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Background: Research indicates that informal caregiving can have intense physical and mental impact on the individual. Relative to caregivers of adults, pediatric palliative caregivers appear less in literature despite experiencing greater mental, physical, financial, and social strain. There is limited research on the creation and evaluation of interventions specifically for this population despite clear need., Objective: This study aims to evaluate the feasibility and engagement of the Photographs of Meaning Program, a modified meaning-making intervention for pediatric palliative caregivers., Design: Participants completed a pre-post intervention meaning-in-life measure. Over a 9-week period, participants followed a meaning-making curriculum whereby they created and shared photo narratives via social media. As part of the intervention, a community photo exhibition was held featuring these photo narratives. Exit interviews were also conducted at study close., Setting/participants: Nine individuals providing informal care to children in a pediatric palliative care program participated in the intervention. All participants were female and are older than 18 years. Settings for research include participant homes and at The Center for Hospice and Palliative Care in Cheektowaga, New York., Results: Participants posted 95 photographs and 96 narratives during the intervention, posting on average once each week. Statistical analysis within the small sample indicated an increased presence of meaning in the lives of participants ( P = .022). Exit interviews conveyed satisfaction with the intervention., Conclusions: Findings suggest that the Photographs of Meaning Program is a practical intervention with life-enhancing potential for pediatric palliative. Future research should aim to collect additional evidence of the intervention's effectiveness.

Background: Delirium is a challenging occurrence among people at end of life. It can be difficult to detect and treat because of its episodic nature. The Buffalo Delirium Scale (BDS) was designed to identify risk factors for hospice patients in the prodromal stage of delirium., Objective: This study evaluated the psychometric properties of items assessing delirium risk factors related to cognitive problems, psychological distress, and sleep problems., Methods: Hospice nursing staff assessed patients with the 11-item BDS over a 6-month period as part of standard weekly visits to monitor for emerging signs of delirium, for example, sleep patterns, cognition, and behavior., Setting/participants: The rating period produced 4992 assessments from 817 hospice home care patients., Results: Factor analysis of nurses' ratings identified 3 factors: (1) cognitive problems, (2) distress, and (3) sleep problems. Coefficient αs for these factors and total score were moderate to high (range = .66-.82). Nurses' ratings of presence of delirium highly correlated with scores on distress ( r = .40, P < .01), while dementia highly correlated with cognitive problems ( r = .50, P < .01). Analysis of at-risk cases with high BDS total scores where no delirium was assessed indicated that quality sleep may mitigate delirium onset., Conclusion: Preliminary psychometric testing suggests BDS to be a valid and appropriate measure for hospice patients. Use of BDS may help differentiate individuals in prodromal stage of delirium versus dementia. Examination of BDS scores may help identify patients for whom sleep interventions may delay onset of or reduce the frequency of delirium.

Background: The age demographic of the incarcerated is quickly shifting from young to old. Correctional facilities are responsible for navigating inmate access to healthcare; currently, there is no standardization for access to end-of-life care. There is growing research support for prison-based end-of-life care programs that incorporate inmate peer caregivers as a way to meet the needs of the elderly and dying who are incarcerated., Aim: This project aims to (a) describe a prison-based end-of-life program utilizing inmate peer caregivers, (b) identify inmate-caregiver motivations for participation, and (c) analyze the role of building trust and meaningful relationships within the correctional end-of-life care setting., Design: A total of 22 semi-structured interviews were conducted with inmate-caregivers. Data were analyzed using Consensual Qualitative Research methodology., Setting/participants: All inmate-caregivers currently participating in the end-of-life peer care program at Briarcliff Correctional Facility were given the opportunity to participate. All participants were male, over the age of 18, and also incarcerated at Briarcliff Correctional Facility, a maximum security, state-level correctional facility., Results: In total, five over-arching and distinct domains emerged; this manuscript focuses on the following three: (a) program description, (b) motivation, and (c) connections with others., Conclusion: Findings suggest that inmate-caregivers believe they provide a unique and necessary adaptation to prison-based end-of-life care resulting in multilevel benefits. These additional perceived benefits go beyond a marginalized group gaining access to patient-centered end-of-life care and include potential inmate-caregiver rehabilitation, correctional medical staff feeling supported, and correctional facilities meeting end-of-life care mandates. Additional research is imperative to work toward greater standardization of and access to end-of-life care for the incarcerated.

