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Clinical characteristics, treatment and 2-year outcomes in Malaysian and Bruneian patients with stable coronary artery within the worldwide CLARIFY registry

Chee KH, Choo GH, Jamaluddin ANB, Mahendran K, Greenlaw N, Chandran A

Med J Malaysia, 2017 10;72(5):282-285.
PMID: 29197883 MyJurnal

INTRODUCTION: The on-going, international, prospective, observational, longitudinal CLARIFY registry is investigating the demographics, clinical profiles, management and outcomes of patients with stable coronary artery disease (CAD). This paper assesses baseline characteristics, treatment, and clinical outcomes at two years' follow-up of Malaysian/Bruneian patients compared with the overall registry population.
METHOD: Between November 2009 and July 2010, outpatients from 45 countries who met the criteria for stable CAD were recruited into the registry. Baseline characteristics were documented at enrolment, and patients were reassessed during their annual visits over a five-year follow-up period. Key outcomes measured were sudden death and cardiovascular (CV) death, non-CV death and CV morbidity.
RESULTS: At baseline, 33,283 patients were available for analysis within the registry; 380 and 27 were Malaysians and Bruneians, respectively. The mean ages of Malaysian/Bruneian patients and the rest of the world (RoW) were 57.83 ±9.98 years and 64.23 ± 10.46 years, respectively (p<0.001). The median body mass index values were 26.6 (24.4-29.6) kg/m2 and 27.3 (24.8-30.3) kg/m2, respectively (p=0.014). Malaysian/Bruneian patients had lower rates of myocardial infarction (54.55% versus 59.76%, p=0.033) and higher rates of diabetes (43.24% versus 28.99%, p<0.001) and dyslipidaemia (90.42% versus 74.66%, p<0.001) compared with the RoW. Measured clinical outcomes in Malaysian and Bruneian patients at 2-years follow-up were low and generally comparable to the RoW.
CONCLUSION: Malaysian/Bruneian patients with stable CAD tend to be younger with poorer diabetic control compared with the RoW. However, they had similar outcomes as the main registry following two years of treatment.

Matched MeSH terms: Coronary Artery Disease/epidemiology; Coronary Artery Disease/therapy*
Application of stacked convolutional and long short-term memory network for accurate identification of CAD ECG signals

Tan JH, Hagiwara Y, Pang W, Lim I, Oh SL, Adam M, et al.

Comput Biol Med, 2018 03 01;94:19-26.
PMID: 29358103 DOI: 10.1016/j.compbiomed.2017.12.023

Coronary artery disease (CAD) is the most common cause of heart disease globally. This is because there is no symptom exhibited in its initial phase until the disease progresses to an advanced stage. The electrocardiogram (ECG) is a widely accessible diagnostic tool to diagnose CAD that captures abnormal activity of the heart. However, it lacks diagnostic sensitivity. One reason is that, it is very challenging to visually interpret the ECG signal due to its very low amplitude. Hence, identification of abnormal ECG morphology by clinicians may be prone to error. Thus, it is essential to develop a software which can provide an automated and objective interpretation of the ECG signal. This paper proposes the implementation of long short-term memory (LSTM) network with convolutional neural network (CNN) to automatically diagnose CAD ECG signals accurately. Our proposed deep learning model is able to detect CAD ECG signals with a diagnostic accuracy of 99.85% with blindfold strategy. The developed prototype model is ready to be tested with an appropriate huge database before the clinical usage.

Matched MeSH terms: Coronary Artery Disease/diagnosis*; Coronary Artery Disease/physiopathology*
Is coronary arteritis a feature in secondary haemophagocytic lymphohistiocytosis?

See BT, Yip KX, Ang HL

Paediatr Int Child Health, 2018 02;38(1):76-79.
PMID: 28222654 DOI: 10.1080/20469047.2017.1289312

Haemophagocytic lymphohistiocytosis (HLH) is rare. Although Kawasaki disease (KD) has been reported as a precursor to HLH, coronary arteritis occurring at the onset of secondary HLH, not in association with KD, has not been reported. An 8-year-old girl presented with virus-induced secondary HLH associated with a giant aneurysm and ectasia of the coronary arteries which was detected incidentally at onset of the disease. She did not fulfill the criteria for diagnosis of KD. The coronary lesions improved after 6 months of treatment with dexamethasone and etoposide. Echocardiography early in the course of HLH is a useful tool to detect the unusual finding of coronary arteritis which may carry significant clinical sequelae.

