Endotoxin-induced microvascular lung injury in mice is a commonly used experimental model of the acute respiratory distress syndrome (ARDS). The present paper aimed to characterize this popular model in a comprehensive and systematic fashion. Male C57bl/6 mice (n = 5) were administered an LD55 dose of E. coli endotoxin (15 mg/kg, i.p.), and lungs were harvested at several time points and evaluated for injury as well as for expression of a variety of inflammatory mediators. Endotoxin induced many features characteristic of acute microvascular lung injury. These included early (1-2 h) expression of inflammatory mediators (IL-1alpha, IL-1beta, IL-4, IL-6, IL-10, TNF-alpha, interferon-alpha, interferon gamma, and MCP-1) and leukocyte accumulation in lung tissue (lung myeloperoxidase activity 18.5 +/- 7.8 U/g tissue, P < 0.05), followed by pulmonary edema (lung water content index 17.4% +/- 2.5%, P < 0.05) and mortality. Histopathological evaluation of lung tissue was compatible with these findings. The characterization of this murine model of endotoxin-induced microvascular injury will facilitate its utilization in ARDS research.
Pre-existing cross-reactivity to SARS-CoV-2 may occur in absence of prior viral exposure. However, this has been difficult to quantify at the population level due to a lack of reliably defined seroreactivity thresholds. Using an orthogonal antibody testing approach, we estimated that 0.6% of non-triaged adults from the greater Vancouver area, Canada between May 17 th and June 19 th 2020 showed clear evidence of a prior SARS-CoV-2 infection, after adjusting for false-positive and false-negative test results. Using a highly sensitive multiplex assay and positive/negative thresholds established in infants in whom maternal antibodies have waned, we determine that more than 90% of uninfected adults showed antibody reactivity against the spike, receptor-binding domain (RBD), N-terminal domains (NTD) or the nucleocapsid (N) protein from SARS-CoV-2. This sero-reactivity was evenly distributed across age and sex, correlated with circulating coronaviruses reactivity, and was partially outcompeted by soluble circulating coronaviruses' spike. Using a custom SARS-CoV-2 peptide mapping array, we found that this antibody reactivity broadly mapped to spike, and to conserved non-structural viral proteins. We conclude that most adults display pre-existing antibody cross-reactivity against SARS-CoV-2, which further supports investigation of how this may impact the clinical severity of COVID-19 or SARS-CoV-2 vaccine responses.
This paper proposes a proof-of-concept, low-cost, and easily deployable Bluetooth low energy- (BLE-) based localization system which actively scans and localizes BLE beacons attached to mobile subjects in a room. Using the received signal strength (RSS) of a BLE signal and the uniqueness of BLE hardware addresses, mobile subjects can be identified and localized within the hospital room. The RSS measurement of the BLE signal from a wearable BLE beacon varies with distance to the wall-anchored BLE scanner. In order to understand and demonstrate the practicality of the relationship between RSS of a BLE beacon and the distance of a beacon from a scanner, the first part of the paper presents the analysis of the experiments conducted in a low-noise and nonreflective environment. Based on the analysis conducted in an ideal environment, the second half of the paper proposes a data-driven localization process for pinpointing the movements of the subject within the experimental room. In order to ensure higher accuracy like fingerprinting techniques and handle the increased number of BLE-anchored scanners like geometric techniques, the proposed algorithm was designed to combine the best aspects of these two techniques for better localization. The paper evaluates the effects of the number of BLE wall-mounted scanners and the number of packets on the performance of the proposed algorithm. The proposed algorithm locates the patient within the room with error less than 1.8 m. It also performs better than other classical approaches used in localization.
Background: Quantifying antibody reactivity against multiple SARS-CoV-2 antigens at the population level may help understand individual differences in COVID-19 severity. Pre-existing low antibody cross-reactivity may be particularly prevalent among childcare providers, including pediatric health care workers (HCW) who may be more exposed to circulating coronaviruses. Methods: Cross-sectional study that included adults in the Vancouver area in British Columbia (BC), Canada, between May 17 and June 19, 2020. SARS-CoV-2 seroprevalence was ascertained by measuring total SARS-CoV-2 IgG/M/A antibodies against a recombinant spike (S1) protein, and adjusted for bias due to false-positive and false-negative test results. A novel, high sensitivity multiplex assay was also used to profile IgGs against four SARS-CoV-2 antigens, SARS-CoV and four circulating coronaviruses. Findings: Among 276 participants (71% HCW), three showed evidence of direct viral exposure, yielding an adjusted seroprevalence of 0.60% [95%CI 0% - 2.71%], with no difference between HCW and non-HCW, or between paediatric and adult HCW. Among the remaining 273 unexposed individuals, 7.3% [95%CI 4.5% - 11.1%], 48.7 [95%CI 42.7% - 54.8%] and 82.4% [95%CI 77.4% - 86.7%] showed antibody reactivity against SARS-CoV-2 RBD, N or Spike proteins, respectively. SARS-CoV-2 reactivity did not correlate with age, sex, did not differ between HCW and non-HCW (prevalence: 1.0% vs 1.0%; P=1.00) and between pediatric and adult HCW (prevalence: 0.7% vs 1.6%; P=0.54), and weakly correlated with reactivity to circulating coronaviruses (Spearman rho range: 0.130 to 0.224 for 7 significant out of 16 correlations; false-discovery rate-adjusted for a total of 36 correlations). Interpretation: A substantial proportion of individuals showed low, but detectable antibody reactivity against SARS-CoV-2 antigens in this population despite a low evidence of direct SARS-CoV-2 exposure.
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