Integration of Substance Use Screening Into the Electronic Health Record for Adolescent Trauma Patients: A Quality Improvement Project.

BACKGROUND: Adolescent substance abuse is a well-acknowledged and increasing concern. Screening brief intervention and referral to treatment for alcohol and drug use in adolescent trauma is a requirement, but program implementation remains a challenge for many trauma centers. OBJECTIVE: This study aims to examine the effect of an integrated electronic health record screening tool and staff training on screening, brief intervention, and referral to treatment compliance in adolescent trauma. METHODS: This is a single-center, pre- and postintervention study of substance use screening compliance in adolescent trauma patients (age 12-21) conducted at a Level I pediatric trauma center in the Southeastern United States following the integration of the CRAFFT substance abuse screening tool into the electronic health record. The study compared 12 months of preintervention data (January 2021 through January 2022) to 15 months of postintervention data (February 2022 through May 2023). RESULTS: A total of N = 241 patients met inclusion criteria, of which most were male, n = 168 (69.7%), White n = 185 (76.8%), and Hispanic n = 179 (74.3%). Screening compliance increased from preintervention 81% to postintervention 92%. CONCLUSION: Our study demonstrates that integrating a digital screening tool into the electronic health record resulted in an average increased screening compliance of 11%.

A genetically-encoded crosslinker screen identifies SERBP1 as a PKCε substrate influencing translation and cell division.

The PKCε-regulated genome protective pathway provides transformed cells a failsafe to successfully complete mitosis. Despite the necessary role for Aurora B in this programme, it is unclear whether its requirement is sufficient or if other PKCε cell cycle targets are involved. To address this, we developed a trapping strategy using UV-photocrosslinkable amino acids encoded in the PKCε kinase domain. The validation of the mRNA binding protein SERBP1 as a PKCε substrate revealed a series of mitotic events controlled by the catalytic form of PKCε. PKCε represses protein translation, altering SERBP1 binding to the 40 S ribosomal subunit and promoting the assembly of ribonucleoprotein granules containing SERBP1, termed M-bodies. Independent of Aurora B, SERBP1 is shown to be necessary for chromosome segregation and successful cell division, correlating with M-body formation. This requirement for SERBP1 demonstrates that Aurora B acts in concert with translational regulation in the PKCε-controlled pathway exerting genome protection.

Co-ordinated control of the Aurora B abscission checkpoint by PKCε complex assembly, midbody recruitment and retention.

A requirement for PKCε in exiting from the Aurora B dependent abscission checkpoint is associated with events at the midbody, however, the recruitment, retention and action of PKCε in this compartment are poorly understood. Here, the prerequisite for 14-3-3 complex assembly in this pathway is directly linked to the phosphorylation of Aurora B S227 at the midbody. However, while essential for PKCε control of Aurora B, 14-3-3 association is shown to be unnecessary for the activity-dependent enrichment of PKCε at the midbody. This localisation is demonstrated to be an autonomous property of the inactive PKCε D532N mutant, consistent with activity-dependent dissociation. The C1A and C1B domains are necessary for this localisation, while the C2 domain and inter-C1 domain (IC1D) are necessary for retention at the midbody. Furthermore, it is shown that while the IC1D mutant retains 14-3-3 complex proficiency, it does not support Aurora B phosphorylation, nor rescues division failure observed with knockdown of endogenous PKCε. It is concluded that the concerted action of multiple independent events facilitates PKCε phosphorylation of Aurora B at the midbody to control exit from the abscission checkpoint.

A cancer-associated, genome protective programme engaging PKCε.

Associated with their roles as targets for tumour promoters, there has been a long-standing interest in how members of the protein kinase C (PKC) family act to modulate cell growth and division. This has generated a great deal of observational data, but has for the most part not afforded clear mechanistic insights into the control mechanisms at play. Here, we review the roles of PKCε in protecting transformed cells from non-disjunction. In this particular cell cycle context, there is a growing understanding of the pathways involved, affording biomarker and interventional insights and opportunities.