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All serotypes of dengue virus induce HLA-A2 major histocompatibility complex class I promoter activity in human liver cells

Othman S, Rahman NA, Yusof R

Trans R Soc Trop Med Hyg, 2010 Dec;104(12):806-8.
PMID: 20800252 DOI: 10.1016/j.trstmh.2010.07.004

In contrast to many viruses that escape the host's immune responses by suppressing the major histocompatibility complex (MHC) class I pathway, flaviviruses have been shown to up-regulate the cell surface expression of MHC class I complex. The mechanism by which dengue virus (DV) achieves this up-regulation remains unclear. Our investigation on the HLA-A2 gene in human liver cells demonstrated that all four serotypes of dengue virus, DV1 to DV4, resulted in variable degrees of promoter induction. This illustrates the importance of MHC class I transcription regulation in primary infections by different DV serotypes that may have even greater impact in secondary infections, associated with increased disease severity.
Fulltext Inhibition of dengue NS2B-NS3 protease and viral replication in Vero cells by recombinant retrocyclin-1

Rothan HA, Han HC, Ramasamy TS, Othman S, Rahman NA, Yusof R

BMC Infect Dis, 2012;12:314.
PMID: 23171075 DOI: 10.1186/1471-2334-12-314

Global resurgence of dengue virus infections in many of the tropical and subtropical countries is a major concern. Therefore, there is an urgent need for the development of successful drugs that are both economical and offer a long-lasting protection. The viral NS2B-NS3 serine protease (NS2B-NS3pro) is a promising target for the development of drug-like inhibitors, which are not available at the moment. In this study, we report retrocyclin-1 (RC-1) production in E. coli as a recombinant peptide to test against dengue NS2B-NS3pro.
Mefenamic acid in combination with ribavirin shows significant effects in reducing chikungunya virus infection in vitro and in vivo

Rothan HA, Bahrani H, Abdulrahman AY, Mohamed Z, Teoh TC, Othman S, et al.

Antiviral Res, 2016 Mar;127:50-6.
PMID: 26794398 DOI: 10.1016/j.antiviral.2016.01.006

Chikungunya virus (CHIKV) infection is a persistent problem worldwide due to efficient adaptation of the viral vectors, Aedes aegypti and Aedes albopictus mosquitoes. Therefore, the absence of effective anti-CHIKV drugs to combat chikungunya outbreaks often leads to a significant impact on public health care. In this study, we investigated the antiviral activity of drugs that are used to alleviate infection symptoms, namely, the non-steroidal anti-inflammatory drugs (NSAIDs), on the premise that active compounds with potential antiviral and anti-inflammatory activities could be directly subjected for human use to treat CHIKV infections. Amongst the various NSAID compounds, Mefenamic acid (MEFE) and Meclofenamic acid (MECLO) showed considerable antiviral activity against viral replication individually or in combination with the common antiviral drug, Ribavirin (RIBA). The 50% effective concentration (EC50) was estimated to be 13 μM for MEFE, 18 μM for MECLO and 10 μM for RIBA, while MEFE + RIBA (1:1) exhibited an EC50 of 3 μM, and MECLO + RIBA (1:1) was 5 μM. Because MEFE is commercially available and its synthesis is easier compared with MECLO, MEFE was selected for further in vivo antiviral activity analysis. Treatment with MEFE + RIBA resulted in a significant reduction of hypertrophic effects by CHIKV on the mouse liver and spleen. Viral titre quantification in the blood of CHIKV-infected mice through the plaque formation assay revealed that treatment with MEFE + RIBA exhibited a 6.5-fold reduction compared with untreated controls. In conclusion, our study demonstrated that MEFE in combination with RIBA exhibited significant anti-CHIKV activity by impairing viral replication in vitro and in vivo. Indeed, this finding may lead to an even broader application of these combinatorial treatments against other viral infections.
Induction of MHC Class I HLA-A2 promoter by dengue virus occurs at the NFκB binding domains of the Class I Regulatory Complex

Othman S, Rahman NA, Yusof R

Virus Res, 2012 Jan;163(1):238-45.
PMID: 22001567 DOI: 10.1016/j.virusres.2011.09.040

