Summary
Enteropathogenic and enterohaemorrhagic Escherichia coli (EPEC and EHEC) are food‐borne pathogens that cause severe diarrhoeal disease in humans. Citrobacter rodentium is a related mouse pathogen that serves as a small animal model for EPEC and EHEC infections. EPEC, EHEC and C. rodentium translocate bacterial virulence proteins directly into host cells via a type III secretion system (T3SS). Non‐LEE‐encoded effector A (NleA) is a T3SS effector that is common to EPEC, EHEC and C. rodentium and is required for bacterial virulence. NleA localizes to the host cell secretory pathway and inhibits vesicle trafficking by interacting with the Sec24 subunit of mammalian coatamer protein II complex (COPII). Mammalian cells express four paralogues of Sec24 (Sec24A–D), which mediate selection of cargo proteins for transport and possess distinct, but overlapping cargo specificities. Here, we show that NleA binds Sec24A–D with two distinct mechanisms. An NleA protein variant with greatly diminished interaction with all Sec24 paralogues does not properly localize, does not inhibit COPII‐mediated vesicle budding, and does not confer virulence in the mouse infection model. Together, this work provides strong evidence that the interaction and inhibition of COPII by NleA is an important aspect of EPEC‐ and EHEC‐mediated disease.
Our observations suggest that higher Hb levels on the day of PBPC collection may be a marker of reduced toxicity associated with HSCT and increased vascular progenitors in PBPC collections. Further, baseline anemia before transplant may reflect an unfavorable hematopoietic microenvironment that leads to increased RBC transfusion requirements.
Objectives
The primary objective of the study was to evaluate patients’ attitudes toward the postponement of their scheduled procedures for pelvic floor disorders (PFD) because of the COVID-19 pandemic. Secondary objectives were to identify patients who were upset with the postponement of their PFD procedures and to identify factors that are associated with being upset because of the delay in care.
Methods
This was a cross-sectional, survey-based study of women from a single urban, academic practice using a novel questionnaire. The study cohort included women whose PFD surgeries or office procedures were postponed between March 17 and April 30, 2020.
Results
Ninety-eight women had surgeries postponed; 68 (70%) responded to our questionnaire. Nearly half of the respondents (32/68, 47.1%) were upset about their procedures being postponed. Upset patients reported a greater impact of PFD symptoms on their mood than those who were not upset (P=0.002). Those who were upset were also more likely to report feelings of isolation (P=0.006), fear that their PFD would worsen because of delayed care (P < 0.001), and anxiety over surgery postponement (P < 0.001) than those who were not upset about the delays. When controlling for anxiety, social isolation, and impact of PFD symptom, anxiety (adjusted odds ratio = 15.7; 95% confidence interval = 3.7–66.6) and feeling of isolation (adjusted odds ratio = 9.7; 95% confidence interval = 1.5–63.7) remained associated with increased odds of being upset because of procedure delays.
Conclusions
Half of women whose pelvic reconstructive procedures were postponed because of the COVID-19 pandemic were upset because of the delay in care, especially those who are emotionally and socially vulnerable during the COVID-19 pandemic.
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