The Safe and Effective Use of Plant-Based Diets with Guidelines for Health Professionals.

Plant-based diets, defined here as including both vegan and lacto-ovo-vegetarian diets, are growing in popularity throughout the Western world for various reasons, including concerns for human health and the health of the planet. Plant-based diets are more environmentally sustainable than meat-based diets and have a reduced environmental impact, including producing lower levels of greenhouse gas emissions. Dietary guidelines are normally formulated to enhance the health of society, reduce the risk of chronic diseases, and prevent nutritional deficiencies. We reviewed the scientific data on plant-based diets to summarize their preventative and therapeutic role in cardiovascular disease, cancer, diabetes, obesity, and osteoporosis. Consuming plant-based diets is safe and effective for all stages of the life cycle, from pregnancy and lactation, to childhood, to old age. Plant-based diets, which are high in fiber and polyphenolics, are also associated with a diverse gut microbiota, producing metabolites that have anti-inflammatory functions that may help manage disease processes. Concerns about the adequate intake of a number of nutrients, including vitamin B12, calcium, vitamin D, iron, zinc, and omega-3 fats, are discussed. The use of fortified foods and/or supplements as well as appropriate food choices are outlined for each nutrient. Finally, guidelines are suggested for health professionals working with clients consuming plant-based diets.

COVID-19 and Oncology: Operationalizing Best Practices Across Collaborative Health Systems.

To plan for a proactive approach to support patients traveling for their treatment during the COVID-19 pandemic, a network of oncology hospitals worked within existing collaborative agreements to define policies and procedures to transition care for patients living in communities in close proximity to a member institution. Nurse leaders were instrumental in collaborating with and leading interprofessional partners to achieve these outcomes. These efforts led to patients' abilities to continue treatment in their local community, ensuring continuity of cancer care.

Professional Organization Membership: The Benefits of Increasing Nursing Participation.

Membership in professional organizations is a way for professionals with similar objectives to join together to have the voice of many, versus the voice of one. Joining an organization can lead to personal growth, enhanced professional prospective and knowledge development, and support for creating change.

A quality improvement approach to reducing hospital readmissions in patients with cancer and heart failure.

BACKGROUND: The management of patients with cancer and concurrent heart failure (HF) is challenging. The increased complexity of treatment and the occurrence of multiple overlapping symptoms may lead to frequent hospital admissions, which may result in cancer treatment delays, a diminished quality of life, and an increased financial burden for the patient's family. To provide holistic care to oncology patients with HF, we implemented the Heart Success Program (HSP), a patient-centered, interprofessional collaborative practice, which decreased the 30-day hospital readmission rate for HF diagnosis from 40 to 27%. However, this rate remains higher than that reported for Medicare beneficiaries. AIM: To identify the factors contributing to frequent readmissions, the HSP committee participated in the institution's Clinical Safety and Effectiveness and utilize quality improvement methodologies and tools to decrease hospital readmission for HF. METHODS: The DMAIC (Define, Measure, Analyze, Improve and Control) method was used to guide this quality improvement. Areas considered as having high impact and requiring low effort to address were patient education barriers, lack of documentation clarity, and care provider knowledge gaps about the HSP. We implemented workflow changes, improved clarity with documentation of HF diagnosis, and increase provider knowledge about the HSP. FINDINGS: After 6 months of implementing quality improvement techniques, the 30-day hospital readmission rate for HF patients fell by 23.43% (from 31.7% for the baseline period to 8.27%), exceeding the target project goal of 10%. Our quality improvement method may also be effective in improving the management of patients with cancer and other comorbid conditions.

Immunotherapy Toxicities: 
A New Electronic Documentation Template to Improve Patient Care.

