I schemia-reperfusion (I/R) injury could lead to ischemic renal failure, which is one of the most common forms of acute renal failure of the native kidneys as well as of the renal allograft (1-5). Despite major advances in understanding the pathogenesis of I/R, no satisfactory therapy is available, and ischemic acute renal failure remains a major cause of morbidity and mortality (6). I/R injury begins with tissue hypoperfusion/hypoxia and leads to depletion of cellular ATP and cytoskeletal damage (7,8). Restoration of blood flow is accompanied by reperfusion injury, which is characterized by production of a number of inflammatory molecules such as cytokines, reactive oxygen species (ROS), activation of leukocyte and endothelial cells, and upregulation of adhesion molecules/chemokines. The interactions of activated leukocytes with injured endothelial cells play a crucial role in the pathogenesis of the disease (6,9,10). There is a growing body of evidence indicating that ischemic renal failure is an inflammatory disease (6,11). Antineutrophil strategies, T cell depletion, and blockade of T cell CD28-B7 co-stimulation have been reported to be beneficial in protection against I/R injury (12-15). Chemokines are 8-to 10-kd proteins that play a central role in inflammation. They regulate all of the steps that are necessary for the recruitment of leukocytes to the sites of inflammation, including leukocyte activation, adhesion, chemoattraction, and transmigration across the endothelial barrier (16 -18). Chemokines are also important regulators of T helper 1 (Th1)/Th2 responses as Th1 chemokines selectively recruit Th1 cells to sites of inflammation (19 -23). A Th1 shift has been shown to have a deleterious effect in the pathogenesis of I/R (24). The CXC chemokine receptor 3 (CXCR3) is expressed predominantly on a majority of activated inflammatory (16). A high expression of CXCR3 receptor and its ligands has been reported in different models of inflammation, including rheumatoid arthritis, multiple sclerosis lesions, type 1 diabetes, and allograft rejection (25-28). Anti-CXCR3 strategies to reduce inflammation have yielded promising results in these disease models (24,25,29 -33). The role of CXCR3 in the pathogenesis of I/R injury remains to be elucidated. Therefore, we tested the hypothesis that CXCR3 signaling plays a role in the induction of inflammation through Th1 cell infiltration, mediating renal I/R injury. Materials and Methods Animals CXCR3Ϫ/Ϫ mice were generated in Craig Gerald's laboratory (30).C57BL/6 mice, purchased from Jackson Laboratory (Bar Harbor, ME),

Rationale Stress experience during adolescence has been linked to the development of psychiatric disorders in adulthood, many of which are associated with impairments in prefrontal cortex function. Objective The current study was designed to determine the immediate and enduring effects of repeated social stress on a prefrontal cortex-dependent cognitive task. Methods Early adolescent (P28), mid-adolescent (P42), and adult (P70) rats were exposed to resident–intruder stress for 5 days and tested in an operant strategy-shifting task (OSST) during the following week or several weeks later during adulthood. Engagement of prefrontal cortical neurons during the task was assessed by expression of the immediate early gene, c-fos. Results Social stress during adolescence had no immediate effects on task performance, but impaired strategy-shifting in adulthood, whereas social stress that occurred during adulthood had no effect. The cognitive impairment produced by adolescent social stress was most pronounced in rats with a passive coping strategy. Notably, strategy-shifting performance was positively correlated with medial prefrontal cortical c-fos in adulthood but not in adolescence, suggesting that the task engages different brain regions in adolescents compared to adults. Conclusions Adolescent social stress produces a protracted impairment in prefrontal cortex-mediated cognition that is related to coping strategy. This impairment may be selectively expressed in adulthood because prefrontal cortical activity is integral to task performance at this age but not during adolescence.

BACKGROUND: Plasma has been shown to mitigate the endotheliopathy of trauma. Protection of the endothelium may be due in part to fibrinogen and other plasma-derived proteins found in cryoprecipitate; however, the exact mechanisms remain unknown. Clinical trials are underway investigating early cryoprecipitate administration in trauma. In this study, we hypothesize that cryoprecipitate will inhibit endothelial cell (EC) permeability in vitro and will replicate the ability of plasma to attenuate pulmonary vascular permeability and inflammation induced by hemorrhagic shock and trauma (HS/T) in mice. METHODS:In vitro, barrier permeability of ECs subjected to thrombin challenge was measured by transendothelial electrical resistance. In vivo, using an established mouse model of HS/T, we compared pulmonary vascular permeability among mice resuscitated with (1) lactated Ringer's solution (LR), (2) fresh frozen plasma (FFP), or (3) cryoprecipitate. Lung tissue from the mice in all groups was analyzed for markers of vascular integrity, inflammation, and inflammatory gene expression via NanoString messenger RNA quantification. RESULTS:Cryoprecipitate attenuates EC permeability and EC junctional compromise induced by thrombin in vitro in a dose-dependent fashion. In vivo, resuscitation of HS/T mice with either FFP or cryoprecipitate attenuates pulmonary vascular permeability (sham, 297 ± 155; LR, 848 ± 331; FFP, 379 ± 275; cryoprecipitate, 405 ± 207; p < 0.01, sham vs. LR; p < 0.01, LR vs. FFP; and p < 0.05, LR vs. cryoprecipitate).Lungs from cryoprecipitate-and FFP-treated mice demonstrate decreased lung injury, decreased infiltration of neutrophils and activation of macrophages, and preserved pericyte-endothelial interaction compared with LR-treated mice. Gene analysis of lung tissue from cryoprecipitate-and FFP-treated mice demonstrates decreased inflammatory gene expression, in particular, IL-1β and NLRP3, compared with LR-treated mice. CONCLUSION: Our data suggest that cryoprecipitate attenuates the endotheliopathy of trauma in HS/T similar to FFP. Further investigation is warranted on active components and their mechanisms of action.

BackgroundOperating room to intensive care unit handoffs are high-risk events for critically ill patients. Studies in selected patient populations show that standardizing operating room to intensive care unit handoffs improves information exchange and decreases errors. To adapt these findings to mixed surgical populations, we propose to study the implementation of a standardized operating room to intensive care unit handoff process in two intensive care units currently without an existing standard process.Methods/DesignThe Handoffs and Transitions in Critical Care (HATRICC) study is a hybrid effectiveness- implementation trial of operating room to intensive care unit handoffs. We will use mixed methods to conduct a needs assessment of the current handoff process, adapt published handoff processes, and implement a new standardized handoff process in two academic intensive care units. Needs assessment: We will use non-participant observation to observe the current handoff process. Focus groups, interviews, and surveys of clinicians will elicit participants’ impressions about the current process. Adaptation and implementation: We will adapt published standardized handoff processes using the needs assessment findings. We will use small group simulation to test the new process’ feasibility. After simulation, we will incorporate the new handoff process into the clinical work of all providers in the study units. Evaluation: Using the same methods employed in the needs assessment phase, we will evaluate use of the new handoff process. Data analysis: The primary effectiveness outcome is the number of information omissions per handoff episode as compared to the pre-intervention period. Additional intervention outcomes include patient intensive care unit length of stay and intensive care unit mortality. The primary implementation outcome is acceptability of the new process. Additional implementation outcomes include feasibility, fidelity and sustainability.DiscussionThe HATRICC study will examine the effectiveness and implementation of a standardized operating room to intensive care unit handoff process. Findings from this study have the potential to improve healthcare communication and outcomes for critically ill patients.Trial registrationClinicalTrials.gov identifier: NCT02267174. Date of registration October 16, 2014.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2482-14-96) contains supplementary material, which is available to authorized users.