Measurement of Total and Free Urinary Phenol and Paraben Concentrations over the Course of Pregnancy: Assessing Reliability and Contamination of Specimens in the Norwegian Mother and Child Cohort Study

BackgroundExposures to environmental phenols and parabens may be harmful, especially in utero. Prior studies have demonstrated high within-person variability of urinary concentrations across pregnancy.ObjectivesWe sought to measure phenol and paraben biomarker concentrations for the Norwegian Mother and Child Cohort (MoBa) study, assess within-person variability, and investigate any possible external phenol or paraben contamination of specimens.MethodsWe collected three spot urine samples at approximately 17, 23, and 29 weeks gestation in a hospital setting and added a preservative containing ethyl paraben. We measured urinary concentrations and within-person variability for phenols and parabens in a MoBa sample (n = 45), including a subgroup of 15 participants previously randomly selected for a bisphenol A (BPA) exposure study who had unusually high total BPA concentrations. Additionally, we compared reliability results for total, conjugated, and free concentrations of phenolic compounds.ResultsWe detected total and free BPA, butyl paraben, propyl paraben, and methyl paraben in 100% of samples, total benzophenone-3 in 95% of samples, and infrequently detected free benzophenone-3 and total and free 2,4-dichlorophenol and 2,5-dichlorophenol. Intraclass correlation coefficients (ICCs) for total, conjugated, and free concentrations ranged from relatively low for BPA to moderate for propyl paraben. ICCs were generally similar overall and by subgroup.ConclusionsUsing conjugated concentrations improved reliability estimates only for BPA. Measuring total and free concentrations, an approach that may be useful for future studies, allowed us to identify likely BPA and butyl paraben contamination of archived MoBa urine specimens.CitationGuidry VT, Longnecker MP, Aase H, Eggesbø M, Zeiner P, Reichborn-Kjennerud T, Knudsen GP, Bertelsen RJ, Ye X, Calafat AM, Engel SM. 2015. Measurement of total and free urinary phenol and paraben concentrations over the course of pregnancy: assessing reliability and contamination of specimens in the Norwegian Mother and Child Cohort Study. Environ Health Perspect 123:705–711; http://dx.doi.org/10.1289/ehp.140832

An Umbrella Review of Self-Management Interventions for Health Conditions With Symptom Overlap With Traumatic Brain Injury

OBJECTIVE: To synthesize evidence for the effectiveness of self-management interventions for chronic health conditions that have symptom overlap with traumatic brain injury (TBI) in order to extract recommendations for self-management intervention in persons with TBI. DESIGN: An umbrella review of existing systematic reviews and/or meta-analyses of randomized controlled trials or nonrandomized studies targeting self-management of chronic conditions and specific outcomes relevant to persons with TBI. METHOD: A comprehensive literature search of 5 databases was conducted using PRISMA guidelines. Two independent reviewers conducted screening and data extraction using the Covidence web-based review platform. Quality assessment was conducted using criteria adapted from the Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2). RESULTS: A total of 26 reviews met the inclusion criteria, covering a range of chronic conditions and a range of outcomes. Seven reviews were of moderate or high quality and focused on self-management in persons with stroke, chronic pain, and psychiatric disorders with psychotic features. Self-management interventions were found to have positive effects on quality of life, self-efficacy, hope, reduction of disability, pain, relapse and rehospitalization rates, psychiatric symptoms, and occupational and social functioning. CONCLUSIONS: Findings are encouraging with regard to the effectiveness of self-management interventions in patients with symptoms similar to those of TBI. However, reviews did not address adaptation of self-management interventions for those with cognitive deficits or for populations with greater vulnerabilities, such as low education and older adults. Adaptations for TBI and its intersection with these special groups may be needed

Administration of the GABAA receptor antagonist picrotoxin into rat supramammillary nucleus induces c-Fos in reward-related brain structures. Supramammillary picrotoxin and c-Fos expression

