Associations of prenatal and childhood Pb exposure with allostatic load in adolescence: Findings from the ELEMENT cohort study.

The biological pathways which link lead (Pb) and long-term outcomes are unclear, though rodent models and a few human studies suggest Pb may alter the body's stress response systems, which over time, can elicit dysregulated stress responses with cumulative impacts. This study examined associations between prenatal and early childhood Pb exposure and adolescent allostatic load, an index of an individual's body burden of stress in multiple biological systems, and further examined sex-based associations. Among 391 (51% male) participants in the ELEMENT birth cohort, we related trimester-specific maternal blood Pb, 1-month postpartum maternal tibia and patella Pb, and child blood Pb at 12-24 months to an allostatic load index in adolescence comprised of biomarkers of cardiovascular, metabolic, neuroendocrine, and immune function. The results were overall mixed, with prenatal exposure, particularly maternal bone Pb, being positively associated with allostatic load, and early childhood Pb showing mixed results for males and females. In adjusted Poisson regression models, 1 mcg/g increase in tibia Pb was associated with a 1% change in expected allostatic load (IRR = 1.01; 95%CI 0.99, 1.02). We found a significant Pb × sex interaction (IRR = 1.05; 95%CI 1.01, 1.10); where males saw an increasing percent change in allostatic load as 12 month Pb levels increased compared to females who saw a decreasing allostatic load. Further examination of allostatic load will facilitate the determination of potential mechanistic pathways between developmental toxicant exposures and later-in-life cardiometabolic outcomes.

A proof-of-principle study of the short-term effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus and neural connectivity.

Background: This study was conducted to investigate the short-term behavioural and neurophysiological effects of 3,4-methylenedioxymethamphetamine (MDMA) on tinnitus perception.Methods: A double-blind randomized controlled cross-over design. Part 1. Behavioural measures of tinnitus following 30 mg MDMA or placebo administration (N = 5 participants) and Part 2. Behavioural measures of tinnitus and correlations between pairs of apriori regions of interest (ROI) using resting-state functional magnetic resonance imaging (rs-fMRI) before and after 70 mg of MDMA or placebo (N = 8 participants).Results: The results to MDMA were similar to placebo. For the 70 mg dose, there was a significant reduction after 4 h in annoyance and ignore ratings. RsMRI showed decreased connectivity compared with placebo administration between the left hippocampal, right hippocampal, left amygdala and right amygdala regions, and between the right posterior parahippocampal cortex and the left amygdala after two hours of 70 mg MDMA administration. Increased connectivity compared to placebo administration was found post MDMA between the right post-central gyrus and right posterior and superior temporal gyrus, and between the thalamus and frontoparietal network.Conclusions: Following 70 mg of MDMA two tinnitus rating scales significantly improved. There was, however, a placebo effect. Compared with placebo the rsMRI following the MDMA showed reductions in connectivity between the amygdala, hippocampus and parahippocampal gyrus. There is sufficient proof of concept to support future investigation of MDMA as a treatment for tinnitus.

Direct Constraints on the Ultralight Boson Mass from Searches of Continuous Gravitational Waves.

Superradiance can trigger the formation of an ultralight boson cloud around a spinning black hole. Once formed, the boson cloud is expected to emit a nearly periodic, long-duration, gravitational-wave signal. For boson masses in the range (10^{-13}-10^{-11}) eV, and stellar mass black holes, such signals are potentially detectable by gravitational-wave detectors, like Advanced LIGO and Virgo. In this Letter, we present full band upper limits for a generic all-sky search for periodic gravitational waves in LIGO O2 data, and use them to derive-for the first time-direct constraints on the ultralight scalar boson field mass.

Development and preliminary validation of the Parenting around SNAcking Questionnaire (P-SNAQ).

Snacking makes significant contributions to children's dietary intake but is poorly understood from a parenting perspective. This research was designed to develop and evaluate the psychometrics of a theoretically grounded, empirically-informed measure of snack parenting. The Parenting around SNAcking Questionnaire (P-SNAQ) was developed using a conceptual model derived from current theory and mixed-methods research to include 20 hypothesized snack parenting practices along 4 parenting dimensions (autonomy support, structure, coercive control and permissiveness). Expert panel evaluation and cognitive interviews were used to refine items and construct definitions. The initial instrument of 105 items was administered to an ethnically diverse, low-income sample of 305 parents (92% mothers) of children aged 1-6 y participating in three existing cohort studies. The sample was randomly split into two equal samples. Exploratory factor analysis was conducted with the first sample to identify snack parenting practices within each parenting dimension, followed by confirmatory factor analysis with the second sample to test the hypothesized factor structure. Internal consistency of sub-scales and associations with existing measures of food parenting practices and styles and child weight status were evaluated. The final P-SNAQ scale included 51 items reflecting 14 snack parenting practices across four parenting dimensions. The factor structure of the P-SNAQ was consistent with prior theoretical frameworks. Internal consistency coefficients were good to very good for 12 out of 14 scales and subscale scores were moderately correlated with previously validated measures. In conclusion, initial evidence suggests that P-SNAQ is a psychometrically sound measure for evaluating a wide range of snack parenting practices in young children.

