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Fulltext Lifestyle management of hypertension: International Society of Hypertension position paper endorsed by the World Hypertension League and European Society of Hypertension

Charchar FJ, Prestes PR, Mills C, Ching SM, Neupane D, Marques FZ, et al.

J Hypertens, 2024 Jan 01;42(1):23-49.
PMID: 37712135 DOI: 10.1097/HJH.0000000000003563

Hypertension, defined as persistently elevated systolic blood pressure (SBP) >140 mmHg and/or diastolic blood pressure (DBP) at least 90 mmHg (International Society of Hypertension guidelines), affects over 1.5 billion people worldwide. Hypertension is associated with increased risk of cardiovascular disease (CVD) events (e.g. coronary heart disease, heart failure and stroke) and death. An international panel of experts convened by the International Society of Hypertension College of Experts compiled lifestyle management recommendations as first-line strategy to prevent and control hypertension in adulthood. We also recommend that lifestyle changes be continued even when blood pressure-lowering medications are prescribed. Specific recommendations based on literature evidence are summarized with advice to start these measures early in life, including maintaining a healthy body weight, increased levels of different types of physical activity, healthy eating and drinking, avoidance and cessation of smoking and alcohol use, management of stress and sleep levels. We also discuss the relevance of specific approaches including consumption of sodium, potassium, sugar, fibre, coffee, tea, intermittent fasting as well as integrated strategies to implement these recommendations using, for example, behaviour change-related technologies and digital tools.
Fulltext Gender-Specific Molecular and Clinical Features Underlie Malignant Pleural Mesothelioma

De Rienzo A, Archer MA, Yeap BY, Dao N, Sciaranghella D, Sideris AC, et al.

Cancer Res, 2016 Jan 15;76(2):319-28.
PMID: 26554828 DOI: 10.1158/0008-5472.CAN-15-0751

Malignant pleural mesothelioma (MPM) is an aggressive cancer that occurs more frequently in men, but is associated with longer survival in women. Insight into the survival advantage of female patients may advance the molecular understanding of MPM and identify therapeutic interventions that will improve the prognosis for all MPM patients. In this study, we performed whole-genome sequencing of tumor specimens from 10 MPM patients and matched control samples to identify potential driver mutations underlying MPM. We identified molecular differences associated with gender and histology. Specifically, single-nucleotide variants of BAP1 were observed in 21% of cases, with lower mutation rates observed in sarcomatoid MPM (P < 0.001). Chromosome 22q loss was more frequently associated with the epithelioid than that nonepitheliod histology (P = 0.037), whereas CDKN2A deletions occurred more frequently in nonepithelioid subtypes among men (P = 0.021) and were correlated with shorter overall survival for the entire cohort (P = 0.002) and for men (P = 0.012). Furthermore, women were more likely to harbor TP53 mutations (P = 0.004). Novel mutations were found in genes associated with the integrin-linked kinase pathway, including MYH9 and RHOA. Moreover, expression levels of BAP1, MYH9, and RHOA were significantly higher in nonepithelioid tumors, and were associated with significant reduction in survival of the entire cohort and across gender subgroups. Collectively, our findings indicate that diverse mechanisms highly related to gender and histology appear to drive MPM.
May Measurement Month 2018: an analysis of blood pressure screening results from Malaysia

Chia YC, Ching SM, Devaraj NK, Chew BN, Ooi PB, Mohamed M, et al.

Eur Heart J Suppl, 2020 Aug;22(Suppl H):H83-H85.
PMID: 32884479 DOI: 10.1093/eurheartj/suaa035

Hypertension continues to be the top global killer, contributing to over 10 million deaths annually. As prevalence and unawareness of hypertension remain high in Malaysia, this study was aimed to screen more individuals to identify those with undiagnosed hypertension. Respondents aged ≥18 years were recruited through opportunistic sampling at various screening sites including health clinics, hospitals, student health centres, universities, community halls, shopping malls, as well as through other health screening campaigns. Each respondent completed a questionnaire on socio-demographic, environmental, and lifestyle data. Anthropometric measurements as well as three blood pressure (BP) measurements were obtained from all participants. Hypertension was defined as a systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or taking antihypertensive medication. The total number of participants was 4866. The mean age of the participants was 39.8 (17.6) years with 61.1% female participants. Of the 4866 participants, 1405 (28.9%) had hypertension. The proportion of those aware of their hypertension status was 76.3% (1073/1405). The proportion of those with hypertension on medication was 71% (998/1405). Of those receiving antihypertensive treatment, 62.4% (623/998) had controlled BP. The proportion of hypertension in this study was 28.9%. The awareness rate of 76.3% compares favourably to a previously reported national level of 43.2%. Hence, BP screening programmes may be effective at increasing awareness and should be conducted annually.
Fulltext Effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine: a single-centre, randomised, double-blind, sham-controlled phase 2 trial (Magnet-EM)

Mohamad Safiai NI, Amir NA, Basri H, Inche Mat LN, Hoo FK, Yusof Khan AHK, et al.

