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Fulltext Fatal airbag-mediated atlanto-occipital dislocation in a child

Hassan R, Mohd Yusof M, Kamarudin NA

Malays J Med Sci, 2010 Oct;17(4):67-70.
PMID: 22135564 MyJurnal

An atlanto-occipital dislocation is a rare airbag-induced injury in trauma patients. We report a case of an atlanto-occipital dislocation in a 6-year-old patient who was an unrestrained passenger in the front seat of a vehicle involved in a low-speed motor vehicle accident. This case illustrates the fatal threat of airbag deployment to the child passenger travelling in the vehicle front seat even in a low-speed collision, and supports the recommendation that children under 12 years of age travelling in vehicles with dual airbag systems should be seated in the back.
Fulltext Retrocaval ureter: the importance of intravenous urography

Hassan R, Aziz AA, Mohamed SK

Malays J Med Sci, 2011 Oct;18(4):84-7.
PMID: 22589677

Retrocaval ureter is a rare cause of hydronephrosis. Its rarity and non-specific presentation pose a challenge to surgeons and radiologists in making the correct diagnosis. Differentiation from other causes of urinary tract obstruction, especially the more common urolithiasis, is important for successful surgical management. Current practice has seen multislice computed tomography (MSCT) rapidly replaces intravenous urography (IVU) in the assessment of patients with hydronephrosis due to suspected urolithiasis, especially ureterolithiasis. However, MSCT, without adequate opacification of the entire ureter, may allow the physician to overlook a retrocaval ureter as the cause of hydronephrosis. High-resolution IVU images can demonstrate the typical appearance that leads to the accurate diagnosis of a retrocaval ureter. We reported a case that illustrates this scenario and highlights the importance of IVU in the assessment of a complex congenital disorder involving the urinary tract.
Fulltext The implementation of teleneurosurgery in the management of referrals to a neurosurgical department in hospital sultanah amninah johor bahru

Hassan R, Siregar JA, A Rahman Mohd NA

Malays J Med Sci, 2014 Mar;21(2):54-62.
PMID: 24876808 MyJurnal

Telemedicine in neurosurgery or teleneurosurgery has been widely used for transmission of clinical data and images throughout the country since its implementation in 2006. The impact is a reduction of patient number that need to be reviewed in the level III hospitals and an increment in the number of patients that are kept in level II hospitals for observation by the primary team. This translates to reduction of unnecessary transfer of patients and subsequently cost benefits for patients and medical providers. The main aim is to determine the amount of reduction in unnecessary transfer by the implementation of teleneurosurgery in the management of referrals to neurosurgical department in Hospital Sultanah Amninah Johor Bahru (HSAJB). Other factors associated with transfer decision are also evaluated.
Molecular Detection of Glycophorins A and B Variant Phenotypes and their Clinical Relevance

Hassan SN, Thirumulu Ponnuraj K, Mohamad S, Hassan R, Wan Ab Rahman WS

Transfus Med Rev, 2019 04;33(2):118-124.
PMID: 30910255 DOI: 10.1016/j.tmrv.2019.02.003

Crossover or conversion between the homologous regions of glycophorin A (GYPA) and glycophorin B (GYPB) gives rise to several different hybrid glycophorin genes encoding a number of different glycophorin variant phenotypes which bear low prevalence antigens in the MNS blood group system. GP.Mur is the main glycophorin variant phenotype which causes hemolytic transfusion reaction (HTR) and hemolytic disease of the fetus and newborn (HDFN) in East and Southeast Asians. The detection of glycophorin variant phenotypes using serological methods is limited to phenotyping reagents that are not commercially available. Moreover, the red blood cells used for antibody identification are usually of the GP.Mur phenotype. The current Polymerase Chain Reaction (PCR)-based methods and loop-mediated isothermal amplification (LAMP) are available alternatives to phenotyping that allow for the specific detection of glycophorin variant phenotypes. This review highlights the molecular detection method for glycophorins A and B variant phenotypes and their clinical relevance.
Prevalence of GP. Mur variant phenotype among Malaysian blood donors

Hassan SN, Mohamad S, Kannan TP, Hassan R, Wei S, Wan Ab Rahman WS

Asian J Transfus Sci, 2023;17(2):169-174.
PMID: 38274953 DOI: 10.4103/ajts.ajts_125_21