BACKGROUND: Emerging immunotherapies are associated with numerous toxicities. Although traditional health records allow nurses to document system-based assessments, few offer immunotherapy-based documentation templates to assess and grade toxicities.
. OBJECTIVES: The aim of this article is to present the development of a standardized template for documenting genetically modified cellular product-related toxicities in an electronic health record (EHR).
. METHODS: Through interprofessional collaboration, a documentation template for genetically modified cellular product-related toxicities was developed in an EHR, allowing for standardized documentation, data reporting, and tracking of immune-related toxicities. 
. FINDINGS: The documentation template has enhanced the quality and safety of practice at the authors' institution and provides a framework for other nursing units when initiating immunotherapy care.
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Accuracy of harm scores entered into an event reporting system.

This quality improvement project evaluated the accuracy of harm scores entered into an event reporting system by inpatient nursing staff at a National Cancer Institute-designated comprehensive cancer center. Nurses scored 10 safety scenarios using 2 versions of the Agency for Healthcare Research and Quality scale to determine interrater reliability. Results indicated inconsistency in the way nurses scored the scenarios, suggesting that the event reporting system may not accurately portray the severity of harm in patient safety events. Nurse executives can use this information to guide the development and implementation of incident reporting systems.

Implementing a standardized home chemotherapy spill kit: a nurse-led interprofessional approach to best practice.

Chemotherapy administration in the home setting poses risks to patients, caregivers, and the environment, particularly in the event of spills. Although the response to chemotherapy spills in the hospital setting is vigorous and includes standard disposal practices for contaminated items, the management of spills in the home setting may vary. A standardized method for managing chemotherapy spills at home that includes education and distribution of spill cleanup materials is imperative to reduce these risks.

Characterization and optimization of a novel protein-protein interaction biosensor high-content screening assay to identify disruptors of the interactions between p53 and hDM2.

We present here the characterization and optimization of a novel imaging-based positional biosensor high-content screening (HCS) assay to identify disruptors of p53-hDM2 protein-protein interactions (PPIs). The chimeric proteins of the biosensor incorporated the N-terminal PPI domains of p53 and hDM2, protein targeting sequences (nuclear localization and nuclear export sequence), and fluorescent reporters, which when expressed in cells could be used to monitor p53-hDM2 PPIs through changes in the subcellular localization of the hDM2 component of the biosensor. Coinfection with the recombinant adenovirus biosensors was used to express the NH-terminal domains of p53 and hDM2, fused to green fluorescent protein and red fluorescent protein, respectively, in U-2 OS cells. We validated the p53-hDM2 PPI biosensor (PPIB) HCS assay with Nutlin-3, a compound that occupies the hydrophobic pocket on the surface of the N-terminus of hDM2 and blocks the binding interactions with the N-terminus of p53. Nutlin-3 disrupted the p53-hDM2 PPIB in a concentration-dependent manner and provided a robust, reproducible, and stable assay signal window that was compatible with HCS. The p53-hDM2 PPIB assay was readily implemented in HCS and we identified four (4) compounds in the 1,280-compound Library of Pharmacologically Active Compounds that activated the p53 signaling pathway and elicited biosensor signals that were clearly distinct from the responses of inactive compounds. Anthracycline (topoisomerase II inhibitors such as mitoxantrone and ellipticine) and camptothecin (topoisomerase I inhibitor) derivatives including topotecan induce DNA double strand breaks, which activate the p53 pathway through the ataxia telangiectasia mutated-checkpoint kinase 2 (ATM-CHK2) DNA damage response pathway. Although mitoxantrone, ellipticine, camptothecin, and topotecan all exhibited concentration-dependent disruption of the p53-hDM2 PPIB, they were much less potent than Nutlin-3. Further, their corresponding cellular images and quantitative HCS data did not completely match the Nutlin-3 phenotypic profile.

Implementation of a 220,000-compound HCS campaign to identify disruptors of the interaction between p53 and hDM2 and characterization of the confirmed hits.

