Browse publications by year: 2020

  1. Naing C, Whittaker MA, Tanner M
    J Infect Dis, 2020 10 29;222(Suppl 8):S717-S725.
    PMID: 33119095 DOI: 10.1093/infdis/jiaa335
    BACKGROUND: Myanmar is a premalaria elimination country with artemisinin-resistant malaria. A strategy for transmission control is focused on vulnerable groups such as mobile and migrant populations (MMPs), and includes improving access to insecticide-treated bed nets in the Myanmar artemisinin resistance containment (MARC) zones using multisectoral approaches (MSA).

    METHODS: This narrative systematic review addressed MSAs targeted to MMPs in Myanmar for malaria prevention. We searched relevant studies in electronic databases and present the narrative findings in 4 domains: stakeholder groups, net coverage and utilization, social determinates, and facilitators/barriers.

    RESULTS: Nine studies were included. The review identified stakeholders involved in intersectoral collaboration. Net ownership was higher than utilization rates in the MARC zones and rates remained below the WHO recommended target of 100%. There was inadequate description of roles and responsibilities for implementation and on channels of communication within the partnerships and with the Government.

    CONCLUSIONS: Findings show that interventions to distribute treated bed nets were supported by the multiple stakeholders. Due to the design of the primary studies, analysis of the added value of intersectoral collaboration was limited. More attention must be paid to designing studies to document and evaluate the contributions and outcomes of intersectoral collaboration.

    MeSH terms: Myanmar/epidemiology; Communicable Disease Control/instrumentation; Communicable Disease Control/legislation & jurisprudence*; Female; Humans; Insecticide Resistance*; Health Knowledge, Attitudes, Practice; Malaria/prevention & control*; Male; Transients and Migrants; Artemisinins/pharmacology; Insecticide-Treated Bednets; Intersectoral Collaboration
  2. Lim JT, Dickens BSL, Chew LZX, Choo ELW, Koo JR, Aik J, et al.
    PLoS Negl Trop Dis, 2020 10;14(10):e0008719.
    PMID: 33119609 DOI: 10.1371/journal.pntd.0008719
    An estimated 105 million dengue infections occur per year across 120 countries, where traditional vector control is the primary control strategy to reduce contact between mosquito vectors and people. The ongoing sars-cov-2 pandemic has resulted in dramatic reductions in human mobility due to social distancing measures; the effects on vector-borne illnesses are not known. Here we examine the pre and post differences of dengue case counts in Malaysia, Singapore and Thailand, and estimate the effects of social distancing as a treatment effect whilst adjusting for temporal confounders. We found that social distancing is expected to lead to 4.32 additional cases per 100,000 individuals in Thailand per month, which equates to 170 more cases per month in the Bangkok province (95% CI: 100-242) and 2008 cases in the country as a whole (95% CI: 1170-2846). Social distancing policy estimates for Thailand were also found to be robust to model misspecification, and variable addition and omission. Conversely, no significant impact on dengue transmission was found in Singapore or Malaysia. Across country disparities in social distancing policy effects on reported dengue cases are reasoned to be driven by differences in workplace-residence structure, with an increase in transmission risk of arboviruses from social distancing primarily through heightened exposure to vectors in elevated time spent at residences, demonstrating the need to understand the effects of location on dengue transmission risk under novel population mixing conditions such as those under social distancing policies.
    MeSH terms: Animals; Communicable Disease Control/methods*; Dengue/epidemiology; Dengue/transmission*; Humans; Malaysia/epidemiology; Pneumonia, Viral/epidemiology*; Pneumonia, Viral/prevention & control; Singapore/epidemiology; Social Isolation; Thailand/epidemiology; Coronavirus Infections/epidemiology*; Coronavirus Infections/prevention & control; Pandemics/prevention & control; Mosquito Vectors
  3. Mansor N, Ahmad N, Rahman HA
    PLoS One, 2020;15(10):e0240842.
    PMID: 33119620 DOI: 10.1371/journal.pone.0240842
    INTRODUCTION: The increasing trend of sexually transmitted infections (STIs) among the young population is a significant public health problem. This study aimed to determine the level of knowledge on STIs among students in higher education institutions and its predicting factors, in Melaka.