BACKGROUND AND OBJECTIVE: A number of glycophorin variant phenotypes or hybrid glycophorin variants of the MNS blood group system bear multiple immunogenic antigens such as Mia, Mur, and MUT. In the East and Southeast Asian populations, glycoprotein (GP.) Mur is the most common glycophorin variant phenotype expressing those three immunogens. The aim of this study was to detect MNS system glycophorin variant phenotypes (GP. Mur, GP. Hop, GP. Bun, GP. HF, and GP. Hut) among Malaysian blood donors.
MATERIALS AND METHODS: In this cross-sectional study, 144 blood donors were selected under stratified random sampling. The deoxyribonucleic acid was extracted from whole blood samples, followed by a polymerase chain reaction assay. Sanger sequencing was used to identify the specific MNS variants and then validated by a serological crossmatch with known anti-Mur and anti-MUT.
RESULTS: GP. Mur was identified among Malaysian blood donors with a prevalence of 6.94%, and no other variants of the MNS system were found.
CONCLUSION: The present study substantiates that GP. Mur is the main variant of the MNS system glycophorin (B-A-B) hybrid in Malaysian blood donors. GP. Mur-negative red blood cells must therefore be considered in the current transfusion policy in order to prevent alloimmunization and immune-mediated transfusion reactions, particularly in transfusion-dependent patients.
Fulltext Occlusion, malocclusion and method of measurements - an overview

Hassan, R., Rahimah, A.K.

Archives of Orofacial Sciences, 2007;2(1):3-9.
MyJurnal

Epidemiological studies of occlusion and malocclusion not only help in orthodontic treatment planning and evaluation of dental health services but also offer a valid research tool for ascertaining the operation of distinct environmental and genetic factors in the aetiology of malocclusion. The objective of this article was to give an overview on occlusion, malocclusion and the various methods on measuring the occlusion. Each index and method of the assessment described was based on the opinion of an individual or a group of individuals. It had been widely agreed that no particular index or method available that are truly inclusive of all occlusal criteria. Therefore, different indices or method had been developed according to different requirements and it may be necessary to use more than one index in order to gather information to suit the objective of the particular study.
Fulltext Exploring Extended White Blood Cell Parameters for the Evaluation of Sepsis among Patients Admitted to Intensive Care Units

Ho SF, Tan SJ, Mazlan MZ, Iberahim S, Lee YX, Hassan R

Diagnostics (Basel), 2023 Jul 21;13(14).
PMID: 37510189 DOI: 10.3390/diagnostics13142445

Sepsis is a major cause of mortality and morbidity in intensive care units. This case-control study aimed to investigate the haematology cell population data and extended inflammatory parameters for sepsis management. The study included three groups of patients: sepsis, non-sepsis, and healthy controls. Patients suspected of having sepsis underwent a Sequential Organ Failure Assessment (SOFA) evaluation and had blood drawn for blood cultures, complete peripheral blood counts (CBC), and measurements of various markers such as C-reactive protein (CRP), procalcitonin (PCT), and interleukin-6 (IL-6). We observed significant changes in numerous CBC parameters and extended inflammation parameters (EIPs), in addition to significant biochemical analysis markers CRP and IL-6 in sepsis cohorts. Multiple logistic regression analyses showed that combining different CBC parameters and EIPs were effective to profile these patients. Two different models have been developed using white blood cell counts and their extended parameters. Our findings indicate that the absolute counts of white blood cells, and the EIPs which reflect their activation states, are important for the prediction and assessment of sepsis, as the body responds to an insult that triggers an immune response. In an emergency situation, having timely updates on patient conditions becomes crucial for guiding the management process. Identifying trends in these specific patient groups will aid early diagnosis, complementing clinical signs and symptoms, especially as CBC is the most commonly ordered test in a diagnostic workup.
Fulltext Naturally occurring hepatitis B virus surface antigen mutant variants in Malaysian blood donors and vaccinees

Hudu SA, Harmal NS, Saeed MI, Alshrari AS, Malik YA, Niazlin MT, et al.