Trials, 2020 Nov 11;21(1):923.
PMID: 33176870 DOI: 10.1186/s13063-020-04832-y

BACKGROUND: This is a phase II randomised, double-blind, sham-controlled trial to evaluate the effectiveness and tolerability of repetitive transcranial magnetic stimulation for preventive treatment of episodic migraine amongst migraine subjects.
METHODS: Subjects age 18 to 60 years will undergo a baseline evaluation to establish the diagnosis of migraine based on the International Classification of Headache Disorder 3rd Edition (ICHD-3). Those who fulfil the ICHD-3 criteria for episodic migraine and compliant to the headache diary during a month run-in period will be enrolled. A total of 76 subjects will be randomised to receive either transcranial magnetic stimulation or sham stimulation for 5 sessions within 2 weeks duration. Follow-up sessions will be conducted monthly for three consecutive months. Prior to treatment, subjects will be required to fill up questionnaires and undergo few procedures such as electroencephalography, transcranial Doppler ultrasound and biochemical analysis for serum serotonin, serum calcitonin gene-related peptide and serum beta-endorphin. These procedures will be repeated at month 3 after receiving the last treatment. The primary outcome measure of this study is the difference in mean monthly migraine days at baseline and at months 1, 2 and 3 after treatment sessions.
DISCUSSION: Following evidence from previous studies showing restoration of dorsolateral prefrontal cortex (DLPFC) activation to almost normal level, the rTMS intervention will target left DLPFC in this study. An intermediate duration of treatment sessions is selected for this study. It is set to five treatment sessions given within 2 weeks duration.
TRIAL REGISTRATION: ClinicalTrials.gov NCT03556722 . Registered on 14 June 2018.
Stroke and Novel Coronavirus Infection in Humans: A Systematic Review and Meta-Analysis

Lee KW, Yusof Khan AHK, Ching SM, Chia PK, Loh WC, Abdul Rashid AM, et al.

Front Neurol, 2020;11:579070.
PMID: 33123082 DOI: 10.3389/fneur.2020.579070

Background: As the world witnessed the devastation caused by the coronavirus disease 2019 (COVID-19) outbreak, a growing body of literature on COVID-19 is also becoming increasingly available. Stroke has increasingly been reported as a complication of COVID-19 infection. However, a systematic synthesis of the available data has not been conducted. Therefore, we performed a systematic review and meta-analysis of currently available epidemiological, clinical, and laboratory data related to both stroke and COVID-19 infection. Methods: We systematically searched Medline, Cinahl, and PubMed for studies related to stroke and COVID-19 from inception up to June 4, 2020. We selected cohort studies, case series, and case reports that reported the occurrence of stroke in COVID-19 patients. A fixed-effects model was used to estimate the pooled frequency of stroke in COVID-19 patients with a 95% confidence interval (CI). Results: Twenty-eight studies were included in the systematic review and seven studies for the meta-analysis. The pooled frequency of stroke in COVID-19 patients was 1.1% (95% CI: 0.8, 1.3). The heterogeneity was low (I2 = 0.0%). Even though the frequency of stroke among patients having COVID-19 infection was low, those with concomitant COVID-19 infection and stroke suffered from a more severe infection and eventually had a poorer prognosis with a higher mortality rate (46.7%) than COVID-19 alone. Many COVID-19 patients shared the common traditional risk factors for stroke. We noted that ischemic stroke involving the anterior circulation with large vessels occlusion is the most common type of stroke with more strokes seen in multi-territorial regions, suggesting systemic thromboembolism. An elevated level of D-dimers, C-reactive protein, ferritin, lactic acid dehydrogenase, troponin, ESR, fibrinogen, and a positive antiphospholipid antibody were also noted in this review. Conclusions: The occurrence of stroke in patients with COVID-19 infection is uncommon, but it may pose as an important prognostic marker and indicator of severity of infection, by causing large vessels occlusion and exhibiting a thrombo-inflammatory vascular picture. Physicians should be made aware and remain vigilant on the possible two-way relationship between stroke and COVID-19 infection. The rate of stroke among patients with COVID-19 infection may increase in the future as they share the common risk factors.
Fulltext May Measurement Month 2017 blood pressure screening: findings from Malaysia-South-East Asia and Australasia

Chia YC, Ching SM, Chew BN, Devaraj NK, Siti Suhaila MY, Tay CL, et al.

