Recruiting Nurse Participants in Ambulatory Care Nursing Research.

Patient care needs in ambulatory care (AC) settings continue to grow and evolve in the United States, with commensurate growth of nursing responsibilities in AC. Conducting research on the nursing workforce and nursing practice is essential to understanding and meeting the needs of nurses and patients in this setting. However, the structures and characteristics of AC settings pose challenges for conducting research on AC nursing practice. This article explains unique barriers to participation in research for nurses in AC, describes recruitment challenges for nurse researchers in AC, and provides strategies to increase recruitment of nurses for AC research. Researchers in AC must find ways to recruit representative participant samples, be clear and precise in defining terms, and report robust demographic information about participants and their practice settings.

Nursing Professional Development in Ambulatory Care: A Phenomenological Study.

Nursing professional development (NPD) practitioners play an important role in ensuring the quality and safety of nursing care and in guiding nurses through practice transitions. Recently, increasing numbers of NPD practitioners have been employed in ambulatory care settings, yet little is known about how the ambulatory practice setting affects or is affected by NPD practice. The aim of this descriptive phenomenology was to describe how the NPD role is experienced in the ambulatory care setting.

Trailblazing New Paths to e-Learning Engagement.

E-learning modules are a common component of orientation and other education initiatives, but their usefulness can be limited by poor engagement. This article presents the results of an experimental cohort study testing interventions designed to improve learner engagement with e-learning modules.

Repeat hospital transfers among long stay nursing home residents: a mixed methods analysis of age, race, code status and clinical complexity.

BACKGROUND: Nursing home residents are at increased risk for hospital transfers resulting in emergency department visits, observation stays, and hospital admissions; transfers that can also result in adverse resident outcomes. Many nursing home to hospital transfers are potentially avoidable. Residents who experience repeat transfers are particularly vulnerable to adverse outcomes, yet characteristics of nursing home residents who experience repeat transfers are poorly understood. Understanding these characteristics more fully will help identify appropriate intervention efforts needed to reduce repeat transfers. METHODS: This is a mixed-methods study using hospital transfer data, collected between 2017 and 2019, from long-stay nursing home residents residing in 16 Midwestern nursing homes who transferred four or more times within a 12-month timeframe. Data were obtained from an acute care transfer tool used in the Missouri Quality Initiative containing closed- and open-ended questions regarding hospital transfers. The Missouri Quality Initiative was a Centers for Medicare and Medicaid demonstration project focused on reducing avoidable hospital transfers for long stay nursing home residents. The purpose of the analysis presented here is to describe characteristics of residents from that project who experienced repeat transfers including resident age, race, and code status. Clinical, resident/family, and organizational factors that influenced transfers were also described. RESULTS: Findings indicate that younger residents (less than 65 years of age), those who were full-code status, and those who were Black were statistically more likely to experience repeat transfers. Clinical complexity, resident/family requests to transfer, and lack of nursing home resources to manage complex clinical conditions underlie repeat transfers, many of which were considered potentially avoidable. CONCLUSIONS: Improved nursing home resources are needed to manage complex conditions in the NH and to help residents and families set realistic goals of care and plan for end of life thus reducing potentially avoidable transfers.

Mixed-Methods Analysis of Evaluations From In-Person and Remote Nursing Symposium Participants.

Many healthcare organizations offer symposia for sharing nursing research, evidence-based practice, and quality improvement efforts across the system. Significant resources are spent in planning events, with added complexity when symposia are conferenced across sites. A mixed-methods study was conducted to examine the relationship between quantitative and qualitative evaluation results of onsite and remote participants at a multisite nursing symposium. Results may be used by nursing professional development practitioners to inform development of future symposia.

Cofactor Biogenesis in Cysteamine Dioxygenase: C-F Bond Cleavage with Genetically Incorporated Unnatural Tyrosine.

