Current ecotoxicity testing needs among selected U.S. federal agencies.

U.S. regulatory and research agencies use ecotoxicity test data to assess the hazards associated with substances that may be released into the environment, including but not limited to industrial chemicals, pharmaceuticals, pesticides, food additives, and color additives. These data are used to conduct hazard assessments and evaluate potential risks to aquatic life (e.g., invertebrates, fish), birds, wildlife species, or the environment. To identify opportunities for regulatory uses of non-animal replacements for ecotoxicity tests, the needs and uses for data from tests utilizing animals must first be clarified. Accordingly, the objective of this review was to identify the ecotoxicity test data relied upon by U.S. federal agencies. The standards, test guidelines, guidance documents, and/or endpoints that are used to address each of the agencies' regulatory and research needs regarding ecotoxicity testing are described in the context of their application to decision-making. Testing and information use, needs, and/or requirements relevant to the regulatory or programmatic mandates of the agencies taking part in the Interagency Coordinating Committee on the Validation of Alternative Methods Ecotoxicology Workgroup are captured. This information will be useful for coordinating efforts to develop and implement alternative test methods to reduce, refine, or replace animal use in chemical safety evaluations.

Implementing peer learning to prepare students for OSCEs.

First-year nursing students undertaking a first-year clinical skills module were given an opportunity to take part in a voluntary peer learning scheme, where they would learn from more senior students. It was envisaged this would help the students prepare for the module's summative assessment-an objective structured clinical examination (OSCE), which students can find stressful. The first-year students found peer learning helped them improve clinical skills, reduced anxiety and increased their self-confidence, and they appreciated the non-threatening learning environment and constructive feedback. The more senior students felt it helped prepare them for their mentoring role after registration. Incorporating peer learning more widely into the curriculum would allow it to be evaluated in more depth.

Splenic angioleiomyoma in an owl monkey (Aotus nancymae).

BACKGROUND: An adult male owl monkey (Aotus nancymae) underwent a splenectomy. When the spleen was removed, a small, nodular mass slightly bulging over the splenic surface was noted. METHODS: The mass was examined by light and transmission electron microscopy and by immunohistochemistry. RESULTS: On light microscopy, the mass was well-circumscribed, non-encapsulated, and composed of haphazardly arranged smooth muscle bundles admixed with numerous small capillary-like structures containing blood. Immunohistochemical (IHC) staining revealed the tumor was strongly positive for smooth muscle actin yielding vascular smooth muscle bundles, and for Factor VIII, staining endothelial cells within the smooth muscle bundles. Transmission electron microscopy (TEM) showed a large portion of the cells to be atypical appearing smooth muscle and a few cells had structures resembling Weibel-Palade bodies indicating endothelial cells. CONCLUSIONS: Based on cell morphology, by light and TEM, and IHC a final diagnosis of splenic angioleiomyoma was made. This is, to our knowledge, the first report of an angioleiomyoma in a non-human primate.

Oxylepitoxin-1, a reversible neurotoxin from the venom of the inland taipan (Oxyuranus microlepidotus).

This study describes the characterization of oxylepitoxin-1 (MW 6789), the first postsynaptic neurotoxin isolated from the venom of the Inland taipan (Oxyuranus microlepidotus), which is the most venomous snake in the world. Oxylepitoxin-1, purified using successive steps of size-exclusion and reverse phase-high performance liquid chromatography, produced concentration-dependent (0.3-1.0 microM) inhibition of nerve-mediated (0.1 Hz, 0.2 ms, supramaximal V) twitches of the chick biventer cervicis nerve-muscle preparation. Taipan antivenom (5units/ml) prevented the neurotoxic activity of whole venom (10 microg/ml), but had no significant effect on oxylepitoxin-1 (1 microM). The toxin-induced inhibition of nerve-mediated twitches was significantly reversed upon washing the tissue at 5 min intervals. Oxylepitoxin-1 (30-300 nM) displayed competitive antagonism at the skeletal muscle nicotinic receptor with a pA(2) value of 7.16+/-0.28 (i.e. approximately 10-fold more potent than tubocurarine). The venom had a high level of PLA(2) activity (765+/-73 micromol/min/mg) while oxylepitoxin-1 displayed no PLA(2) activity. Partial N-terminal sequencing of oxylepitoxin-1 shows high sequence identity (i.e. 93%) to postsynaptic toxins isolated from the venom of the closely related coastal taipan (Oxyuranus scutellatus scutellatus).