    METHODOLOGY: A cross-sectional study was conducted among 600 students from higher education institutions in Melaka aged between 18 to 30 years old. Multistage sampling of the institutions was performed. Valid and reliable self-administered questionnaire in the national language, Bahasa Malaysia, was used as to collect data on sociodemographic, personal background, knowledge on STIs and sources of information for STIs. Univariate, bivariate and multivariate analyses were conducted using IBM SPSS software version 25.

    RESULTS: The response rate for this study was 88%. The mean knowledge score was 24.1 ±5.1 out of 38. HIV was the most known STIs while gonorrhoea, trichomoniasis and chlamydial infections were among the least known STIs. Oral intercourse was the least known sexual activity that could transmit STIs. Higher proportion of respondents had correct knowledge on control and preventive measures of STIs (between 78% and 95%) compared to correct knowledge on sign and symptoms of STIs (between 8.5% and 67.8%). More than 90% of the respondents were unaware that a person infected with STIs could be symptom free. Four variables were identified as the determinants of the knowledge on STIs, which were level of education, place of stay, history of sexual and reproductive health education and involvement in STIs awareness programs (F (4,445) = 11.405, p <0.001, R2 = 0.093).

    CONCLUSIONS: The knowledge on STIs among students in higher education institutions was unsatisfactory. The existing sexual education programs can be strengthened by delivering more information on other STIs rather than focusing on HIV only. The future program should focus on students of diploma and/or skill certificate and staying off-campus.

