Training and Educational Pathways for Clinicians (Post-graduation) for the Assessment and Diagnosis of Autism Spectrum Disorders: A Scoping Review.

This review aimed to identify the post-graduation training pathways available for both clinicians and trainers in the assessment and diagnosis of Autism Spectrum Disorder (ASD). The study was guided by two research questions: What is known about ASD-specific educational, training, or other pathways available to support clinicians of any discipline, post-graduation, to meet the required expertise relevant to assessments of ASD concerns? What is known about the educational pathways available to clinicians seeking to provide training to other clinicians, post-graduation, in the assessment of ASD concerns? A scoping review was undertaken with searches completed across five databases (PubMed, PsycINFO, PsycEXTRA, ERIC and CINAHL). A Google search strategy was also executed using the "advanced" search function. Eligible records were literature, written in English, that examined post-graduation training and/ or education of clinicians to assess and/ or diagnose ASD. Fourteen relevant records were identified. Post-graduate training has the potential to enhance clinician confidence and service provision in ASD assessment and diagnosis. System-wide training approaches show promise in building large-scale, diagnostic capacity and the use of tele-mentoring offers a cost-effective, convenient mode of training delivery. A lack of evidence to support ASD diagnostic training pathways was found and may pose a challenge for clinicians and service users. The limited evidence found suggests that high quality research will be fundamental in determining how to build clinician capacity in ASD assessment and diagnosis and to ascertain whether training pathways are a necessary component.

Differential Susceptibility to Benzo[a]pyrene Exposure during Gestation and Lactation in Mice with Genetic Variations in the Aryl Hydrocarbon Receptor and Cyp1 Genes.

Polycyclic aromatic hydrocarbons are ubiquitous air pollutants, with additional widespread exposure in the diet. PAH exposure has been linked to adverse birth outcomes and long-term neurological consequences. To understand genetic differences that could affect susceptibility following developmental exposure to polycyclic aromatic hydrocarbons, we exposed mice with variations in the aryl hydrocarbon receptor and the three CYP1 enzymes from gestational day 10 (G10) to weaning at postnatal day 25 (P25). We found unexpectedly high neonatal lethality in high-affinity AhrbCyp1b1(-/-) knockout mice compared with all other genotypes. Over 60% of BaP-exposed pups died within their first 5 days of life. There was a significant effect of BaP on growth rates in surviving pups, with lower weights observed from P7 to P21. Again, AhrbCyp1b1(-/-) knockout mice were the most susceptible to growth retardation. Independent of treatment, this line of mice also had impaired development of the surface righting reflex. We used high-resolution mass spectrometry to measure BaP and metabolites in tissues from both dams and pups. We found the highest BaP levels in adipose from poor-affinity AhrdCyp1a2(-/-) dams and identified three major BaP metabolites (BaP-7-OH, BaP-9-OH, and BaP-4,5-diol), but our measurements were limited to a single time point. Future work is needed to understand BaP pharmacokinetics in the contexts of gestation and lactation and how differential metabolism leads to adverse developmental outcomes.

The behavioral effects of gestational and lactational benzo[a]pyrene exposure vary by sex and genotype in mice with differences at the Ahr and Cyp1a2 loci.

Benzo[a]pyrene (BaP) is a polycyclic aromatic hydrocarbon (PAH) and known carcinogen in the Top 10 on the United States' list of priority pollutants. Humans are exposed through a variety of sources including tobacco smoke, grilled foods and fossil fuel combustion. Recent studies of children exposed to higher levels of PAHs during pregnancy and early life have identified numerous adverse effects on the brain and behavior that persist into school age and adolescence. Our studies were designed to look for genotype and sex differences in susceptibility to gestational and lactational exposure to BaP using a mouse model with allelic differences in the aryl hydrocarbon receptor and the xenobiotic metabolizing enzyme CYP1A2. Pregnant dams were exposed to 10 mg/kg/day of BaP in corn oil-soaked cereal or the corn oil vehicle alone from gestational day 10 until weaning at postnatal day 25. Neurobehavioral testing began at P60 using one male and one female per litter. We found main effects of sex, genotype and treatment as well as significant gene x treatment and sex x treatment interactions. BaP-treated female mice had shorter latencies to fall in the Rotarod test. BaP-treated high-affinity AhrbCyp1a2(-/-) mice had greater impairments in Morris water maze. Interestingly, poor-affinity AhrdCyp1a2(-/-) mice also had deficits in spatial learning and memory regardless of treatment. We believe our findings provide future directions in identifying human populations at highest risk of early life BaP exposure, because our model mimics known human variation in our genes of interest. Our studies also highlight the value of testing both males and females in all neurobehavioral studies.

