Nucleation of fibronectin fibril assembly requires binding between heparin and the 13th type III module of fibronectin.

Fibronectin (FN), a critical component of the extracellular matrix, is assembled into fibrils through a cell-mediated process. Heparan sulfate (HS) binds to the III13 module of FN, and fibroblasts lacking this glycosaminoglycan exhibit reduced FN fibril assembly. To determine if HS depends on III13 to control FN assembly, we deleted both III13 alleles in NIH 3T3 cells using the CRISPR-Cas9 system. ΔIII13 cells assembled fewer FN matrix fibrils and less DOC-insoluble FN matrix than wildtype cells. Little if any mutant FN matrix was assembled when purified ΔIII13 FN was provided to Chinese hamster ovary (CHO) cells, showing that lack of III13 caused the deficiency in assembly by ΔIII13 cells. Addition of heparin promoted the assembly of wildtype FN by CHO cells, but it had no effect on the assembly of ΔIII13 FN. Furthermore, heparin binding stabilized the folded conformation of III13 and prevented it from self-associating with increasing temperature suggesting that stabilization by HS/heparin binding might regulate interactions between III13 and other FN modules. This effect would be particularly important at matrix assembly sites where our data show that ΔIII13 cells require both exogenous wildtype FN and heparin in the culture medium to maximize assembly site formation. Our results show that heparin-promoted growth of fibril nucleation sites is dependent on III13. We conclude that HS/heparin binds to III13 to promote and control the nucleation and development of FN fibrils.

A Quality Improvement Initiative to Improve Pediatric Discharge Medication Safety and Efficiency.

Medication errors are a leading safety concern, especially for families with limited English proficiency and health literacy, and patients discharged on multiple medications with complex schedules. Integration of a multilanguage electronic discharge medication platform may help decrease medication errors. This quality improvement (QI) project's primary aim (process measure) was to increase utilization in the electronic health record (EHR) of the integrated MedActionPlanPro (MAP) for cardiovascular surgery and blood and marrow transplant patients at hospital discharge and for the first clinic follow-up visit to 80% by July 2021. Methods: This QI project occurred between August 2020 and July 2021 on 2 subspecialty pediatric acute care inpatient units and respective outpatient clinics. An interdisciplinary team developed and implemented interventions, including integration of MAP within EHR; the team tracked and analyzed outcomes for discharge medication matching, and efficacy and safety MAP integration occurred with a go-live date of February 1, 2021. Statistical process control charts tracked progress. Results: Following the implementation of the QI interventions, there was an increase from 0% to 73% in the utilization of the integrated MAP in the EHR across the acute care cardiology unit-cardiovascular surgery/blood and marrow transplant units. The average user hours per patient (outcome measure) decreased 70% from the centerline of 0.89 hours during the baseline period to 0.27 hours. In addition, the medication matching between Cerner inpatient and MAP inpatient increased significantly from baseline to postintervention by 25.6% (P < 0.001). Conclusion: MAP integration into the EHR was associated with improved inpatient discharge medication reconciliation safety and provider efficiency.

A Novel Method to Determine Patient Skin Type: The Skin Analyzer.

Measuring skin color for medical research in an objective and nonbiased manner usually requires expensive equipment such as spectrophotometry and requires the subject to be present in person. We present a novel method to measure skin color from photographs using the Skin Analyzer application as a more effective, accessible, and efficient alternative. A desktop application, the Skin Analyzer, was developed to convert skin samples collected from digital images to the L*a*b color space and uses those values to calculate an individual typology angle that correlates to a Fitzpatrick skin type. To assess accuracy in variable lighting, six known colors representing the six Fitzpatrick skin types were printed and photographed in 15 separate locations within the hospital. To account for user variability in sample selection, interrater reliability was calculated with data generated by 13 untrained users testing the app on six subjects. The accuracy of measuring known values, which is the classification accuracy, was calculated to be 80%. Krippendorff alpha test was used to evaluate interrater reliability. The obtained alpha of 0.84 indicates a high interrater reliability. The high accuracy and reliability make the Skin Analyzer a suitable method of objectively determining Fitzpatrick skin type from images. The app may be used to investigate the effects of skin tone in various areas of interest, especially in retrospective studies where skin colorimeters cannot be used.