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Background Ethical challenges in clinical practice significantly affect frontline nurses, leading to moral distress, burnout, and job dissatisfaction, which can undermine safety, quality, and compassionate care. Objectives To examine the impact of a longitudinal, experiential educational curriculum to enhance nurses’ skills in mindfulness, resilience, confidence, and competence to confront ethical challenges in clinical practice. Methods A prospective repeated-measures study was conducted before and after a curricular intervention at 2 hospitals in a large academic medical system. Intervention participants (192) and comparison participants (223) completed study instruments to assess the objectives. Results Mindfulness, ethical confidence, ethical competence, work engagement, and resilience increased significantly after the intervention. Resilience and mindfulness were positively correlated with moral competence and work engagement. As resilience and mindfulness improved, turnover intentions and burnout (emotional exhaustion and depersonalization) decreased. After the intervention, nurses reported significantly improved symptoms of depression and anger. The intervention was effective for intensive care unit and non–intensive care unit nurses (exception: emotional exhaustion) and for nurses with different years of experience (exception: turnover intentions). Conclusions Use of experiential discovery learning practices and high-fidelity simulation seems feasible and effective for enhancing nurses’ skills in addressing moral adversity in clinical practice by cultivating the components of moral resilience, which contributes to a healthy work environment, improved retention, and enhanced patient care.

To address the growing need for new antimicrobial agents, we explored whether inhibition of bacterial signaling machinery could inhibit bacterial growth. Because bacteria rely on two-component signaling systems to respond to environmental changes, and because these systems are both highly conserved and mediated by histidine kinases, inhibiting histidine kinases may provide broad spectrum antimicrobial activity. The histidine kinase ATP binding domain is conserved with the ATPase domain of eukaryotic Hsp90 molecular chaperones. To find a chemical scaffold for compounds that target histidine kinases, we leveraged this conservation. We screened ATP competitive Hsp90 inhibitors against CckA, an essential histidine kinase in Caulobacter crescentus that controls cell growth, and showed that the diaryl pyrazole is a promising scaffold for histidine kinase inhibition. We synthesized a panel of derivatives and found that they inhibit the histidine kinases C. crescentus CckA and Salmonella PhoQ but not C. crescentus DivJ; and they inhibit bacterial growth in both Gram-negative and Gram-positive bacterial strains.

Financial conflicts of interest exist between industry and physicians, and these relationships have the power to influence physicians’ medical practice. Transparency about conflicts matters for ensuring adequate informed consent, controlling healthcare expenditure, and encouraging physicians’ reflection on professionalism. The US Centers for Medicare & Medicaid Services (CMS) launched the Open Payments Program (OPP) to publicly disclose and bring transparency to the relationships between industry and physicians in the United States. We set out to explore user awareness of the database and the ease of accessibility to disclosed information, however, as we show, both awareness and actual use are very low. Two practical policies can greatly enhance its intended function and help alleviate ethical tension. The first is to provide data for individual physicians not merely in absolute terms, but in meaningful context, that is, in relation to the zip code, city, and state averages. The second increases access to the OPP dataset by adding hyperlinks from physicians’ professional websites directly to their Open Payments disclosure pages. These changes considerably improve transparency and the utility of available data, and can furthermore enhance professionalism and accountability by encouraging physicians to reflect more actively on their own practices.

Background Nurses experience moral distress, which has led to emotional distress, frustration, anger, and nurse attrition. Overcoming moral distress has become a significant focus in nursing research. Purpose The continued focus on moral distress has not produced sustainable solutions within the nursing profession. Since positive language may alter the outcomes of morally distressing situations, we look to better understand one such positive phrase, moral resilience. Methods We explored moral resilience through a literature search using 11 databases to identify instances of the phrase. Occurrences of moral resilience were then divided into three distinct categories: antecedents, attributes, and consequences, and following this, major themes within each category were identified. Discussion There is a dearth of scholarship on moral resilience, and additionally, there is currently no unifying definition. Despite this, our analysis offers promising direction in refining the concept. Conclusion This concept analysis reveals differences in how moral resilience is understood. More conceptual work is needed to refine the definition of moral resilience and understand how the concept is useful in mitigating the negative consequences of moral distress and other types of moral adversity.

