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Uncovering the experiences and needs of patients with chronic hepatitis B infection at diagnosis: a qualitative study

Ng CJ, Low WY, Wong LP, Sudin MR, Mohamed R

Asia Pac J Public Health, 2013 Jan;25(1):32-40.
PMID: 21807630 DOI: 10.1177/1010539511413258

Patients with hepatitis B face uncertainty at diagnosis. Information and support they receive at the early stage of the disease determine their adherence to follow up and treatment. This study aimed to explore the experiences and needs of patients with hepatitis B at diagnosis. A qualitative methodology was used. Nine focus groups (n = 44) were conducted to explore patients' feelings and reaction to the diagnosis, encounters with health care professionals, and their needs. The transcribed data were analyzed using a thematic approach. Most patients were not prepared for the diagnosis and many felt anxious and distressed. This was attributed to poor patients' knowledge, doctor's emphasis on disease complications, and associated stigma. Information about the disease was lacking and patients wanted to know more about the mode of transmission, natural progression of the disease, complications, and treatment options. There was a feeling of "passivity" among patients because there was often no active treatment available at diagnosis. This resulted in patients defaulting surveillance visits and missing the opportunity to start antiviral treatment. Therefore, there is an urgent need to provide sufficient information and education about hepatitis B to newly diagnosed patients, break "bad news" to patients with sensitivity, address their emotional needs, and emphasize on the rationale and importance of surveillance and treatment. This may entail public awareness campaign, implementation of pretest and posttest counseling, and educating doctors on how to communicate the diagnosis and management to patients accurately and sensitively.
Analysis of antibiotic susceptibility patterns of Helicobacter pylori isolates from Malaysia

Ahmad N, Zakaria WR, Mohamed R

Helicobacter, 2011 Feb;16(1):47-51.
PMID: 21241412 DOI: 10.1111/j.1523-5378.2010.00816.x

The prevalence of antibiotic resistance varies in geographic areas. The information on the antibiotic susceptibility patterns of Helicobacter pylori (H. pylori) in our local setting is therefore relevant as a guide for the treatment options.
Combined use of wild-type HBV precore and high serum iron marker as a potential tool for the prediction of cirrhosis in chronic hepatitis B infection

Chook JB, Ngeow YF, Yap SF, Tan TC, Mohamed R

J Med Virol, 2011 Apr;83(4):594-601.
PMID: 21328372 DOI: 10.1002/jmv.22016

Hepatitis B virus (HBV) and high liver iron deposits have both been associated with the development of cirrhosis. Among HBV factors, genotype and mutations in the basal core promoter (BCP) and precore regions have been most frequently studied but the evidence for a positive association with cirrhosis has been inconsistent. In this study, sera from persons with chronic HBV infection with and without cirrhosis were used for whole HBV genome analysis and for the estimation of serum iron marker (serum iron or ferritin) levels. Single codon analysis showed that the precore wild-type, TGG (nt 1,895-1,897), gave the highest accuracy (77.5%) for the identification of cirrhosis compared to other codons. When TGG was analyzed together with the precore start codon wild-type, ATG (nt 1,814-1,816), the accuracy was improved to 80.0% (odds ratio=35.29; 95% confidence interval=3.87-321.93; Phi=0.629; P<0.001). When the serum iron marker was included for analysis, it was clear that a combination of a precore wild-type and high serum iron marker gave a better accuracy (90.0%) (odds ratio=107.67; 95% confidence interval=10.21-1,135.59; Phi=0.804; P<0.001) for the identification of cirrhosis than either biomarker alone. It appeared that a combined use of both these biomarkers might help to predict the development of cirrhosis in a person with chronic HBV infection, but longitudinal studies are required to test this hypothesis.
Genome-wide prediction and annotation of Burkholderia pseudomallei AraC/XylS family transcription regulator