Eur Heart J Suppl, 2019 Apr;21(Suppl D):D77-D79.
PMID: 31043885 DOI: 10.1093/eurheartj/suz061

Elevated blood pressure (BP) is a growing burden worldwide, leading to over 10 million deaths each year. However there are still many individuals, particularly in many countries in Asia, who have poor BP control. In Malaysia, less than two-fifths have achieved BP control. We participated in BP screening in Malaysia in conjunction with the May Measurement Month 2017 (MMM17), a global initiative by the International Society of Hypertension (ISH) aimed at screening more individuals for earlier detection of hypertension. A nationwide screening of adults aged ≥18 was carried out through health campaigns at clinics, hospitals, during family day events, and charity runs from 1 April 2017 to 31 May 2017 in 42 centres. We used the detailed protocol provided by ISH for data collection. A total of 4116 individuals were screened during MMM17. After multiple imputation, 32.4% (n = 1317/4059) had hypertension. Out of this, 63.9% (842/1317) of those with hypertension were on treatment. Of individuals receiving antihypertensive medication with an imputed BP, 59.5% (n = 496/834) of them had controlled BP. MMM17 was the largest organized BP screening campaign undertaken by health professionals in Malaysia. This study identified that 32.4% of screened individuals had hypertension and 59.5% individuals with treated hypertension had achieved BP control.
Fulltext May Measurement Month 2019: an analysis of blood pressure screening results from Malaysia

Chia YC, Devaraj NK, Chook JB, Chew MT, Ooi PB, Mohamed M, et al.

Eur Heart J Suppl, 2021 May;23(Suppl B):B98-B100.
PMID: 34054370 DOI: 10.1093/eurheartj/suab058

Despite hypertension remaining the leading cause of death worldwide, awareness of hypertension and its control rate is still suboptimal in Malaysia. This study aims to determine the proportion of both diagnosed and undiagnosed hypertension, awareness and its control rate during the yearly May Measurement Month (MMM) campaign that has been coordinated by the International Society of Hypertension. Participants aged ≥18 years were recruited at various screening sites namely universities, health facilities, shopping malls, and other sites. Participant's socio-demographic, environmental, and lifestyle data were captured using a questionnaire. Three blood pressure (BP) readings as well as anthropometric measurements were obtained from all participants. The mean of the second and third BP readings was used in analyses. Hypertension was defined as a systolic BP ≥140 mmHg and/or diastolic BP ≥90 mmHg or taking antihypertensive medication. A total of 3062 participants were recruited. The proportion with hypertension in our study was 18.7% (n = 572). The proportion who were aware of their BP status was 63.2%. More than half (57.2%) of the hypertensives were on antihypertensive medication and 70.3% of those treated were controlled. In conclusion, in this BP screening campaign, one in five were hypertensive with almost two thirds aware of their hypertensive status. BP control among those who are taking medications was high at 70% but under 60% of hypertensives were on treatment. Hypertension screening programmes are important to promote awareness and control of hypertension as well as to reduce the devastating complications associated with this disorder.
Fulltext Protocol for a qualitative study exploring the perception of need, importance and acceptability of a digital diabetes prevention intervention for women with gestational diabetes mellitus during and after pregnancy in Malaysia (Explore-MYGODDESS)

Sobri NHM, Ismail IZ, Hassan F, Papachristou Nadal I, Forbes A, Ching SM, et al.

BMJ Open, 2021 08 26;11(8):e044878.
PMID: 34446477 DOI: 10.1136/bmjopen-2020-044878

INTRODUCTION: Women who develop gestational diabetes mellitus (GDM) have an increased risk of developing type 2 diabetes, and to reduce this risk the women have to adopt healthy behaviour changes. Although previous studies have explored the challenges and facilitators to initiate behaviour change among women with GDM, there is limited data from Malaysian women. Thus, this study will explore the factors affecting the uptake of healthy behaviour changes and the use of digital technology among women and their healthcare providers (HCPs) to support healthy behaviour changes in women with GDM.
METHODS AND ANALYSIS: The study will be modelled according to the Capability, Opportunity, Motivation and Behaviour and Behaviour Change Wheel techniques, and use the DoTTI framework to identify needs, solutions and testing of a preliminary mobile app, respectively. In phase 1 (design and development), a focus group discussion (FGDs) of 5-8 individuals will be conducted with an estimated 60 women with GDM and 40 HCPs (doctors, dietitians and nurses). Synthesised data from the FGDs will then be combined with content from an expert committee to inform the development of the mobile app. In phase 2 (testing of early iterations), a preview of the mobile app will undergo alpha testing among the team members and the app developers, and beta testing among 30 women with GDM or with a history of GDM, and 15 HCPs using semi-structured interviews. The outcome will enable us to optimise an intervention using the mobile app as a diabetes prevention intervention which will then be evaluated in a randomised controlled trial.
ETHICS AND DISSEMINATION: The project has been approved by the Malaysia Research Ethics Committee. Informed consent will be obtained from all participants. Outcomes will be presented at both local and international conferences and submitted for publications in peer-reviewed journals.
Fulltext A Mobile Phone App for the Prevention of Type 2 Diabetes in Malaysian Women With Gestational Diabetes Mellitus: Protocol for a Feasibility Randomized Controlled Trial

Benton M, Iman I, Goldsmith K, Forbes A, Ching SM, Papachristou Nadal I, et al.

