New mutations at the imprinted Gnas cluster show gene dosage effects of Gsα in postnatal growth and implicate XLαs in bone and fat metabolism, but not in suckling

The imprinted Gnas cluster is involved in obesity, energy metabolism, feeding behavior, and viability. Relative contribution of paternally expressed proteins XLαs, XLN1, and ALEX or a double dose of maternally expressed Gsα to phenotype has not been established. In this study, we have generated two new mutants (Ex1A-T-CON and Ex1A-T) at the Gnas cluster. Paternal inheritance of Ex1A-T-CON leads to loss of imprinting of Gsα, resulting in preweaning growth retardation followed by catch-up growth. Paternal inheritance of Ex1A-T leads to loss of imprinting of Gsα and loss of expression of XLαs and XLN1. These mice have severe preweaning growth retardation and incomplete catch-up growth. They are fully viable probably because suckling is unimpaired, unlike mutants in which the expression of all the known paternally expressed Gnasxl proteins (XLαs, XLN1 and ALEX) is compromised. We suggest that loss of ALEX is most likely responsible for the suckling defects previously observed. In adults, paternal inheritance of Ex1A-T results in an increased metabolic rate and reductions in fat mass, leptin, and bone mineral density attributable to loss of XLαs. This is, to our knowledge, the first report describing a role for XLαs in bone metabolism. We propose that XLαs is involved in the regulation of bone and adipocyte metabolism

Hypothalamic over-expression of VGF in the Siberian hamster increases energy expenditure and reduces body weight gain

VGF (non-acronymic) was first highlighted to have a role in energy homeostasis through experiments involving dietary manipulation in mice. Fasting increased VGF mRNA in the Arc and levels were subsequently reduced upon refeeding. This anabolic role for VGF was supported by observations in a VGF null (VGF-/-) mouse and in the diet-induced and gold-thioglucose obese mice. However, this anabolic role for VGF has not been supported by a number of subsequent studies investigating the physiological effects of VGF-derived peptides. Intracerebroventricular (ICV) infusion of TLQP-21 increased resting energy expenditure and rectal temperature in mice and protected against diet-induced obesity. Similarly, ICV infusion of TLQP-21 into Siberian hamsters significantly reduced body weight, but this was due to a decrease in food intake, with no effect on energy expenditure. Subsequently NERP-2 was shown to increase food intake in rats via the orexin system, suggesting opposing roles for these VGF-derived peptides. Thus to further elucidate the role of hypothalamic VGF in the regulation of energy homeostasis we utilised a recombinant adeno-associated viral vector to over-express VGF in adult male Siberian hamsters, thus avoiding any developmental effects or associated functional compensation. Initially, hypothalamic over-expression of VGF in adult Siberian hamsters produced no effect on metabolic parameters, but by 12 weeks post-infusion hamsters had increased oxygen consumption and a tendency to increased carbon dioxide production; this attenuated body weight gain, reduced interscapular white adipose tissue and resulted in a compensatory increase in food intake. These observed changes in energy expenditure and food intake were associated with an increase in the hypothalamic contents of the VGF-derived peptides AQEE, TLQP and NERP-2. The complex phenotype of the VGF-/- mice is a likely consequence of global ablation of the gene and its derived peptides during development, as well as in the adult

The Effects of Including a Callous Unemotional Specifier for the Diagnosis of Conduct Disorder

“With Significant Callous-Unemotional Traits” has been proposed as a specifier for Conduct Disorder (CD) in the upcoming revision of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5). The impact of this specifier on children diagnosed with CD should be considered

Reward Dysregulation and Mood Symptoms in an Adolescent Outpatient Sample

Research on bipolar spectrum disorders (BPSD) in adolescence has burgeoned in the last decade, but continued work is needed to identify endophenotypic markers associated with illness onset and course. The present study examined reward dysregulation – measured via the behavioral activation system (BAS) – as one putative marker of BPSD in adolescence. A diverse group of 425 outpatient adolescents between 11–17 years of age (52% male) completed the Behavioral Inhibition and Activation Scale (BIS-BAS) scale to measure reward dysregulation. Semi-structured interviews determined diagnoses and severity of mood symptoms. Parent-reported BAS was associated with increased symptoms of mania, and parent and adolescent-reported BAS were associated with symptoms of depression. Parent-reported BIS scores were associated with increased symptoms of mania. Results held independent of diagnostic status. Furthermore, parent BIS/BAS reports were stronger predictors for manic symptoms compared to adolescent-reports. Results extend work in adults with BPSD, suggesting a transdiagnostic association between reward dysregulation and mood symptom severity in adolescence

