Data Science Implementation Trends in Nursing Practice: A Review of the 2021 Literature.

OBJECTIVES: The goal of this work was to provide a review of the implementation of data science-driven applications focused on structural or outcome-related nurse-sensitive indicators in the literature in 2021. By conducting this review, we aim to inform readers of trends in the nursing indicators being addressed, the patient populations and settings of focus, and lessons and challenges identified during the implementation of these tools. METHODS: We conducted a rigorous descriptive review of the literature to identify relevant research published in 2021. We extracted data on model development, implementation-related strategies and measures, lessons learned, and challenges and stakeholder involvement. We also assessed whether reports of data science application implementations currently follow the guidelines of the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by AI (DECIDE-AI) framework. RESULTS: Of 4,943 articles found in PubMed (NLM) and CINAHL (EBSCOhost), 11 were included in the final review and data extraction. Systems leveraging data science were developed for adult patient populations and were primarily deployed in hospital settings. The clinical domains targeted included mortality/deterioration, utilization/resource allocation, and hospital-acquired infections/COVID-19. The composition of development teams and types of stakeholders involved varied. Research teams more frequently reported on implementation methods than implementation results. Most studies provided lessons learned that could help inform future implementations of data science systems in health care. CONCLUSION: In 2021, very few studies report on the implementation of data science-driven applications focused on structural- or outcome-related nurse-sensitive indicators. This gap in the sharing of implementation strategies needs to be addressed in order for these systems to be successfully adopted in health care settings.

Activation-Induced Cytidine Deaminase Impacts the Primary Antibody Repertoire in Naive Mice.

Genetic and environmental cues shape the evolution of the B cell Ig repertoire. Activation-induced cytidine deaminase (AID) is essential to generating Ig diversity through isotype class switching and somatic mutations, which then directly influence clonal selection. Impaired B cell development in AID-knockout mice has made it difficult to study Ig diversification in an aging repertoire. Therefore, in this report, we used a novel inducible AID-knockout mouse model and discovered that deleting AID in adult mice caused spontaneous germinal center formation. Deep sequencing of the IgH repertoire revealed that Ab diversification begins early in life and evolves over time. Our data suggest that activated B cells form germinal centers at steady state and facilitate continuous diversification of the B cell repertoire. In support, we identified shared B cell lineages that were class switched and showed age-dependent rates of mutation. Our data provide novel context to the genesis of the B cell repertoire that may benefit the understanding of autoimmunity and the strength of an immune response to infection.

Early crestal bone loss around implants placed at previously failed sites compared with initially integrated implants: A retrospective cohort study.

BACKGROUND: There is minimal information on early crestal bone loss (CBL) associated with implants placed at failed sites. PURPOSE: This retrospective cohort study aimed to evaluate CBL of surviving and restored implants placed at previously failed sites (replaced implants [RIs]) compared to that of implants initially integrated and restored (pristine implants [PIs]), within the same subjects from implant placement to 17 months post-delivery of restoration. METHODS: Subjects who had both PI(s) and RI(s) were recruited. The following data were retrieved: patient demographics, implant locations, types of implant failure, use of bone graft procedure(s), and intraoral radiographs at implant placement (T0), restoration delivery (T1), and the post-restoration follow-up (T2). A blinded evaluator measured crestal bone levels at T0, T1, and T2. RESULTS: Forty-four implants (22 in the RI and 22 in the PI group) from the 22 subjects were reviewed. The 22 implants in the RI group were placed either at early failure (17) or late failure (5) sites. There was a 4.6 times higher likelihood of bone graft procedures performed in association with RIs compared to PIs when using a generalized linear mixed model. Differences in crestal bone levels were compared between the two groups at each time point. There were no significant differences in the mesial and mean crestal bone levels between the PI and RI groups. The RI group exhibited lower crestal bone levels on the distal side compared to the PI group at all time points. However, this difference was due to crestal bone level at T0 (p = 0.039) not due to implant replacement (p = 0.413) or bone graft procedure (p = 0.302) when using mixed regression modeling. CONCLUSION: The effect of replacements of implants at failed sites on CBL was not significant. RIs, once integrated, exhibited the same pattern of CBL as pristine implants.

Data Science Trends Relevant to Nursing Practice: A Rapid Review of the 2020 Literature.