    MeSH terms: Adolescent; Adult; Cross-Sectional Studies; Female; Humans; Health Knowledge, Attitudes, Practice*; Malaysia/epidemiology; Male; Surveys and Questionnaires; Schools; Sexual Behavior; Sex Education*; Sexually Transmitted Diseases/epidemiology*; Sexually Transmitted Diseases/pathology; Students; Universities; Condoms; Young Adult
  4. Lim LWK, Kamar CKA, Roja JS, Chung HH, Liao Y, Lam TT, et al.
    Comput Biol Chem, 2020 Dec;89:107403.
    PMID: 33120127 DOI: 10.1016/j.compbiolchem.2020.107403
    The Blueline Rasbora (Rasbora sarawakensis) is a small ray-finned fish categorized under the genus Rasbora in the Cyprinidae family. In this study, the complete mitogenome sequence of R. sarawakensis was sequenced using four primers targeting overlapping regions. The mitogenome is 16,709 bp in size, accommodating 22 transfer RNA genes, 13 protein-coding genes, two ribosomal RNA genes and a putative control region. Identical gene organisation was detected between this species and other genus counterparts. The heavy strand houses 28 genes while the light strand stores the other nine genes. Most protein-coding genes employ ATG as start codon, excluding COI gene, which utilizes GTG instead. The central conserved sequence blocks (CSB-F, CSB-E and CSB-D), variable sequence blocks (CSB-3, CSB-2 and CSB-1) as well as the terminal associated sequence (TAS) are conserved in the control region. The maximum likelihood phylogenetic tree revealed the divergence of R. sarawakensis from the basal region of the Rasbora clade, where its evolutionary relationships with R. maculatus and R. pauciperforata are poorly resolved as indicated by the low bootstrap values. This work acts as steppingstone towards further molecular evolution and population genetics studies of Rasbora genus in future.
    MeSH terms: Animals; Cyprinidae/genetics*; DNA, Mitochondrial/analysis*; DNA, Mitochondrial/genetics; Genes; Phylogeny; Polymerase Chain Reaction; Sequence Analysis, DNA; Genome, Mitochondrial*
  5. Sipin Q, Mustaffa Kamal F, Watanabe M, Megat Abdul Rani PA, Low VL, Abdul Aziz NA
    PMID: 33120297 DOI: 10.1016/j.cimid.2020.101563
    Ticks are important vectors in transmitting various pathogens and they could jeopardize the health and welfare of humans and animals worldwide. The present study aimed to investigate the presence of important tick-borne haemopathogens (TBH) in dogs and ticks via polymerase chain reaction (PCR) assays. A total of 220 blood samples and 140 ticks were collected from 10 animal shelters in Peninsular Malaysia. Of 220 blood samples, 77 (35 %) were positive to TBH, of which 20 % were E. canis, 12 % were A. platys, 7 % were B. gibsoni and 7 % were B. vogeli. All ticks were identified as Rhipicephalus sanguineus with five samples (3.57 %) positive with TBH. Co-infections of TBH (0.45-9.55 %) in dogs were also observed in this study.
    MeSH terms: Anaplasma/classification; Anaplasma/isolation & purification; Animals; Arachnid Vectors/microbiology*; Babesia/classification; Babesia/isolation & purification; Dog Diseases/blood; Dog Diseases/diagnosis*; Dog Diseases/epidemiology; Dog Diseases/parasitology; Dogs; Female; Malaysia/epidemiology; Male; Tick-Borne Diseases/blood; Tick-Borne Diseases/diagnosis; Tick-Borne Diseases/epidemiology; Tick-Borne Diseases/veterinary*; Ehrlichia canis/classification; Ehrlichia canis/isolation & purification; Rhipicephalus sanguineus/microbiology*
  6. Lee CC, Lin CY, Hsu HW, Yang CS
    Arch Virol, 2020 Nov;165(11):2715-2719.
    PMID: 32776255 DOI: 10.1007/s00705-020-04769-2
    We report two novel RNA viruses from yellow crazy ants, (Anoplolepis gracilipes) detected using next-generation sequencing. The complete genome sequences of the two viruses were 10,662 and 8,238 nucleotides in length, respectively, with both possessing two open reading frames with three conserved protein domains. The genome organization is characteristic of members of the genus Triatovirus in the family Dicistroviridae. The two novel viruses were tentatively named "Anoplolepis gracilipes virus 1" and "Anoplolepis gracilipes virus 2" (AgrV-1 and AgrV-2). Phylogenetic analyses based on amino acid sequences of the non-structural polyprotein (ORF1) suggest that the two viruses are triatovirus-like viruses. This is the first report on the discovery of novel triatovirus-like viruses in yellow crazy ants with a description of their genome structure (two ORFs and conserved domains of RNA helicase, RNA-dependent RNA polymerase, and capsid protein), complete sequences, and viral prevalence across the Asia-Pacific region.
    MeSH terms: Amino Acid Sequence; Animals; Ants/virology*; Japan; Malaysia; Phylogeny*; RNA Replicase/genetics; RNA, Viral/genetics; Open Reading Frames; Genome, Viral*; RNA Helicases/genetics; Capsid Proteins/genetics; Dicistroviridae/classification*; Dicistroviridae/isolation & purification*
  7. Kow CS, Hasan SS
    Rheumatol Int, 2020 12;40(12):2117-2118.
    PMID: 33044704 DOI: 10.1007/s00296-020-04715-0
    MeSH terms: Rituximab/adverse effects; Humans; Pneumonia, Viral*; Coronavirus Infections*; Pandemics*
  8. Wadhwa R, Paudel KR, Mehta M, Shukla SD, Sunkara K, Prasher P, et al.
    CNS Neurol Disord Drug Targets, 2020;19(9):698-708.
    PMID: 33109069 DOI: 10.2174/1871527319999200817112427
    Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders, and lung and oral cancers, but also causes neurological disorders such as Alzheimer 's disease. Tobacco smoke consists of more than 4500 toxic chemicals, which form free radicals and can cross blood-brain barrier resulting in oxidative stress, an extracellular amyloid plaque from the aggregation of amyloid β (Aβ) peptide deposition in the brain. Further, respiratory infections such as Chlamydia pneumoniae, respiratory syncytial virus have also been involved in the induction and development of the disease. The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. The review article sheds light on the role of smoking and respiratory infections in causing oxidative stress and neuroinflammation, resulting in Alzheimer's disease (AD). This review will be of interest to scientists and researchers from biological and medical science disciplines, including microbiology, pharmaceutical sciences and the translational researchers, etc. The increasing understanding of the relationship between chronic lung disease and neurological disease is two-fold. First, this would help to identify the risk factors and possible therapeutic interventions to reduce the development and progression of both diseases. Second, this would help to reduce the probable risk of development of AD in the population prone to chronic lung diseases.
    MeSH terms: Alzheimer Disease/epidemiology*; Animals; Brain/metabolism; Humans; Neurons/metabolism; Neurotoxins; Respiratory Tract Infections/epidemiology*; Risk Factors; Smoking/epidemiology*; Amyloid beta-Peptides/metabolism; Amyloid beta-Protein Precursor; Oxidative Stress; Plaque, Amyloid
  9. Aladdin NA, Husain K, Jalil J, Sabandar CW, Jamal JA
    BMC Complement Med Ther, 2020 Oct 27;20(1):324.
    PMID: 33109178 DOI: 10.1186/s12906-020-03119-8
    BACKGROUND: In traditional Malay medicine, Marantodes pumilum (Blume) Kuntze (family Primulaceae) is commonly used by women to treat parturition, flatulence, dysentery, dysmenorrhea, gonorrhea, and bone diseases. Preliminary screening of some Primulaceae species showed that they possess xanthine oxidase inhibitory activity. Thus, this study aimed to investigate the xanthine oxidase inhibitory activity of three varieties of M. pumilum and their phytochemical compounds.