Matched MeSH terms: Coronary Artery Disease/diagnosis*; Coronary Artery Disease/pathology*
Fulltext Cytokine and Chemokine Profiling in Patients with Hand, Foot and Mouth Disease in Singapore and Malaysia

Teo FMS, Nyo M, Wong AA, Tan NWH, Koh MT, Chan YF, et al.

Sci Rep, 2018 03 06;8(1):4087.
PMID: 29511232 DOI: 10.1038/s41598-018-22379-6

Hand, foot and mouth disease (HFMD) is a prevalent contagious childhood disease typically associated with fever, oral lesions and limb exanthema. While HFMD is caused by a plethora of serotypes of viruses under the genus Enterovirus within the Picornaviridae family, Coxsackievirus A16 (CV-A16) and Enterovirus 71 (EV-A71) are considered the main etiological agents. In recent years however, other viruses have also been isolated in considerable numbers from infected individuals in many regions, joining the legion commonly associated with HFMD. The present study investigated the cytokine and chemokine profiles of HFMD patients from Singapore and Malaysia for the first time. Comparative cohort studies of EV-A71-associated HFMD cases revealed that the Malaysia cohort had a distinct profile from the Singapore cohort, and this could be partly attributed by different EV-A71 genotypes. As the isolation of CV-A6, instead of CV-A16, had become prevalent in the Singapore cohort, it was also of particular interest to study the differential cytokine and chemokine profiles. Our data revealed that overlapping as well as unique profiles exist between the two major causative clinical isolates in the Singapore cohort. Having a better understanding of the respective immunological profiles could be useful for more accurate HFMD diagnosis, which is imperative for disease transmission control until multi-valent vaccines and/or broad-spectrum anti-viral drugs become available.

Matched MeSH terms: Hand, Foot and Mouth Disease/pathology*; Hand, Foot and Mouth Disease/virology
International Parkinson and movement disorder society evidence-based medicine review: Update on treatments for the motor symptoms of Parkinson's disease

Fox SH, Katzenschlager R, Lim SY, Barton B, de Bie RMA, Seppi K, et al.

Mov Disord, 2018 08;33(8):1248-1266.
PMID: 29570866 DOI: 10.1002/mds.27372

OBJECTIVE: The objective of this review was to update evidence-based medicine recommendations for treating motor symptoms of Parkinson's disease (PD).
BACKGROUND: The Movement Disorder Society Evidence-Based Medicine Committee recommendations for treatments of PD were first published in 2002 and updated in 2011, and we continued the review to December 31, 2016.
METHODS: Level I studies of interventions for motor symptoms were reviewed. Criteria for inclusion and quality scoring were as previously reported. Five clinical indications were considered, and conclusions regarding the implications for clinical practice are reported.
RESULTS: A total of 143 new studies qualified. There are no clinically useful interventions to prevent/delay disease progression. For monotherapy of early PD, nonergot dopamine agonists, oral levodopa preparations, selegiline, and rasagiline are clinically useful. For adjunct therapy in early/stable PD, nonergot dopamine agonists, rasagiline, and zonisamide are clinically useful. For adjunct therapy in optimized PD for general or specific motor symptoms including gait, rivastigmine is possibly useful and physiotherapy is clinically useful; exercise-based movement strategy training and formalized patterned exercises are possibly useful. There are no new studies and no changes in the conclusions for the prevention/delay of motor complications. For treating motor fluctuations, most nonergot dopamine agonists, pergolide, levodopa ER, levodopa intestinal infusion, entacapone, opicapone, rasagiline, zonisamide, safinamide, and bilateral STN and GPi DBS are clinically useful. For dyskinesia, amantadine, clozapine, and bilateral STN DBS and GPi DBS are clinically useful.
CONCLUSIONS: The options for treating PD symptoms continues to expand. These recommendations allow the treating physician to determine which intervention to recommend to an individual patient. © 2018 International Parkinson and Movement Disorder Society.

