Managing DNP projects in student/faculty groups to facilitate learning with large cohorts.

Despite the initial intent of the 2004 American Association of Colleges of Nursing (AACN) position statement to move all advanced nursing practice education to the doctoral level, many schools remain at the master's degree level. Many schools successfully transitioned their programs but struggled with adequate resources for the growing number of students and the faculty, staff, and preceptor workload associated with the Doctor of Nursing Practice (DNP) project courses. The AACN 2015 taskforce made many recommendations related to quality of DNP projects, but there is little in the literature on best operational practices. The goal of this paper is to describe how one school modified the DNP project courses from a traditional chair and committee driven format to a class driven format with multiple smaller sections to successfully manage large numbers of DNP students across nine specialties. Specifically, a new model with its successes and challenges is described as well as details regarding finances, course coordination, project advisors, project team, annual offerings and grouping of students.

Structuring Doctor of Nursing Practice project courses to facilitate success and ensure rigor.

There is currently a lack of consensus on the best format for Doctor of Nursing Practice project deliverables. In this article the project course history, current format, and evaluation methods are described for a Doctor of Nursing Practice program during the transition from a sole post-master's option to one that also admitted post-baccalaureate students. The project course format shifted focus from one in which students independently implemented multiple types of projects under the direction of a chairperson and committee to one in which students carried out projects utilizing quality improvement methods and tools under the mentorship of a project faculty advisor and clinical site representative. The integration of quality improvement models is exemplified through course objectives and assignments. Lessons learned through this transition are provided in the hope that the work may benefit other nursing schools with similar programs.

Impact of Electronic Reminders on Student Grades and Attitudes in Online Courses.

BACKGROUND: Reminders guide students in meeting course expectations for submitting assignments. PROBLEM: Variables linked to the effective use of reminders are unclear. The purpose of this study was to evaluate the impact on student grades and attitudes of using routine reminders for assignments in an online course. APPROACH: Students enrolled in online graduate and undergraduate nursing courses were emailed weekly reminders for discussion board assignments. Students received reminders for half of the semester and served as their own control to evaluate the impact of reminders on grades. OUTCOMES: There was no significant impact of reminders on grades or overall attitude. However, when undergraduate and graduate students were compared on individual questions on an attitude toward reminders' scale, undergraduate students reported that reminders were necessary, had a positive impact on their grades, and should be included in all courses. CONCLUSIONS: Reminders should be routinely used in undergraduate online courses.

Evaluating the Impact of Wikis on Student Learning Outcomes: An Integrative Review.

Although wikis appear to have been reported as effective tools for educators, uncertainty exists as to their effectiveness in achieving student learning outcomes. The aim of this integrative review was to examine the current evidence on the impact of wikis on student learning in courses requiring collaborative or co-developed assignments or activities. The authors searched several electronic databases for relevant articles and used R. Whittemore and K. Knafl's (2005) integrative review method to analyze and synthesize the evidence. Twenty-five articles met the selection criteria for this review, and four major themes for wiki use were identified: (a) writing skills, (b) collaboration, (c) knowledge acquisition, and (d) centralized repository. Although wikis have been found useful in improving student learning outcomes and hold great potential as an instructional strategy to aid students in learning various skills and gaining new knowledge, more research is needed on their effectiveness, especially in the area of nursing education.

High salt induces autocrine actions of ET-1 on inner medullary collecting duct NO production via upregulated ETB receptor expression.