Despite aggressive efforts in dengue research, the control of dengue diseases and discovery of therapeutics against them await complete elucidation of its complex immune-pathogenesis. Unlike many viruses that escape the host's immune responses by suppressing the major histocompatibility complex (MHC) Class I pathway, many Flaviviruses up-regulate the cell surface expression of MHC Class I complex. We recently reported MHC Class I HLA-A2 promoter activation by all serotypes of dengue virus (DV). The mechanism by which DV regulates this is further explored here in HepG2 human liver cell line. Using real-time PCR, evidence that, similar to infections by other Flaviviruses, DV infection has the ability to up-regulate the MHC Class I transcription and mRNA synthesis, is presented. The region responsive towards DV infection of all serotypes was mapped to the Class I Regulatory Complex (CRC) of the HLA-A2 promoter. Competition electrophoretic mobility shift assay (EMSA) with NFκB probe established the presence of specific DNA-protein complex in DV-infected nuclear extracts. Antibody-supershift assays identified the MHC Class I promoter activation by DV to occur through binding of p65/p50 heterodimers and p65 homodimers to κB1 and κB2 cis-acting elements, respectively, within the CRC, and not with the interferon consensus sequence (ICS). This study presents evidence of MHC Class I gene modulation by DV, hence providing a better understanding of dengue immune-pathogenesis that would consequently facilitate the discovery of antiviral therapeutics against dengue.
Fulltext Protegrin-1 inhibits dengue NS2B-NS3 serine protease and viral replication in MK2 cells

Rothan HA, Abdulrahman AY, Sasikumer PG, Othman S, Rahman NA, Yusof R

J Biomed Biotechnol, 2012;2012:251482.
PMID: 23093838 DOI: 10.1155/2012/251482

Dengue diseases have an economic as well as social burden worldwide. In this study, the antiviral activity of protegrin-1 (PG-1, RGGRLCYCRRRFCVCVGR) peptide towards dengue NS2B-NS3pro and viral replication in Rhesus monkey kidney (MK2) cells was investigated. The peptide PG-1 was synthesized by solid-phase peptide synthesis, and disulphide bonds formation followed by peptide purification was confirmed by LC-MS and RPHPLC. Dengue NS2B-NS3pro was produced as a single-chain recombinant protein in E. coli. The NS2B-NS3pro assay was carried out by measuring the florescence emission of catalyzed substrate. Real-time PCR was used to evaluate the inhibition potential of PG-1 towards dengue serotype-2 (DENV-2) replication in MK2 cells. The results showed that PG-1 inhibited dengue NS2B-NS3pro at IC(50) of 11.7 μM. The graded concentrations of PG-1 at nontoxic range were able to reduce viral replication significantly (P < 0.001) at 24, 48, and 72 hrs after viral infection. However, the percentage of inhibition was significantly (P < 0.01) higher at 24 hrs compared to 48 and 72 hrs. These data show promising therapeutic potential of PG-1 against dengue infection, hence it warrants further analysis and improvement of the peptide features as a prospective starting point for consideration in designing attractive dengue virus inhibitors.
Fulltext Boesenbergia rotunda: From Ethnomedicine to Drug Discovery

Eng-Chong T, Yean-Kee L, Chin-Fei C, Choon-Han H, Sher-Ming W, Li-Ping CT, et al.

Evid Based Complement Alternat Med, 2012;2012:473637.
PMID: 23243448 DOI: 10.1155/2012/473637

Boesenbergia rotunda is a herb from the Boesenbergia genera under the Zingiberaceae family. B. rotunda is widely found in Asian countries where it is commonly used as a food ingredient and in ethnomedicinal preparations. The popularity of its ethnomedicinal usage has drawn the attention of scientists worldwide to further investigate its medicinal properties. Advancement in drug design and discovery research has led to the development of synthetic drugs from B. rotunda metabolites via bioinformatics and medicinal chemistry studies. Furthermore, with the advent of genomics, transcriptomics, proteomics, and metabolomics, new insights on the biosynthetic pathways of B. rotunda metabolites can be elucidated, enabling researchers to predict the potential bioactive compounds responsible for the medicinal properties of the plant. The vast biological activities exhibited by the compounds obtained from B. rotunda warrant further investigation through studies such as drug discovery, polypharmacology, and drug delivery using nanotechnology.
Diagnostic performance of COVID-19 serology assays