    METHOD: Dichloromethane, methanol, and water extracts of the leaves and roots of M. pumilum var. alata, M. pumilum var. pumila, and M. pumilum var. lanceolata were tested using an in vitro xanthine oxidase inhibitory assay. Bioassay-guided fractionation and isolation were carried out on the most active extract using chromatographic techniques. The structures of the isolated compounds were determined using spectroscopic techniques.

    RESULTS: The most active dichloromethane extract of M. pumilum var. pumila leaves (IC50 = 161.6 μg/mL) yielded one new compound, 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), and five known compounds, viz. ardisiaquinone A (2), maesanin (3), stigmasterol (4), tetracosane (5), and margaric acid (6). The new compound was found to be the most active xanthine oxidase inhibitor with an IC50 value of 0.66 ± 0.01 μg/mL, which was not significantly different (p > 0.05) from that of the positive control, allopurinol (IC50 = 0.24 ± 0.00 μg/mL).

    CONCLUSION: This study suggests that the new compound 3,7-dihydroxy-5-methoxy-4,8-dimethyl-isocoumarin (1), which was isolated from the dichloromethane extract of M. pumilum var. pumila leaves, could be a potential xanthine oxidase inhibitor.

    MeSH terms: Humans; Malaysia; Plant Extracts/pharmacology*; Plant Extracts/chemistry*; Xanthine Oxidase/antagonists & inhibitors*; Plant Leaves; Plant Roots; Primulaceae; Isocoumarins/pharmacology*; Isocoumarins/chemistry*; In Vitro Techniques
  10. Balakrishnan KN, Abdullah AA, Bala JA, Jesse FFA, Abdullah CAC, Noordin MM, et al.
    Virol J, 2020 Oct 27;17(1):164.
    PMID: 33109247 DOI: 10.1186/s12985-020-01436-5
    BACKGROUND: Cytomegalovirus (CMV) is an opportunistic pathogen that causes severe complications in congenitally infected newborns and non-immunocompetent individuals. Developing an effective vaccine is a major public health priority and current drugs are fronting resistance and side effects on recipients. In the present study, with the aim of exploring new strategies to counteract CMV replication, several anti-CMV siRNAs targeting IE2 and DNA polymerase gene regions were characterized and used as in combinations for antiviral therapy.

