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Fulltext Anti-amoebic properties of carbonyl thiourea derivatives

Ibrahim MA, Yusof MS, Amin NM

Molecules, 2014 Apr 22;19(4):5191-204.
PMID: 24759076 DOI: 10.3390/molecules19045191

Thiourea derivatives display a broad spectrum of applications in chemistry, various industries, medicines and various other fields. Recently, different thiourea derivatives have been synthesized and explored for their anti-microbial properties. In this study, four carbonyl thiourea derivatives were synthesized and characterized, and then further tested for their anti-amoebic properties on two potential pathogenic species of Acanthamoeba, namely A. castellanii (CCAP 1501/2A) and A. polyphaga (CCAP 1501/3A). The results indicate that these newly-synthesized thiourea derivatives are active against both Acanthamoeba species. The IC50 values obtained were in the range of 2.39-8.77 µg·mL⁻¹ (9.47-30.46 µM) for A. castellanii and 3.74-9.30 µg·mL⁻¹ (14.84-31.91 µM) for A. polyphaga. Observations on the amoeba morphology indicated that the compounds caused the reduction of the amoeba size, shortening of their acanthopodia structures, and gave no distinct vacuolar and nuclear structures in the amoeba cells. Meanwhile, fluorescence microscopic observation using acridine orange and propidium iodide (AOPI) staining revealed that the synthesized compounds induced compromised-membrane in the amoeba cells. The results of this study proved that these new carbonyl thiourea derivatives, especially compounds M1 and M2 provide potent cytotoxic properties toward pathogenic Acanthamoeba to suggest that they can be developed as new anti-amoebic agents for the treatment of Acanthamoeba keratitis.
Fulltext A novel and stable way for energy harvesting from Bi2Te3Se alloy based semitransparent photo-thermoelectric module

Fatima N, Karimov KS, Qasuria TA, Ibrahim MA

J Alloys Compd, 2020 Dec 30;849:156702.
PMID: 32834521 DOI: 10.1016/j.jallcom.2020.156702

In this research, due to the present pandemic of COVID-19, we are proposing a stable and fixed semitransparent photo-thermoelectric cell (PTEC) module for green energy harvesting. This module is based on the alloy of Bismuth Telluride Selenide (Bi2Te3Se), designed in a press tablet form and characterized under solar energy. Here, both aspects of solar energy i.e., light and heat are utilized for both energy production and water heating. The semitransparent PTEC converts heat energy directly to electrical energy due to the gradient of temperature between two electrodes (top and bottom) of thermoelectric cells. The PTEC is 25% transparent, which can be varied according to the necessity of the utilizer. The X-ray diffraction of material and electric characterization of module i.e., open-circuited voltage (VOC) and Seebeck coefficient were performed. The experimental observations disclose that in the proposed PTEC module with an increment in the average temperature (TAvg) from 34 to 60 °C, results in the rise of VOC ∼ 2.4 times. However, by modifying the size of heat-absorbing top electrode and by increasing the temperature gradient through the addition of water coolant under the bottom electrode, an uplift in the champion device results in as increment of VOC ∼5.5 times and Seebeck coefficient obtained was -250 μV/0C, respectively. Results show that not only the selection of material but also the external modifications in the device highly effective the power efficiency of the devices. The proposed modules can generate electric power from light and utilize the penetrating sunlight inside the room and for the heating of the water which also acts as a coolant. These semitransparent thermoelectric cells can be built-in within windows and roofs of buildings and can potentially contribute to green energy harvesting, in situations where movement is restricted locally or globally.
Fulltext Comparing the Effectiveness of Different Dentinal Desensitizing Agents: In Vitro Study