BACKGROUND: The term "data science" encompasses several methods, many of which are considered cutting edge and are being used to influence care processes across the world. Nursing is an applied science and a key discipline in health care systems in both clinical and administrative areas, making the profession increasingly influenced by the latest advances in data science. The greater informatics community should be aware of current trends regarding the intersection of nursing and data science, as developments in nursing practice have cross-professional implications. OBJECTIVES: This study aimed to summarize the latest (calendar year 2020) research and applications of nursing-relevant patient outcomes and clinical processes in the data science literature. METHODS: We conducted a rapid review of the literature to identify relevant research published during the year 2020. We explored the following 16 topics: (1) artificial intelligence/machine learning credibility and acceptance, (2) burnout, (3) complex care (outpatient), (4) emergency department visits, (5) falls, (6) health care-acquired infections, (7) health care utilization and costs, (8) hospitalization, (9) in-hospital mortality, (10) length of stay, (11) pain, (12) patient safety, (13) pressure injuries, (14) readmissions, (15) staffing, and (16) unit culture. RESULTS: Of 16,589 articles, 244 were included in the review. All topics were represented by literature published in 2020, ranging from 1 article to 59 articles. Numerous contemporary data science methods were represented in the literature including the use of machine learning, neural networks, and natural language processing. CONCLUSION: This review provides an overview of the data science trends that were relevant to nursing practice in 2020. Examinations of such literature are important to monitor the status of data science's influence in nursing practice.

Data Science Methods for Nursing-Relevant Patient Outcomes and Clinical Processes: The 2019 Literature Year in Review.

Data science continues to be recognized and used within healthcare due to the increased availability of large data sets and advanced analytics. It can be challenging for nurse leaders to remain apprised of this rapidly changing landscape. In this article, we describe our findings from a scoping literature review of papers published in 2019 that use data science to explore, explain, and/or predict 15 phenomena of interest to nurses. Fourteen of the 15 phenomena were associated with at least one paper published in 2019. We identified the use of many contemporary data science methods (eg, natural language processing, neural networks) for many of the outcomes. We found many studies exploring Readmissions and Pressure Injuries. The topics of Artificial Intelligence/Machine Learning Acceptance, Burnout, Patient Safety, and Unit Culture were poorly represented. We hope that the studies described in this article help readers: (1) understand the breadth and depth of data science's ability to improve clinical processes and patient outcomes that are relevant to nurses and (2) identify gaps in the literature that are in need of exploration.

Motor Impairment and Its Influence in Gait Velocity and Asymmetry in Community Ambulating Hemiplegic Individuals.

OBJECTIVES: To determine the most important motor impairments that are predictors of gait velocity and spatiotemporal symmetrical ratio in patients with stroke. DESIGN: Cross-sectional, descriptive analysis study. SETTING: Human performance laboratory of the University of Santo Tomas. PARTICIPANTS: Individuals with chronic stroke (N=55; 34 men, 21 women) who are community dwellers. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The gait velocity and spatiotemporal symmetrical ratio (step length; step, stance, swing, single-leg support, and double-leg support stance times) was determined using Vicon motion capture. We also calculated motor impairment of the leg and foot using Brunnstrom's stages of motor recovery, evaluated muscle strength using the scoring system described by Collin and Wade, and assessed spasticity using by the modified Ashworth Scale. RESULTS: Regression analysis showed that plantarflexor strength is a predictor of gait velocity and all temporospatial symmetry ratio. Knee flexor and extensor strength are predictors in single-leg support time and double-leg support time symmetry ratio, respectively. On the other hand, hip adductor and quadriceps spasticity are predictors of swing time and step length symmetry ratio. CONCLUSION: Different motor impairments are predictors of stroke gait abnormality. Interventions should be focused on these motor impairments to allow for optimal gait rehabilitation results.

The promise of curriculum in the post-Covid world: Eclecticism, deliberation, and a return to the practical and the prophetic.

This article focuses on the possibilities through which curriculum on the other side of the Covid-19 pandemic might contribute more proactively to future social and political crises that are multifarious yet interconnected in nature. The Covid-19 pandemic is a global crisis that touches every aspect of social life, including politics, the economy, healthcare systems, poverty, forced human migration, climate change, and importantly, education. To potentially address future crises through curriculum, the article first problematizes the present in education and society-specifically, the 50-year neoliberal project that has transformed society and education. It connects the crisis in education to a transformed social, political, and economic system that has introduced what Gordon Lafer has called a revolution of falling expectations through a hollowing-out of public institutions. The article then returns to the crisis of curriculum, contextualized in Joseph Schwab's The Practical: A Language for Curriculum, which presaged the reconceptualization of the curriculum field. It dialogues with Schwab's advocacy for an eclectic, deliberative, and practical curricular ethic as a form of post-reconceptualization curriculum study to contribute to understanding and managing future disruptions, such as those inevitably associated with the climate crisis. Finally, the article connects to the concept of liquidity in curriculum, through which to embody curricular eclecticism and provoke teachers and students to author a vision for a more just future that will not reinscribe the pathologies of the past.