Cysteamine dioxygenase (ADO) is a thiol dioxygenase whose study has been stagnated by the ambiguity as to whether or not it possesses an anticipated protein-derived cofactor. Reported herein is the discovery and elucidation of a Cys-Tyr cofactor in human ADO, crosslinked between Cys220 and Tyr222 through a thioether (C-S) bond. By genetically incorporating an unnatural amino acid, 3,5-difluoro-tyrosine (F2 -Tyr), specifically into Tyr222 of human ADO, an autocatalytic oxidative carbon-fluorine bond activation and fluoride release were identified by mass spectrometry and 19 F NMR spectroscopy. These results suggest that the cofactor biogenesis is executed by a powerful oxidant during an autocatalytic process. Unlike that of cysteine dioxygenase, the crosslinking results in a minimal structural change of the protein and it is not detectable by routine low-resolution techniques. Finally, a new sequence motif, C-X-Y-Y(F), is proposed for identifying the Cys-Tyr crosslink.

Transition From Clinical to Educator Roles in Nursing: An Integrative Review.

This review identified barriers to and facilitators of nurses' transition from clinical positions into nursing professional development and other nurse educator roles. The author conducted literature searches using multiple databases. Twenty-one articles met search criteria, representing a variety of practice settings. The findings, both barriers and facilitators, were remarkably consistent across practice settings. Four practice recommendations were drawn from the literature to promote nurses' successful transition to nursing professional development roles.

Durability of a vesicular stomatitis virus-based marburg virus vaccine in nonhuman primates.

The filoviruses, Marburg virus (MARV) and Ebola virus, causes severe hemorrhagic fever with high mortality in humans and nonhuman primates. A promising filovirus vaccine under development is based on a recombinant vesicular stomatitis virus (rVSV) that expresses individual filovirus glycoproteins (GPs) in place of the VSV glycoprotein (G). These vaccines have shown 100% efficacy against filovirus infection in nonhuman primates when challenge occurs 28-35 days after a single injection immunization. Here, we examined the ability of a rVSV MARV-GP vaccine to provide protection when challenge occurs more than a year after vaccination. Cynomolgus macaques were immunized with rVSV-MARV-GP and challenged with MARV approximately 14 months after vaccination. Immunization resulted in the vaccine cohort of six animals having anti-MARV GP IgG throughout the pre-challenge period. Following MARV challenge none of the vaccinated animals showed any signs of clinical disease or viremia and all were completely protected from MARV infection. Two unvaccinated control animals exhibited signs consistent with MARV infection and both succumbed. Importantly, these data are the first to show 100% protective efficacy against any high dose filovirus challenge beyond 8 weeks after final vaccination. These findings demonstrate the durability of VSV-based filovirus vaccines.

Interferon-ß therapy prolongs survival in rhesus macaque models of Ebola and Marburg hemorrhagic fever.

There is a clear need for novel, effective therapeutic approaches to hemorrhagic fever due to filoviruses. Ebola virus hemorrhagic fever is associated with robust interferon (IFN)-α production, with plasma concentrations of IFN-α that greatly (60- to 100-fold) exceed those seen in other viral infections, but little IFN-ß production. While all of the type I IFNs signal through the same receptor complex, both quantitative and qualitative differences in biological activity are observed after stimulation of the receptor complex with different type I IFNs. Taken together, this suggested potential for IFN-ß therapy in filovirus infection. Here we show that early postexposure treatment with IFN-ß significantly increased survival time of rhesus macaques infected with a lethal dose of Ebola virus, although it failed to alter mortality. Early treatment with IFN-ß also significantly increased survival time after Marburg virus infection. IFN-ß may have promise as an adjunctive postexposure therapy in filovirus infection.

Pathogenesis of Marburg hemorrhagic fever in cynomolgus macaques.