<p>Abstract</p> <p>Background</p> <p>Picrotoxin blocks GABA_Areceptors, whose activation typically inhibits neuronal firing activity. We recently found that rats learn to selectively self-administer picrotoxin or bicuculline, another GABA_Areceptor antagonist, into the supramammillary nucleus (SuM), a posterior hypothalamic structure localized anterior to the ventral tegmental area. Other drugs such as nicotine or the excitatory amino acid AMPA are also self-administered into the SuM. The SuM appears to be functionally linked with the mesolimbic dopamine system and is closely connected with other brain structures that are implicated in motivational processes, including the prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus. Here, we hypothesized that these brain structures are activated by picrotoxin injections into the SuM.</p> <p>Results</p> <p>Picrotoxin administration into the SuM markedly facilitated locomotion and rearing. Further, it increased c-Fos expression in this region, suggesting blockade of tonic inhibition and thus the disinhibition of local neurons. This manipulation also increased c-Fos expression in structures including the ventral tegmental area, medial shell of the nucleus accumbens, medial prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus.</p> <p>Conclusions</p> <p>Picrotoxin administration into the SuM appears to disinhibit local neurons and recruits activation of brain structures associated with motivational processes, including the mesolimbic dopamine system, prefrontal cortex, septal area, preoptic area, lateral hypothalamic area and dorsal raphe nucleus. These regions may be involved in mediating positive motivational effects triggered by intra-SuM picrotoxin.</p

Risk factors for progression from severe maternal morbidity to death: a national cohort study.

Women continue to die unnecessarily during or after pregnancy in the developed world. The aim of this analysis was to compare women with severe maternal morbidities who survived with those who died, to quantify the risk associated with identified factors to inform policy and practice to improve survival

Access to infertility consultations: what women tell us about it?

The main objective of the present paper is to evaluate the perception of women concerning the barriers and access to infertility consultations. Socio cultural and economic access to infertility consultations is detached and three municipalities of the northwest of Portugal were chosen as an example of a peripheral country. A quantitative/qualitative study was done with 60 women. Three dimensions were evaluated: geographic and structural and functional access; economic access; and sociocultural access. The main barriers were mainly identified in the last two dimensions. The economic access was the less well evaluated by women being the cost of treatment (medication, and concentration of costs in a short period) difficult to bear. This can justify a greater involvement of the Portuguese Government, by developing policies for the reimbursement of part of the costs. Also, some changes in structural and functional access must be done with special regard to the separation of the infertility consultations from the reproductive medicine section. The setting of the teams, with a follow-up by the same team of health professionals is also needed

Cyclic AMP signalling pathways in the regulation of uterine relaxation

Studying the mechanism(s) of uterine relaxation is important and will be helpful in the prevention of obstetric difficulties such as preterm labour, which remains a major cause of perinatal mortality and morbidity. Multiple signalling pathways regulate the balance between maintaining relative uterine quiescence during gestation, and the transition to the contractile state at the onset of parturition. Elevation of intracellular cyclic AMP promotes myometrial relaxation, and thus quiescence, via effects on multiple intracellular targets including calcium channels, potassium channels and myosin light chain kinase. A complete understanding of cAMP regulatory pathways (synthesis and hydrolysis) would assist in the development of better tocolytics to delay or inhibit preterm labour. Here we review the enzymes involved in cAMP homoeostasis (adenylyl cyclases and phosphodiesterases) and possible myometrial substrates for the cAMP dependent protein kinase. We must emphasise the need to identify novel pharmacological targets in human pregnant myometrium to achieve safe and selective uterine relaxation when this is indicated in preterm labour or other obstetric complications

A multilevel intervention to increase physical activity and improve healthy eating and physical literacy among young children (ages 3-5) attending early childcare centres: the Healthy Start-Départ Santé cluster randomised controlled trial study protocol

