A Comprehensive Study of Historical Detection Data for Pathogen Isolates from U.S. Cattle.

Foodborne pathogens pose substantial health hazards and result in considerable economic losses in the U.S. Fortunately, the National Center for Biotechnology Information Pathogen Detection Isolates Browser (NPDIB) provides valuable access to antimicrobial resistance (AMR) genes and antimicrobial assay data. This study aimed to conduct the first comprehensive investigation of AMR genes in pathogens isolated from U.S. cattle over the past decade, driven by the urgent need to address the dangers of AMR specifically originating in pathogens isolated from U.S. cattle. In this study, around 28,000 pathogen isolate samples were extracted from the NPDIB and then analyzed using multivariate statistical methods, mainly principal component analysis (PCA) and hierarchical clustering (H-clustering). These approaches were necessary due to the high dimensions of the raw data. Specifically, PCA was utilized to reduce the dimensions of the data, converting it to a two-dimensional space, and H-clustering was used to better identify the differences among data points. The findings from this work highlighted Salmonella enterica and Escherichia coli as the predominant pathogens among the isolates, with E. coli being the more concerning pathogen due to its increasing prevalence in recent years. Moreover, tetracycline was observed as the most commonly resistant antimicrobial, with the resistance genes mdsA, mdsB, mdtM, blaEC, and acrF being the most prevalent in pathogen isolates from U.S. cattle. The occurrence of mdtM, blaEC, acrF, and glpT_E448k showed an increase in pathogens isolated from U.S. cattle in recent years. Furthermore, based on the data collected for the locations of AMR cases, Texas, California, and Nebraska were the major areas carrying major AMR genes or antimicrobials with detected resistance. The results from this study provide potential directions for targeted interventions to mitigate pathogens' antimicrobial resistance in U.S. cattle.

Free lung desmosine: a potential biomarker for elastic fiber injury in pulmonary emphysema.

INTRODUCTION: Desmosine and isodesmosine (DID) are biomarkers for elastic fibre damage in pulmonary emphysema. However, current methods for measuring lung DID involve tissue hydrolysis and lack specificity for those fibres undergoing breakdown. To address this limitation, free (nonpeptide-bound) DID content in unhydrolyzed tissues was evaluated as a more accurate biomarker in an animal model of pulmonary emphysema. METHODS: Hamsters were treated with either cigarette smoke and lipopolysaccharide (LPS), room air and LPS, or room air alone (controls). Free DID levels in fresh and formalin-fixed lungs were measured by LC-MS/MS and correlated with the mean linear intercept (MLI) measure of airspace size. RESULTS: There was no significant difference in free DID between fresh and formalin-fixed lungs. Animals treated with smoke and LPS had significantly higher levels of free DID than the LPS only group (359 vs. 93.1 ng/g wet lung, respectively; p = 0.0012) and room air controls (undetectable levels; p = 0.0002). There was a significant positive correlation between free DID and MLI (p < 0.0001). CONCLUSIONS: The results support the hypothesis that free lung DID is a sensitive indicator of alveolar wall injury that may be used to study the development of pulmonary emphysema in both animal models and post-mortem human lung tissue.

The Proinflammatory Activity of Structurally Altered Elastic Fibers.

The mechanisms responsible for the increased loss of pulmonary function following acute lung inflammation in chronic obstructive pulmonary disease remain poorly understood. To investigate this process, our laboratory developed a hamster model that uses a single intratracheal instillation of LPS to superimpose an inflammatory response on lungs treated with intratracheal elastase 1 week earlier. Parameters measured at 2 days after LPS included total leukocyte content and percent neutrophils in BAL fluid (BALF), and BALF levels of both total and peptide-free elastin-specific crosslinks, desmosine and isodesmosine (DID). Airspace enlargement, measured by the mean linear intercept method, and relative interstitial elastic fiber surface area were determined at 1 week after LPS. Compared with animals only treated with elastase, those receiving elastase/LPS showed statistically significant increases in mean linear intercept (156.2 vs. 85.5 µm), BALF leukocytes (187 vs. 37.3 × 104 cells), neutrophils (39% vs. 3.4%), and free DID (182% vs. 97% of controls), which exceeded the sum of the individual effects of the two agents. Despite increased elastin breakdown, the elastase/LPS group had significantly greater elastic fiber surface area than controls (49% vs. 26%) owing to fragmentation and splaying of the fibers. Additional experiments showed that the combination of elastin peptides and LPS significantly enhanced their separate effects on BALF neutrophils and BALF DID in vivo and leukocyte chemotaxis in vitro. The results suggest that structural changes in elastic fibers have proinflammatory activity and may contribute to the decline in pulmonary function related to chronic obstructive pulmonary disease exacerbations.

Techniques Used to Determine Extreme Wave Heights from the NESS Data Set.

The objective of the present paper is to explore the application of different extreme value procedures to a selected grid point in the NESS (North European Storm Study) data set. For the purpose of the present benchmark study, each of the participants was invited to submit estimates of a significant wave height with a high return period at a given grid point in the North Sea, together with a detailed description and a rationale of the approach used in deriving extreme wave heights. Submissions from five industry groups were received, compared, and benchmarked against one another. This analysis leads to a number of conclusions regarding the actual use and misuse of extreme value techniques in the fields of engineering and oceanography.