Eur J Clin Microbiol Infect Dis, 2015 Jul;34(7):1349-59.
PMID: 25792010 DOI: 10.1007/s10096-015-2358-1

Hepatitis B virus surface mutants are of enormous importance because they are capable of escaping detection by serology and can infect both vaccinated and unvaccinated populations, thus putting the whole population at risk. This study aimed to detect and characterise hepatitis B-escaped mutants among blood donors and vaccinees. One thousand serum samples were collected for this study from blood donors and vaccinees. Hepatitis B surface antigen, antibodies and core antibodies were tested using a commercial enzyme-linked immunosorbent assay (ELISA) kit. DNA detection was performed via nested polymerase chain reaction (PCR), and the S gene was sequenced and analysed using bioinformatics. Of the 1,000 samples that were screened, 5.5% (55/1,000) were found to be HBsAg-negative and anti-HBc- and HBV DNA-positive. All 55 isolates were found to belong to genotype B. Several mutations were found across all the sequences from synonymous and non-synonymous mutations, with the most nucleotide mutations occurring at position 342, where adenine was replaced by guanine, and cytosine at position 46 was replaced by adenine in 96.4% and 98% of the isolates, respectively. Mutation at position 16 of the amino acid sequence was found to be common to all the Malaysian isolates, with 85.7% of the mutations occurring outside the major hydrophilic region. This study revealed a prevalence of 5.5% for hepatitis B-escaped mutations among blood donors and vaccinated undergraduates, with the most common mutation being found at position 16, where glutamine was substituted with lysine.
Molecular and serological detection of occult hepatitis B virus among healthy hepatitis B surface antigen-negative blood donors in Malaysia

Hudu SA, Harmal NS, Saeed MI, Alshrari AS, Malik YA, Niazlin MT, et al.

Afr Health Sci, 2016 Sep;16(3):677-683.
PMID: 27917199

BACKGROUND: Occult hepatitis B infections are becoming a major global threat, but the available data on its prevalence in various parts of the world are often divergent.
OBJECTIVE: This study aimed to detect occult hepatitis B virus in hepatitis B surface antigen-negative serum using anti-HBc as a marker of previous infection.
PATIENT AND METHODS: A total of 1000 randomly selected hepatitis B surface antigen-negative sera from blood donors were tested for hepatitis B core antibody and hepatitis B surface antibody using an ELISA and nested polymerase chain reaction was done using primers specific to the surface gene (S-gene).
RESULTS: Of the 1000 samples 55 (5.5%) were found to be reactive, of which 87.3% (48/55) were positive for hepatitis B surface antibody, indicating immunity as a result of previous infection however, that does not exclude active infection with escaped mutant HBV. Nested PCR results showed the presence of hepatitis B viral DNA in all the 55 samples that were positive for core protein, which is in agreement with the hepatitis B surface antibody result.
CONCLUSION: This study reveals the 5.5% prevalence of occult hepatitis B among Malaysian blood donors as well as the reliability of using hepatitis B core antibody in screening for occult hepatitis B infection in low endemic, low socioeconomic settings.
Robustness evaluations of pathway activity inference methods on gene expression data

Hui TX, Kasim S, Aziz IA, Fudzee MFM, Haron NS, Sutikno T, et al.

BMC Bioinformatics, 2024 Jan 12;25(1):23.
PMID: 38216898 DOI: 10.1186/s12859-024-05632-w

BACKGROUND: With the exponential growth of high-throughput technologies, multiple pathway analysis methods have been proposed to estimate pathway activities from gene expression profiles. These pathway activity inference methods can be divided into two main categories: non-Topology-Based (non-TB) and Pathway Topology-Based (PTB) methods. Although some review and survey articles discussed the topic from different aspects, there is a lack of systematic assessment and comparisons on the robustness of these approaches.
RESULTS: Thus, this study presents comprehensive robustness evaluations of seven widely used pathway activity inference methods using six cancer datasets based on two assessments. The first assessment seeks to investigate the robustness of pathway activity in pathway activity inference methods, while the second assessment aims to assess the robustness of risk-active pathways and genes predicted by these methods. The mean reproducibility power and total number of identified informative pathways and genes were evaluated. Based on the first assessment, the mean reproducibility power of pathway activity inference methods generally decreased as the number of pathway selections increased. Entropy-based Directed Random Walk (e-DRW) distinctly outperformed other methods in exhibiting the greatest reproducibility power across all cancer datasets. On the other hand, the second assessment shows that no methods provide satisfactory results across datasets.
CONCLUSION: However, PTB methods generally appear to perform better in producing greater reproducibility power and identifying potential cancer markers compared to non-TB methods.
Fulltext The Short-Term Effect of Active Skeletonized Sutural Distractor Appliance on Temporomandibular Joint Morphology of Class III Malocclusion Subjects

