Medical ethics education as translational bioethics.

We suggest that in the particular context of medical education, ethics can be considered in a similar way to other kinds of knowledge that are categorised and shaped by academics in the context of wider society. Moreover, the study of medical ethics education is translational in a manner loosely analogous to the study of medical education as adjunct to translational medicine. Some have suggested there is merit in the idea that much as translational research attempts to connect the laboratory scientist's work to its implications for patient care, translational ethics focuses on bringing ethics scholarship into the sphere of personal and public action. We distinguish the term 'translational ethics' (the study of ethics being translated between academy, classroom and clinic) from other prominent definitions in the bioethics literature. To do this, we build off a notion of knowledge translation that focuses on the nonlinear movement of information that comes to professionals through multiple competing sources. We suggest that this knowledge, and particularly knowledge about ethics, becomes embodied by the individual. It is through a reflective practice that internally embedded ethics knowledge might be modified, and this work might be best carried out with a moral community that maintains a sense of practical wisdom. Applying this translational approach to the study of medical ethics education can be both academically relevant and practically useful. This view of translation can help bridge the evident, multidirectional relationships between research, education and performance. It might also create further opportunities to develop medical ethics education theory.

Repurposing Hsp90 inhibitors as antibiotics targeting histidine kinases.

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.

A concept analysis of moral resilience.

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.

Mindful Ethical Practice and Resilience Academy: Equipping Nurses to Address Ethical Challenges.

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.

Towards Patient-Centered Conflicts of Interest Policy.

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.

Disabling of the erbB Pathway Followed by IFN-γ Modifies Phenotype and Enhances Genotoxic Eradication of Breast Tumors.

Reversion of the malignant phenotype of erbB2-transformed cells can be driven by anti-erbB2/neu monoclonal antibodies (mAbs), which disrupt the receptor's kinase activity. We examined the biologic effects of IFN-γ alone or after anti-erbB2/neu mAb treatment of erbB2-positive cells. IFN-γ had no effect on its own. Treatment of the tumors with anti-erbB2/neu mAbs followed by IFN-γ led to dramatic inhibition of tumor growth in vitro and in vivo with minimal mAb dosing. Sequential therapy enhanced the effects of chemotherapy. Moreover, IFN-γ with mAb treatment of mice with IFNγR knockdown tumors did not demonstrate marked synergistic eradication effects, indicating an unexpected role of IFN-γ on the tumor itself. Additionally, mAb and IFN-γ treatment also induced immune host responses that enhanced tumor eradication. Biochemical analyses identified loss of Snail expression in tumor cells, reflecting diminution of tumor-stem-cell-like properties as a consequence of altered activity of GSK3-ß and KLF molecules.

Basal and stress-induced Hsp70 are modulated by ataxin-3.

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.