Arslanian-Engoren, Cynthia PhD, RN, ACNS-BC; Tschannen, Dana PhD, RN; Low, Lisa Kane PhD, RN, CNM; Hurn, Patricia D. PhD, RN; Patel, Rushika PhD Author Information

“An eye toward the future: Pressing questions for our discipline in today's academic and research climate” (Algase, 2021Algase D. An eye toward the future: Pressing questions for our discipline in today's academic and research climate.Nursing outlook. 2021; 69: 57-64https://doi.org/10.1016/j.outlook.2020.08.010Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar) in the January/February issue poses questions that are framed from a perspective of concern over the employment of multidisciplinary scientists as faculty in Schools of Nursing – referred to as so-called non-nursing faculty. We write not to make specific rebuttal to each question posed nor to their overall recommendations. We recognize the paper's intent is to drive comment in the community on an issue that the authors believe is still relevant to academic nursing. However, our perspective differs in that the subject of the paper is dated, centers our intellectual energy on a backwards-looking issue that offers little to contemporary schools of nursing. We suggest also, as discussed below, that the article poses the wrong questions imbedded in a flawed premise that centers on a “zero sum game.” By that we mean, the view that opening faculty positions to individuals of differing degrees and credentials in some way will disenfranchise or withdraw support from those who are nurses. In this framework, one would be led to believe that nursing needs protection. In fact, nursing thrives on diversity, partnerships, and colleagues.The National Institute of Nursing Research states on the front page of the ninr.nih.gov website that nursing research develops knowledge to “Build the scientific foundation for clinical practice; Prevent disease and disability; Manage and eliminate symptoms caused by illness and Enhance end-of-life and palliative care.” (National Institute of Nursing Research, 2021National Institute of Nursing Research (2/4/21) https://www.ninr.nih.gov/Google Scholar). On its face, this framework speaks to the broad scope of clinical problems of interest to NINR, complexities that require the tools and skills of multiple disciplines and specialties. Moreover, rapidly expanding research models, data sources, and technologies afford new and challenging avenues for advancing scientific understanding of these phenomena and the solutions that promote better health. The need for integrating science and using interdisciplinary team approaches to solve real issues in human health has never been greater – and portends only further expansion with new discoveries.We cannot imagine any health discipline thriving in future decades that chooses to take regressive and insular perspectives in defining and generating its research approaches. In an article published by Grey and Connolly in 2008, they state “It is clear that tomorrow's nurse scientist must embrace the transdisciplinary future. Because of the complexity of human disease, the solutions to chronic conditions will most likely lie in such approaches….for research to contribute to lasting improvements in practice and policy, clinical research must transcend disciplinary perspectives.” (Grey and Connolly, 2008Grey M. Connolly C.A. Coming together, keeping together, working together”: Interdisciplinary to transdisciplinary research and nursing.Nursing outlook. 2008; 56: 102-107Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar) (p.105). Grey and Connolly further emphasize that to continue to be relevant, all clinical sciences need to focus on problems and solutions, their translation and application in clinical and community settings, and that “the time for intradisciplinary arguing about the definition of nursing science is over.” (Grey and Connolly, 2008Grey M. Connolly C.A. Coming together, keeping together, working together”: Interdisciplinary to transdisciplinary research and nursing.Nursing outlook. 2008; 56: 102-107Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar) (p. 106).Rather than the questions posed in Algase et al., one might center on generative queries within nursing schools: (a) What are the research questions that will transform health care and impact the future of our patients, clients and communities? (b) How to amass the highest quality of multidisciplinary science expertise within our schools to create teams needed to adequately address these formidable research questions? (c) How to assure a culture of respect, equity in opportunity, and career advancement for all faculty? None of these questions are answered by minimizing or marginalizing the contributions of any faculty on the basis of having or not having a nursing credential. Dividing faculty into ‘nurses’ and ‘non-nurses’ as a basis for contributions in ‘nursing science’ undermines the very essence of sound contemporary scientific inquiry. We have known for many years that diverse voices are needed to ask the right research questions and to contrive meaningful solutions to put to scientific evaluation. It is this diversity that is the bedrock of basic science, the means of how other academic health disciplines like public health and medicine have flourished. Nursing should not under-value or fail to embrace the power of many voices, joined in interest around our missions.All Schools of Nursing manage a balanced portfolio of faculty, some with the credentials and background to teach clinical nursing, others with expertise to serve other curricular elements. All Schools hire faculty based on their resources and their mission foci. Some will choose to hire an array of multidisciplinary faculty from which to establish core research teams within their schools. Others may choose to foster more collaborative cross campus networks to foster interdisciplinary team research. Many schools will engage in both strategies to maximize the growth of team science. The good news about the research productivity in Schools of Nursing in the United States, as measured by research funding support, is that it has increased 28.5% in total dollars over the last 5 years and represents an expanding array of NIH institutes (Schnall, 2020Schnall R. National Institute of Health (NIH) funding patterns in Schools of Nursing: Who is funding nursing science research and who is conducting research at Schools of Nursing?.Journal of Professional Nursing. 2020; 36: 34-41Crossref PubMed Scopus (13) Google Scholar). This suggests a growing interest among funding sources in the focus of research programs embedded in Schools of Nursing. We will thrive as a discipline only if such interest expands based on the relevance of our discovery to health care and on the quality of our science. That is the framework that will meet our challenges.Credit StatementThe enclosed manuscript “Commentary” in response to the Nursing Outlook article, “An eye toward the future: Pressing questions for our discipline in today's academic and research climate” by Algase et al. (2021) in the January/February issue is submitted for your consideration.This Commentary was not supported by external funding. “An eye toward the future: Pressing questions for our discipline in today's academic and research climate” (Algase, 2021Algase D. An eye toward the future: Pressing questions for our discipline in today's academic and research climate.Nursing outlook. 