Farook MS, Mahmoud O, Ibrahim MA, Berkathullah M

Biomed Res Int, 2021;2021:6652250.
PMID: 33628801 DOI: 10.1155/2021/6652250

Objectives: To evaluate the in vitro effectiveness of desensitizing agents in reducing dentine permeability.
Methods: The efficacy of desensitizing agents in reducing dentine permeability by occluding dentine tubules was evaluated using a fluid filtration device that conducts at 100 cmH2O (1.4 psi) pressure, and SEM/EDX analyses were evaluated and compared. Forty-two dentine discs (n = 42) of 1 ± 0.2 mm width were obtained from caries-free permanent human molars. Thirty dentine discs (n = 30) were randomly divided into 3 groups (n = 10): Group 1: 2.7% wt. monopotassium-monohydrogen oxalate (Mp-Mh oxalate), Group 2: RMGI XT VAR, and Group 3: LIQ SiO2. Dentine permeability was measured following treatment application after 10 minutes, storage in artificial saliva after 10 minutes and 7 days, and citric acid challenge for 3 minutes. Data were analysed with a repeated measures ANOVA test. Dentine discs (n = 12) were used for SEM/EDX analyses to acquire data on morphological changes on dentine surface and its mineral content after different stages of treatment.
Results: Desensitizing agents' application on the demineralized dentine discs exhibited significant reduction of permeability compared to its maximum acid permeability values. Mp-Mh oxalate showed a significant reduction in dentine permeability (p < 0.05) when compared to RMGI XT VAR and LIQ SiO2. On SEM/EDX analysis, all the agents formed mineral precipitates that occluded the dentine tubules.
Conclusions: 2.7% wt. monopotassium-monohydrogen oxalate was significantly effective in reducing dentine permeability compared to RMGI XT VAR and LIQ SiO2.
Fulltext Management of the dead during COVID-19 outbreak in Malaysia

Khoo LS, Hasmi AH, Ibrahim MA, Mahmood MS

Forensic Sci Med Pathol, 2020 09;16(3):463-470.
PMID: 32519316 DOI: 10.1007/s12024-020-00269-6

The emergence of a novel human coronavirus, SARS-CoV-2, causing severe respiratory tract infections in humans, is affecting all countries of the world and has become a global health concern. Since the virus was first identified in December 2019, the number of deaths have been propagating exponentially, causing countries across the world, including Malaysia, to increase emergency measures to combat the virus. Due to the fact that the COVID-19 pandemic does not discriminate its victims, it is of paramount importance to construct a plan for management of the dead for all suspected or confirmed COVID-19 cases, including the unidentified deceased, as an essential portion of the humanitarian forensic action approach. This document provides an overview on ways to maximize the local collective capacity from various government agencies to manage the dead based on the prevailing regulations and legislation in the country, in preparation for possible large scale deaths from this pandemic. The National Institute of Forensic Medicine Malaysia has improvised procedures and guidelines for management of the dead within the existing regulations in order to achieve a balance between medicolegal requirements and the safety of personnel managing the bodies of the deceased with suspected or confirmed COVID-19 infection; at the site of death, during transport, during postmortem procedures, storage and preparation before and during burial or cremation as well as environmental cleaning and disinfection, involving various agencies in the country. A form of temporary controlled burial is as an option to allow the reinvestigation of a decedent to help formally identify victims of the pandemic such as undocumented migrants or refugees who were previously not identified. Due to the different legal requirements and mortality rates between countries, there is no one-size-fits-all approach to the management of the dead. Whenever possible, every opportunity and assistance must be given to families to mourn their loved ones, even in times of crisis or an outbreak, in order to sustain an appropriate level of dignity and respect.
Management of unidentified and unclaimed bodies: a comparison of model from four countries in the Asia Pacific Region

Khoo LS, Lai PS, Siew SF, Ibrahim MA

Forensic Sci Med Pathol, 2023 Jul 31.
PMID: 37523136 DOI: 10.1007/s12024-023-00683-6

Managing mass fatality incidents or disasters involving multiple deaths are not uncommon among forensic practitioners. In fact, management of unidentified or unknown bodies is also a vital component of the day-to-day mortuary work practice. The unidentified and subsequently unclaimed bodies have always been a "silent mass disaster," a problem that needs to be tackled within the forensic community and raises the global issue of ethics, law, and human rights. Unidentified bodies' in Malaysia make up an average of 4.02% of all death cases where a total postmortem examination was performed which is comparable with other developing countries within 4-10% which can go up to 25%. Moreover, unstandardized procedures in all mortuaries in different states and districts in Malaysia have worsened the scenario even with guidelines in place. This study aims to address the issues surrounding unidentified and unclaimed bodies including body disposal from a social and legal perspective using case study methodology by comparing four different countries in the Asia Pacific Region through document analysis and interview methods. One of the major findings is evident in 3 out of the 4 models, whereby there is a considerable gap in consolidating the missing person report and information to match with the unidentified bodies received in forensic institutions in an attempt to enhance the identification process which ultimately intends as a closure for the family members. It is also timely to think out of the box beyond dental records and DNA profiling to improve the identification rate for skeletonized remains through means of anthropology biometrics comparison. With the limited literature published surrounding this domain, it is hoped that the suggestions and recommendations to standardize the management of unidentified and unclaimed bodies can benefit many forensic institutions and public mortuaries in this region.
Fulltext An Overview of the Strategies for Tin Selenide Advancement in Thermoelectric Application