Huqh MZU, Hassan R, Rahman RA, Yusof A, Narmada IB, Ahmad WMAW

Eur J Dent, 2021 Jul;15(3):523-532.
PMID: 33622009 DOI: 10.1055/s-0040-1722483

OBJECTIVES: The purpose of this study was to evaluate the short-term effect of active skeletonized sutural distractor (ASSD) appliance on temporomandibular joint morphology of class III malocclusion subjects.
MATERIALS AND METHODS: This was a prospective interventional study. Cone-beam computerized tomography (CBCT) images of 22 patients were taken before and after treatment by using Planmeca Promax 3D CBCT machine version 2.9.2 (Planmeca OY Helsinki, Finland). The condylar width, height, length, roof of glenoid fossa thickness, and all joint spaces were measured. The condylar position was determined based on Pullinger and Hollander formula. The condylar shape was determined as per Kinzinger et al. The condylar volume was calculated by using Mimics software (Materialize, Belgium).
STATISTICAL ANALYSIS: Data analysis was performed by using SPSS software version 24. Wilcoxon paired signed-rank test was used to compare the difference in temporomandibular joint morphology and condylar volume between pre- and post-treatment measurements. Chi-square test was used to compare the condylar position and shape.
RESULTS: The superior (p = 0.000 on the right side, p = 0.005 on the left side) and posterior joint spaces (p = 0.000 on both sides) were decreased after the treatment, respectively. The condyles were rotated upward and backward, thereby increasing the anterior joint spaces (p = 0.000 on both sides) after the treatment. The condylar volume increases after treatment, but no significant differences were observed (p = 0.903 on the right side, p = 0.062 on the left side).
CONCLUSION: The significant changes were observed in joint spaces. The condyles were more anteriorly placed before treatment. Condylar position and shape alter in response to ASSD treatment. The condylar volume did not show any significant change.
Variations in tooth size and arch dimensions in Malay schoolchildren

Hussein KW, Rajion ZA, Hassan R, Noor SN

Aust Orthod J, 2009 Nov;25(2):163-8.
PMID: 20043553

To compare the mesio-distal tooth sizes and dental arch dimensions in Malay boys and girls with Class I, Class II and Class III malocclusions.
Fulltext Coagulation Status Using Clot Wave Analysis in Patients With Prolonged Immobilization

Iberahim S, Muhamat Yusoff R, Mohd Noor NH, Hassan R, Ramli NN, Bahar R, et al.

Cureus, 2024 Jan;16(1):e51483.
PMID: 38304638 DOI: 10.7759/cureus.51483

Background Prolonged immobilization is widely recognized as a risk factor for thromboembolism. In this prospective study, we investigated the changes in clot waveform analysis (CWA) parameters in prolonged immobilized patients following lower limb trauma. CWA is an advanced method for assessing global coagulation that involves continuously monitoring changes in light transmittance, absorbance, or light scattering during routine clotting tests. Additionally, we also aim to determine the CWA parameters between day one and after day three of immobilization. Methods A total of 30 patients with prolonged immobilization were enrolled in this study. The plasma of these patients was collected on the first day of their admission and subsequently obtained again after day three of immobilization. Prothrombin time (PT)-based CWA and activated partial thromboplastin time (aPTT)-based CWA were performed using the ACL TOP 300 CTS (Werfen: Bedford, USA) coagulation analyzer, which utilizes the optical method for clot detection. Plasma samples for 20 normal controls were recruited from a healthy blood donor. The CWA parameters generated during clot formation were analyzed. For the comparison of CWA parameters between patients with prolonged immobilization and healthy controls, the Mann-Whitney test was used. A paired t-test was used for the comparison of clot wave parameters between day one and after day three of immobilization. This study was approved by the Universiti Sains Malaysia Research Ethics Committee. Result The mean values of PT and aPTT in healthy controls were 11.66 seconds and 33.98 seconds, respectively. There was no statistically significant difference between the patients and the healthy controls in the median values of aPTT (P=0.935). However, patients with prolonged immobilization exhibited significantly higher median PT CWA parameter values than controls (P=0.007). These parameters included the delta change (P<0.001), peak time velocity (P=0.008), and height velocity (P<0.001). On the other hand, the delta change (P<0.001) and height velocity (P<0.001) of the aPTT CWA parameters were significantly higher in patients with prolonged immobilization than in controls. In patients with prolonged immobilization, there was no significant difference in PT CWA parameters between day one and after day three of immobilization, while for aPTT CWA, all parameters were higher on day three, except for the endpoint time. Conclusion Patients with prolonged immobilization exhibit increased PT and aPTT CWA parameters compared to normal controls. CWA parameters could aid in identifying patients at risk of developing thrombosis through changes in the clot waveform. However, further study is needed to fully utilize additional information from routine coagulation testing.
Polycythaemia Vera among Sudanese Patients with Special Emphasis on JAK2 Mutations