Seasonal variation of Mastophorus muris (Nematoda: Spirurida) in the water vole Arvicola amphibius from southern Sweden.

This study focused on the spirurid nematode Mastophorus muris in water voles (Arvicola amphibius) trapped in three regions in southern Sweden during spring and fall 2013. The collection of water voles formed part of a larger project (EMIRO) on the cestode Echinococcus multilocularis in rodents. The voles' stomach contents were examined for the presence of M. muris. Prevalence, mean abundance and mean intensity of infection were calculated. A generalized linear model model was used to examine the effects of sex, functional group, season and region on the number of M. muris individuals in each vole. Forty-seven of 181 (26%) voles were infected with M. muris, with up to 74 worms each. The overall mean intensity (worms per infected vole) was 15 (95% CI 10-21), and abundance (mean number of worms in all voles) was 4 (95% CI 2-6). Model output indicated a significant effect of season and region with respect to abundance of nematode infection, which was independent of sex and functional group of the investigated host.

Low-income mothers' feeding goals predict observed home mealtime and child feeding practices.

BACKGROUND: Mothers' goals are important for health behavior change, and engagement in child obesity interventions. It is unknown if maternal feeding goals are associated with observed home mealtime or feeding practices. The objective of this study was to examine the association of four common feeding goals (restrict junk food, promote fruit or vegetable intake, promote autonomy in eating and prevent obesity) with mothers' observed home mealtime and feeding practices. METHODS: Low-income mothers (N = 265) of children (mean child age 70.8 months) participated in a semi-structured interview about child feeding. A coding scheme was developed and reliably applied to identify mothers' feeding goals from transcripts. Mothers' observed home mealtime and feeding practices were reliably coded from home mealtimes and a laboratory eating protocol. Mothers completed a questionnaire and reported demographics. Participant weights and heights were obtained. Regression models were used to test the association of each feeding goal with observed maternal practices, controlling for covariates. RESULTS: The goal of restricting junk food was associated with the child always eating at a table (OR 2.87, 95% CI (1.39-5.96) p = 0.005), but not with the mother restricting junk food. The goal of promoting fruit or vegetable intake was associated with observationally promoting vegetables (OR 1.41, 95% CI (1.09-1.84), p = 0.01). The goals of promoting autonomy and preventing obesity were not associated with any observed maternal home mealtime or feeding practices. CONCLUSIONS: While mothers' goals to restrict junk food and promote fruit or vegetable intake were associated with observed home mealtime and feeding practices, promoting autonomy and preventing obesity were not. Increased understanding of why low-income mothers may not translate certain feeding goals into practices may inform childhood obesity interventions.

Evaluation of Simultaneous Transmission of Chikungunya Virus and Dengue Virus Type 2 in Infected Aedes aegypti and Aedes albopictus (Diptera: Culicidae).

The simultaneous transmission of chikungunya virus (CHIKV) and dengue viruses (DENV) has been a major public health concern because of their sympatric distribution and shared mosquito vectors. Groups of Aedes aegypti (L.) and Aedes albopictus (Skuse) were orally infected with 1.5 × 10(5) PFU/ml of CHIKV and 3.2 × 10(6) FFU/ml of DENV-2 simultaneously or separately in inverse orders and evaluated for dissemination and transmission by qRT-PCR. Simultaneous dissemination of both viruses was detected for all groups in Ae. aegypti and Ae. albopictus while cotransmission of CHIKV and DENV-2 only occurred at low rates after sequential but not simultaneous infection.

Perceptions of low-income mothers about the causes and ways to prevent overweight in children.