Md Aspan R, Fatima N, Mohamed R, Syafiq U, Ibrahim MA

Micromachines (Basel), 2021 Nov 27;12(12).
PMID: 34945312 DOI: 10.3390/mi12121463

Chalcogenide, tin selenide-based thermoelectric (TE) materials are Earth-abundant, non-toxic, and are proven to be highly stable intrinsically with ultralow thermal conductivity. This work presented an updated review regarding the extraordinary performance of tin selenide in TE applications, focusing on the crystal structures and their commonly used fabrication methods. Besides, various optimization strategies were recorded to improve the performance of tin selenide as a mid-temperature TE material. The analyses and reviews over the methodologies showed a noticeable improvement in the electrical conductivity and Seebeck coefficient, with a noticeable decrement in the thermal conductivity, thereby enhancing the tin selenide figure of merit value. The applications of SnSe in the TE fields such as microgenerators, and flexible and wearable devices are also discussed. In the future, research in low-dimensional TE materials focusing on nanostructures and nanocomposites can be conducted with the advancements in material science technology as well as microtechnology and nanotechnology.
Fulltext A dynamic forensic medicine approach: Management of the dead during COVID-19 outbreak in Malaysia

Khoo LS, Hasmi AH, Mahmood MS, Ibrahim MA

Forensic Sci Int Rep, 2021 Nov;4:100245.
PMID: 38620858 DOI: 10.1016/j.fsir.2021.100245

It has been a difficult year ahead since the announcement of COVID-19 as a pandemic by the Director General of the World Health Organization (WHO). Many countries including Malaysia have struggled to take urgent and aggressive measures to advise, detect, screen, test, isolate and treat their citizens in order to fight against the virus. All countries must strike a balance between protecting health, minimizing economic and social disruption and at the same time, preserving human rights which includes managing the dead with dignity and respect. The National Institute of Forensic Medicine (IPFN) Malaysia has been proactively engaging the various agencies involved in a concerted effort to ensure smooth flow in the management of the dead for all COVID-19 and non-COVID-19 cases since the beginning of the outbreak in February 2020. This is in accordance with all existing guidelines and regulations vis-a-vis infection prevention and control in the country. However, new situations that arise during the pandemic are always challenging and dynamic. The COVID-19 crisis has uncovered a plethora of issues surrounding the margin of the Forensic Medicine fraternity. Therefore, this article highlights various emerging issues encountered by the IPFN and how they are resolved through good leadership to guide and direct operations and activities during the exponential rise of COVID-19 infection in Malaysia. In the provision of the management of the dead, it is of utmost importance to note that the humanitarian aspect needs to be emphasized even in times of an outbreak to give closure to the family and the opportunity to mourn their loved ones.
Fulltext A novel and stable ultraviolet and infrared intensity sensor in impedance/capacitance modes fabricated from degraded CH3NH3PbI3-xClx perovskite materials

Qasuria TA, Fatima N, Karimov KS, Ibrahim MA

J Mater Res Technol, 2020;9(6):12795-12803.
PMID: 38620721 DOI: 10.1016/j.jmrt.2020.09.025

