Tumor necrosis factor alpha (TNF‐α) is known to exacerbate ischemic brain injury; however, the mechanism is unknown. Previous studies have evaluated the effects of TNF‐α on neurons with long ...exposures to high doses of TNF‐α, which is not pathophysiologically relevant. We characterized the rapid effects of TNF‐α on basal respiration, ATP production, and maximal respiration using pathophysiologically relevant, post‐stroke concentrations of TNF‐α. We observed a reduction in mitochondrial function as early as 1.5 h after exposure to low doses of TNF‐α, followed by a decrease in cell viability in HT‐22 cells and primary neurons. Subsequently, we used the HT‐22 cell line to determine the mechanism by which TNF‐α causes a rapid and profound reduction in mitochondrial function. Pre‐treating with TNF‐R1 antibody, but not TNF‐R2 antibody, ameliorated the neurotoxic effects of TNF‐α, indicating that TNF‐α exerts its neurotoxic effects through TNF‐R1. We observed an increase in caspase 8 activity and a decrease in mitochondrial membrane potential after exposure to TNF‐α which resulted in a release of cytochrome c from the mitochondria into the cytosol. These novel findings indicate for the first time that an acute exposure to pathophysiologically relevant concentrations of TNF‐α has neurotoxic effects mediated by a rapid impairment of mitochondrial function.
This study focuses on the neurotoxic mechanism of a pro‐inflammatory cytokine, tumor necrosis factor alpha (TNF‐α). We demonstrate a prompt mitochondrial dysfunction followed by nerve cell loss after exposure to TNF‐α. These studies may provide evidence that the immune system can rapidly and adversely affect brain function and that TNF‐α signaling may be a target for neuroprotection.
This study focuses on the neurotoxic mechanism of a pro‐inflammatory cytokine, tumor necrosis factor alpha (TNF‐α). We demonstrate a prompt mitochondrial dysfunction followed by nerve cell loss after exposure to TNF‐α. These studies may provide evidence that the immune system can rapidly and adversely affect brain function and that TNF‐α signaling may be a target for neuroprotection.
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Sleep disturbances are among the most common symptoms of military personnel who return from deployment. The objective of our study was to determine the presence of sleep disorders in US military ...personnel referred for evaluation of sleep disturbances after deployment and examine associations between sleep disorders and service-related diagnoses of depression, mild traumatic brain injury, pain, and posttraumatic stress disorder (PTSD).
This was a cross-sectional study of military personnel with sleep disturbances who returned from combat within 18 months of deployment. Sleep disorders were assessed by clinical evaluation and polysomnogram with validated instruments to diagnose service-related illnesses.
Of 110 military personnel included in our analysis, 97.3% were men (mean age, 33.6 ± 8.0 years; mean BMI, 30.0 ± 4.3 kg/m2), and 70.9% returned from combat within 12 months. Nearly one-half (47.3%) met diagnostic criteria for two or more service-related diagnoses. Sleep disorders were diagnosed in 88.2% of subjects; 11.8% had a normal sleep evaluation and served as control subjects. Overall, 62.7% met diagnostic criteria for obstructive sleep apnea (OSA) and 63.6% for insomnia. The exclusive diagnoses of insomnia and OSA were present in 25.5% and 24.5% of subjects, respectively; 38.2% had comorbid insomnia and OSA. Military personnel with comorbid insomnia and OSA were significantly more likely to meet criteria for depression (P < .01) and PTSD (P < .01) compared with control subjects and those with OSA only.
Comorbid insomnia and OSA is a frequent diagnosis in military personnel referred for evaluation of sleep disturbances after deployment. This diagnosis, which is difficult to treat, may explain the refractory nature of many service-related diagnoses.
Inflammatory mechanisms both in the periphery and in the CNS are important in the pathophysiologic processes occurring after the onset of ischemic stroke (IS). Cytokines are key players in the ...inflammatory mechanism and contribute to the progression of ischemic damage. This literature review focuses on the effects of inflammation on ischemic stroke, and the role pro-inflammatory and anti-inflammatory cytokines play on deleterious or beneficial stroke outcome. The discovery of biomarkers and novel therapeutics for stroke has been the focus of extensive research recently; thus, understanding the roles of pro-inflammatory and anti-inflammatory cytokines that are up-regulated during stroke will help us further understand how inflammation contributes to the progression of ischemic damage and provide potential targets for novel therapeutics and biomarkers for diagnosis and prognosis of stroke.