BACKGROUND: Childhood overweight and obesity remain major health conditions, affecting nearly one-third of children in the USA. Multiple factors have been identified that contribute to children becoming overweight; however, little is known regarding what low-income mothers perceive to be the causes of and the ways to prevent children from becoming overweight. METHODS: Low-income mothers (n = 286) with children aged 4-8 years participated in semi-structured interviews, during which they were asked for their opinions about the causes of and ways to prevent children from becoming overweight. After themes were identified, interviews were coded for the presence or absence of each theme. RESULTS: The majority of mothers were non-Hispanic White (69.2%) and overweight or obese (77.3%). Additionally, many of the children (41.9%) were overweight or obese. Six causes of children becoming overweight were identified by mothers: types or quantities of food eaten (90.9%); parenting behaviours (44.9%); lack of activity (42.3%); genetics, slow metabolism or medical issues (24.5%); stress or emotion (5.2%); and limited access to resources (3.5%). Five ways to prevent children from becoming overweight identified by mothers included the following: healthy eating (84.9%), more activity (54.8%), limiting screen time (19.9%), limiting sugar-sweetened beverages (12.2%) and drinking more water (6.6%). The majority of mothers (77.1%) reported that they carried out their suggestions to prevent their children from becoming overweight. CONCLUSION: Within this cohort with a high prevalence of maternal and child overweight, most mothers identified many of the evidence-based strategies for childhood obesity prevention. Future intervention development may benefit from focusing on content areas that were less commonly identified by mothers as well as helping mothers translate knowledge to implementation.

Cryptic genetic diversity and complex phylogeography of the boreal North American scorpion, Paruroctonus boreus (Vaejovidae).

Diverse studies in western North America have revealed the role of topography for dynamically shaping genetic diversity within species though vicariance, dispersal and range expansion. We examined patterns of phylogeographical diversity in the widespread but poorly studied North American vaejovid scorpion, Paruroctonus boreus Girard 1854. We used mitochondrial sequence data and parsimony, likelihood, and Bayesian inference to reconstruct phylogenetic relationships across the distributional range of P. boreus, focusing on intermontane western North America. Additionally, we developed a species distribution model to predict its present and historical distributions during the Last Glacial Maximum and the Last Interglacial Maximum. Our results documented complex phylogeographic relationships within P. boreus, with multiple, well-supported crown clades that are either geographically-circumscribed or widespread and separated by short, poorly supported internodes. We also observed subtle variation in predicted habitat suitability, especially at the northern, eastern and southern edges of the predicted distributional range under past climatic conditions. The complex phylogenetic relationships of P. boreus suggests that historical isolation and expansion of populations may have occurred. Variation in the predicted distributional range over time may implicate past climatic fluctuations in generating the patterns of genetic diversity observed in P. boreus. These findings highlight both the potential for cryptic biodiversity in widespread North American scorpion species and the importance of phylogeographical studies for understanding the factors responsible for generating the biodiversity of western North America.

Lead exposure, glucocorticoids, and physiological stress across the life course: A systematic review.

The biological pathways linking lead exposure to adverse outcomes are beginning to be understood. Rodent models suggest lead exposure induces dysfunction within the hypothalamic-pituitary-adrenal (HPA) axis and glucocorticoid regulation, a primary physiological stress response system. Over time, HPA axis and glucocorticoid dysfunction has been associated with adverse neurocognitive and cardiometabolic health, much like lead exposure. This systematic review utilized PRISMA guidelines to synthesize the literature regarding associations between lead exposure and downstream effector hormones of the HPA axis, including cortisol, a glucocorticoid, and dehydroepiandrosterone (DHEA), a glucocorticoid antagonist. We additionally determined the state of the evidence regarding lead exposure and allostatic load, a measure of cumulative body burden resultant of HPA axis and glucocorticoid dysfunction. A total of 18 articles were included in the review: 16 assessed cortisol or DHEA and 3 assessed allostatic load. Generally, the few available child studies suggest a significant association between early life lead exposure and altered cortisol, potentially suggesting the impact of developmental exposure. In adulthood, only cross sectional studies were available. These reported significant associations between lead and reduced cortisol awakening response and increased cortisol reactivity, but few associations with fasting serum cortisol. Two studies reported significant associations between increasing lead exposure and allostatic load in adults and another between early life lead exposure and adolescent allostatic load. The paucity of studies examining associations between lead exposure and allostatic load or DHEA and overall heterogeneity of allostatic load measurements limit conclusions. However, these findings cautiously suggest associations between lead and dysregulation of physiological stress pathways (i.e., glucocorticoids) as seen through cortisol measurement in children and adults. Future research would help to elucidate these associations and could further examine the physiological stress pathway as a mediator between lead exposure and detrimental health outcomes.

MRI of congenital and developmental abnormalities of the knee.