BACKGROUND: Marburg virus (MARV) infection causes a severe and often fatal hemorrhagic disease in primates; however, little is known about the development of MARV hemorrhagic fever. In this study we evaluated the progression of MARV infection in nonhuman primates. METHODS: Eighteen cynomolgus monkeys were infected with MARV; blood and tissues were examined sequentially over an 8-day period to investigate disease pathogenesis. RESULTS: Disease caused by MARV in cynomolgus macaques was very similar to disease previously described for Ebola virus-infected macaques. Monocytes, macrophages, Kupffer cells, and dendritic cells (DCs) were identified as the initial targets of MARV infection. Bystander lymphocyte apoptosis occurred at early stages in the disease course in intravascular and extravascular locations. The loss of splenic and lymph node DCs or downregulation of dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) on DCs as early as day 2 and continuing through day 8 after MARV infection was a prominent finding. Evidence of disseminated intravascular coagulation was noted; however, the degree of fibrin deposition in tissues was less prominent than was reported in Ebola-infected macaques. CONCLUSIONS: The sequence of pathogenic events identified in this study provides an understanding of the development of disease processes and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

Pathogenesis of Lassa fever in cynomolgus macaques.

BACKGROUND: Lassa virus (LASV) infection causes an acute and sometimes fatal hemorrhagic disease in humans and nonhuman primates; however, little is known about the development of Lassa fever. Here, we performed a pilot study to begin to understand the progression of LASV infection in nonhuman primates. METHODS: Six cynomolgus monkeys were experimentally infected with LASV. Tissues from three animals were examined at an early- to mid-stage of disease and compared with tissues from three animals collected at terminal stages of disease. RESULTS: Dendritic cells were identified as a prominent target of LASV infection in a variety of tissues in all animals at day 7 while Kupffer cells, hepatocytes, adrenal cortical cells, and endothelial cells were more frequently infected with LASV in tissues of terminal animals (days 13.5-17). Meningoencephalitis and neuronal necrosis were noteworthy findings in terminal animals. Evidence of coagulopathy was noted; however, the degree of fibrin deposition in tissues was less prominent than has been reported in other viral hemorrhagic fevers. CONCLUSION: The sequence of pathogenic events identified in this study begins to shed light on the development of disease processes during Lassa fever and also may provide new targets for rational prophylactic and chemotherapeutic interventions.

Management of a partial molar pregnancy: a case study report.

Partial molar pregnancy with coexisting fetus is a rare complication of pregnancy and carries significant risks to both the mother and the fetus. Maternal risks include abnormal bleeding and the development of preeclampsia. The fetus frequently develops abnormally, often due to abnormal karyotype. This case presents a woman with a partial molar pregnancy with coexisting fetus, including diagnosis, plan of care, and delivery information.

Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses.

Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.

Cellular immune response to Marburg virus infection in cynomolgus macaques.

Marburg virus (MARV) causes a severe and usually lethal hemorrhagic disease in humans and non-human primates. Here, 16 cynomolgus macaques were experimentally infected with the Ci67 strain of MARV. Blood and spleen samples were collected at various time points after infection to study the immunological response to MARV. Beginning at day 2 and continuing throughout the course of the infection there was a rise in antigen-presenting cells in both the blood and spleen expressing MARV glycoprotein. Natural killer (NK) cells declined in the blood after infection (from 15% on day 0 to 5% on day 6), but a small increase was seen in the spleen samples. Little or no change in CD4(+) or CD8(+) T cells was observed out to day 6 post-exposure in blood, while there was a continual decline in the percentage of CD8(+) T cells in spleen samples. Circulating B cells (defined as CD20(+)) increased during the course of the infection as did CD4(+) CD8(+) (double-positive) T cells. Intracellular cytokine staining indicated that by day 6 a large population of leukocytes in the spleen were producing IFN-alpha; analysis of surface markers indicated that these cells were plasmacytoid dendritic cells based on their expression of CD123(+), but these cells had decreased expression of class II MHC. IL-6 production was detected late in the infection in CD14(+) spleen cells. These results suggest a robust innate immune response to MARV; however, this response was delayed relative to the infection.

Marburg virus Angola infection of rhesus macaques: pathogenesis and treatment with recombinant nematode anticoagulant protein c2.

