Beyond competence and retention: Developing a comprehensive evaluation framework for a rural primary care nurse practitioner residency program.

ABSTRACT: With the rise in nurse practitioner (NP) residency programs, evaluations have largely focused on retention and competency completion for residents. There is a need for expanded evaluation to ensure the sustainability of NP residency programs, to ensure timely adaptations to address resident satisfaction, and to solidify a long-term pathway of NPs well prepared for rural practice. We created a family nurse practitioner (FNP) residency program with a comprehensive evaluation framework to prepare residents for practice in rural settings. The evaluation framework was developed through collaborative engagement of an external evaluation team, program leadership, and clinical site representatives. The evaluation framework of the FNP residency program combined resident assessment and holistic program evaluation, using a rapid continuous quality improvement (QI) approach. The evaluation considered three distinct perspectives: the resident, the peer coach, and the clinical site. The rapid continuous QI approach allowed program leadership to respond swiftly to programmatic challenges, improve the residency program in response to residents' reported experiences, and emphasize sustainability for continued program impact, while assessing residents' learning and performance. The program's data-driven evaluation approach has demonstrated its success in meeting the goals of the Health Resources and Services Administration funding by increasing the number of primary care providers in rural settings. The program's expansion and continued success have further validated the efficacy of this evaluation framework in assessing, improving, and ensuring the sustainability of APRN residency programs. This article calls for the adoption of similar evaluation strategies in future residency programs to promote their long-term success and impact in rural health care settings.

Barriers to diabetic foot care in a disadvantaged population: A qualitative assessment.

OBJECTIVE: We explored barriers to proper foot care in this population using a qualitative approach with focus group discussions (FGD). METHODS: Participants were recruited from clinics at a safety-net hospital in Atlanta, Georgia and stratified into two groups: diabetic foot ulcer (DFU) and minor amputation (below ankle). The FGDs addressed patient experience in receiving care with a goal of understanding: foot care knowledge, barriers to care, and preferred educational methods. Surveys were performed to supplement FGDs. RESULTS: Forty participants (90% Black) were enrolled. Dominant themes emerging from FGDs were: 1-Patients reported adequate understanding of recommended foot care practices; 2-Personal barriers to self-care included lack of motivation, high cost, poor insurance coverage of supplies, and difficulty limiting activity for proper offloading; 3-Hospital system barriers included difficulty making timely appointments and reaching a provider to arrange care; 4-Access to footcare-related information and services improved with greater disease severity. Participants stressed that improved access often came too late to alter their course. They expressed interest in developing peer support groups to facilitate learning and sharing information relating to DFU. CONCLUSION: We found that patients with DFU or minor amputations have adequate footcare-related knowledge, but personal and systemic barriers limited appropriate foot care.

BORIS Expression in Ovarian Cancer Precursor Cells Alters the CTCF Cistrome and Enhances Invasiveness through GALNT14.

High-grade serous carcinoma (HGSC) is the most aggressive and predominant form of epithelial ovarian cancer and the leading cause of gynecologic cancer-related death. We have previously shown that CTCFL (also known as BORIS, Brother of the Regulator of Imprinted Sites) is expressed in most ovarian cancers, and is associated with global and promoter-specific DNA hypomethylation, advanced tumor stage, and poor prognosis. To explore its role in HGSC, we expressed BORIS in human fallopian tube secretory epithelial cells (FTSEC), the presumptive cells of origin for HGSC. BORIS-expressing cells exhibited increased motility and invasion, and BORIS expression was associated with alterations in several cancer-associated gene expression networks, including fatty acid metabolism, TNF signaling, cell migration, and ECM-receptor interactions. Importantly, GALNT14, a glycosyltransferase gene implicated in cancer cell migration and invasion, was highly induced by BORIS, and GALNT14 knockdown significantly abrogated BORIS-induced cell motility and invasion. In addition, in silico analyses provided evidence for BORIS and GALNT14 coexpression in several cancers. Finally, ChIP-seq demonstrated that expression of BORIS was associated with de novo and enhanced binding of CTCF at hundreds of loci, many of which correlated with activation of transcription at target genes, including GALNT14. Taken together, our data indicate that BORIS may promote cell motility and invasion in HGSC via upregulation of GALNT14, and suggests BORIS as a potential therapeutic target in this malignancy. IMPLICATIONS: These studies provide evidence that aberrant expression of BORIS may play a role in the progression to HGSC by enhancing the migratory and invasive properties of FTSEC.

Blocked transcription through KvDMR1 results in absence of methylation and gene silencing resembling Beckwith-Wiedemann syndrome.