The kinase IRAK4 promotes endosomal TLR and immune complex signaling in B cells and plasmacytoid dendritic cells.

The dysregulation of multiple signaling pathways, including those through endosomal Toll-like receptors (TLRs), Fc gamma receptors (FcγR), and antigen receptors in B cells (BCR), promote an autoinflammatory loop in systemic lupus erythematosus (SLE). Here, we used selective small-molecule inhibitors to assess the regulatory roles of interleukin-1 receptor (IL-1R)-associated kinase 4 (IRAK4) and Bruton's tyrosine kinase (BTK) in these pathways. The inhibition of IRAK4 repressed SLE immune complex- and TLR7-mediated activation of human plasmacytoid dendritic cells (pDCs). Correspondingly, the expression of interferon (IFN)-responsive genes (IRGs) in cells and in mice was positively regulated by the kinase activity of IRAK4. Both IRAK4 and BTK inhibition reduced the TLR7-mediated differentiation of human memory B cells into plasmablasts. TLR7-dependent inflammatory responses were differentially regulated by IRAK4 and BTK by cell type: In pDCs, IRAK4 positively regulated NF-κB and MAPK signaling, whereas in B cells, NF-κB and MAPK pathways were regulated by both BTK and IRAK4. In the pristane-induced lupus mouse model, inhibition of IRAK4 reduced the expression of IRGs during disease onset. Mice engineered to express kinase-deficient IRAK4 were protected from both chemical (pristane-induced) and genetic (NZB/W_F1 hybrid) models of lupus development. Our findings suggest that kinase inhibitors of IRAK4 might be a therapeutic in patients with SLE.

Low quality diet and challenging temperatures affect vital rates, but not thermal tolerance in a tropical insect expanding its diet to an exotic plant.

Determining responses of organisms to changing temperatures is a research priority, as global warming threatens populations and ecosystems worldwide. Upper thermal limits are frequently measured as the critical thermal maximum (CTmax), a quick bioassay where organisms are exposed to increasing temperatures until individuals are not able to perform basic motor activities such as walking or flying. A more informative approach to understand organism responses to global warming is to evaluate how vital rates, such as growth or survival, change with temperatures. The main objectives of this study are: (1) to determine if factors affecting insect vital rates such as diet quality, developmental temperatures or acclimation also affect CTmax and (2) to determine if vital rates of different life stages (i.e., insect larvae or adults) display different responses to temperature changes. If different life stages have particular thermal requirements, this may indicate different susceptibility to global warming. This study focuses on Cephaloleia belti (Coleoptera: Chrysomelidae), a tropical insect currently expanding its diet to an exotic host plant. We determined how high and low-quality diets (i.e., native vs novel host), as well as exposure temperatures affect CTmax of adult beetles. We also estimated larval and adult survival when feeding on high and low quality host plants, when exposed to temperatures typical of the elevational distribution of this species, or when exposed to projected temperatures in 100 years. We did not detect an effect of diet quality or acclimation on CTmax. However, larvae and adults had different thermal requirements. CTmax is not affected by previous diet or acclimation as an adult. We propose that to understand processes involved in the adaptation and persistence of ectotherm populations in a warming world, studies must explore responses beyond CTmax, and focus on the response of vital rates to changing temperatures.

Validation and Refinement of a Pain Information Model from EHR Flowsheet Data.

