Bacillus anthracis edema toxin (ET), composed of protective antigen and an adenylate cyclase edema factor (EF), elicits edema in host tissues, but the target cells and events leading from EF-mediated cyclic-AMP production to edema are unknown. We evaluated the direct effect of ET on several cell types in vitro and tested the possibility that mediators of vascular leakage, such as histamine, contribute to edema in rabbits given intradermal ET. ET increased the transendothelial electrical resistance of endothelial monolayers, a response that is mechanistically inconsistent with the in vivo vascular leakage induced by ET. Screening of several drugs by intradermal treatment prior to toxin injection demonstrated reduced ET-induced vascular leakage with a cyclo-oxygenase inhibitor (indomethacin), agents that interfere with histamine (pyrilamine or cromolyn), or a neurokinin antagonist (spantide). Systemic administration of indomethacin or celecoxib (cyclo-oxygenase inhibitors), pyrilamine, aprepitant (a neurokinin 1 receptor antagonist), or indomethacin with pyrilamine significantly reduced vascular leakage associated with ET. Although the effects of pyrilamine, cromolyn, or aprepitant on ET-induced vascular leakage suggest a possible role for mast cells (MC) and sensory neurons in ET-induced edema, ET did not elicit degranulation of human skin MC or substance P release from NT2N cells in vitro. Our results indicate that ET, acting indirectly or directly on a target yet to be identified, stimulates the production/release of multiple inflammatory mediators, specifically neurokinins, prostanoids, and histamine. These mediators, individually and through complex interactions, increase vascular permeability, and interventions directed at these mediators may benefit hosts infected with B. anthracis.Bacillus anthracis is a gram-positive, spore-forming bacillus that causes the disease known as anthrax. The vegetative form of B. anthracis results from spore inoculation of the host animal via cutaneous, gastrointestinal, or inhalational routes (57). Subsequently, spores germinate in a complex process that involves phagocytosis of spores by macrophages and transport of germinating spores within macrophages to regional lymphatics. The vegetative bacilli may then gain entry to the systemic circulation and spread to other sites in the host. This process is facilitated by virulence factors expressed by vegetative bacilli: (i) an antiphagocytic capsule and (ii) lethal toxin (LT) and edema toxin (ET). LT consists of protective antigen (PA) and lethal factor (LF), while ET consists of PA and edema factor (EF) (57).PA undergoes proteolytic cleavage to a 63-kDa monomer, with subsequent formation of a heptamer capable of binding up to three molecules of EF or LF (15). PA heptamers bind to two different widely expressed cell surface receptors, anthrax toxin receptor/tumor endothelial marker 8 and/or capillary morphogenesis protein 2, and undergo receptor-mediated endocytosis with trafficking to an acidic endosomal compartment (5,6,54). Aci...

Background Treatment decision-making regarding immunosuppressive therapy is challenging for individuals with lupus. We assessed the effectiveness of a decision aid for immunosuppressive therapy in lupus nephritis. Methods and findings In a United States multicenter, open-label, randomized controlled trial (RCT), adult women with lupus nephritis, mostly from racial/ethnic minority backgrounds with low socioeconomic status (SES), seen in in- or outpatient settings, were randomized to an individualized, culturally tailored, computerized decision aid versus American College of Rheumatology (ACR) lupus pamphlet (1:1 ratio), using computer-generated randomization. We hypothesized that the co-primary outcomes of decisional conflict and informed choice regarding immunosuppressive medications would improve more in the decision aid group. Of 301 randomized women, 298 were analyzed; 47% were African-American, 26% Hispanic, and 15% white. Mean age (standard deviation [SD]) was 37 (12) years, 57% had annual income of <$40,000, and 36% had a high school education or less. Compared with the provision of the ACR lupus pamphlet ( n = 147), participants randomized to the decision aid ( n = 151) had (1) a clinically meaningful and statistically significant reduction in decisional conflict, 21.8 (standard error [SE], 2.5) versus 12.7 (SE, 2.0; p = 0.005) and (2) no difference in informed choice in the main analysis, 41% versus 31% ( p = 0.08), but clinically meaningful and statistically significant difference in sensitivity analysis (net values for immunosuppressives positive [in favor] versus negative [against]), 50% versus 35% ( p = 0.006). Unresolved decisional conflict was lower in the decision aid versus pamphlet groups, 22% versus 44% ( p < 0.001). Significantly more patients in the decision aid versus pamphlet group rated information to be excellent for understanding lupus nephritis (49% versus 33%), risk factors (43% versus 27%), medication options (50% versus 33%; p ≤ 0.003 for all); and the ease of use of materials was higher in the decision aid versus pamphlet groups (51% versus 38%; p = 0.006). Key study limitations were the exclusion of men, short follow-up, and the lack of clinical outcomes, including medication adherence. Conclusions An individualized decision aid was more effective than usual care in reducing decisional conflict for choice of immunosuppressive medications in women with lupus nephritis. Trial registration Clinicaltrials.gov, NCT02319525 .

