Interleukin-1 Receptor Antagonist Polymorphism and Birth Timing: Pathway Analysis Among African American Women.

BACKGROUND: Timing of birth is a major determinant of newborn health. African American women are at increased risk for early birth, particularly via the inflammatory pathway. Variants of the IL1RN gene, which encode the interleukin-1 receptor antagonist (IL-1Ra) protein, are implicated in early birth. The biological pathways linking these variables remain unclear. Evidence also suggests that inflammatory pathways differ by race; however, studies among African American women are lacking. OBJECTIVES: We assessed whether an IL1RN variant was associated with timing of birth among African American women and whether this relationship was mediated by lower anti-inflammatory IL-1Ra production or related to a decrease in inhibition of proinflammatory IL-1ß production. METHODS: A candidate gene study using a prospective cohort design was used. We collected blood samples at 28-32 weeks of gestation among African American women experiencing an uncomplicated pregnancy (N = 89). IL1RN single-nucleotide polymorphism (SNP) rs2637988 was genotyped, and lipopolysaccharide-stimulated IL-1Ra and IL-1ß production was quantified. Medical record review determined timing of birth. RESULTS: Women with GG genotype gave birth earlier than women with AA/AG genotypes (b* = .21, p = .04). There was no indirect effect of IL1RN SNP rs2637988 allele status on timing of birth through IL-1Ra production, as evidenced by a nonsignificant product of coefficients in mediational analyses (ab = .006, 95% CI [-0.05, 0.13]). Women with GG genotype showed less inhibition of IL-1ß production for a unit positive difference in IL-1Ra production than women with AA/AG genotypes (b* = .93, p = .03). Greater IL-1ß production at 28-32 weeks of pregnancy was marginally associated with earlier birth (b* = .21, p = .05). DISCUSSION: Women with GG genotype may be at risk for earlier birth because of diminished IL-1ß inhibition, allowing for initiation of a robust inflammatory response upon even mild immune challenge. Study of inflammatory contributions to early birth among African American women may be key to identifying potential prognostic markers of risk and targeted preventive interventions.

Feasibility of Hair Collection for Cortisol Measurement in Population Research on Adolescent Health.

BACKGROUND: Black-White disparities in adolescent health are widespread and thought to be explained, in part, by exposure to chronic stress. Cortisol assayed from hair is increasingly recognized as a valid and reliable measure for chronic physiological stress, but the feasibility of collecting hair among large probability samples of diverse adolescents is unknown. PURPOSE: The aim of the study was to investigate participation in hair collection for cortisol analyses in a probability sample of racially and socioeconomically diverse adolescents, including the extent to which sociodemographic factors and adverse exposures were associated with participation. METHODS: The study included a probability sample of 516 adolescents conducted in conjunction with a prospective cohort study on adolescent health. Data were collected over 1 week via in-home interviews, ecological momentary assessment, global positioning system methods, and in-home hair collection at the end of the week. RESULTS: Of the 516 eligible youth, 471 (91.3%) participated in the hair collection. Of the 45 youth who did not provide hair samples, 18 had insufficient hair, 25 refused, and 2 did not participate for unknown reasons. Multivariable logistic regression results indicated that non-Hispanic Black youth were less likely than their non-Hispanic White peers to participate due to insufficient hair or refusal (OR = 0.24, 95% CI [0 .09, 0.60]). Despite lower rates of participation, the proportion of Black youth in the participating sample was representative of the study area. No significant differences in participation were found by other sociodemographic characteristics or adverse exposures. CONCLUSIONS: Hair collection for cortisol measurement is feasible among a probability sample of racially and socioeconomically diverse adolescents. Hair cortisol analyses may accelerate research progress to understand the biological and psychosocial bases of health disparities.

Losartan treatment attenuates tumor-induced myocardial dysfunction.

UNLABELLED: Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin-angiotensin-aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. METHODS AND RESULTS: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8weeks of age. Simultaneously, mice were administered Losartan (10mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. CONCLUSIONS: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation.

Bidirectional psychoneuroimmune interactions in the early postpartum period influence risk of postpartum depression.

