The interaction between IgE-Fc (Fc⑀) and its high affinity receptor Fc⑀RI on the surface of mast cells and basophils is a key event in allergen-induced allergic inflammation. Recently, several therapeutic strategies have been developed based on this interaction, and some include Fc⑀-containing moieties. Unlike well characterized IgG therapeutics, the stability and folding properties of IgE are not well understood. Here, we present comparative biophysical analyses of the pH stability and thermostability of Fc⑀ and IgG1-Fc (Fc␥). Fc⑀ was found to be significantly less stable than Fc␥ under all pH and NaCl conditions tested. Additionally, the C⑀3C⑀4 domains of Fc⑀ were shown to become intrinsically unfolded at pH values below 5.0. The interaction between Fc⑀ and an Fc␥-Fc⑀RI␣ fusion protein was studied between pH 4.5 and 7.4 using circular dichroism and a combination of differential scanning calorimetry and isothermal titration calorimetry. Under neutral pH conditions, the apparent affinity of Fc⑀ for the dimeric fusion protein was extremely high compared with published values for the monomeric receptor (K D < 10 ؊12 M). Titration to pH 6.0 did not significantly change the binding affinity, and titration to pH 5.5 only modestly attenuated affinity. At pH values below 5.0, the receptor binding domains of Fc⑀ unfolded, and interaction of Fc⑀ with the Fc␥-Fc⑀RI␣ fusion protein was abrogated. The unusual pH sensitivity of Fc⑀ may play a role in antigen-dependent regulation of receptor-bound, non-circulating IgE.
Potatoes are rich in phenolic compounds which have been reported to impact starch digestion and intestinal glucose transport in model systems through phenolic–starch interactions.
Background: Hospital performance quality assessments inform patients, providers, payers, and purchasers in making healthcare decisions. These assessments have been developed by government, private and non-profit organizations, and academic institutions. Given the number and variability in available assessments, a knowledge gap exists regarding what assessments are available and how each assessment measures quality to identify top performing hospitals. This study aims to: (a) comprehensively identify current hospital performance assessments, (b) compare quality measures from each methodology in the context of the Institute of Medicine's (IOM) six domains of STEEEP (safety, timeliness, effectiveness, efficiency, equitable, and patient-centeredness), and (c) formulate policy recommendations that improve value-based, patient-centered care to address identified gaps. Methods: A scoping review was conducted using a systematic search of MEDLINE and the grey literature along with handsearching to identify studies that provide assessments of US-based hospital performance whereby the study cohort examined a minimum of 250 hospitals in the last two years (2017-2019). Results: From 3058 unique records screened, 19 hospital performance assessments met inclusion criteria. Methodologies were analyzed across each assessment and measures were mapped to STEEEP. While safety and effectiveness were commonly identified measures across assessments, efficiency, and patient-centeredness were less frequently represented. Equity measures were also limited to risk-and severity-adjustment methods to balance patient characteristics across populations, rather than stand-alone indicators to evaluate health disparities that may contribute to community-level inequities. Conclusions: To further improve health and healthcare value-based decision-making, there remains a need for methodological transparency across assessments and the standardization of consensus-based measures that reflect the IOM's quality framework. Additionally, a large opportunity exists to improve the assessment of health equity in the communities that hospitals serve.
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