Pathway focused protein profiling indicates differential function for IL-1B, -18 and VEGF during initiation and resolution of lung inflammation evoked by carbon nanoparticle exposure in mice

<p>Abstract</p> <p>Background</p> <p>Carbonaceous nanoparticles possess an emerging source of human exposure due to the massive release of combustion products and the ongoing revolution in nanotechnology. Pulmonary inflammation caused by deposited nanoparticles is central for their adverse health effects. Epidemiological studies suggest that individuals with favourable lung physiology are at lower risk for particulate matter associated respiratory diseases probably due to efficient control of inflammation and repair process. Therefore we selected a mouse strain C3H/HeJ (C3) with robust lung physiology and exposed it to moderately toxic carbon nanoparticles (CNP) to study the elicited pulmonary inflammation and its resolution.</p> <p>Methods</p> <p>5 μg, 20 μg and 50 μg CNP were intratracheally (i.t.) instilled in C3 mice to identify the optimal dose for subsequent time course studies. Pulmonary inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers.</p> <p>Results</p> <p>1 day after instillation of CNP, C3 mice exhibited a typical dose response, with the lowest dose (5 μg) representing the 'no effect level' as reflected by polymorphonuclear leucocyte (PMN), and BAL/lung concentrations of pro-inflammatory proteins. Histological analysis and BAL-protein concentration did not reveal any evidence of tissue injury in 20 μg CNP instilled animals. Accordingly time course assessment of the inflammatory response was performed after 3 and 7 days with this dose (20 μg). Compared to day 1, BAL PMN counts were significantly decreased at day 3 and completely returned to normal by day 7. We have identified protein markers related to the acute response and also to the time dependent response in lung and BAL. After complete resolution of PMN influx on day 7, we detected elevated concentrations of 20 markers that included IL1B, IL18, FGF2, EDN1, and VEGF in lung and/or BAL. Biological pathway analysis revealed these factors to be involved in a closely regulated molecular cascade with IL1B/IL18 as upstream and FGF2/EDN1/VEGF as downstream molecules.</p> <p>Conclusion</p> <p>Considering the role of VEGF, FGF2 and EDN1 in lung development and morphogenesis together with the lack of any evident tissue damage we suggest a protective/homeostatic machinery to be associated in lungs of stable organisms to counter the CNP challenge as a precautionary measure.</p

Impaired resolution of inflammatory response in the lungs of JF1/Msf mice following carbon nanoparticle instillation

<p>Abstract</p> <p>Background</p> <p>Declined lung function is a risk factor for particulate matter associated respiratory diseases like asthma and chronic obstructive pulmonary disease (COPD). Carbon nanoparticles (CNP) are a prominent component of outdoor air pollution that causes pulmonary toxicity mainly through inflammation. Recently we demonstrated that mice (C3H/HeJ) with higher than normal pulmonary function resolved the elicited pulmonary inflammation following CNP exposure through activation of defense and homeostasis maintenance pathways. To test whether CNP-induced inflammation is affected by declined lung function, we exposed JF1/Msf (JF1) mice with lower than normal pulmonary function to CNP and studied the pulmonary inflammation and its resolution.</p> <p>Methods</p> <p>5 μg, 20 μg and 50 μg CNP (Printex 90) were intratracheally instilled in JF1 mice to determine the dose response and the time course of inflammation over 7 days (20 μg dosage). Inflammation was assessed using histology, bronchoalveolar lavage (BAL) analysis and by a panel of 62 protein markers.</p> <p>Results</p> <p>24 h after instillation, 20 μg and 50 μg CNP caused a 25 fold and 19 fold increased polymorphonuclear leucocytes (PMN) respectively while the 5 μg represented the 'no observable adverse effect level' as reflected by PMN influx (9.7 × 10E3 vs 8.9 × 10E3), and BAL/lung concentrations of pro-inflammatory cytokines. Time course assessment of the inflammatory response revealed that compared to day1 the elevated BAL PMN counts (246.4 × 10E3) were significantly decreased at day 3 (72.9 × 10E3) and day 7 (48.5 × 10E3) but did not reach baseline levels indicating slow PMN resolution kinetics. Strikingly on day 7 the number of macrophages doubled (455.0 × 10E3 vs 204.7 × 10E3) and lymphocytes were 7-fold induced (80.6 × 10E3 vs 11.2 × 10E3) compared to day1. At day 7 elevated levels of IL1B, TNF, IL4, MDC/CCL22, FVII, and vWF were detected in JF1 lungs which can be associated to macrophage and lymphocyte activation.</p> <p>Conclusion</p> <p>This explorative study indicates that JF1 mice with impaired pulmonary function also exhibits delayed resolution of particle mediated lung inflammation as evident from elevated PMN and accumulation of macrophages and lymphocytes on day7. It is plausible that elevated levels of IL1B, IL4, TNF, CCL22/MDC, FVII and vWF counteract defense and homeostatic pathways thereby driving this phenomenon.</p

Social media guidelines and best practices - Recommendations from the council of residency directors (cord) social media taskforce

Social media has become a staple of everyday life among over one billion people worldwide. A social networking presence has become a hallmark of vibrant and transparent communications. It has quickly become the preferred method of communication and information sharing. It offers the ability for various entities, especially residency programs, to create an attractive internet presence and “brand� the program. Social media, while having significant potential for communication and knowledge transfer, carries with it legal, ethical, personal, and professional risks. Implementation of a social networking presence must be deliberate, transparent, and optimize potential benefits while minimizing risks. This is especially true with residency programs. The power of social media as a communication, education, and recruiting tool is undeniable. Yet the pitfalls of misuse can be disastrous, including violations in patient confidentiality, violations of privacy, and recruiting misconduct. These guidelines were developed to provide emergency medicine residency programs leadership with guidance and best practices in the appropriate use and regulation of social media, but are applicable to all residency programs that wish to establish a social media presence

Case files : Emergency medicine

xvii+542hlm.;22c

Predictors of a Top Performer During Emergency Medicine Residency.

BACKGROUND: Emergency Medicine (EM) residency program directors and faculty spend significant time and effort creating a residency rank list. To date, however, there have been few studies to assist program directors in determining which pre-residency variables best predict performance during EM residency. OBJECTIVE: To evaluate which pre-residency variables best correlated with an applicant\u27s performance during residency. METHODS: This was a retrospective multicenter sample of all residents in the three most recent graduating classes from nine participating EM residency programs. The outcome measure of top residency performance was defined as placement in the top third of a resident\u27s graduating class based on performance on the final semi-annual evaluation. RESULTS: A total of 277 residents from nine institutions were evaluated. Eight of the predictors analyzed had a significant correlation with the outcome of resident performance. Applicants\u27 grade during home and away EM rotations, designation as Alpha Omega Alpha (AOA), U.S. Medical Licensing Examination (USMLE) Step 1 score, interview scores, global rating and competitiveness on nonprogram leadership standardized letter of recommendation (SLOR), and having five or more publications or presentations showed a significant association with residency performance. CONCLUSION: We identified several predictors of top performers in EM residency: an honors grade for an EM rotation, USMLE Step 1 score, AOA designation, interview score, high SLOR rankings from nonprogram leadership, and completion of five or more presentations and publications. EM program directors may consider utilizing these variables during the match process to choose applicants who have the highest chance of top performance during residency