PET imaging of TREM1 identifies CNS-infiltrating myeloid cells in a mouse model of multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated demyelinating disease of the central nervous system (CNS) that causes substantial morbidity and diminished quality of life. Evidence highlights the central role of myeloid lineage cells in the initiation and progression of MS. However, existing imaging strategies for detecting myeloid cells in the CNS cannot distinguish between beneficial and harmful immune responses. Thus, imaging strategies that specifically identify myeloid cells and their activation states are critical for MS disease staging and monitoring of therapeutic responses. We hypothesized that positron emission tomography (PET) imaging of triggering receptor expressed on myeloid cells 1 (TREM1) could be used to monitor deleterious innate immune responses and disease progression in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. We first validated TREM1 as a specific marker of proinflammatory, CNS-infiltrating, peripheral myeloid cells in mice with EAE. We show that the 64Cu-radiolabeled TREM1 antibody-based PET tracer monitored active disease with 14- to 17-fold higher sensitivity than translocator protein 18 kDa (TSPO)-PET imaging, the established approach for detecting neuroinflammation in vivo. We illustrate the therapeutic potential of attenuating TREM1 signaling both genetically and pharmacologically in the EAE mice and show that TREM1-PET imaging detected responses to an FDA-approved MS therapy with siponimod (BAF312) in these animals. Last, we observed TREM1+ cells in clinical brain biopsy samples from two treatment-naïve patients with MS but not in healthy control brain tissue. Thus, TREM1-PET imaging has potential for aiding in the diagnosis of MS and monitoring of therapeutic responses to drug treatment.

Impact of Resident-Led Small-Group Learning Sessions on Preclinical Students' Perceptions of Ophthalmology.

Introduction Resident physicians have a significant role in the education of medical students, and limited research has demonstrated that positive interactions with residents are linked with enhanced students' perceptions of a specialty. Minimal research on residents as teachers has been done in ophthalmology, and no research has examined the impact of residents as teachers on the perceptions of preclinical students. This is an important area of interest because ophthalmology conducts an early match. The competitiveness of the field increases the importance of early involvement in research and clinical activities. This study aimed to assess the role of a resident-led workshops as a vehicle for exposing preclinical students to ophthalmology. Methods A 2-hour workshop on the Ophthalmology Clinical Skills was held at the University of Cincinnati College of Medicine in November 2018. The workshop was conducted by seven ophthalmology residents, and the learners were 15 first-year and 11 second-year medical students. The workshop format consisted of a 30-minute introductory lecture on the field of ophthalmology, followed by a 60-minute small-group clinical skills' session focusing on direct ophthalmoscopy and slit lamp examination. Preworkshop and postworkshop surveys were administered to the medical students, and Student's paired sample t -test was used to assess the differences in responses before and after the workshop. Results Students' average interest in ophthalmology rose ( p = 0.049) as did their likeliness to approach a resident for career advice ( p = 4.65 × 10 -6 ) and their likeliness to attend the Secrets of the Match Lunch talk, a yearly talk held by a student matched into ophthalmology ( p = 0.002). Conclusion These results suggest that resident intervention can have a positive impact on preclinical students' perceptions of ophthalmology and may be a good educational strategy to foster their positive attitudes toward the field.