Cortezlehmann7802

Pneumonic plague, caused by Yersinia pestis, is a rapidly progressing bronchopneumonia involving focal bacterial growth, neutrophilic congestion, and alveolar necrosis. Within a short time after inhalation of Y. pestis, inflammatory cytokines are expressed via the Toll/interleukin-1 (IL-1) adaptor myeloid differentiation primary response 88 (MyD88), which facilitates the primary lung infection. We previously showed that Y. selleck chemicals llc pestis lacking the 102-kb chromosomal pigmentation locus (pgm) is unable to cause inflammatory damage in the lungs, whereas the wild-type (WT) strain induces the toxic MyD88 pulmonary inflammatory response. In this work, we investigated the involvement of the pgm in skewing the inflammatory response during pneumonic plague. We show that the early MyD88-dependent and -independent cytokine responses to pgm- Y. pestis infection of the lungs are similar yet distinct from those that occur during pgm+ infection. Furthermore, we found that MyD88 was necessary to prevent growth of the iron-starved pgm- Y. pestis despite the presence of iron chelators lactoferrin and transferrin. However, while this induced neutrophil recruitment, there was no hyperinflammatory response, and pulmonary disease was mild without MyD88. In contrast, growth in blood and tissues progressed rapidly in the absence of MyD88, due to an almost total loss of serum interferon gamma (IFN-γ). We further show that the expression of MyD88 by myeloid cells is important to control bacteremia but not the primary lung infection. The combined data indicate distinct roles for myeloid and nonmyeloid MyD88 and suggest that expression of the pgm is necessary to skew the inflammatory response in the lungs to cause pneumonic plague.Yersinia pestis is a highly virulent pathogen and the causative agent of bubonic, septicemic, and pneumonic plague. Primary pneumonic plague caused by inhalation of respiratory droplets contaminated with Y. pestis is nearly 100% lethal within 4 to 7 days without antibiotic intervention. Pneumonic plague progresses in two phases, beginning with extensive bacterial replication in the lung with minimal host responsiveness, followed by the abrupt onset of a lethal proinflammatory response. The precise mechanisms by which Y. pestis is able to colonize the lung and survive two very distinct disease phases remain largely unknown. To date, a few bacterial virulence factors, including the Ysc type 3 secretion system, are known to contribute to the pathogenesis of primary pneumonic plague. The bacterial GTPase BipA has been shown to regulate expression of virulence factors in a number of Gram-negative bacteria, including Pseudomonas aeruginosa, Escherichia coli, and Salmonella enterica serovar Typhi. However, the role of BipA in Y. pestis has yet to be investigated. Here, we show that BipA is a Y. pestis virulence factor that promotes defense against early neutrophil-mediated bacterial killing in the lung. This work identifies a novel Y. pestis virulence factor and highlights the importance of early bacterial/neutrophil interactions in the lung during primary pneumonic plague.With the onset of the COVID-19 pandemic, hospitals nationwide have been presented with a number of potential challenges, including possible increased volume of patient attendances, acuity of illness and potential for patients to present with an infection that requires isolation. At the Bristol Royal Infirmary, an innercity teaching hospital that manages patients aged 16 and over, we present our response to these projected changes in ED attendances, with the initiation of the incident triage area (ITA). The ITA is a triage station situated outside the ED and staffed by a senior clinician, healthcare assistant and patient flow coordinator. It receives patients presenting as walk-in or via ambulance, and on their arrival aims to establish their risk of COVID-19 and their acuity of illness. This allows for triage of the patient to one of the four zones of the hospital, as well as providing clinical guidance on any initial interventions that patients may require. The benefits of the ITA are that it enables an early senior review of patients to establish their acuity of illness and initiate time-critical medical intervention as required. In addition, patients are immediately cohorted to zones within the hospital based on their infection risk, thereby reducing patient footfall throughout the hospital. Its aim is to reduce the spread of infection, by efficiently triaging and streaming patients who present to the hospital prior to them entering clinical areas, while maintaining patient safety and flow through the ED and initiating rapid management of acutely unwell patients.Successful retrieval of an item from visual working memory (VWM) often requires an associated representation of the trial-unique context in which that item was presented. In experiment 1, fMRI of 16 male and female humans replicated a previous dissociation of the effects of manipulating memory load in comparison to the effects of manipulating context binding, by comparing VWM for one oriented line versus for three lines individuated by their location versus for three "heterogeneous" items drawn from different categories (orientation, color, and luminance) delay-period fMRI signal in frontal cortex and intraparietal sulcus (IPS) was sensitive to stimulus homogeneity rather than to memory load per se. Additionally, inspection of behavioral performance revealed a broad range of individual differences in the probability of responses to nontargets (also known as "swap errors"), and a post hoc comparison of high swap-error versus low swap-error groups generated several intriguing results at recall, high swap-error subjects were seen to represent both the orientation and the location of the probed item less strongly, and with less differentiation from nonprobed items, and delay-period signal in IPS predicted behavioral and neural correlates of context binding at recall. In experiment 2, which was a preregistered replication, the 27 male and female humans were grouped into low and high swap-error groups by median split, and the results were broadly consistent with experiment 1. These results present a neural correlate of swap errors, and suggest that delay-period activity of the IPS may be more important for the operation of context binding than for representation per se of stimulus identity.