T he coronavirus disease 2019 (COVID-19) pandemic is the largest public health crisis in over a century. 1 As of Jan. 15, 2021, COVID-19 has resulted in over 113 million infections and almost 2.5 million deaths globally. 2 The global crude mortality rate among patients diagnosed with COVID-19 is about 3%, but some countries have reported rates that are up to 3 times higher. 2,3 Factors explaining these variations include population differences in demographics, health status and socioeconomics, as well as system factors such as the availability of testing, pandemic preparedness and response, with others yet to be uncovered. 4,5 There is an urgent need for high-quality, populationlevel data to understand modifiable risks for disease severity
The PmrAB two-component system of enterobacteria regulates a number of genes whose protein products modify lipopolysaccharide (LPS). The LPS is modified during transport to the bacterial outer membrane (OM). A subset of PmrAB-mediated LPS modifications consists of the addition of phosphoethanolamine (pEtN) to lipid A by PmrC and to the core by CptA. In Salmonella enterica, pEtN modifications have been associated with resistance to polymyxin B and to excess iron. To investigate putative functions of pEtN modifications in Citrobacter rodentium, ⌬pmrAB, ⌬pmrC, ⌬cptA, and ⌬pmrC ⌬cptA deletion mutants were constructed. Compared to the wild type, most mutant strains were found to be more susceptible to antibiotics that must diffuse across the LPS layer of the OM. All mutant strains also showed increased influx rates of ethidium dye across their OM, suggesting that PmrAB-regulated pEtN modifications affect OM permeability. This was confirmed by increased partitioning of the fluorescent dye 1-N-phenylnaphthylamine (NPN) into the OM phospholipid layer of the mutant strains. In addition, substantial release of periplasmic -lactamase was observed for the ⌬pmrAB and ⌬pmrC ⌬cptA strains, indicating a loss of OM integrity. This study attributes a new role for PmrAB-mediated pEtN LPS modifications in the maintenance of C. rodentium OM integrity.
Background: The rise of free open-access medical education (FOAM) has led to a wide range of online resources in emergency medicine. Canadian physicians have been active contributors to FOAM.Objectives: We aimed to create a virtual community of practice that would serve as a national platform for collaboration, learning, and knowledge dissemination.Methods: CanadiEM was formed in 2016 from the merger of two Canadian websites and a podcast. Using a community-of-practice model, we introduced two training programs to support junior community members in becoming core editorial team members and employed asynchronous Web technologies to facilitate collaboration. We also introduced a coached peer review process and formed strategic alliances that aim to ensure a high quality of publication.Results: CanadiEM has become a portal for readers to access a broad range of FOAM content. The website has published 782 articles. Of these, 71 have undergone a coached peer review process. The website has received over 2.5 million page views from 217 countries, and the associated CRACKCast podcast has been downloaded over 750,000 times.Conclusions: CanadiEM has succeeded in building a national multi-interface dissemination network that fosters collaboration and knowledge sharing in emergency medicine while fostering junior digital scholars. The construction of a community of practice has been facilitated by quality assurance, training programs, and the use of asynchronous Web technologies. Ongoing challenges in sustainability include a volunteer workforce with high turnover.
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