Displaying publications 1 - 20 of 173 in total

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  1. Zifruddin AN, Mohamad-Khalid KA, Suhaimi SA, Mohamed-Hussein ZA, Hassan M
    Biosci Biotechnol Biochem, 2021 Jun 24;85(7):1628-1638.
    PMID: 33890631 DOI: 10.1093/bbb/zbab072
    Juvenile hormone III (JH III) plays an important role in insect reproduction, development, and behavior. The second branch of JH III production includes oxidation of farnesol to farnesal by farnesol dehydrogenase. This study reported the identification and characterization of Plutella xylostella farnesol dehydrogenase (PxFoLDH). Our results showed that PxFoLDH belongs to the short-chain dehydrogenase/reductase superfamily, consisting of a single domain with a structurally conserved Rossman fold, an NAD(P) (H)-binding region and a structurally diverse C-terminal region. The purified enzyme displayed maximum activity at 55$\ $°C with pH 9.5 and was stable in the temperature below 70$\ ^\circ $C. PxFoLDH was determined to be a monomer with a relative molecular weight of 27 kDa and highly specific for trans, trans-farnesol, and NADP+. Among analog inhibitors tested, farnesyl acetate was the most effective inhibitor with the lowest Ki value of 0.02 µm. Our findings showed this purified enzyme may represent as NADP+-farnesol dehydrogenase.
  2. Zifruddin AN, Mohamad Yusoff MA, Abd Ghani NS, Nor Muhammad NA, Lam KW, Hassan M
    Comput Biol Chem, 2023 Apr;103:107811.
    PMID: 36645937 DOI: 10.1016/j.compbiolchem.2023.107811
    Metisa plana (Lepidoptera: Psychidae) bagworm is a leaf-eater caterpillar ubiquitously found as a damaging pest in oil palm plantations, specifically in Malaysia. Various strategies have been implemented, including the usage of chemical insecticides. However, the main challenges include the development of insecticide resistance and its detrimental effects on the environment and non-target organisms. Therefore, a biorational insecticide is introduced by targeting the juvenile hormone (JH) biosynthetic pathway, which is mainly present in the insect and vital for the insect's growth, diapause, metamorphosis, and adult reproduction. This study aimed to investigate the potential inhibitor for the rate-limiting enzyme involved in the JH pathway known as farnesol dehydrogenase. A 255 amino acids sequence encoded for the putative M. plana farnesol dehydrogenase (MpFolDH) open reading frame had been identified and isolated. The three-dimensional structure of MpFolDH was predicted to have seven β- sheets with α-helices at both sides, showing typical characteristics for classical short-chain dehydrogenase and associated with oxidoreductase activity. Then, the ensemble-based virtual screening was conducted based on the ZINC20 database, in which 43 768 compounds that fulfilled pesticide-likeness criteria were screened by site-specific molecular docking. After a short molecular dynamics simulation (5 ns) was conducted towards 102 compounds, only the top 10 compounds based on their most favourable binding energy were selected for a more extended simulation (100 ns). Based on the protein-ligand stability, protein compactness, residues rigidity, binding interaction, binding energy throughout the 100 ns simulation, and physicochemical analysis, ZINC000408743205 was selected as a potential inhibitor for this enzyme. Amino acids decomposition analysis indicates Ile18, Ala95, Val198 and Val202 were the critical contributor residues for MpFolDH-inhibitors(s) complex.
  3. Zhang M, Wang Z, Obazee O, Jia J, Childs EJ, Hoskins J, et al.
    Oncotarget, 2016 Oct 11;7(41):66328-66343.
    PMID: 27579533 DOI: 10.18632/oncotarget.11041
    Genome-wide association studies (GWAS) have identified common pancreatic cancer susceptibility variants at 13 chromosomal loci in individuals of European descent. To identify new susceptibility variants, we performed imputation based on 1000 Genomes (1000G) Project data and association analysis using 5,107 case and 8,845 control subjects from 27 cohort and case-control studies that participated in the PanScan I-III GWAS. This analysis, in combination with a two-staged replication in an additional 6,076 case and 7,555 control subjects from the PANcreatic Disease ReseArch (PANDoRA) and Pancreatic Cancer Case-Control (PanC4) Consortia uncovered 3 new pancreatic cancer risk signals marked by single nucleotide polymorphisms (SNPs) rs2816938 at chromosome 1q32.1 (per allele odds ratio (OR) = 1.20, P = 4.88x10 -15), rs10094872 at 8q24.21 (OR = 1.15, P = 3.22x10 -9) and rs35226131 at 5p15.33 (OR = 0.71, P = 1.70x10 -8). These SNPs represent independent risk variants