JMIR Res Protoc, 2022 Sep 08;11(9):e37288.
PMID: 36074545 DOI: 10.2196/37288

BACKGROUND: Over 50% of women with a history of gestational diabetes mellitus (GDM) will develop type 2 diabetes (T2D) in later life. Asian women experience a disproportionate risk of both GDM and T2D compared to women from other ethnic backgrounds. Lifestyle interventions and behavior change can delay or even prevent the onset of T2D. We have developed a digitalized diabetes prevention intervention for the prevention of T2D in Malaysian women with GDM.
OBJECTIVE: The protocol describes a randomized controlled trial (RCT) to test the feasibility of undertaking a definitive trial of a diabetes prevention intervention, including a smartphone app and group support. Secondary aims are to summarize anthropometric, biomedical, psychological, and lifestyle outcomes overall and by allocation group, and to undertake a process evaluation.
METHODS: This is a two-arm parallel feasibility RCT. A total of 60 Malaysian women with GDM will be randomized in the antenatal period to receive the intervention or standard care until 12 months post partum. The intervention is a diabetes prevention intervention delivered via a smartphone app developed based on the Information-Motivation-Behavioral Skills model of behavior change and group support using motivational interviewing. The intervention provides women with tailored information and support to encourage weight loss through adapted dietary intake and physical activity. Women in the control arm will receive standard care. The Malaysian Ministry of Health's Medical Research and Ethics Committee has approved the trial (NMRR-21-1667-60212).
RESULTS: Recruitment and enrollment began in February 2022. Future outcomes will be published in peer-reviewed health-related research journals and presented at national, regional, or state professional meetings and conferences. This publication is based on protocol version 2, January 19, 2022.
CONCLUSIONS: To our knowledge, this will be the first study in Malaysia that aims to determine the feasibility of a digital intervention in T2D prevention among women with GDM. Findings from this feasibility study will inform the design of a full-scale RCT in the future.
TRIAL REGISTRATION: ClinicalTrials.gov NCT05204706; https://clinicaltrials.gov/ct2/show/NCT05204706.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/37288.
Fulltext Level of fear towards COVID-19 and its determinants among healthcare providers in Malaysia: A cross-sectional study

Ching SM, Cheong AT, Yee A, Thurasamy R, Lim PY, Ismail IZ, et al.

Malays Fam Physician, 2023;18:56.
PMID: 37814673 DOI: 10.51866/oa.238

INTRODUCTION: Malaysia is one of the hardest-hit countries by COVID-19 in Asia. The rapidly rising number of cases had sparked fear among healthcare providers. This study aimed to assess the determinants of fear towards COVID-19 among healthcare providers in primary care settings.
METHOD: This online-based cross-sectional study was conducted among 1280 healthcare providers aged ≥18 years from 30 primary care clinics in the state of Selangor, Malaysia. The Fear of COVID-19 Scale was used to assess the level of fear, and the results were analysed using multiple linear regression.
RESULTS: The mean age of the respondents was 36 years, and the mean working experience was 11 years. The majority of the respondents were women (82.4%) and Malays (82.3%). The factors that were significantly correlated with higher levels of fear were underlying chronic disease (ß=1.12, P=0.002, 95% confidence interval [CI]=0.08, 3.15), concern about mortality from COVID-19 (ß=3.3, P<0.001, 95% CI=0.19, 7.22), higher risk of exposure (ß=0.8, P<0.001, 95% CI=0.14, 5.91), concern for self at work (ß=2.8, P=0.002, 95% CI=0.08, 3.10) and work as a nurse (ß=3.6, P<0.001, 95% CI=0.30, 7.52), medical laboratory worker (ß=3.0, P<0.001, 95% CI=0.12, 4.27) and healthcare assistant (ß=3.9, P<0.001, 95% CI=0.17, 5.73). The level of fear was inversely correlated with a higher work-related stress management score (ß=-0.9, P<0.001, 95% CI=-0.14, -5.07) and a higher sleep quality score (ß=-1.8, P<0.001, 95% CI=-0.28, -10.41).
CONCLUSION: Family physicians should be vigilant and identify healthcare providers at risk of developing COVID-19-related fear to initiate early mental health intervention.
Fulltext Relationship of an adherence score with blood pressure control status among patients with hypertension and their determinants: Findings from a nationwide blood pressure screening program

Chia YC, Devaraj NK, Ching SM, Ooi PB, Chew MT, Chew BN, et al.