Matched MeSH terms: Parkinson Disease/physiopathology*; Parkinson Disease/therapy*
Bone marrow transplantation in Malaysia

Lin HP, Chan LL, Tan A, Ariffin WA, Lam SK

Bone Marrow Transplant, 1994 Jun;13(6):725-9.
PMID: 7920303

The sole BMT centre in Malaysia caters only for children. Since 1987, 89 transplants have been performed using reverse barrier nursing techniques. The overall survival rate is 73% with the majority of survivors leading normal lives. The early and late infection rates of 46% and 13%, respectively, are comparable to those of other centres. Although the early septicaemia rate is 36% the immediate mortality rate is < 10%. GVHD is less frequent and severe and the interstitial pneumonitis rate lower than that in the West. The average cost of US $8000 per transplant is much lower than the cost of a transplant performed overseas. Thus we believe that our paediatric BMT programme is simple and cost-effective.

Matched MeSH terms: Graft vs Host Disease/mortality; Graft vs Host Disease/epidemiology
Fulltext APOE, TOMM40, and sex interactions on neural network connectivity

Li T, Pappas C, Le ST, Wang Q, Klinedinst BS, Larsen BA, et al.

Neurobiol Aging, 2022 Jan;109:158-165.
PMID: 34740077 DOI: 10.1016/j.neurobiolaging.2021.09.020

The Apolipoprotein E ε4 (APOE ε4) haplotype is the strongest genetic risk factor for late-onset Alzheimer's disease (AD). The Translocase of Outer Mitochondrial Membrane-40 (TOMM40) gene maintains cellular bioenergetics, which is disrupted in AD. TOMM40 rs2075650 ('650) G versus A carriage is consistently related to neural and cognitive outcomes, but it is unclear if and how it interacts with APOE. We examined 21 orthogonal neural networks among 8,222 middle-aged to aged participants in the UK Biobank cohort. ANOVA and multiple linear regression tested main effects and interactions with APOE and TOMM40 '650 genotypes, and if age and sex acted as moderators. APOE ε4 was associated with less strength in multiple networks, while '650 G versus A carriage was related to more language comprehension network strength. In APOE ε4 carriers, '650 G-carriage led to less network strength with increasing age, while in non-G-carriers this was only seen in women but not men. TOMM40 may shift what happens to network activity in aging APOE ε4 carriers depending on sex.

Matched MeSH terms: Alzheimer Disease/genetics; Alzheimer Disease/psychology
Fulltext Caroli's disease: functional diagnosis using 99mTc diethyl-iminodiacetic acid (IDA) hepatobiliary scintigraphy

Lai FM, Paramsothy M, Goh KL, Boey C

Singapore Med J, 1997 Apr;38(4):164-5.
PMID: 9269396

A case of Caroli's disease is presented and the findings of various imaging modalities are discussed with emphasis on the role of Technetium 99mTc diethyl-iminodiacetic acid scan in reaching the final diagnosis. The 'beaded' appearance of the dilated intrahepatic ducts seen in this scan is believed to be pathognomonic for this condition.

Matched MeSH terms: Caroli Disease/diagnosis; Caroli Disease/radionuclide imaging*
Rheumatic fever is a major cause of acquired heart disease in children and young adults throughout the developing world

Chadha S, Inechen B

Singapore Med J, 1997 Mar;38(3):138.
PMID: 9269387
Matched MeSH terms: Rheumatic Heart Disease/etiology*; Rheumatic Heart Disease/epidemiology
Fulltext The health farm concept in the primary prevention of coronary artery disease