The collecting duct endothelin-1 (ET-1), endothelin B (ETB) receptor, and nitric oxide synthase-1 (NOS1) pathways are critical for regulation of fluid-electrolyte balance and blood pressure control during high-salt feeding. ET-1, ETB receptor, and NOS1 are highly expressed in the inner medullary collecting duct (IMCD) and vasa recta, suggesting that there may be cross talk or paracrine signaling between the vasa recta and IMCD. The purpose of this study was to test the hypothesis that endothelial cell-derived ET-1 (paracrine) and collecting duct-derived ET-1 (autocrine) promote IMCD nitric oxide (NO) production through activation of the ETB receptor during high-salt feeding. We determined that after 7 days of a high-salt diet (HS7), there was a shift to 100% ETB expression in IMCDs, as well as a twofold increase in nitrite production (a metabolite of NO), and this increase could be prevented by acute inhibition of the ETB receptor. ETB receptor blockade or NOS1 inhibition also prevented the ET-1-dependent decrease in ion transport from primary IMCDs, as determined by transepithelial resistance. IMCD were also isolated from vascular endothelial ET-1 knockout mice (VEETKO), collecting duct ET-1 KO (CDET-1KO), and flox controls. Nitrite production by IMCD from VEETKO and flox mice was similarly increased twofold with HS7. However, IMCD NO production from CDET-1KO mice was significantly blunted with HS7 compared with flox control. Taken together, these data indicate that during high-salt feeding, the autocrine actions of ET-1 via upregulation of the ETB receptor are critical for IMCD NO production, facilitating inhibition of ion reabsorption.

You Are Not Alone: PARISH NURSES BRIDGE CHALLENGES FOR FAMILY CAREGIVERS.

In 2015, there were 43.5 million informal, unpaid caregivers in the United States. Caregivers reported a moderate to high level of burden of care, including performing medical and nursing tasks they were not trained to do. A study of family caregiver experiences with parish/faith community nurses reveals four key ways parish nurses support caregivers and offers important implications for parish nurse preparation and practice.

Rapamycin up-regulation of autophagy reduces infarct size and improves outcomes in both permanent MCAL, and embolic MCAO, murine models of stroke.

BACKGROUND AND PURPOSE: The role of autophagy in response to ischemic stroke has been confusing with reports that both enhancement and inhibition of autophagy decrease infarct size and improve post-stroke outcomes. We sought to clarify this by comparing pharmacologic modulation of autophagy in two clinically relevant murine models of stroke. METHODS: We used rapamycin to induce autophagy, and chloroquine to block completion of autophagy, by treating mice immediately after stroke and at 24 hours post-stroke in two different models; permanent Middle Cerebral Artery Ligation (MCAL), which does not allow for reperfusion of distal trunk of middle cerebral artery, and Embolic Clot Middle Cerebral Artery Occlusion (eMCAO) which allows for a slow reperfusion similar to that seen in most human stroke patients. Outcome measures at 48 hours post-stroke included infarct size analysis, behavioral assessment using Bederson neurological scoring, and survival. RESULTS: Chloroquine treatment reduced the lesion size by approximately 30% and was significant only in the eMCAO model, where it also improved the neurological score, but did not increase survival. Rapamycin reduced lesion size by 44% and 50% in the MCAL and eMCAO models, respectively. Rapamycin also improved the neurological score to a greater degree than chloroquine and improved survival. CONCLUSIONS: While both inhibition and enhancement of autophagy by pharmacological intervention decreased lesion size and improved neurological scores, the enhancement with rapamycin showed a greater degree of improvement in outcomes as well as in survival. The protective action seen with chloroquine may be in part due to off-target effects on apoptosis separate from blocking lysosomal activity in autophagy. We conclude pharmacologic induction of autophagy is more advantageous than its blockade in physiologically-relevant permanent and slow reperfusion stroke models.

Reconceptualization of a doctoral EBP course from in-class to blended format: lessons learned from a successful transition.

In 2008, the University of Maryland School of Nursing transitioned the doctor of nursing practice core courses from an in-class to a blended (hybrid) course delivery method. As part of this transition, the evidence-based practice course was reconceptualized, implemented in its new format, and evaluated after being completed by 2 cohorts. The transition was successful because of a strong open interprofessional team, faculty training in blended course best practices, support by experts in instructional design and Web-based learning throughout the transition, and continual formative evaluation by students and faculty. The resulting course received strong positive evaluations by students and was certified by Quality Matters, indicating the incorporation of best practices in online teaching.