2021; 69: 57-64https://doi.org/10.1016/j.outlook.2020.08.010Abstract Full Text Full Text PDF PubMed Scopus (14) Google Scholar) in the January/February issue poses questions that are framed from a perspective of concern over the employment of multidisciplinary scientists as faculty in Schools of Nursing – referred to as so-called non-nursing faculty. We write not to make specific rebuttal to each question posed nor to their overall recommendations. We recognize the paper's intent is to drive comment in the community on an issue that the authors believe is still relevant to academic nursing. However, our perspective differs in that the subject of the paper is dated, centers our intellectual energy on a backwards-looking issue that offers little to contemporary schools of nursing. We suggest also, as discussed below, that the article poses the wrong questions imbedded in a flawed premise that centers on a “zero sum game.” By that we mean, the view that opening faculty positions to individuals of differing degrees and credentials in some way will disenfranchise or withdraw support from those who are nurses. In this framework, one would be led to believe that nursing needs protection. In fact, nursing thrives on diversity, partnerships, and colleagues. The National Institute of Nursing Research states on the front page of the ninr.nih.gov website that nursing research develops knowledge to “Build the scientific foundation for clinical practice; Prevent disease and disability; Manage and eliminate symptoms caused by illness and Enhance end-of-life and palliative care.” (National Institute of Nursing Research, 2021National Institute of Nursing Research (2/4/21) https://www.ninr.nih.gov/Google Scholar). On its face, this framework speaks to the broad scope of clinical problems of interest to NINR, complexities that require the tools and skills of multiple disciplines and specialties. Moreover, rapidly expanding research models, data sources, and technologies afford new and challenging avenues for advancing scientific understanding of these phenomena and the solutions that promote better health. The need for integrating science and using interdisciplinary team approaches to solve real issues in human health has never been greater – and portends only further expansion with new discoveries. We cannot imagine any health discipline thriving in future decades that chooses to take regressive and insular perspectives in defining and generating its research approaches. In an article published by Grey and Connolly in 2008, they state “It is clear that tomorrow's nurse scientist must embrace the transdisciplinary future. Because of the complexity of human disease, the solutions to chronic conditions will most likely lie in such approaches….for research to contribute to lasting improvements in practice and policy, clinical research must transcend disciplinary perspectives.” (Grey and Connolly, 2008Grey M. Connolly C.A. Coming together, keeping together, working together”: Interdisciplinary to transdisciplinary research and nursing.Nursing outlook. 2008; 56: 102-107Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar) (p.105). Grey and Connolly further emphasize that to continue to be relevant, all clinical sciences need to focus on problems and solutions, their translation and application in clinical and community settings, and that “the time for intradisciplinary arguing about the definition of nursing science is over.” (Grey and Connolly, 2008Grey M. Connolly C.A. Coming together, keeping together, working together”: Interdisciplinary to transdisciplinary research and nursing.Nursing outlook. 2008; 56: 102-107Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar) (p. 106). Rather than the questions posed in Algase et al., one might center on generative queries within nursing schools: (a) What are the research questions that will transform health care and impact the future of our patients, clients and communities? (b) How to amass the highest quality of multidisciplinary science expertise within our schools to create teams needed to adequately address these formidable research questions? (c) How to assure a culture of respect, equity in opportunity, and career advancement for all faculty? None of these questions are answered by minimizing or marginalizing the contributions of any faculty on the basis of having or not having a nursing credential. Dividing faculty into ‘nurses’ and ‘non-nurses’ as a basis for contributions in ‘nursing science’ undermines the very essence of sound contemporary scientific inquiry. We have known for many years that diverse voices are needed to ask the right research questions and to contrive meaningful solutions to put to scientific evaluation. It is this diversity that is the bedrock of basic science, the means of how other academic health disciplines like public health and medicine have flourished. Nursing should not under-value or fail to embrace the power of many voices, joined in interest around our missions. All Schools of Nursing manage a balanced portfolio of faculty, some with the credentials and background to teach clinical nursing, others with expertise to serve other curricular elements. All Schools hire faculty based on their resources and their mission foci. Some will choose to hire an array of multidisciplinary faculty from which to establish core research teams within their schools. Others may choose to foster more collaborative cross campus networks to foster interdisciplinary team research. Many schools will engage in both strategies to maximize the growth of team science. The good news about the research productivity in Schools of Nursing in the United States, as measured by research funding support, is that it has increased 28.5% in total dollars over the last 5 years and represents an expanding array of NIH institutes (Schnall, 2020Schnall R. National Institute of Health (NIH) funding patterns in Schools of Nursing: Who is funding nursing science research and who is conducting research at Schools of Nursing?.Journal of Professional Nursing. 2020; 36: 34-41Crossref PubMed Scopus (13) Google Scholar). This suggests a growing interest among funding sources in the focus of research programs embedded in Schools of Nursing. We will thrive as a discipline only if such interest expands based on the relevance of our discovery to health care and on the quality of our science. That is the framework that will meet our challenges. Credit StatementThe enclosed manuscript “Commentary” in response to the Nursing Outlook article, “An eye toward the future: Pressing questions for our discipline in today's academic and research climate” by Algase et al. (2021) in the January/February issue is submitted for your consideration.This Commentary was not supported by external funding. The enclosed manuscript “Commentary” in response to the Nursing Outlook article, “An eye toward the future: Pressing questions for our discipline in today's academic and research climate” by Algase et al. (2021) in the January/February issue is submitted for your consideration. This Commentary was not supported by external funding.