at previously identified pancreatic cancer risk loci on chr1q32.1 ( NR5A2), chr8q24.21 ( MYC) and chr5p15.33 ( CLPTM1L- TERT) as per analyses conditioned on previously reported susceptibility variants. We assessed expression of candidate genes at the three risk loci in histologically normal ( n = 10) and tumor ( n = 8) derived pancreatic tissue samples and observed a marked reduction of NR5A2 expression (chr1q32.1) in the tumors (fold change -7.6, P = 5.7x10 -8). This finding was validated in a second set of paired ( n = 20) histologically normal and tumor derived pancreatic tissue samples (average fold change for three NR5A2 isoforms -31.3 to -95.7, P = 7.5x10 -4-2.0x10 -3). Our study has identified new susceptibility variants independently conferring pancreatic cancer risk that merit functional follow-up to identify target genes and explain the underlying biology.
  4. Zeb A, Abbasi MA, Siddiqui SZ, Hassan M, Javed Q, Rafiq M, et al.
    Chem Biodivers, 2024 Feb 16.
    PMID: 38363553 DOI: 10.1002/cbdv.202400133
    In the aimed research study, a new series of N-(aryl)-3-[(4-phenyl-1-piperazinyl)methyl]benzamides was synthesized, which was envisaged as tyrosinase inhibitor. The structures of these newly designed molecules were verified by IR, 1H-NMR, 13C-NMR, EI-MS and CHN analysis data. These molecules were screened against tyrosinase and their inhibitory activity explored that these 3-substituted-benzamides exhibit good to excellent potential, comparative to the standard. The Kinetics mechanism was investigated through Lineweaver-Burk plots which depicted that molecules inhibited this enzyme in a competitive mode. Moreover, molecular docking was also performed to determine the binding interaction of all synthesized molecules (ligands) with the active site of tyrosinase enzyme and the results showed that most of the ligands exhibited efficient binding energy values. Therefore, it is anticipated that these molecules might serve as auspicious therapeutic scaffolds for treatment of the tyrosinase associated skin disorders.
  5. Zakaria ZA, Hassan MH, Nurul Aqmar MN, Abd Ghani M, Mohd Zaid SN, Sulaiman MR, et al.
    Methods Find Exp Clin Pharmacol, 2007 Oct;29(8):515-20.
    PMID: 18040526
    This study was carried out in mice to determine the nonopioid receptor signaling pathway(s) that might modulate the antinociceptive activity of the aqueous and chloroform extracts of Muntingia calabura (M. calabura) leaves, using the hot-plate test. The leaves of M. calabura were sequentially soaked [1:2 (w/v); 72 h] in distilled water (dH(2)O) and chloroform. The 50% concentration extracts were selected for this study based on the plant's previously established antinociceptive profiles. The mice (n = 7) were pretreated (s.c.) for 10 min with the selected nonopioid receptor antagonists, followed by the (s.c.) administration of the respective extract. The latency of discomfort was recorded at the interval time of 0.5, 1, 2, 3, 4 and 5 h after the extract administration. The 5 mg/kg atropine, 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol, 1 mg/kg haloperidol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the aqueous extract-induced antinociceptive activity. The 10 mg/kg phenoxybenzamine, 10 mg/kg yohimbine, 10 mg/kg pindolol and 10 mg/kg bicuculline caused significant (p < 0.05) reduction in the chloroform extract-induced antinociceptive activity. In conclusion, the central antinociceptive activity of M. calabura leaves appears to be involved in the modulation of various nonopioid receptor signaling pathways. Its aqueous extract antinociceptive activity is mediated via modulation of the muscarinic, alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic, dopaminergic and GABAergic receptors, while its chloroform extract activity is mediated via modulation of the alpha(1)-adrenergic, alpha(2)-adrenergic, beta-adrenergic and GABAergic receptors.
  6. Zainudin MH, Mustapha NA, Maeda T, Ramli N, Sakai K, Hassan M
    Waste Manag, 2020 Apr 01;106:240-249.
    PMID: 32240940 DOI: 10.1016/j.wasman.2020.03.029