More than 500,000 U.S. women develop postpartum depression (PPD) annually. Although psychosocial risks are known, the underlying biology remains unclear. Dysregulation of the immune inflammatory response and the hypothalamic-pituitary-adrenal (HPA) axis are associated with depression in other populations. While significant research on the contribution of these systems to the development of PPD has been conducted, results have been inconclusive. This is partly because few studies have focused on whether disruption in the bidirectional and dynamic interaction between the inflammatory response and the HPA axis together influence PPD. In this study, we tested the hypothesis that disruption in the inflammatory-HPA axis bidirectional relationship would increase the risk of PPD. Plasma pro- and anti-inflammatory cytokines were measured in women during the 3rd trimester of pregnancy and on Days 7 and 14, and Months 1, 2, 3, and 6 after childbirth. Saliva was collected 5 times the day preceding blood draws for determination of cortisol area under the curve (AUC) and depressive symptoms were measured using the Edinburgh Postpartum Depression Survey (EPDS). Of the 152 women who completed the EPDS, 18% were depressed according to EDPS criteria within the 6months postpartum. Cortisol AUC was higher in symptomatic women on Day 14 (p=.017). To consider the combined effects of cytokines and cortisol on predicting symptoms of PPD, a multiple logistic regression model was developed that included predictors identified in bivariate analyses to have an effect on depressive symptoms. Results indicated that family history of depression, day 14 cortisol AUC, and the day 14 IL8/IL10 ratio were significant predictors of PPD symptoms. One unit increase each in the IL8/IL10 ratio and cortisol AUC resulted in 1.50 (p=0.06) and 2.16 (p=0.02) fold increases respectively in the development of PPD. Overall, this model correctly classified 84.2% of individuals in their respective groups. Findings suggest that variability in the complex interaction between the inflammatory response and the HPA axis influence the risk of PPD.

Tumor growth increases neuroinflammation, fatigue and depressive-like behavior prior to alterations in muscle function.

Cancer patients frequently suffer from fatigue, a complex syndrome associated with loss of muscle mass, weakness, and depressed mood. Cancer-related fatigue (CRF) can be present at the time of diagnosis, during treatment, and persists for years after treatment. CRF negatively influences quality of life, limits functional independence, and is associated with decreased survival in patients with incurable disease. Currently there are no effective treatments to reduce CRF. The aim of this study was to use a mouse model of tumor growth and discriminate between two main components of fatigue: loss of muscle mass/function and altered mood/motivation. Here we show that tumor growth increased fatigue- and depressive-like behaviors, and reduced body and muscle mass. Decreased voluntary wheel running activity (VWRA) and increased depressive-like behavior in the forced swim and sucrose preference tests were evident in tumor-bearing mice within the first two weeks of tumor growth and preceded the loss of body and muscle mass. At three weeks, tumor-bearing mice had reduced grip strength but this was not associated with altered expression of myosin isoforms or impaired contractile properties of muscles. These increases in fatigue and depressive-like behaviors were paralleled by increased expression of IL-1ß mRNA in the cortex and hippocampus. Minocycline administration reduced tumor-induced expression of IL-1ß in the brain, reduced depressive-like behavior, and improved grip strength without altering muscle mass. Taken together, these results indicate that neuroinflammation and depressed mood, rather than muscle wasting, contribute to decreased voluntary activity and precede major changes in muscle contractile properties with tumor growth.

Differences in inflammatory markers between nulliparous women admitted to hospitals in preactive vs active labor.

OBJECTIVE: To determine whether labor-associated inflammatory markers differ between low-risk, nulliparous women in preactive vs active labor at hospital admission and over time. STUDY DESIGN: Prospective comparative study of low-risk, nulliparous women with spontaneous labor onset at term (n = 118) sampled from 2 large Midwestern hospitals. Circulating concentrations of inflammatory markers were measured at admission and again 2 and 4 hours later: namely, neutrophil, and monocyte counts; and serum inflammatory cytokines (interleukin -1ß, interleukin-6, tumor necrosis factor-α, interleukin-10) and chemokines (interleukin-8). Biomarker concentrations and their patterns of change over time were compared between preactive (n = 63) and active (n = 55) labor admission groups using Mann-Whitney U tests. RESULTS: Concentrations of interleukin-6 and interleukin-10 in the active labor admission group were significantly higher than concentrations in the preactive labor admission group at all 3 time points. Neutrophil levels were significantly higher in the active group at 2 and 4 hours after admission. The rate of increase in neutrophils and interleukin-10 between admission and 2 hours later was faster in the active group (P < .001 and P = .003, respectively). CONCLUSION: Circulating concentrations of several inflammatory biomarkers are higher and their rate of change over time since admission is faster among low-risk, nulliparous women admitted to hospitals in active labor, as compared with those admitted in preactive labor. More research is needed to determine if progressive changes in inflammatory biomarkers might be a useful adjunct to improving the assessment of labor progression and determining the optimal timing of labor admission.