J Clin Hypertens (Greenwich), 2021 03;23(3):638-645.
PMID: 33586334 DOI: 10.1111/jch.14212

This study aimed to examine the relationship of adherence with blood pressure (BP) control and its associated factors in hypertensive patients. This cross-sectional nationwide BP screening study was conducted in Malaysia from May to October 2018. Participants with self-declared hypertension completed the Hill-Bone Compliance to High Blood Pressure Therapy Scale (Hill-Bone CHBPTS) which assesses three important domains of patient behavior to hypertension management namely medication taking, appointment keeping and reduced salt intake. Lower scores indicate better compliance while higher scores indicate otherwise. Participant's body mass index and seated BP were measured based on standard measurement protocol. Determinants of adherence to treatment were analyzed using multiple linear regression. Out of 5167 screened subjects, 1705 were known hypertensives. Of these, 927 (54.4%) answered the Hill-Bone CHBPTS and were entered into analysis. The mean age was 59.0 ± 13.2 years, 55.6% were female and 42.2% were Malays. The mean Hill-Bone CHBPTS score was 20.4 ± 4.4 (range 14-47), and 52.1% had good adherence. The mean systolic BP and diastolic BP were 136.4 ± 17.9 and 80.6 ± 11.6 mmHg, respectively. BP was controlled in 58.3% of those with good adherence compared to 50.2% in those with poor adherence (p = .014). Based on multiple linear regression analysis, female gender (β = -0.72, 95% confidence interval [CI] -1.30, -0.15, p = .014), older age (β = -0.05, 95% CI -0.07, -0.03, p
Fulltext Methanol extract of Melastoma malabathricum leaves exerted antioxidant and liver protective activity in rats

Mamat SS, Kamarolzaman MF, Yahya F, Mahmood ND, Shahril MS, Jakius KF, et al.

BMC Complement Altern Med, 2013;13:326.
PMID: 24267313 DOI: 10.1186/1472-6882-13-326

Melastoma malabathricum L. (Melastomaceae) is a small shrub with various medicinal uses. The present study was carried out to determine the hepatoprotective activity of methanol extract of M. malabathricum leaves (MEMM) against the paracetamol-induced liver toxicity in rats model.
Fulltext Complementary alternative medicine use among patients with dengue fever in the hospital setting: a cross-sectional study in Malaysia

Ching SM, Ramachandran V, Gew LT, Lim SMS, Sulaiman WAW, Foo YL, et al.

BMC Complement Altern Med, 2016 Jan 29;16:37.
PMID: 26825057 DOI: 10.1186/s12906-016-1017-0

BACKGROUND: In Malaysia, the number of reported cases of dengue fever demonstrates an increasing trend. Since dengue fever has no vaccine or antiviral treatment available, it has become a burden. Complementary and alternative medicine (CAM) has become one of the good alternatives to treat the patients with dengue fever. There is limited study on the use of CAM among patients with dengue fever, particularly in hospital settings. This study aims to determine the prevalence, types, reasons, expenditure, and resource of information on CAM use among patients with dengue fever.
METHODS: This is a descriptive, cross-sectional study of 306 patients with dengue fever, which was carried out at the dengue clinic of three hospitals. Data were analysed using IBM SPSS Statistics version 21.0 and logistic regression analysis was used to determine the factors associated with CAM use.
RESULTS: The prevalence of CAM use was 85.3% among patients with dengue fever. The most popular CAMs were isotonic drinks (85.8%), crab soup (46.7%) and papaya leaf extract (22.2%). The most common reason for CAM use was a good impression of CAM from other CAM users (33.3%). The main resource of information on CAM use among patients with dengue fever was family (54.8%). In multiple logistic regression analysis, dengue fever patients with a tertiary level are more likely to use CAM 5.8 (95% confidence interval (CI 1.62-20.45) and 3.8 (95% CI 1.12-12.93) times than secondary level and primary and below respectively.
CONCLUSION: CAM was commonly used by patients with dengue fever. The predictor of CAM use was a higher level of education.
Study site: Dengue clinic, Hospital Serdang, Hospital Kajang and Hospital Kuala Lumpur, Selangor, Malaysia.
Fulltext Cue-Reactivity Among Young Adults With Problematic Instagram Use in Response to Instagram-Themed Risky Behavior Cues: A Pilot fMRI Study

Nasser NS, Sharifat H, Rashid AA, Hamid SA, Rahim EA, Loh JL, et al.