Family treatment of child anxiety: outcomes, limitations and future directions

Anxiety of childhood is a common and serious condition. The past decade has seen an increase in treatment-focussed research, with recent trials tending to give greater attention to parents in the treatment process. This review examines the efficacy of family-based cognitive behaviour therapy and attempts to delineate some of the factors that might have an impact on its efficacy. The choice and timing of outcome measure, age and gender of the child, level of parental anxiety, severity and type of child anxiety and treatment format and content are scrutinised. The main conclusions are necessarily tentative, but it seems likely that Family Cognitive Behaviour Therapy (FCBT) is superior to no treatment, and, for some outcome measures, also superior to Child Cognitive Behaviour Therapy (CCBT). Where FCBT is successful, the results are consistently maintained at follow-up. It appears that where a parent is anxious, and this is not addressed, outcomes are less good. However, for children of anxious parents, FCBT is probably more effective than CCBT. What is most clear is that large, well-designed studies, examining these factors alone and in combination, are now needed

The collateral impact of COVID-19 emergency on neonatal intensive care units and family-centered care: Challenges and opportunities

The ongoing Coronavirus disease 2019 (COVID-19) pandemic is disrupting most specialized healthcare services worldwide, including those for high-risk newborns and their families. Due to the risk of contagion, critically ill infants, relatives and professionals attending neonatal intensive care units (NICUs) are undergoing a profound remodeling of the organization and quality care. In particular, mitigation strategies adopted to combact the COVID-19 pandemic may hinder the implementation of family-centered care within the NICU. This may put newborns at risk for several adverse effects, e.g., less weight gain, more nosocomial infections, increased length of NICU stay as well as long-term worse cognitive, emotional, and social development. This article aims to contribute to deepening the knowledge on the psychological impact of the COVID-19 on parents and NICU staff members based on empirical data from the literature. We also provided evidence-based indications on how to safely empower families and support NICU staffs facing such a threatening emergency, while preserving the crucial role of family-centered developmental care practices

Distinguishing primary and secondary variants of callous-unemotional traits among adolescents in a clinic-referred sample.

The current study used model-based cluster analyses to determine if there are two distinct variants of adolescents (ages 11 - 18) high on callous-unemotional (CU) traits that differ on their level of anxiety and history of trauma. The sample (n = 272) consisted of clinic-referred youths who were primarily African-American (90%) and from low income families. Consistent with hypotheses, three clusters emerged, including a group low on CU traits, as well as two groups high on CU traits that differed in their level of anxiety and past trauma. Consistent with past research on incarcerated adults and adolescents, the group high on anxiety (i.e., secondary variant) was more likely to have histories of abuse and had higher levels of impulsivity, externalizing behaviors, aggression, and behavioral activation. In contrast, the group low on anxiety (i.e., primary variant) scored lower on a measure of behavioral inhibition. On measures of impulsivity and externalizing behavior, the higher scores for the secondary cluster only were found for self-report measures, not on parent-report measures. Youths in the primary cluster also were perceived as less credible reporters than youth in the secondary or cluster low on CU traits. These reporter and credibility differences suggest that adolescents within the primary variant may underreport their level of behavioral disturbance, which has important assessment implications

Working with bipolar disorder during the covid-19 pandemic: Both crisis and opportunity

© 2020, WikiJournal User Group. All rights reserved. Beyond public health and economic costs, the COVID-19 pandemic adds strain, disrupts daily routines, and com-plicates mental health and medical service delivery for those with mental health and medical conditions. Bipolar disorder can increase vulnerability to infection; it can also enhance stress, complicate treatment, and heighten interpersonal stigma. Yet there are successes when people proactively improve social connections, prioritize self-care, and learn to use mobile and telehealth effectively

The impact of detergents on the tissue decellularization process: a ToF-SIMS study

Biologic scaffolds are derived from mammalian tissues, which must be decellularized to remove cellular antigens that would otherwise incite an adverse immune response. Although widely used clinically, the optimum balance between cell removal and the disruption of matrix architecture and surface ligand landscape remains a considerable challenge. Here we describe the use of time of flight secondary ion mass spectroscopy (ToF-SIMS) to provide sensitive, molecular specific, localized analysis of detergent decellularized biologic scaffolds. We detected residual detergent fragments, specifically from Triton X-100, sodium deoxycholate and sodium dodecyl sulphate (SDS) in decellularized scaffolds; increased SDS concentrations from 0.1% to 1.0% increased both the intensity of SDS fragments and adverse cell outcomes. We also identified cellular remnants, by detecting phosphate and phosphocholine ions in PAA and CHAPS decellularized scaffolds. The present study demonstrates ToF-SIMS is not only a powerful tool for characterization of biologic scaffold surface molecular functionality, but also enables sensitive assessment of decellularization efficacy