Burnout in health care employees and leaders is at an all-time high. Strategies to address burnout can fall short of addressing the broad range of underlying causes, including both organizational ...culture and personal factors. The National Academies of Medicine has set forth recommendations to address health care burnout from a leadership-based systems level that focuses on the whole employee, body, mind, and spirit. Across generations and societies, there is a growing trend toward spirituality and meaning as a critical component of both personal life and work. Among the working-age millennials, values of purpose and greater societal good take precedent and impact work choices and behaviors. Spiritually based values such as a sense of purpose, the transcendence of the self and ego, and the acknowledgment of something greater than our collective selves, are present in both popular culture and research on transcendental models of leadership. This article presents a model of holistic transcendental leadership that can be leveraged in the health care workplace to enhance innovation and creativity, while placing a novel emphasis on the physical, emotional, and spiritual well-being at the individual, group, and organizational level.
Immune dysregulation influences outcome following acute ischemic stroke (AIS). Admission white blood cell (WBC) counts are routinely obtained, making the neutrophil-lymphocyte ratio (NLR) a readily ...available biomarker of the immune response to stroke. This study sought to identify the relationship between NLR and 90 day AIS outcome.
A retrospective analysis was performed on patients who underwent endovascular therapy for AIS at West Virginia University Hospitals, Morgantown, West Virginia. Admission WBC differentials were analyzed as the NLR. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS) score and outcome by the modified Rankin Scale (mRS) score at 90 days. Univariate relationships between NLR, age, NIHSS, and mRS were established by correlation coefficients; the t test was used to compare NLR with recanalization and stroke location (anterior vs posterior). Logistic regression models were developed to identify the ability of NLR to predict mRS when controlling for age, recanalization, and treatment with IV tissue plasminogen activator (tPA).
116 patients were reviewed from 2008 to 2011. Mean age of the sample was 67 years, and 54% were women. Mean baseline NIHSS score was 17 and 90 day mRS score was 4. There was a significant relationship between NLR and mRS (p=0.02) that remained when controlling for age, treatment with IV tPA, and recanalization. NLR ≥5.9 predicted poor outcome and death at 90 days.
This study shows that the NLR, a readily available biomarker, may be a clinically useful tool for risk stratification when evaluating AIS patients as candidates for endovascular therapies.
•Innovative organizations create structures to support innovation and by doing so increase financial return on investment, quality of care, patient safety and overall employee wellbeing and ...satisfaction.•There are few nursing-based centers in the US with a focus on innovation, thus there is a tremendous opportunity to create and establish innovation-based centers in academic and practice-based nursing institutions.•Funding, engagement, leadership, interprofessional collaboration, partnerships, and overcoming the innovation paradox are central to the success and sustainability of innovation centers and initiatives.•Current and future centers are encouraged to enhance opportunities for diverse and underrepresented groups to participate in innovation centers and initiatives to overcome the innovation diversity paradox.
The interest in and demand for healthcare innovation has heightened amid the COVID-19 pandemic. Organizations are challenged to balance the goals of daily operations with innovation to stay relevant and compete in the marketplace. Innovation is critical for not only the success and sustainability of organizations, but the well-being of the faculty, staff, and clients they serve.
In this article, we present an overview of several Nursing Innovation Centers in the United States as well as examples of colleges without formal innovation centers but who are addressing innovation in their programs.
We examined the subjective experience of nursing innovation in seven colleges of nursing using semi-structured intervieweds and thematic analysis.
We discuss four themes for creating an innovation center or innovation focus and six themes important for sustainability and impact. In addition, we provide a working model for these themes and provide lessons learned along with trends and recommendations for the future.