    METHODS: The rat embryo fibroblast (REF) cells were transfected with multi siRNA before infecting with CMV strain ALL-03. Viral growth inhibition was measured by tissue culture infectious dose (TCID50), cytopathic effect (CPE) and droplet digital PCR (ddPCR) while IE2 and DNA polymerase gene knockdown was determined by real-time PCR. Ganciclovir was deployed as a control to benchmark the efficacy of antiviral activities of respective individual siRNAs.

    RESULTS: There was no significant cytotoxicity encountered for all the combinations of siRNAs on REF cells analyzed by MTT colorimetric assay (P > 0.05). Cytopathic effects (CPE) in cells infected by RCMV ALL-03 had developed significantly less and at much slower rate compared to control group. The expression of targeted genes was downregulated successfully resulted in significant reduction (P 

    MeSH terms: Animals; Antiviral Agents; Colorimetry; Cytomegalovirus Infections; Cytomegalovirus; Cytopathogenic Effect, Viral; DNA; DNA-Directed DNA Polymerase; Pharmaceutical Preparations; Fibroblasts; Flow Cytometry; Health Priorities; Mutation; RNA, Messenger; Transfection; Vaccines; Ganciclovir; Apoptosis; Benchmarking; RNA, Small Interfering; Control Groups; Rats; Gene Knockdown Techniques; Real-Time Polymerase Chain Reaction
  11. Nor WMFSBW, Chung I, Said NABM
    Oncol Res, 2020 Oct 27.
    PMID: 33109304 DOI: 10.3727/096504020X16037933185170
    Breast cancer is the most commonly diagnosed cancer among women and one of the leading causes of cancer mortality worldwide, in which the most severe form happens when it metastasizes to other regions of the body. Metastasis is responsible for most treatment failures in advanced breast cancer. Epithelial-mesenchymal transition (EMT) plays a significant role in promoting metastatic processes in breast cancer. MicroRNAs (miRNAs) are highly conserved endogenous short non-coding RNAs that play a role in regulating a broad range of biological processes, including cancer initiation and development, by functioning as tumor promoters or tumor suppressors. Expression of miR-548m has been found in various types of cancers, but the biological function and molecular mechanisms of miR-548m in cancers have not been fully studied. Here, we demonstrated the role of miR-548m in modulating EMT in the breast cancer cell lines MDA-MB-231 and MCF-7. Expression data for primary breast cancer obtained from NCBI GEO datasets showed that miR-548m expression was downregulated in breast cancer patients compared with healthy group. We hypothesize that miR-548m acts as a tumor suppressor in breast cancer. Overexpression of miR-548m in both cell lines increased E-cadherin expression and decreased the EMT-associated transcription factors SNAI1, SNAI2, ZEB1 and ZEB2, as well as MMP9 expression. Consequently, migration and invasion capabilities of both MDA-MB-231 and MCF-7 cells were significantly inhibited in miR-548m-overexpressing cells. Analysis of 1059 putative target genes of miR-548m revealed common pathways involving both tight junction and the mTOR signaling pathway, which has potential impacts on cell migration and invasion. Furthermore, this study identified aryl hydrocarbon receptor (AHR) as a direct target of miR-548m in breast cancer cells. Taken together, our findings suggest a novel function of miR-548m in reversing the EMT of breast cancer by reducing their migratory and invasive potentials, at least in part via targeting AHR expression.
    MeSH terms: Carcinogens; Cell Movement; Female; Humans; Signal Transduction; Down-Regulation; Antigens, CD; Cadherins; Receptors, Aryl Hydrocarbon; Tight Junctions; Matrix Metalloproteinase 9; MicroRNAs; Basic Helix-Loop-Helix Transcription Factors; Epithelial-Mesenchymal Transition; MCF-7 Cells
  12. Vijayasingham L, Govender V, Witter S, Remme M
    BMJ, 2020 10 27;371:m3384.
    PMID: 33109510 DOI: 10.1136/bmj.m3384
    MeSH terms: Health Equity/economics*; Delivery of Health Care/economics; Female; Health Benefit Plans, Employee/economics; Health Benefit Plans, Employee/organization & administration; Humans; Pregnancy; Global Health; Women's Health*; Universal Coverage/organization & administration*; Healthcare Financing
  13. Ravindran TS, Teerawattananon Y, Tannenbaum C, Vijayasingham L
    BMJ, 2020 10 27;371:m3808.
    PMID: 33109511 DOI: 10.1136/bmj.m3808
    MeSH terms: Drug Industry/legislation & jurisprudence*; Female; Humans; Policy Making*; Product Surveillance, Postmarketing; Patient Selection; Sexism*; Pharmaceutical Research/standards*
  14. Musa M, Ouaret D, Bodmer WF
    Anticancer Res, 2020 Nov;40(11):6063-6073.
    PMID: 33109544 DOI: 10.21873/anticanres.14627
    BACKGROUND/AIM: Interactions between colorectal cancer (CRC) cells and myofibroblasts govern many processes such as cell growth, migration, invasion and differentiation, and contribute to CRC progression. Robust experimental tests are needed to investigate the nature of these interactions for future anticancer studies. The purpose of the study was to design and validate in vitro assays for studying the communication between myofibroblasts and CRC epithelial cell lines.