Supplemental taurine during adolescence and early adulthood has sex-specific effects on cognition, behavior and neurotransmitter levels in C57BL/6J mice dependent on exposure window.

The mammalian brain goes through final maturation during late adolescence and early adulthood with sex differences in timing. The key cellular processes, including changes in neurotransmitter receptor density and synaptic pruning, make this age uniquely vulnerable to neurotoxic insults. Teenagers and young adults are the major consumers of energy drinks, which contain high levels of taurine and caffeine. Taurine is one of the most abundant amino acids in the central nervous system, but the effects of supplemental taurine consumption during adolescence has not been well studied. We conducted an initial short-term exposure study with 0.12% taurine in drinking water and a long-term exposure dose-response study using 0.06 and 0.12% taurine in male and female C57BL/6J mice. We examined a broad range of cognitive functions and behaviors and measured neurotransmitter levels. We found no significant differences in anxiety, open field locomotor activity, or sensorimotor gating. However, we found impairments in novel object recognition and sex differences in Morris water maze. When taurine treatment stopped before behavioral experiments began, male mice had significant impairments in spatial learning and memory. In the dose-response study when taurine treatment continued throughout behavioral experiments, females had significant impairments. We also found sex differences in neurotransmitter levels with females having higher levels of glutamate, DOPAC and 5-HIAA. We conclude that both females and males are at risk from excess taurine consumption during final brain maturation.

Society of Toxicology Develops Learning Framework for Undergraduate Toxicology Courses Following the Vision and Change Core Concepts Model.

The Society of Toxicology announces the development of a Learning Framework (https://www.toxicology.org/education/docs/SOT-Toxicology-Learning-Objectives.pdf) for undergraduate toxicology that will facilitate the development and sharing of evidence-based teaching materials for undergraduate toxicology educators throughout the world. This Learning Framework was modeled on the "Vision and Change Report" (www.visionandchange.org), an effort of the National Science Foundation and American Association for the Advancement of Science defining Core Concepts and Core Competencies to inform undergraduate biology course design. Vision and Change (V&C) has gained national acceptance, becoming a foundation for 14 upper-level courses designed by professional life science scientific societies. The undergraduate toxicology Learning Framework includes 5 Core Concepts aligned with V&C that encompass the discipline of toxicology: Evolution; Biological Information, Risk and Risk Management; Systems Toxicology; and Pathways and Transformations for Energy and Matter. Underpinning the Core Concepts are Level 2 Toxicology Concepts, which are broad disciplinary categories, Level 3 Learning Objectives, which address specific learning goals, and Level 4 Example Learning Objectives and Case Studies, which provide examples of how content might be taught. Syllabi from more than 20 undergraduate toxicology courses and several undergraduate toxicology textbooks were surveyed to determine toxicology-related Learning Objectives. From these, undergraduate educators can design courses tailored to their institutional needs by selecting a subset of Learning Objectives. Publication of a Learning Framework for toxicology will enable integration into other disciplines and facilitate the development and sharing of evidenced-based teaching materials for toxicology to educators in allied disciplines. Ultimately this will expand toxicology's impact to a broader audience.