The knee joint is the one of the most common locations for congenital and developmental musculoskeletal abnormalities. Initial imaging of the knee joint should always begin with conventional radiographs. However, evaluation of the bone marrow, cartilaginous, ligamentous, and other soft-tissue components of the knee joint are better characterized with magnetic resonance imaging (MRI). We present the MRI findings of prevalent congenital and developmental abnormalities in the paediatric knee with particular emphasis on the components of the growing skeleton.

Comparison of the FilmArray Respiratory Panel and Prodesse real-time PCR assays for detection of respiratory pathogens.

We compared the diagnostic performance and overall respiratory pathogen detection rate of the premarket version of the FilmArray Respiratory Panel (RP) multiplex PCR assay (Idaho Technology, Inc., Salt Lake City, UT) with those of the Food and Drug Administration (FDA)-cleared Prodesse ProFlu+, ProFAST+, ProParaflu+, Pro hMPV+, and ProAdeno+ real-time PCR assays (Gen-Probe, San Diego, CA). The assays were performed on a panel of 192 nasopharyngeal-secretion specimens collected from 81 children under 1 year of age with upper respiratory tract symptoms. To resolve discordant results and confirm pathogens detected only by the larger FilmArray panel, we performed laboratory-developed real-time PCR assays. Among viruses detectable by both commercial assays (adenovirus, human metapneumovirus, influenza A virus, influenza B virus, parainfluenza viruses 1 to 3, and respiratory syncytial virus), the FilmArray and Prodesse assays showed good overall agreement (181/192 [94.3%]; kappa = 0.87; 95% CI, 0.79 to 0.94). FilmArray RP detected more parainfluenza viruses 1 and 3 than ProParaflu+ (18 versus 13) while ProAdeno+ detected more adenoviruses (11 versus 6), but these differences were not statistically significant. Additionally, FilmArray RP detected 138 pathogens (confirmed as true positives) not included in the Prodesse assays (rhinovirus [RV]/enterovirus [EV], 118; bocavirus, 8; coronavirus, 7; parainfluenza virus 4, 4; Mycoplasma pneumoniae, 1). FilmArray RP was cleared by the FDA following the completion of this study. The FDA-cleared version includes the following targets: adenovirus, coronaviruses HKU1 and NL63, human metapneumovirus (hMPV), influenza A virus (to type level only), influenza A H1 seasonal virus, influenza A H3 seasonal virus, influenza A virus H1-2009, influenza B virus, parainfluenza viruses 1 to 4, respiratory syncytial virus (RSV), and RV/EV (no differentiation). The larger panel in the FilmArray RP assay allowed the detection of additional respiratory pathogens compared to the Prodesse assays. In this population of young children with upper respiratory tract infection, RV/EV accounted for the majority of the additional pathogens detected by FilmArray RP.

Academic-community partnership: an orientation for employees of a community mental health agency to its research program.

CONTEXT: Community agency employees' interest and involvement in academic-community research partnerships are keys to successful collaborations. One main barrier to success can be employees' lack of knowledge about research. We present data on an "orientation to research" program for community agency employees in a large U.S. city designed to improve knowledge about research in general and that specific to the agency. METHODS: We developed an agency intranet website, a scavenger hunt to facilitate learning through the intranet research website, and a ten-item quantitative knowledge assessment tool. Academic and agency partners were actively involved in the design of the program and its evaluation. FINDINGS: More educated and long-term employees had higher pre-test scores but not post-test scores. Significant improvement in post-test scores was observed for employees after completion of the program. Informal feedback about course content and the academic-community partnership was positive. CONCLUSIONS: This report examines the feasibility of a structured knowledge program targeted at community agency employees at all levels within an agency. We believe that this approach is generalizable to other settings to the extent that there are shared interests, resources, and investment of the academic partner and agency.

Nanopore sequencing of the glucocerebrosidase (GBA) gene in a New Zealand Parkinson's disease cohort.

INTRODUCTION: Bi-allelic mutations in the gene for glucocerebrosidase (GBA) cause Gaucher disease, an autosomal recessive lysosomal storage disorder. Gaucher disease causing GBA mutations in the heterozygous state are also high risk factors for Parkinson's disease (PD). GBA analysis is challenging due to a related pseudogene and structural variations (SVs) that can occur at this locus. We have applied and refined a recently developed nanopore DNA sequencing method to analyze GBA variants in a clinically assessed New Zealand longitudinal cohort of PD. METHOD: We examined amplicons encompassing the coding region of GBA (8.9 kb) from 229 PD cases and 50 healthy controls using the GridION nanopore sequencing platform, and Sanger validation. RESULTS: We detected 23 variants in 21 PD cases (9.2% of patients). We detected modest PD risk variant p.N409S (rs76763715) in one case, p.E365K (rs2230288) in 12 cases, and p.T408 M (rs75548401) in seven cases, one of whom also had p.E365K. We additionally detected the possible risk variants p.R78C (rs146774384) in one case, p.D179H (rs147138516) in one case which occurred on the same haplotype as p.E365K, and one novel variant c.335C > T or p.(L335 = ), that potentially impacts splicing of GBA transcripts. Additionally, we found a higher prevalence of dementia among patients with GBA variants. CONCLUSION: This work confirmed the utility of nanopore sequencing as a high-throughput method to identify known and novel GBA variants, and to assign precise haplotypes. Our observations may contribute to improved understanding of the effects of variants on disease pathogenesis, and to the development of more targeted treatments.