The present situation of COVID-19 diverted our focus towards utilizing the degraded solar cells for sensor application, this will help in global energy harvesting. So, here is our successful effort to reuse already degraded solar cells as ultraviolet (UV) and infrared (IR) sensor. The spin-coated perovskite (CH3NH3PbI3-XClX) has been already tested for visible light spectrum, as an extension to that now it is utilized as UV and IR intensity sensors to cover the whole spectrum. The employed CH3NH3PbI3-XClX material was used after its efficiency loss has been reached to a saturation point in photovoltaic devices. Each deposited layer was investigated from UV to the IR absorption spectrum for deepening study through UV-vis spectroscopy. In the sandwiched architecture possessing FTO/PEDOT: PSS/Perovskite/PC61BM/CdS/Au symmetry, the perovskite film has been employed as an absorbent layer, however, other layers participation also plays a key role. The resultant device yielded very good sensing performance because of the enhanced excitons generation which is attributed to the precise selection of the interfacial materials, e.g. CdS and PC61BM as an ETM and PEDOT: PSS as HTM. The impedance and capacitance of the devices within 0.01-200 kHz under varied UV and IR illumination intensities were investigated. Measurements showed that as the intensity of the light increased i.e., UV (0-200 W/m2) and IR (0-5800 W/m2), impedance decreased while capacitance increased. The current results are attributed to the increase in the concentration of charges i.e., electron-hole pairs generation depending on the built-in capacitance and frequency of the charges.
Fulltext MH17: the Malaysian experience

Khoo LS, Hasmi AH, Abdul Ghani Aziz SA, Ibrahim MA, Mahmood MS

Malays J Pathol, 2016 Apr;38(1):1-10.
PMID: 27126658 MyJurnal

A disaster is a natural or man-made (or technological) hazard resulting in an event of substantial extent causing significant physical damage or destruction, loss of life, or drastic change to the environment. It is a phenomenon that can cause damage to life and property and destroy the economic, social and cultural life of the people; and overwhelms the capacity of the community to cope with the event. The recent tragic aviation accidents in 2014 involving Malaysia Airlines flights MH370 and MH17 shocked the world in an unprecedented manner. This paper focuses on the Malaysian experience in the MH17 mission in Ukraine as well as the first ever international Disaster Victim Identification (DVI) operation for the Malaysian DVI team. The DVI operations in Hilversum, the Netherlands were well described in stages. The Netherlands' Landelijk Team Forensische Opsporing as the lead DVI team in Hilversum operated systematically, ensuring the success of the whole mission. This paper discusses the lessons learned by the Malaysian team on proper DVI structure, inter- and intra-agency cooperation, facilities planning and set up, logistics and health and safety aspects, as well as effective communication and collaboration with other international delegates. Several issues and challenges faced by the Malaysian team were also documented. In addition, the authors shared views, opinions and recommendations for a more comprehensive DVI operation in the future.
Fulltext Embryonic toxicity of 3,4-dichloroaniline (3,4-DCA) on Javanese medaka (Oryzias javanicus Bleeker, 1854)

Ibrahim MA, Zulkifli SZ, Azmai MNA, Mohamat-Yusuff F, Ismail A

Toxicol Rep, 2020;7:1039-1045.
PMID: 32913717 DOI: 10.1016/j.toxrep.2020.08.011

Early-life exposure to toxic chemicals causes irreversible morphological and physiological abnormalities that may last for a lifetime. The present study aimed to determine the toxicity effect of 3,4-Dichloroaniline (3,4-DCA) on Javanese medaka (Oryzias javanicus) embryos. Healthy embryos were exposed to various 3,4-DCA concentrations for acute toxicity (5, 10, 25, 50, and 100 mg.L-1) and sublethal toxicity (0.10, 0.50, 1.25, 2.50, and 5.00 mg.L-1) for 96 h and 20 days respectively. Acute toxicity test revealed that the median lethal concentration (96h-LC50) was 32.87 mg.L-1 (95 % CI = 27.90-38.74, R2 = 0.95). Sublethal exposure revealed that 1.25 mg.L-1 at 3 days post-exposure (3 dpe) has a significant lower heartrate (120 ± 12.3 beats/min., p
Fulltext Reproductive Toxicity of 3,4-dichloroaniline (3,4-DCA) on Javanese Medaka (Oryziasjavanicus, Bleeker 1854)