Building a vision of dietitian services in primary health care.

PURPOSE: Primary health care (PHC) reform, especially efforts to implement interdisciplinary teams, has implications for dietetic practice. A consistent, clear vision of the registered dietitian's (RD's) role in PHC is needed to develop a successful advocacy agenda. METHODS: The Dietitians of Canada (DC) Central and Southern Ontario Primary Health Care Action Group organized a four-step process to engage dietitians in developing an advocacy agenda for RD PHC services in Ontario. Two facilitated workshops brought together dietitian opinion leaders to enhance the understanding of current roles, find common ground, and develop a shared vision. All DC members were invited to review the draft vision, and feedback was integrated into a revised vision. RESULTS: Registered dietitians saw PHC reform through many lenses, and were uncertain about how reforms would affect their practices. In a national review, the majority of reviewers (approximately 85% of 270) supported the draft vision; additional clarity was needed on resources and the breadth of services that RDs would provide. CONCLUSION: Development of a PHC vision for RDs should be helpful in advocating for dietitian services in PHC.

A new path forward: the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) and National Toxicology Program's Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM).

In 2000, the Interagency Coordinating Committee on the Validation of Alternative Methods (ICCVAM) was congressionally established, with representatives from Federal regulatory and research agencies that require, use, generate, or disseminate toxicologic and safety testing information. For over 15 y, ICCVAM and the National Toxicology Program's Interagency Center for the Evaluation of Alternative Toxicological Methods (NICEATM) have worked together to promote the development, validation, and regulatory acceptance of test methods that replace, reduce, or refine the use of animals in regulatory testing. In 2013, both NICEATM and ICCVAM underwent major changes to their operating paradigms, to increase the speed and efficiency of regulatory approval and industry adoption of 3Rs testing methods within the United States and internationally. Accordingly, increased emphasis has been placed on international activities, primarily through interaction with the Organization for Economic Cooperation and Development and participation in the International Cooperation on Alternative Test Methods. In addition, ICCVAM has committed to increasing public awareness of and transparency about federal agencies' 3R activities and to fostering interactions with stakeholders. Finally, although it continues to support ICCVAM, NICEATM's work now includes validation support for Tox21, a collaboration aimed at identifying in vitro methods and computational approaches for testing chemicals to better understand and predict hazards to humans and the environment. The combination of more efficient operating paradigms, increased international collaboration, improved communication and interaction with stakeholders, and active participation in Tox21 likely will substantially increase the number of 3Rs methods developed and used in the United States and internationally.

Organization, Development and Enucleation-induced Alterations in the Visual Callosal Projection of the Hamster: Single Axon Tracing with Phaseolus vulgaris leucoagglutinin and Di-I.

The distribution of callosal axons interconnecting lateral area 17 and medial area 18 of the rodent's occipital cortex is dramatically altered by neonatal enucleation, but it is not known how this manipulation affects the morphology of individual callosal axons or whether the enucleation-induced changes in this pathway reflect maintenance of a transient developmental state by these fibres. In the present study, these questions were addressed by tracing the individual callosal axons in normal adult and neonatally enucleated adult hamsters with Phaseolus vulgaris leucoagglutinin (PHAL) and by anterograde labelling of developing callosal axons with the carbocyanine dye, Di-I. In normal adults, injections of PHAL into the region of the 17 - 18a border produced dense labelling in all layers in the region of the contralateral 17 - 18a border. Larger injections resulted in callosal labelling that extended across the lateral one-half of area 17, primarily in layers I and V. Thirty-four callosal axons from normal adult hamsters were reconstructed through all the cortical laminae. Most of these had very simple terminal arbors. They gave off short collaterals in the infragranular layers and branched more extensively in the uppermost part of layer II - III and in lamina I. Small injections of PHAL into the occipital cortex of neonatally enucleated adult hamsters resulted in labelled axons throughout most of areas 17 and 18a in the contralateral hemisphere. The terminal arbors of most individual callosal axons in eyeless hamsters were not appreciably different from those in sighted animals. However, 26.8% of 28 fibres reconstructed through all cortical laminae in the neonatally enucleated hamsters had much more widespread branches than any of the axons recovered from normal hamsters. As a result, the average total length of the callosal axons from the blinded hamsters was significantly greater than that for such fibres from the sighted animals. Anterograde labelling with Di-I demonstrated axons in the anterior commissure and anterior part of the corpus callosum on P-0. Labelled fibres extended into the white matter underlying the occipital cortex on P-1 and entered the cortical plate on P-2. Some of these axons reached into the marginal layer. Many developing callosal axons had short branches in the white matter, but generally extended only a single collateral into the cortical grey matter. Callosal axons in perinatal animals branched very little within the cortex and, in this respect, resembled fibres labelled with PHAL in adult hamsters. These results support the conclusion that the expanded tangential distribution of the occipital callosal projection in neonatally enucleated adult hamsters results, at least in part, from individual axons with abnormally widespread terminal arbors which are not present in large numbers at any time during normal development.

