Nursing Academic Leadership: An Urgent Workforce Shortage in Nursing Education.

AIM: The aim of the study was to describe the California nursing academic leader workforce shortage, identify succession planning activities, analyze driving and restraining forces of the role, and distinguish critical leadership competencies and onboarding strategies. BACKGROUND: Several studies have projected a workforce shortage for nursing academic leaders and studied the leadership competencies and driving and restraining forces impacting the role. METHOD: The study was a secondary descriptive analysis of an existing cross-sectional needs assessment survey administered to California nursing academic leaders of prelicensure programs. RESULTS: The results validated an impending workforce shortage for California nurse academic leaders, with 66 percent planning to leave their positions in the next five years and 46 percent not having a succession plan in place. CONCLUSION: To avoid threatening the success of nursing programs, a sustainable plan to address the workforce shortage of well-prepared academic nurse leaders is urgently needed.

Improved efficacy of a tolerizing DNA vaccine for reversal of hyperglycemia through enhancement of gene expression and localization to intracellular sites.

Insulin is a major target for the autoimmune-mediated destruction of pancreatic beta cells during the pathogenesis of type I diabetes. A plasmid DNA vaccine encoding mouse proinsulin II reduced the incidence of diabetes in a mouse model of type I diabetes when administered to hyperglycemic (therapeutic mode) or normoglycemic (prophylactic mode) NOD mice. Therapeutic administration of proinsulin DNA was accompanied by a rapid decrease in the number of insulin-specific IFN-gamma-producing T cells, whereas prophylactic treatment was accompanied by enhanced IFN-gamma-secreting cells and a decrease in insulin autoantibodies. Adoptive transfer experiments demonstrated that the protection was not mediated by induction of CD25(+)/CD4(+) T regulatory cells. The efficacy of the DNA vaccine was enhanced by increasing the level of expression of the encoded Ag, more frequent dosing, increasing dose level, and localization of the protein product to the intracellular compartment. The efficacy data presented in this study demonstrate that Ag-specific plasmid DNA therapy is a viable strategy for preventing progression of type I diabetes and defines critical parameters of the dosing regime that influences tolerance induction.

Preclinical validation of anti-TMEFF2-auristatin E-conjugated antibodies in the treatment of prostate cancer.

Current treatments for advanced stage, hormone-resistant prostate cancer are largely ineffective, leading to high patient mortality and morbidity. To fulfill this unmet medical need, we used global gene expression profiling to identify new potential antibody-drug conjugate (ADC) targets that showed maximal prostate cancer-specific expression. TMEFF2, a gene encoding a plasma membrane protein with two follistatin-like domains and one epidermal growth factor-like domain, had limited normal tissue distribution and was highly overexpressed in prostate cancer. Immunohistochemistry analysis using a specific monoclonal antibody (mAb) to human TMEFF2 showed significant protein expression in 74% of primary prostate cancers and 42% of metastatic lesions from lymph nodes and bone that represented both hormone-naïve and hormone-resistant disease. To evaluate anti-TMEFF2 mAbs as potential ADCs, one mAb was conjugated to the cytotoxic agent auristatin E via a cathepsin B-sensitive valine-citrulline linker. This ADC, Pr1-vcMMAE, was used to treat male severe combined immunodeficient mice bearing xenografted LNCaP and CWR22 prostate cancers expressing TMEFF2. Doses of 3 to 10 mg/kg of this specific ADC resulted in significant and sustained tumor growth inhibition, whereas an isotype control ADC had no significant effect. Similar efficacy and specificity was shown with huPr1-vcMMAE, a humanized anti-TMEFF2 ADC. No overt in vivo toxicity was observed with either murine or human ADC, despite significant cross-reactivity of anti-TMEFF2 mAb with the murine TMEFF2 protein, implying minimal toxicity to other body tissues. These data support the further evaluation and clinical testing of huPr1-vcMMAE as a novel therapeutic for the treatment of metastatic and hormone-resistant prostate cancer.

Plasmid-encoded proinsulin preserves C-peptide while specifically reducing proinsulin-specific CD8⁺ T cells in type 1 diabetes.

In type 1 diabetes (T1D), there is an intense inflammatory response that destroys the ß cells in the pancreatic islets of Langerhans, the site where insulin is produced and released. A therapy for T1D that targets the specific autoimmune response in this disease while leaving the remainder of the immune system intact, has long been sought. Proinsulin is a major target of the adaptive immune response in T1D. We hypothesized that an engineered DNA plasmid encoding proinsulin (BHT-3021) would preserve ß cell function in T1D patients through reduction of insulin-specific CD8⁺ T cells. We studied 80 subjects over 18 years of age who were diagnosed with T1D within the past 5 years. Subjects were randomized 2:1 to receive intramuscular injections of BHT-3021 or BHT-placebo, weekly for 12 weeks, and then monitored for safety and immune responses in a blinded fashion. Four dose levels of BHT-3021 were evaluated: 0.3, 1.0, 3.0, and 6.0 mg. C-peptide was used both as an exploratory efficacy measure and as a safety measure. Islet-specific CD8⁺ T cell frequencies were assessed with multimers of monomeric human leukocyte antigen class I molecules loaded with peptides from pancreatic and unrelated antigens. No serious adverse events related to BHT-3021 were observed. C-peptide levels improved relative to placebo at all doses, at 1 mg at the 15-week time point (+19.5% BHT-3021 versus -8.8% BHT-placebo, P < 0.026). Proinsulin-reactive CD8⁺ T cells, but not T cells against unrelated islet or foreign molecules, declined in the BHT-3021 arm (P < 0.006). No significant changes were noted in interferon-γ, interleukin-4 (IL-4), or IL-10 production in CD4 T cells. Thus, we demonstrate that a plasmid encoding proinsulin reduces the frequency of CD8⁺ T cells reactive to proinsulin while preserving C-peptide over the course of dosing.