BACKGROUND: Secondary use of electronic health record (EHR) data can reduce costs of research and quality reporting. However, EHR data must be consistent within and across organizations. Flowsheet data provide a rich source of interprofessional data and represents a high volume of documentation; however, content is not standardized. Health care organizations design and implement customized content for different care areas creating duplicative data that is noncomparable. In a prior study, 10 information models (IMs) were derived from an EHR that included 2.4 million patients. There was a need to evaluate the generalizability of the models across organizations. The pain IM was selected for evaluation and refinement because pain is a commonly occurring problem associated with high costs for pain management. OBJECTIVE: The purpose of our study was to validate and further refine a pain IM from EHR flowsheet data that standardizes pain concepts, definitions, and associated value sets for assessments, goals, interventions, and outcomes. METHODS: A retrospective observational study was conducted using an iterative consensus-based approach to map, analyze, and evaluate data from 10 organizations. RESULTS: The aggregated metadata from the EHRs of 8 large health care organizations and the design build in 2 additional organizations represented flowsheet data from 6.6 million patients, 27 million encounters, and 683 million observations. The final pain IM has 30 concepts, 4 panels (classes), and 396 value set items. Results are built on Logical Observation Identifiers Names and Codes (LOINC) pain assessment terms and extend the need for additional terms to support interoperability. CONCLUSION: The resulting pain IM is a consensus model based on actual EHR documentation in the participating health systems. The IM captures the most important concepts related to pain.

Effect of a Health Care System Respiratory Fluoroquinolone Restriction Program To Alter Utilization and Impact Rates of Clostridium difficile Infection.

Fluoroquinolones are one of the most commonly prescribed antibiotic classes in the United States despite their association with adverse consequences, including Clostridium difficile infection (CDI). We sought to evaluate the impact of a health care system antimicrobial stewardship-initiated respiratory fluoroquinolone restriction program on utilization, appropriateness of quinolone-based therapy based on institutional guidelines, and CDI rates. After implementation, respiratory fluoroquinolone utilization decreased from a monthly mean and standard deviation (SD) of 41.0 (SD = 4.4) days of therapy (DOT) per 1,000 patient days (PD) preintervention to 21.5 (SD = 6.4) DOT/1,000 PD and 4.8 (SD = 3.6) DOT/1,000 PD posteducation and postrestriction, respectively. Using segmented regression analysis, both education (14.5 DOT/1,000 PD per month decrease; P = 0.023) and restriction (24.5 DOT/1,000 PD per month decrease; P < 0.0001) were associated with decreased utilization. In addition, the CDI rates decreased significantly (P = 0.044) from preintervention using education (3.43 cases/10,000 PD) and restriction (2.2 cases/10,000 PD). Mean monthly CDI cases/10,000 PD decreased from 4.0 (SD = 2.1) preintervention to 2.2 (SD = 1.35) postrestriction. A significant increase in appropriate respiratory fluoroquinolone use occurred postrestriction versus preintervention in patients administered at least one dose (74/130 [57%] versus 74/232 [32%]; P < 0.001), as well as in those receiving two or more doses (47/65 [72%] versus 67/191 [35%]; P < 0.001). A significant reduction in the annual acquisition cost of moxifloxacin, the formulary respiratory fluoroquinolone, was observed postrestriction compared to preintervention within the health care system ($123,882 versus $12,273; P = 0.002). Implementation of a stewardship-initiated respiratory fluoroquinolone restriction program can increase appropriate use while reducing overall utilization, acquisition cost, and CDI rates within a health care system.

Big data science: A literature review of nursing research exemplars.

BACKGROUND: Big data and cutting-edge analytic methods in nursing research challenge nurse scientists to extend the data sources and analytic methods used for discovering and translating knowledge. PURPOSE: The purpose of this study was to identify, analyze, and synthesize exemplars of big data nursing research applied to practice and disseminated in key nursing informatics, general biomedical informatics, and nursing research journals. METHODS: A literature review of studies published between 2009 and 2015. There were 650 journal articles identified in 17 key nursing informatics, general biomedical informatics, and nursing research journals in the Web of Science database. After screening for inclusion and exclusion criteria, 17 studies published in 18 articles were identified as big data nursing research applied to practice. DISCUSSION: Nurses clearly are beginning to conduct big data research applied to practice. These studies represent multiple data sources and settings. Although numerous analytic methods were used, the fundamental issue remains to define the types of analyses consistent with big data analytic methods. CONCLUSION: There are needs to increase the visibility of big data and data science research conducted by nurse scientists, further examine the use of state of the science in data analytics, and continue to expand the availability and use of a variety of scientific, governmental, and industry data resources. A major implication of this literature review is whether nursing faculty and preparation of future scientists (PhD programs) are prepared for big data and data science.

Abdominal Lymphatic Malformation Presenting as Acute Abdominal Pain: A Common Pediatric Complaint, but an Unusual Diagnosis.

We present the clinical and radiological findings involving a mesenteric lymphatic malformation causing volvulus in a toddler presenting with acute abdominal pain, as well as its treatment options.