Abstract: Background: Childhood obesity is a growing concern for public health. Given a majority of children in many countries spend approximately 30 h per week in early childcare centers, this environment represents a promising setting for implementing strategies to foster healthy behaviours for preventing and controlling childhood obesity. Healthy Start-Départ Santé was designed to promote physical activity, physical literacy, and healthy eating among preschoolers. The objectives of this study are to assess the effectiveness of the Healthy Start-Départ Santé intervention in improving physical activity levels, physical literacy, and healthy eating among preschoolers attending early childcare centers. Methods/Design: This study follows a cluster randomized controlled trial design in which the childcare centers are randomly assigned to receive the intervention or serve as usual care controls. The Healthy Start-Départ Santé intervention is comprised of interlinked components aiming to enable families and educators to integrate physical activity and healthy eating in the daily lives of young children by influencing factors at the intrapersonal, interpersonal, organizational, community, physical environment and policy levels. The intervention period, spanning 6-8 months, is preceded and followed by data collections. Participants are recruited from 61 childcare centers in two Canadian provinces, New Brunswick and Saskatchewan. Centers eligible for this study have to prepare and provide meals for lunch and have at least 20 children between the ages of 3 and 5. Centers are excluded if they have previously received a physical activity or nutrition promoting intervention. Eligible centers are stratified by province, geographical location (urban or rural) and language (English or French), then recruited and randomized using a one to one protocol for each stratum. Data collection is ongoing. The primary study outcomes are assessed using accelerometers (physical activity levels), the Test of Gross Motor Development-II (physical literacy), and digital photography-assisted weighted plate waste (food intake). Discussion: The multifaceted approach of Healthy Start-Départ Santé positions it well to improve the physical literacy and both dietary and physical activity behaviors of children attending early childcare centers. The results of this study will be of relevance given the overwhelming prevalence of overweight and obesity in children worldwide. Trial registration: NCT02375490 (ClinicalTrials.gov registry)

Critical evaluation of key evidence on the human health hazards of exposure to bisphenol A

Despite the fact that more than 5000 safety-related studies have been published on bisphenol A (BPA), there seems to be no resolution of the apparently deadlocked controversy as to whether exposure of the general population to BPA causes adverse effects due to its estrogenicity. Therefore, the Advisory Committee of the German Society of Toxicology reviewed the background and cutting-edge topics of this BPA controversy. The current tolerable daily intake value (TDI) of 0.05 mg/kg body weight [bw]/day, derived by the European Food Safety Authority (EFSA), is mainly based on body weight changes in two- and three-generation studies in mice and rats. Recently, these studies and the derivation of the TDI have been criticized. After having carefully considered all arguments, the Committee had to conclude that the criticism was scientifically not justified; moreover, recently published additional data further support the reliability of the two-and three-generation studies demonstrating a lack of estrogen-dependent effects at and below doses on which the current TDI is based. A frequently discussed topic is whether doses below 5 mg/ kg bw/day may cause adverse health effects in laboratory animals. Meanwhile, it has become clear that positive results from some explorative studies have not been confirmed in subsequent studies with higher numbers of animals or a priori defined hypotheses. Particularly relevant are some recent studies with negative outcomes that addressed effects of BPA on the brain, behavior, and the prostate in rodents for extrapolation to the human situation. The Committee came to the conclusion that rodent data can well be used as a basis for human risk evaluation. Currently published conjectures that rats are insensitive to estrogens compared to humans can be refuted. Data from toxicokinetics studies show that the half-life of BPA in adult human subjects is less than 2 hours and BPA is completely recovered in urine as BPA-conjugates. Tissue deconjugation of BPA-glucuronide and -sulfate may occur. Because of the extremely low quantities, it is only of minor relevance for BPA toxicity. Biomonitoring studies have been used to estimate human BPA exposure and show that the daily intake of BPA is far below the TDI for the general population. Further topics addressed in this article include reasons why some studies on BPA are not reproducible; the relevance of oral versus non-oral exposure routes; the degree to which newborns are at higher systemic BPA exposure; increased BPA exposure by infusions in intensive care units; mechanisms of action other than estrogen receptor activation; and the current regulatory status in Europe, as well as in the USA, Canada, Japan, New Zealand, and Australia. Overall, the Committee concluded that the current TDI for BPA is adequately justified and that the available evidence indicates that BPA exposure represents no noteworthy risk to the health of the human population, including newborns and babies