Zainol Rashid Z, Othman SN, Abdul Samat MN, Ali UK, Wong KK

Malays J Pathol, 2020 Apr;42(1):13-21.
PMID: 32342927

INTRODUCTION: The World Health Organization (WHO) declared COVID-19 outbreak as a world pandemic on 12th March 2020. Diagnosis of suspected cases is confirmed by nucleic acid assays with real-time PCR, using respiratory samples. Serology tests are comparatively easier to perform, but their utility may be limited by the performance and the fact that antibodies appear later during the disease course. We aimed to describe the performance data on serological assays for COVID-19.
MATERIALS AND METHODS: A review of multiple reports and kit inserts on the diagnostic performance of rapid tests from various manufacturers that are commercially available were performed. Only preliminary data are available currently.
RESULTS: From a total of nine rapid detection test (RDT) kits, three kits offer total antibody detection, while six kits offer combination SARS-CoV-2 IgM and IgG detection in two separate test lines. All kits are based on colloidal gold-labeled immunochromatography principle and one-step method with results obtained within 15 minutes, using whole blood, serum or plasma samples. The sensitivity for both IgM and IgG tests ranges between 72.7% and 100%, while specificity ranges between 98.7% to 100%. Two immunochromatography using nasopharyngeal or throat swab for detection of COVID-19 specific antigen are also reviewed.
CONCLUSIONS: There is much to determine regarding the value of serological testing in COVID-19 diagnosis and monitoring. More comprehensive evaluations of their performance are rapidly underway. The use of serology methods requires appropriate interpretations of the results and understanding the strengths and limitations of such tests.
Fulltext Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling

Hariono M, Choi SB, Roslim RF, Nawi MS, Tan ML, Kamarulzaman EE, et al.

PLoS One, 2019;14(1):e0210869.
PMID: 30677071 DOI: 10.1371/journal.pone.0210869

Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC50 = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC50 of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.
Inapparent dengue in a community living among dengue-positive Aedes mosquitoes and in a hospital in Klang Valley, Malaysia

Tan W, Liew JWK, Selvarajoo S, Lim XY, Foo CJ, Refai WF, et al.

Acta Trop, 2020 Apr;204:105330.
PMID: 31917959 DOI: 10.1016/j.actatropica.2020.105330

The public health burden of dengue is most likely under reported. Current dengue control measures only considered symptomatic dengue transmission. Hence, there is a paucity of information on the epidemiology of inapparent dengue. This study reports that many people have been unknowingly exposed to dengue infection. Almost 10% and 70% of individuals without any history of dengue infection and living in a dengue hotspot, in Selangor, Malaysia, were dengue IgM and IgG positive respectively. When dengue-positive mosquitoes were detected in the hotspot, 11 (6.3%) of the 174 individuals tested were found to have dengue viremia, of which 10 were asymptomatic. Besides, upon detection of a dengue-infected mosquito, transmission was already widespread. In a clinical setting, it appears that people living with dengue patients have been exposed to dengue, whether asymptomatic or symptomatic. They can either have circulating viral RNA and/or presence of NS1 antigen. It is also possible that they are dengue seropositive. Collectively, the results indicate that actions taken to control dengue transmission after the first report of dengue cases may be already too late. The current study also revealed challenges in diagnosing clinically inapparent dengue in hyperendemic settings. There is no one best method for diagnosing inapparent dengue. This study demonstrates empirical evidence of inapparent dengue in different settings. Early dengue surveillance in the mosquito population and active serological/virological surveillance in humans can go hand in hand. More studies are required to investigate the epidemiology, seroprevalence, diagnostics, and control of inapparent dengue. It is also crucial to educate the public, health staff and medical professionals on asymptomatic dengue and to propagate awareness, which is important for controlling transmission.
Iron-associated protein interaction networks reveal the key functional modules related to survival and virulence of Pasteurella multocida

Jatuponwiphat T, Chumnanpuen P, Othman S, E-Kobon T, Vongsangnak W

Microb Pathog, 2019 Feb;127:257-266.
PMID: 30550841 DOI: 10.1016/j.micpath.2018.12.013