Building health information technology capacity: they may come but will they use it?

Medical errors remain a major safety problem more than a decade after the Institute of Medicine reported 98 000 related deaths occur yearly in US hospitals. Medication errors account for one-third of these errors. Although medication reconciliation is an accepted care standard for patient safety, little evidence is available to make practice recommendations for primary care. The purpose of this study was to evaluate the effectiveness of using secure e-mail alerts within the reconciliation process on patient medication safety in clinics where electronic and personal health records are used. A nonexperimental, descriptive design with a convenience sample of 62 patients from two Veterans Health Administration clinics was used. Patients received secure e-mail instructing them to review their online medication list, update it based on home medications, and bring it to the appointment for discussion with their provider. A retrospective chart review was conducted examining changes made to medication lists in the electronic record after reconciliation. Data revealed the organization's adoption of secure e-mail did not guarantee its meaningful use by providers and patients, a clear barrier to implementing technology as an adjunct to care in context of complex clinical processes such as medication reconciliation. Lessons learned from the project's implementation are discussed.

Revision of a Parental Stress Scale for use on a pediatric general care unit.

The purpose of this descriptive correlational study was to test and evaluate the psychometric properties of a revised Parental Stressor Scale: Pediatric Intensive Care Unit (PSS:PICU) for use on a pediatric general care unit (PSS:GCU). The sample consisted of 403 parents of hospitalized children in a large military Mid-Atlantic medical center. Reliability and validity were assessed by examining the modified scale using factor analysis, Cronbach's alpha, item analysis, and concurrent validity. Factor analysis supported the subscales on the PSS:PICU. Internal consistency of the PSS:GCU produced a Cronbach's alpha of 0.92 for the total scale similar to the PSS:PICU scale, with the reliabilities for the subscales ranging from 0.70 to 0.92. Significant correlations were found between the total scores of the PSS:GCU and the Family Inventory of Life Events (FILE), a measure of general life stress. The results of psychometric testing suggest that the PSS:GCU is a reliable and valid scale to measure parental stress in general pediatric care units.

Pan-histone deacetylase inhibitor panobinostat depletes CXCR4 levels and signaling and exerts synergistic antimyeloid activity in combination with CXCR4 antagonists.

Stromal cell derived factor-1 (SDF-1 or CXCL12) and its receptor CXCR4 are involved in the directional homing to the bone marrow niches and in peripheral mobilization of normal and transformed hematopoietic stem and myeloid progenitor cells. Elevated CXCR4 expression confers poor prognosis, whereas inhibition of CXCR4 signaling overcomes stroma-mediated chemoresistance in acute myeloid leukemia (AML). Here, we demonstrate that treatment with the pan-histone deacetylase inhibitor panobinostat (PS) depleted the mRNA and protein levels of CXCR4 in the cultured and primary AML cells. PS-induced acetylation of the heat shock protein (hsp) 90 reduced the chaperone association between CXCR4 and hsp90, directing CXCR4 to degradation by the 20S proteasome. PS treatment also depleted G protein-coupled receptor kinase 3, as well as attenuated the phosphorylation of AKT and ERK1/2 in AML cells, which was not affected by cotreatment with CXCL12. Compared with each agent alone, cotreatment with PS and CXCR4 antagonist AMD3100 or FC-131 synergistically induced apoptosis of cultured and primary AML cells. PS and FC-131 exerted more lethal effects on primary AML versus normal CD34(+) bone marrow progenitor cells. These findings support the rationale to test the in vivo efficacy of PS in enhancing the lethal effects of CXCR4 antagonists against AML cells.

Finding a balance: health promotion challenges of military women.