Ibrahim MA, Zulkifli SZ, Azmai MNA, Mohamat-Yusuff F, Ismail A

Animals (Basel), 2021 Mar 12;11(3).
PMID: 33809309 DOI: 10.3390/ani11030798

Compound 3,4-dichloroaniline (3,4-DCA) is a metabolite of several urea herbicides and intermediate chemical of several industrial products. Moreover, 3,4-DCA has been frequently detected in aquatic ecosystems around the world. This aniline is more toxic than the parent chemicals, and it affects non-target organisms. This study evaluated a 21-day reproductive response of an emerging aquatic vertebrate model, Javanese medaka (Oryzias javanicus), exposed to 3,4-DCA. Fecundity and gonads histopathology were observed. The spawning rate and fertilisation reduced significantly in the highest exposed-group (250 µg/L). Gonadosomatic index (GSI) was significantly low in females exposed to 250 µg/L. No substantial structural alteration of male gonads. However, oocyte development and ovarian cell structure were disrupted in 250 µg/L exposed females. The gonadal developmental was not affected in the males; however, a significant reduction in the developmental of female gonads was observed at 250 µg/L. These results show that 3,4-DCA interfere with the reproduction of Javanese medaka through fecundity and alteration of gonadal tissues.
Radiological results of Shelf acetabuloplasty in adolescent hip dysplasia with aspherical femoral head: how to get an ideal placement of the Shelf graft

Ramdhan Ibrahim MA, Kamegaya M, Morita M, Saisu T, Kakizaki J, Oikawa Y

J Pediatr Orthop B, 2020 May;29(3):261-267.
PMID: 31688334 DOI: 10.1097/BPB.0000000000000681

Shelf acetabuloplasty continues to be effective in the prevention or delay of osteoarthritis in adolescent dysplastic hips. We aimed to evaluate the efficacy and to determine the correct level of the bone graft objectively. We retrospectively analyzed 16 hips underwent Shelf acetabuloplasty originated by Spitzy. The mean age at surgery was 15.3 years old with the mean caput index at 39.7%. The average follow-up was 11 years. The radiological evaluation was based on acetabular-head index (AHI) at preoperative and latest radiographs, acetabular-Shelf distance (ASD) and Shelf-head ratio at immediate postoperative and latest radiographs. The cutoff value for the ideal ASD was determined by receiver operating characteristic (ROC) and the Pearson correlation test used in statistical analysis to assess the relationship between ASD and Shelf graft resorption. Clinical evaluation was performed using Harris Hip Score (HHS) at the latest follow-up. The AHI was improved in all cases, from mean 56.9 to 91.0% (P
The clandestine multiple graves in Malaysia: The first mass identification operation of human skeletal remains

Mohd Noor MS, Khoo LS, Zamaliana Alias WZ, Hasmi AH, Ibrahim MA, Mahmood MS

Forensic Sci Int, 2017 Sep;278:410.e1-410.e9.
PMID: 28698062 DOI: 10.1016/j.forsciint.2017.05.014

The first ever mass identification operation of skeletal remains conducted for the clandestine graves in Malaysia consisted of 165 individuals unearthed from 28 human trafficking transit camps located in Wang Kelian, along the Thai-Malaysia border. A DVI response was triggered in which expert teams comprising of pathologists, anthropologists, odontologists, radiologists and DNA experts were gathered at the identified operation centre. The Department of Forensic Medicine, Hospital Sultanah Bahiyah, Alor Star, Kedah, located approximately 75km away from Wang Kelian, was temporarily converted into a victim identification centre (VIC) as it is the nearest available forensic facility to the mass grave site. The mortuary operation was conducted over a period of 3 months from June to September 2015, and was divided into two phases; phase 1 involving the postmortem examination of the remains of 116 suspected individuals and for phase 2 the remains of 49 suspected individuals. The fact that the graves were of unknown individuals afforded the mass identification operation a sufficient duration of 2 weeks as preparatory phase enabling procedurals and daily victim identification workflow to be established, and the setting up of a temporary body storage for the designated mortuary. The temporary body storage has proven to be a significant factor in enabling the successful conclusion of the VIC operation to the final phase of temporary controlled burials. Recognition from two international observers, Mr. Andréas Patiño Umaña, from the International Committee of Red Cross (ICRC) and Prof. Noel Woodford from Victoria Institute of Forensic Medicine (VIFM) had proven the mortuary operation was in compliance to the international quality and standards. The overall victim identification and mortuary operation identified a number of significant challenges, in particular the management of commingled human remains as well as the compilation of postmortem data in the absence of antemortem data for future reconciliation. CF Index in this DVI operation is 9%, indicating the primary identifications in this operation were effective. Limitations and further improvements of the mass identification operation will be discussed. This paper details the planning, preparations and management of the mass identification operation on the exhumed human remains which was also a forensic humanitarian service for the dead with dignity and respect.
Light transmission and internal scattering in pulsed laser-etched partially-transparent silicon wafers

Rohaizar MH, Sepeai S, Surhada N, Ludin NA, Ibrahim MA, Sopian K, et al.

