Browse publications by year: 2021

  1. Hariono M, Hariyono P, Dwiastuti R, Setyani W, Yusuf M, Salin N, et al.
    Results Chem, 2021 Jan;3:100195.
    PMID: 34567959 DOI: 10.1016/j.rechem.2021.100195
    This present study reports some natural products and one hydroxamic acid synthetic compound which were previously reported as matrix metalloproteinase-9 (MMP-9) inhibitors to be evaluated for their inhibition toward severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) 3-chymotrypsin-like protease (3CLpro). This enzyme is one of the proteins responsible for this coronaviral replication. Two herbal methanolic extracts i.e., Averrhoa carambola leaves and Ageratum conyzoides aerial part demonstrate >50% inhibition at 1000 µg/mL. Interestingly, apigenin, one of flavonoids, demonstrates 92% inhibition at 250 µg/mL (925 µM) as well as hydroxamic acid compound, N-isobutyl-N-(4-methoxyphenylsulfonyl)glycyl hydroxamic acid (NNGH), which shows 69% inhibition at 100 µM. The in vitro results are supported by the docking studies revealing that the binding mode of both compounds is mainly by interacting with GLU166 residue in the hydrophobic pocket of the 3CLpro. Pharmacophore mapping further supported the results by confirming that the in vitro activities of both compounds are due to their pharmacophore features employing hydrogen bond acceptor (HBA), hydrogen bond donor (HBD) and hydrophobic. Gas Chromatography-Mass Spectrometry (GC-MS) analysis reported chromene compounds in Ageratum conyzoides aerial part methanolic extract are potential to be this enzyme inhibitor candidate. These all results reflect their potencies to be SARS-CoV-2 inhibitors through 3CLpro inhibition mechanism.
  2. Chaubey I, Vignesh R, Babu H, Wagoner I, Govindaraj S, Velu V
    PMID: 34568094 DOI: 10.3389/fcimb.2021.717104
    MeSH terms: Female; Humans; Pregnancy; Pregnancy Complications, Infectious*; Infectious Disease Transmission, Vertical; Pregnant Women
  3. Li ZZ, Liu G, Tao R, Lobont OR
    Front Public Health, 2021;9:699821.
    PMID: 34568255 DOI: 10.3389/fpubh.2021.699821
    This paper aims to determine the existence of convergence in health expenditures among Association for South East Asian Nations (ASEAN) countries. Based on the SPSM procedure and panel KSS unit root test results, the public health expenditures (PUHE) in Indonesia, Lao PDR, Cambodia, the Philippines, and Myanmar are converging, while that of Brunei Darussalam, Malaysia, Vietnam, Singapore, and Thailand are diverging. In addition, the sequences of private health expenditures (PRHE) in ASEAN member states are stationary, which implies convergence. This finding is in accordance with Wagner's law, that is, as nations develop, they are forced to expand public expenditure. Specifically, countries with low levels of PUHE tend to catch up with the high health spending countries. This research has policy implications with regard to the convergence of health expenditure across countries. The government in low- and lower-middle income countries should raise PUHE to provide access to health services for those who are unaffordable individuals.
    MeSH terms: Asia, Southeastern/epidemiology; Health Expenditures*; Humans; Indonesia/epidemiology; Philippines; Thailand
  4. Zakaria AA, Noor MHM, Ahmad H, Hassim HA, Mazlan M, Latip MQA
    Biomed Res Int, 2021;2021:9928199.
    PMID: 34568497 DOI: 10.1155/2021/9928199
    The Labisia pumila (LP) is a traditional plant that is locally known as Kacip Fatimah, Selusuh Fatimah, or Pokok Ringgang by the Malaysian indigenous people. It is believed to facilitate their childbirth, treating their postchild birth and menstrual irregularities. The water extract of LP has shown to contain bioactive compounds such as flavonoids, ascorbic acid, β-carotene, anthocyanin, and phenolic acid, which contribute extensive antioxidant, anti-inflammatory, antimicrobial, and antifungal. The LP ethanolic extract exhibits significant estrogenic effects on human endomentrial adenocarcinoma cell in