newly gazetted Setiu Wetlands State Park covering more than 400 hectares of lands and water bodies.
Fulltext Precursors to non-invasive clinical dengue screening: Multivariate signature analysis of in-vivo diffuse skin reflectance spectroscopy on febrile patients in Malaysia

Poh AH, Mahamd Adikan FR, Moghavvemi M, Syed Omar SF, Poh K, Mahyuddin MBH, et al.

PLoS One, 2020;15(4):e0228923.
PMID: 32236132 DOI: 10.1371/journal.pone.0228923

Dengue diagnostics have come a long way. Attempts at breaking away from lab-oriented dengue detection, such as NS1 antigen, IgM or IgG antibodies detection have extensively received numerous coverage. As a result, rapid detection tests (RDTs) have started to gain inroads in medical practice. Rapid detection tests notwithstanding, analysis of blood serum is still a relatively complicated task. This includes the necessity of phlebotomy, centrifugation for blood serum, and other reagent-based tests. Therefore, a non-invasive method of dengue detection was considered. In this study, we present the utility of diffuse reflectance skin spectroscopy (bandwidth of 200-2500nm) on the forearm during the triaging period for dengue screening potential. This is performed with multivariate analysis of 240 triaged febrile/suspected dengue patients. The data is then scrutinized for its clinical validity to be included as either confirmed or probable dengue, or a control group. Based on discriminant analysis of several data normalization models, we can predict the patients' clinical dengue-positivity at ranges of accuracy between ~93-98% depending on mode of the data, with a probably optimal sensitivity and specificity to the clinical diagnosis of ~89% and ~100% respectively. From the outcomes of this study, we recommend further trials with cautious optimism. With these findings, it is hoped that the elusive non-invasive detection of tropical diseases may gain platform in the near future.
Fulltext Complete Genome Sequences of SARS-CoV-2 Strains Detected in Malaysia

Chong YM, Sam IC, Ponnampalavanar S, Syed Omar SF, Kamarulzaman A, Munusamy V, et al.

Microbiol Resour Announc, 2020 May 14;9(20).
PMID: 32409547 DOI: 10.1128/MRA.00383-20

We sequenced four severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genomes from Malaysia during the second wave of infection and found unique mutations which suggest local evolution. Circulating Malaysian strains represent introductions from different countries, particularly during the first wave of infection. Genome sequencing is important for understanding local epidemiology.
Fulltext Indoor microbiome, environmental characteristics and asthma among junior high school students in Johor Bahru, Malaysia

Fu X, Norbäck D, Yuan Q, Li Y, Zhu X, Hashim JH, et al.

Environ Int, 2020 05;138:105664.
PMID: 32200316 DOI: 10.1016/j.envint.2020.105664

Indoor microbial diversity and composition are suggested to affect the prevalence and severity of asthma by previous home microbiome studies, but no microbiome-health association study has been conducted in a school environment, especially in tropical countries. In this study, we collected floor dust and environmental characteristics from 21 classrooms, and health data related to asthma symptoms from 309 students, in junior high schools in Johor Bahru, Malaysia. The bacterial and fungal composition was characterized by sequencing 16s rRNA gene and internal transcribed spacer (ITS) region, and the absolute microbial concentration was quantified by qPCR. In total, 326 bacterial and 255 fungal genera were characterized. Five bacterial (Sphingobium, Rhodomicrobium, Shimwellia, Solirubrobacter, Pleurocapsa) and two fungal (Torulaspora and Leptosphaeriaceae) taxa were protective for asthma severity. Two bacterial taxa, Izhakiella and Robinsoniella, were positively associated with asthma severity. Several protective bacterial taxa including Rhodomicrobium, Shimwellia and Sphingobium have been reported as protective microbes in previous studies, whereas other taxa were first time reported. Environmental characteristics, such as age of building, size of textile curtain per room volume, occurrence of cockroaches, concentration of house dust mite allergens transferred from homes by the occupants, were involved in shaping the overall microbial community but not asthma-associated taxa; whereas visible dampness and mold, which did not change the overall microbial community for floor dust, was negatively associated with the concentration of protective bacteria Rhodomicrobium (β = -2.86, p = 0.021) of asthma. The result indicates complex interactions between microbes, environmental characteristics and asthma symptoms. Overall, this is the first indoor microbiome study to characterize the asthma-associated microbes and their environmental determinant in the tropical area, promoting the understanding of microbial exposure and respiratory health in this region.
In silico studies, nitric oxide, and cholinesterases inhibition activities of pyrazole and pyrazoline analogs of diarylpentanoids

Mohd Faudzi SM, Leong SW, Auwal FA, Abas F, Wai LK, Ahmad S, et al.