Lim BS, Chong CE, Zamrod Z, Nathan S, Mohamed R

In Silico Biol. (Gedrukt), 2007;7(4-5):389-97.
PMID: 18391231

Many members of the AraC/XylS family transcription regulator have been proven to play a critical role in regulating bacterial virulence factors in response to environmental stress. By using the Hidden Markov Model (HMM) profile built from the alignment of a 99 amino acid conserved domain sequence of 273 AraC/XylS family transcription regulators, we detected a total of 45 AraC/XylS family transcription regulators in the genome of the Gram-negative pathogen, Burkholderia pseudomallei. Further in silico analysis of each detected AraC/XylS family transcription regulatory protein and its neighboring genes allowed us to make a first-order guess on the role of some of these transcription regulators in regulating important virulence factors such as those involved in three type III secretion systems and biosynthesis of pyochelin, exopolysaccharide (EPS) and phospholipase C. This paper has demonstrated an efficient and systematic genome-wide scale prediction of the AraC/XylS family that can be applied to other protein families.
In silico analysis of Burkholderia pseudomallei genome sequence for potential drug targets

Chong CE, Lim BS, Nathan S, Mohamed R

In Silico Biol. (Gedrukt), 2006;6(4):341-6.
PMID: 16922696

Recent advances in DNA sequencing technology have enabled elucidation of whole genome information from a plethora of organisms. In parallel with this technology, various bioinformatics tools have driven the comparative analysis of the genome sequences between species and within isolates. While drawing meaningful conclusions from a large amount of raw material, computer-aided identification of suitable targets for further experimental analysis and characterization, has also led to the prediction of non-human homologous essential genes in bacteria as promising candidates for novel drug discovery. Here, we present a comparative genomic analysis to identify essential genes in Burkholderia pseudomallei. Our in silico prediction has identified 312 essential genes which could also be potential drug candidates. These genes encode essential proteins to support the survival of B. pseudomallei including outer-inner membrane and surface structures, regulators, proteins involved in pathogenenicity, adaptation, chaperones as well as degradation of small and macromolecules, energy metabolism, information transfer, central/intermediate/miscellaneous metabolism pathways and some conserved hypothetical proteins of unknown function. Therefore, our in silico approach has enabled rapid screening and identification of potential drug targets for further characterization in the laboratory.
Fulltext Susceptibility and gene interaction study of the angiotensin II type 1 receptor (AGTR1) gene polymorphisms with non-alcoholic fatty liver disease in a multi-ethnic population

Zain SM, Mohamed Z, Mahadeva S, Rampal S, Basu RC, Cheah PL, et al.

PLoS One, 2013;8(3):e58538.
PMID: 23484035 DOI: 10.1371/journal.pone.0058538

Angiotensin II type 1 receptor (AGTR1) has been reported to play a fibrogenic role in non-alcoholic fatty liver disease (NAFLD). In this study, five variants of the AGTR1 gene (rs3772622, rs3772627, rs3772630, rs3772633, and rs2276736) were examined for their association with susceptibility to NAFLD. Subjects made up of 144 biopsy-proven NAFLD patients and 198 controls were genotyped using TaqMan assays. The liver biopsy specimens were histologically graded and scored according to the method of Brunt. Single locus analysis in pooled subjects revealed no association between each of the five variants with susceptibility to NAFLD. In the Indian ethnic group, the rs2276736, rs3772630 and rs3772627 appear to be protective against NAFLD (p = 0.010, p = 0.016 and p = 0.026, respectively). Haplotype ACGCA is shown to be protective against NAFLD for the Indian ethnic subgroup (p = 0.03). Gene-gene interaction between the AGTR1 gene and the patatin-like phospholipase domain-containing 3 (PNPLA3) gene, which we previously reported as associated with NAFLD in this sample, showed a strong interaction between AGTR1 (rs3772627), AGTRI (rs3772630) and PNPLA3 (rs738409) polymorphisms on NAFLD susceptibility (p = 0.007). Further analysis of the NAFLD patients revealed that the G allele of the AGTR1 rs3772622 is associated with increased fibrosis score (p = 0.003). This is the first study that replicates an association between AGTR1 polymorphism and NAFLD, with further details in histological features of NAFLD. There is lack of evidence to suggest an association between any of the five variants of the AGTR1 gene and NAFLD in the Malays and Chinese. In the Indians, the rs2276736, rs3772630 and rs3772627 appear to protect against NAFLD. We report novel findings of an association between the G allele of the rs3772622 with occurrence of fibrosis and of the gene-gene interaction between AGTR1gene and the much-studied PNPLA3 gene.
Impact of leptin receptor gene variants on risk of non-alcoholic fatty liver disease and its interaction with adiponutrin gene

Zain SM, Mohamed Z, Mahadeva S, Cheah PL, Rampal S, Chin KF, et al.