Detection and clearance of Syphacia obvelata infection in Swiss Webster and athymic nude mice.

Our routine health-surveillance program is based on use of the Swiss Webster mouse, with sentinels submitted for testing every 7 weeks. Athymic nude (nu/nu) mice are used as an adjunct method to detect pinworm infections. The premise for the use of the nude mouse was based on research that revealed the thymus as necessary to confer resistance to pinworm infections. In light of this finding, it was inferred that an athymic mouse would be more susceptible to pinworm infections than a euthymic mouse, and hence a better sentinel animal for pinworm detection. To test the validity of this assumption, the Syphacia obvelata detection ability of the athymic nude mouse was compared to that of the Swiss Webster. Our results indicate no significant temporal difference in the detection ability of the two genotypes of mice. A clearance study for the parasite was also performed, in which the majority of Swiss Webster mice cleared the infection whereas athymic nude mice did not. In light of our results, we conclude that use of the athymic nude mouse for Syphacia obvelata detection offered no significant advantage over the euthymic Swiss Webster mouse for our program.

Developing and examining an Objective Structured Clinical Examination.

Objective Structured Clinical Examinations are commonly used within pre-registration and post-qualification nurse education to test clinical competence. Station development and refinement of the pass mark is essential to the examination process. In this paper the process of blue-printing and standardisation are described as one method of agreeing examination content and subsequent pass mark. Issues of validity and reliability are discussed in relation to these and to the process of examining. The development of good practice guidelines to ensure consistency between different markers of the same station and of a single marker examining different students on one station is described. Recommendations in relation to transparency are made to optimise student understanding of what they are being tested on and hence their performance in the examination.

The development and evaluation of a computer-based resource to assist pre-registration nursing students with their preparation for objective structured clinical examinations (OSCEs).

This paper presents a narrative discussion of an innovative, computer-based resource developed, implemented and evaluated by a small project team at a school of nursing and midwifery in London. The interactive resource was designed to assist first and second year pre-registration nursing students with both their clinical skills revision and formative preparation for Objective Structured Clinical Examinations and involved a small range of clinical skills. These included: skin assessment; hand hygiene; reading a drug prescription chart, weighing a baby and assessment of an intravenous cannulae site. The processes involved in the development of the tool are described and, the key drivers informing its development are identified. Although a formal research approach was not adopted a summary of feedback obtained from anonymous student evaluations is included. This provides important insights into the perceived usefulness of the tool and is discussed in light of the challenges and practicalities associated with the content development and technical issues. The paper concludes by identifying proposed future developments and wider applications of this innovative clinical skills education initiative within nursing and healthcare education.

Peripheral edema with hypoalbuminemia in a nonhuman primate infected with simian-human immunodeficiency virus: a case report.

A rhesus macaque (Macaca mulatta) infected with simian-human immunodeficiency virus (SHIV) while undergoing AIDS research, required a comprehensive physical examination when it presented with slight peripheral edema, hypoalbuminemia, and proteinuria. Many of the clinical findings were consistent with nephrotic syndrome, which is an indication of glomerular disease, but the possibility of concurrent disease needed to be considered because lentiviral induced immune deficiency disease manifests multiple clinical syndromes. The animal was euthanized when its condition deteriorated despite supportive care that included colloidal fluid therapy. Histopathology confirmed membranoproliferative glomerulonephritis, the result of immune complex deposition most likely due to chronic SHIV infection. Clinical symptoms associated with this histopathology in SHIV-infected macaques have not previously been described. Here we offer suggestions for the medical management of this condition, which entails inhibition of the renin-angiotensin-aldosterone system and diet modifications.