This information provides guidance and a framework for academic and practice organizations aspiring to create opportunities for innovation to flourish in their institutions. We also encourage leadership to critically evaluate and address biases in faculty hiring, research evaluation, publication practices, educational opportunities and mentoring to overcome the diversity innovation paradox.
CD163 is a scavenger receptor expressed on innate immune cell populations which can be shed from the plasma membrane via the metalloprotease ADAM17 to generate a soluble peptide with ...lympho-inhibitory properties. The purpose of this study was to investigate CD163 as a possible effector of stroke-induced adaptive immune system suppression. Liquid biopsies were collected from ischemic stroke patients (n = 39), neurologically asymptomatic controls (n = 20), and stroke mimics (n = 20) within 24 hours of symptom onset. Peripheral blood ADAM17 activity and soluble CD163 levels were elevated in stroke patients relative to non-stroke control groups, and negatively associated with post-stroke lymphocyte counts. Subsequent in vitro experiments suggested that this stroke-induced elevation in circulating soluble CD163 likely originates from activated monocytic cells, as serum from stroke patients stimulated ADAM17-dependant CD163 shedding from healthy donor-derived monocytes. Additional in vitro experiments demonstrated that stroke-induced elevations in circulating soluble CD163 can elicit direct suppressive effects on the adaptive immune system, as serum from stroke patients inhibited the proliferation of healthy donor-derived lymphocytes, an effect which was attenuated following serum CD163 depletion. Collectively, these observations provide novel evidence that the innate immune system employs protective mechanisms aimed at mitigating the risk of post-stroke autoimmune complications driven by adaptive immune system overactivation, and that CD163 is key mediator of this phenomenon.
Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early ...expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging. Early heightened expression levels of AKAP7, a gene encoding a protein kinase A-binding scaffolding molecule, were significantly associated with BBB disruption 24 hours post-hospital admission. We then determined that AKAP7 is predominantly expressed by lymphocytes in peripheral blood, and strongly co-expressed with ITGA3, a gene encoding the adhesion molecule integrin alpha 3. Subsequent in vitro experiments revealed that heightened expression of AKAP7 and ITGA3 in primary human lymphocytes is associated with a highly adherent phenotype. Collectively, our results suggest that AKAP7 expression levels may have clinical utility as a prognostic biomarker for post-stroke BBB complications, and are likely elevated early in patients who later develop post-stroke BBB disruption due to the presence of an invasive lymphocyte population in the peripheral blood.
Highlights • Expression prolife data suggest stroke involves a complex inflammatory response. • Neutrophil and lymphocyte ratio may be a useful biomarker for stroke outcome. • Arginase from ...neutrophil may play a role in stroke-associated immunosuppression.
The development of tools that could help emergency department clinicians recognize stroke during triage could reduce treatment delays and improve patient outcomes. Growing evidence suggests that ...stroke is associated with several changes in circulating cell counts. The aim of this study was to determine whether machine-learning can be used to identify stroke in the emergency department using data available from a routine complete blood count with differential.
Red blood cell, platelet, neutrophil, lymphocyte, monocyte, eosinophil, and basophil counts were assessed in admission blood samples collected from 160 stroke patients and 116 stroke mimics recruited from three geographically distinct clinical sites, and an ensemble artificial neural network model was developed and tested for its ability to discriminate between groups.
Several modest but statistically significant differences were observed in cell counts between stroke patients and stroke mimics. The counts of no single cell population alone were adequate to discriminate between groups with high levels of accuracy; however, combined classification using the neural network model resulted in a dramatic and statistically significant improvement in diagnostic performance according to receiver-operating characteristic analysis. Furthermore, the neural network model displayed superior performance as a triage decision making tool compared to symptom-based tools such as the Cincinnati Prehospital Stroke Scale (CPSS) and the National Institutes of Health Stroke Scale (NIHSS) when assessed using decision curve analysis.
Our results suggest that algorithmic analysis of commonly collected hematology data using machine-learning could potentially be used to help emergency department clinicians make better-informed triage decisions in situations where advanced imaging techniques or neurological expertise are not immediately available, or even to electronically flag patients in which stroke should be considered as a diagnosis as part of an automated stroke alert system.
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