A Role of Glutathione-Encoding Gene (gshA) in Oxidative Stress and Antibiotic Susceptibility in Multidrug Resistant Pseudomonas aeruginosa: A Possible Drug Target

Background: Pseudomonas aeruginosa is a major causative agent of hospital- and community-acquired infections. Antibacterial treatment of the infections is often difficult due to presence of antibiotic resistant P. aeruginosa. A number of intrinsic and acquired antibiotic resistance mechanisms reported in P. aeruginosa. Recently, scavenging intracellular reactive oxygen species (ROS) has suggested as an intrinsic antibiotic resistance mechanism to all bacterial species since antibiotics induce oxidative stress in the bacterial species. However, this intrinsic resistance mechanism is currently controversial and further clarification requires. Glutathione is a sulfuhydryl (-SH)-containing tri-peptide intracellular antioxidant and serves as a scavenger of the intracellular ROS. Aim: In this study, a mutant P. aeruginosa knocked-out a gene (gshA) encoding glutathione synthetase, a gshA-complemented mutant P. aeruginosa, and their parental wild type (MPAO1) used to understand the role of glutathione in the neutralization of oxidative stress (H2O2) and antibiotic susceptibility. Approaches and Results: Bacterial killing assays showed that the mutant strain (gshA::Tn-Tc) was completely killed at 0.005% of H2O2 while the gshA-complemented and their parental strains were both completely killed at 0.01% of H2O2. Antibiotic susceptibility testing showed that the mutant strain was at least 2-fold more susceptible to all tested antibiotics than that of its parental strain. The gshA-complemented strain fully restored the susceptibility to the same antibiotics as the same levels of the parental strain. Conclusions and Discussion: The results indicate that i) glutathione is associated with neutralization of oxidative stress, ii) antibiotics induce the oxidative stress, and iii) the antibiotic-induced oxidative stress in the mutant strain may have more ROS than its parental strain which results in the increased-susceptibility to antibiotics. Overall, the results suggest that glutathione is one of the intrinsic antibiotic resistance mechanisms and may be a possible drug target to treat the untreatable multidrug resistant P. aeruginosa

Economic impact of COVID-19 on community pharmacy

The onset of COVID-19 has harmed community pharmacy. As a result, the cur-rent study sought to investigate how the coronavirus disease affected community pharmacies from an economic perspective. Short interviews were con-ducted with 158 community pharmacies located in Riyadh, Saudi Arabia. The findings showed that most of the community pharmacies incurred losses of over 10% as a result of the COVID-19 pandemic during its first month in Saudi Arabia. Specifically, the findings revealed that 19.6% of the pharmacies had a 0.1-2% profit during the first month,1.9% had 10%+ profit, while 13.9% expe-rienced a drop in profits. According to the findings, 41.8% (n = 66) of the pharmacists were not sure what they dispensed during the first month of COVID 19. However, almost one out of every five pharmacies (n = 31, 19.6%) accepted that they mostly dispensed antipyretic, vitamins, face mask and sanitisers. It could take many years from now until researchers can understand and mea-sure the coronavirus disease as required. Based on these outcomes and possi-bilities, the study recommends that the Saudi Arabia Ministry of Health inter-vene to enlighten the public on appropriate health practices. Besides, the Ministry of Health may consider engaging with policymakers in developing finan-cial policies that protect community pharmacies and the private sector from potential losses. Moreover, the Ministry of Health may expand the role of community pharmacies to allow them to offer home care services

Cardea: An Open Automated Machine Learning Framework for Electronic Health Records

An estimated 180 papers focusing on deep learning and EHR were published between 2010 and 2018. Despite the common workflow structure appearing in these publications, no trusted and verified software framework exists, forcing researchers to arduously repeat previous work. In this paper, we propose Cardea, an extensible open-source automated machine learning framework encapsulating common prediction problems in the health domain and allows users to build predictive models with their own data. This system relies on two components: Fast Healthcare Interoperability Resources (FHIR) -- a standardized data structure for electronic health systems -- and several AUTOML frameworks for automated feature engineering, model selection, and tuning. We augment these components with an adaptive data assembler and comprehensive data- and model- auditing capabilities. We demonstrate our framework via 5 prediction tasks on MIMIC-III and Kaggle datasets, which highlight Cardea's human competitiveness, flexibility in problem definition, extensive feature generation capability, adaptable automatic data assembler, and its usability

Design of dual band microstrip patch antenna using metamaterial

Metamaterial has received great attention due to their novel electromagnetic properties. It consists of artificial metallic structures with negative permittivity (ɛ) and permeability (µ). The average cell size of metamaterial must be less than a quarter of wavelength, hence, size reduction for the metamaterial antenna is possible. In addition, metamaterial can be used to enhance the low gain and efficiency in conventional patch antenna, which is important in wireless communication. In this paper, dual band microstrip patch antenna design using metamaterial for mobile GSM and WiMax application is introduced. The antenna structure consists of microstrip feed line connected to a rectangular patch. An array of five split ring resonators (SRRs) unit cells is inserted under the patch. The presented antenna resonates at 1.8 GHz for mobile GSM and 2.4 GHz for WIMAX applications. The return loss in the FR4 antenna at 1.8 GHz is -22.5 dB. Using metamaterial the return loss has improved to -25 dB at 2.4 GHz and -23.5 dB at 1.8 GHz. A conventional microstrip patch antenna using pair of slots is also designed which resonates at 1.8 GHz and 2.4 GHz. The return loss at 1.8 GHz and 2.4 GHz were -12.1 dB and -21.8 dB respectively. The metamaterial antenna achieved results with major size reduction of 45%, better bandwidth and better returns loss if it is compared to the pair of slots antenna. The software used to design, simulate and optimize is CST microwave studio