Educating future nursing scientists: Recommendations for integrating omics content in PhD programs.

Preparing the next generation of nursing scientists to conduct high-impact, competitive, sustainable, innovative, and interdisciplinary programs of research requires that the curricula for PhD programs keep pace with emerging areas of knowledge and health care/biomedical science. A field of inquiry that holds great potential to influence our understanding of the underlying biology and mechanisms of health and disease is omics. For the purpose of this article, omics refers to genomics, transcriptomics, proteomics, epigenomics, exposomics, microbiomics, and metabolomics. Traditionally, most PhD programs in schools of nursing do not incorporate this content into their core curricula. As part of the Council for the Advancement of Nursing Science's Idea Festival for Nursing Science Education, a work group charged with addressing omics preparation for the next generation of nursing scientists was convened. The purpose of this article is to describe key findings and recommendations from the work group that unanimously and enthusiastically support the incorporation of omics content into the curricula of PhD programs in nursing. The work group also calls to action faculty in schools of nursing to develop strategies to enable students needing immersion in omics science and methods to execute their research goals.

Integrating emerging areas of nursing science into PhD programs.

The Council for the Advancement of Nursing Science aims to "facilitate and recognize life-long nursing science career development" as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2010 American Association of Colleges of Nursing Position Statement "The Research-Focused Doctoral Program in Nursing: Pathways to Excellence," Idea Festival Advisory Committee members focused on emerging areas of science and technology that impact the ability of research-focused doctoral programs to prepare graduates for competitive and sustained programs of nursing research using scientific advances in emerging areas of science and technology. The purpose of this article is to describe the educational and scientific contexts for the Idea Festival, which will serve as the foundation for recommendations for incorporating emerging areas of science and technology into research-focused doctoral programs in nursing.

Emerging areas of science: Recommendations for Nursing Science Education from the Council for the Advancement of Nursing Science Idea Festival.

The Council for the Advancement of Nursing Science aims to "facilitate and recognize life-long nursing science career development" as an important part of its mission. In light of fast-paced advances in science and technology that are inspiring new questions and methods of investigation in the health sciences, the Council for the Advancement of Nursing Science convened the Idea Festival for Nursing Science Education and appointed the Idea Festival Advisory Committee (IFAC) to stimulate dialogue about linking PhD education with a renewed vision for preparation of the next generation of nursing scientists. Building on the 2005 National Research Council report Advancing The Nation's Health Needs and the 2010 American Association of Colleges of Nursing Position Statement on the Research-Focused Doctorate Pathways to Excellence, the IFAC specifically addressed the capacity of PhD programs to prepare nursing scientists to conduct cutting-edge research in the following key emerging and priority areas of health sciences research: omics and the microbiome; health behavior, behavior change, and biobehavioral science; patient-reported outcomes; big data, e-science, and informatics; quantitative sciences; translation science; and health economics. The purpose of this article is to (a) describe IFAC activities, (b) summarize 2014 discussions hosted as part of the Idea Festival, and (c) present IFAC recommendations for incorporating these emerging areas of science and technology into research-focused doctoral programs committed to preparing graduates for lifelong, competitive careers in nursing science. The recommendations address clearer articulation of program focus areas; inclusion of foundational knowledge in emerging areas of science in core courses on nursing science and research methods; faculty composition; prerequisite student knowledge and skills; and in-depth, interdisciplinary training in supporting area of science content and methods.