The maternally methylated KvDMR1 ICR regulates imprinted expression of a cluster of maternally expressed genes on human chromosome 11p15.5. Disruption of imprinting leads to Beckwith-Wiedemann syndrome (BWS), an overgrowth and cancer predisposition condition. In the majority of individuals with BWS, maternal-specific methylation at KvDMR1 is absent and genes under its control are repressed. We analyzed a mouse model carrying a poly(A) truncation cassette inserted to prevent RNA transcripts from elongation through KvDMR1. Maternal inheritance of this mutation resulted in absence of DNA methylation at KvDMR1, which led to biallelic expression of Kcnq1ot1 and suppression of maternally expressed genes. This study provides further evidence that transcription is required for establishment of methylation at maternal gametic DMRs. More importantly, this mouse model recapitulates the molecular phenotypic characteristics of the most common form of BWS, including loss of methylation at KvDMR1 and biallelic repression of Cdkn1c, suggesting that deficiency of maternal transcription through KvDMR1 may be an underlying cause of some BWS cases.

Genetic determinants of FOXM1 overexpression in epithelial ovarian cancer and functional contribution to cell cycle progression.

The FOXM1 transcription factor network is frequently activated in high-grade serous ovarian cancer (HGSOC), the most common and lethal subtype of epithelial ovarian cancer (EOC). We used primary human EOC tissues, HGSOC cell lines, mouse and human ovarian surface epithelial (OSE) cells, and a murine transgenic ovarian cancer model to investigate genetic determinants of FOXM1 overexpression in EOC, and to begin to define its functional contribution to disease pathology. The Cancer Genome Atlas (TCGA) data indicated that the FOXM1 locus is amplified in ~12% of HGSOC, greater than any other tumor type examined, and that FOXM1 amplification correlates with increased expression and poor survival. In an independent set of primary EOC tissues, FOXM1 expression correlated with advanced stage and grade. Of the three known FOXM1 isoforms, FOXM1c showed highest expression in EOC. In murine OSE cells, combined knockout of Rb1 and Trp53 synergistically induced FOXM1. Consistently, human OSE cells immortalized with SV40 Large T antigen (IOSE-SV) had significantly higher FOXM1 expression than OSE immortalized with hTERT (IOSE-T). FOXM1 was overexpressed in murine ovarian tumors driven by combined Rb1/Trp53 disruption. FOXM1 induction in IOSE-SV cells was partially dependent on E2F1, and FOXM1 expression correlated with E2F1 expression in human EOC tissues. Finally, FOXM1 functionally contributed to cell cycle progression and relevant target gene expression in human OSE and HGSOC cell models. In summary, gene amplification, p53 and Rb disruption, and E2F1 activation drive FOXM1 expression in EOC, and FOXM1 promotes cell cycle progression in EOC cell models.

Origin of the vasculature supporting growth of primary patient tumor xenografts.

BACKGROUND: Studies of primary patient tumor xenografts grown in immunodeficient mice have shown that these tumors histologically and genetically closely resemble the original tumors. These patient xenograft models are becoming widely used for therapeutic efficacy studies. Because many therapies are directed at tumor stromal components and because the tumor microenvironment also is known to influence the response of a tumor to therapy, it is important to understand the nature of the stroma and, in particular, the vascular supply of patient xenografts. METHODS: Patient tumor xenografts were established by implanting undisrupted pieces of patient tumors in SCID mice. For this study, formalin fixed, paraffin embedded specimens from several types of solid tumors were selected and, using species-specific antibodies which react with formalin fixed antigens, we analyzed the species origin of the stroma and blood vessels that supported tumor growth in these models. Additionally, we investigated the kinetics of the vascularization process in a colon tumor and a mesothelioma xenograft. In mice bearing a head and neck xenograft, a perfusion study was performed to compare the functionality of the human and mouse tumor vessels. RESULTS: In patient tumors which successfully engrafted, the human stroma and vessels which were engrafted as part of the original tumor did not survive and were no longer detectable at the time of first passage (15-25 weeks). Uniformly, the stroma and vessels supporting the growth of these tumors were of murine origin. The results of the kinetic studies showed that the loss of the human vessels and vascularization by host vessels occurred more rapidly in a colon tumor (by 3 weeks) than in a mesothelioma (by 9 weeks). Finally, the perfusion studies revealed that while mouse vessels in the periphery of the tumor were perfused, those in the central regions were rarely perfused. No vessels of human origin were detected in this model. CONCLUSIONS: In the tumors we investigated, we found no evidence that the human stromal cells and vessels contained in the original implant either survived or contributed in any substantive way to the growth of these xenografts.