Gene Editing of α6 Integrin Inhibits Muscle Invasive Networks and Increases Cell-Cell Biophysical Properties in Prostate Cancer.

Human prostate cancer confined to the gland is indolent (low-risk), but tumors outside the capsule are aggressive (high-risk). Extracapsular extension requires invasion within and through a smooth muscle-structured environment. Because integrins respond to biomechanical cues, we used a gene editing approach to determine if a specific region of laminin-binding α6ß1 integrin was required for smooth muscle invasion both in vitro and in vivo. Human tissue specimens showed prostate cancer invasion through smooth muscle and tumor coexpression of α6 integrin and E-cadherin in a cell-cell location and α6 integrin in a cell-extracellular matrix (ECM) distribution. Prostate cancer cells expressing α6 integrin (DU145 α6WT) produced a 3D invasive network on laminin-containing Matrigel and invaded into smooth muscle both in vitro and in vivo. In contrast, cells without α6 integrin (DU145 α6KO) and cells expressing an integrin mutant (DU145 α6AA) did not produce invasive networks, could not invade muscle both in vitro and in vivo, and surprisingly formed 3D cohesive clusters. Using electric cell-substrate impedance testing, cohesive clusters had up to a 30-fold increase in normalized resistance at 400 Hz (cell-cell impedance) as compared with the DU145 α6WT cells. In contrast, measurements at 40,000 Hz (cell-ECM coverage) showed that DU145 α6AA cells were two-fold decreased in normalized resistance and were defective in restoring resistance after a 1 µmol/L S1P challenge as compared with the DU145 α6WT cells. The results suggest that gene editing of a specific α6 integrin extracellular region, not required for normal tissue function, can generate a new biophysical cancer phenotype unable to invade the muscle, presenting a new therapeutic strategy for metastasis prevention in prostate cancer. SIGNIFICANCE: This study shows an innovative strategy to block prostate cancer metastasis and invasion in the muscle through gene editing of a specific α6 integrin extracellular region.

Senior NCLEX-RN Coaching Model: Development and Implementation.

BACKGROUND: A host of interventions have been used to improve NCLEX outcomes, yet scant evidence exists to show the influence of academic coaching on pass rates. PURPOSE: To improve NCLEX confidence/readiness and pass rates in a baccalaureate nursing program, an NCLEX Coaching Model was developed and implemented. METHOD: Senior students were paired with faculty for 6 weeks of NCLEX coaching. Students self-assessed strengths, risk factors, and challenges related to NCLEX preparation. Coaches and students co-developed the NCLEX Preparation and Success Plan using standardized NCLEX predictor scores. Success plans represented individualized preparation strategies focused on specific NCLEX Client Needs categories. RESULT: National Council Licensure Examination confidence/readiness scores improved significantly, and first-time NCLEX pass rates improved slightly after coaching. CONCLUSION: An NCLEX Coaching Model can build student confidence/readiness and promote NCLEX success among nursing students. Peplau's Theory of Interpersonal Relations was useful in guiding development and implementation of a coaching model.

Predicting student attrition using social determinants: Implications for a diverse nursing workforce.

BACKGROUND: Attrition of academically qualified nursing students affects the size of the nursing workforce. A better understanding of the multifaceted predictive factors of attrition is needed to inform targeted interventions to promote program progression and maintain an adequate nursing workforce. PURPOSE: The purpose of this study was to identify demographic, academic, and social determinant factors associated with attrition at the end of the first semester in an upper-division baccalaureate nursing program. METHOD: Students' demographic and academic data from an administrative database were combined with social determinants data collected via a web-based survey. RESULTS: Among this cohort (n=164), social determinants were significantly associated with attrition. A significantly greater percentage of students who failed were born outside the United States (U.S.), had one or both parents born outside the U.S., reported English was not the primary language spoken in the home, and were racially/ethnically diverse. CONCLUSIONS: Attrition was primarily among students with diverse racial, ethnic, and/or cultural backgrounds, which has implications for achieving a diverse nursing workforce. Proactive strategies to support success should be especially targeted on diverse students.

Subjective cognitive complaints, psychosocial factors and nursing work function in nurses providing direct patient care.

AIMS: The aim of this study was to examine relationships among subjective cognitive complaints, psychosocial factors and nursing work function in nurses providing direct patient care. BACKGROUND: Cognitive functioning is a critical component for nurses in the assurance of error prevention, identification and correction when caring for patients. Negative changes in nurses' cognitive and psychosocial functioning can adversely affect nursing care and patient outcomes. DESIGN: A descriptive correlational design with stratified random sampling. METHOD: The sample included 96 nurses from the major geographic regions of the United States. Over 9 months in 2016-2017, data were collected using a web-based survey. Stepwise multiple linear regression analyses were used to examine relationships among subjective cognitive complaints, psychosocial factors and nursing work function. RESULTS: Overall, participants reported minimal work function impairment and low levels of subjective cognitive complaints, depression and stress. In multivariate analyses, depression was not associated with nurses' work function. However, perceived stress and subjective concerns about cognitive function were associated with greater impairment of work function. CONCLUSION: Nurses experiencing subjective cognitive complaints should be encouraged to address personal and environmental factors that are associated with their cognitive status. Additionally, stress reduction in nurses should be a high priority as a potential intervention to promote optimal functioning of nurses providing direct patient care. Healthcare institutions should integrate individual and institutional strategies to reduce factors contributing to workplace stress.