Emerging areas of nursing science and PhD education for the 21(st) century: response to commentaries.

We respond to commentaries from the American Academy of Nursing, the American Association of Colleges of Nursing, and the National Institute of Nursing Research on our thoughts about integrating emerging areas of science into nursing PhD programs. We identify areas of agreement and focus our response on cross-cutting issues arising from cautions about the unique focus of nursing science and how best to proceed with incorporation of emerging areas of science into nursing PhD programs.

Agonistic anti-DCIR antibody inhibits ITAM-mediated inflammatory signaling and promotes immune resolution.

DC inhibitory receptor (DCIR) is a C-type lectin receptor selectively expressed on myeloid cells, including monocytes, macrophages, DCs, and neutrophils. Its role in immune regulation has been implicated in murine models and human genome-wide association studies, suggesting defective DCIR function associates with increased susceptibility to autoimmune diseases such as rheumatoid arthritis, lupus, and Sjögren's syndrome. However, little is known about the mechanisms underlying DCIR activation to dampen inflammation. Here, we developed anti-DCIR agonistic antibodies that promote phosphorylation on DCIR's immunoreceptor tyrosine-based inhibitory motifs and recruitment of SH2 containing protein tyrosine phosphatase-2 for reducing inflammation. We also explored the inflammation resolution by depleting DCIR+ cells with antibodies. Utilizing a human DCIR-knock-in mouse model, we validated the antiinflammatory properties of the agonistic anti-DCIR antibody in experimental peritonitis and colitis. These findings provide critical evidence for targeting DCIR to develop transformative therapies for inflammatory diseases.

Application of the anatomical method to estimate the maximum adult stature and the age-at-death stature.

This study focuses on the age adjustment of statures estimated with the anatomical method. The research material includes 127 individuals from the Terry Collection. The cadaveric stature (CSTA)-skeletal height (SKH) ratios indicate that stature loss with age commences before SKH reduction. Testing three equations to estimate CSTA at the age at death and CSTA corrected to maximum stature from SKH indicates that the age correction of stature should reflect the pattern of age-related stature loss to minimize estimation error. An equation that includes a continuous and linear age correction through the entire adult age range [Eq. (1)] results in curvilinear stature estimation error. This curvilinear stature estimation error can be largely avoided by applying a second linear equation [Eq. (2)] to only individuals older than 40 years. Our third equation [Eq. (3)], based on younger individuals who have not lost stature, can be used to estimate maximum stature. This equation can also be applied to individuals of unknown or highly uncertain age, because it provides reasonably accurate estimates until about 60/70 years at least for males.

Nasogastric bridles are associated with improved tube-related outcomes in children.

OBJECTIVE: To compare tube-related outcomes in children with standard tape vs nasal bridle securement of nasogastric tubes (NGTs). STUDY DESIGN: This was a single-center, retrospective, correlational study of outcomes from the time of NGT placement until full oral feeds or durable-tube placement. Outcomes of interest included NGT dislodgments, length of stay, emergency department (ED) encounters, radiographic exposures, and adverse skin outcomes. Negative binomial regression and logistic regression were used to analyze differences between groups. RESULTS: Five hundred eighty-two children had NGTs secured traditionally (43% female; age at therapy initiation of 2.6 months [SD 8.1]), and 173 received nasal bridles (55.5% female; age at therapy initiation of 8.4 months [SD 11.8]). Children with bridled NGTs were 16.67 times less likely to experience one or more dislodgments (odds ratio [OR] = 0.06; 95% CI, 0.04-0.09); 2.5 times less likely to have one more ED visit (OR = 0.4; 95% CI, 0.19-0.82), and 4.76 times less likely to require one more radiographic exposure (OR = 0.21; 95% CI, 0.14-0.33) than unbridled children (all P values < 0.02). The mean initial hospital length of stay was 28 and 54 days in the bridled-NGT and standard-care groups, respectively (P < 0.001). Overall, 62.4% children with bridled NGTs and 77.1% children with unbridled NGTs progressed to full oral feedings and discontinued therapy (P < 0.001). Adverse skin outcomes were rare in both groups. CONCLUSION: Children with bridled NGTs experienced fewer dislodgments, hospital days, ED encounters, and radiographic exposures than unbridled NGTs. Most children in both groups progressed to full oral feedings.