Ahmad AM

Singapore Med J, 1995 Dec;36(6):600-5.
PMID: 8781629

The purpose of the study is as a preliminary outline of the effectiveness of initiating high-risk individuals into the Health Farm concept in the primary prevention of coronary artery disease (CAD). Thirty-five (35) Army personnel, all male, with risk-factors for CAD were brought together on a Health Farm concept to go through a predesigned ten-day Farm programme comprising CAD risk-assessment, comprehensive medical examination, relevant blood chemistry analysis, physical fitness evaluation, individualised weekly exercise routine, physical fitness workouts, individualised diet, lectures, group discussion and individual counselling. Description of the participants (as measurements of various relevant parameters) are made at the start and as participant-achievement. The results show general participant-compliance to the programme which was reflected by significant changes in weight (p < 0.005), percentile VO2Max (p < 0.005), percentile push-ups (p < 0.005) and girth-difference (p < 0.005). The study showed that the Health Farm concept is effective in initiating high-risk individuals into lifestyles conducive to the primary prevention of CAD. Sustained results towards primary prevention of CAD can be expected with compliance to a long-term follow-up that has been identified and to which participants have been made aware of. Other previous intervention studies are briefly discussed.

Matched MeSH terms: Coronary Disease/etiology; Coronary Disease/prevention & control*
Fulltext Association of diabetic autonomic neuropathy with painless myocardial ischaemia induced by exercise

Quek DK, Khor PG, Ong SB

Singapore Med J, 1992 Apr;33(2):177-81.
PMID: 1621124

Silent myocardial ischaemia is now well-recognised in patients with symptomatic coronary artery disease. Its pathogenesis remains speculative, though diminished sensitivity to pain is thought to be one of the mechanisms involved. Because cardiovascular autonomic dysfunction occurs frequently in diabetic patients, we postulate that it contributes towards painless myocardial ischaemia among them. Forty consecutive diabetic (type II) male patients and ten normal volunteers were studied. Using 5 previously-validated noninvasive tests for autonomic dysfunction, 14 of these diabetic men had definite autonomic neuropathy (at least 2 abnormal tests). All 50 subjects were then exercised on a motor-driven treadmill to either exhaustion or chest pains. Thirty-three diabetic subjects were tested positive, with significant (greater than 1 mm) ST segment depression over at least 2 contiguous leads. Of these, 18 were associated with typical angina but the other 15 stopped because of fatigue or exhaustion (ie painless). Thirteen subjects who had definite autonomic neuropathy (AN+) had positive exercise ECG tests-10 had painless ischaemia, and only 3 had angina. This contrasted with 15 patients who had painful ischaemia and 5 who had painless ischaemia among the group without (AN-)autonomic dysfunction (p = 0.0047, Fisher's exact test). There were no significant differences among the various groups for peak rate-pressure-product, all subjects attaining similar maximal oxygen consumption states during which ischaemic ST segment changes were noted (painful AN+: 21917 +/- 4753; painless AN+: 20117 +/- 6752; painful AN-: 16544 +/- 4063; painless AN-: 22220 +/- 4341, p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Matched MeSH terms: Coronary Disease/diagnosis; Coronary Disease/etiology*
Role of Liver Growth Factor (LGF) in Parkinson's Disease: Molecular Insights and Therapeutic Opportunities

Angelopoulou E, Paudel YN, Piperi C

Mol Neurobiol, 2021 Jul;58(7):3031-3042.
PMID: 33608826 DOI: 10.1007/s12035-021-02326-9

Parkinson's disease is the most common neurodegenerative movement disorder with unclear etiology and only symptomatic treatment to date. Toward the development of novel disease-modifying agents, neurotrophic factors represent a reasonable and promising therapeutic approach. However, despite the robust preclinical evidence, clinical trials using glial-derived neurotrophic factor (GDNF) and neurturin have been unsuccessful. In this direction, the therapeutic potential of other trophic factors in PD and the elucidation of the underlying molecular mechanisms are of paramount importance. The liver growth factor (LGF) is an albumin-bilirubin complex acting as a hepatic mitogen, which also exerts regenerative effects on several extrahepatic tissues including the brain. Accumulating evidence suggests that intracerebral and peripheral administration of LGF can enhance the outgrowth of nigrostriatal dopaminergic axonal terminals; promote the survival, migration, and differentiation of neuronal stem cells; and partially protect against dopaminergic neuronal loss in the substantia nigra of PD animal models. In most studies, these effects are accompanied by improved motor behavior of the animals. Potential underlying mechanisms involve transient microglial activation, TNF-α upregulation, and activation of the extracellular signal-regulated kinases 1/2 (ERK1/2) and of the transcription factor cyclic AMP response-element binding protein (CREB), along with anti-inflammatory and antioxidant pathways. Herein, we summarize recent preclinical evidence on the potential role of LGF in PD pathogenesis, aiming to shed more light on the underlying molecular mechanisms and reveal novel therapeutic opportunities for this debilitating disease.