Front Psychol, 2020;11:556060.
PMID: 33224051 DOI: 10.3389/fpsyg.2020.556060

Background: Problematic Instagram use (PIGU), a specific type of internet addiction, is prevalent among adolescents and young adults. In certain instances, Instagram acts as a platform for exhibiting photos of risk-taking behavior that the subjects with PIGU upload to gain likes as a surrogate for gaining peer acceptance and popularity.
Aims: The primary objective was to evaluate whether addiction-specific cues compared with neutral cues, i.e., negative emotional valence cues vs. positive emotional valence cues, would elicit activation of the dopaminergic reward network (i.e., precuneus, nucleus accumbens, and amygdala) and consecutive deactivation of the executive control network [i.e., medial prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC)], in the PIGU subjects.
Method: An fMRI cue-induced reactivity study was performed using negative emotional valence, positive emotional valence, and truly neutral cues, using Instagram themes. Thirty subjects were divided into PIGU and healthy control (HC) groups, based on a set of diagnostic criteria using behavioral tests, including the Modified Instagram Addiction Test (IGAT), to assess the severity of PIGU. In-scanner recordings of the subjects' responses to the images and regional activity of the neural addiction pathways were recorded.
Results: Negative emotional valence > positive emotional valence cues elicited increased activations in the precuneus in the PIGU group. A negative and moderate correlation was observed between PSC at the right mPFC with the IGAT scores of the PIGU subjects when corrected for multiple comparisons [r = -0.777, (p < 0.004, two-tailed)].
Conclusion: Addiction-specific Instagram-themed cues identify the neurobiological underpinnings of Instagram addiction. Activations of the dopaminergic reward system and deactivation of the executive control network indicate converging neuropathological pathways between Instagram addiction and other types of addictions.
Exosomal microRNAs in the development of essential hypertension and its potential as biomarkers

Tan PPS, Hall D, Chilian WM, Chia YC, Mohd Zain S, Lim HM, et al.

Am J Physiol Heart Circ Physiol, 2021 04 01;320(4):H1486-H1497.
PMID: 33577433 DOI: 10.1152/ajpheart.00888.2020

MicroRNAs (miRNAs) are small regulatory molecules that are involved in posttranscriptional modifications. These noncoding RNAs are usually ferried by extracellular carriers such as exosomes or other protein and lipid carriers inside a range of body fluids including plasma and urine. Due to their ability to withstand harsh external conditions, exosomal miRNAs possess enormous potential as noninvasive disease biomarkers for, notably hypertension, whereby exosomal miRNAs have been implicated in its pathophysiological processes. More importantly, alterations in the microenvironment as a result of disease progression can induce active and selective loading of miRNAs into exosomes. In this paper, we first review the mechanisms of miRNA loading into exosomes, followed by the roles of exosomal miRNAs in the development of hypertension, and the potentials of exosomal miRNAs as biomarkers in comparison with other free circulating miRNAs. Finally, challenges and future research surrounding exosomal miRNAs will also be discussed. This review will aid in the understanding of noninvasive biomarkers for the early diagnosis of hypertension and for probing therapeutic efficacy.
Fulltext Psychometric properties of the Malay version of the Diabetes Empowerment Scale among Hospital Serdang type 2 diabetes mellitus patients using exploratory factor analysis

Ching SM, Yee A, Lee PY, Ramachandran V, Shum KM, Ismael NF, et al.

Health Qual Life Outcomes, 2020 Feb 07;18(1):23.
PMID: 32033609 DOI: 10.1186/s12955-020-1280-0

BACKGROUND: This study was initiated to examine the psychometric components of the Diabetes Empowerment Scale (DES) by translating and validating the scale into the Malay language (DES-M) which is the main language spoken in Malaysia. This study can determine the level of empowerment among diabetic patients towards diabetes management. In addition, the reliability and validity of the DES-M was also demonstrated.
METHODS: A total of 151 patients with type 2 diabetes mellitus were recruited (between June 2016 and October 2016) to complete sets of questionnaires, which were DES-M, the Malay versions of the Diabetes Quality of Life (DQOL) for Adults and Summary of Diabetes Self Care Activities Questionnaire (SDSCA). Confirmatory and Exploratory factor analysis (CFA and EFA) were carried out to determine the factor structures of the DES-M.
RESULTS: There were 100 males and 51 females with ages ranging from 19 to 81 years old (55 ± 13) included in this study. The instrument displayed good internal consistency (Cronbach's α =0.920) and the respective coefficients ranged from 0.65-0.84. Discriminant validity showed adequate correlations ranged from 0.257-0.744. Concurrent validity with SDSCA (Pearson's correlation = 0.313, p = 0.012). Predictive validity with DQOL (B = 0.27, p = 0.016). CFA indicated that four factor model of the DES-M has good fit to the data.
CONCLUSION: This study indicates that the DES-M has a good internal consistency and validity. Therefore, it is a valid and reliable instrument for assessing empowerment score among patients with diabetes in Malaysia.
TRIAL REGISTRATION: NMRR-16-805-30503 (IIR).
Fulltext PUTRA-Adol study: protocol for an observational follow-up study to assess the tracking of dietary patterns linked to cardiometabolic risk factors and its prospective relationship with non-alcoholic fatty liver disease, carotid intima-medial thickness and mental well-being during adolescence in Malaysia