    Biochar has proven to be a feasible additive for mitigating nitrogen loss during the composting process. This study aims to evaluate the influence of biochar addition on bacterial community and physicochemical properties changes, including ammonium (NH4+), nitrite (NO2-) and nitrate (NO3-) contents during the composting of poultry manure. The composting was carried out by adding 20% (w/w) of biochar into the mixture of poultry manure and rice straw with a ratio of 2:1, and the same treatment without biochar was prepared as a control. The finished product of control compost recorded the high contents of NO2- and NO3- (366 mg/kg and 600 mg/kg) with reduced the total NH4+ content to 10 mg/kg. Meanwhile, biochar compost recorded a higher amount of total NH4+ content (110 mg/kg) with low NO2- and NO3- (161 mg/kg and 137 mg/kg) content in the final composting material. The principal component analysis showed that the dynamics of dominant genera related to Halomonas, Pusillimonas, and Pseudofulvimonas, all of which were known as nitrifying and denitrifying bacteria, was significantly correlated with the dynamic of NO2- and NO3- content throughout the composting process. The genera related to Pusillimonas, and Pseudofulvimonas appeared as the dominant communities as the NO2- and NO3- increased. In contrast, as the NO2- and NO3- concentration decreased, the Halomonas genus were notably enriched in biochar compost. This study revealed the bacterial community shifts corresponded with the change of physicochemical properties, which provides essential information for a better understanding of monitoring and improving the composting process.
  7. Yusuf J, Sapuan SM, Ansari MA, Siddiqui VU, Jamal T, Ilyas RA, et al.
    Int J Biol Macromol, 2024 Jan;255:128121.
    PMID: 37984579 DOI: 10.1016/j.ijbiomac.2023.128121
    Material is an inseparable entity for humans to serve different purposes. However, synthetic polymers represent a major category of anthropogenic pollutants with detrimental impacts on natural ecosystems. This escalating environmental issue is characterized by the accumulation of non-biodegradable plastic materials, which pose serious threats to the health of our planet's ecosystem. Cellulose is becoming a focal point for many researchers due to its high availability. It has been used to serve various purposes. Recent scientific advancements have unveiled innovative prospects for the utilization of nanocellulose within the area of advanced science. This comprehensive review investigates deeply into the field of nanocellulose, explaining the methodologies employed in separating nanocellulose from cellulose. It also explains upon two intricately examined applications that emphasize the pivotal role of nanocellulose in nanocomposites. The initial instance pertains to the automotive sector, encompassing cutting-edge applications in electric vehicle (EV) batteries, while the second exemplifies the use of nanocellulose in the field of biomedical applications like otorhinolaryngology, ophthalmology, and wound dressing. This review aims to provide comprehensive information starting from the definitions, identifying the sources of the nanocellulose and its extraction, and ending with the recent applications in the emerging field such as energy storage and biomedical applications.
  8. Yusoff N, Abd Ghani I, Othman NW, Aizat WM, Hassan M
    Insects, 2021 Jan 27;12(2).
    PMID: 33513706 DOI: 10.3390/insects12020109
    The diamondback moth, Plutella xylostella (L.) (Lepidoptera: Plutellidae), is the most important pest of cruciferous vegetables worldwide. In this study, we evaluated the properties of selected farnesyl derivative compounds against P. xylostella. The toxicity and sublethal concentration (LC50) of farnesyl acetate, farnesyl acetone, farnesyl bromide, farnesyl chloride, and hexahydrofarnesyl acetone were investigated for 96 h. The leaf-dip bioassays showed that farnesyl acetate had a high level of toxicity against P. xylostella compared to other tested farnesyl derivatives. The LC50 value was 56.41 mg/L on the second-instar larvae of P. xylostella. Then, the sublethal effects of farnesyl acetate on biological parameters of P. xylostella were assessed. Compared to the control group, the sublethal concentration of farnesyl acetate decreased pupation and emergence rates, pupal weight, fecundity, egg hatching rate, female ratio, and oviposition period. Furthermore, the developmental time of P. xylostella was extended after being exposed to farnesyl acetate. Moreover, the application of farnesyl acetate on P. xylostella induced morphogenetic abnormalities in larval-pupal intermediates, adults that emerged with twisted wings, or complete adults that could not emerge from the cocoon. These results suggested that farnesyl acetate was highly effective against P. xylostella. The sublethal concentration of farnesyl acetate could reduce the population of P. xylostella by increasing abnormal pupal and adults, and by delaying its development period.
  9. Yusof N, Haraguchi A, Hassan MA, Othman MR, Wakisaka M, Shirai Y
    Waste Manag, 2009 Oct;29(10):2666-80.
    PMID: 19564103 DOI: 10.1016/j.wasman.2009.05.022