In this study, we explored what may determine, or predict, United States military women's health promotion behaviors. Using a descriptive correlational design grounded in Pender's Health Promotion model, 491 military women completed instruments measuring their demographic variables, perception of health, definition of health, self-efficacy, and interpersonal influences to determine the significant factors affecting participation in health promotion activities. The outcome indicated that self-efficacy and interpersonal influences were the most influential in determining health promotion. This research illuminates some of the challenges working women face in meeting health promotion activities and how best to support their ability to participate in healthy behaviors.

Role of CAAT/enhancer binding protein homologous protein in panobinostat-mediated potentiation of bortezomib-induced lethal endoplasmic reticulum stress in mantle cell lymphoma cells.

PURPOSE: Bortezomib induces unfolded protein response (UPR) and endoplasmic reticulum stress, as well as exhibits clinical activity in patients with relapsed and refractory mantle cell lymphoma (MCL). Here, we determined the molecular basis of the improved in vitro and in vivo activity of the combination of the pan-histone deacetylase inhibitor panobinostat and bortezomib against human, cultured, and primary MCL cells. EXPERIMENTAL DESIGN: Immunoblot analyses, reverse transcription-PCR, and immunofluorescent and electron microscopy were used to determine the effects of panobinostat on bortezomib-induced aggresome formation and endoplasmic reticulum stress in MCL cells. RESULTS: Treatment with panobinostat induced heat shock protein 90 acetylation; depleted the levels of heat shock protein 90 client proteins, cyclin-dependent kinase 4, c-RAF, and AKT; and abrogated bortezomib-induced aggresome formation in MCL cells. Panobinostat also induced lethal UPR, associated with induction of CAAT/enhancer binding protein homologous protein (CHOP). Conversely, knockdown of CHOP attenuated panobinostat-induced cell death of MCL cells. Compared with each agent alone, cotreatment with panobinostat increased bortezomib-induced expression of CHOP and NOXA, as well as increased bortezomib-induced UPR and apoptosis of cultured and primary MCL cells. Cotreatment with panobinostat also increased bortezomib-mediated in vivo tumor growth inhibition and improved survival of mice bearing human Z138C MCL cell xenograft. CONCLUSION: These findings suggest that increased UPR and induction of CHOP are involved in enhanced anti-MCL activity of the combination of panobinostat and bortezomib.

Heat shock protein 90 inhibition depletes TrkA levels and signaling in human acute leukemia cells.

Nerve growth factor (NGF) induces autophosphorylation and downstream progrowth and prosurvival signaling from the receptor tyrosine kinase TrkA. Overexpression or activating mutation of TrkA has been described in human acute myeloid leukemia cells. In the present study, we show the chaperone association of TrkA with heat shock protein 90 (hsp90) and the inhibitory effect of the hsp90 inhibitor, 17-DMAG, on TrkA levels and signaling in cultured and primary myeloid leukemia cells. Treatment with 17-DMAG disrupted the binding of TrkA with hsp90 and the cochaperone cdc37, resulting in polyubiquitylation, proteasomal degradation, and depletion of TrkA. Exposure to 17-DMAG inhibited NGF-induced p-TrkA, p-AKT, and p-ERK1/2 levels, as well as induced apoptosis of K562, 32D cells with ectopic expression of wild-type TrkA or the constitutively active mutant Delta TrkA, and of primary myeloid leukemia cells. Additionally, 17-DMAG treatment inhibited NGF-induced neurite formation in the rat pheochromocytoma PC-12 cells. Cotreatment with 17-DMAG and K-252a, an inhibitor of TrkA-mediated signaling, induced synergistic loss of viability of cultured and primary myeloid leukemia cells. These findings show that TrkA is an hsp90 client protein, and inhibition of hsp90 depletes TrkA and its progrowth and prosurvival signaling in myeloid leukemia cells. These findings also support further evaluation of the combined activity of an hsp90 inhibitor and TrkA antagonist against myeloid leukemia cells.

Treatment with panobinostat induces glucose-regulated protein 78 acetylation and endoplasmic reticulum stress in breast cancer cells.

