Improving epinephrine autoinjector usability and carriage frequency among patients at risk of anaphylaxis: a quality improvement initiative.

Although epinephrine autoinjectors (EAIs) are crucial for the management of anaphylaxis, patient carriage frequency of EAI is as low as 57% and usage of EAIs is erroneous 35%-43% of the time. Our objective was to improve patient carrying frequency of EAI and understanding of EAI usage.We implemented a quality improvement initiative using consistent closed-loop education, redesigned clinic workflow, electronic medical record reminder-based interventions, and educational materials to improve patient EAI carriage compliance and understanding of EAI indications and proper technique.

Novel bioinformatics method for identification of genome-wide non-canonical spliced regions using RNA-Seq data.

Setting: During endoplasmic reticulum (ER) stress, the endoribonuclease (RNase) Ire1α initiates removal of a 26 nt region from the mRNA encoding the transcription factor Xbp1 via an unconventional mechanism (atypically within the cytosol). This causes an open reading frame-shift that leads to altered transcriptional regulation of numerous downstream genes in response to ER stress as part of the unfolded protein response (UPR). Strikingly, other examples of targeted, unconventional splicing of short mRNA regions have yet to be reported.

Active site inhibitors protect protein kinase C from dephosphorylation and stabilize its mature form.

Conformational changes acutely control protein kinase C (PKC). We have previously shown that the autoinhibitory pseudosubstrate must be removed from the active site in order for 1) PKC to be phosphorylated by its upstream kinase phosphoinositide-dependent kinase 1 (PDK-1), 2) the mature enzyme to bind and phosphorylate substrates, and 3) the mature enzyme to be dephosphorylated by phosphatases. Here we show an additional level of conformational control; binding of active site inhibitors locks PKC in a conformation in which the priming phosphorylation sites are resistant to dephosphorylation.