Despite recent advances in our understanding of the pathogenesis of attaching and effacing (A/E) Escherichia coli infections, the mechanisms by which the host defends against these microbes are ...unclear. The goal of this study was to determine the role of goblet cell-derived Muc2, the major intestinal secretory mucin and primary component of the mucus layer, in host protection against A/E pathogens. To assess the role of Muc2 during A/E bacterial infections, we inoculated Muc2 deficient (Muc2-/-) mice with Citrobacter rodentium, a murine A/E pathogen related to diarrheagenic A/E E. coli. Unlike wildtype (WT) mice, infected Muc2-/- mice exhibited rapid weight loss and suffered up to 90% mortality. Stool plating demonstrated 10-100 fold greater C. rodentium burdens in Muc2-/- vs. WT mice, most of which were found to be loosely adherent to the colonic mucosa. Histology of Muc2-/- mice revealed ulceration in the colon amid focal bacterial microcolonies. Metabolic labeling of secreted mucins in the large intestine demonstrated that mucin secretion was markedly increased in WT mice during infection compared to uninfected controls, suggesting that the host uses increased mucin release to flush pathogens from the mucosal surface. Muc2 also impacted host-commensal interactions during infection, as FISH analysis revealed C. rodentium microcolonies contained numerous commensal microbes, which was not observed in WT mice. Orally administered FITC-Dextran and FISH staining showed significantly worsened intestinal barrier disruption in Muc2-/- vs. WT mice, with overt pathogen and commensal translocation into the Muc2-/- colonic mucosa. Interestingly, commensal depletion enhanced C. rodentium colonization of Muc2-/- mice, although colonic pathology was not significantly altered. In conclusion, Muc2 production is critical for host protection during A/E bacterial infections, by limiting overall pathogen and commensal numbers associated with the colonic mucosal surface. Such actions limit tissue damage and translocation of pathogenic and commensal bacteria across the epithelium.
A growing number of total knee arthroplasty (TKA) patients are candidates for same-day discharge (SDD). Previous research has shown that internet-based remote physical therapy (RPT) can produce ...equivalent outcomes to supervised outpatient physical therapy (OPT) after TKA. We sought to compare outcomes between RPT and OPT in patients undergoing SDD TKA using an electronic remote perioperative management (ERPM) program.
Patients undergoing SDD TKA were enrolled in an ERPM program and randomized to ERPM + RPT or ERPM + OPT. Preoperative and 6-week functional assessments included knee range of motion, timed up and go, and 4-meter gait speed. Numerical Rating Scale pain scores were evaluated preoperatively, at 6 and 12 weeks, and satisfaction was assessed at 6, 12, and 52 weeks postoperatively. Participants completed the Veterans Rand 12 Item Health Survey and Knee Injury and Osteoarthritis Outcome Score preoperatively and at 6, 12, and 52 weeks postoperatively. OPT utilization was collected 90 days postoperatively.
Of 197 initially randomized patients, 76 remained in the ERPM + RPT group and 95 in the ERPM + OPT group after withdrawals and crossovers. Baseline characteristics showed no differences between the 2 groups. No clinically relevant differences were observed in knee range of motion, Numerical Rating Scale pain, patient-reported outcomes, functional assessments, or satisfaction at any follow-up time. Participants in the ERPM + OPT group attended an average of 11.57 physical therapy sessions, incurring a total cost of $462.8 and 133 minutes of travel. Conversely, the ERPM + RPT group experienced no expenses or travel time.
Patients in the ERPM + RPT group had similar outcomes, lower costs, and saved time compared to patients in the ERPM + OPT group after SDD TKA. Further analysis is needed to determine predictive indicators for crossovers.
On the basis of phenotypic identification methods, Aspergillus fumigatus is reported as the most commonly identified aetiological agent of canine sino-nasal aspergillosis (SNA). However, definitive ...identification of Aspergillus spp. using phenotypic features alone is unreliable. The aim of this study was to determine the molecular identities of fungal species causing SNA in dogs. Genomic DNA was extracted from 91 fungal isolates from 90 dogs diagnosed with SNA in Australia, the USA and Belgium, and the ITS1-5.8S-ITS2 ribosomal DNA and partial β-tubulin regions were sequenced. Eighty-eight of 91 (96.7%) isolates were identified as A. fumigatus and 3/91 (3.3%) belonged to Aspergillus section Nigri spp. (Aspergillus tubingensis: 2/91; Aspergillus uvarum: 1/91). These findings confirm that A. fumigatus is the most common aetiological agent of canine SNA. This is the first report to document a pathogenic role for A. tubingensis and A. uvarum in dogs.
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