Matched MeSH terms: Parkinson Disease/drug therapy*; Parkinson Disease/metabolism*
Unwinding circular RNA's role in inflammatory pulmonary diseases

Bhat AA, Gupta G, Goyal A, Thapa R, Almalki WH, Kazmi I, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2024 May;397(5):2567-2588.
PMID: 37917370 DOI: 10.1007/s00210-023-02809-7

Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications.

Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/genetics; Pulmonary Disease, Chronic Obstructive/immunology
Fulltext 18-β-glycyrrhetinic acid-loaded polymeric nanoparticles attenuate cigarette smoke-induced markers of impaired antiviral response in vitro

De Rubis G, Paudel KR, Yeung S, Mohamad S, Sudhakar S, Singh SK, et al.

Pathol Res Pract, 2024 May;257:155295.
PMID: 38603841 DOI: 10.1016/j.prp.2024.155295

Tobacco smoking is a leading cause of preventable mortality, and it is the major contributor to diseases such as COPD and lung cancer. Cigarette smoke compromises the pulmonary antiviral immune response, increasing susceptibility to viral infections. There is currently no therapy that specifically addresses the problem of impaired antiviral response in cigarette smokers and COPD patients, highlighting the necessity to develop novel treatment strategies. 18-β-glycyrrhetinic acid (18-β-gly) is a phytoceutical derived from licorice with promising anti-inflammatory, antioxidant, and antiviral activities whose clinical application is hampered by poor solubility. This study explores the therapeutic potential of an advanced drug delivery system encapsulating 18-β-gly in poly lactic-co-glycolic acid (PLGA) nanoparticles in addressing the impaired antiviral immunity observed in smokers and COPD patients. Exposure of BCi-NS1.1 human bronchial epithelial cells to cigarette smoke extract (CSE) resulted in reduced expression of critical antiviral chemokines (IP-10, I-TAC, MIP-1α/1β), mimicking what happens in smokers and COPD patients. Treatment with 18-β-gly-PLGA nanoparticles partially restored the expression of these chemokines, demonstrating promising therapeutic impact. The nanoparticles increased IP-10, I-TAC, and MIP-1α/1β levels, exhibiting potential in attenuating the negative effects of cigarette smoke on the antiviral response. This study provides a novel approach to address the impaired antiviral immune response in vulnerable populations, offering a foundation for further investigations and potential therapeutic interventions. Further studies, including a comprehensive in vitro characterization and in vivo testing, are warranted to validate the therapeutic efficacy of 18-β-gly-PLGA nanoparticles in respiratory disorders associated with compromised antiviral immunity.

Matched MeSH terms: Pulmonary Disease, Chronic Obstructive/drug therapy; Pulmonary Disease, Chronic Obstructive/immunology
Purification of recombinant nucleocapsid protein of Newcastle disease virus from unclarified feedstock using expanded bed adsorption chromatography

Tan YP, Ling TC, Tan WS, Yusoff K, Tey BT

Protein Expr Purif, 2006 Mar;46(1):114-21.
PMID: 16139513

In the present work, a single-step purification of recombinant nucleocapsid protein (NP) of the Newcastle disease virus (NDV) directly from unclarified feedstock using an expanded bed adsorption chromatography (EBAC) was developed. Streamline 25 column (ID = 25 mm) was used as a contactor and Streamline chelating adsorbent immobilized with Ni2+ ion was used as affinity adsorbent. The dynamic binding capacity of Ni2+ -loaded Streamline chelating adsorbent for the NP protein in unclarified feedstock was found to be 2.94 mg ml(-1) adsorbent at a superficial velocity of 200 cm h(-1). The direct purification of NP protein from unclarified feedstock using expanded bed adsorption has resulted in a 31% adsorption and 9.6% recovery of NP protein. The purity of the NP protein recovered was about 70% and the volume of processing fluid was reduced by a factor of 10. The results of the present study show that the IMA-EBAC developed could be used to combine the clarification, concentration and initial purification steps into a single-step operation.