Ibrahim IK, Hassan R, Ali EW, Omer A

Asian Pac J Cancer Prev, 2019 Jan 25;20(1):41-44.
PMID: 30677867

Background: In recent years, a somatic point mutation in the Janus Kinase 2 (JAK2) gene (1849 G→T, V617F)
has been reported to occur in over 90% of patients with polycythemia vera (PV). Another JAK2 mutation in exon 12
had been described and shown capable of activating erythropoietin signaling pathways. Objective: In this study, we
aimed to determine the frequency of Jak2 mutations (JAK2V617F and JAK2 exon 12) as well as their relationships
with hematological parameters in Sudanese patients with myeloproliferative disorders (MPD). A comparison with
findings of published studies from other geographic regions was included. Materials and Methods: From each of
a total of 83 polycythaemia patients, six milliliters (ml) of venous blood were collected and processed for molecular
analysis and measurement of serum erythropoietin level by enzyme-linked immunoassay (ELISA). The JAK2 V617F
mutation was determined using an allele-specific competitive blocker (ACB) -PCR assay and High Resolution Melting
(HRM) analysis was applied for the JAK2 exon 12 mutation. Results: According to patients’ history and the results
for EPO levels, nine (10.7 %) out of 83 patients were found to have secondary polycythaemia and 74 (89.3%) PV. The
overall frequency of the 2 JAK2 mutations was 94.6% in our Sudanese PV patients, JAK2V617F being found in 91%
and JAK2 exon 12 mutations in 8.1%.Conclusion: In summary JAK2 V617F and JAK2 exon 12 mutations are very
common in Sudanese PC cases.
Vitamin D status in patients with systemic lupus erythematosus (SLE): A systematic review and meta-analysis

Islam MA, Khandker SS, Alam SS, Kotyla P, Hassan R

Autoimmun Rev, 2019 Sep 11.
PMID: 31520805 DOI: 10.1016/j.autrev.2019.102392

BACKGROUND: Systemic lupus erythematosus (SLE) is a systemic autoimmune disease where chronic inflammation and tissue or organ damage is observed. Due to various suspected causes, inadequate levels of vitamin D (a steroid hormone with immunomodulatory effects) has been reported in patients with SLE, however, contradictory.
AIMS: The aim of this systematic review and meta-analysis was to evaluate the serum levels of vitamin D in patients with SLE in compared to healthy controls.
METHODS: PubMed, SCOPUS, ScienceDirect and Google Scholar electronic databases were searched systematically without restricting the languages and year (up to March 2, 2019) and studies were selected based on the inclusion criteria. Mean difference (MD) along with 95% confidence intervals (CI) were used and the analyses were carried out by using a random-effects model. Different subgroup and sensitivity analyses were conducted. Study quality was assessed by the modified Newcastle-Ottawa Scale (NOS) and publication bias was evaluated by a contour-enhanced funnel plot, Begg's and Egger's tests.
RESULTS: We included 34 case-control studies (2265 SLE patients and 1846 healthy controls) based on the inclusion criteria. Serum levels of vitamin D was detected significantly lower in the SLE patients than that in the healthy controls (MD: -10.44, 95% CI: -13.85 to -7.03; p 
Fulltext Prevalence and characteristics of fever in adult and paediatric patients with coronavirus disease 2019 (COVID-19): A systematic review and meta-analysis of 17515 patients