J Gastroenterol Hepatol, 2013 May;28(5):873-9.
PMID: 23278404 DOI: 10.1111/jgh.12104

Genetic polymorphism has been implicated as a factor for the occurrence of non-alcoholic fatty liver disease (NAFLD). This study attempted to assess whether polymorphisms in the leptin receptor (LEPR) gene and its combined effect with patatin-like phospholipase domain-containing protein 3 (PNPLA3/adiponutrin) are associated with risk of NAFLD.
Comparative analysis of viral genomes from acute and chronic hepatitis B reveals novel variants associated with a lower rate of chronicity

Chook JB, Ngeow YF, Khang TF, Ng KP, Tiang YP, Mohamed R

J Med Virol, 2013 Mar;85(3):419-24.
PMID: 23297244 DOI: 10.1002/jmv.23500

Infection with the hepatitis B virus (HBV) may lead to an acute or chronic infection. It is generally accepted that the clinical outcome of infection depends on the balance between host immunity and viral survival strategies. In order to persist, the virus needs to have a high rate of replication and some immune-escape capabilities. Hence, HBVs lacking these properties are likely to be eliminated more rapidly by the host, leading to a lower rate of chronicity. To test this hypothesis, 177 HBV genomes from acute non-fulminant cases and 1,149 from chronic cases were retrieved from GenBank for comparative analysis. Selection of candidate nucleotides associated with the disease state was done using random guess cut-off and the Bonferroni correction. Five significant nucleotides were detected using this filtering step. Their predictive values were assessed using the support vector machine classification with five-fold cross-validation. The average prediction accuracy was 61% ± 1%, with a sensitivity of 24% ± 1%, specificity of 98% ± 1%, positive predictive value of 92% ± 4% and negative predictive value of 56% ± 1%. BCP/X, enhancer I and surface/polymerase variants were found to be associated almost exclusively with acute hepatitis. These HBV variants are novel potential markers for non-progression to chronic hepatitis.
ProLysED: an integrated database and meta-server of bacterial protease systems

Firdaus Raih M, Ahmad HA, Sharum MY, Azizi N, Mohamed R

Appl. Bioinformatics, 2005;4(2):147-50.
PMID: 16128617

Bacterial proteases are an important group of enzymes that have very diverse biochemical and cellular functions. Proteases from prokaryotic sources also have a wide range of uses, either in medicine as pathogenic factors or in industry and therapeutics. ProLysED (Prokaryotic Lysis Enzymes Database), our meta-server integrated database of bacterial proteases, is a useful, albeit very niche, resource. The features include protease classification browsing and searching, organism-specific protease browsing, molecular information and visualisation of protease structures from the Protein Data Bank (PDB) as well as predicted protease structures.
Solvent accessibility in native and isolated domain environments: general features and implications to interface predictability

Raih MF, Ahmad S, Zheng R, Mohamed R

Biophys Chem, 2005 Apr 1;114(1):63-9.
PMID: 15792862

A non-redundant database of 4536 structural domains, comprising more than 790,000 residues, has been used for the calculation of their solvent accessibility in the native protein environment and then in the isolated domain environment. Nearly 140,000 (18%) residues showed a change in accessible surface area in the above two conditions. General features of this change under these two circumstances have been pointed out. Propensities of these interfacing amino acid residues have been calculated and their variation for different secondary structure types has been analyzed. Actual amount of surface area lost by different secondary structures is higher in the case of helix and strands compared to coil and other conformations. Overall change in surface area in hydrophobic and uncharged residues is higher than that in charged residues. An attempt has been made to know the predictability of interface residues from sequence environments. This analysis and prediction results have significant implications towards determining interacting residues in proteins and for the prediction of protein-protein, protein-ligand, protein-DNA and similar interactions.
Fulltext Copy number variation in exportin-4 (XPO4) gene and its association with histological severity of non-alcoholic fatty liver disease

Zain SM, Mohamed Z, Pirmohamed M, Tan HL, Alshawsh MA, Mahadeva S, et al.