Heliyon, 2019 Nov;5(11):e02790.
PMID: 31768436 DOI: 10.1016/j.heliyon.2019.e02790

Continuing trend in silicon wafer thickness directed at cost reduction approaches basic boundaries created by: (a) mismatch between Al paste and Si wafer thermal expansion and (b) incomplete optical absorption. With its symmetrical front and back electrical contacts, the bifacial solar cell setup reduces stress due to mismatch thermal expansion, decreases metal use and increases high temperature efficiency. Efficiency improvement is accomplished in bifacial solar cells by capturing light from the back surface. Partially transparent wafers provide an option to improve near-infrared radiation absorption within Si wafer. To fully absorb optical radiation, three-dimensional texture of these kinds of wafers is essential. Pulsed laser interactions, thermal oxidation, and wet chemical etching are included in this research. A feature of its energy and pattern setup is the interaction of pulsed laser with Si, running at 1.064 μm wavelength and micro-second length. Two experimental settings were explored: (a) post-laser chemical etching with potassium hydro-oxide etching with thermal oxide as etching mask and (b) post-laser heat Si surface oxidation. Due to fast melting and recrystallization, laser pulsed processing inherently produces its own texture. Some of these spherically-shaped, randomly focused characteristics improve inner scattering and boost near-infrared absorption within the wafer. These characteristics are separated during chemical etching with the thermally-grown oxide layer as an etch mask. Comparison of optical absorption in both surfaces shows almost a rise in the magnitude of absorption in non-etched surfaces. Detailed optical (optical microscope and IR absorption), morphological (field emission scanning electron microscope) and heat imaging (far IR camera) analyses were performed to comprehend physical processes that contribute to near-IR absorption improvement. Such kinds of partially-transparent, three-dimensional textured Si wafers are anticipated to discover applications for bifacial solar cells as substrates.
The first case of C4-Blast related death in Malaysia: A multidisciplinary approach illustrated with emphasis on conjoint anthropologic and radiologic expertise in forensic identification of skeletal remains

Wong YL, Khoo LS, Ibrahim MA, Mohamad Noor MH, Mahmood MS

J Forensic Leg Med, 2021 Oct;83:102253.
PMID: 34543893 DOI: 10.1016/j.jflm.2021.102253

BACKGROUND: Blast related deaths are often shrouded by diagnostic and medicolegal complexities requiring multidisciplinary expertise in order to gauge accurate identification of the victims and document scientific investigations comprehensively. In the advent of more sophisticated technology, anthropologic methods can now be applied into post mortem imaging interpretation. The traditional imaging roles of characterizing osseous fragmentation, detecting and localizing foreign bodies can be expanded to simulate and support physical anthropologic examination to assist in documentation for court proceedings.
CASE PRESENTATION: An assemblage of unidentified, incomplete, highly fragmented skeletal remains were found scattered on a bare area of land in a forest. There was evidence of an explosion given the pattern of scattered evidentiary material of explosive and ballistic nature. Laboratory analysis of white powder found within the explosive material confirmed the presence of high impact C4-explosive trace containing cyclotrimethylene trinitramin [Royal Demolition Explosive (RDX)] & pentaerythritol tetranitrate (PETN). It took meticulous multidisciplinary efforts to confirm the identity of the victim that was marred by the severe fragmentation and skeletalization of the remains. The initial radiologic interpretation focused more on identification of foreign bodies and supporting documentation of fragmentation. With the current availability of post computed tomography (PMCT) in our center, we reexamined the value and potential of PMXR and PMCT as an adjunctive tool for biological profiling.
CONCLUSION: This was the first case of C4-blast related death reported in Malaysia. The multidisciplinary approach in efforts to identify the victim may serve as a guide in managing, coordinating and maximizing the expertise of different forensic specialists, with emphasis on anthropologic and radiologic collaboration.
Fulltext Use of Post-Mortem Computed Tomography During the COVID-19 Pandemic: The Malaysian Experience