    MATERIALS AND METHODS: The influence of co-culture of myofibroblasts and CRC cell lines is discussed using various in vitro assays including direct co-culture, transwell assays, Matrigel-based differentiation and cell invasion experiments.

    RESULTS: The results from these in vitro assays clearly demonstrated various aspects of the crosstalk between myofibroblasts and CRC cell lines, which include cell growth, differentiation, migration and invasion.

    CONCLUSION: The reported in vitro assays provide a basis for investigating the factors that control the myofibroblast-epithelial cell interactions in CRC in vivo.

    MeSH terms: Antineoplastic Agents/pharmacology*; Cell Communication/drug effects*; Cell Differentiation/drug effects; Cell Movement/drug effects; Colon/pathology*; Epithelial Cells/drug effects; Humans; Male; Neoplasm Invasiveness; Colorectal Neoplasms/pathology*; Cell Line, Tumor; Cell Proliferation/drug effects; Myofibroblasts/pathology*
  15. Paudyal P, Kulasabanathan K, Cassell JA, Memon A, Simkhada P, Wasti SP
    BMJ Open, 2020 10 26;10(10):e038439.
    PMID: 33109656 DOI: 10.1136/bmjopen-2020-038439
    OBJECTIVE: To summarise the evidence on health and well-being of Nepalese migrant workers in the Gulf Cooperation Council (GCC) countries and Malaysia.

    DESIGN: Systematic review.

    DATA SOURCES: EMBASE, MEDLINE, Scopus and Global Health databases.

    ELIGIBILITY CRITERIA: Studies were eligible if they: (1) included Nepalese migrant workers aged 18 or older working in the GCC countries or Malaysia or returnee migrant workers from these countries; (2) were primary studies that investigated health and well-being status/issues; and (3) were published in English language before 8 May 2020.

    STUDY APPRAISAL: All included studies were critically appraised using Joanna Briggs Institute study specific tools.

    RESULTS: A total of 33 studies were eligible for inclusion; 12 studies were conducted in Qatar, 8 in Malaysia, 9 in Nepal, 2 in Saudi Arabia and 1 each in UAE and Kuwait. In majority of the studies, there was a lack of disaggregated data on demographic characteristics of Nepalese migrant workers. Nearly half of the studies (n=16) scored as 'high' quality and the rest (n=17) as 'moderate' quality. Five key health and well-being related issues were identified in this population: (1) occupational hazards; (2) sexual health; (3) mental health; (4) healthcare access and (5) infectious diseases.

    CONCLUSION: To our knowledge, this is the most comprehensive review of the health and well-being of Nepalese migrant workers in the GCC countries and Malaysia. This review highlights an urgent need to identify and implement policies and practices across Nepal and destination countries to protect the health and well-being of migrant workers.