Islam MA, Kundu S, Alam SS, Hossan T, Kamal MA, Hassan R

PLoS One, 2021;16(4):e0249788.
PMID: 33822812 DOI: 10.1371/journal.pone.0249788

BACKGROUND: Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 started to spread globally since December 2019 from Wuhan, China. Fever has been observed as one of the most common clinical manifestations, although the prevalence and characteristics of fever in adult and paediatric COVID-19 patients is inconclusive. We aimed to conduct a systematic review and meta-analysis to estimate the overall pooled prevalence of fever and chills in addition to fever characteristics (low, medium, and high temperature) in both adult and paediatric COVID-19 patients.
METHODS: The protocol of this systematic review and meta-analysis was registered with PROSPERO (CRD42020176327). PubMed, Scopus, ScienceDirect and Google Scholar databases were searched between 1st December 2019 and 3rd April 2020 without language restrictions. Both adult (≥18 years) and paediatric (<18 years) COVID-19 patients were considered eligible. We used random-effects model for the meta-analysis to obtain the pooled prevalence and risk ratio (RR) with 95% confidence intervals (CIs). Quality assessment of included studies was performed using the Joanna Briggs Institute critical appraisal tools. Heterogeneity was assessed using the I² statistic and Cochran's Q test. Robustness of the pooled estimates was checked by different subgroups and sensitivity analyses.
RESULTS: We identified 2055 studies, of which 197 studies (n = 24266) were included in the systematic review and 167 studies with 17142 adults and 373 paediatrics were included in the meta-analysis. Overall, the pooled prevalence of fever in adult and paediatric COVID-19 patients were 79.43% [95% CI: 77.05-81.80, I2 = 95%] and 45.86% [95% CI: 35.24-56.48, I2 = 78%], respectively. Besides, 14.45% [95% CI: 10.59-18.32, I2 = 88%] of the adult COVID-19 patients were accompanied with chills. In adult COVID-19 patients, the prevalence of medium-grade fever (44.33%) was higher compared to low- (38.16%) and high-grade fever (14.71%). In addition, the risk of both low (RR: 2.34, 95% CI: 1.69-3.22, p<0.00001, I2 = 84%) and medium grade fever (RR: 2.79, 95% CI: 2.21-3.51, p<0.00001, I2 = 75%) were significantly higher compared to high-grade fever, however, there was no significant difference between low- and medium-grade fever (RR: 1.17, 95% CI: 0.94-1.44, p = 0.16, I2 = 87%). 88.8% of the included studies were of high-quality. The sensitivity analyses indicated that our findings of fever prevalence for both adult and paediatric patients are reliable and robust.
CONCLUSIONS: The prevalence of fever in adult COVID-19 patients was high, however, 54.14% of paediatric COVID-19 patients did not exhibit fever as an initial clinical feature. Prevalence and risk of low and medium-grade fevers were higher compared to high-grade fever.
Fulltext Immunomodulatory Effects of Diet and Nutrients in Systemic Lupus Erythematosus (SLE): A Systematic Review

Islam MA, Khandker SS, Kotyla PJ, Hassan R

Front Immunol, 2020;11:1477.
PMID: 32793202 DOI: 10.3389/fimmu.2020.01477

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by multiple organ involvement, including the skin, joints, kidneys, lungs, central nervous system and the haematopoietic system, with a large number of complications. Despite years of study, the etiology of SLE remains unclear; thus, safe and specifically targeted therapies are lacking. In the last 20 years, researchers have explored the potential of nutritional factors on SLE and have suggested complementary treatment options through diet. This study systematically reviews and evaluates the clinical and preclinical scientific evidence of diet and dietary supplementation that either alleviate or exacerbate the symptoms of SLE. For this review, a systematic literature search was conducted using PubMed, Scopus and Google Scholar databases only for articles written in the English language. Based on the currently published literature, it was observed that a low-calorie and low-protein diet with high contents of fiber, polyunsaturated fatty acids, vitamins, minerals and polyphenols contain sufficient potential macronutrients and micronutrients to regulate the activity of the overall disease by modulating the inflammation and immune functions of SLE.
Fulltext Prevalence of antiphospholipid antibodies in Behçet's disease: A systematic review and meta-analysis

Islam MA, Alam SS, Kundu S, Prodhan AHMSU, Khandker SS, Reshetnyak T, et al.