    Since landfilling is the common method of waste disposal in Malaysia, river water is greatly exposed to the risk of contamination from leachate unless proper leachate management is carried out. In this study, leachates from three different types of landfills, namely active uncontrolled, active controlled and closed controlled, were characterized, and their relationships with river water chemistry were examined monthly for a year. The influence of leachate on river water chemistry from each type of landfill depended on many factors, including the presence of a leachate control mechanism, leachate characteristics, precipitation, surface runoff and the applied treatment. The impact of leachate from an active uncontrolled landfill was the highest, as the organic content, NH(4)(+)-N, Cd and Mn levels appeared high in the river. At the same time, influences of leachate were also observed from both types of controlled landfills in the form of inorganic nitrogen (NH(4)(+)-N, NO(3)(-)-N and NO(2)(-)-N) and heavy metals (Fe, Cr, Ni and Mn). Improper treatment practice led to high levels of some contaminants in the stream near the closed controlled landfill. Meanwhile, the active controlled landfill, which was located near the coastline, was exposed to the risk of contamination resulting from the pyrite oxidation of the surrounding area.
  10. Yusof MI, Hassan MN, Abdullah MS
    Malays Orthop J, 2018 Mar;12(1):21-25.
    PMID: 29725508 MyJurnal DOI: 10.5704/MOJ.1803.004
    Introduction: The vertical diameter of the foramen is dependent upon the vertical diameter of the corresponding intervertebral disc. A decrease in disc vertical diameter has direct anatomic consequences to the foraminal diameter and area available for the nerve root passing through it. This study is to establish the relationship amongst the intervertebral disc vertical diameter, lateral foramen diameters and nerve root compression in the lumbar vertebra. Materials and Methods: Measurements of the study parameters were performed using sagittal MRI images. The parameters studied were: intervertebral disc vertical diameter (DVD), foraminal vertical diameter (FVD), foraminal transverse diameter (FTD) and nerve root diameter (NRD) of both sides. The relationship between the measured parameters were then analyzed. Results: A total of 62 MRI images were available for this study. Statistical analysis showed moderate to strong correlation between DVD and FVD at all the lumbar levels except at left L23 and L5S1 and right L3L4 and L4L5. Correlation between DVD and FTD were not significant at all lumbar levels. Regression analysis showed that a decrease of 1mm of DVD was associated with 1.3, 1.7, 3.3, 3.3 and 1.3mm reduction of FVD at L1L2, L2L3, L3L4, L4L5 and L5S1 respectively. Conclusion: Reduction of DVD was associated with reduction of FVD. However, FVD was relatively wide for the nerve root even with complete loss of DVD. FTD was much narrower than the FVD making it more likely to cause nerve root compression at the exit foramina. These anatomical details should be given consideration in treating patients with lateral canal stenosis.
  11. Yunus N, Rashid AA, Azmi LL, Abu-Hassan MI
    J Oral Rehabil, 2005 Jan;32(1):65-71.
    PMID: 15634304
    Nylon denture base material could be a useful alternative to poly (methyl methacrylate) (PMMA) in special circumstances such as patient allergy to the monomer. The aim of this study was to evaluate the flexural properties of a nylon denture base material (Lucitone FRS), a conventional compression-moulded heat-polymerized (Meliodent), a compression-moulded microwave-polymerized (Acron MC) and an injection-moulded microwave-polymerized (Lucitone 199) PMMA polymers. The effect of aldehyde-free, oxygen releasing disinfectant solution (Perform) on these properties was also investigated. The flexural modulus and the flexural strength were assessed with a three-point bending test. Specimens were stored in water at a temperature of 37 degrees C for 30 days. For each material, half of the prepared specimens were randomly selected and immersed in the disinfectant 24 h prior to testing. Results were compared statistically at a confidence level of 95%. The result showed that in both the control and disinfected groups, the flexural modulus of nylon was significantly lower than the three PMMA polymers. The flexural strength of nylon was significantly lower than those of Meliodent and Acron MC but was comparable with Lucitone 199. A 24-h immersion in the disinfecting solution increased the rigidity of nylon denture base material.
  12. Yacob S, Ali Hassan M, Shirai Y, Wakisaka M, Subash S