BACKGROUND: The procoagulant tissue factor (TF) is thought to play a role in the coagulation disorders that characterize filoviral infections. In this study, we evaluated the pathogenesis of lethal infection with the Angola strain of Marburg virus (MARV-Ang) in rhesus macaques and tested the efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2), an inhibitor of TF/factor VIIa, as a potential treatment. METHODS: Twelve rhesus macaques were challenged with a high dose (1000 pfu) of MARV-Ang. Six macaques were treated with rNAPc2, and 6 macaques served as control animals. RESULTS: All 6 control animals succumbed to MARV-Ang challenge by day 8 (mean, 7.3 days), whereas 5 of 6 rNAPc2-treated animals died on day 9 and 1 rNAPc2-treated animal survived. The disease course for MARV-Ang infection appeared to progress more rapidly in rhesus macaques than has been previously reported for other strains of MARV. In contrast to Ebola virus (EBOV) infection in macaques, up-regulation of TF was not as striking, and deposition of fibrin was a less prominent pathologic feature of disease in these animals. CONCLUSIONS: These data show that the pathogenicity of MARV-Ang infection appears to be consistent with the apparent increased human virulence attributed to this strain. The apparent reduced efficacy of rNAPc2 against MARV-Ang infection, compared with its efficacy against EBOV infection, appears to be associated with differences in TF induction and fibrin deposition.

Effective post-exposure treatment of Ebola infection.

Ebola viruses are highly lethal human pathogens that have received considerable attention in recent years due to an increasing re-emergence in Central Africa and a potential for use as a biological weapon. There is no vaccine or treatment licensed for human use. In the past, however, important advances have been made in developing preventive vaccines that are protective in animal models. In this regard, we showed that a single injection of a live-attenuated recombinant vesicular stomatitis virus vector expressing the Ebola virus glycoprotein completely protected rodents and nonhuman primates from lethal Ebola challenge. In contrast, progress in developing therapeutic interventions against Ebola virus infections has been much slower and there is clearly an urgent need to develop effective post-exposure strategies to respond to future outbreaks and acts of bioterrorism, as well as to treat laboratory exposures. Here we tested the efficacy of the vesicular stomatitis virus-based Ebola vaccine vector in post-exposure treatment in three relevant animal models. In the guinea pig and mouse models it was possible to protect 50% and 100% of the animals, respectively, following treatment as late as 24 h after lethal challenge. More important, four out of eight rhesus macaques were protected if treated 20 to 30 min following an otherwise uniformly lethal infection. Currently, this approach provides the most effective post-exposure treatment strategy for Ebola infections and is particularly suited for use in accidentally exposed individuals and in the control of secondary transmission during naturally occurring outbreaks or deliberate release.

Cross-protection against Marburg virus strains by using a live, attenuated recombinant vaccine.

Marburg virus (MARV) has been associated with sporadic episodes of hemorrhagic fever, including a recent highly publicized outbreak in Angola that produced severe disease and significant mortality in infected patients. MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV) expressing the glycoprotein of the Musoke strain of MARV (VSVDeltaG/MARVGP-Musoke). We used this vaccine to demonstrate complete protection of cynomolgus monkeys against a homologous MARV challenge. While these results are highly encouraging, an effective vaccine would need to confer protection against all relevant strains of MARV. Here, we evaluated the protective efficacy of the VSVDeltaG/MARVGP-Musoke vaccine against two heterologous MARV strains, the seemingly more pathogenic Angola strain and the more distantly related Ravn strain. In this study, seven cynomolgus monkeys were vaccinated with the VSVDeltaG/MARVGP-Musoke vector. Three of these animals were challenged with the Angola strain, three with the Ravn strain, and a single animal with the Musoke strain of MARV. Two animals served as controls and were each injected with a nonspecific VSV vector; these controls were challenged with the Angola and Ravn strains, respectively. Both controls succumbed to challenge by day 8. However, none of the specifically vaccinated animals showed any evidence of illness either from the vaccination or from the MARV challenges and all of these animals survived. These data suggest that the VSVDeltaG/MARVGP-Musoke vaccine should be sufficient to protect against all known MARV strains.