Ahr and Cyp1a2 genotypes both affect susceptibility to motor deficits following gestational and lactational exposure to polychlorinated biphenyls.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants known to cause adverse health effects and linked to neurological deficits in both human and animal studies. Children born to exposed mothers are at highest risk of learning and memory and motor deficits. We developed a mouse model that mimics human variation in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) to determine if genetic variation increases susceptibility to developmental PCB exposure. In our previous studies, we found that high-affinity AhrbCyp1a2(-/-) and poor-affinity AhrdCyp1a2(-/-) knockout mice were most susceptible to learning and memory deficits following developmental PCB exposure compared with AhrbCyp1a2(+/+) wild type mice (C57BL/6J strain). Our follow-up studies focused on motor deficits, because human studies have identified PCBs as a potential risk factor for Parkinson's disease. Dams were treated with an environmentally relevant PCB mixture at gestational day 10 and postnatal day 5. We used a motor battery that included tests of nigrostriatal function as well as cerebellar function, because PCBs deplete thyroid hormone, which is essential to normal cerebellar development. There was a significant effect of PCB treatment in the rotarod test with impaired performance in all three genotypes, but decreased motor learning as well in the two Cyp1a2(-/-) knockout lines. Interestingly, we found a main effect of genotype with corn oil-treated control Cyp1a2(-/-) mice performing significantly worse than Cyp1a2(+/+) wild type mice. In contrast, we found that PCB-treated high-affinity Ahrb mice were most susceptible to disruption of nigrostriatal function with the greatest deficits in AhrbCyp1a2(-/-) mice. We conclude that differences in AHR affinity combined with the absence of CYP1A2 protein affect susceptibility to motor deficits following developmental PCB exposure.

Genetic differences in the aryl hydrocarbon receptor and CYP1A2 affect sensitivity to developmental polychlorinated biphenyl exposure in mice: relevance to studies of human neurological disorders.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants that remain a human health concern with newly discovered sources of contamination and ongoing bioaccumulation and biomagnification. Children exposed during early brain development are at highest risk of neurological deficits, but highly exposed adults reportedly have an increased risk of Parkinson's disease. Our previous studies found allelic differences in the aryl hydrocarbon receptor and cytochrome P450 1A2 (CYP1A2) affect sensitivity to developmental PCB exposure, resulting in cognitive deficits and motor dysfunction. High-affinity Ahr b Cyp1a2(-/-) mice were most sensitive compared with poor-affinity Ahr d Cyp1a2(-/-) and wild-type Ahr b Cyp1a2(+/+) mice. Our follow-up studies assessed biochemical, histological, and gene expression changes to identify the brain regions and pathways affected. We also measured PCB and metabolite levels in tissues to determine if genotype altered toxicokinetics. We found evidence of AHR-mediated toxicity with reduced thymus and spleen weights and significantly reduced thyroxine at P14 in PCB-exposed pups. In the brain, the greatest changes were seen in the cerebellum where a foliation defect was over-represented in Cyp1a2(-/-) mice. In contrast, we found no difference in tyrosine hydroxylase immunostaining in the striatum. Gene expression patterns varied across the three genotypes, but there was clear evidence of AHR activation. Distribution of parent PCB congeners also varied by genotype with strikingly high levels of PCB 77 in poor-affinity Ahr d Cyp1a2(-/-) while Ahr b Cyp1a2(+/+) mice effectively sequestered coplanar PCBs in the liver. Together, our data suggest that the AHR pathway plays a role in developmental PCB neurotoxicity, but we found little evidence that developmental exposure is a risk factor for Parkinson's disease.

Taurine, caffeine, and energy drinks: Reviewing the risks to the adolescent brain.

Energy drinks are emerging as a major component of the beverage market with sales projected to top $60 billion globally in the next five years. Energy drinks contain a variety of ingredients, but many of the top-selling brands include high doses of caffeine and the amino acid taurine. Energy drink consumption by children has raised concerns, due to potential caffeine toxicity. An additional risk has been noted among college-aged consumers of energy drinks who appear at higher risk of over-consumption of alcohol when the two drinks are consumed together. The differential and combinatorial effects of caffeine and taurine on the developing brain are reviewed here with an emphasis on the adolescent brain, which is still maturing. Key data from animal studies are summarized to highlight both reported benefits and adverse effects reported following acute and chronic exposures. The data suggest that age is an important factor in both caffeine and taurine toxicity. Although the aged or diseased brain might benefit from taurine or caffeine supplementation, it appears that adolescents are not likely to benefit from supplementation and may, in fact, suffer ill effects from chronic ingestion of high doses. Additional work is needed though to address gaps in our understanding of how taurine affects females, since the majority of animal studies focused exclusively on male subjects.

Patient Portals and Patient Engagement: A State of the Science Review.