In recent years, advances in structure-based drug design and the development of an impressive variety of high-throughput screening (HTS) assay formats have yielded an expanding list of protein-protein interaction inhibitors. Despite these advances, protein-protein interaction targets are still widely considered difficult to disrupt with small molecules. The authors present here the results from screening 220,017 compounds from the National Institute of Health's small-molecule library in a novel p53-hDM2 protein-protein interaction biosensor (PPIB) assay. The p53-hDM2 positional biosensor performed robustly and reproducibly throughout the high-content screening (HCS) campaign, and analysis of the multiparameter data from images of the 3 fluorescent channels enabled the authors to identify and eliminate compounds that were cytotoxic or fluorescent artifacts. The HCS campaign yielded 3 structurally related methylbenzo-naphthyridin-5-amine (MBNA) hits with IC(50)s between 30 and 50 microM in the p53-hDM2 PPIB. In HCT116 cells with wild-type (WT) p53, the MBNAs enhanced p53 protein levels, increased the expression of p53 target genes, caused a cell cycle arrest in G1, induced apoptosis, and inhibited cell proliferation with an IC(50) ~4 microM. The prototype disruptor of p53-hDM2 interactions Nutlin-3 was more potent than the MBNAs in the p53-hDM2 PPIB assay but produced equivalent biological results in HCT116 cells WT for p53. Unlike Nutlin-3, however, MBNAs also increased the percentage of apoptosis in p53 null cells and exhibited similar potencies for growth inhibition in isogenic cell lines null for p53 or p21. Neither the MBNAs nor Nutin-3 caused cell cycle arrest in p53 null HCT116 cells. Despite the relatively modest size of the screening library, the combination of a novel p53-hDM2 PPIB assay together with an automated imaging HCS platform and image analysis methods enabled the discovery of a novel chemotype series that disrupts p53-hDM2 interactions in cells.

Early safety assessment using cellular systems biology yields insights into mechanisms of action.

The integration of high-content screening (HCS) readers with organ-specific cell models, panels of functional biomarkers, and advanced informatics is a powerful approach to identifying the toxic liabilities of compounds early in the development process and forms the basis of "early safety assessment." This cellular systems biology (CSB) approach (CellCiphr profile) has been used to integrate rodent and human cellular hepatic models with panels of functional biomarkers measured at multiple time points to profile both the potency and specificity of the cellular toxicological response. These profiles also provide initial insights on the mechanism of the toxic response. The authors describe here mechanistic assay profiles designed to further dissect the toxic mechanisms of action and elucidate subtle effects apparent in subpopulations of cells. They measured 8 key mechanisms of toxicity with multiple biomarker feature measurements made simultaneously in populations of living primary hepatocytes and HepG2 cells. Mining the cell population response from these mechanistic profiles revealed the concentration dependence and nature of the heterogeneity of the response, as well as relationships between the functional responses. These more detailed mechanistic profiles define differences in compound activities that are not apparent in the average population response. Because cells and tissues encounter wide ranges of drug doses in space and time, these mechanistic profiles build on the CellCiphr profile and better reflect the complexity of the response in vivo.

Cellular systems biology profiling applied to cellular models of disease.

Building cellular models of disease based on the approach of Cellular Systems Biology (CSB) has the potential to improve the process of creating drugs as part of the continuum from early drug discovery through drug development and clinical trials and diagnostics. This paper focuses on the application of CSB to early drug discovery. We discuss the integration of protein-protein interaction biosensors with other multiplexed, functional biomarkers as an example in using CSB to optimize the identification of quality lead series compounds.

Development and implementation of three mitogen-activated protein kinase (MAPK) signaling pathway imaging assays to provide MAPK module selectivity profiling for kinase inhibitors: MK2-EGFP translocation, c-Jun, and ERK activation.

