Maintenance of Enteral ACE2 Prevents Diabetic Retinopathy in Type 1 Diabetes.

BACKGROUND: We examined components of systemic and intestinal renin-angiotensin system on gut barrier permeability, glucose homeostasis, systemic inflammation, and progression of diabetic retinopathy (DR) in human subjects and mice with type 1 diabetes (T1D). METHODS: T1D individual with (n=18) and without (n=20) DR and controls (n=34) were examined for changes in gut-regulated components of the immune system, gut leakage markers (FABP2 [fatty acid binding protein 2] and peptidoglycan), and Ang II (angiotensin II); Akita mice were orally administered a Lactobacillus paracasei (LP) probiotic expressing humanized ACE2 (angiotensin-converting enzyme 2) protein (LP-ACE2) as either a prevention or an intervention. Akita mice with genetic overexpression of humanAce2 by small intestine epithelial cells (Vil-Cre.hAce2KI-Akita) were similarly examined. After 9 months of T1D, circulatory, enteral, and ocular end points were assessed. RESULTS: T1D subjects exhibit elevations in gut-derived circulating immune cells (ILC1 cells) and higher gut leakage markers, which were positively correlated with plasma Ang II and DR severity. The LP-ACE2 prevention cohort and genetic overexpression of intestinal ACE2 preserved barrier integrity, reduced inflammatory response, improved hyperglycemia, and delayed development of DR. Improvements in glucose homeostasis were due to intestinal MasR activation, resulting in a GSK-3ß (glycogen synthase kinase-3 beta)/c-Myc (cellular myelocytomatosis oncogene)-mediated decrease in intestinal glucose transporter expression. In the LP-ACE2 intervention cohort, gut barrier integrity was improved and DR reversed, but no improvement in hyperglycemia was observed. These data support that the beneficial effects of LP-ACE2 on DR are due to the action of ACE2, not improved glucose homeostasis. CONCLUSIONS: Dysregulated systemic and intestinal renin-angiotensin system was associated with worsening gut barrier permeability, gut-derived immune cell activation, systemic inflammation, and progression of DR in human subjects. In Akita mice, maintaining intestinal ACE2 expression prevented and reversed DR, emphasizing the multifaceted role of the intestinal renin-angiotensin system in diabetes and DR.

Improving surgical patient education materials using informational design with visual elements.

Patient education materials (PEMs) serve as a foundation for educating patients and families across all surgical fields but are often not understandable. The National Institute of Health (NIH) recommends that PEMs be written at a grade 6-7 reading level; however, most current materials exceed that measure.3 Lack of understandable and appropriate surgical PEMs compounds the difficulties that low health literacy patients face with resultant poor surgical outcomes.2,3 The challenge for surgeons is to adequately educate patients pre-operatively and post-operatively on the complexities of surgery. Another challenge is to compact decades of education and training into an easy-to-understand medium for patients. To address this challenge, many physicians have utilized visual aids to improve PEM efficacy. While visual aids are a critical piece of education materials, they must be designed intentionally to be effective. The most important consideration is that the PEM communicates the information clearly to users. With this in mind, we created a framework for productive utilization of visual aids by integrating the C.A.R.P. graphic design technique into an existing surgical PEM to enhance communication and understandability.