BACKGROUND: Patient portals (ie, electronic personal health records tethered to institutional electronic health records) are recognized as a promising mechanism to support greater patient engagement, yet questions remain about how health care leaders, policy makers, and designers can encourage adoption of patient portals and what factors might contribute to sustained utilization. OBJECTIVE: The purposes of this state of the science review are to (1) present the definition, background, and how current literature addresses the encouragement and support of patient engagement through the patient portal, and (2) provide a summary of future directions for patient portal research and development to meaningfully impact patient engagement. METHODS: We reviewed literature from 2006 through 2014 in PubMed, Ovid Medline, and PsycInfo using the search terms "patient portal" OR "personal health record" OR "electronic personal health record". Final inclusion criterion dictated that studies report on the patient experience and/or ways that patients may be supported to make competent health care decisions and act on those decisions using patient portal functionality. RESULTS: We found 120 studies that met the inclusion criteria. Based on the research questions, explicit and implicit aims of the studies, and related measures addressed, the studies were grouped into five major topics (patient adoption, provider endorsement, health literacy, usability, and utility). We discuss the findings and conclusions of studies that address the five topical areas. CONCLUSIONS: Current research has demonstrated that patients' interest and ability to use patient portals is strongly influenced by personal factors such age, ethnicity, education level, health literacy, health status, and role as a caregiver. Health care delivery factors, mainly provider endorsement and patient portal usability also contribute to patient's ability to engage through and with the patient portal. Future directions of research should focus on identifying specific populations and contextual considerations that would benefit most from a greater degree of patient engagement through a patient portal. Ultimately, adoption by patients and endorsement by providers will come when existing patient portal features align with patients' and providers' information needs and functionality.

Comparison of Neurological Function in Males and Females from Two Substrains of C57BL/6 Mice.

The C57BL/6 (B6) mouse is the background strain most frequently used for genetically-modified mice. Previous studies have found significant behavioral and genetic differences between the B6J (The Jackson Laboratory) and B6N substrains (National Institutes of Health); however, most studies employed only male mice. We performed a comprehensive battery of motor function and learning and memory tests on male and female mice from both substrains. The B6N male mice had greater improvement in the rotarod test. In contrast, B6J female mice had longer latencies to falling from the rotarod. In the Morris water maze (MWM), B6J males had significantly shorter latencies to finding the hidden platform. However, B6N females had significantly shorter path lengths in the reversal and shifted-reduced phases. In open field locomotor activity, B6J males had higher activity levels, whereas B6N females took longer to habituate. In the fear conditioning test, B6N males had a significantly longer time freezing in the new context compared with B6J males, but no significant differences were found in contextual or cued tests. In summary, our findings demonstrate the importance of testing both males and females in neurobehavioral studies. Both factors (sex and substrain) must be taken into account when designing developmental neurotoxicology studies.

Functional outcomes of community-based brain injury rehabilitation clients.

BACKGROUND: Community-based rehabilitation can help to maximize function following acquired brain injury (ABI); however, data on treatment outcome is limited in quantity. OBJECTIVE: To describe and evaluate client outcomes of an outpatient programme for adults with moderate-to-severe traumatic and non-traumatic ABI. METHODS: Two phase design involving retrospective and longitudinal study of programme completers with ABI (n = 47). Changes in functioning were measured with the Mayo-Portland Inventory (MPAI-4), administered pre- and immediately post-rehabilitation and at 3 years follow-up. Self-ratings were supplemented with MPAI-4 data from significant others (n = 32) and staff (n = 32). RESULTS: Injured individuals and informants reported improved physical and psychosocial functioning immediately following the completion of community rehabilitation, with medium-to-large and significant treatment gains noted on the MPAI-4 ability, adjustment and participation sub-scales (Cohen's d range = 0.31-1.10). A deterioration in individuals' adjustment was further reported at follow-up, although this was based on limited data. Issues with longer-term rehabilitation service provision were additionally noted. CONCLUSIONS: The data support the need for continuity of care, including ongoing emotional support, to cater to the complex and dynamic needs of the ABI population. However, these results need to be considered in the context of a small sample size and quasi-experimental design.

The teratology society 2012-2017 strategic plan: pushing the boundaries.