Sci Rep, 2015 Aug 21;5:13306.
PMID: 26293807 DOI: 10.1038/srep13306

A recent genome-wide copy number (CNV) scan identified a 13q12.11 duplication in the exportin-4 (XPO4) gene to be associated with non-alcoholic steatohepatitis (NASH). We sought to confirm the finding in a larger cohort and to assess the serum XPO4 pattern in a broad spectrum of non-alcoholic fatty liver disease (NAFLD) cases. We analysed 249 NAFLD patients and 232 matched controls using TaqMan assay and serum XPO4 was measured. Copy number distribution was as follows: copy number neutral (NAFLD: 53.8%, controls: 68.6%), copy number losses (NAFLD: 13.3%, controls: 12.9%), copy number gains (NAFLD: 32.9%, controls: 18.5%). CNV gain was significantly associated with a greater risk of NAFLD (adjusted OR 2.22, 95% CI 1.42-3.46, P = 0.0004) and NASH (adjusted OR 2.33, 95% CI 1.47-3.68, P = 0.0003). Interestingly, subjects carrying extra copy number showed significantly higher serum ALT and triglyceride (P
Plant cytochrome P450s: nomenclature and involvement in natural product biosynthesis

Rasool S, Mohamed R

Protoplasma, 2016 Sep;253(5):1197-209.
PMID: 26364028 DOI: 10.1007/s00709-015-0884-4

Cytochrome P450s constitute the largest family of enzymatic proteins in plants acting on various endogenous and xenobiotic molecules. They are monooxygenases that insert one oxygen atom into inert hydrophobic molecules to make them more reactive and hydro-soluble. Besides for physiological functions, the extremely versatile cytochrome P450 biocatalysts are highly demanded in the fields of biotechnology, medicine, and phytoremediation. The nature of reactions catalyzed by P450s is irreversible, which makes these enzymes attractions in the evolution of plant metabolic pathways. P450s are prime targets in metabolic engineering approaches for improving plant defense against insects and pathogens and for production of secondary metabolites such as the anti-neoplastic drugs taxol or indole alkaloids. The emerging examples of P450 involvement in natural product synthesis in traditional medicinal plant species are becoming increasingly interesting, as they provide new alternatives to modern medicines. In view of the divergent roles of P450s, we review their classification and nomenclature, functions and evolution, role in biosynthesis of secondary metabolites, and use as tools in pharmacology.
Fulltext Neonatal group B beta-haemolytic streptococcal infection in Kuala Lumpur

Minhaj AA, Jamal F, Mohamed R

Med J Malaysia, 1980 Dec;35(2):117-21.
PMID: 7022149

First six cases of neonatal group B beta-haemolytic streptococcal sepsis in GHKL & Maternity Hospital K.L. were reported and in one third, it was fatal. Five of the cases were 'early - onset' type and one was 'late - onset' type. While maternal infant transmission of the disease is important in the 'early - onset' type, environmental sources of infection are also significant. No gestational age or birthweight is spared from the disease. Finally, there are cases of 'early - onset' GBS sepsis presenting like hyaline membrane disease of the newborn and it is important to find ways to distinguish them which so far has not been satisfactory.
Fulltext The mediating role of procedural justice on the relationship between job analysis and employee performance in Jordan Industrial Estates

Khtatbeh MM, Mahomed ASB, Rahman SBA, Mohamed R

Heliyon, 2020 Oct;6(10):e04973.
PMID: 33083583 DOI: 10.1016/j.heliyon.2020.e04973