Appannah G, Emi NA, Magendiran M, Mohd Shariff Z, Anuar Zaini A, Shamsuddin NH, et al.

BMJ Open, 2021 05 25;11(5):e044747.
PMID: 34035098 DOI: 10.1136/bmjopen-2020-044747

INTRODUCTION: Growing evidence suggesting that dietary intakes of adolescents are generally of poor quality but not adequately assessed in relation to the early manifestation of non-communicable diseases. This study aimed; (1) to examine tracking of an empirical dietary pattern (DP) linked to cardiometabolic risk factors and, (2) to assess prospective relationships between a DP characterised by high intakes of dietary energy density (DED) and added sugar, and cardiometabolic risk factors, non-alcoholic fatty liver disease (NAFLD), carotid intima-medial thickness (CIMT) and mental well-being during adolescence.
METHODS AND ANALYSIS: The PUTRA-Adol is a prospective follow-up study that builds up from 933 Malaysian adolescents who were initially recruited from three southern states in Peninsular Malaysia in 2016 (aged 13 years then). Two sessions are planned; the first session will involve the collection of socio-economy, physical activity, dietary intakes, mental well-being, body image, risk taking behaviour, sun exposure, family functioning and menstrual (in women) information. The second session of data collection will be focused on direct assessments such as venesection for blood biochemistry, anthropometry and ultrasonography imaging of liver and bilateral carotid arteries. Z-scores for an empirical DP will be identified at 16 years using reduced rank regression. Multilevel modelling will be conducted to assess the tracking of DP and prospective analysis between the DP, cardiometabolic health, NAFLD, CIMT and mental well-being.
ETHICS AND DISSEMINATION: Ethical approval for the conduct of this follow-up study was obtained from the Universiti Putra Malaysia's Ethics Committee for Research Involving Human Subjects (JKEUPM) (Reference number: JKEUPM-2019-267). The findings from this study will be disseminated in conferences and peer-reviewed journals.
DISCUSSION: The findings gathered from this study will provide evidence on prospective relationships between DPs, cardiometabolic risk factors, NAFLD, early atherosclerosis and mental well-being and that it may be mediated particularly DED and added sugar during adolescence.
Fulltext Analysis of the association between CFH Y402H polymorphism and response to intravitreal ranibizumab in patients with neovascular age-related macular degeneration (nAMD)

Mohamad NA, Ramachandran V, Ismail P, Mohd Isa H, Chan YM, Ngah NF, et al.

Bosn J Basic Med Sci, 2018 Aug 01;18(3):260-267.
PMID: 29579408 DOI: 10.17305/bjbms.2018.2493

Pharmacogenetic studies indicate that a variable response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular form of AMD (nAMD) may be due to polymorphisms in the complement factor H gene (CFH). This study is the first to investigate the association between CFH Y402H polymorphism and the response to ranibizumab therapy in Malaysian patients with nAMD. We included 134 patients with nAMD, examined between September 2014 and February 2016. The diagnosis of nAMD was confirmed by ophthalmologic examination, before ranibizumab therapy was started. Each patient received an intravitreal injection of 0.5 mg/0.05 ml ranibizumab following a treat-and-extend (TE) regimen. Best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were recorded after 3 and 6 months following the first injection and compared with the baseline values. Genotyping of Y402H (rs1061170) polymorphism was performed using PCR-RFLP and the amplified product was digested with MluCI restriction enzyme. Association between the Y402H genotypes and response to treatment was determined by a logistic regression analysis of responder (n = 49) and non-responder (n = 84) group. Significantly worse mean BCVA was observed for the CC genotype compared to the TT + CT genotype in the total sample after 6-month follow-up (p = 0.018). Comparing the baseline and 6-month point measurements, improved mean BCVA was observed in responder group, while worse mean BCVA was recorded for non-responder group. However, our regression analysis, adjusted for confounding factors, showed no significant association between the Y402H genotypes and response to treatment in nAMD patients under the recessive model (p > 0.05). Overall, our results suggest that factors other than Y402H polymorphism may be involved in the progression of nAMD after treatment with anti-VEGF agents, in Malaysian population.
Fulltext Comparing and determining factors associated with hypertension self-care profiles of patients in two multi-ethnic Asian countries: cross-sectional studies between two study populations

Wee SY, Salim H, Mawardi M, Koh YLE, Ali H, Shariff Ghazali S, et al.