Chainchel Singh MK, Mohd Noor MH, Ibrahim MA, Siew SF, Lai PS

Malays J Med Sci, 2022 Oct;29(5):83-92.
PMID: 36474535 DOI: 10.21315/mjms2022.29.5.9

BACKGROUND: COVID-19 was declared a pandemic by the World Health Organization (WHO). COVID-19 is highly contagious, making it a threat to healthcare workers, including those working in mortuaries. Therefore, it is important to determine if the cause of death (COD) could be identified using limited autopsy, diagnostic tests and post-mortem imaging modalities instead of full autopsy. This study aims to examine the effectiveness of post-mortem imaging, specifically post-mortem computed tomography (PMCT) at determining the COD during a pandemic.
METHODS: This cross-sectional study included 172 subjects with suspected or unknown COVID-19 status brought in dead to the institute's mortuary during the pandemic in Malaysia. PMCT images reported by forensic radiologists and their agreement with conventional autopsy findings by forensic pathologists regarding COD were analysed to look at the effectiveness of PMCT in determining COD during a pandemic.
RESULTS: Analysis showed that 78.7% (133) of cases reported by forensic radiologists concurred with the COD certified by forensic pathologists. Of these cases, 85 (63.9%) had undergone only external examination and real-time reverse transcriptase polymerase chain reaction (rRT-PCR) COVID-19 testing, meaning that imaging was the sole method used to determine the COD besides history from available medical records and the investigating police officer.
CONCLUSION: PMCT can be used as a complement to medicolegal autopsies in pandemic contexts, as it provides significant information on the possible COD without jeopardising the safety of mortuary health care workers.
Relationship between ABCB1 polymorphisms and serum methadone concentration in patients undergoing methadone maintenance therapy (MMT)

Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.

Am J Drug Alcohol Abuse, 2016 09;42(5):587-596.
PMID: 27284701 DOI: 10.3109/00952990.2016.1172078

BACKGROUND: Methadone is a substrate of the permeability glycoprotein (P-gp) efflux transporter, which is encoded by the ABCB1 (MDR1) gene. Large interindividual variability in serum methadone levels for therapeutic response has been reported. Genetic variations in ABCB1 gene may be responsible for the variability in observed methadone concentrations.
OBJECTIVE: This study investigated the associations of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval in opioid-dependent patients on methadone maintenance therapy (MMT).
METHODS: One hundred and forty-eight male opioid-dependent patients receiving MMT were recruited. Genomic deoxyribonucleic acid (DNA) was extracted from whole blood and genotyped for ABCB1 polymorphisms [i.e. 1236C>T (dbSNP rs1128503), 2677G>T/A (dbSNP rs2032582), and 3435C>T (dbSNP rs1045642)] using the allelic discrimination real-time polymerase chain reaction (PCR). Blood samples were collected at 0, 0.5, 1, 2, 4, 8, 12, and 24 hours after the dose. Serum methadone concentrations were measured using the Methadone ELISA Kit.
RESULTS: Our results revealed an association of CGC/TTT diplotype (1236C>T, 2677G>T/A, and 3435C>T) with dose-adjusted serum methadone concentration over the 24-hour dosing interval. Patients with CGC/TTT diplotype had 32.9% higher dose-adjusted serum methadone concentration over the 24-hour dosing interval when compared with those without the diplotype [mean (SD) = 8.12 (0.84) and 6.11 (0.41) ng ml-1mg-1, respectively; p = 0.033].
CONCLUSION: There was an association between the CGC/TTT diplotype of ABCB1 polymorphisms and serum methadone concentration over the 24-hour dosing interval among patients on MMT. Genotyping of ABCB1 among opioid-dependent patients on MMT may help individualize and optimize methadone substitution treatment.
Study site: Psychiatric Clinic, Hospital Universiti Sains Malaysia (HUSM), and other MMT clinics in Kelantan,
Malaysia
Fulltext The Opposing Roles of IVS2+691 CC Genotype and AC/AG Diplotype of 118A>G and IVS2+691G>C of OPRM1 Polymorphisms in Cold Pain Tolerance Among Opioid-Dependent Malay Males on Methadone Therapy

Zahari Z, Lee CS, Ibrahim MA, Musa N, Yasin MA, Lee YY, et al.