Increased levels of misfolded polypeptides in the endoplasmic reticulum (ER) triggers the dissociation of glucose-regulated protein 78 (GRP78) from the three transmembrane ER-stress mediators, i.e., protein kinase RNA-like ER kinase (PERK), activating transcription factor-6 (ATF6), and inositol-requiring enzyme 1alpha, which results in the adaptive unfolded protein response (UPR). In the present studies, we determined that histone deacetylase-6 (HDAC6) binds and deacetylates GRP78. Following treatment with the pan-histone deacetylase inhibitor panobinostat (Novartis Pharmaceuticals), or knockdown of HDAC6 by short hairpin RNA, GRP78 is acetylated in 11 lysine residues, which dissociates GRP78 from PERK. This is associated with the activation of a lethal UPR in human breast cancer cells. Coimmunoprecipitation studies showed that binding of HDAC6 to GRP78 requires the second catalytic and COOH-terminal BUZ domains of HDAC6. Treatment with panobinostat increased the levels of phosphorylated-eukaryotic translation initiation factor (p-eIF2alpha), ATF4, and CAAT/enhancer binding protein homologous protein (CHOP). Panobinostat treatment also increased the proapoptotic BIK, BIM, BAX, and BAK levels, as well as increased the activity of caspase-7. Knockdown of GRP78 sensitized MCF-7 cells to bortezomib and panobinostat-induced UPR and cell death. These findings indicate that enforced acetylation and decreased binding of GRP78 to PERK is mechanistically linked to panobinostat-induced UPR and cell death of breast cancer cells. Mol Cancer Ther; 9(4); 942-52. (c)2010 AACR.

Benefits & barriers to adoption of health IT in an elderly low-income, minority community-based environment.

This paper provides a detailed discussion regarding the attitudes, benefits, and barriers to adoption of health IT for low income, minority, elderly populations in a community-based affordable housing setting. Results show that despite challenges to adoption of technology amongst minority populations, senior residents will adopt technology if they understand the benefits of these technologies for improving their health and for remaining independent, thereby enabling them to age-in-place.

Cotreatment with panobinostat and JAK2 inhibitor TG101209 attenuates JAK2V617F levels and signaling and exerts synergistic cytotoxic effects against human myeloproliferative neoplastic cells.

The mutant JAK2V617F tyrosine kinase (TK) is present in the majority of patients with BCR-ABL-negative myeloproliferative neoplasms (MPNs). JAK2V617F activates downstream signaling through the signal transducers and activators of transcription (STAT), RAS/mitogen-activated protein kinase (MAPK), and phosphatidylinositol 3 (PI3)/AKT pathways, conferring proliferative and survival advantages in the MPN hematopoietic progenitor cells (HPCs). Treatment with the pan-histone deacetylase (HDAC) inhibitor panobinostat (PS) is known to inhibit the chaperone function of heat shock protein 90, as well as induce growth arrest and apoptosis of transformed HPCs. Here, we demonstrate that PS treatment depletes the autophosphorylation, expression, and downstream signaling of JAK2V617F. Treatment with PS also disrupted the chaperone association of JAK2V617F with hsp90, promoting proteasomal degradation of JAK2V617F. PS also induced apoptosis of the cultured JAK2V617F-expressing human erythroleukemia HEL92.1.7 and Ba/F3-JAK2V617F cells. Treatment with the JAK2 TK inhibitor TG101209 attenuated JAK2V617F autophosphorylation and induced apoptosis of HEL92.1.7 and Ba/F3-JAK2V617F cells. Cotreatment with PS and TG101209 further depleted JAK/STAT signaling and synergistically induced apoptosis of HEL92.1.7 and Ba/F3-JAK2V617F cells. Cotreatment with TG101209 and PS exerted greater cytotoxicity against primary CD34(+) MPN cells than normal CD34(+) HPCs. These in vitro findings suggest combination therapy with HDAC and JAK2V617F inhibitors is of potential value for the treatment of JAK2V617F-positive MPN.