    MeSH terms: Animals; Cross-Sectional Studies; Health Status*; Humans; Malaysia/epidemiology; Middle East/epidemiology; Nepal/ethnology; Quality of Life; Retrospective Studies
  16. Xiao Hong C, Abd Wahab S, Azman M
    BMJ Case Rep, 2020 Oct 27;13(10).
    PMID: 33109696 DOI: 10.1136/bcr-2020-236484
    Penetrating foreign body in the head and neck can be catastrophic from injury to the constellation of vascular and neural structures in the neck. Early recognition and prompt surgical intervention is imperative to save lives. Herein, we present an unusual case of iatrogenic foreign body-a coiled guidewire embedded in the deep neck space. The complications, radiological investigation and multidisciplinary surgical management are further discussed.
    MeSH terms: Aged; Foreign Bodies/diagnosis*; Foreign Bodies/etiology; Foreign Bodies/surgery; Craniocerebral Trauma/diagnosis*; Craniocerebral Trauma/etiology; Craniocerebral Trauma/surgery; Renal Dialysis/adverse effects*; Humans; Male; Patient Care Team*; Tomography, X-Ray Computed; Wounds, Penetrating/diagnosis*; Wounds, Penetrating/etiology; Wounds, Penetrating/surgery; Neck Injuries/diagnosis*; Neck Injuries/etiology; Neck Injuries/surgery; Device Removal/methods; Catheters/adverse effects*; Computed Tomography Angiography
  17. Serebruany V, Tanguay JF, Benavides MA, Cabrera-Fuentes H, Eisert W, Kim MH, et al.
    Am J Ther, 2020 10 29;27(6):e563-e572.
    PMID: 33109913 DOI: 10.1097/MJT.0000000000001286
    BACKGROUND: Excess vascular deaths in the PLATO trial comparing ticagrelor to clopidogrel have been repeatedly challenged by the Food and Drug Administration (FDA) reviewers and academia. Based on the Freedom of Information Act, BuzzFeed won a court order and shared with us the complete list of reported deaths for the ticagrelor FDA New Drug Application (NDA) 22-433. This dataset was matched against local patient-level records from PLATO sites monitored by the sponsor.

    STUDY QUESTION: Whether FDA death data in the PLATO trial matched the local site records.

    STUDY DESIGN: The NDA spreadsheet contains 938 precisely detailed PLATO deaths. We obtained and validated local evidence for 52 deaths among 861 PLATO patients from 14 enrolling sites in 8 countries and matched those with the official NDA dataset submitted to the FDA.

    MEASURES AND OUTCOMES: Existence, precise time, and primary cause of deaths in PLATO.

    RESULTS: Discrepant to the NDA document, sites confirmed 2 extra unreported deaths (Poland and Korea) and failed to confirm 4 deaths (Malaysia). Of the remaining 46 deaths, dates were reported correctly for 42 patients, earlier (2 clopidogrel), or later (2 ticagrelor) than the actual occurrence of death. In 12 clopidogrel patients, cause of death was changed to "vascular," whereas 6 NDA ticagrelor "nonvascular" or "unknown" deaths were site-reported as of "vascular" origin. Sudden death was incorrectly reported in 4 clopidogrel patients, but omitted in 4 ticagrelor patients directly affecting the primary efficacy PLATO endpoint.

    CONCLUSIONS: Many deaths were inaccurately reported in PLATO favoring ticagrelor. The full extent of mortality misreporting is currently unclear, while especially worrisome is a mismatch in identifying primary death cause. Because all PLATO events are kept in the cloud electronic Medidata Rave capture system, securing the database content, examining the dataset changes or/and repeated entries, identifying potential interference origin, and assessing full magnitude of the problem are warranted.

