Impact of Dance Movement Psychotherapy on the wellbeing of caregivers of children with Autism Spectrum Disorder.

OBJECTIVES: Sustaining the wellbeing of caregivers of children with Autism Spectrum Disorder (ASD) can be highly demanding. This study explored the impact of Dance Movement Psychotherapy (DMP) intervention on the wellbeing of caregivers in comparison with their standard care routine. STUDY DESIGN: This pilot evaluation study used a quasi-experimental design. METHODS: Thirty-seven caregivers of children with ASD were recruited from two special educational needs settings and were allocated to the DMP intervention or the control group depending on their availability to attend the sessions. The participants in the intervention group received five DMP sessions lasting 90 min each. Adult Wellbeing Scale (AWS) and Parenting Stress Index-Short Form (PSI-SF) were the two outcome measures administered before and after DMP to measure the impact of DMP intervention on caregivers' wellbeing and parental stress. RESULTS: The retention rates were poor, with only 50% of participants in the DMP intervention arm attending at least 70% of the sessions until its end. The Minimal Clinically Important Difference (MCID) was achieved for a small effect size in both outcome measures in the DMP intervention group but not in the control group. Results from the Analyses of Covariance (ANCOVAs) showed a significant difference in post-intervention scores between the DMP intervention and the control group for AWS (F1,33 = 106.474, P < 0.001) but not for PSI-SF. In addition, a significant association was found between pre-intervention scores and the number of sessions attended with the postintervention scores of both AWS and PSI-SF. CONCLUSIONS: The results of this pilot DMP study are promising. However, before running a larger randomised controlled trial, strategies to support caregivers to attend the intervention need to be considered carefully.

Changes in serum leptin levels as well as sICAM-1 and sVCAM-1 soluble adhesion molecules during carotid endarterectomy.

OBJECTIVE: Leptin is an adipokine, known to be associated with oxidative stress, inflammation, and atherogenesis. Leptin plays an essential role in atheromatosis-associated inflammatory cascade through stimulation of inflammatory mediators such as soluble intracellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). However, little is known about this association in patients with atherosclerosis and severe internal carotid artery (ICA) stenosis undergoing carotid endarterectomy (CEA). Our objective was to evaluate the variations of serum leptin levels, as well as sICAM-1 and sVCAM-1 levels in these patients during the process of CEA and 24 hours postoperatively. PATIENTS AND METHODS: The study group enrolled 50 patients undergoing CEA for ICA stenosis (> 70%). Serum leptin, sICAM-1 and sVCAM-1 plasma concentration measurements were performed at 4 distinct time points: before clamping of the ICA, 30 minutes after clamping of the ICA, 60 minutes after declamping of ICA and 24 hours postoperatively. RESULTS: Leptin was significantly decreased during CEA, but an overshooting in its levels was observed at 24 hours after the operation. Both sICAM-1 and sVCAM-1 initially followed the pattern of leptin changes but after completing CEA and up to 24 hours postoperatively a steep increase in their levels was not established. sVCAM-1 and sICAM-1 correlated with indices of oxidative stress at peak inflammatory burden. CONCLUSIONS: Leptin is a circulating marker of carotid atherosclerosis. Oxidative stress and expression of sVCAM-1 and sICAM-1 on vascular endothelial cells are key features in the pathophysiological process of atherosclerosis.

Group membership and racial bias modulate the temporal estimation of in-group/out-group body movements.

Social group categorization has been mainly studied in relation to ownership manipulations involving highly-salient multisensory cues. Here, we propose a novel paradigm that can implicitly activate the embodiment process in the presence of group affiliation information, whilst participants complete a task irrelevant to social categorization. Ethnically White participants watched videos of White- and Black-skinned models writing a proverb. The writing was interrupted 7, 4 or 1 s before completion. Participants were tasked with estimating the residual duration following interruption. A video showing only hand kinematic traces acted as a control condition. Residual duration estimates for out-group and control videos were significantly lower than those for in-group videos only for the longest duration. Moreover, stronger implicit racial bias was negatively correlated to estimates of residual duration for out-group videos. The underestimation bias for the out-group condition might be mediated by implicit embodiment, affective and attentional processes, and finalized to a rapid out-group categorization.

Evaluation of the ToxRTool's ability to rate the reliability of toxicological data for human health hazard assessments.

Regulatory agencies often utilize results from peer reviewed publications for hazard assessments. A problem in doing so is the lack of well-accepted tools to objectively, efficiently and systematically assess the quality of published toxicological studies. Herein, we evaluated the publicly available software-based ToxRTool (Toxicological data Reliability assessment Tool) for use in human health hazard assessments. The ToxRTool was developed by the European Commission's Joint Research Center in 2009. It builds on Klimisch categories, a rating system established in 1997, by providing additional criteria and guidance for assessing the reliability of toxicological studies. It also transparently documents the study-selection process. Eight scientists used the ToxRTool to rate the same 20 journal articles on thyroid toxicants. Results were then compared using the Finn coefficient and "AC1" to determine inter-rater consistency. Ratings were most consistent for high-quality journal articles, but less consistent as study quality decreased. Primary reasons for inconsistencies were that some criteria were subjective and some were not clearly described. It was concluded, however, that the ToxRTool has potential and, with refinement, could provide a more objective approach for screening published toxicology studies for use in health risk evaluations, although the ToxRTool ratings are primarily based on study reporting quality.