estrogen-free basal medium and promoting an increase in secretion of alkaline phosphate. Water based has been used for many generations, and studies had reported that it could displace in binding the antibodies and increase the estradiol production making it similar to esterone and estradiol hormone. LP extract poses a potential and beneficial aspect in medical and cosmeceutical applications. This is mainly due to its phytoestrogen properties of the LP. However, there is a specific functionality in the application of LP extract, due to specific functional group in phytoconstituent of LP. Apart from that, the extraction solvent is important in preparing the LP extract as it poses some significant and mild side effects towards consuming the LP extracts. The current situation of women reproductive disease such as postmenopausal syndrome and polycystic ovary syndrome is increasing. Thus, it is important to find ways in alternative treatment for women reproductive disease that is less costly and low side effects. In conclusion, these studies proven that LP has the potential to be an alternative way in treating female reproductive related diseases such as in postmenopausal and polysystic ovarian syndrome women.
    MeSH terms: Animals; Estrogens/metabolism; Female; Humans; Plant Extracts/pharmacology; Plant Extracts/therapeutic use*; Bone Density/drug effects; Primulaceae/chemistry*; Phytoestrogens/pharmacology; Phytoestrogens/therapeutic use; Female Urogenital Diseases/drug therapy*; Female Urogenital Diseases/physiopathology
  5. Zainal Ariffin NH, Mohammad Haniff MAS, Syono MI, Ambri Mohamed M, Hamzah AA, Hashim AM
    ACS Omega, 2021 Sep 21;6(37):23710-23722.
    PMID: 34568651 DOI: 10.1021/acsomega.1c01520
    We report a viable method to produce nanocrystalline graphene films on polycrystalline nickel (Ni) with enhanced N doping at low temperatures by a cold-wall plasma-assisted chemical vapor deposition (CVD) method. The growth of nanocrystalline graphene films was carried out in a benzene/ammonia/argon (C6H6/NH3/Ar) system, in which the temperature of the substrate heated by Joule heating can be further lowered to 100 °C to achieve a low sheet resistance of 3.3 kΩ sq-1 at a high optical transmittance of 97.2%. The morphological, structural, and electrical properties and the chemical compositions of the obtained N-doped nanocrystalline graphene films can be tailored by controlling the growth parameters. An increase in the concentration of atomic N from 1.42 to 11.28 atomic percent (at.%) is expected due to the synergetic effects of a high NH3/Ar ratio and plasma power. The possible growth mechanism of nanocrystalline graphene films is also discussed to understand the basic chemical reactions that occur at such low temperatures with the presence of plasma as well as the formation of pyridinic-N- and pyrrolic-N-dominated nanocrystalline graphene. The realization of nanocrystalline graphene films with enhanced N doping at 100 °C may open great potential in developing future transparent nanodevices.
  6. Saida K, Tamaoki J, Sasaki M, Haniffa M, Koshimizu E, Sengoku T, et al.
    Clin Genet, 2021 12;100(6):722-730.
    PMID: 34569062 DOI: 10.1111/cge.14066
    Cerebellar ataxia is a genetically heterogeneous disorder. GEMIN5 encoding an RNA-binding protein of the survival of motor neuron complex, is essential for small nuclear ribonucleoprotein biogenesis, and it was recently reported that biallelic loss-of-function variants cause neurodevelopmental delay, hypotonia, and cerebellar ataxia. Here, whole-exome analysis revealed compound heterozygous GEMIN5 variants in two individuals from our cohort of 162 patients with cerebellar atrophy/hypoplasia. Three novel truncating variants and one previously reported missense variant were identified: c.2196dupA, p.(Arg733Thrfs*6) and c.1831G > A, p.(Val611Met) in individual 1, and c.3913delG, p.(Ala1305Leufs*14) and c.4496dupA, p.(Tyr1499*) in individual 2. Western blotting analysis using lymphoblastoid cell lines derived from both affected individuals showed significantly reduced levels of GEMIN5 protein. Zebrafish model for null variants p.(Arg733Thrfs*6) and p.(Ala1305Leufs*14) exhibited complete lethality at 2 weeks and recapitulated a distinct dysplastic phenotype. The phenotypes of affected individuals and the zebrafish mutant models strongly suggest that biallelic loss-of-function variants in GEMIN5 cause cerebellar atrophy/hypoplasia.