    MeSH terms: Data Accuracy*; Cause of Death*; Humans; Platelet Aggregation Inhibitors/administration & dosage*; Platelet Aggregation Inhibitors/adverse effects; United States; United States Food and Drug Administration/legislation & jurisprudence; United States Food and Drug Administration/standards; Randomized Controlled Trials as Topic; Treatment Outcome; Drug Approval; Clinical Trials, Phase III as Topic; Acute Coronary Syndrome/complications; Acute Coronary Syndrome/drug therapy; Acute Coronary Syndrome/mortality*; Datasets as Topic
  18. Boo SY, Tan SW, Alitheen NB, Ho CL, Omar AR, Yeap SK
    Sci Rep, 2020 10 27;10(1):18348.
    PMID: 33110122 DOI: 10.1038/s41598-020-75340-x
    The infectious bursal disease (IBD) is an acute immunosuppressive viral disease that significantly affects the economics of the poultry industry. The IBD virus (IBDV) was known to infect B lymphocytes and activate macrophage and T lymphocytes, but there are limited studies on the impact of IBDV infection on chicken intraepithelial lymphocyte natural killer (IEL-NK) cells. This study employed an mRNA sequencing approach to investigate the early regulation of gene expression patterns in chicken IEL-NK cells after infection with very virulent IBDV strain UPM0081. A total of 12,141 genes were expressed in uninfected chicken IEL-NK cells, and most of the genes with high expression were involved in the metabolic pathway, whereas most of the low expressed genes were involved in the cytokine-cytokine receptor pathway. A total of 1,266 genes were differentially expressed (DE) at 3 day-post-infection (dpi), and these DE genes were involved in inflammation, antiviral response and interferon stimulation. The innate immune response was activated as several genes involved in inflammation, antiviral response and recruitment of NK cells to the infected area were up-regulated. This is the first study to examine the whole transcriptome profile of chicken NK cells towards IBDV infection and provides better insight into the early immune response of chicken NK cells.
    MeSH terms: Animals; Chickens/immunology; Chickens/metabolism; Chickens/virology*; Interferons/metabolism; Killer Cells, Natural/metabolism*; Poultry Diseases/immunology; Poultry Diseases/metabolism; Poultry Diseases/virology*; Gene Expression Regulation, Viral; Cytokines/metabolism; Sequence Analysis, RNA/veterinary; Birnaviridae Infections/immunology; Birnaviridae Infections/metabolism; Birnaviridae Infections/veterinary*; Birnaviridae Infections/virology; Chemokines/metabolism; Viral Load; Gene Expression Profiling/veterinary; Metabolic Networks and Pathways; Transcriptome
  19. Rajendran P, Bhat S, Anand M
    Contemp Clin Dent, 2020 08 07;11(2):190-194.
    PMID: 33110336 DOI: 10.4103/ccd.ccd_354_19
    An unavoidable consequence of periodontal flap procedure is gingival recession (GR). Achieving both pocket depth reduction and GR coverage remains a challenge to periodontists. The present case report provides a new innovative technique that will enable all clinicians to achieve pocket depth reduction as well as recession coverage in esthetic zone. The clinical parameters that were assessed at baseline, 1 month, 3 months, and 6 months are probing depth (PD), clinical attachment level (CAL), height of GR (HGR), and gingival biotype. The patient reported with a faulty post and core with crown in relation to maxillary right central incisor with a PD of 8 mm and HGR of 2.5 mm. Following replacement of the crown with respect to the tooth, semilunar incision was made and flap was reflected to visualize the underlying bone. This technique does not involve the interdental papilla at the same time allows the coronal advancement of the flap. A chorion membrane was placed to accelerate the healing as well to provide stable clinical outcome. The patient was evaluated at 10 days, 1 month, 3 months, and 6 months. There was a considerable reduction in PD, GR, and thus gain in CAL. The results remained stable over a period of 6 months.
    MeSH terms: Chorion; Dentists; Esthetics; Gingiva; Gingival Recession; Humans; Incisor; Surgical Flaps; Reconstructive Surgical Procedures; Patient Reported Outcome Measures
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