Matched MeSH terms: Newcastle disease virus/enzymology*; Newcastle disease virus/isolation & purification
Fulltext Breeding for Anthracnose Disease Resistance in Chili: Progress and Prospects

Ridzuan R, Rafii MY, Ismail SI, Mohammad Yusoff M, Miah G, Usman M

Int J Mol Sci, 2018 Oct 11;19(10).
PMID: 30314374 DOI: 10.3390/ijms19103122

Chili anthracnose is one of the most devastating fungal diseases affecting the quality and yield production of chili. The aim of this review is to summarize the current knowledge concerning the chili anthracnose disease, as well as to explore the use of marker-assisted breeding programs aimed at improving anthracnose disease resistance in this species. This disease is caused by the Colletotrichum species complex, and there have been ongoing screening methods of chili pepper genotypes with resistance to anthracnose in the field, as well as in laboratories. Conventional breeding involves phenotypic selection in the field, and it is more time-consuming compared to molecular breeding. The use of marker-assisted selection (MAS) on the basis of inheritance, the segregation ratio of resistance to susceptibility, and the gene-controlling resistance may contribute to the development of an improved chili variety and speed up the selection process, while also reducing genetic drag in the segregating population. More importantly, by using molecular markers, the linkage groups are determined dominantly and co-dominantly, meaning that the implementation of a reliable method to produce resistant varieties is crucial in future breeding programs. This updated information will offer a supportive direction for chili breeders to develop an anthracnose-resistant chili variety.

Matched MeSH terms: Disease Susceptibility; Disease Resistance/genetics*
Fulltext Role of neurotoxicants in the pathogenesis of Alzheimer's disease: a mechanistic insight

Nisa FY, Rahman MA, Hossen MA, Khan MF, Khan MAN, Majid M, et al.

Ann Med, 2021 Dec;53(1):1476-1501.
PMID: 34433343 DOI: 10.1080/07853890.2021.1966088

Alzheimer's disease (AD) is the most conspicuous chronic neurodegenerative syndrome, which has become a significant challenge for the global healthcare system. Multiple studies have corroborated a clear association of neurotoxicants with AD pathogenicity, such as Amyloid beta (Aβ) proteins and neurofibrillary tangles (NFTs), signalling pathway modifications, cellular stress, cognitive dysfunctions, neuronal apoptosis, neuroinflammation, epigenetic modification, and so on. This review, therefore, aimed to address several essential mechanisms and signalling cascades, including Wnt (wingless and int.) signalling pathway, autophagy, mammalian target of rapamycin (mTOR), protein kinase C (PKC) signalling cascades, cellular redox status, energy metabolism, glutamatergic neurotransmissions, immune cell stimulations (e.g. microglia, astrocytes) as well as an amyloid precursor protein (APP), presenilin-1 (PSEN1), presenilin-2 (PSEN2) and other AD-related gene expressions that have been pretentious and modulated by the various neurotoxicants. This review concluded that neurotoxicants play a momentous role in developing AD through modulating various signalling cascades. Nevertheless, comprehension of this risk agent-induced neurotoxicity is far too little. More in-depth epidemiological and systematic investigations are needed to understand the potential mechanisms better to address these neurotoxicants and improve approaches to their risk exposure that aid in AD pathogenesis.Key messagesInevitable cascade mechanisms of how Alzheimer's Disease-related (AD-related) gene expressions are modulated by neurotoxicants have been discussed.Involvement of the neurotoxicants-induced pathways caused an extended risk of AD is explicited.Integration of cell culture, animals and population-based analysis on the clinical severity of AD is addressed.

Matched MeSH terms: Alzheimer Disease/etiology; Alzheimer Disease/pathology*
Fulltext Possible Epigenetic Role of Vitexin in Regulating Neuroinflammation in Alzheimer's Disease

Yahaya MAF, Zolkiffly SZI, Moklas MAM, Hamid HA, Stanslas J, Zainol M, et al.