  7. Chee CS, Do Ha I, Seo B, Lee Y
    Stat Methods Med Res, 2021 Nov;30(11):2485-2502.
    PMID: 34569366 DOI: 10.1177/09622802211037072
    A consequence of using a parametric frailty model with nonparametric baseline hazard for analyzing clustered time-to-event data is that its regression coefficient estimates could be sensitive to the underlying frailty distribution. Recently, there has been a proposal for specifying both the baseline hazard and the frailty distribution nonparametrically, and estimating the unknown parameters by the maximum penalized likelihood method. Instead, in this paper, we propose the nonparametric maximum likelihood method for a general class of nonparametric frailty models, i.e. models where the frailty distribution is completely unspecified but the baseline hazard can be either parametric or nonparametric. The implementation of the estimation procedure can be based on a combination of either the Broyden-Fletcher-Goldfarb-Shanno or expectation-maximization algorithm and the constrained Newton algorithm with multiple support point inclusion. Simulation studies to investigate the performance of estimation of a regression coefficient by several different model-fitting methods were conducted. The simulation results show that our proposed regression coefficient estimator generally gives a reasonable bias reduction when the number of clusters is increased under various frailty distributions. Our proposed method is also illustrated with two data examples.
  8. Hod R, Mokhtar SA, Muharam FM, Shamsudin UK, Hisham Hashim J
    PMID: 34569889 DOI: 10.1177/10105395211048620
    Plasmodium knowlesi is an emerging species for malaria in Malaysia, particularly in East Malaysia. This infection contributes to almost half of all malaria cases and deaths in Malaysia and poses a challenge in eradicating malaria. The aim of this study was to develop a predictive model for P. knowlesi susceptibility areas in Sabah, Malaysia, using geospatial data and artificial neural networks (ANNs). Weekly malaria cases from 2013 to 2014 were used to identify the malaria hotspot areas. The association of malaria cases with environmental factors (elevation, water bodies, and population density, and satellite images providing rainfall, land surface temperature, and normalized difference vegetation indices) were statistically determined. The significant environmental factors were used as input for the ANN analysis to predict malaria cases. Finally, the malaria susceptibility index and zones were mapped out. The results suggested integrating geospatial data and ANNs to predict malaria cases, with overall correlation coefficient of 0.70 and overall accuracy of 91.04%. From the malaria susceptibility index and zoning analyses, it was found that areas located along the Crocker Range of Sabah and the East part of Sabah were highly susceptible to P. knowlesi infections. Following this analysis, targetted entomological mapping and malaria control programs can be initiated.
  9. Aithal Padur A, Kumar N, Lewis MG, Sekaran VC
    Surg Radiol Anat, 2021 Dec;43(12):2039-2046.
    PMID: 34570285 DOI: 10.1007/s00276-021-02837-z
    PURPOSE: Morphometric analysis of the patella and the patellar ligament is crucial in diagnosing and surgical corrections of knee injuries and patellofemoral joint disorders. Dimensions of the patella and the patellar ligament are frequently used in implant design and ACL reconstruction. This study aims to obtain detailed morphometric data on the patellar ligament and its localization based on gross anatomical dissections in the adult cadavers.

