Objective The interplay between neuronal innervation and other cell types underlies the physiological functions of the dura mater and contributes to pathophysiological conditions such as migraine. We characterized the extensive, but understudied, non-arterial diffuse dural innervation (DDI) of the rat and Rhesus monkey. Methods We used a comprehensive integrated multi-molecular immunofluorescence labeling strategy to extensively profile the rat DDI and to a lesser extent that of the Rhesus monkey. Results The DDI was distributed across a dense, pervasive capillary network and included free nerve endings of peptidergic CGRP-expressing C fibers that were closely intertwined with noradrenergic (NA) sympathetic fibers and thin-caliber nonpeptidergic "C/Aδ" fibers. These newly identified C/Aδ fibers were unmyelinated, like C fibers, but expressed NF200, usually indicative of Aδ fibers, and uniquely co-labeled for the CGRP co-receptor, RAMP1. Slightly-larger caliber NF200-positive fibers co-labeled for myelin basic protein (MBP) and terminated as unbranched corpuscular endings. The DDI peptidergic fibers co-labeled for the lectin IB4 and expressed presumably excitatory α1-adrenergic receptors, as well as inhibitory 5HT1D receptors and the delta opioid receptor (δOR), but rarely the mu opioid receptor (µOR). Labeling for P2X3, TRPV1, TRPA1, and parasympathetic markers was not observed in the DDI. Interpretation These results suggest potential functional interactions, wherein peptidergic DDI fibers may be activated by stress-related sympathetic activity, resulting in CGRP release that could be detected in the circulation. CGRP may also activate nonpeptidergic C/Aδ fibers that are likely mechanosensitive or polymodal, leading to activation of post-synaptic pain transmission circuits. The distribution of α1-adrenergic receptors, RAMP1, and the unique expression of the δOR on CGRP-expressing DDI fibers suggest strategies for functional modulation and application to therapy.

OBJECTIVES Retrospective matched-cohort study evaluating association between penicillin allergy and empirical carbapenem use in gram-negative bloodstream infections (BSIs) and utility of antimicrobial stewardship interventions in reducing carbapenem utilization. METHODS Hospitalized adults with community-onset gram-negative BSI from January 1, 2010, to June 30, 2015, at two large community hospitals in Columbia, SC, were identified. Antimicrobial stewardship interventions targeting penicillin allergy and carbapenem utilization were fully implemented January 1, 2014. Multivariate logistic regression was used to examine impact of penicillin allergy and antimicrobial stewardship interventions on empirical carbapenem use. Kaplan-Meier analysis was used to evaluate time to carbapenem deescalation in patients with penicillin allergy before and after interventions. RESULTS Patients with penicillin allergy (n=140) were more likely to receive empirical carbapenem therapy for community-onset gram-negative BSI compared to those without penicillin allergy (n=140) (27% vs 12%, p=0.002). After adjustments in the multivariate model, penicillin allergy (odds ratio [OR] 3.98, 95% confidence interval [CI] 1.98-8.45) and prior b-lactam use (OR 2.72, 95% CI 1.07-6.64) were independently associated with empirical carbapenem use, whereas antimicrobial stewardship interventions were associated with decline in carbapenem utilization (OR 0.41, 95% CI 0.16-0.94). Among patients with penicillin allergy who were prescribed empirical carbapenems, median time to carbapenem deescalation was significantly shorter in the postintervention versus preintervention period (2.0 vs 4.2 days, p=0.004). CONCLUSION Penicillin allergy was a significant contributor to carbapenem use in community-onset gram-negative BSI. This was subject to modification by antimicrobial stewardship interventions, which successfully reduced overall carbapenem use and duration of carbapenem therapy in patients with penicillin allergy.

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Date Presented 04/20/2023 This correlational study examined the relationship among social support, self-efficacy, parental competence, and satisfaction with assistive technology (AT) for mothers with multiple sclerosis (MS). Results show significant correlations, supporting OT interventions in this population. Primary Author and Speaker: Yan-hua Huang Additional Authors and Speakers: Emily Acker, Hannah Chang, Annabelle Clegg, Megan Gibson