The Teratology Society held its fourth strategic planning session in Albuquerque, NM, April 10-12, 2012, and launched the 2012-2017 Strategic Plan in conjunction with the 2012 annual meeting in Baltimore, MD. Building on the energy of the successful implementation of prior strategic plans (San Diego, 2007; Nashville,TN 2002; Cincinnati, OH 1998), session participants worked to identify barriers to success as a scientific society, as well as impending challenges and opportunities to which the Society needs to respond. The following report provides an overview of the Strategic Planning process, objectives, activities, and conclusions. A total of 23 members were present at the session, and the group included representation from Council, various committees, and different member constituencies. This plan, Pushing the Boundaries, and its three strategic intents: Broaden Our Identity, Expand Our Membership, and Increase Our Influence, will drive the direction of the Teratology Society for the next five years.

Ahrd Cyp1a2(-/-) mice show increased susceptibility to PCB-induced developmental neurotoxicity.

Polychlorinated biphenyls (PCBs) are developmental neurotoxicants that produce cognitive and behavioral changes in children exposed during gestation and lactation. Coplanar PCBs bind the aryl hydrocarbon receptor (AHR) and can be sequestered in liver by cytochrome P450 1A2 (CYP1A2). The AHR is a ligand-activated transcription factor which increases expression of the CYP1 family, including CYP1A2. Our previous work examining genetic susceptibility to developmental PCB neurotoxicity showed that Ahr(b)Cyp1a2(-/-) mice with the high-affinity Ahr(b) allele and lacking CYP1A2 were most susceptible while Ahr(b)Cyp1a2(+/+) and poor-affinity Ahr(d)Cyp1a2(+/+) mice were resistant. To follow up, a fourth line of mice was generated with the Ahr(d)Cyp1a2(-/-) genotype and compared with the background strain Ahr(b)Cyp1a2(+/+). Dams received a PCB mixture or the corn oil vehicle at gestational Day 10 (GD10) and postnatal Day 5 (PND5). Offspring were tested at PND60 in open field locomotor, acoustic startle with pre-pulse inhibition (PPI), novel object recognition and Morris water maze. Locomotor activity was increased in PCB-treated Ahr(b)Cyp1a2(+/+) mice, but no differences were seen in control vs. PCB-treated Ahr(d)Cyp1a2(-/-) mice. PCB-treated Ahr(d)Cyp1a2(-/-) mice had a higher baseline startle response and significantly reduced pre-pulse inhibition at the 74dB level compared with corn oil-treated controls (P<0.05). PCB-treated Ahr(d)Cyp1a2(-/-) mice had impairments in novel objective recognition (P<0.05) and during all three hidden platform phases of Morris water maze (P<0.01). Combined with our previous findings, these results indicate Cyp1a2 genotype is more important in susceptibility to PCB-induced deficits in learning and memory, but Ahr genotype appears more important when assessing acoustic startle-PPI and locomotor activity.

Effect of chronic glutathione deficiency on the behavioral phenotype of Gclm-/- knockout mice.

Enhanced oxidative stress or deficient oxidative stress response in the brain is associated with neurodegenerative disorders and behavioral abnormalities. Previously we generated a knockout mouse line lacking the gene encoding glutamate-cysteine ligase modifier subunit (GCLM). Gclm(-/-) knockout (KO) mice are viable and fertile, yet exhibit only 9-35% of wild-type levels of reduced glutathione (GSH) in tissues, making them a useful model for chronic GSH depletion. Having the global absence of this gene, KO mice--from the time of conception and throughout postnatal life--experience chronic oxidative stress in all tissues, including brain. Between postnatal day (P) 60 and P100, we carried out behavioral phenotyping tests in adults, comparing male and female Gclm(-/-) with Gclm(-/-) wild-type (WT) littermates. Compared with WT, KO mice exhibited: subnormal anxiety in the elevated zero maze; normal overall exploratory open-field activity, but slightly more activity in the peripheral zones; normal acoustic startle and prepulse inhibition reactions; normal novel object recognition with increased time attending to the stimulus objects; slightly reduced latencies to reach a random marked platform in the Morris water maze; normal spatial learning and memory in multiple phases of the Morris water maze; and significantly greater hyperactivity in response to methamphetamine in the open field. These findings are generally in agreement with two prior studies on these mice and suggest that the brain is remarkably resilient to lowered GSH levels, implying significant reserve capacity to regulate reactive oxygen species-but with regional differences such that anxiety and stimulated locomotor control brain regions might be more vulnerable.