    METHODS: The present study consisted of 50 lower limbs from formalin-fixed male adult cadavers aged about 70 years (45-85) belonging to the South Indian population. Total length of the quadriceps tendon, patellar height, patellar ligament height, proximal width, distal width and thickness of the patellar ligament were measured meticulously. Mean, standard deviation, median scores of each parameter were computed for groups using SPSS 16.0. Level of significance was considered as p 

    MeSH terms: Adult; Aged; Cadaver; Humans; Male; Patella/surgery; Tendons; Patellar Ligament*; Patellofemoral Joint*; Anterior Cruciate Ligament Injuries*
  10. Zhang Y, Yu J, Tan L, Wang X, Li R, Kim DY
    J Microbiol, 2021 Nov;59(11):1044-1055.
    PMID: 34570337 DOI: 10.1007/s12275-021-1361-8
    Getah virus (GETV), which was first isolated in Malaysia in 1955, and Sagiyama virus (SAGV), isolated in Japan in 1956, are members of the genus Alphavirus in the family Togaviridae. It is a consensus view that SAGV is a variant of GETV. In the present study, we determined the complete sequences of the prototype GETV MM2021 and SAGV M6-Mag132 genomic RNA extracted from plaque-purified viruses. The MM2021 genome was 11,692 nucleotides (nt) in length in the absence of 3' poly(A) tail, and the length of M6-Mag132 genome was 11,698 nt. Through sequence alignment of MM2021 and M6-Mag132, we located all the amino acid differences between these two strains, which were scattered in all the encoded proteins. Subsequently, we validated the close evolutionary relationship between GETV and SAGV by constructing phylogenetic trees based on either complete genomes or structural genomes. We eventually analyzed the growth kinetics of GETV and SAGV as well as other representative alphaviruses in various mammalian and insect cell lines. It was shown that human-oriented cell lines such as HEK-293T and Hela cells were relatively resistant to GETV and SAGV infection due to absence of proviral factors or species-specific barrier. On the other hand, both GETV and SAGV replicated efficiently in non-human cell lines. Our results provide essential genetic information for future epidemiological surveillance on Alphaviruses and lay the foundation for developing effective interventions against GETV and SAGV.
    MeSH terms: Alphavirus/classification; Alphavirus/genetics*; Alphavirus/isolation & purification; Alphavirus/physiology; Animals; Cell Line; Humans; Phylogeny; RNA, Viral/genetics; Ross River virus/classification; Ross River virus/genetics*; Ross River virus/isolation & purification; Ross River virus/physiology; Genome, Viral*; Sequence Analysis, DNA; Host Specificity*
  11. Abdi M, Pasbakhsh P, Shabani M, Nekoonam S, Sadeghi A, Fathi F, et al.
    Neurotox Res, 2021 Dec;39(6):1732-1746.
    PMID: 34570348 DOI: 10.1007/s12640-021-00417-y
    Multiple sclerosis (MS) is a chronic disorder characterized by reactive gliosis, inflammation, and demyelination. Microglia plays a crucial role in the pathogenesis of MS and has the dynamic plasticity to polarize between pro-inflammatory (M1) and anti-inflammatory (M2) phenotypes. Metformin, a glucose-lowering drug, attenuates inflammatory responses by activating adenosine monophosphate protein kinase (AMPK) which suppresses nuclear factor kappa B (NF-κB). In this study, we indirectly investigated whether metformin therapy would regulate microglia activity in the cuprizone (CPZ)-induced demyelination mouse model of MS via measuring the markers associated with pro- and anti-inflammatory microglia. Evaluation of myelin by luxol fast blue staining revealed that metformin treatment (CPZ + Met) diminished demyelination, in comparison to CPZ mice. In addition, metformin therapy significantly alleviated reactive microgliosis and astrogliosis in the corpus callosum, as measured by Iba-1 and GFAP staining. Moreover, metformin treatment significantly downregulated the expression of pro-inflammatory associated genes (iNOS, H2-Aa, and TNF-α) in the corpus callosum, whereas expression of anti-inflammatory markers (Arg1, Mrc1, and IL10) was not promoted, compared to CPZ mice. Furthermore, protein levels of iNOS (pro-inflammatory marker) were significantly decreased in the metformin group, while those of Trem2 (anti-inflammatory marker) were increased. In addition, metformin significantly increased AMPK activation in CPZ mice. Finally, metformin administration significantly reduced the activation level of NF-κB in CPZ mice. In summary, our data revealed that metformin attenuated pro-inflammatory microglia markers through suppressing NF-κB activity. The positive effects of metformin on microglia and remyelination suggest that it could be used as a promising candidate to lessen the incidence of inflammatory neurodegenerative diseases such as MS.