The Bcl-2 family antagonist ABT-737 significantly inhibits multiple animal models of autoimmunity.

The Bcl-2 family of proteins plays a critical role in controlling immune responses by regulating the expansion and contraction of activated lymphocyte clones by apoptosis. ABT-737, which was originally developed for oncology, is a potent inhibitor of Bcl-2, Bcl-x(L), and Bcl-w protein function. There is evidence that Bcl-2-associated dysregulation of lymphocyte apoptosis may contribute to the pathogenesis of autoimmunity and lead to the development of autoimmune diseases. In this study, we report that ABT-737 treatment resulted in potent inhibition of lymphocyte proliferation as measured by in vitro mitogenic or ex vivo Ag-specific stimulation. More importantly, ABT-737 significantly reduced disease severity in tissue-specific and systemic animal models of autoimmunity. Bcl-2 family antagonism by ABT-737 was efficacious in treating animal models of arthritis and lupus. Our results suggest that treatment with a Bcl-2 family antagonist represents a novel and potentially attractive therapeutic approach for the clinical treatment of autoimmunity.

Simultaneous targeting of multiple disease mediators by a dual-variable-domain immunoglobulin.

For complex diseases in which multiple mediators contribute to overall disease pathogenesis by distinct or redundant mechanisms, simultaneous blockade of multiple targets may yield better therapeutic efficacy than inhibition of a single target. However, developing two separate monoclonal antibodies for clinical use as combination therapy is impractical, owing to regulatory hurdles and cost. Multi-specific, antibody-based molecules have been investigated; however, their therapeutic use has been hampered by poor pharmacokinetics, stability and manufacturing feasibility. Here, we describe a generally applicable model of a dual-specific, tetravalent immunoglobulin G (IgG)-like molecule--termed dual-variable-domain immunoglobulin (DVD-Ig)--that can be engineered from any two monoclonal antibodies while preserving activities of the parental antibodies. This molecule can be efficiently produced from mammalian cells and exhibits good physicochemical and pharmacokinetic properties. Preclinical studies of a DVD-Ig protein in an animal disease model demonstrate its potential for therapeutic application in human diseases.

Validity and Reliability of the Antepartum Gastrointestinal Symptom Assessment Instrument.

OBJECTIVE: To examine the psychometric properties of the nine-item Antepartum Gastrointestinal Symptom Assessment (AP-GI-SA) instrument. DESIGN: Single-group prospective design. SETTING: Urban prenatal clinic serving a diverse population. PARTICIPANTS: Convenience sample of 45 pregnant women. METHODS: Participants completed the AP-GI-SA before a scheduled prenatal care appointment. We used Bayesian structural equation modeling to evaluate the construct validity of the scale and assessed known-groups validity. We assessed reliability through maximal reliability coefficient estimate and measured internal consistency with Cronbach's alpha coefficient. RESULTS: Participants completed the instrument in 2 minutes or less. Construct validity was supported by confirmatory factor analysis (posterior predictive p value = 0.49, gamma-hat = 0.970, and root mean square error of approximation = 0.065), which indicated that the single-factor model is a plausible data-generative model for GI symptoms. The maximal reliability coefficient of 0.75 and Cronbach's alpha coefficient of 0.67 supported reliability. Average AP-GI-SA scores were the highest for women in the third trimester. Of all nine GI symptoms, heartburn in the third trimester received the highest score. CONCLUSION: Our findings provide preliminary support for the validity and reliability of the AP-GI-SA. The instrument may be used as a measure in intervention studies where GI symptoms of pregnancy are an outcome. The AP-GI-SA could also be useful in clinical settings to quickly evaluate GI symptoms.

CRISPR/Cas9-targeting of CD40 in hematopoietic stem cells limits immune activation mediated by anti-CD40.