Pasteurella multocida causes respiratory infectious diseases in a multitude of birds and mammals. A number of virulence-associated genes were reported across different strains of P. multocida, including those involved in the iron transport and metabolism. Comparative iron-associated genes of P. multocida among different animal hosts towards their interaction networks have not been fully revealed. Therefore, this study aimed to identify the iron-associated genes from core- and pan-genomes of fourteen P. multocida strains and to construct iron-associated protein interaction networks using genome-scale network analysis which might be associated with the virulence. Results showed that these fourteen strains had 1587 genes in the core-genome and 3400 genes constituting their pan-genome. Out of these, 2651 genes associated with iron transport and metabolism were selected to construct the protein interaction networks and 361 genes were incorporated into the iron-associated protein interaction network (iPIN) consisting of nine different iron-associated functional modules. After comparing with the virulence factor database (VFDB), 21 virulence-associated proteins were determined and 11 of these belonged to the heme biosynthesis module. From this study, the core heme biosynthesis module and the core outer membrane hemoglobin receptor HgbA were proposed as candidate targets to design novel antibiotics and vaccines for preventing pasteurellosis across the serotypes or animal hosts for enhanced precision agriculture to ensure sustainability in food security.
Case Series

Vetrayan J, Othman S, Victor Paulraj SJ

J Atten Disord, 2017 01;21(2):168-179.
PMID: 23529885 DOI: 10.1177/1087054713479665

OBJECTIVE: To assess the effectiveness and feasibility of behavioral sleep intervention for medicated children with ADHD.
METHOD: Six medicated children (five boys, one girl; aged 6-12 years) with ADHD participated in a 4-week sleep intervention program. The main behavioral strategies used were Faded Bedtime With Response Cost (FBRC) and positive reinforcement. Within a case-series design, objective measure (Sleep Disturbance Scale for Children [SDSC]) and subjective measure (sleep diaries) were used to record changes in children's sleep.
RESULTS: For all six children, significant decrease was found in the severity of children's sleep problems (based on SDSC data). Bedtime resistance and mean sleep onset latency were reduced following the 4-week intervention program according to sleep diaries data. Gains were generally maintained at the follow-up. Parents perceived the intervention as being helpful.
CONCLUSION: Based on the initial data, this intervention shows promise as an effective and feasible treatment.
Fulltext Factors Associated With Falls Among Urban-Dwellers Aged 55 Years and Over in the Malaysian Elders Longitudinal Research (MELoR) Study

Alex D, Khor HM, Chin AV, Hairi NN, Cumming RG, Othman S, et al.

Front Public Health, 2020;8:506238.
PMID: 33304870 DOI: 10.3389/fpubh.2020.506238

Falls are major issues affecting the older population with potentially serious complications, including fractures, head injury, institutionalization, fear of falling and depression. While risk factors for falls have been established across Western Europe and North America, geographical differences in falls risk have not been well researched. We aim to examine the clinical and physical risk factors for falls in a middle-income South East Asian country. Cross-sectional data from the Malaysian Elders Longitudinal Research (MELoR) study involving 1,362 community dwelling individuals aged 55 years and above was utilized. Information on sociodemographic and medical history was obtained by computer-assisted questionnaires completed during home visits and hospital-based detailed health checks. Univariate and multivariate analyses compared non-fallers and fallers in the previous 12 months. Urinary incontinence, hearing impairment, depression, arthritis and cognitive impairment were risk factors for falls in the past 12 months after adjustment for age in our study population. Awareness about the risk factors in a population helps the design of fall prevention strategies that target specific or multiple risk factors.
Vitamin D deficiency is associated with ethnicity and knee pain in a multi-ethnic South-East Asian nation: Results from Malaysian Elders Longitudinal Research (MELoR)

Mat S, Jaafar MH, Sockalingam S, Raja J, Kamaruzzaman SB, Chin AV, et al.

Int J Rheum Dis, 2018 May;21(5):930-936.
PMID: 29611292 DOI: 10.1111/1756-185X.13279

AIM: To determine the association between vitamin D and knee pain among participants of the Malaysian Elders Longitudinal Research (MELoR) study.