    Sci Total Environ, 2006 Jul 31;366(1):187-96.
    PMID: 16125215
    The world currently obtains its energy from the fossil fuels such as oil, natural gas and coal. However, the international crisis in the Middle East, rapid depletion of fossil fuel reserves as well as climate change have driven the world towards renewable energy sources which are abundant, untapped and environmentally friendly. Malaysia has abundant biomass resources generated from the agricultural industry particularly the large commodity, palm oil. This paper will focus on palm oil mill effluent (POME) as the source of renewable energy from the generation of methane and establish the current methane emission from the anaerobic treatment facility. The emission was measured from two anaerobic ponds in Felda Serting Palm Oil Mill for 52 weeks. The results showed that the methane content was between 35.0% and 70.0% and biogas flow rate ranged between 0.5 and 2.4 L/min/m(2). Total methane emission per anaerobic pond was 1043.1 kg/day. The total methane emission calculated from the two equations derived from relationships between methane emission and total carbon removal and POME discharged were comparable with field measurement. This study also revealed that anaerobic pond system is more efficient than open digesting tank system for POME treatment. Two main factors affecting the methane emission were mill activities and oil palm seasonal cropping.
  13. Wang YG, Hassan MD, Shariff M, Zamri SM, Chen X
    Dis Aquat Organ, 1999 Dec 22;39(1):1-11.
    PMID: 11407399
    Since 1994, white spot syndrome virus (WSSV) has been detected in cultured shrimp Penaeus monodon in Peninsular Malaysia. The gross signs, target organs and histo-cytopathology for the viral infection were studied and it was found to infect most organs and tissues including oocytes, but not hepatopancreatocytes and epithelial cells of the midgut, which were regarded as refractory tissues. Based on a time-sequence of ultrastructural cytopathology, 4 cytopathic profiles and 6 phases of viral morphogenesis were described. The virions were elliptical to short rods with trilamilar envelopes that measured 305 +/- 30 x 127 +/- 11 nm. Viral nucleosomes were often present singly in infected nuclei and were associated with the early stages of viral replication. The structure of WSSV pathognomonic white, cuticular lesions was examined at the microscopic and ultrastructural levels and the mechanism of their formation appeared to be related to the disruption of exudate transfer from epithelial cells to the cuticle via cuticular pore canals.
  14. Wang YG, Lee KL, Najiah M, Shariff M, Hassan MD
    Dis Aquat Organ, 2000 May 25;41(1):9-18.
    PMID: 10907134
    This paper describes a new bacterial white spot syndrome (BWSS) in cultured tiger shrimp Penaeus monodon. The affected shrimp showed white spots similar to those caused by white spot syndrome virus (WSSV), but the shrimp remained active and grew normally without significant mortalities. The study revealed no evidence of WSSV infection using electron microscopy, histopathology and nested polymerase chain reaction. Electron microscopy indicated bacteria associated with white spot formation, and with degeneration and discoloration of the cuticle as a result of erosion of the epicuticle and underlying cuticular layers. Grossly the white spots in BWSS and WSS look similar but showed different profiles under wet mount microscopy. The bacterial white spots were lichen-like, having perforated centers unlike the melanized dots in WSSV-induced white spots. Bacteriological examination showed that the dominant isolate in the lesions was Bacillus subtilis. The occurrence of BWSS may be associated with the regular use of probiotics containing B. subtilis in shrimp ponds. The externally induced white spot lesions were localized at the integumental tissues, i.e., cuticle and epidermis, and connective tissues. Damage to the deeper tissues was limited. The BWS lesions are non-fatal in the absence of other complications and are usually shed through molting.
  15. Wan Masliza WD, Bajuri MY, Hassan MR, Naim NM, Shuhaila A, Das S
    Clin Ter, 2017 10 19;168(5):e283-e289.
    PMID: 29044348 DOI: 10.7417/T.2017.2021
    BACKGROUND: The placenta is a most interesting but unfortunately often ignored and misunderstood organ. Placental abnormalities, therefore, can be an "early warning system" for fetal problems. A complete prenatal sonographic examination of the placenta is an essential component as its abnormalities can have a direct effect on fetal or maternal outcomes, obstetrical management and future fertility.