European Position Paper on Rhinosinusitis and Nasal Polyps 2020

The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 is the update of similar evidence based position papers published in 2005 and 2007 and 2012. The core objective of the EPOS2020 guideline is to provide revised, up-to-date and clear evidence-based recommendations and integrated care pathways in ARS and CRS. EPOS2020 provides an update on the literature published and studies undertaken in the eight years since the EPOS2012 position paper was published and addresses areas not extensively covered in EPOS2012 such as paediatric CRS and sinus surgery. EPOS2020 also involves new stakeholders, including pharmacists and patients, and addresses new target users who have become more involved in the management and treatment of rhinosinusitis since the publication of the last EPOS document, including pharmacists, nurses, specialised care givers and indeed patients themselves, who employ increasing self-management of their condition using over the counter treatments. The document provides suggestions for future research in this area and offers updated guidance for definitions and outcome measurements in research in different settings. EPOS2020 contains chapters on definitions and classification where we have defined a large number of terms and indicated preferred terms. A new classification of CRS into primary and secondary CRS and further division into localized and diffuse disease, based on anatomic distribution is proposed. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, allergic rhinitis, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. All available evidence for the management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is systematically reviewed and integrated care pathways based on the evidence are proposed. Despite considerable increases in the amount of quality publications in recent years, a large number of practical clinical questions remain. It was agreed that the best way to address these was to conduct a Delphi exercise. The results have been integrated into the respective sections. Last but not least, advice for patients and pharmacists and a new list of research needs are included.Peer reviewe

T cell phenotypes in COVID-19 - a living review

COVID-19 is characterized by profound lymphopenia in the peripheral blood, and the remaining T cells display altered phenotypes, characterized by a spectrum of activation and exhaustion. However, antigen-specific T cell responses are emerging as a crucial mechanism for both clearance of the virus and as the most likely route to long-lasting immune memory that would protect against re-infection. Therefore, T cell responses are also of considerable interest in vaccine development. Furthermore, persistent alterations in T cell subset composition and function post-infection have important implications for patients’ long-term immune function. In this review, we examine T cell phenotypes, including those of innate T cells, in both peripheral blood and lungs, and consider how key markers of activation and exhaustion correlate with, and may be able to predict, disease severity. We focus on SARS-CoV-2-specific T cells to elucidate markers that may indicate formation of antigen-specific T cell memory. We also examine peripheral T cell phenotypes in recovery and the likelihood of long-lasting immune disruption. Finally, we discuss T cell phenotypes in the lung as important drivers of both virus clearance and tissue damage. As our knowledge of the adaptive immune response to COVID-19 rapidly evolves, it has become clear that while some areas of the T cell response have been investigated in some detail, others, such as the T cell response in children remain largely unexplored. Therefore, this review will also highlight areas where T cell phenotypes require urgent characterisation

The role and uses of antibodies in COVID-19 infections: a living review

Coronavirus disease 2019 has generated a rapidly evolving field of research, with the global scientific community striving for solutions to the current pandemic. Characterizing humoral responses towards SARS-CoV-2, as well as closely related strains, will help determine whether antibodies are central to infection control, and aid the design of therapeutics and vaccine candidates. This review outlines the major aspects of SARS-CoV-2-specific antibody research to date, with a focus on the various prophylactic and therapeutic uses of antibodies to alleviate disease in addition to the potential of cross-reactive therapies and the implications of long-term immunity

Multi-OMICS analyses unveil STAT1 as a potential modifier gene in mevalonate kinase deficiency

International audienceObjectives The objective of the present study was to explain why two siblings carrying both the same homozygous pathogenic mutation for the autoinflammatory disease hyper IgD syndrome, show opposite phenotypes, that is, the first being asymptomatic, the second presenting all classical characteristics of the disease.Methods Where single omics (mainly exome) analysis fails to identify culprit genes/mutations in human complex diseases, multiomics analyses may provide solutions, although this has been seldom used in a clinical setting. Here we combine exome, transcriptome and proteome analyses to decipher at a molecular level, the phenotypic differences between the two siblings.Results This multiomics approach led to the identification of a single gene—STAT1—which harboured a rare missense variant and showed a significant overexpression of both mRNA and protein in the symptomatic versus the asymptomatic sister. This variant was shown to be of gain of function nature, involved in an increased activation of the Janus kinase/signal transducer and activator of transcription signalling (JAK/STAT) pathway, known to play a critical role in inflammatory diseases and for which specific biotherapies presently exist. Pathway analyses based on information from differentially expressed transcripts and proteins confirmed the central role of STAT1 in the proposed regulatory network leading to an increased inflammatory phenotype in the symptomatic sibling.Conclusions This study demonstrates the power of a multiomics approach to uncover potential clinically actionable targets for a personalised therapy. In more general terms, we provide a proteogenomics analysis pipeline that takes advantage of subject-specific genomic and transcriptomic information to improve protein identification and hence advance individualised medicine.This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/