A growing number of correctional facilities train inmates to provide end-of-life care for dying inmates. This study explores the phenomenological perspective of inmate-caregivers participating in an inmate-facilitated hospice program (IFHP) with regard to meaning and purpose in life, attitudes on death and dying, and perceived personal impact of participation. Twenty-two inmate-caregivers were interviewed at a maximum-security state correctional facility in the United States. The interviews were transcribed verbatim and analyzed using the Consensual Qualitative Research Methodology. Results suggest that participating in an IFHP may facilitate personal growth and transformation that mirrors the tenets of posttraumatic growth.

High-throughput test methods including molecular, cellular, and alternative species-based assays that examine critical events of normal brain development are being developed for detection of developmental neurotoxicants. As new assays are developed, a "training set" of chemicals is used to evaluate the relevance of individual assays for specific endpoints. Different training sets are necessary for each assay that would comprise a developmental neurotoxicity test battery. In contrast, evaluation of the predictive ability of a comprehensive test battery requires a set of chemicals that have been shown to alter brain development after in vivo exposure ("test set"). Because only a small number of substances have been well documented to alter human neurodevelopment, we have proposed an expanded test set that includes chemicals demonstrated to adversely affect neurodevelopment in animals. To compile a list of potential developmental neurotoxicants, a literature review of compounds that have been examined for effects on the developing nervous system was conducted. The search was limited to mammalian studies published in the peer-reviewed literature and regulatory studies submitted to the U.S. EPA. The definition of developmental neurotoxicity encompassed changes in behavior, brain morphology, and neurochemistry after gestational or lactational exposure. Reports that indicated developmental neurotoxicity was observed only at doses that resulted in significant maternal toxicity or were lethal to the fetus or offspring were not considered. As a basic indication of reproducibility, we only included a chemical if data on its developmental neurotoxicity were available from more than one laboratory (defined as studies originating from laboratories with a different senior investigator). Evidence from human studies was included when available. Approximately 100 developmental neurotoxicity test set chemicals were identified, with 22% having evidence in humans., (Published by Elsevier Inc.)

Toxicogenomics is the application of toxicology, genetics, molecular biology and environmental health to describe the response of organisms to environmental stimuli. The field of toxicogenomics has developed over the past 15 years mainly due to advances in toxicology, molecular genetics and cell biology. Its prospective use to resolve crucial data gaps and data inconsistencies could improve risk assessment by providing additional data to increase the understanding of mechanisms and modes of action (MOA) and enhance the reliability of dose-response extrapolation. Thus, toxicogenomics holds promise for advancing the scientific basis of risk assessments. However, one of the current issues is how genomic/transcriptional data is being used to further describe a MOA for oncogenicity and, in turn, its potential uses in cancer risk assessment. This commentary identifies how toxicogenomics could be used on a case by case basis to add information to a MOA addressing both the opportunities and challenges this technology holds. In addition, some pitfalls to avoid in the generation and interpretation of toxicogenomic data and validation issues that need to be addressed before toxicogenomics can be used in the risk assessment process and regulatory decisions are discussed., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In vitro, high-throughput methods have been widely recommended as an approach to screen chemicals for the potential to cause developmental neurotoxicity and prioritize them for additional testing. The choice of cellular models for such an approach will have important ramifications for the accuracy, predictivity and sensitivity of the screening assays. In recent years neuroprogenitor cells from rodents and humans have become more widely available and may offer useful models having advantages over primary neuronal cultures and/or transformed cell lines. To date, these models have been utilized in only a limited number of toxicity studies. This review summarizes the state of the science regarding stem and neuroprogenitor models that could be used for screening assays, provides researchers in this field with examples of how these cells have been utilized to date, and discusses the advantages, limitations and knowledge gaps regarding these models. Data are available from both rodent and human stem and neuroprogenitor cell models that indicate that these models will be a valid and useful tool for developmental neurotoxicity testing. Full potential of these models will only be achieved following advances in neurobiology that elucidate differentiation pathways more clearly, and following further evaluation of larger sets of developmentally neurotoxic and non-toxic chemicals to define the sensitivity and predictivity of assays based on stem or progenitor cell models., (Published by Elsevier Inc.)