    OBJECTIVE: To determine whether any association exists between the finding of an increased thickness of placenta, abnormal placenta shape, placental calcification, placental lake and abnormal cord insertion site at 20-22 and 30-32 weeks gestation with an increased risk of uteroplacental complications or a poor pregnancy outcome.

    METHODOLOGY: A real-time ultrasound was used at the time of detail scan (at 20-22 weeks gestation) and at 30-32 weeks gestation to look for placenta appearance, fetal growth and anomaly. The main outcome measures were risk of hypertension disease in pregnancy, fetal growth restriction and poor fetal outcomes such as low Apgar score and low cord pH.

    RESULT: The majority of the participants were Malay (77.9%). Abnormal placenta found at both gestations were placental lakes and thickness, and only one case had marginal cord insertion. Approximately 6% of the cases were confirmed placenta previa. No abnormal shape or abnormal calcification found at both gestations. About 10% patient developed hypertensive disease in pregnancy, 15% of the fetus was found to have growth restriction and another 16% have low umbilical cord pH. Majority of them delivered at term (90%) and via vaginal delivery (81%). There was no significance between presence of abnormal placental lake and thickness at both gestations with the maternal and fetal outcome.

    CONCLUSION: Presence of abnormal placental thickness and lakes at 30-32 weeks scan associated with maternal hypertensive disease, fetal growth restriction and low umbilical cord pH, however these were not statistically significant.

  16. Wan Ab Rahman WS, Abdullah WZ, Husin A, Nik Mohd Hassan NFF, Hassan MN, Zulkafli Z
    Malays J Pathol, 2019 Aug;41(2):185-189.
    PMID: 31427554
    INTRODUCTION: Acquired haemophilia A (AHA) is a rare acquired bleeding disorder caused by polyclonal immunoglobulin G autoantibodies against clotting factor VIII (FVIII). The incidence was reported to be rare occurring in 0.2- 4 cases/million/year. Patients may present with different clinical manifestations to various specialties. Early recognition of the disease contributes to favourable clinical outcome.

    CASE SERIES: Here, we reported five cases of this disorder with different clinical presentations from two tertiary hospitals in Kelantan state, Malaysia within a two year-period. Most of them were elderly, except for one who presented at the age of 36 years old. No direct or secondary cause was identified except for one patient who had developed from pregnancy-related at 3 weeks postpartum. These patients presented with spontaneous bleeding typically into skin, muscles, and mucous membranes but also at rare site in the epidural space. All patients denied previous history of bleeding or family history of bleeding disorder. FVIII activities were recorded between <1% to 19%, while the inhibitor titre levels were between 3.9 BU to 340 BU. The treatment approaches especially at presentation were complicated by unfamiliarity of managing this rare condition but all these patients received appropriate medical attention.

    DISCUSSION: Prompt diagnosis and management in the right hand are critical. Awareness of this disorder by medical personnel at all levels in the community and in various specialties is important.