Facial attractiveness ratings from video-clips and static images tell the same story.

Most of what we know about what makes a face attractive and why we have the preferences we do is based on attractiveness ratings of static images of faces, usually photographs. However, several reports that such ratings fail to correlate significantly with ratings made to dynamic video clips, which provide richer samples of appearance, challenge the validity of this literature. Here, we tested the validity of attractiveness ratings made to static images, using a substantial sample of male faces. We found that these ratings agreed very strongly with ratings made to videos of these men, despite the presence of much more information in the videos (multiple views, neutral and smiling expressions and speech-related movements). Not surprisingly, given this high agreement, the components of video-attractiveness were also very similar to those reported previously for static-attractiveness. Specifically, averageness, symmetry and masculinity were all significant components of attractiveness rated from videos. Finally, regression analyses yielded very similar effects of attractiveness on success in obtaining sexual partners, whether attractiveness was rated from videos or static images. These results validate the widespread use of attractiveness ratings made to static images in evolutionary and social psychological research. We speculate that this validity may stem from our tendency to make rapid and robust judgements of attractiveness.

In utero and lactational exposure to PCBs in mice: adult offspring show altered learning and memory depending on Cyp1a2 and Ahr genotypes.

BACKGROUND: Both coplanar and noncoplanar polychlorinated biphenyls (PCBs) exhibit neurotoxic effects in animal studies, but individual congeners do not always produce the same effects as PCB mixtures. Humans genetically have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2)-uninduced basal levels and > 12-fold variability in aryl hydrocarbon receptor (AHR)affinity; because CYP1A2 is known to sequester coplanar PCBs and because AHR ligands include coplanar PCBs, both genotypes can affect PCB response. OBJECTIVES: We aimed to develop a mouse paradigm with extremes in Cyp1a2 and Ahr genotypes to explore genetic susceptibility to PCB-induced developmental neurotoxicity using an environmentally relevant mixture of PCBs. METHODS: We developed a mixture of eight PCBs to simulate human exposures based on their reported concentrations in human tissue, breast milk, and food supply. We previously characterized specific differences in PCB congener pharmacokinetics and toxicity, comparing high-affinity-AHR Cyp1a2 wild-type [Ahrb1_Cyp1a2(+/+)], poor-affinity-AHR Cyp1a2 wild-type [Ahrd_Cyp1a2(+/+)], and high-affinity-AHR Cyp1a2 knockout [Ahrb1_Cyp1a2(-/-)] mouse lines [Curran CP, Vorhees CV, Williams MT, Genter MB, Miller ML, Nebert DW. 2011. In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes. Toxicol Sci 119:189-208]. Dams received a mixture of three coplanar and five noncoplanar PCBs on gestational day 10.5 and postnatal day (PND) 5. In the present study we conducted behavioral phenotyping of exposed offspring at PND60, examining multiple measures of learning, memory, and other behaviors. RESULTS: We observed the most significant deficits in response to PCB treatment in Ahrb1_Cyp1a2(-/-) mice, including impaired novel object recognition and increased failure rate in the Morris water maze. However, all PCB-treated genotypes showed significant differences on at least one measure of learning or behavior. CONCLUSIONS: High levels of maternal hepatic CYP1A2 offer the most important protection against deficits in learning and memory in offspring exposed to a mixture of coplanar and noncoplanar PCBs. High-affinity AHR is the next most important factor in protection of offspring.

In utero and lactational exposure to a complex mixture of polychlorinated biphenyls: toxicity in pups dependent on the Cyp1a2 and Ahr genotypes.