This chapter describes the development and implementation of three independent imaging assays for the major mitogen-activated protein kinase (MAPK) signaling modules: p38, JNK, and ERK. There are more than 500 protein kinases encoded in the human genome that share an ATP-binding site and catalytic domain conserved in both sequence and structure. The majority of kinase inhibitors have been found to be competitive with ATP, raising concerns regarding kinase selectivity and potency in an environment of millimolar intracellular concentrations of ATP, as well as the potential for off-target effects via the many other cellular proteins that bind and/or utilize ATP. The apparent redundancy of the kinase isoforms and functions in the MAPK signaling modules present additional challenges for kinase inhibitor selectivity and potency. Imaging assays provide a method to address many of these concerns. Cellular imaging approaches facilitate analysis of the targets expressed in the context of their endogenous substrates and scaffolding proteins and in a complex environment for which subcellular localization, cross talk between pathways, phosphatase regulatory control, and intracellular ATP concentrations are relevant to the functions of the kinase. The assays described herein provide a strategy to profile kinase inhibitors for MAPK pathway selectivity while simultaneously providing information on cell morphology or toxicity. Results suggest that the MAPK pathways are indeed susceptible to nonselective kinase inhibitors such as staurosporin and inhibitors that inhibit upstream MAPK Kinase Kinases (MKKKs) and MAPK Kinases (MKKs) in the MAPK signaling pathway, especially those involved in cross talk between the pathways. However, selective MAPK inhibitors were identified that exhibited pathway selectivity as evidenced by significantly lower IC(50) values for their respective p38, JNK, or ERK signaling pathway assays.

Systems cell biology based on high-content screening.

A new discipline of biology has emerged since 2004, which we call "systems cell biology" (SCB). Systems cell biology is the study of the living cell, the basic unit of life, an integrated and interacting network of genes, proteins, and myriad metabolic reactions that give rise to function. SCB takes advantage of high-content screening platforms, but delivers more detailed profiles of cellular systemic function, including the application of advanced reagents and informatics tools to sophisticated cellular models. Therefore, an SCB profile is a cellular systemic response as measured by a panel of reagents that quantify a specific set of biomarkers.

Data concordance from a comparison between filter binding and fluorescence polarization assay formats for identification of ROCK-II inhibitors.

The Rho-associated coiled-coil-containing protein serine/threonine kinases ROCK-I and ROCK-II are thought to play a major role in cytoskeletal dynamics by serving as downstream effectors of the Rho/Rac family of cytokine- and growth factor-activated small GTPases. As such, the ROCK family members are attractive intervention targets for a variety of pathologies, including cancer and cardiovascular disease. The authors developed a high-throughput screen to identify ROCK-II inhibitors and report results from a direct comparison of 2 screening campaigns for ROCK-II inhibitors using fluorescence polarization (FP) and filter binding (FB). Screening protocols to identify inhibitors of ROCK-II were developed in FB and FP formats under similar assay and kinetic conditions. A 30,000-member compound library was screened using FB ((33)P) and FP detection systems, and compounds that were active in either assay were retested in 5-point curve confirmation assays. Analysis of these data showed an approximate 95% agreement of compounds identified as active in both assay formats. Also, compound potency determinations from FB and FP had a high degree of correlation and were considered equivalent. These data suggest that the assay methodology has little impact on the quality and productivity of the screen, provided that the assays are developed to standardize kinetic conditions.

Algorithm for using a long-pulsed Nd:YAG laser in the treatment of deep cutaneous vascular lesions.

BACKGROUND: Conventional therapies for deep cutaneous vascular anomalies have demonstrated poor efficacy and many side effects. New laser systems offer greater potential to treat these difficult lesions, but the lack of specific treatment guidelines has restricted consistent success. OBJECTIVE: To establish a rational, user-friendly algorithm that incorporates basic components of deep vascular lesions to define the correct laser settings required for safe, effective, and reproducible treatment. METHODS: Within 18 months, 162 deep vascular lesions of various types and anatomic sites were evaluated for vessel size, depth, color, and pressure. An algorithm incorporating these characteristics was employed to determine laser parameter settings. Using a high-peak power, long-pulse 1064-nm Nd:YAG laser system, the vascular lesions were then treated. RESULTS: Within 6 months of follow-up, 80% of treated areas demonstrated a 50% or greater resolution after a single treatment session, with complete clearance shown in 19%. Only minimal and transient side effects were observed. Of note, 74% of areas on the extremities and 83% within the oral cavity showed a 50% or greater resolution after one treatment. CONCLUSION: Previously challenging deep cutaneous vascular anomalies may be safely reduced or cleared with the use of an appropriate laser system and this algorithm-directed technique. This represents a significant breakthrough in the management of vascular lesions.