Inflammatory bowel diseases (IBD) are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. IBD is diagnosed around 1 in 1000 individuals in Western countries with globally increasing incident rates. Association studies have identified hundreds of genes that are linked to IBD and potentially regulate its pathology. The further dissection of the genetic network underlining IBD pathogenesis and pathophysiology is hindered by the limited capacity to functionally characterize each genetic association, including generating knockout animal models for every associated gene. Cutting-edge CRISPR/Cas9-based technology may transform the field of IBD research by efficiently and effectively introducing genetic alterations. In the present study, we used CRISPR/Cas9-based technologies to genetically modify hematopoietic stem cells. Through cell sorting and bone marrow transplantation, we established a system to knock out target gene expression by over 90% in the immune system of reconstituted animals. Using a CD40-mediated colitis model, we further validated our CRISPR/Cas9-based platform for investigating gene function in experimental IBD. In doing so, we developed a model system that delivers genetically modified mice in a manner much faster than conventional methodology, significantly reducing the time from target identification to in vivo target validation and expediting drug development.

Chronic Stress and Ovarian Function in Female Childhood Cancer Survivors.

OBJECTIVES: To explore the relationships among perceived stress, biomarkers of hypothalamic-pituitary-adrenal (HPA) activity, gonadotropin levels, and anti-Müllerian hormone (AMH) in female childhood cancer survivors (CCSs). SAMPLE & SETTING: 24 female CCSs from the Royal Hospital for Sick Children in Edinburgh, Scotland, were included in the study. METHODS & VARIABLES: Perceived stress was measured using the Perceived Stress Scale. HPA activity was measured using salivary cortisol and hair cortisol. Ovarian function was measured using serum gonadotropin levels and serum AMH levels. Latent growth curve modeling was used to determine diurnal cortisol slope and intercept. Bayesian structural equation modeling was used to explore the relationship among perceived stress, biomarkers of HPA activity, and ovarian function. RESULTS: The authors found an inverse association between perceived stress and ovarian function and a positive association between biomarkers of HPA activity and ovarian function. IMPLICATIONS FOR NURSING: Further research is needed to understand factors contributing to risk for post-treatment reproductive dysfunction in female CCSs.

Exploring the Ovarian Reserve Within Health Parameters: A Latent Class Analysis.

The process of ovarian aging is influenced by a complex and poorly understood interplay of endocrine, metabolic, and environmental factors. The purpose of this study was to explore the feasibility of using latent class analysis to identify subgroups based on cardiometabolic, psychological, and reproductive parameters of health and to describe patterns of anti-Müllerian hormone levels, a biomarker of the ovarian reserve, within these subgroups. Sixty-nine lean (body mass index [BMI] ⩽ 25 kg/m2) and severely obese (BMI ⩾ 40 kg/m2) postpartum women in Edinburgh, Scotland, were included in this exploratory study. The best fitting model included three classes: Class 1, n = 23 (33.5%); Class 2, n = 30 (42.2%); Class 3, n = 16 (24.3%). Postpartum women with lower ovarian reserve had less favorable cardiometabolic and psychological profiles. Examining the ovarian reserve within distinct subgroups based on parameters of health that affect ovarian aging may facilitate risk stratification in the context of ovarian aging.

An Online Educational Program Improves Pediatric Oncology Nurses' Knowledge, Attitudes, and Spiritual Care Competence.

This study evaluated the potential impact of an online spiritual care educational program on pediatric nurses' attitudes toward and knowledge of spiritual care and their competence to provide spiritual care to children with cancer at the end of life. It was hypothesized that the intervention would increase nurses' positive attitudes toward and knowledge of spiritual care and increase nurses' level of perceived spiritual care competence. A positive correlation was expected between change in nurses' perceived attitudes toward and knowledge of spiritual care and change in nurses' perceived spiritual care competence. A prospective, longitudinal design was employed, and analyses included one-way repeated-measures analysis of variance, linear regression, and partial correlation. Statistically significant differences were found in nurses' attitudes toward and knowledge of spiritual care and nurses' perceived spiritual care competence. There was a positive relationship between change scores in nurses' attitudes toward and knowledge of spiritual care and nurses' spiritual care competence. Online spiritual care educational programs may exert a lasting impact on nurses' attitudes toward and knowledge of spiritual care and their competence to provide spiritual care to children with cancer at the end of life. Additional studies are required to evaluate the direct effects of educational interventions patient outcomes.