Progesterone has shown neuroprotective effects in preclinical studies in traumatic brain injury (TBI), various types of stroke, spinal cord injury and peripheral nerve damage, neonatal hypoxic/ischemic injury, and some neurodegenerative diseases. This chapter discusses evidence for progesterone's wide range of endogenous effects, sex differences in response to nervous system damage, and the major strands of animal research in progesterone treatment for a range of indications. Finally, it surveys the outcomes and issues in the clinical trials for progesterone in TBI, which failed to corroborate preclinical findings, and suggests approaches for improving preclinical research and clinical trial design for this field.

In June 2015, the National Institutes of Health (NIH) released a Guide notice (NOT-OD-15–102) that highlighted the expectation of the NIH that the possible role of sex as a biologic variable be factored into research design, analyses, and reporting of vertebrate animal and human studies. Anticipating these guidelines, the NIH Office of Research on Women's Health, in October 2014, convened key stakeholders to discuss methods and techniques for integrating sex as a biologic variable in preclinical research. The workshop focused on practical methods, experimental design, and approaches to statistical analyses in the use of both male and female animals, cells, and tissues in preclinical research. Workshop participants also considered gender as a modifier of biology. This article builds on the workshop and is meant as a guide to preclinical investigators as they consider methods and techniques for inclusion of both sexes in preclinical research and is not intended to prescribe exhaustive/specific approaches for compliance with the new NIH policy.—Miller, L. R., Marks, C., Becker, J.B., Hurn, P.D., Chen, W.-J., Woodruff, T., McCarthy, M.M., Sohrabji, F., Schiebinger, L., Wetherington, C.L., Makris, S., Arnold, A. P., Einstein, G., Miller, V. M., Sandberg, K., Maier, S., Cornelison, T. L., Clayton, J. A. Considering sex as a biological variable in preclinical research. FASEB J. 31, 29–34 (2017) www.fasebj.org