Student and Faculty Perceptions of iPad Integration in a Prelicensure Program.

This article provides an overview of strategies for integration of iPads into a prelicensure nursing program. The study evaluated the actual use of iPads in the classroom, skills and simulation laboratories, and clinical settings and examined the satisfaction of students and faculty with the iPad platform. The study findings provide guidance for a phased-in iPad implementation for prelicensure nursing programs.

The Cohesive Metastasis Phenotype in Human Prostate Cancer.

A critical barrier for the successful prevention and treatment of recurrent prostate cancer is detection and eradication of metastatic and therapy-resistant disease. Despite the fall in diagnoses and mortality, the reported incidence of metastatic disease has increased 72% since 2004. Prostate cancer arises in cohesive groups as intraepithelial neoplasia, migrates through muscle and leaves the gland via perineural invasion for hematogenous dissemination. Current technological advances have shown cohesive-clusters of tumor (also known as microemboli) within the circulation. Circulating tumor cell (CTC) profiles are indicative of disseminated prostate cancer, and disseminated tumor cells (DTC) are found in cohesive-clusters, a phenotypic characteristic of both radiation- and drug-resistant tumors. Recent reports in cell biology and informatics, coupled with mass spectrometry, indicate that the integrin adhesome network provides an explanation for the biophysical ability of cohesive-clusters of tumor cells to invade thorough muscle and nerve microenvironments while maintaining adhesion-dependent therapeutic resistance. Targeting cohesive-clusters takes advantage of the known ability of extracellular matrix (ECM) adhesion to promote tumor cell survival and represents an approach that has the potential to avoid the progression to drug- and radiotherapy-resistance. In the following review we will examine the evidence for development and dissemination of cohesive-clusters in metastatic prostate cancer.

Intracellular modifiers of integrin alpha 6p production in aggressive prostate and breast cancer cell lines.

Cancer metastasis is a multi-step process in which tumor cells gain the ability to invade beyond the primary tumor and colonize distant sites. The mechanisms regulating the metastatic process confer changes to cell adhesion receptors including the integrin family of receptors. Our group previously discovered that the α6 integrin (ITGA6/CD49f) is post translationally modified by urokinase plasminogen activator (uPA) and its receptor, urokinase plasminogen activator receptor (uPAR), to form the variant ITGA6p. This variant of ITGA6 is a cleaved form of the receptor that lacks the ligand-binding domain. Although it is established that the uPA/uPAR axis drives ITGA6 cleavage, the mechanisms regulating cleavage have not been defined. Intracellular integrin dependent "inside-out" signaling is a major regulator of integrin function and the uPA/uPAR axis. We hypothesized that intracellular signaling molecules play a role in formation of ITGA6p to promote cell migration during cancer metastasis. In order to test our hypothesis, DU145 and PC3B1 prostate cancer and MDA-MB-231 breast cancer cell lines were treated with small interfering RNA targeting actin and the intracellular signaling regulators focal adhesion kinase (FAK), integrin linked kinase (ILK), and paxillin. The results demonstrated that inhibition of actin, FAK, and ILK expression resulted in significantly increased uPAR expression and ITGA6p production. Inhibition of actin increased ITGA6p, although inhibition of paxillin did not affect ITGA6p formation. Taken together, these results suggest that FAK and ILK dependent "inside-out" signaling, and actin dynamics regulate extracellular production of ITGA6p and the aggressive phenotype.

Student evaluations of teaching tools: a qualitative examination of student perceptions.

Student evaluations of teaching (SET) are common and controversial, yet there is limited understanding of student perceptions of these evaluation tools. The authors examined an evidence-based SET tool for content validity using BSN, RN-to-BSN, and MSN student focus groups to explore individual question items and identify themes. Through communication and relationships with students, SET can influence teaching effectiveness and student learning, although student perceptions of individual items vary greatly.

An integrative review of student evaluations of teaching: implications for evaluation of nursing faculty.

Student evaluations of teaching often play an important role in the promotion and tenure of faculty. Many of the instruments in use within the university setting are self-developed and have not undergone psychometric testing. More specifically, nursing education has many unique challenges, yet the effectiveness of student evaluations of teaching in nursing is understudied. The purposes of this integrative review were to review the current research literature on the design and psychometric testing of teaching evaluation scales, to synthesize the results, and to propose implications specific to nursing programs that are evidence based and will provide guidance on faculty teaching evaluations. A systematic literature review was conducted using Cooper, H. (1998). Synthesizing research: A guide for literature review (3rd ed.). Thousand Oaks, CA: Sage Publications methodology. Data analysis led to the identification of 6 themes: faculty characteristics and perceptions, student characteristics and perceptions, course characteristics, on-line versus paper student evaluations, reliability and validity, and development of new instruments. This literature review provides the context in which to interpret student evaluations of teaching and discusses implications for practice.

Faculty and staff development strategies to prevent childhood obesity.

Childhood obesity prevention and management is currently a priority health focus in the United States. Graduates of nursing programs and practicing registered nurses must be competent to implement interventions and programs to assess, prevent, and manage childhood obesity in acute care and community settings. This article provides an overview of the scope of the problem and recommendations from relevant health organizations. Nurse and staff educators are provided with specific content and teaching strategies for the prevention and management of childhood obesity for developing the knowledge and skills of nursing students, staff nurses, and advanced practice nurses.