Inter-laboratory control data for reproductive endpoints required in the OPPTS 870.3800/OECD 416 reproduction and fertility test.

BACKGROUND: The U.S. EPA revised the Reproduction and Fertility Effects Test Guideline (OPPTS 870.3800/OECD 416) in 1998, adding numerous endpoints in an effort to incorporate new methodologies, improve the sensitivity for detecting reproductive toxicants, and more efficiently utilize study animals. Many of these new endpoints have not been used in regulatory reproductive toxicology studies prior to their inclusion in the test guidelines; thus, the Health and Environmental Sciences Institute (HESI) of the International Life Sciences Institute (ILSI) initiated the Reproductive Endpoints Project to examine the utility of these new endpoints. METHODS: This report provides a retrospective analysis of 43 multi-generation studies (16 in Wistar rats, 27 in Sprague-Dawley rats) conducted according to the latest version of the test guidelines. It focuses on vehicle (negative) control values (means and ranges) for the various endpoints to examine inter-laboratory variability. RESULTS: Based on the compiled data, the most variable endpoints across laboratories and their associated coefficients of variation (CV) for each generation were: percent abnormal sperm (166-205%), testicular spermatid concentration (126-147%), postimplantation loss (97-104%), primordial follicle counts (69%, only measured in P2 females), and epididymal sperm concentration (52-57%). Absolute and relative prostate and thymus weights, weanling uterine weights, and anogenital distance had CVs of 25-50%. Sources of variability included procedural differences between laboratories, inherent biological variability, and/or small sample sizes for some endpoints. CONCLUSIONS: These inter-laboratory control data provide a means for laboratories to review their performance on reproductive toxicity measures, and provide perspective for interpreting their own control data and data from treated animals.

An "all-comers" venous duplex scan policy for patients with lower limb varicose veins attending a one-stop vascular clinic: is it justified?

OBJECTIVE: To determine whether clinical assessment could predict the correct management of patients with varicose veins (VVs), select those who would need duplex scanning, and identify deep venous reflux (DVR). METHODS: Prospective study of 342 consecutive limbs with VVs. These were divided into 3 groups: 170 (50%) limbs with primary VVs without skin changes (group I), 37 (11%) with recurrent VVs without skin changes (group II), and 135 (39%) with primary or recurrent VVs with skin changes (group III). Clinicians were asked to document whether they would normally request a duplex scan because of clinical uncertainty. Agreement between decision-making based on clinical and on duplex findings was documented. RESULTS: Agreement between clinical and duplex findings for groups I, II, and III was 82%, 59%, and 67%, respectively. In 112 cases (66%) in group I, clinicians felt certain about the diagnosis and yet duplex scanning revealed they were wrong in 12% of cases. In group II, clinicians would request a duplex scan because of clinical uncertainty in 30 (81%) cases. In group III, the sensitivity, specificity, positive and negative predictive value of clinical assessment in detecting DVR was 32%, 77%, 24%, and 83%, respectively. CONCLUSIONS: Clinical evaluation of patients with VVs is unreliable in planning their management. Clinicians can neither predict those who will require duplex scanning nor correctly identify DVR. Even experienced surgeons often "get it wrong" when assessing primary uncomplicated veins despite being certain about the diagnosis. Therefore, an "all-comers" duplex imaging policy should be implemented if optimal management is to be achieved.

A qualitative retrospective analysis of positive control data in developmental neurotoxicity studies.

Testing for neurodevelopmental effects commonly involves both functional and neuropathological assessments in offspring during and following maternal exposure. The use of positive controls in neurotoxicity screening has been advocated by numerous expert groups. Evaluation of positive control data allows evaluation of laboratory proficiency in detecting changes in the structure and function of the developing nervous system and comparison of the sensitivity of assessments in different studies and laboratories. This project surveyed approaches taken in contract and industrial laboratories in generating and providing these data. Positive control data submitted in support of 34 developmental neurotoxicity (DNT) studies from 16 different laboratories were summarized by test method for information on the following: age relevance of test subjects, the presence of a dose-response relationship, gender, group size, statistics, report quality, quality assurance, and the year the study was conducted. Endpoints included the following: developmental landmarks, clinical observations (CO), motor activity, startle response, learning and memory, qualitative neuropathology, and quantitative brain morphometry (linear measurements of selected brain regions). Results ranged from no positive control data for three laboratories, to one laboratory that submitted 17 separate positive control reports. The qualitative range was similarly broad, from excellent to poor. Various problems were identified, including the following: inappropriate report structure (e.g., copies of poster presentations), lack of individual data, inadequate methodological details, submission of very old data (>10 years) or data from completely different laboratories, use of inappropriate positive control chemicals or doses that were without effect, lack of statistical analysis, use of only one sex, and use of incompatibly aged animals. Analyses revealed that there were only 3 out of 16 laboratories that had submitted positive control data adequate for proficiency purposes for all of the major endpoints in the DNT study. Adequate positive control data are very useful in a weight-of-evidence approach to help determine the biological significance of results, and also to increase the confidence in negative results from DNT studies.