Pain Ther, 2015 Dec;4(2):179-96.
PMID: 26581429 DOI: 10.1007/s40122-015-0041-y

We recently reported that a majority of opioid-dependent Malay males on methadone therapy are cold pain sensitive. It is postulated that common OPRM1 polymorphisms may be responsible. This study investigated the association between 118A>G (dbSNP rs1799971) and IVS2+691G>C (dbSNP rs2075572) variants on cold pain responses among opioid-dependent Malay males on methadone maintenance therapy.
Fulltext Comparison of Pain Tolerance between Opioid Dependent Patients on Methadone Maintenance Therapy (MMT) and Opioid Naive Individuals

Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.

J Pharm Pharm Sci, 2016;19(1):127-36.
PMID: 27096697 DOI: 10.18433/J3NS49

PURPOSE: This study compared pain sensitivity among opioid dependent patients on methadone maintenance therapy (MMT) and opioid naive subjects.
METHODS: The three hundred participants comprised 152 opioid naive subjects and 148 opioid dependent patients. Opioid naive subjects had not taken any opioids including morphine and methadone to their best knowledge and were presumed so after two consecutive negative urine screenings for drugs. All opioid dependent patients were stabilized in treatment, defined as having been enrolled in the program for more than one month with no change of methadone dosage over the past one month. Excluded from the study were individuals with chronic or ongoing acute pain and individuals with a history of analgesics ingestion within 3 d before the cold pressor test (CPT). Pain tolerance to CPT was evaluated at 0 h, and at 2, 4, 8, 12, and 24 h post-methadone dose.
RESULTS: Patients exhibited a significantly shorter mean pain tolerance time of 34.17 s (95% CI 24.86, 43.49) versus 61.36 (52.23, 70.48) [p < 0.001] compared with opioid naive subjects. Time-dependent mean pain tolerance was also significantly different when naive subjects were compared to patients (p = 0.016).
CONCLUSIONS: This study revealed hyperalgesia amongst patients on MMT, as manifested by their quicker hand withdrawal. The complaints of pain in this population should not be underestimated and the pain should be evaluated seriously and managed aggressively.
Relationship between CYP2B6*6 and cold pressor pain sensitivity in opioid dependent patients on methadone maintenance therapy (MMT)

Zahari Z, Lee CS, Ibrahim MA, Musa N, Mohd Yasin MA, Lee YY, et al.

Drug Alcohol Depend, 2016 08 01;165:143-50.
PMID: 27289271 DOI: 10.1016/j.drugalcdep.2016.05.028

BACKGROUND: CYP2B6 polymorphisms contribute to inter-individual variations in pharmacokinetics of methadone. Increased pain sensitivity is frequently reported by opioid dependent patients on methadone maintenance therapy (MMT). It is possible, therefore, that genetic polymorphisms in CYP2B6, which affects the metabolism of methadone, influence pain sensitivity among patients on MMT. This study investigated CYP2B6 polymorphisms and pain sensitivity in this group.
METHODS: The cold pressor pain responses of 148 opioid dependent patients receiving MMT were evaluated using the cold pressor test (CPT). DNA was extracted from whole blood and subjected to polymerase chain reaction (PCR)-genotyping.
RESULTS: Of the 148 subjects, 77 (52.0%) were carriers of CYP2B6*6 allele. CYP2B6*6 allele carriers had shorter cold pain threshold and pain tolerance times than non-carriers of CYP2B6*6 allele (21.05s vs 33.69s, p=0.036 and 27.15s vs 44.51s, p=0.020, respectively). Pain intensity scores of the CYP2B6*6 allele carriers was 67.55, whereas that of the CYP2B6*6 allele non-carriers was 64.86 (p=0.352).
CONCLUSION: Our study indicates that the CYP2B6*6 allele is associated with a lower pain threshold and lower pain tolerance among males with opioid dependence on MMT. The CYP2B6*6 allele may provide a mechanistic explanation for clinical observations of heightened pain sensitivity among opioid dependent patients receiving MMT.

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