Arch Pharm (Weinheim), 2021 Jan;354(1):e2000161.
PMID: 32886410 DOI: 10.1002/ardp.202000161

A new series of pyrazole, phenylpyrazole, and pyrazoline analogs of diarylpentanoids (excluding compounds 3a, 4a, 5a, and 5b) was pan-assay interference compounds-filtered and synthesized via the reaction of diarylpentanoids with hydrazine monohydrate and phenylhydrazine. Each analog was evaluated for its anti-inflammatory ability via the suppression of nitric oxide (NO) on IFN-γ/LPS-activated RAW264.7 macrophage cells. The compounds were also investigated for their inhibitory capability toward acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), using a modification of Ellman's spectrophotometric method. The most potent NO inhibitor was found to be phenylpyrazole analog 4c, followed by 4e, when compared with curcumin. In contrast, pyrazole 3a and pyrazoline 5a were found to be the most selective and effective BChE inhibitors over AChE. The data collected from the single-crystal X-ray diffraction analysis of compound 5a were then applied in a docking simulation to determine the potential binding interactions that were responsible for the anti-BChE activity. The results obtained signify the potential of these pyrazole and pyrazoline scaffolds to be developed as therapeutic agents against inflammatory conditions and Alzheimer's disease.
Fulltext SARS-CoV-2 lineage B.6 was the major contributor to early pandemic transmission in Malaysia

Chong YM, Sam IC, Chong J, Kahar Bador M, Ponnampalavanar S, Syed Omar SF, et al.

PLoS Negl Trop Dis, 2020 11;14(11):e0008744.
PMID: 33253226 DOI: 10.1371/journal.pntd.0008744

Malaysia had 10,219 confirmed cases of COVID-19 as of September 20, 2020. About 33% were associated with a Tablighi Jamaat religious mass gathering held in Kuala Lumpur between February 27 and March 3, 2020, which drove community transmission during Malaysia's second wave. We analysed genome sequences of SARS-CoV-2 from Malaysia to better understand the molecular epidemiology and spread. We obtained 58 SARS-CoV-2 whole genome sequences from patients in Kuala Lumpur and performed phylogenetic analyses on these and a further 57 Malaysian sequences available in the GISAID database. Nine different SARS-CoV-2 lineages (A, B, B.1, B.1.1, B.1.1.1, B.1.36, B.2, B.3 and B.6) were detected in Malaysia. The B.6 lineage was first reported a week after the Tablighi mass gathering and became predominant (65.2%) despite being relatively rare (1.4%) globally. Direct epidemiological links between lineage B.6 viruses and the mass gathering were identified. Increases in reported total cases, Tablighi-associated cases, and community-acquired B.6 lineage strains were temporally linked. Non-B.6 lineages were mainly travel-associated and showed limited onward transmission. There were also temporally correlated increases in B.6 sequences in other Southeast Asian countries, India and Australia, linked to participants returning from this event. Over 95% of global B.6 sequences originated from Asia Pacific. We also report a nsp3-C6310A substitution found in 47.3% of global B.6 sequences which was associated with reduced sensitivity using a commercial diagnostic real-time PCR assay. Lineage B.6 became the predominant cause of community transmission in Malaysia after likely introduction during a religious mass gathering. This event also contributed to spikes of lineage B.6 in other countries in the Asia-Pacific. Mass gatherings can be significant causes of local and global spread of COVID-19. Shared genomic surveillance can be used to identify SARS-CoV-2 transmission chains to aid prevention and control, and to monitor diagnostic molecular assays. Clinical Trial Registration: COVID-19 paper.
An overview of the methodology and general findings from the National Health and Morbidity Survey (NHMS) 2018: Older persons' health in Malaysia

Sooryanarayana R, Wong NI, Ahmad NA, Razak MAA, Yusoff MFM, Chan YY, et al.

Geriatr Gerontol Int, 2020 Dec;20 Suppl 2:7-15.
PMID: 33370855 DOI: 10.1111/ggi.14094

AIM: This article describes the methodology of the 2018 Malaysian National Health and Morbidity Survey, and provides an overview of the sociodemographic details of the respondents and key findings on the health of older adults.
METHODS: The survey included 3977 community-dwelling respondents, aged ≥60 years across Malaysia. Two-stage stratified random sampling with selection of enumeration blocks from both urban and rural areas ensured the findings were representative of the Malaysian older population.
RESULTS: Complex sampling analyses ensured that findings on various geriatric syndromes, non-communicable diseases, nutritional status, functional status, social well-being and quality of life are representative of the Malaysian older population. Among the limitations are that the composition of older persons varied slightly from the general older population.
CONCLUSIONS: This article presents the methodology of the survey, and a baseline of the major health issues for older persons in Malaysia to provide clear guidance to researchers, program managers and policymakers to fully utilize the data from the Malaysian National Health and Morbidity Survey toward achieving healthy aging. The findings might stimulate more research on the health problems faced by older people to provide inputs for policymaking and program implementation. Geriatr Gerontol Int 2020; 20: 7-15.

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