  12. Malik A, Hussain M, Uddin F, Raza W, Hussain S, Habiba UE, et al.
    Water Environ Res, 2021 Sep 27.
    PMID: 34570384 DOI: 10.1002/wer.1639
    In this current work, the performance of an aerobic granular sludge (AGS) for real textile wastewater was investigated based on system operational parameters evaluation. The study was performed for 90 days, and sampling was done once a week in which textile dyeing effluent from the textile mill was collected and subjected to laboratory-scale treatment. The samples from the inlet, the outlet of the wastewater plant, and within the bioreactor were collected at various concentrations of MLSS, and hydraulic retention remained the same in the investigated period of 53 hours. The objective of this study was to analyze the AGS system performance assessment by evaluating the effect of different MLSS concentrations on chemical oxygen demand (COD), TSS, and oil/grease removal from real-based textile water. The results showed that removal of organic material from the process water increases with an increase in MLSS concentration in the bioreactor and gradually shifts removal of COD from 91.2% to 94.5%. As the concentration of microorganisms in the reactor (aeration tank) increases, the degradation of waste organics in the wastewater increases as well. Moreover, the % removal of total suspended solids (83.5 to 98 %) and removal of oil/grease (62.5 to 76.4%) were also increased. These results ultimately suggest that the utilization of an activated sludge system can effectively treat complex and highly polluted denim textile wastewater to avoid secondary pollution posed by this industry.
  13. Ashraf MA, Islam A, Butt MA, Hussain T, Khan RU, Bashir S, et al.
    Int J Biol Macromol, 2021 Nov 30;191:872-880.
    PMID: 34571131 DOI: 10.1016/j.ijbiomac.2021.09.131
    Mixed matrix membranes (MMMs) of cellulose acetate/poly(vinylpyrrolidone) (CA/PVP) infused with acid functionalized multiwall carbon nanotubes (f-MWCNTs) were fabricated by an immersion phase separation technique for hemodialysis application. Membranes were characterized using FTIR, water uptake, contact angle, TGA, DMA and SEM analysis. The FTIR was used to confirm the bonding interaction between CA/PVP membrane matrix and f-MWCNTs. Upon addition of f-MWCNTs, TGA thermograms and glass transition temperature indicated improved thermal stability of MMMs. The surface morphological analysis demonstrated revealed uniform distribution of f-MWCNTs and asymmetric membrane structure. The water uptake and contact angle confirmed that hydrophilicity was increased after incorporation of f-MWCNTs. The membranes demonstrated enhancement in water permeate flux, bovine serum albumin (BSA) rejection with the infusion of f-MWCNTs; whereas BSA based anti-fouling analysis using flux recovery ratio test shown up to 8.4% improvement. The urea and creatinine clearance performance of MMMs were evaluated by dialysis experiment. It has been found that f-MWCNTs integrated membranes demonstrated the higher urea and creatinine clearance with increase of 12.6% and 10.5% in comparison to the neat CA/PVP membrane. Thus, the prepared CA/PVP membranes embedded with f-MWCNTs can be employed for wide range of dialysis applications.
    MeSH terms: Cellulose/analogs & derivatives*; Cellulose/chemistry; Creatinine/chemistry; Renal Dialysis/instrumentation*; Renal Dialysis/methods; Membranes, Artificial*; Povidone/chemistry*; Nanotubes, Carbon/chemistry*; Hydrophobic and Hydrophilic Interactions
  14. Thavagnanam S, H'ng SY, Nathan AM, Eg KP, Chinna K, Hajar Bte Turbirin S, et al.
    Int J Pediatr Otorhinolaryngol, 2021 Dec;151:110930.
    PMID: 34571207 DOI: 10.1016/j.ijporl.2021.110930
    INTRODUCTION: Overnight pulse oximetry is an alternative to polysomnography (PSG) in diagnosing obstructive sleep apnoea syndrome, but its sensitivity is reported to be low.

