Cortisol as a Marker of Pain and Distress After Acute Musculoskeletal Trauma.

OBJECTIVES: The best available predictors of chronic pain development broadly encompass baseline metrics of cognition (ie, beliefs/expectations) about the trauma and resulting symptoms. In the context of musculoskeletal trauma, we have previously shown the Traumatic Injuries Distress Scale (TIDS) capable of risk-stratifying cohorts for chronic pain development. Here, we explore whether the physiological marker cortisol shows meaningful associations with cognitions predictive of pain outcomes. METHODS: Data for these cross-sectional analyses were drawn from an observational study that recruited 130 participants presenting to the hospital with pain related to a recent noncatastrophic Musculoskeletal trauma. Cortisol was measured from the participant's hair, saliva, and blood. In addition to pain and distress questionnaires, metadata such as age, sex, body mass index (BMI), adverse childhood events, pretrauma stress levels, and pre-existing physical/psychological comorbidities were collected. RESULTS: We found no significant associations between cortisol levels and pain or distress in isolation. When stratified by person-level variables, associations were revealed with distress (TIDS) in young age and low pretrauma stress subgroups (hair cortisol) and low BMI (blood cortisol). Through hierarchical regression analysis, we found the "cortisol X age" or "cortisol X stress" interaction terms significantly improved TIDS prediction beyond either variable in isolation (Age: ∆ R2 =15.1%; pretrauma stress: ∆ R2 =9.1%). DISCUSSION: Our findings suggest that while linear correlations between pain-related distress and cortisol may be overly simplistic, certain person-level variables such as age, pretrauma stress, and BMI are worthy of consideration for experimental design or confounder characterization in future studies of pain and distress following musculoskeletal injuries especially when "trait" (hair) cortisol is the predictor variable.

Medical Students as Educators: Addressing Teaching Skills Through a Pre-clerkship Development Group.

In medicine, effective teaching is requisite for both successful patient care and trainee development. However, opportunities for medical students to gain exposure to pedagogical principles and hone teaching skills are currently limited. Our initiative provides avenues for medical students to intentionally develop their teaching skill set from an early stage.

Peptide-Based Approach to Inhibition of the Multidrug Resistance Efflux Pump AcrB.

Clinically relevant multidrug-resistant bacteria often arise due to overproduction of membrane-embedded efflux proteins that are capable of pumping antibiotics out of the bacterial cell before the drugs can exert their intended toxic effect. The Escherichia coli membrane protein AcrB is the archetypal protein utilized for bacterial efflux study because it can extrude a diverse range of antibiotic substrates and has close homologues in many Gram-negative pathogens. Three AcrB subunits, each of which contains 12 transmembrane (TM) helices, are known to trimerize to form the minimal functional unit, stabilized noncovalently by helix-helix interactions between TM1 and TM8. To inhibit the efflux activity of AcrB, we have rationally designed synthetic peptides aimed at destabilizing the AcrB trimerization interface by outcompeting the subunit interaction sites within the membrane. Here we report that peptides mimicking TM1 or TM8, with flanking N-terminal peptoid tags, and C-terminal lysine tags that aid in directing the peptides to their membrane-embedded target, decrease the AcrB-mediated efflux of the fluorescent substrate Nile red and potentiate the effect of the antimicrobials chloramphenicol and ethidium bromide. To further characterize the motif encompassing the interaction between TM1 and TM8, we used Förster resonance energy transfer to demonstrate dimerization. Using the TM1 and TM8 peptides, in conjunction with several selected mutant peptides, we highlight residues that may increase the potency and specificity of the peptide drug candidates. In targeting membrane-embedded protein-protein interactions, this work represents a novel approach to AcrB inhibition and, more broadly, a potential route to a new category of efflux pump inhibitors.