METHOD: This was a cross-sectional study from the MELoR study consisting of a representative group of 1011 community-dwelling older persons (57% female), mean age 86.5 (54-94) years; 313 were Malays, 367 Chinese and 330 Indians. Participants were asked if they had knee pain. Levels of serum 25-hydroxy cholecalciferol (25-[OH]D), an indicator of vitamin D status, were measured using routine laboratory techniques.

RESULTS: In unadjusted analysis, presence of knee pain was significantly associated with vitamin D deficiency (odds ratio [OR] 1.42; 95% confidence interval (CI) 1.08-1.85, P 0.011). Vitamin D levels were significantly associated with ethnicity differences where Malays (OR 7.08; 95% CI 4.94-10.15) and Indians (OR 6.10; 95% CI 4.28-9.71) have lower levels of vitamin D compared to Chinese. Subsequent multivariate analysis revealed that the association between vitamin D deficiency and knee pain was confounded by ethnic differences.

CONCLUSION: A previous study suggested that vitamin D deficiency was associated with knee pain. This relationship was reproduced in our study, but we further established that the association was explained by ethnic variations. As vitamin D status is dependent on skin tone, diet and sunlight exposure, which are all effected by ethnicity, future studies are now required to determine whether a true relationship exists between vitamin D and knee pain.
Fulltext Cross-sectional analysis of ethnic differences in fall prevalence in urban dwellers aged 55 years and over in the Malaysian Elders Longitudinal Research study

Alex D, Khor HM, Chin AV, Hairi NN, Othman S, Khoo SPK, et al.

BMJ Open, 2018 07 17;8(7):e019579.
PMID: 30018093 DOI: 10.1136/bmjopen-2017-019579

OBJECTIVES: Falls represent major health issues within the older population. In low/middle-income Asian countries, falls in older adults remain an area which has yet to be studied in detail. Using data from the Malaysian Elders Longitudinal Research (MELoR), we have estimated the prevalence of falls among older persons in an urban population, and performed ethnic comparisons in the prevalence of falls.
DESIGN: Cross-sectional analysis was carried out using the first wave data from MELoR which is a longitudinal study.
SETTING: Urban community dwellers in a middle-income South East Asian country.
PARTICIPANTS: 1565 participants aged ≥55 years were selected by simple random sampling from the electoral rolls of three parliamentary constituencies.
OUTCOME MEASURES: Consenting participants from the MELoR study were asked the question 'Have you fallen down in the past 12 months?' during their computer-assisted home-based interviews. Logistic regression analyses were conducted to compare the prevalence of falls among various ethnic groups.
RESULTS: The overall estimated prevalence of falls for individuals aged 55 years and over adjusted to the population of Kuala Lumpur was 18.9%. The estimated prevalence of falls for the three ethnic populations of Malays, Chinese and Indian aged 55 years and over was 16.2%, 19.4% and 23.8%, respectively. Following adjustment for ethnic discrepancies in age, gender, marital status and education attainment, the Indian ethnicity remained an independent predictor of falls in our population (relative risk=1.45, 95% CI 1.08 to 1.85).
CONCLUSION: The prevalence of falls in this study is comparable to other previous Asian studies, but appears lower than Western studies. The predisposition of the Indian ethnic group to falls has not been previously reported. Further studies may be needed to elucidate the causes for the ethnic differences in fall prevalence.
Fulltext Ethnic differences in the prevalence, socioeconomic and health related risk factors of knee pain and osteoarthritis symptoms in older Malaysians

Mat S, Jaafar MH, Ng CT, Sockalingam S, Raja J, Kamaruzzaman SB, et al.