    AIMS: To determine the (a) diagnostic accuracy, interobserver reliability and reliable oxygen desaturation index of 4% (ODI4) score at diagnosing obstructive sleep apnoea syndrome in children and (b) correlation between the apnoea hypopnoea index (AHI) with ODI4 and oxygen nadir between both PSG and oximetry.

    METHODS: This cross-sectional study included children aged 1-18 years old, undergoing a fully attended overnight PSG for suspected obstructive sleep apnoea syndrome. The Nonin 3150 WristOx2 ™ [Fig. 2] was worn simultaneously during the PSG. Poor oximetry recordings were excluded. Pulse oximetry was scored using the McGill Oximetry Score (MOS) whereby a score of 2-4 was positive for OSAS. Specificity, sensitivity, positive predictive values (PPV), negative predictive values (NPV) and interobserver reliability of the WristOx2 were calculated.

    RESULTS: One hundred and sixty-two children with a mean (SD) age of 9.3 (±3.5) years (range 2 years 6 months old - 17 years old) were included after excluding 18 children (poor oximetry data [n = 16] and incomplete PSG [n = 2]). Interobserver agreement of the WristOx2 was 0.8763 (95% CI:0.80, 0.95). WristOx2 had a sensitivity 50%, specificity 96.7%, PPV 96% and NPV 53% at diagnosing OSAS. ODI4 ≥ 2 events/hour in oximetry had a sensitivity of 97.6% and negative predictive value of 85.7% at diagnosing OSA.

    CONCLUSION: Overnight pulse oximetry with the Nonin 3150 WristOx2 ™ is an accurate and reliable tool in diagnosing significant OSAS in children.

  15. Asif S, Ahmad B, Hamza SA, Taib H, Kassim NK, Zainuddin SLA
    Eur J Dent, 2021 Sep 27.
    PMID: 34571567 DOI: 10.1055/s-0041-1731930
    BACKGROUND: This study was aimed to determine the levels of salivary receptor activator of NF-κB ligand (RANKL) and osteoprotegerin (OPG) and its association with periodontal status among periodontitis patients.

    PATIENTS AND METHODS: A cross-sectional study was designed and performed at the Dental Clinic, Hospital Universiti Sains Malaysia (HUSM). Random sampling was employed to identify 88 participants into three groups: 30 mild periodontitis, 30 moderate to severe periodontitis, and 28 healthy (nonperiodontitis) patients. Periodontal parameters: periodontal pocket depth (PPD), clinical attachment level (CAL), plaque score (PS), and gingival bleeding index (GBI) were recorded. In total, 4 mL of unstimulated whole saliva was collected to determine the levels of salivary RANKL and OPG proteins by using ELISA technique. Data were analyzed by using SPSS software version 24.0.

    RESULTS: Mean values for PPD (5.3 ± 0.5) and CAL (5.6 ± 0.5) were observed higher for moderate to severe periodontitis as compared with values (4.4 ± 0.2) (4.5 ± 0.2) in mild periodontitis patients. The mean salivary RANKL and OPG was 0.23 ± 0.07 ng/mL and 1.78 ± 0.70 ng/mL respectively in moderate to severe periodontitis. Only salivary RANKL levels were significantly and positively correlated with all the clinical periodontal parameters.

    CONCLUSION: The levels of salivary RANKL were higher as opposed to lower OPG levels in periodontitis patients in contrast to healthy (nonperiodontitis) patients. RANKL levels were significantly associated with the periodontal parameters. Therefore, we can conclude that RANKL can potentially aid as an adjunctive diagnostic protein in evaluating periodontal disease.

  16. Mohd Tariq MN, Shahar HK, Baharudin MR, Ismail SNS, Manaf RA, Salmiah MS, et al.
    BMC Public Health, 2021 09 24;21(1):1735.
    PMID: 34560858 DOI: 10.1186/s12889-021-11719-3
    BACKGROUND: Flood disaster preparedness among the community seldom received attention. Necessary intervention must be taken to prevent the problem. Health Education Based Intervention (HEBI) was developed following the Health Belief Model, particularly in improving flood disaster preparedness among the community. The main objective of this study is to assess the effect of HEBI on improving flood disaster preparedness among the community in Selangor. This study aims to develop, implement, and evaluate the impact of health education-based intervention (HEBI) based on knowledge, skills, and preparedness to improve flood disaster preparedness among the community in Selangor.

    METHOD: A single-blind cluster randomized controlled trial will conduct at six districts in Selangor. Randomly selected respondents who fulfilled the inclusion criteria will be invited to participate in the study. Health education module based on Health Believed Theory will be delivered via health talks and videos coordinated by liaison officers. Data at three-time points at baseline, immediate, and 3 months post-intervention will be collected. A validated questionnaire will assess participants' background characteristics, knowledge, skill, and preparedness on disaster preparedness and perception towards disaster. Descriptive and inferential statistics will be applied for data analysis using IBM Statistical Package for Social Sciences version 25. Longitudinal correlated data on knowledge, skills, preparedness, and perception score at baseline, immediate post-intervention, and 6 months post-intervention will be analyzed using Generalized Estimating Equations (GEE).

