Collectively these data suggest that extracellular Hsp72 is released from virally infected airway epithelial cells resulting in the recruitment and activation of neutrophils.

Heat shock proteins are generally regarded as intracellular proteins acting as molecular chaperones; however, Hsp72 is also detected in the extracellular compartment. Hsp72 has been identified in the bronchoalveolar lavage fluid (BALF) of patients with acute lung injury. To address whether Hsp72 directly activated airway epithelium, human bronchial epithelial cells (16HBE14o-) were treated with recombinant Hsp72. Hsp72 induced a dose-dependent increase in IL-8 expression, which was inhibited by the NF-κB inhibitor parthenolide. Hsp72 induced activation of NF-κB, as evidenced by NF-κB trans-activation and by p65 RelA and p50 NF-κB1 binding to DNA. Endotoxin contamination of the Hsp72 preparation was not responsible for these effects. Next, BALB/c mice were challenged with a single intratracheal inhalation of Hsp72 and killed 4 h later. Hsp72 induced significant up-regulation of KC, TNF-α, neutrophil recruitment, and myeloperoxidase in the BALF. A similar challenge with Hsp72 in TLR4 mutant mice did not stimulate the inflammatory response, stressing the importance of TLR4 in Hsp72-mediated lung inflammation. Last, cultured mouse tracheal epithelial cells (MTEC) from BALB/c and TLR4 mutant and wild-type mice were treated ex vivo with Hsp72. Hsp72 induced a significant increase in KC expression from BALB/c and wild-type MTEC in an NF-κB-dependent manner; however, TLR4 mutant MTEC had minimal cytokine release. Taken together, these data suggest that Hsp72 is released and biologically active in the BALF and can regulate airway epithelial cell cytokine expression in a TLR4 and NF-κB-dependent mechanism.

Drug death victims, both for accidents and for suicides, have a broad range of ages. About two-thirds of decedents are between 30 and 50, with a mean age of 40. Sixty-eight percent of accidental overdoses and 49% of suicides are male. Selected demographic comparisons between overdose victims and the general (Maine 2000 Census) population include the following notable statistics. Compared to the general population, among victims, there are 14% more males, 9% fewer Maine natives, and 34% fewer who are married. About 6% fewer victims have earned at least a high school diploma. (Table 3): Table 3. Highlighted demographic characteristics for all drug related deaths, 1997-2002, compared to the Maine 2000 Census population Drug Overdose Victims Maine 2000 Census Males 62% 48% Born in Maine 58% 67% Married 24% 58% 71% 36% 79% Single/Divorced Education high school or greater 85%

Residency is a high-risk period for physician burnout. We aimed to determine the short-term stability of factors associated with burnout, application of these data to previous conceptual models, and the relationship of these factors over 3 months. Physician wellness questionnaire results were analyzed at 2 time points 3 months apart. Associations among variables within and across time points were analyzed. Logistic regression was used to predict burnout and compassionate care. A total of 74% of residents completed surveys. Over 3 months, burnout (P = .005) and empathy (P = .04) worsened. The most significant cross-sectional relationship was between stress and emotional exhaustion (time 1 r = 0.61, time 2 r = 0.68). Resilience was predictive of increased compassionate care and decreased burnout (P < .05). Mindfulness was predictive of decreased burnout (P < .05). Mitigating stress and fostering mindfulness and resilience longitudinally may be key areas of focus for improved wellness in pediatric residents. Larger studies are needed to better develop targeted wellness interventions.