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Background: A number of acute ischemic stroke (AIS) cases may be misdiagnosed as transient ischemic attack (TIA), due to no infarct on initial computed tomography scan and/or mild deficits upon presentation. Several studies have found that the neutrophil–lymphocyte ratio (NLR) is an accurate differential diagnostic biomarker for AIS versus TIA; however, no study has evaluated the use of the NLR in differentiating CT negative AIS from TIA. Furthermore, the systemic immune-inflammation index (SII) is a relatively novel immune biomarker that has been shown to be positively correlated with AIS severity, poor functional outcomes and mortality. The purpose of this study is to determine if NLR or SII can be used as a diagnostic biomarker for the differential diagnosis of mild AIS with a negative CT upon admission and TIA. Methods: We performed a retrospective medical record review of patients diagnosed with either AIS or TIA. We collected peripheral white blood cell counts within 24 h of symptom onset and calculated the NLR and SII. Logistic regression was utilized to determine if NLR or SII are significant predictors of CT negative mild AIS. Results: CT negative mild AIS patients were 2 times as likely to have an NLR ≥ 2.71 compared to TIA patients, and CT negative mild AIS patients were 2.1 times as likely to have an SII ≥ 595 compared to TIA patients. Conclusion: NLR and SII are easily obtained biomarkers that can be used in early clinical decision making in cases of mild AIS with negative CT scan upon admission. [ABSTRACT FROM AUTHOR]

Strengths-based coaching has emerged in past decades as an asset-based approach that can help individuals identify, harness, and leverage their strengths to achieve professional and personal goals. This paper shares the design and outcomes of a year-long strengths-based coaching program to support leadership development within the context of one university's women's leadership initiative. Program outcomes and changes in participants' perceived confidence in identifying and applying their strengths in different contexts were evaluated through an online survey using a Likert-based REDCap survey tool after participation in the program. Findings strongly suggest that most participants lacked the self-confidence and/or self-awareness to recognize their own strengths in a granular way prior to the program. Themes that emerged in the survey findings point to the following program outcomes: participants gained an increased ability to identify and value one's own leadership strengths, an increased ability to recognize and value the strengths of others, and a supportive community of women leaders to share experiences and reflect on the application of their strengths as part of their leadership journey. Further studies are needed to understand and measure how a program such as this can impact one's leader identity, self-awareness, and self-confidence. Given the critical need for women's leadership opportunities, this program shows promise as a means to strengthen women's leadership across career stages and disciplines. [ABSTRACT FROM AUTHOR]

Background: The use of reference genes for normalization of whole blood qRT-PCR data may be problematic in conditions such as stroke which induce alterations in white blood cell differential. In this study, we assessed the influence of stroke on the stability of commonly employed reference genes, and we evaluated data-driven normalization as an alternative. Methods: Peripheral whole blood was sampled from 33 stroke patients and 29 controls, and qRT-PCR was used to measure the expression levels of 10 target genes whose transcripts are known stroke biomarkers. Target gene expression levels were normalized via those of 2 frequently cited reference genes (ACTB and B2M) as well as with the NORMA-Gene data-driven normalization algorithm. Results: Whole blood expression levels of reference genes were significantly altered in stroke patients relative to controls. In comparison to normalization via reference genes, NORMA-Gene produced more robust target gene expression data in terms of differential expression dynamics, variance properties, and diagnostic performance. Conclusions: Our findings suggest that whole blood expression levels of commonly used reference genes may be sensitive to changes in white blood cell differential, and that data-driven qRT-PCR normalization approaches offer a powerful alternative. [ABSTRACT FROM AUTHOR]

Objective: The objective of this work was to assess the ability of peripheral blood cell-free DNA (cfDNA) levels to identify ischaemic stroke early in the acute phase of care, as well as to examine the relationship between peripheral blood cfDNA levels and stroke-induced innate immune system activation.Methods: Upon emergency department admission, peripheral blood samples were obtained from 43 patients experiencing acute ischaemic stroke and 20 patients identified as stroke mimics. Plasma cfDNA levels were measured using quantitative polymerase chain reaction (qPCR), infarct volume and NIH stroke scale (NIHSS) were used to assess injury severity, and peripheral blood neutrophil count was used as a measure of innate immune system status.Results: Peripheral blood cfDNA levels were significantly elevated in patients suffering stroke relative to those diagnosed as stroke mimics, and could differentiate between groups with 86% (95% CI = 72–95%) sensitivity and 75% (95% CI = 51–91%) specificity. Furthermore, cfDNA levels displayed significant positive associations between both infarct volume and peripheral blood neutrophil count within the stroke group.Conclusions: These findings suggest that assessment of peripheral blood cfDNA levels may be useful for the identification of ischaemic stroke in the acute care setting, and provide associative evidence that cfDNA is a potential activator of the peripheral innate immune system in response to cerebral ischaemia. [ABSTRACT FROM PUBLISHER]

Although typically associated with maintenance of female reproductive function, estrogens mediate physiological processes in nearly every body tissue, including the central nervous system. Numerous pre-clinical studies have shown that estrogen, specifically 17-beta-estradiol (17β-E2), protects the brain from ischemic injury following stroke. There are multiple mechanisms of 17β-E2's neuroprotection, including activation of several neuroprotective pathways in the brain, but 17β-E2 also mediates the local and systemic immune response to ischemic stroke. This review summarizes the immune response to stroke, sex differences in stroke pathophysiology, and the role of estrogen as an immunomodulator. This review will focus almost entirely on the role of 17β-E2; however, there will be a brief review and comparison to other forms of estrogen. Understanding the immunomodulatory action of estrogens may provide an opportunity for the use of estrogens in treatment of stroke and other inflammatory disease. [ABSTRACT FROM AUTHOR]

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.

Early and accurate diagnosis of stroke improves the probability of positive outcome. The objective of this study was to identify a pattern of gene expression in peripheral blood that could potentially be optimised to expedite the diagnosis of acute ischaemic stroke (AIS). A discovery cohort was recruited consisting of 39 AIS patients and 24 neurologically asymptomatic controls. Peripheral blood was sampled at emergency department admission, and genome-wide expression profiling was performed via microarray. A machine-learning technique known as genetic algorithm k-nearest neighbours (GA/kNN) was then used to identify a pattern of gene expression that could optimally discriminate between groups. This pattern of expression was then assessed via qRT-PCR in an independent validation cohort, where it was evaluated for its ability to discriminate between an additional 39 AIS patients and 30 neurologically asymptomatic controls, as well as 20 acute stroke mimics. GA/kNN identified 10 genes ( ANTXR2 , STK3 , PDK4 , CD163 , MAL , GRAP , ID3 , CTSZ , KIF1B and PLXDC2 ) whose coordinate pattern of expression was able to identify 98.4% of discovery cohort subjects correctly (97.4% sensitive, 100% specific). In the validation cohort, the expression levels of the same 10 genes were able to identify 95.6% of subjects correctly when comparing AIS patients to asymptomatic controls (92.3% sensitive, 100% specific), and 94.9% of subjects correctly when comparing AIS patients with stroke mimics (97.4% sensitive, 90.0% specific). The transcriptional pattern identified in this study shows strong diagnostic potential, and warrants further evaluation to determine its true clinical efficacy., Competing Interests: GCO and TLB have a patent pending re: genomic patterns of expression for stroke diagnosis. TLB serves as chief scientific officer for CereDx Incorporated, a biotech firm which develops diagnostics for brain injury. The remaining authors declare no conflict of interest.