PLoS One, 2020;15(1):e0227836.
PMID: 31929597 DOI: 10.1371/journal.pone.0227836

Behçet's disease (BD) is a multifactorial systemic inflammatory disease of unknown aetiology characterised by several clinical manifestations including vascular involvements (i.e., both arterial and venous thrombosis). Antiphospholipid antibodies (aPLs)-including anticardiolipin (aCL), anti-β2-glycoprotein I (β2-GPI) antibodies and lupus anticoagulant (LA) are detected in systemic autoimmune diseases which contribute to thrombosis. The aim of this systematic review and meta-analysis was to evaluate the prevalence of aPLs in patients with BD as compared to controls. A protocol was registered in PROSPERO (Registration No. CRD42018088125) and a systematic literature search was conducted through PubMed, Web of Science, Embase, Scopus and ScienceDirect databases. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects model. Quality assessment was carried out by using the modified 9-star Newcastle-Ottawa Scale (NOS). Publication bias was evaluated via visualisation of contour- enhanced and trim and fill funnel plots along with Begg's and Egger's tests. We included ten case-control studies (a total of 999 participants from 380 BD patients and 619 controls) based on the inclusion criteria. The prevalence of aCL (OR: 12.10, 95% CI: 5.15-28.41, p<0.00001) and anti-β2-GPI antibodies (OR: 23.57, 95% CI: 1.31-423.63, p = 0.03) were statistically significant, however, the prevalence of LA was not significant (OR: 13.77, 95% CI: 0.65-293.59, p = 0.09). The results remained statistically significant from different sensitivity analyses which represented the robustness of this meta-analysis. According to the NOS, 50.0% of the studies were considered as of high methodological quality (low risk of bias). No significant publication bias was detected from contour-enhanced and trim and fill funnel plots or Begg's and Egger's tests. This meta-analysis established that there is a significantly high prevalence of aPLs (i.e., aCL and anti-β2-GPI antibodies) in patients with BD when compared to controls.
Gene Therapy Approaches in an Autoimmune Demyelinating Disease: Multiple Sclerosis

Islam MA, Kundu S, Hassan R

Curr Gene Ther, 2020;19(6):376-385.
PMID: 32141417 DOI: 10.2174/1566523220666200306092556

Multiple Sclerosis (MS) is the most common autoimmune demyelinating disease of the Central Nervous System (CNS). It is a multifactorial disease which develops in an immune-mediated way under the influences of both genetic and environmental factors. Demyelination is observed in the brain and spinal cord leading to neuro-axonal damage in patients with MS. Due to the infiltration of different immune cells such as T-cells, B-cells, monocytes and macrophages, focal lesions are observed in MS. Currently available medications treating MS are mainly based on two strategies; i) to ease specific symptoms or ii) to reduce disease progression. However, these medications tend to induce different adverse effects with limited therapeutic efficacy due to the protective function of the blood-brain barrier. Therefore, researchers have been working for the last four decades to discover better solutions by introducing gene therapy approaches in treating MS generally by following three strategies, i) prevention of specific symptoms, ii) halt or reverse disease progression and iii) heal CNS damage by promoting remyelination and axonal repair. In last two decades, there have been some remarkable successes of gene therapy approaches on the experimental mice model of MS - experimental autoimmune encephalomyelitis (EAE) which suggests that it is not far that the gene therapy approaches would start in human subjects ensuring the highest levels of safety and efficacy. In this review, we summarised the gene therapy approaches attempted in different animal models towards treating MS.
Fulltext The Role of Epigenetics in the Development and Progression of Multiple Myeloma

Ismail NH, Mussa A, Zakaria NA, Al-Khreisat MJ, Zahidin MA, Ramli NN, et al.

Biomedicines, 2022 Oct 31;10(11).
PMID: 36359286 DOI: 10.3390/biomedicines10112767

Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.

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