Regulation of basal and induced levels of hsp70 is critical for cellular homeostasis. Ataxin-3 is a deubiquitinase with several cellular functions including transcriptional regulation and maintenance of protein homeostasis. While investigating potential roles of ataxin-3 in response to cellular stress, it appeared that ataxin-3 regulated hsp70. Basal levels of hsp70 were lower in ataxin-3 knockout (KO) mouse brain from 2 to 63 weeks of age and hsp70 was also lower in fibroblasts from ataxin-3 KO mice. Transfecting KO cells with ataxin-3 rescued basal levels of hsp70 protein. Western blots of representative chaperones including hsp110, hsp90, hsp70, hsc70, hsp60, hsp40/hdj2, and hsp25 indicated that only hsp70 was appreciably altered in KO fibroblasts and KO mouse brain. Turnover of hsp70 protein was similar in wild-type (WT) and KO cells; however, basal hsp70 promoter reporter activity was decreased in ataxin-3 KO cells. Transfecting ataxin-3 restored hsp70 basal promoter activity in KO fibroblasts to levels of promoter activity in WT cells; however, mutations that inactivated deubiquitinase activity or the ubiquitin interacting motifs did not restore full activity to hsp70 basal promoter activity. Hsp70 protein and promoter activity were higher in WT compared to KO cells exposed to heat shock and azetidine-2-carboxylic acid, but WT and KO cells had similar levels in response to cadmium. Heat shock factor-1 had decreased levels and increased turnover in ataxin-3 KO fibroblasts. Data in this study are consistent with ataxin-3 regulating basal level of hsp70 as well as modulating hsp70 in response to a subset of cellular stresses.

Oncogenic erbB2/HER2 is a major transforming determinant of human breast cancer and its amplification is prognostic of poor survival. Monoclonal antibody (mAb)-based therapy to specifically target erbB2/HER2 has been effective in patients with HER2-positive breast cancer; however, some patients do not respond and those who do frequently relapse despite ongoing therapy. The evolution of tumors that resist targeted therapy is complex and involves the emergence of complex transcriptional functions. Snail is overexpressed in recurrent tumors of transgenic HER2/neu mice and snail expression participates in tumor recurrence. Previous studies from our laboratory and others have revealed that targeted therapy requires cooperation with elements of the endogenous immune system for optimal tumor regression activity. The cytokine interferon-gamma (IFN-γ) is relevant to the regression process although the mechanism by which IFN operates on targeted cells remains undefined and the effects of IFN on the transformed cell have not been studied during phenotypic reversion. In the present study, we utilized cell biological and biochemical-based assays to define if targeted therapy could be improved through the addition of IFN-γ and unexpectedly defined a unique mechanism operative to achieve this end. Cell culture model systems were used to examine the co-treatment of erbB2/HER2 targeting with IFN-γ to eliminate issues such as aberrant immune responses, which arise as a consequence of adding IFN-γ to cells. We defined that while mAb targeting of erbB2 reversed the transformed phenotype of HER2-positive breast cancer cells reversion of phenotype was increased upon inclusion of IFN-γ. Co-treatment with the erbB2 mAb and IFN-γ resulted in a greater reduction of snail protein levels compared to either modality alone. Snail degradation was dependent on GSK3-β and active proteasome dependent elimination processes. Furthermore, IFN-γ activated GSK3-β in mAb treated cells to the extent of that observed in cells treated with specific small molecule inhibitors to erbB receptors. Our findings provide a mechanistic explanation as to how to use IFN-γ to optimize mAb-mediated tumor regression. The implication of this study is improvement of targeted efficacy could lead to more comprehensive therapy options that may eliminate tumor recurrence. Citation Format: Edwin Aaron Runkle, Peter Young, Yasuhiro Nagai, Hiromichi Tsuchiya, Hongtao Zhang, Mark I. Greene. Interferon-gamma potentiates the targeted phenotypic reversion of erbb2/her2/neu transformed human tumor cells. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1390. doi:10.1158/1538-7445.AM2014-1390

An active source electrical conductivity sounding was carried out near the East Pacific Rise at 21°N. The average electrical conductivity from 2 km beneath the seafloor into the upper mantle was found to be about 0.004 S/m. There is no evidence of fully molten magma at a distance of 7 km from the spreading axis. The inferred conductivity with depth of the crustal rock is consistent with Brace’s model of connected, seawater filled pores in rocks heated from beneath.

There are two categories of magnetic anomalies associated with the ocean. Primary anomalies are induced directly by interaction of ocean flow with the geomagnetic field, or induced by ionospheric fluctuations, or are the expression of the remnant magnetization of the ocean floor rocks. Secondary anomalies are created by interaction of electric current flow in the ocean, with irregularities of the electrical conductivity distribution within the ocean, or with irregularities of the boundaries of the ocean (seafloor ridges and troughs or ocean surface waves). Our focus in this report is on secondary anomalies, although some attention is paid to primary effects for completeness.