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ide-induced breast cancer progression. As recently described, the administration of extremely low doses (pg/kg) of CCL4 (Macrophage inflammatory protein 1β, MIP-1β) can induce antinociceptive effects in mice (García-Domínguez et al., 2019b). We describe here that hydrodynamic delivery of a plasmid containing CCL4 cDNA provokes a biphasic response consisting in an initial thermal hyperalgesic reaction for 8 days followed by analgesia at days 10-12, being both responses blocked after the administration of the CCR5 antagonist DAPTA. Both the luminiscence evoked in liver after the administration of a plasmid containing CCL4 and luciferase cDNAs and the hepatic concentration of CCL4 measured by ELISA were maximal 4 days after plasmid administration and markedly diminished at day 10. A dose-effect curve including a wide dose range of exogenous CCL4 revealed thermal analgesia after the administration of 10-100 pg/kg whereas 1000 times higher doses (30-100 ng/kg) induced, instead, thermal hyperalgesia inhibited by DAPTA. This hyperalgesia was absent in mice with reduced white blood cells after cyclophosphamide treatment, thus supporting the involvement of circulating leukocytes. A multiarray bioluminescent assay revealed increased plasma levels of IL-1α, CCL2, CXCL1, CXCL13, IL-16 and TIMP-1 in mice treated with 100 ng/kg of CCL4. The hyperalgesic response evoked by CCL4 was prevented by IL-1R, CXCR2 or CCR2 antagonists or by the neutralization of CXCL13 or IL-16, but not TIMP-1, with selective antibodies. The administration of the anti-IL-16 antibody was the unique treatment able to convert hyperalgesia evoked by 100 ng/kg of CCL4 in an analgesic effect. The ability of IL-16 to evoke hypernociception was confirmed by studying the response to its exogenous administration (10-30 ng/kg). In summary, the present results demonstrate that CCL4 induces a dual modulation of nociception and describe some mechanisms involved in the hyperalgesic response evoked by this chemokine. this website Producing intact recombinant membrane proteins for structural studies is an inherently challenging task due to their requirement for a cell-lipid environment. Most of the procedures developed involve isolating the protein by solubilization with detergent and further reconstitutions into artificial membranes. These procedures are highly time consuming and suffer from further drawbacks, including low yields and high cost. We describe here an alternative method for rapidly obtaining recombinant cell-surface membrane proteins displayed on extracellular vesicles (EVs) derived from cells in culture. Interaction between these membrane proteins and ligands can be analyzed directly on EVs. Moreover, EVs can also be used for protein structure determination or immunization purposes. BACKGROUND Prior work has demonstrated the impact of gender on the relationship between confidence and competence, with women having less confidence and less self-perceived competence. Recent recruitment of examiners by the American Board of Surgery (ABS) allowed exploration of confidence and perceived competence. METHODS 23,869 eligible board-certified surgeons (4,382 women) were solicited via email to serve as examiners for the ABS General Surgery Certifying Examination (GCE). Volunteers were asked about practice and comfort examining in the 14 GCE content areas. Regression models investigated the relationship between reported practice and confidence examining. RESULTS 2,157 surgeons volunteered, of which 420 (19.5%) were female. Men reported practicing in a greater number of content areas than women (6.59 vs 5.36, p less then .001) and selected more content areas in which they felt comfortable examining (7.69 vs 6.64, p less then .001). The average male volunteer was comfortable examining in 0.70 more content areas than women, controlling for self-reported practice. CONCLUSION Men reported practicing more broadly and were more confident than women in their ability to examine across ABS CE content areas. However, the confidence of male surgeons was not restricted to those areas in which they reported practicing. These data have important implications for training, leadership, and professional development. BACKGROUND The common use of laparoscopic interventions produces impressive amounts of video data that are difficult to review for surgeons wishing to evaluate and improve their skills. Therefore, a need exists for the development of computer-based analysis of laparoscopic videos to accelerate surgical training and assessment. We developed a surgical instrument detection system for video recordings of laparoscopic gastrectomy procedures. This system, whose use may increase the efficiency of the video reviewing process, is based on the open source neural network platform, YOLOv3. STUDY DESIGN A total of 10,716 images extracted from 52 laparoscopic gastrectomy videos were included in the training and validation data sets. We performed 200,000 iterations of training. Video recordings of ten laparoscopic gastrectomies, independent of the training and validation data set, were analyzed by our system, and heat maps visualizing trends of surgical instrument usage were drawn. Three skilled surgeons evaluated whether each heat map represented the features of the corresponding operation. RESULTS After training, the testing dataset precision and sensitivity (recall) was 0.87 and 0.83, respectively. The heat maps perfectly represented the devices used during each operation. Without reviewing the video recordings, the surgeons accurately recognized the type of anastomosis, time taken to initiate duodenal and gastric dissection, and whether any irregular procedure was performed from the heat maps (correct answer rates ≥ 90%). CONCLUSION A new automated system to detect manipulations of surgical instruments in video recordings of laparoscopic gastrectomies based on the open source neural network platform, YOLOv3, was successfully developed and validated. BACKGROUND The ACGME requires diversity in residency. The self-identified race/ethnicity of general surgery applicants, residents, and core teaching faculty were assessed to evaluate underrepresented minority (URM) representation in surgery residency programs and to determine the impact of URM faculty and resident on URM applicants' selection for interview or match. STUDY DESIGN Data from the 2018 application cycle was collated for 10 general surgery programs. Applicants without a self-identified race/ethnicity were excluded. URMs were defined as those identifying as Black/African American, Hispanic/Latino/of Spanish origin, American Indian/Alaskan Native/Native Hawaiian/Pacific Islander-Samoan. Statistical analyses included chi-square tests, and a multivariate model. RESULTS Ten surgery residency programs received 9,143 applications from 3,067 unique applicants. Applications from White, Asian, Hispanic/Latino, Black/African American and American Indian applicants constituted 66%, 19%, 8%, 7% and 1% of those applications selected to interview and 66%, 13%, 11%, 8% and 2% of applications resulting in a match.
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