Atg5 Supports Rickettsia australis Infection in Macrophages In Vitro and In Vivo.

Rickettsiae can cause life-threatening infections in humans. Macrophages are one of the initial targets for rickettsiae after inoculation by ticks. However, it remains poorly understood how rickettsiae remain free in macrophages prior to establishing their infection in microvascular endothelial cells. Here, we demonstrated that the concentration of Rickettsia australis was significantly greater in infected tissues of Atg5flox/flox mice than in the counterparts of Atg5flox/flox Lyz-Cre mice, in association with a reduced level of interleukin-1ß (IL-1ß) in serum. The greater concentration of R. australis in Atg5flox/flox bone marrow-derived macrophages (BMMs) than in Atg5flox/flox Lyz-Cre BMMs in vitro was abolished by exogenous treatment with recombinant IL-1ß. Rickettsia australis induced significantly increased levels of light chain 3 (LC3) form II (LC3-II) and LC3 puncta in Atg5-competent BMMs but not in Atg5-deficient BMMs, while no p62 turnover was observed. Further analysis found the colocalization of LC3 with a small portion of R. australis and Rickettsia-containing double-membrane-bound vacuoles in the BMMs of B6 mice. Moreover, treatment with rapamycin significantly increased the concentrations of R. australis in B6 BMMs compared to those in the untreated B6 BMM controls. Taken together, our results demonstrate that Atg5 favors R. australis infection in mouse macrophages in association with a suppressed level of IL-1ß production but not active autophagy flux. These data highlight the contribution of Atg5 in macrophages to the pathogenesis of rickettsial diseases.

Orthopaedic Resident Practice Management and Health Policy Education: Evaluation of Experience and Expectations.

Introduction Practice management and health policy have generally not been considered integral to orthopaedic resident education. Our objective was to evaluate residents' current experience and knowledge, formal training, and desire for further education in practice management and health policy. Methods We developed a 29-question survey that was divided into three sections: practice management, initial employment opportunity, and health policy. Within each section, questions were directed at a resident's current experience and knowledge, formal training, and interest in further education. The survey was distributed at the end of the academic year through an Internet-based survey tool (www.surveymonkey.com) to orthopaedic residents representing multiple programs and all postgraduate years. Results The survey was distributed to 121 residents representing eight residency programs. Of those, 87 residents responded, resulting in a 72% response rate. All postgraduate years were represented. Regarding practice management, 66% had "no confidence" or "some confidence" in coding clinical encounters. When asked if practice models, finance management, and coding should be taught in residency, 95%, 93%, and 97% responded "yes," respectively. When evaluating first employment opportunities, the three most important factors were location, operating room block time, and call. Regarding health policy, 28% were "moderately familiar" or "very familiar" with the Physician Payments Sunshine Act, and 72% were "not familiar" or "somewhat familiar" with bundled payments for arthroplasty. Finally, when asked if yearly lectures in political activities would enhance resident education, 90% responded "yes." Discussion and conclusion Regarding practice management, the survey suggests that current orthopaedic residents are not familiar with basic topics, do not receive formal training, and want further education. The survey suggests that residents also receive minimal training in health policy. Residents feel that health policy will be important in their careers, and they would benefit from formal training in residency.