RESUMEN
Sera of immune mice that were previously cured of their melanoma through a combined radiation and immunocytokine immunotherapy regimen consisting of 12 Gy of external beam radiation and the intratumoral administration of an immunocytokine (anti-GD2 mAb coupled to IL-2) with long-term immunological memory showed strong antibody-binding against melanoma tumor cell lines via flow cytometric analysis. Using a high-density whole-proteome peptide array (of 6.090.593 unique peptides), we assessed potential protein-targets for antibodies found in immune sera. Sera from 6 of these cured mice were analyzed with this high-density, whole-proteome peptide array to determine specific antibody-binding sites and their linear peptide sequence. We identified thousands of peptides that were targeted by these 6 mice and exhibited strong antibody binding only by immune (after successful cure and rechallenge), not naïve (before tumor implantation) sera and developed a robust method to detect these differentially targeted peptides. Confirmatory studies were done to validate these results using 2 separate systems, a peptide ELISA and a smaller scale peptide array utilizing a slightly different technology. To the best of our knowledge, this is the first study of the full set of germline encoded linear peptide-based proteome epitopes that are recognized by immune sera from mice cured of cancer via radio-immunotherapy. We furthermore found that although the generation of B-cell repertoire in immune development is vastly variable, and numerous epitopes are identified uniquely by immune serum from each of these 6 immune mice evaluated, there are still several epitopes and proteins that are commonly recognized by at least half of the mice studied. This suggests that every mouse has a unique set of antibodies produced in response to the curative therapy, creating an individual "fingerprint." Additionally, certain epitopes and proteins stand out as more immunogenic, as they are recognized by multiple mice in the immune group.
Asunto(s)
Melanoma , Animales , Ratones , Proteoma , Ratones Endogámicos C57BL , Inmunoterapia , Péptidos , Epítopos , Sueros InmunesRESUMEN
Hyalella azteca is a cryptic species complex of epibenthic amphipods of interest to ecotoxicology and evolutionary biology. It is the primary crustacean used in North America for sediment toxicity testing and an emerging model for molecular ecotoxicology. To provide molecular resources for sediment quality assessments and evolutionary studies, we sequenced, assembled, and annotated the genome of the H. azteca U.S. Lab Strain. The genome quality and completeness is comparable with other ecotoxicological model species. Through targeted investigation and use of gene expression data sets of H. azteca exposed to pesticides, metals, and other emerging contaminants, we annotated and characterized the major gene families involved in sequestration, detoxification, oxidative stress, and toxicant response. Our results revealed gene loss related to light sensing, but a large expansion in chemoreceptors, likely underlying sensory shifts necessary in their low light habitats. Gene family expansions were also noted for cytochrome P450 genes, cuticle proteins, ion transporters, and include recent gene duplications in the metal sequestration protein, metallothionein. Mapping of differentially expressed transcripts to the genome significantly increased the ability to functionally annotate toxicant responsive genes. The H. azteca genome will greatly facilitate development of genomic tools for environmental assessments and promote an understanding of how evolution shapes toxicological pathways with implications for environmental and human health.
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Anfípodos , Contaminantes Químicos del Agua , Animales , Ecotoxicología , Sedimentos Geológicos , América del Norte , Pruebas de ToxicidadRESUMEN
Prior to evidence-based practice, policies and procedures were reviewed annually or even triennially to ensure that they reflected current practice and demonstrated adherence to regulatory standards. With the publication of the Institute of Medicine report, a shift to operationalization of best evidence practices, formal statements, and frameworks for care has gained increased importance. Processes for policy and protocol development and revision are now based on the inclusion of best evidence, clinician expertise, and patient values or preference. Policies and protocols are now updated when new evidence justifies a revision and are designed to share the most recent evidence and facilitate staff adherence to new practices. This article describes the essential practices for policy and protocol development, including leadership support, team commitment, identification of current resources, recognition of current practices, development of the policy and protocol to logically flow with nursing practices, effective dissemination methods, and evaluation and sustainability practices. J Contin Nurs Educ. 2017;48(2):87-92.
Asunto(s)
Enfermería Basada en la Evidencia/normas , Guías de Práctica Clínica como Asunto/normas , Adulto , Femenino , Política de Salud , Humanos , Masculino , Persona de Mediana Edad , Estados UnidosRESUMEN
A unique approach to disseminate an evidence-based protocol for urinary catheter management was led by a staff-driven catheter-associated urinary tract infection (CAUTI) reduction team in one hospital. The nurseeducators, faculty from a local university, and the facility's clinical nurse leader mentored the team. As an approachto reduce CAUTIs in the transplant care and intensive care units, the team developed an interdisciplinary CAUTIEducation Fair, which provided a safe, nonthreateningenvironment to unlearn prior behaviors and showcompetency in new evidence-based ones.