Job analysis and employees' perception of justice have a significant influence on employee performance within an organization. This study examined the relationships between job analysis, job performance, and procedural justice among local employees in Jordan Industrial Estates. The literature demonstrated gaps in knowledge regarding the relationships between these variables in developing countries, which are intended to be filled by this study. The study drew from the pay model and equity theory. Data were collected with a survey questionnaire from 690 Jordanian employees working in three industrial estates. The data were analyzed through structural equation modelling (SEM) using SPSS and AMOS software tools. The results indicated to a significant positive relationship between job analysis and job performance, job analysis and procedural justice, and a positive relationship between procedural justice and job performance. Also, it is found that procedural justice mediates the relationship between job analysis and job performance. It is expected that the results of this study would have an impact on employee's performance through the fair implementation of one of the human resources practices, namely, job analysis, and thus organizational performance. Also, it contributes to the body of knowledge and supports the mediating role of procedural justice in decisions taken within the organization.
Fulltext Interleukin-6 gene variants are associated with reduced risk of chronicity in hepatitis B virus infection in a Malaysian population

Riazalhosseini B, Mohamed Z, Apalasamy YD, Shafie NS, Mohamed R

Biomed Rep, 2018 Sep;9(3):213-220.
PMID: 30271596 DOI: 10.3892/br.2018.1126

Interleukin-6 (IL-6) is a cytokine with a critical role in regulating the immune response to infectious disease. Studies have indicated that polymorphisms in the IL-6 gene may be linked to hepatitis B virus (HBV) infection. The purpose of the present study was to examine the association among IL-6 SNPs and haplotypes with HBV infection risk in a Malaysian population. A total of 1,246 Malaysian subjects with and without chronic hepatitis B were recruited for this study. Three IL-6 polymorphisms (rs2069837, rs1800796 and rs2066992) were genotyped using a Sequenom MassARRAY® platform. The results suggested that GC and CC genotypes of rs1800796 as well as GT and TT genotypes of rs2066992 were associated with protection against HBV infection (P<0.001). Furthermore, haplotypes GG and CT exhibited a significant association with protection against HBV (P=0.003 and =0.005, respectively); and haplotypes GG and CT exhibited a significant association with clearance of HBV infection (P=0.035 and =0.037, respectively). The present study indicates that two IL-6 SNPs (rs1800796 and rs2066992) are associated with clearance of chronic HBV or protection against HBV infection at allelic, genotypic and haplotypic levels.
Fulltext Cross-amplification of microsatellite markers across agarwood-producing species of the Aquilarieae tribe (Thymelaeaceae)

Pern YC, Lee SY, Ng WL, Mohamed R

3 Biotech, 2020 Mar;10(3):103.
PMID: 32099744 DOI: 10.1007/s13205-020-2072-2

Tree species in the Aquilarieae tribe of the Thymelaeaceae family produce agarwood, a natural product highly valued for its fragrance, but the species are under threat due to indiscriminate harvesting. For conservation of these species, molecular techniques such as DNA profiling have been used. In this study, we assessed cross-amplification of microsatellite markers, initially developed for three Aquilaria species (A.crassna, A.malaccensis, and A.sinensis), on ten other agarwood-producing species, including members of Aquilaria (A.beccariana, A.hirta, A.microcarpa, A.rostrata, A.rugosa, A.subintegra, and A.yunnanensis) and Gyrinops (G.caudata, G.versteegii, and G.walla), both from the Aquilarieae tribe. Primers for 18 out of the 30 microsatellite markers successfully amplified bands of expected sizes in 1 sample each of at least 10 species. These were further used to genotype 74 individuals representing all the 13 studied species, yielding 13 cross-amplifiable markers, of which only 1 being polymorphic across all species. At each locus, the number of alleles ranged from 7 to 23, indicating a rather high variability. Four markers had relatively high species discrimination power. Our results demonstrated that genetic fingerprinting can be an effective tool in helping to manage agarwood genetic resources by potentially supporting the chain-of-custody of agarwood and its products in the market.
Fulltext The complete chloroplast genome sequence of Chengal (Neobalanocarpus heimii, Dipterocarpaceae), a durable tropical hardwood