PLoS One, 2019;14(11):e0225075.
PMID: 31751378 DOI: 10.1371/journal.pone.0225075

Knee pain is often underreported, underestimated and undertreated. This study was conducted to estimate the prevalence, burden and further identify socioeconomic factors influencing ethnic differences in knee pain and symptoms of OA among older adults aged 55 years and over in Greater Kuala Lumpur (the capital city of Malaysia). The sample for the Malaysian Elders Longitudinal Research (MELoR) was selected using stratified random sampling, by age and ethnicity from the electoral rolls of three parliamentary constituencies. Information on knee pain was available in 1226 participants, mean age (SD) 68.96 (1.57) years (409 Malay, 416 Chinese, 401 Indian). The crude and weighted prevalence of knee pain and self-reported knee OA symptoms were 33.3% and 30.8% respectively. There were significant ethnic differences in knee pain (crude prevalence: Malays 44.6%, Chinese 23.5% and Indians 31.9%, p<0.001). The presence of two or more non-communicable diseases (NCD) attenuated the increased risk of knee pain among the ethnic Indians compared to the ethnic Chinese. The prevalence of knee pain remained significantly higher among the ethnic Malays after adjustment for confounders. While the prevalence of knee pain in our older population appears similar to that reported in other published studies in Asia, the higher prevalence among the ethnic Malays has not previously been reported. Further research to determine potential genetic susceptibility to knee pain among the ethnic Malays is recommended.
Fulltext Factors Determining the Increased Risk of Falls in Individuals With Knee Pain in the Malaysian Elders Longitudinal Research (MELoR) Study

Mat S, Razack AH, Lim J, Khong SY, Kamaruzzaman SB, Chin AV, et al.

Front Med (Lausanne), 2019;6:277.
PMID: 31850355 DOI: 10.3389/fmed.2019.00277

Objectives: While the negative impact of falls in older persons has been recognized, the association between knee pains and falls remains inconclusive due to underreporting and undertreatment of knee pain. This study was conducted to evaluate the relationship between knee pain and knee pain severity with falls risk and to further determine factors which influence this potential relationship. Design: This was cross-sectional study from the Malaysian Elders Longitudinal Research (MELoR) study. Setting: Urban community dwellers in a middle-income South East Asian country. Participants: One thousand two hundred twelve of a representative sample of community dwelling older persons aged 55 years and older. Outcome measures: Falls in the preceding 12 months and knee pain were collected during a home-based computer-assisted interview. Physical and functional performance were measured using the Timed Up and Go test and the Katz and Lawton scales, respectively. Psychological status was determined using the Depression Anxiety and Stress Scale (DASS-21). Results: Of the 1,212 participants included in this analysis, knee pain was present in 402 (33.17%) individuals (124 (30.85%) mild, 210 (52.24%) moderate, 68 (16.92%) severe). The presence of knee pain was associated with increased risk of falls [odds Ratio, OR(95% confidence interval, CI): 1.81 (1.37-2.38)]. Severe knee pain was an independent predictor for falls after adjustment for functional impairment and psychological status. Mild, moderate, and severe knee pain had a specific indirect effect on falls through reducing functional impairment, which in turn increases their psychological concern. Conclusion: Future studies should explore this relationship prospectively and evaluate whether interventions which alleviate psychological concerns and improve function will reduce falls risk in those with mild to moderate knee pain.
Neurosyphilis and psychosis

Wahab S, Md Rani SA, Sharis Othman S

Asia Pac Psychiatry, 2013 Apr;5 Suppl 1:90-4.
PMID: 23857843 DOI: 10.1111/appy.12050

Neurosyphilis may presents with a range of psychiatric symptoms. This report illustrates a case of neurosyphilis in a man who presented with psychosis and cognitive dysfunction. Clinical findings and investigations done in the present case showed positive results for syphilis. Reduction of symptoms was noted after treatment with antibiotic. This case further highlights the importance of having high index of suspicion for neurosyphilis in patients presenting with psychiatric symptoms.
Prevalence and determinants of hearing disability among older persons in Malaysia: Finding of National Health Morbidity Survey (NHMS) 2018

Harith AA, Ahmad NA, Sahril N, Wahab NA, Kassim NA, Othman S, et al.