J Immunol Res, 2020;2020:9469210.
PMID: 32258178 DOI: 10.1155/2020/9469210

Alzheimer's disease (AD) has been clinically characterized by a progressive degeneration of neurons which resulted in a gradual and irreversible cognitive impairment. The accumulation of Aβ and τ proteins in the brain contribute to the severity of the disease. Recently, vitexin compound has been the talk amongst researchers due to its pharmacological properties as anti-inflammation and anti-AD. However, the epigenetic mechanism of the compound in regulating the neuroinflammation activity is yet to be fully elucidated. Hence, this review discusses the potential of vitexin compound to have the pharmacoepigenetic property in regulating the neuroinflammation activity in relation to AD. It is with hope that the review would unveil the potential of vitexin as the candidate in treating AD.

Matched MeSH terms: Alzheimer Disease/genetics; Alzheimer Disease/immunology*
Fulltext Modelling the Effectiveness of Epidemic Control Measures in Preventing the Transmission of COVID-19 in Malaysia

Gill BS, Jayaraj VJ, Singh S, Mohd Ghazali S, Cheong YL, Md Iderus NH, et al.

Int J Environ Res Public Health, 2020 Jul 30;17(15).
PMID: 32751669 DOI: 10.3390/ijerph17155509

Malaysia is currently facing an outbreak of COVID-19. We aim to present the first study in Malaysia to report the reproduction numbers and develop a mathematical model forecasting COVID-19 transmission by including isolation, quarantine, and movement control measures. We utilized a susceptible, exposed, infectious, and recovered (SEIR) model by incorporating isolation, quarantine, and movement control order (MCO) taken in Malaysia. The simulations were fitted into the Malaysian COVID-19 active case numbers, allowing approximation of parameters consisting of probability of transmission per contact (β), average number of contacts per day per case (ζ), and proportion of close-contact traced per day (q). The effective reproduction number (Rt) was also determined through this model. Our model calibration estimated that (β), (ζ), and (q) were 0.052, 25 persons, and 0.23, respectively. The (Rt) was estimated to be 1.68. MCO measures reduce the peak number of active COVID-19 cases by 99.1% and reduce (ζ) from 25 (pre-MCO) to 7 (during MCO). The flattening of the epidemic curve was also observed with the implementation of these control measures. We conclude that isolation, quarantine, and MCO measures are essential to break the transmission of COVID-19 in Malaysia.

Matched MeSH terms: Disease Outbreaks/prevention & control; Disease Susceptibility
Mutations, associated with early-onset Alzheimer's disease, discovered in Asian countries

Bagyinszky E, Youn YC, An SS, Kim S

Clin Interv Aging, 2016;11:1467-1488.
PMID: 27799753

Alzheimer's disease (AD), the most common form of senile dementia, is a genetically complex disorder. In most Asian countries, the population and the number of AD patients are growing rapidly, and the genetics of AD has been extensively studied, except in Japan. However, recent studies have been started to investigate the genes and mutations associated with AD in Korea, the People's Republic of China, and Malaysia. This review describes all of the known mutations in three early-onset AD (EOAD) causative genes (APP, PSEN1, and PSEN2) that were discovered in Asian countries. Most of the EOAD-associated mutations have been detected in PSEN1, and several novel PSEN1 mutations were recently identified in patients from various parts of the world, including Asia. Until 2014, no PSEN2 mutations were found in Asian patients; however, emerging studies from Korea and the People's Republic of China discovered probably pathogenic PSEN2 mutations. Since several novel mutations were discovered in these three genes, we also discuss the predictions on their pathogenic nature. This review briefly summarizes genome-wide association studies of late-onset AD and the genes that might be associated with AD in Asian countries. Standard sequencing is a widely used method, but it has limitations in terms of time, cost, and efficacy. Next-generation sequencing strategies could facilitate genetic analysis and association studies. Genetic testing is important for the accurate diagnosis and for understanding disease-associated pathways and might also improve disease therapy and prevention.

Matched MeSH terms: Alzheimer Disease/genetics*; Alzheimer Disease/epidemiology

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