Polychlorinated biphenyls (PCBs) are persistent toxic pollutants occurring as complex mixtures in the environment. Humans are known genetically to have > 60-fold differences in hepatic cytochrome P450 1A2 (CYP1A2) levels and > 12-fold differences in aryl hydrocarbon receptor (AHR) affinity, both of which could affect PCB pharmacokinetics. Thus, we compared Ahr(b1)_Cyp1a2(+/+) high-affinity AHR wild-type, Ahr(d)_Cyp1a2(+/+) poor affinity AHR wild-type, Ahr(b1)_Cyp1a2(-/-) knockout, and Ahr(d)_Cyp1a2(-/-) knockout mouse lines. We chose a mixture of three coplanar and five noncoplanar PCBs to reproduce that seen in human tissues, breast milk, and the food supply. The mixture was given by gavage to the mother on gestational day 10.5 (GD10.5) and postnatal day 5 (PND5); tissues were collected from pups and mothers at GD11.5, GD18.5, PND6, PND13, and PND28. Ahr(b1)_Cyp1a2(-/-) pups showed lower weight at birth and slower rate of growth postnatally. Absence of CYP1A2 resulted in significant splenic atrophy at PND13 and PND28. Presence of high-affinity AHR enhanced thymic atrophy and liver hypertrophy in the pups. Concentrations of each congener were analyzed at all time points: maximal noncoplanar congener levels in maternal tissues were observed from GD18 until PND6, whereas the highest levels in pups were found between PND6 and PND28. Coplanar PCB concentrations were generally higher in Ahr(d)-containing pup tissues; these findings are consistent with earlier studies demonstrating the crucial importance of AHR-mediated inducible CYP1 in the gastrointestinal tract as a means of detoxication of oral planar polycyclic aromatic hydrocarbons.

Incorporating genetics and genomics in risk assessment for inhaled manganese: from data to policy.

Manganese is an essential nutrient, and a healthy human with good liver and kidney function can easily excrete excess dietary manganese. Inhaled manganese is a greater concern, because it bypasses the body's normal homeostatic mechanisms and can accumulate in the brain. Prolonged exposure to high manganese concentrations (>1mg/m(3)) in air leads to a Parkinsonian syndrome known as "manganism." Of greatest concern are recent studies which indicate that neurological and neurobehavioral deficits can occur when workers are exposed to much lower levels (<0.2mg/m(3)) of inhaled manganese in welding fumes. Consequently, researchers at NIOSH are conducting a risk assessment for inhaled manganese. Novel components of this risk assessment include an attempt to quantify the range of inter-individual differences using data generated by the Human Genome Project and experimental work to identify genetically based biomarkers of exposure, disease and susceptibility. The difficulties involved in moving from epidemiological and in vivo data to health-based quantitative risk assessment and ultimately enforceable government standards are discussed.

Building a virtual community for nursing education: the town of Mirror Lake.

RNs take pride in delivering high-quality individualized care to their patients. However, how do nursing students learn the principles of professional nursing or develop the competencies necessary to individualize patient care? At the Ohio State University College of Nursing, we embarked on deploying a virtual community of patients to enhance our students' learning experience. Our community, the town of Mirror Lake, contains 165 people and 62 households, with an apartment complex, a medical center, and a retirement center with assisted and skilled nursing care. This community serves as the main source of patients for Mirror Lake Medical Center, our virtual hospital. We think we can teach many key principles of sound nursing care using this virtual community of patients. This article presents the rationale behind the decision to take on this endeavor, as well as the processes used for development of our community.

Use of buffered lidocaine in bone marrow biopsies: a randomized, controlled trial.

PURPOSE/OBJECTIVES: To determine whether a difference exists in perceived pain during preprocedure anesthetic injection for bone marrow biopsy between buffered and unbuffered lidocaine, to determine whether pain levels change over time, and to investigate relationships between perceived pain scores and other variables. DESIGN: A double-blind, randomized, experimental, crossover design. SETTING: A large hospital in the midwestern region of the United States. SAMPLE: 48 patients undergoing bone marrow biopsy. METHODS: The patients served as their own controls for the bilateral procedure. A 100 mm visual analog scale measured pain. A demographic questionnaire gathered the between-subjects exploratory variables. MAIN RESEARCH VARIABLES: Perceived pain scores and type of lidocaine anesthetic solution (buffered versus unbuffered). FINDINGS: Participants reported significantly lower pain scores on the side anesthetized with buffered lidocaine compared with the side anesthetized with unbuffered lidocaine. Higher pain scores were reported on the treatment side for participants who had received more than two surgical procedures. Patients who were members of a minority group had higher mean pain scores than Caucasians on the control side. CONCLUSIONS: Buffered lidocaine is superior to unbuffered lidocaine as an anesthetic for bone marrow biopsy procedures. IMPLICATIONS FOR NURSING: Advanced practice nurses perform a significant number of bone marrow biopsies and aim to improve patient comfort during invasive procedures. Use of unbuffered lidocaine should be questioned.