Lee SY, Ng WL, Hishamuddin MS, Mohamed R

Mitochondrial DNA B Resour, 2019;4(1):19-20.
PMID: 33365402 DOI: 10.1080/23802359.2018.1535848

Known for its durable timber quality, Neobalanocarpus heimii (King) Ashton is a highly sought after tree species endemic to the Malay Peninsula. Due to its scarcity and high value, the tree is classified under the IUCN Red List categories of Vulnerable. In this study, we assembled the complete chloroplast (cp) genome of N. heimii using data from high-throughput Illumina sequencing. The Chengal cp genome is 151,191 bp in size and includes two inverted repeat regions of 23,721 bp each, which is separated by a large single copy region of 83,801 bp and a small single copy region of 19,948 bp. A total of 130 genes were predicted, including 37 tRNA, 8 rRNA, and 85 protein-coding genes. Phylogenetic analysis placed N. heimii within the order Malvales.
Fulltext Use of simple scoring systems for a public health approach in the management of non-alcoholic fatty liver disease patients

Zain SM, Tan HL, Mohamed Z, Chan WK, Mahadeva S, Basu RC, et al.

JGH Open, 2020 Dec;4(6):1155-1161.
PMID: 33319051 DOI: 10.1002/jgh3.12414

Background and Aim: Advanced fibrosis is the most important predictor of liver-related mortality in non-alcoholic fatty liver disease (NAFLD). The aim of this study was to compare the diagnostic performance of noninvasive scoring systems in identifying advanced fibrosis in a Malaysian NAFLD cohort and propose a simplified strategy for the management of NAFLD in a primary care setting.
Methods: We enrolled and reviewed 122 biopsy-proven NAFLD patients. Advanced fibrosis was defined as fibrosis stages 3-4. Noninvasive assessments included aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, AST-to-platelet ratio index (APRI), AST/ALT ratio, diabetes (BARD) score, fibrosis-4 (FIB-4) score, and NAFLD fibrosis score.
Results: FIB-4 score had the highest area under the receiver operating characteristic curve (AUROC) and negative predictive value (NPV) of 0.86 and 94.3%, respectively, for the diagnosis of advanced fibrosis. FIB-4 score
Fulltext Interaction between Metarhizium anisopliae and Its Host, the Subterranean Termite Coptotermes curvignathus during the Infection Process

Syazwan SA, Lee SY, Sajap AS, Lau WH, Omar D, Mohamed R

Biology (Basel), 2021 Mar 25;10(4).
PMID: 33806225 DOI: 10.3390/biology10040263

Metarhizium anisopliae (Metchnikoff) Sorokin, a pathogenic fungus to insects, infects the subterranean termite, Coptotermes curvignathus Holmgren, a devastating pest of plantation trees in the tropics. Electron microscopy and proteomics were used to investigate the infection and developmental process of M. anisopliae in C. curvignathus. Fungal infection was initiated by germ tube penetration through the host's cuticle as observed at 6 h post-inoculation (PI), after which it elongated into the host's integumental tissue. The colonization process continued as seen from dissemination of blastospores in the hemocoel at 96 h PI. At this time point, the emergent mycelia had mummified the host and forty-eight hours later, new conidia were dispersed on the termites' body surface. Meanwhile, hyphal bodies were observed in abundance in the intercellular space in the host's body. The proteomes of the pathogen and host were isolated separately using inoculated termite samples withdrawn at each PI-time point and analyzed in two-dimensional electrophoresis (2-DE) gels. Proteins expressed in termites showed evidence of being related to cell regulation and the immune response, while those expressed in M. anisopliae, to transportation and fungal virulence. This study provides new information on the interaction between termites and its entomopathogen, with potential utilization for developing future biopesticide to control the termite population.
Fulltext Author Correction: Comparison of eight complete chloroplast genomes of the endangered Aquilaria tree species (Thymelaeaceae) and their phylogenetic relationships

Hishamuddin MS, Lee SY, Ng WL, Ramlee SI, Lamasudin DU, Mohamed R

Sci Rep, 2021 Apr 22;11(1):9160.
PMID: 33888845 DOI: 10.1038/s41598-021-88638-1

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