Research is limited on how nurses in community settings manage ethical conflicts. To address this gap, we conducted a study to uncover the process of behaviors enacted by community nurses when experiencing ethical conflicts. Guided by Glaserian grounded theory, we developed a theoretical model (Moral Compassing) that enables us to explain the process how 24 community nurses managed challenging ethical situations. We discovered that the main concern with which nurses wrestle is moral uncertainty (“Should I be addressing what I think is a moral problem?”). Moral Compassing comprises processes that resolve this main concern by providing community nurses with the means to attain the moral agency necessary to decide to act or to decide not to act. The processes are undergoing a visceral reaction, self-talk, seeking validation, and mobilizing support for action or inaction. We also discovered that community nurses may experience continuing distress that we labeled moral residue.

Objective The aim of this study was to report patient-centered outcomes and finalization of key study procedures from a 9-month pilot internet randomized controlled trial of cherry extract versus diet modification. Methods We randomized 84 people with physician-confirmed gout in an internet study to cherry extract (n = 41) or dietitian-assisted diet modification for gout (n = 43). All study outcomes were collected via internet and phone calls. We finalized key study procedures. We assessed acceptability and feasibility of the intervention and satisfaction with study website. Results Study participant satisfaction with the intervention was high. The intervention was perceived as easy, enjoyable, understandable, and helpful (scores 65–88 for all; higher = better). The amount of time spent for the study was acceptable. Participant satisfaction with website interaction and content was very high; 85% or more were moderately to extremely satisfied. Significantly lower total calories, total carbohydrate, and saturated fat intake were noted at 6 months in the diet modification versus cherry extract group; differences were insignificant at 9 months. Six of the 8 Health Assessment Questionnaire sections/domains improved significantly from baseline to 9 months in cherry extract versus 2 Health Assessment Questionnaire sections/domains in the diet modification group. Key study procedures were finalized for a future trial, including an internet diet assessment tool, gout flare assessment, provider confirmation of gout diagnosis, patient reporting of classification criteria, and centralized laboratory-assisted serum urate testing. Conclusions High patient acceptability and feasibility of study/intervention and finalization of key study procedures indicate that hypothesis-testing internet gout trials of cherry extract and/or diet modification can be conducted in the future.

BackgroundSystemic Lupus erythematosus (SLE), also commonly referred to as lupus, is a rare, but sometimes, fatal disease, that primarily affects young women. Lupus nephritis, a common manifestation of lupus, is more common and more devastating in patients of minority race/ethnicity. Patients have negative views of immunosuppressive drugs for lupus nephritis due to a concern about side effects and under-appreciation of its benefit. We designed a study to assess the effectiveness of individualized, computerized patient decision-aid for immunosuppressive drugs for lupus nephritis compared to a standard pamphlet for patient decision-making.MethodsAdult women with lupus nephritis, with a current lupus nephritis flare or at risk of a future lupus nephritis flare will be randomized to individualized, computerized patient decision-aid for immunosuppressive drugs vs. standard pamphlet with information about lupus and its treatment including immunosuppressive drugs and outcomes. Patients will complete outcome assessments immediately after the intervention has been administered. Patients will be followed at 3-months with a brief survey, either in person or on the phone, and at 6-months with medical record review for exploratory outcomes. Co-primary outcomes are decisional conflict and informed choice regarding immunosuppressive drugs (combines values, knowledge and choice). Secondary outcomes include: (1) assessment of patient-physician communication by assessing audio-taped physician-patient communication after intervention administration; (2) concordance between patient’s desired and actual role in immunosuppressive drugs decision-making using the control preference scale (CPS); and (3) patient perception of physician interaction using the interpersonal process of care- short form (IPC-SF).DiscussionThis is one of the first studies to evaluate the effectiveness of an educational intervention targeting minorities with lupus nephritis. This patient-centered lupus nephritis decision-aid will be available in the public domain in English and Spanish.Trial registrationClinicalTrials.gov Identifier: NCT02319525; registered on November 5, 2014.