Preclinical behavioral pharmacological and neuropharmacological evidence indicates that the NMDA receptor plays an important role in opioid dependence, however, the neural substrates subserving these actions are poorly understood. The central nucleus of the amygdala (CeA) is a critical coordinator of autonomic, behavioral, and emotional systems impacted by opioids, however there is no evidence that the essential NMDA-NR1 (NR1) subunit gene in the amygdala plays a role in opioid dependence. To determine the role of the NR1 subunit gene in the amygdala with respect to physical and psychological opioid withdrawal, a spatial-temporal deletion of this gene was produced by microinjecting a recombinant adeno-associated virus (rAAV) expressing the GFP reporter and Cre recombinase (rAAV-GFP-Cre) into the CeA of adult "floxed" NR1 mice (fNR1). Amygdala microinjection of rAAV-GFP-Cre produced a decrease in NR1 gene expression and protein immunolabeling in postsynaptic sites of neurons without signs of compromised ultrastructural neuronal morphology. Amygdala NR1 gene deletion also did not affect locomotor, somatosensory, or sensory-motor behaviors. In addition, bilateral local NR1 gene deletion did not impact somatic or visceral withdrawal symptoms precipitated by naloxone in morphine-dependent mice. However, there was a significant deficit in the expression of an opioid withdrawal-induced conditioned place aversion in mice with amygdala NR1 deletion. These results indicate that functional amygdala NMDA receptors are involved in aversive psychological Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. NIH Public Access

The central nucleus of the amygdala (CeA) is an important neuroanatomical substrate of emotional processes that are critically involved in addictive behaviors. Glutamate and opioid systems in the CeA play significant roles in neural plasticity and addictive processes, however the cellular sites of interaction between agonists of N-methyl-d-aspar-tate (NMDA) and μ-opioid receptors (μOR) in the CeA are unknown. Dual labeling immunocytochemistry was used to determine the ultrastructural relationship between the essential NMDA-NR1 receptor subunit and μOR in the CeA. It was found that over 80% of NR1-labeled profiles were dendrites while less than 10% were axons. In the case of μOR-labeled profiles, approximately 60% were dendritic, and over 35% were axons. Despite their somewhat distinctive patterns of cellular location, numerous dual-labeled profiles were observed. Approximately 80% of these were dendritic, and less than 10% were axonal. Moreover, many dual-labeled dendritic profiles were contacted by axon terminals receiving asymmetric-type synapses indicative of excitatory signaling. These results indicate that NMDA and μORs are strategically localized in dendrites, including those receiving excitatory synapses, of central amygdala neurons. Thus, postsynaptic co-modulation of central amygdala neurons may be a key cellular substrate mediating glutamate and opioid interaction on neural signaling and plasticity associated with normal and pathological emotional processes associated with addictive behaviors.

ObjectiveDistinguishing aortitis‐induced aneurysms from noninflammatory aortic aneurysms is difficult and often incidentally diagnosed on histologic examination after surgical repair. This study was undertaken to examine surgically diagnosed aortitis and identify patient characteristics and imaging findings associated with the disease.MethodsIn this case–control study, cases had newly diagnosed, biopsy‐proven noninfectious aortitis after open thoracic aortic aneurysm surgical repair. Five controls were matched with cases for year of surgery and lacked significant inflammation on surgical pathology analysis. Data on comorbidities, demographic characteristics, and laboratory and imaging abnormalities prior to surgery were collected. Associations between exposures and outcomes were evaluated using conditional logistic regression. Backward stepwise logistic regression was used to determine factors independently associated with aortitis. Odds ratios (ORs) with 95%confidence intervals (95%CIs) were calculated.ResultsThe study included 262 patients (43 patients with aortitis and 219 controls). Patients with aortitis were older at the time of surgery, predominantly female, and less likely to have a history of coronary artery disease (CAD). Multivariable analysis revealed that aortitis was independently associated with an older age at the time of surgery (OR 1.08 [95%CI 1.03–1.13], P < 0.01), female sex (OR 2.36 [95%CI 1.01–5.51], P = 0.04), absence of CAD (OR 6.92 [95%CI 2.14–22.34], P = 0.04), a larger aneurysm diameter (OR 1.74 [95%CI 1.02–2.98], P = 0.04), and arterial wall thickening on imaging (OR 56.93 [95%CI 4.31–752.33], P < 0.01).ConclusionAmong patients who undergo open surgical repair of an aortic aneurysm, elderly women with no history of CAD who have evidence of other aortic or arterial wall thickening on imaging are more likely to have histologic evidence of aortitis. Patients with these characteristics may benefit from further rheumatologic evaluation.

Background Internal medicine (IM) residents lack confidence in rheumatology. Due to the wide variety of topics in rheumatology, identifying the most important subjects to learn during training is vital to create future interventions to increase confidence and knowledge. The preferred teaching modality for both attendings/fellows and residents is not known. Methods An electronic survey was distributed to all IM residents, rheumatology fellows, and rheumatology faculty at the University of Chicago during the 2020–2021 academic year. Residents reported self-confidence levels on 10 rheumatology topics, while rheumatology attendings/fellows were asked to rank these from most to least important to learn during IM residency. All groups were asked preferred teaching modality. Results Median confidence level [interquartile range] among residents for caring for patients with rheumatological conditions was 6 [3.6–7.5] for inpatient and 5 [3.7–6.5] for outpatient settings (10 being very confident). Attendings and fellows identified the most important topics to learn during the rheumatology rotation as ordering and interpreting autoimmune serologies and musculoskeletal exam. Both attendings/fellows and residents preferred bedside teaching in the inpatient setting and case-based learning in the outpatient setting. Conclusions While some disease-specific topics such as autoimmune serologies were identified as important rheumatology topics for IM residents to learn, more practical topics like musculoskeletal exam skills were also deemed important. This highlights the need for comprehensive interventions that focus on more than standardized exam topics alone to improve rheumatology confidence in IM residents. There are different preferences of teaching styles in various clinical settings.

Objective The optimal management of patients with incidentally found clinically isolated aortitis (CIA) after aneurysm repair is unclear. This study compared long‐term surgical and clinical outcomes after surgical repair of thoracic aortic aneurysm between patients with CIA and patients with noninflammatory etiologies. Methods This is a matched cohort study. Patients with CIA were identified by histopathology following open thoracic aortic aneurysm repair. Two comparators without inflammation on pathology were matched to each patient by year of surgical repair. Outcomes included surgical complications, new vascular abnormalities on imaging, and death. Results One hundred sixty‐two patients were included: 53 with CIA and 109 matched comparators. Median follow‐up time was similar between groups (CIA 3.7 vs. comparator 3.3 years, P = 0.64). There was no difference in postoperative complications, surgical revision, or death between groups. Only 32% of patients with CIA saw a rheumatologist in the outpatient setting and 33% received immunosuppressive treatment. On surveillance imaging, no difference was seen in new or worsening aortic aneurysms, but there were significantly more vascular abnormalities in branch arteries of the thoracic aorta in patients with CIA (39% vs. 11%, P < 0.01). Conclusion Among patients who underwent surgical repair of a thoracic aortic aneurysm, patients with CIA were more likely than noninflammatory comparators to develop radiographic abnormalities in aortic branch arteries. Notably, there was no difference in risk of new aortic aneurysms or surgical complications despite most patients with CIA never receiving immunosuppression. This suggests that more selective initiation of immunosuppression in CIA may be considered after aortic aneurysm repair.