Enterohemorrhagic Escherichia coli (EHEC) O157:H7 is responsible for causing outbreaks of bloody diarrhea and hemolytic-uremic syndrome throughout the world. The locus of enterocyte effacement (LEE) consists of five major operons and is required for the formation of attaching and effacing lesions that disrupt intestinal epithelial microvilli. We have previously reported that expression of EHEC LEE genes is regulated by the luxS quorum-sensing system. The luxS gene in EHEC affects the production of autoinducer 3 (AI-3), which activates the LEE. Epinephrine and norepinephrine also activate the LEE in a manner similar to that of AI-3. Previous studies of quorum-sensing regulation of LEE transcription have thus far been restricted to using reporter systems in an E. coli K-12 background. Here, we examined the kinetics of LEE gene transcription, protein expression, and function of the LEE type III secretion apparatus in wild-type (WT) EHEC and an isogenic luxS mutant. The results revealed that the luxS mutant had diminished transcription from the LEE promoters during the mid-exponential growth phase; decreased protein levels of EscJ, Tir, and EspA; and reduced secretion of EspA and EspB. The luxS mutation also caused a delay in the formation of attaching and effacing lesions on cultured epithelial cells compared to the wild type. Epinephrine enhanced LEE expression in both the WT and the luxS mutant, but the WT still exhibited greater LEE activation. The results suggest a possible synergistic relationship between AI-3 and epinephrine. The combined effects of these two signaling molecules may lead to greater LEE expression and a more efficient infection.
Background Recently, amongst other hemostatic modalities, Hemospray (TC-325) has emerged as an effective method for managing patients with non-variceal upper gastrointestinal bleeding (GIB). We conducted this systematic review and meta-analysis to assess the efficacy of Hemospray in patients with non-variceal upper GIB. Methods Our primary outcomes were clinical and technical success; secondary outcomes were aggregate rebleeding, early rebleeding, delayed rebleeding, refractory bleeding, mortality, and treatment failure. A meta-analysis of proportions was conducted for all reported primary and secondary outcomes. A relative risk meta-analysis was conducted for studies reporting direct comparisons between Hemospray and other hemostatic measures. Results A total of 20 studies with 1280 patients were included in the final analysis. Technical success of Hemospray was seen in 97% of cases (95% confidence interval [CI] 94-98%, I 2 =52.89%) and a significant trend towards increasing technical success was seen during publication years 2011-2019. Clinical success of Hemospray was seen in 91% of cases (95%CI 88-94%, I 2 =47.72%), compared to 87% (95%CI 75-94%, I 2 =0.00%) for other hemostatic measures. The secondary outcomes of aggregate rebleeding, early rebleeding, delayed rebleeding, refractory rebleeding, mortality and treatment failure following the use of Hemospray were seen in 27%, 20%, 9%, 8%, 8%, and 31% of cases, respectively. Conclusion Hemospray is safe, effective and non-inferior to traditional hemostatic measures for the management of non-variceal upper GIB, and can thus be used as an alternative option.
Background: Immunosuppressive therapy is being increasingly used in the management of inflammatory bowel disease (IBD) which comprises of ulcerative colitis (UC) and Crohn's disease (CD). Patients on immunosuppressive therapy are at increased risk of developing opportunistic fungal infections. We conducted this analysis to describe the epidemiology of opportunistic fungal infections in this cohort. Methods: We analyzed the National Inpatient Sample (NIS) database for all subjects with discharge diagnosis of IBD (UC and Crohn's disease) & Fungal infections (Histoplasmosis, Pneumocystosis, Cryptococcosis, Aspergillosis, Blastomycosis, candidiasis, Coccidioidomycosis) as primary or secondary diagnosis via ICD 9 codes during the period from 2002-2014. Results: In UC, the incidence of all fungal infections was more in age above 50 (except for pneumoconiosis) male gender (except Candidiasis) and in Caucasians. In CD, the incidence was more in age above 50 (except Pneumocystosis, Blastomycosis & Coccidioidomycosis), female gender (except Histoplasmosis, Pneumocystosis & Cryptococcosis) and in Caucasians. Histoplasmosis and Blastomycosis were more prevalent in Midwest, Cryptococcosis and Candidiasis in South, Coccidioidomycosis in west in both UC and CD. Age above 50, south region, HIV, Congestive heart failure, underlying malignancies, diabetes mellitus with complications, chronic pulmonary disease, anemia, rheumatoid arthritis, collagen vascular disease, pulmonary circulation disorders, weight loss were significant predictors of fungal infections in IBD. The yearly trend showed a consistent small rise in incidence, and the mortality dropped till 2006 to peak again in 2008 with a subsequent decline.Conclusions: Our study is the first one to describe the basic demographics features and characteristics of opportunistic fungal infections in hospitalized patients with IBD. The yearly incidence of fungal infections did not show a significant rise. The mortality increased between 2006-2008 and a significant difference remains between IBD patients with and without fungal infections. One explanation of rise in mortality but a consistent incidence could be due to the use of biologics that did not increase but compromised the ability of IBD patients to fight opportunistic fungal infections.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.