Geriatr Gerontol Int, 2020 Dec;20 Suppl 2:43-48.
PMID: 33370862 DOI: 10.1111/ggi.14039

AIM: An aging population is a potential burden for unprepared developing countries. Malaysia is foreseen to be an aging country by 2035. Thus, this study aimed to determine the prevalence and factors associated with hearing disability among older persons in Malaysia.
METHODS: Data from a nationwide survey implemented using a stratified cluster sampling design were analyzed. This study was carried out through face-to-face interviews and guided questionnaires. The questions were based on the Washington Group of Disability (WG) questionnaires, which produce multiple disability identifiers. Hearing disability is defined as at least one domain or question out of four questions coded as "A lot of difficulty" or "Cannot hear at all".
RESULTS: The prevalence of hearing disability among older persons aged ≥60 years was 6.4% (95% CI 5.0-8.3), whereas 1.5% (95% CI 0.90, 2.50) older persons were reported to be using a hearing aid. The determinants of hearing disability are being male (aOR 2.67, 95% CI 1.94-3.66), being unemployed (retired, homemaker, unemployed; aOR 1.86, 95% CI 1.86-4.14) and had no formal education (aOR 18.25, 95% CI 4.18-79.55).
CONCLUSIONS: Promoting healthy aging is important and crucial for Malaysia, in preparation toward an aging nation, as it could reduce the country's financial burden in the long term. Health-related agencies should promote health awareness and treatment centers in relation to hearing disability among older persons, as they should be educated and informed about healthcare choices availability, which is aligned with the Global Disability Action Plan 2014-2021. Geriatr Gerontol Int 2020; 20: 43-48.
High prevalence of thyroid function test abnormalities in chronic schizophrenia

Othman SS, Abdul Kadir K, Hassan J, Hong GK, Singh BB, Raman N

Aust N Z J Psychiatry, 1994 Dec;28(4):620-4.
PMID: 7794205

The thyroid status of 249 patients with chronic schizophrenia (males = 136, females = 113) with a median age of 36 years (range: 16 to 58 years) and a median duration of hospitalisation of 10 years (range: 1 to 30 years) was assessed. Thyroid antibodies (TAb) were found in 51 patients (20%). In female patients, 32 (28%) were TAb positive compared to 13% (n = 152, p = 0.01) in healthy female blood donors. In male patients, the prevalence of TAb was 14% compared to 7% (n = 449, p = 0.01) in healthy male blood donors. Of the 183 patients who had thyroid hormone measurements, 60% had normal test, 5% had elevated TSH and 17% had low TSH. The T4, FT41 and FT31 were significantly lower in those with low or high TSH (p < 0.001) compared to those with normal TSH. Of the 143 patients with normal TSH, 33 (23%) had low T3. In conclusion, there is a spectrum of thyroid function test abnormalities in chronic schizophrenia; this may be related to an abnormality in the central regulation of the hypothalamo-pituitary thyroid axis as well as at the peripheral level. However the association between chronic schizophrenia and the presence of thyroid antibodies, and the clinical relevance of these biochemical abnormalities, are still not clear.
Current approaches in antiviral drug discovery against the Flaviviridae family

Baharuddin A, Hassan AA, Sheng GC, Nasir SB, Othman S, Yusof R, et al.

Curr Pharm Des, 2014;20(21):3428-44.
PMID: 24001228

Viruses belonging to the Flaviviridae family primarily spread through arthropod vectors, and are the major causes of illness and death around the globe. The Flaviviridae family consists of 3 genera which include the Flavivirus genus (type species, yellow fever virus) as the largest genus, the Hepacivirus (type species, hepatitis C virus) and the Pestivirus (type species, bovine virus diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted by mosquitoes and ticks that take over host cell machinery in order to propagate. However, hepaciviruses and pestiviruses are not antropod-borne. Despite the extensive research and public health concern associated with flavivirus diseases, to date, there is no specific treatment available for any flavivirus infections, though commercially available vaccines for yellow fever, Japanese encephalitis and tick-born encephalitis exist. Due to the global threat of viral pandemics, there is an urgent need for new drugs. In many countries, patients with severe cases of flavivirus infections are treated only by supportive care, which includes intravenous fluids, hospitalization, respiratory support, and prevention of secondary infections. This review discusses the strategies used towards the discovery of antiviral drugs, focusing on rational drug design against Dengue virus (DENV), West Nile virus (WNV), Japanese encephalitis virus (JEV), Yellow Fever virus (YFV) and Hepatitis C virus (HCV). Only modified peptidic, nonpeptidic, natural compounds and fragment-based inhibitors (typically of mass less than 300 Da) against structural and non-structural proteins are discussed.

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