    DISCUSSION: It is expected that knowledge, skills, preparedness, and flood disaster perception score are more significant in the intervention group than the control group, indicating the Health Education Based Intervention (HEBI).

    TRIAL REGISTRATION: Thai Clinical Trial TCTR20200202002 .

    MeSH terms: Disasters*; Health Education; Humans; Malaysia; Randomized Controlled Trials as Topic; Single-Blind Method; Floods*
  17. Chung PY, Khoo REY, Liew HS, Low ML
    Ann Clin Microbiol Antimicrob, 2021 Sep 24;20(1):67.
    PMID: 34560892 DOI: 10.1186/s12941-021-00473-4
    BACKGROUND: Methicillin-resistance S. aureus (MRSA) possesses the ability to resist multiple antibiotics and form biofilm. Currently, vancomycin remains the last drug of choice for treatment of MRSA infection. The emergence of vancomycin-resistant S. aureus (VRSA) has necessitated the development of new therapeutic agents against MRSA. In this study, the antimicrobial and antibiofilm activities of two copper-complexes derived from Schiff base (SBDs) were tested individually, and in combination with oxacillin (OXA) and vancomycin (VAN) against reference strains methicillin-susceptible and methicillin-resistant Staphylococcus aureus. The toxicity of the SBDs was also evaluated on a non-cancerous mammalian cell line.

    METHODS: The antimicrobial activity was tested against the planktonic S. aureus cells using the microdilution broth assay, while the antibiofilm activity were evaluated using the crystal violet and resazurin assays. The cytotoxicity of the SBDs was assessed on MRC5 (normal lung tissue), using the MTT assay.

    RESULTS: The individual SBDs showed significant reduction of biomass and metabolic activity in both S. aureus strains. Combinations of the SBDs with OXA and VAN were mainly additive against the planktonic cells and cells in the biofilm. Both the compounds showed moderate toxicity against the MRC5 cell line. The selectivity index suggested that the compounds were more cytotoxic to S. aureus than the normal cells.

    CONCLUSION: Both the SBD compounds demonstrated promising antimicrobial and antibiofilm activities and have the potential to be further developed as an antimicrobial agent against infections caused by MRSA.

    MeSH terms: Anti-Infective Agents; Anti-Bacterial Agents/pharmacology*; Methicillin; Schiff Bases/pharmacology*; Staphylococcus aureus; Vancomycin/pharmacology*; Biofilms; Methicillin-Resistant Staphylococcus aureus/drug effects*; Methicillin-Resistant Staphylococcus aureus/isolation & purification
  18. Mat Yusoff Y, Ahid F, Abu Seman Z, Abdullah J, Kamaluddin NR, Esa E, et al.
    Mol Cytogenet, 2021 Sep 24;14(1):45.
    PMID: 34560908 DOI: 10.1186/s13039-021-00561-2
    BACKGROUND: Relapsed acute myeloid leukemia (AML) is associated with the acquisition of additional somatic mutations which are thought to drive phenotypic adaptability, clonal selection and evolution of leukemic clones during treatment. We performed high throughput exome sequencing of matched presentation and relapsed samples from 6 cytogenetically normal AML (CN-AML) patients treated with standard remission induction chemotherapy in order to contribute with the investigation of the mutational landscape of CN-AML and clonal evolution during AML treatment.

    RESULT: A total of 24 and 32 somatic variants were identified in presentation and relapse samples respectively with an average of 4.0 variants per patient at presentation and 5.3 variants per patient at relapse, with SNVs being more frequent than indels at both disease stages. All patients have somatic variants in at least one gene that is frequently mutated in AML at both disease presentation and relapse, with most of these variants are classic AML and recurrent hotspot mutations including NPM1 p.W288fs, FLT3-ITD, NRAS p.G12D and IDH2 p.R140Q. In addition, we found two distinct clonal evolution patterns of relapse: (1) a leukemic clone at disease presentation acquires additional mutations and evolves into the relapse clone after the chemotherapy; (2) a leukemic clone at disease presentation persists at relapse without the addition of novel somatic mutations.

    CONCLUSIONS: The findings of this study suggest that the relapse-initiating clones may pre-exist prior to therapy, which harbor or acquire mutations that confer selective advantage during chemotherapy, resulting in clonal expansion and eventually leading to relapse.

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