Recent developments in regulatory requirements for developmental toxicology.

A number of legislative and regulatory changes have occurred over the past 5 years to prompt the re-evaluation of the regulatory requirements for developmental toxicity testing and use of the data for risk assessment. In particular, passage of the 1996 Food Quality Protection Act (FQPA) in the United States required the USEPA to evaluate children's health risks in a more rigorous fashion, and to apply an additional 10-fold safety factor if data were inadequate or children appeared to be more sensitive than adults. A review of the testing protocols required by USEPA led to extension of the dosing period to term in the prenatal developmental toxicity study and the addition of endpoints to the 2-generation reproduction study protocol as indicators of possible neurologic, reproductive, or immune alterations. Revised testing guidelines for pesticides and toxic substances were published by USEPA in 1998, including a developmental neurotoxicity testing protocol. Further review for FQPA implementation resulted in the proposal for a core set of required toxicology studies, including routine developmental neurotoxicity, adult neurotoxicity, and adult immunotoxicity studies. In addition, development of new testing guidelines in several areas was recommended, these guidelines to be used in conjunction with or as follow-up when indicated from standard testing: developmental immunotoxicity, carcinogenesis, specialized neurotoxicity studies, endocrine disruptor studies, pharmacokinetics, and direct dosing of neonates. The impact of these efforts on the policies for toxicity testing of pesticides are discussed, and these issues are currently being reviewed on a broader scale, in particular, by evaluating the adequacy of the methods used for reference values (e.g. chronic RfD, RfC). Three major areas of focus for this review include life stages evaluated, endpoints assessed, and the duration of exposure used in various studies. A major focus of these efforts is to ensure that children's health risks are being adequately addressed in the risk assessment process.

Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: pharmacokinetic and pharmacodynamic considerations.

We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. In addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood--brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose--response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the test chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic.

Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. ILSI Risk Science Institute Expert Working Group on Sperm Evaluation.

Reproductive toxicity studies are increasingly including assessments of sperm parameters including motility, morphology, and counts. While these assessments can provide valuable information for the determination of potential reproductive toxicity, the methods for conducting the assessments have not been well developed in all laboratories and are continually evolving. The use of different methods in different laboratories makes comparison of data among laboratories difficult. To address the differences in methods, a working group was convened to discuss methods currently in use, share data, and try to reach consensus about optimal methods for assessing sperm parameters in rats, rabbits, and dogs. This article presents the consensus report, as well as future research needs, with the hope that optimized common methods will aid in the detection of reproductive effects and enhance interlaboratory comparisons.

Chronic toxicity and three-generation reproduction study of styrene monomer in the drinking water of rats.

Chronic toxicity and reproductive performance were evaluated in groups of rats receiving styrene monomer in their drinking water at nominal concentrations of 0, 125, or 250 ppm. Fifty male and 70 female rats in each test group and 76 males and 104 females in the control group were placed on a 2-year study and followed for observations of general health which included measurement of body weight, food and water consumption, hemograms, clinical chemistries, urinalysis, and histopathological examination. Ten males and 20 females from each group in the study were mated to produce F1 pups. These pups were subsequently mated to produce three generations of offspring, all maintained on styrene-treated drinking water. For each generation, the following were evaluated: fertility, litter size, pup viability, pup survival, sex ratio, pup body weight, weanling liver and kidney weight, and marrow cytogenetics. Except for a statistically significant reduction in water consumption for styrene-treated rats, no treatment-related changes, including mortality patterns, were reported for animals in the chronic study. The data evaluated for reproductive performance also showed no evidence of styrene-related changes. It was concluded that the administration of styrene in the drinking water of rats for 2 years produced no deleterious dose-related effects or decrements in reproductive performance.

Teratology study in mice subjected to inhalation of diethylhydroxylamine, nitroethane, and diethylamine hydrogen sulfite.

Pregnant female mice were exposed from Days 6 to 17 of pregnancy to 8.9 +/- 2.0 ppm of diethylhydroxylamine and 14.3 +/- 2.0 ppm of nitroethane. Exposures were for 8.25 +/- 2.25 hours/day including weekends. The mice were also exposed continuously for 24 hours a day to the vapor of diethylamine hydrogen sulfite. The exposure produced no effect on the dams compared to the control group. There was no evidence of compound-induced terata, variation in sex ratio, embryotoxicity, or inhibition of fetal growth and development.