Comportamiento del Geriatric/General Oral Health Assessment Index (GOHAI) y Oral Impacts on Daily Performances (OIDP) en una población de adultos mayores de la Ciudad de México / Behavior of the Geriatric/General Oral Health Assessment Index (GOHAI) and Oral Impacts on Daily Performances (OIDP) in a senior adult population in Mexico City

Objetivo: Determinar el comportamiento del Geriatric/General Oral Health Assessment Index y Oral Impacts on Daily Performances como medidas de efecto de la salud bucodental relacionada con la calidad de vida en adultos mayores en una misma población. Métodos: Muestra representativa de adultos mayores derechohabientes del Instituto Mexicano del Seguro Social del suroeste de la Ciudad de México. Se realizaron entrevistas domiciliarias para conocer las características de la muestra y aplicación de los instrumentos Geriatric/General Oral Health Assessment Index y Oral Impacts on Daily Performances. Evaluación clínica para determinar la experiencia de caries coronal y caries radicular. Resultados: Un total de 531 sujetos de 60 años y más participaron, 68.4% mujeres. La media (desviación estándar) de edad fue de 71.4 (7.0) años. El Geriatric/General Oral Health Assessment Index presentó una media de 46.8 (6.2), y 4.1 (12.4) para el Oral Impacts on Daily Performances. La escolaridad mayor de seis años, no presentar limitaciones, con deterioro cognitivo y sin depresión, presentaron una media mayor del puntaje del Geriatric/General Oral Health Assessment Index en comparación con los que no presentaban (p < 0.05). La escolaridad mayor de seis años, con una actividad laboral remunerada y sin depresión, presentaron una media menor del puntaje del Oral Impacts on Daily Performances en comparación a los que no presentaban (p < 0.05). Existe una correlación entre el Geriatric/General Oral Health Assessment Index y componentes obturados, dientes funcionales (p < 0.05). Los componentes perdidos, obturados e índice caries coronal, así como coronas sanas y dientes funcionales presentaron una correlación con el Oral Impacts on Daily Performances (p < 0.05). Conclusión: El Geriatric/General Oral Health Assessment Index tuvo mayor discriminación en las características de la población y el Oral Impacts on Daily Performances presentó mayor correlación con el estado de la dentición.

Objective: To determine the behavior of the Geriatric/General Oral Health Assessment Index as well as the Oral Impacts on Daily Performances as effective measures in oral-dental health related to quality of life in senior citizens in a given population. Methods: A representative sample of senior citizens entitled to medical services at the Instituto Mexicano del Seguro Social (Mexican Institute of Social Security) located in the southwest region of Mexico City. Home interviews were conducted in order to ascertain the sample's characteristics as well as the application of the Geriatric/General Oral Health Assessment Index and Oral Impacts on Daily Performances instruments. Clinical evaluation in order to determine experience of crown caries (CPO-D) and root caries CO-R). Results: A total of 531 subjects aged 60 years and over participated in the study, of which 68.4% were female. Age average (AA) was 71.4 years (7.0). Geriatric/General Oral Health Assessment Index exhibited a mean of 46.8 (6.2) and Oral Impacts on Daily Performances showed 4.1 (12.4). Subjects included in the sample had attended school for over 6 years, did not present limitations of cognitive deterioration, and were depression-free, exhibited a higher mean in Oral Impacts on Daily Performances score than those which did not present those characteristics (p < 0.05). Six or more years of schooling with paid work and depression-free subjects presented lesser Oral Impacts on Daily Performances scores when compared to those who did not. (p < 0.05) A correlation was found between the Geriatric/General Oral Health Assessment Index and filled components, functional teeth (p > 0.05). Filled and lost components and CPO-D index as well as healthy crowns and functional teeth exhibited a correlation with Oral Impacts on Daily Performances (p < 0.05). Conclusion: Geriatric/General Oral Health Assessment Index exhibited higher discrimination in the population's characteristics whereas Oral Impacts on Daily Performances showed higher correlation with the state of the dentition.

Andes hantavirus variant in rodents, southern Amazon Basin, Peru.

We investigated hantaviruses in rodents in the southern Amazon Basin of Peru and identified an Andes virus variant from Neacomys spinosus mice. This finding extends the known range of this virus in South America and the range of recognized hantaviruses in Peru. Further studies of the epizoology of hantaviruses in this region are warranted.

Impacted button-battery masquerading as croup.