Slow calcium waves accompany cytokinesis in medaka fish eggs.

Animal cells are cleaved by the formation and contraction of an extremely thin actomyosin band. In most cases this contractile band seems to form synchronously around the whole equator of the cleaving cell; however in giant cells it first forms near the mitotic apparatus and then slowly grows outwards over the cell. We studied the relationship of calcium to such contractile band growth using aequorin injected medaka fish eggs: we see two successive waves of faint luminescence moving along each of the first three cleavage furrows at approximately 0.5 micron/s. The first, narrower waves accompany furrow extension, while the second, broader ones, accompany the subsequent apposition or slow zipping together of the separating cells. If the first waves travel within the assembling contractile band, they would indicate local increases of free calcium to concentrations of about five to eight micromolar. This is the first report to visualize high free calcium within cleavage furrows. Moreover, this is also the first report to visualize slow (0.3-1.0 micron/s) as opposed to fast (10-100 microns/s) calcium waves. We suggest that these first waves are needed for furrow growth; that in part they further furrow growth by speeding actomyosin filament shortening, while such shortening in turn acts to mechanically release calcium and thus propagates these waves as well as furrow growth. We also suggest that the second waves act to induce the exocytosis which provides new furrow membrane.

Phenylketonuria: phenylalanine inhibits brain pyruvate kinase in vivo.

The hypothesis that brain damage in phenylketonuria is related to inhibition of pyruvate kinase by phenylalanine was examined in rat brain in vivo. One hour after a single injection of phenylalanine into the rat, the brains were removed and completely frozen in less than a second. The concentration of phenylalanine in the brain was comparable to that found in phenylketonuric patients. Changes in brain glycolytic intermediates were consistent with inhibition of pyruvate kinase in vivo. The inhibition of pyruvate kinase was apparently compensated for by an increase in phosphoenolpyruvate; no decrease in adenosine triphosphate or creatine phosphate was found.

Sanfilippo disease type B: enzyme replacement and metabolic correction in cultured fibroblasts.

alpha-Acetylglucosaminidase, purified from human placent, corrected the defect in mucopolysaccharide degradation when added to culture fibroblasts from patients with Sanfilippo disease type B. A small cellular concentration of enzyme gave a large corrective effect. The half-life of disappearance of enzyme activity was 4 to 7 days.

[Dialectical behaviour therapy for adolescents; a literature review]. / Dialectische gedragstherapie bij adolescenten;een literatuuronderzoek.

BACKGROUND: According to several randomised controlled trials (rct's) dialectical behaviour therapy (dbt) is effective in treating adults diagnosed with borderline personality disorder (bpd) who present with self-injurious and suicidal behaviour. In recent years there have been several studies about dbt in adolescents with varying problems and disorders. AIM: To review the literature for evidence of the effectiveness of dbt in adolescents aged 12 to 18. METHOD: With the help of PubMed and Medline and using the search-terms 'dialectical', 'adolescent', 'suicide attempt' and 'deliberate self harm', we searched the literature for references to dbt in adolescents. RESULTS: There were no rct's involving dbt in adolescents, but we did find one quasi-experimental design and several other studies with a pre-post treatment design. However, the studies were difficult to compare. In some cases it was doubtful whether the treatment could still be called dbt. The results suggested that dbt may be just as effective with adolescents as it is with adults in reducing bpd symptoms, suicidal ideation, and comorbid depressive disorder symptoms, and in reducing the need for hospitalisation. The results also indicated that dbt might be effective in treating eating disorders, bipolar disorder, oppositionality, aggression and nonsuicidal self-injurious behaviour (nsib) in a variety of treatment settings. CONCLUSION: dbt is possibly effective for treating adolescents with nsib and/or bpd symptoms. It may also be an effective treatment for various other affective and behavioural disorders. rct's are needed.