  17. Wan Ab Rahman WS, Abdullah WZ, Hassan MN, Ahmed S, Zulkafli Z, Wan Ahmed WA, et al.
    Malays J Pathol, 2021 Dec;43(3):449-452.
    PMID: 34958066
    Plasma protein-C is a natural anticoagulant that inactivates factors Va and VIIIa. Familial protein C deficiency is inherited as an autosomal dominant disorder. The homozygous or compound heterozygous type may present early as purpura fulminant, while the heterozygous type can present as thromboembolism later in life. Presented in this report is a case of a 21-year-old female patient with protein-C deficiency, confirmed by thrombophilia investigations. She experienced recurrent deep vein thrombosis and cerebral sinus thrombosis due to thrombotic occlusion. She had a family history of deep vein thrombosis. Hence, high-risk cases should be seriously considered for long term anticoagulation therapy. The utility versus futility of thrombophilia testing in a particular situation is discussed to address and ensure safe practice among patients with thromboembolism.
  18. Wan Ab Rahman WS, Abdullah WZ, Hassan MN, Hussin A, Zulkafli Z, Haron J
    Malays J Pathol, 2017 Aug;39(2):197-200.
    PMID: 28866705 MyJurnal
    Patients with low antithrombin III (AT III) has increased risk for arteriovenous thromboembolic (TE) disease. We report a 28-year-old Malay lady who presented with spontaneous right calf pain and swelling of one week duration. She was on oral contraceptive pills and had a history of travelling for a long distance prior to the presentation. Her brother who was diagnosed with AT III deficiency had arterial thrombosis at a young age. She was diagnosed as having right popliteal vein thrombosis by ultrasound and treated with subcutaneous fondaparinux. While on treatment, she developed massive bilateral pulmonary embolism (PE). Thrombophilia study showed reduced AT III activity (38μl/dl) and normal results for protein C, protein S, activated protein C resistance and lupus anticoagulant assays. This patient has heterozygous AT III deficiency added with significant acquired factors responsible for the TE events. Those with AT III deficiency may have resistance to heparin therapy and require higher doses of heparin.
  19. Waiho K, Fazhan H, Zhang Y, Afiqah-Aleng N, Moh JHZ, Ikhwanuddin M, et al.
    Genomics, 2020 09;112(5):2959-2969.
    PMID: 32437851 DOI: 10.1016/j.ygeno.2020.05.007
    Infection by the rhizocephalan parasite Sacculina beauforti can have detrimental effects on mud crab Scylla olivacea. However, the molecular changes that occur during rhizocephalan infection are poorly understood. Due to the disruption in the reproductive system after infection, the gonadal transcriptomic profiles of non-infected and infected Scylla olivacea were compared. A total of 686 and 843 unigenes were differentially expressed between non-infected and infected males, and females, respectively. The number of DEGs increased after infection. By comparing shared DEGs of non-infected and infected individuals, potential immune- and reproduction-related of host, and immune- and metabolism-related genes of parasite are highlighted. The only shared KEGG pathway between non-infected and infected individuals was the ribosome pathway. In summary, findings in this study provide new insights into the host-parasite relationship of rhizocephalan parasites and their crustacean hosts.
  20. WHO Solidarity Trial Consortium, Pan H, Peto R, Henao-Restrepo AM, Preziosi MP, Sathiyamoorthy V, et al.
    N Engl J Med, 2021 Feb 11;384(6):497-511.
    PMID: 33264556 DOI: 10.1056/NEJMoa2023184
    BACKGROUND: World Health Organization expert groups recommended mortality trials of four repurposed antiviral drugs - remdesivir, hydroxychloroquine, lopinavir, and interferon beta-1a - in patients hospitalized with coronavirus disease 2019 (Covid-19).

    METHODS: We randomly assigned inpatients with Covid-19 equally between one of the trial drug regimens that was locally available and open control (up to five options, four active and the local standard of care). The intention-to-treat primary analyses examined in-hospital mortality in the four pairwise comparisons of each trial drug and its control (drug available but patient assigned to the same care without that drug). Rate ratios for death were calculated with stratification according to age and status regarding mechanical ventilation at trial entry.

    RESULTS: At 405 hospitals in 30 countries, 11,330 adults underwent randomization; 2750 were assigned to receive remdesivir, 954 to hydroxychloroquine, 1411 to lopinavir (without interferon), 2063 to interferon (including 651 to interferon plus lopinavir), and 4088 to no trial drug. Adherence was 94 to 96% midway through treatment, with 2 to 6% crossover. In total, 1253 deaths were reported (median day of death, day 8; interquartile range, 4 to 14). The Kaplan-Meier 28-day mortality was 11.8% (39.0% if the patient was already receiving ventilation at randomization and 9.5% otherwise). Death occurred in 301 of 2743 patients receiving remdesivir and in 303 of 2708 receiving its control (rate ratio, 0.95; 95% confidence interval [CI], 0.81 to 1.11; P = 0.50), in 104 of 947 patients receiving hydroxychloroquine and in 84 of 906 receiving its control (rate ratio, 1.19; 95% CI, 0.89 to 1.59; P = 0.23), in 148 of 1399 patients receiving lopinavir and in 146 of 1372 receiving its control (rate ratio, 1.00; 95% CI, 0.79 to 1.25; P = 0.97), and in 243 of 2050 patients receiving interferon and in 216 of 2050 receiving its control (rate ratio, 1.16; 95% CI, 0.96 to 1.39; P = 0.11). No drug definitely reduced mortality, overall or in any subgroup, or reduced initiation of ventilation or hospitalization duration.

    CONCLUSIONS: These remdesivir, hydroxychloroquine, lopinavir, and interferon regimens had little or no effect on hospitalized patients with Covid-19, as indicated by overall mortality, initiation of ventilation, and duration of hospital stay. (Funded by the World Health Organization; ISRCTN Registry number, ISRCTN83971151; ClinicalTrials.gov number, NCT04315948.).

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