Content Validation of an Emergency Department Skin Risk Assessment Instrument.

Pressure injuries (PIs) are an important quality and patient safety metric for health care organizations. PI monitoring and treatment are often overlooked in the emergency department (ED). Emergency care professionals must be proactive about PI early identification and prevention strategies. A team at a Level 1 trauma center recognized the need for ED-friendly documentation and a validated ED skin risk assessment instrument. The Bjorklund 25-item ED Skin/Risk Assessment Tool was selected. However, because the tool was not fully validated, permission to validate/use was obtained from the author. The purpose of this research study was to determine the content validity of the Bjorklund Tool. Using a prospective survey design, content experts were recruited from wound, quality, and ED and participated in two rounds of content validation. The experts reviewed the Tool for relevance, clarity, and appropriateness for the ED population. Item-level content validity index (I-CVI) and scale-level CVI (S-CVI) were calculated, with 0.78 and 0.90 as the lower limits of acceptability for individual items and the overall scale, respectively. Of the first round I-CVI ratings, 24 of 75 were below 0.78, including 14 for relevance, four for clarity, and six for appropriateness. S-CVI was 0.7574 for relevance, 0.8809 for clarity, 0.8592 for appropriateness, and 0.8325 overall. The Bjorklund Tool was determined to be invalid in its current form. A novel tool was thus created in the second round per content experts' recommendations. After redesign and simplifying items and images, all I-CVIs rated above 0.78. S-CVI was 0.923 for relevance, 0.9743 for clarity, 0.9615 for appropriateness, and 0.9529 overall. These CVIs indicate excellent content validity of the new UCHealth ED Skin Risk Assessment Instrument. This research contributes to establishment of content validity of a skin risk assessment instrument which can be used in the unique ED setting.

Dynamic regulation and requirement for ribosomal RNA transcription during mammalian development.

Ribosomal RNA (rRNA) transcription by RNA polymerase I (Pol I) is a critical rate-limiting step in ribosome biogenesis, which is essential for cell survival. Despite its global function, disruptions in ribosome biogenesis cause tissue-specific birth defects called ribosomopathies, which frequently affect craniofacial development. Here, we describe a cellular and molecular mechanism underlying the susceptibility of craniofacial development to disruptions in Pol I transcription. We show that Pol I subunits are highly expressed in the neuroepithelium and neural crest cells (NCCs), which generate most of the craniofacial skeleton. High expression of Pol I subunits sustains elevated rRNA transcription in NCC progenitors, which supports their high tissue-specific levels of protein translation, but also makes NCCs particularly sensitive to rRNA synthesis defects. Consistent with this model, NCC-specific deletion of Pol I subunits Polr1a, Polr1c, and associated factor Tcof1 in mice cell-autonomously diminishes rRNA synthesis, which leads to p53 protein accumulation, resulting in NCC apoptosis and craniofacial anomalies. Furthermore, compound mutations in Pol I subunits and associated factors specifically exacerbate the craniofacial anomalies characteristic of the ribosomopathies Treacher Collins syndrome and Acrofacial Dysostosis-Cincinnati type. Mechanistically, we demonstrate that diminished rRNA synthesis causes an imbalance between rRNA and ribosomal proteins. This leads to increased binding of ribosomal proteins Rpl5 and Rpl11 to Mdm2 and concomitantly diminished binding between Mdm2 and p53. Altogether, our results demonstrate a dynamic spatiotemporal requirement for rRNA transcription during mammalian cranial NCC development and corresponding tissue-specific threshold sensitivities to disruptions in rRNA transcription in the pathogenesis of congenital craniofacial disorders.

Gadd45γ and Map3k4 interactions regulate mouse testis determination via p38 MAPK-mediated control of Sry expression.

Loss of the kinase MAP3K4 causes mouse embryonic gonadal sex reversal due to reduced expression of the testis-determining gene, Sry. However, because of widespread expression of MAP3K4, the cellular basis of this misregulation was unclear. Here, we show that mice lacking Gadd45γ also exhibit XY gonadal sex reversal caused by disruption to Sry expression. Gadd45γ is expressed in a dynamic fashion in somatic cells of the developing gonads from 10.5 days postcoitum (dpc) to 12.5 dpc. Gadd45γ and Map3k4 genetically interact during sex determination, and transgenic overexpression of Map3k4 rescues gonadal defects in Gadd45γ-deficient embryos. Sex reversal in both mutants is associated with reduced phosphorylation of p38 MAPK and GATA4. In addition, embryos lacking both p38α and p38ß also exhibit XY gonadal sex reversal. Taken together, our data suggest a requirement for GADD45γ in promoting MAP3K4-mediated activation of p38 MAPK signaling in embryonic gonadal somatic cells for testis determination in the mouse.