Live vaccines historically afford superior protection, yet the cellular and molecular mechanisms mediating protective immunity remain unclear. Here we found that vaccination of mice with live, but not dead, Gram-negative bacteria heightened follicular T helper cell (Tfh) differentiation, germinal center formation, and protective antibody production through the signaling adaptor TRIF. Complementing the dead vaccine with an innate signature of bacterial viability, bacterial RNA, recapitulated these responses. The interferon (IFN) and inflammasome pathways downstream of TRIF orchestrated Tfh responses extrinsically to B cells and classical dendritic cells. Instead, CX3CR1CCR2 monocytes instructed Tfh differentiation through interleukin-1β (IL-1β), a tightly regulated cytokine secreted upon TRIF-dependent IFN licensing of the inflammasome. Hierarchical production of IFN-β and IL-1β dictated Tfh differentiation and elicited the augmented humoral responses characteristic of live vaccines. These findings identify bacterial RNA, an innate signature of microbial viability, as a trigger for Tfh differentiation and suggest new approaches toward vaccine formulations for coordinating augmented Tfh and B cell responses.

Current clinical screening for infantile hip dysplasia relies on combined Ortolani and Barlow maneuvers, which have a quoted sensitivity and specificity of 74–98 and 84–99%, respectively. Teaching this delicate physical examination maneuver is difficult as it requires a distinct tactile feel. The purpose of this study is to validate a benchtop learning grocery-bought chicken simulator model of newborn hip instability through a pre- and post-test surveys. This model of hip dysplasia uses whole chickens. A posterior capsulotomy of the chicken’s hip joint was performed to create instability. Provocative maneuvers to dislocate and relocate the hip were taught by a pediatric orthopedic surgeon. All participants completed an anonymous pre- and post-training surveys. A total of 58 participants were included in the study: 10 medical students, 13 pediatric residents, 15 orthopedic residents, and 20 orthopedic or pediatric attending physicians. The pediatric residents had performed the Barlow/Ortolani tests more than the orthopedic residents (96.15 ± 83.19 vs. 37.53 ± 60.89; P = 0.01); however, fewer pediatric residents reported feeling a positive examination (31 vs. 67%). The majority of the group agreed that the simulation felt and moved like an infant’s hip (3.95 and 4.13; Likert five-point scale). The participants unanimously agreed that the model could be used to teach someone new to pediatrics the basic steps of the examination (4.91; Likert five-point scale) and should be implemented in the teaching curriculum (100%). The current study validates the benchtop model in teaching the clinical steps in detecting hip dysplasia. The model improved confidence and comfort level for all participants and proved to be a valuable tool for resident education in multiple specialties. By improving education with this model, we hope to improve early identification of hip dysplasia with increased accuracy across subspecialties.

Category: Other Introduction/Purpose: Foot and ankle (FA) pain can be found in up to 20% of the adult population.1 Etiologies are multifactorial and include neurologic injury, trauma, deformity, tendinopathies and psychological factors. The purpose of this investigation is to assess psychological factors contributing to FA pain in surgical and nonsurgical patients. By identifying how psychological factors influence patient reported pain and disability, clinicians may be able to develop interventions to decrease catastrophic thinking and improve psychological well-being prior to considering surgical intervention Methods: All patients seen in a FA clinic by a single fellowship trained orthopaedic surgeon from August 2016 to October 2016 were included. All patients completed 5 functional assessments prior to their visit (PHQ-2, VAS Pain Scale, FAAM, PSEQ, PCS). We divided the patients into two groups based on their performance on the PHQ (PHQ < 3, or PHQ = 3), which measures depression. Scores = 3 are indicative of clinical depression. Nonparametric Wilcoxon testing was used to determine whether the distributions of the other scores (VAS Pain Scale, FAAM, PSEQ and PCS) were significantly different between these two groups. Results: Of the 225 patients included in our analysis, there were 175 (88%) had PHQ-2 depression scores of < 3 (Group 1) and 50 (22%) had scores = 3 (Group 2). Group 2 demonstrated a statistically significant increase in VAS Pain Scale and PCS. In addition, patients in Group 2 showed statistically significant decreases in FAAM and PSEQ. Patients in Group 2 were statistically more likely to be obese, use tobacco, and be unemployed. Conclusion: In patients with common FA complaints, those with clinical depression, as assessed by the PHQ-2, demonstrated increased pain scores, decreased ability to cope with pain, and lower functional outcome scores compared to patients without depression. Tobacco use, obesity and employment status were found to independently affect pain, coping, and function of patients. These data suggest that depression can significantly affect a patient’s ability to cope with pain and to achieve a higher functional outcome. This data suggests patients with depression may have increased difficulty coping with their FA ailment leading to the need for increased counseling regarding expected outcomes.

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