Female sex steroids, particularly estrogens, contribute to the sexually dimorphic response observed in cerebral ischemic outcome, with females being relatively protected compared to males. Using a mouse model of cardiac arrest and cardiopulmonary resuscitation, we previously demonstrated that estrogen neuroprotection is mediated in part by the estrogen receptor β, with no involvement of estrogen receptor α. In this study, we examined the neuroprotective effect of the novel estrogen receptor, G protein-coupled estrogen receptor 1 (GPER1/GPR30). Male mice administered with the GPR30 agonist G1 exhibited significantly reduced neuronal injury in the hippocampal CA1 region and striatum. The magnitude of neuroprotection observed in G1-treated mice was indistinguishable from estrogen-treated mice, implicating GPR30 in estrogen neuroprotection. Real-time quantitative RT-PCR indicates that G1 treatment increases expression of the neuroprotective ion channel, small-conductance calcium-activated potassium channel 2. We conclude that GPR30 agonists show promise in reducing brain injury following global cerebral ischemia.

Sex steroids are essential for reproduction and development in animals and humans, and sex steroids also play an important role in neuroprotection following brain injury. New data indicate that sex-specific responses to brain injury occur at the cellular and molecular levels. This review summarizes the current understanding of neuroprotection by sex steroids, particularly estrogen, androgen, and progesterone, based on both in vitro and in vivo studies. Better understanding of the role of sex steroids under physiological and pathological conditions will help us to develop novel effective therapeutic strategies for brain injury.

Activation of poly (ADP-ribose) polymerases (PARP) contributes to ischemic damage by causing neuronal nicotinamide adenine dinucleotide (NAD+) depletion, release of apoptosis-inducing factor and consequent caspase-independent cell death. PARP-mediated cell death is sexually dimorphic, participating in ischemic damage in the male brain, but not the female brain. We tested the hypothesis that androgen signaling is required for this male-specific neuronal cell death pathway. We observed smaller damage following focal cerebral ischemia (MCAO) in male PARP-1 knockout mice compared to wild type (WT) as well as decreased damage in male mice treated with the PARP inhibitor PJ34. Protection from ischemic damage provided by PJ-34 in WT mice is lost after removal of testicular androgens (CAST) and rescued by androgen replacement. CAST PARP-1 KO mice exhibit increased damage compared to intact male KO mice, an effect reversed by androgen replacement in an androgen receptor-dependent manner. Lastly, we observed that ischemia causes an increase in PARP-1 expression that is diminished in the absence of testicular androgens. Our data indicate that PARP-mediated neuronal cell death in the male brain requires intact androgen-androgen receptor signaling.

Isoflurane preconditioning neuroprotection in experimental stroke is male-specific. The role of androgens in the ischemic sensitivity of isoflurane preconditioned male brain and whether androgen effects are androgen receptor dependent were assessed. Male C57BL/6 mice were implanted with flutamide (androgen receptor antagonist), or castrated and implanted with testosterone, dihydrotestosterone, flutamide, letrozole (aromatase inhibitor), or vehicle 7-13 days before preconditioning. P450 estrogen aromatase wild-type and knockout mice were also evaluated. All mice were preconditioned for 4 h with 0% (sham preconditioning) or 1% isoflurane (isoflurane preconditioning) and recovered for 24 h. Mice then underwent 2 h of middle cerebral artery occlusion and were evaluated 22 h later for infarct volume. For neurobehavioral outcomes, sham and isoflurane preconditioned castrated male+/-dihydrotestosterone groups underwent 1 h of middle cerebral artery occlusion followed by 9 days of reperfusion. Isoflurane preconditioning neuroprotection relative to infarct volume outcomes were testosterone and dihydrotestosterone dose-specific and androgen receptor-dependent. Relative to long-term neurobehavioral outcomes, front paw sensorimotor function improved in isoflurane preconditioned mice regardless of androgen status while androgen replacement independently improved sensorimotor function. In contrast, isoflurane preconditioning improved cognitive function in castrates lacking endogenous androgens, but this improvement was absent in androgen replaced mice. Our findings suggest that androgen availability during isoflurane preconditioning may influence infarct volume and neurobehavioral outcomes in male mice following experimental stroke.