BMJ Open, 2021 06 14;11(6):e044192.
PMID: 34127489 DOI: 10.1136/bmjopen-2020-044192

OBJECTIVES: To compare the sociodemography, disease characteristics and hypertension self-care profiles and to determine the factors influencing Hypertension Self-Care Profiles (HTN-SCP) in two populations in primary care settings from Singapore and Malaysia.
DESIGN: Cross-sectional, cross national.
SETTING: Multi-centre, primary care clinics Malaysia and Singapore.
PARTICIPANTS: 1123 adults with hypertension enrolled and analysed.
PRIMARY AND SECONDARY OUTCOME MEASURES: Comparison between sociodemography, disease characteristics and the mean scores of HTN-SCP domains (behaviour, motivation and self-efficacy) and the factors influencing hypertension self-care.
RESULTS: 1123 adults with hypertension attending primary care clinics in Malaysia and Singapore were involved. The participants' mean age was 63.6 years (SD 9.7) in Singapore and 60.4 (SD 9.1) in Malaysia. Most of the participants in Singapore had tertiary education (22.3%) compared with Malaysia (13.0%), p<0.001. A higher proportion of participants from Singapore had controlled blood pressure (74.6%) compared with Malaysia (33.8%), p<0.001. The mean total score of HTN-SCP was significantly higher among Singapore participants compared with Malaysia participants 190 (SD 28) versus 184 (SD 23) (p<0.001). Similarly, the mean score for motivation domain 67 (SD 10) versus 65 (SD 9), followed by self-efficacy score 65 (SD 11) versus 62 (SD 9) and behaviour score (58 SD 9 vs 56 SD 9) were higher among Singapore participants. In both countries, the factors which influenced higher HTN-SCP mean scores across all domains were being Indian and had tertiary education.
CONCLUSIONS: The study population in Singapore had a higher HTN-SCP mean score compared with Malaysia. The common factors influencing higher HTN-SCP mean scores at both study sites were ethnicity and level of education. Future intervention to improve self-care among people with hypertension may need to be tailored to their behaviour, motivation and self-efficacy levels.
Fulltext Antinociceptive Activity of Methanolic Extract of Clinacanthus nutans Leaves: Possible Mechanisms of Action Involved

Zakaria ZA, Abdul Rahim MH, Roosli RAJ, Mohd Sani MH, Omar MH, Mohd Tohid SF, et al.

Pain Res Manag, 2018;2018:9536406.
PMID: 29686743 DOI: 10.1155/2018/9536406

Methanolic extract of Clinacanthus nutans Lindau leaves (MECN) has been proven to possess antinociceptive activity that works via the opioid and NO-dependent/cGMP-independent pathways. In the present study, we aimed to further determine the possible mechanisms of antinociception of MECN using various nociceptive assays. The antinociceptive activity of MECN was (i) tested against capsaicin-, glutamate-, phorbol 12-myristate 13-acetate-, bradykinin-induced nociception model; (ii) prechallenged against selective antagonist of opioid receptor subtypes (β-funaltrexamine, naltrindole, and nor-binaltorphimine); (iii) prechallenged against antagonist of nonopioid systems, namely, α2-noradrenergic (yohimbine), β-adrenergic (pindolol), adenosinergic (caffeine), dopaminergic (haloperidol), and cholinergic (atropine) receptors; (iv) prechallenged with inhibitors of various potassium channels (glibenclamide, apamin, charybdotoxin, and tetraethylammonium chloride). The results demonstrated that the orally administered MECN (100, 250, and 500 mg/kg) significantly (p < 0.05) reversed the nociceptive effect of all models in a dose-dependent manner. Moreover, the antinociceptive activity of 500 mg/kg MECN was significantly (p < 0.05) inhibited by (i) antagonists of μ-, δ-, and κ-opioid receptors; (ii) antagonists of α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and (iii) blockers of different K+ channels (voltage-activated-, Ca2+-activated, and ATP-sensitive-K+ channels, resp.). In conclusion, MECN-induced antinociception involves modulation of protein kinase C-, bradykinin-, TRVP1 receptors-, and glutamatergic-signaling pathways; opioidergic, α2-noradrenergic, β-adrenergic, adenosinergic, dopaminergic, and cholinergic receptors; and nonopioidergic receptors as well as the opening of various K+ channels. The antinociceptive activity could be associated with the presence of several flavonoid-based bioactive compounds and their synergistic action with nonvolatile bioactive compounds.

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