BACKGROUND: Foreign body ingestion is a frequent complaint in the Pediatric Emergency Department. OBJECTIVE: Button-battery ingestion is discussed, with particular attention being given to its management. CASE REPORT: Here is an interesting case of a button-battery ingestion by a 1-year-old boy with known asthma who presented to our Emergency Department. He presented in acute respiratory distress with signs of upper airway obstruction. Failing conventional therapy, a chest radiograph was obtained, which led to the diagnosis and subsequent removal. CONCLUSION: The management of a button-battery ingestion depends on the patient's age, the presence or absence of symptoms, the size of the object, and location of the object within the gastrointestinal tract. In years past, every esophageal button battery required emergent endoscopic removal. But revised guidelines from the National Battery Ingestion Hotline at the National Capital Poison Center have adjusted this management, which is discussed.

Critical role of activation induced cytidine deaminase in experimental autoimmune encephalomyelitis.

Multiple Sclerosis (MS) is a neurodegenerative autoimmune disorder caused by chronic inflammation and demyelination within the central nervous system (CNS). Clinical studies in MS patients have demonstrated efficacy with B cell targeted therapies such as anti-CD20. However, the exact role that B cells play in the disease process is unclear. Activation Induced cytidine deaminase (AID) is an essential enzyme for the processes of antibody affinity maturation and isotype switching. To evaluate the impact of affinity maturation and isotype switching, we have interrogated the effect of AID-deficiency in an animal model of MS. Here, we show that the severity of experimental autoimmune encephalomyelitis (EAE) induced by the extracellular domain of human myelin oligodendrocyte glycoprotein (MOG1-125) is significantly reduced in Aicda deficient mice, which, unlike wild-type mice, lack serum IgG to myelin associated antigens. MOG specific T cell responses are comparable between wild-type and Aicda knockout mice suggesting an active role for antigen experienced B cells. Thus affinity maturation and/or class switching are critical processes in the pathogenesis of EAE.

Inducible nitric oxide synthase and estradiol exhibit complementary neuroprotective roles after ischemic brain injury.

Estradiol-17beta exerts profound neuroprotective actions following cerebral ischemia through multiple molecular mechanisms. To examine the putative anti-inflammatory mechanisms employed by estradiol during stroke, we explored the interactions between estradiol and inducible nitric oxide synthase (iNOS) in both wildtype and iNOS knockout (iNOSKO) female mice following permanent middle cerebral artery occlusion (MCAO). Female mice were ovariectomized and treated with estradiol. One week later, they were subjected to MCAO, and then killed 24 h later. Analysis of total, cortical and striatal infarct volumes confirmed that estradiol is neuroprotective in wildtype mice. Infarct volumes were also significantly smaller in female iNOSKO female mice, but estradiol did not further decrease injury. We found that one mechanism by which estradiol may act is by decreasing nitric oxide synthase 2 gene expression in the cortex and in the striatum of wildtype mice. These results show that the pro-inflammatory actions of iNOS exacerbate stroke-induced injury within the cortex and striatum, and that iNOS deletion is neuroprotective in ovariectomized and estrogen-replaced female mice.

Timing of estrogen therapy after ovariectomy dictates the efficacy of its neuroprotective and antiinflammatory actions.

Recent studies describing the seemingly contradictory actions of estrogens in ischemic stroke injury have led us to reevaluate the circumstances under which estrogen therapy (ET) provides benefits against cerebral stroke and decipher its mechanisms of action. One prominent feature that follows stroke injury is massive central and peripheral inflammatory responses. Evidence now suggests that postischemic inflammatory responses strongly contribute to the extent of brain injury, and 17beta-estradiol (E(2)) may protect the ischemic brain by exerting antiinflammatory actions. In an attempt to explain recently reported dichotomous effects of E(2) in stroke injury, we tested the hypothesis that an extended period of hypoestrogenicity both prevents E(2) from protecting the brain against ischemia and simultaneously suppresses its antiinflammatory actions. We report that E(2) exerts profound neuroprotective action when administered immediately upon ovariectomy, but not when administered after 10 weeks of hypoestrogenicity. Consistently, E(2) treatment given immediately at the time of ovariectomy attenuated central and peripheral production of proinflammatory cytokines after ischemic stroke. In contrast, E(2) did not suppress production of proinflammatory molecules when it was administered after 10 weeks postovariectomy. These results demonstrate that a prolonged period of hypoestrogenicity disrupts both neuroprotective and antiinflammatory actions of E(2). Our findings may help to explain the results of the Women's Health initiative that reported no beneficial effect of ET against stroke because the majority of the subjects initiated ET after an extended period of hypoestrogenicity.