There is considerable public concern that the majority of commercial chemicals have not been evaluated for their potential to cause developmental neurotoxicity. Although several chemicals are assessed annually under the current developmental neurotoxicity guidelines, time, resource, and animal constraints prevent testing of large numbers of chemicals using this approach. Thus, incentive is mounting to develop in vitro methods to screen chemicals for their potential to harm the developing human nervous system. As an initial step toward this end, the present studies evaluated an automated, high-throughput method for screening chemical effects on proliferation and viability using ReNcell CX cells, a human neural progenitor cell (hNPC) line. ReNcell CX cells doubled in approximately 36 h and expressed the neural progenitor markers nestin and SOX2. High-throughput assays for cell proliferation (5-bromo-2'-deoxyuridine incorporation) and viability (propidium iodide exclusion) were optimized and tested using known antiproliferative compounds. The utility of this in vitro screen was evaluated further using a set of compounds containing eight known to cause developmental neurotoxicity and eight presumably nontoxic compounds. Six out of eight developmental neurotoxicants significantly inhibited ReNcell CX cell proliferation and/or viability, whereas two out of eight nontoxic chemicals caused only minimal effects. These results demonstrate that chemical effects on cell proliferation and viability can be assessed via high-throughput methods using hNPCs. Further development of this approach as part of a strategy to screen compounds for potential effects on nervous system development is warranted.

Identification of chemicals that pose a hazard to the developing nervous system is the first step in reducing human exposure and preventing health risks to infants and children. In response to the need for more efficient methods to identify potential developmental neurotoxicants, the present study evaluated the utility of an automated high content screening system to detect chemical effects on neurite outgrowth in Neuroscreen-1 cells (NS-1), a subclone of PC12 cells. Plating 2000 NS-1 cells per well with 100 ng/ml nerve growth factor for 96 h produced optimal neurite growth in a 96-well format. Using this protocol, five chemicals that had been previously shown to inhibit neurite outgrowth in PC12 cells were examined. Inhibition of neurite outgrowth (assessed as total neurite length per cell) was observed for all five chemicals. For three of the chemicals, inhibition was associated with decreased cell viability. To demonstrate the utility of this approach for screening, a further set of chemicals (eight known in vivo developmental neurotoxicants and eight chemicals with little evidence of in vivo neurotoxicity) were tested over a wide concentration range (1 nM-100 microM). Trans-retinoic acid, dexamethasone, cadmium, and methylmercury inhibited neurite outgrowth, although dexamethasone and cadmium only affected neurite outgrowth at concentrations that decreased viability. Amphetamine facilitated neurite outgrowth, whereas valproic acid, diphenylhydantoin, and lead had no effect. Of the chemicals that were not neurotoxic, there were no effects on cell viability, but two (dimethyl phthalate and omeprazole) increased neurite outgrowth at the highest concentration tested. These results demonstrate that a high content screening system can rapidly quantify chemical effects on neurite outgrowth in vitro. Concentration-response data for both neurite outgrowth and cell viability allowed for the determination of the specificity of chemical effects on a neurodevelopmental endpoint. Further studies will examine the utility of other in vitro preparations for cell-based assays of neurite outgrowth.

The specific mechanisms underlying (+)-3,4-methylenedioxymethamphetamine (MDMA)-induced damage to 5-HT terminals are unknown. Despite the hypothesized role for dopamine (DA) and DA-derived free radicals in mediating this damage, it remains unclear why MDMA produces long-term depletions of 5-HT in brain regions that are sparsely innervated by DA neurons. We hypothesized that the precursor to DA biosynthesis, tyrosine, mediates MDMA-induced 5-HT depletions. Extracellular tyrosine concentrations increased fivefold in striatum and 2.5-fold in hippocampus during the administration of neurotoxic doses of MDMA. In vitro results show that L-tyrosine can be hydroxylated nonenzymatically to the DA precursor l-3,4-dihydroxyphenylalanine (DOPA) under pro-oxidant conditions. The local infusion of L-tyrosine into the striatum or hippocampus during MDMA administration potentiated the acute increase in extracellular DA and the long-term depletion of 5-HT after MDMA. Coinfusion of the aromatic amino acid decarboxylase (AADC) inhibitor m-hydroxybenzylhydrazine attenuated these effects in hippocampus and decreased basal extracellular DA in the striatum. In contrast, the reverse dialysis of the tyrosine hydroxylase inhibitor alpha-methyl-p-tyrosine into the hippocampus did not affect MDMA-induced increases in extracellular DA or the long-term depletion in 5-HT. These results show that MDMA increases the concentration of tyrosine in the brain to cause a long-term depletion of 5-HT via the nonenzymatic, tyrosine hydroxylase-independent, hydroxylation of tyrosine to DOPA and subsequently to DA via AADC. Overall, the findings suggest that MDMA depletes 5-HT by increasing tyrosine and its eventual conversion to DA within 5-HT terminals.