Caring for a child with an eating disorder: Understanding differences among mothers and fathers of adolescent and adult children.

OBJECTIVE: This study investigated treatment-engagement fears, self-efficacy, and accommodating and enabling in mothers and fathers of adolescent and adult children with eating disorders. METHODS: This study involved a secondary analysis of pre-treatment data from a subsample of 143 parents (95 mothers; 48 fathers) from a Canada-wide multi-site study. Parents completed the Caregiver Traps Scale, Parents Versus Anorexia Scale, and the Accommodation and Enabling Scale for Eating Disorders. Data were analysed using factorial Multivariate Analysis of Variance and mediation via multiple regression. RESULTS: Mothers reported higher levels of treatment-engagement fears than fathers. Among mothers, higher fear predicted lower self-efficacy and more accommodating and enabling behaviours. Among fathers, neither fear nor self-efficacy predicted accommodating and enabling. No differences in treatment-engagement fear or self-efficacy between parents of adolescent child and adult children were found at pre-treatment. CONCLUSIONS: Mothers' and fathers' experience different levels of fear related to their involvement in their ill-child's treatment at pre-treatment, and that fear is uniquely related to variables that impact treatment outcomes. There is a need to support parents even when their child is an adult. This study can inform family-based treatments vis-a-vis tailoring interventions for mothers and fathers and providing support to parents of children with eating disorders across the lifespan.

miR-196b target screen reveals mechanisms maintaining leukemia stemness with therapeutic potential.

We have shown that antagomiR inhibition of miRNA miR-21 and miR-196b activity is sufficient to ablate MLL-AF9 leukemia stem cells (LSC) in vivo. Here, we used an shRNA screening approach to mimic miRNA activity on experimentally verified miR-196b targets to identify functionally important and therapeutically relevant pathways downstream of oncogenic miRNA in MLL-r AML. We found Cdkn1b (p27Kip1) is a direct miR-196b target whose repression enhanced an embryonic stem cell-like signature associated with decreased leukemia latency and increased numbers of leukemia stem cells in vivo. Conversely, elevation of p27Kip1 significantly reduced MLL-r leukemia self-renewal, promoted monocytic differentiation of leukemic blasts, and induced cell death. Antagonism of miR-196b activity or pharmacologic inhibition of the Cks1-Skp2-containing SCF E3-ubiquitin ligase complex increased p27Kip1 and inhibited human AML growth. This work illustrates that understanding oncogenic miRNA target pathways can identify actionable targets in leukemia.

The cell polarity determinant CDC42 controls division symmetry to block leukemia cell differentiation.

As a central regulator of cell polarity, the activity of CDC42 GTPase is tightly controlled in maintaining normal hematopoietic stem and progenitor cell (HSC/P) functions. We found that transformation of HSC/P to acute myeloid leukemia (AML) is associated with increased CDC42 expression and activity in leukemia cells. In a mouse model of AML, the loss of Cdc42 abrogates MLL-AF9-induced AML development. Furthermore, genetic ablation of CDC42 in both murine and human MLL-AF9 (MA9) cells decreased survival and induced differentiation of the clonogenic leukemia-initiating cells. We show that MLL-AF9 leukemia cells maintain cell polarity in the context of elevated Cdc42-guanosine triphosphate activity, similar to nonmalignant, young HSC/Ps. The loss of Cdc42 resulted in a shift to depolarized AML cells that is associated with a decrease in the frequency of symmetric and asymmetric cell divisions producing daughter cells capable of self-renewal. Importantly, we demonstrate that inducible CDC42 suppression in primary human AML cells blocks leukemia progression in a xenograft model. Thus, CDC42 loss suppresses AML cell polarity and division asymmetry, and CDC42 constitutes a useful target to alter leukemia-initiating cell fate for differentiation therapy.

DNMT3A Haploinsufficiency Transforms FLT3ITD Myeloproliferative Disease into a Rapid, Spontaneous, and Fully Penetrant Acute Myeloid Leukemia.

UNLABELLED: Cytogenetically normal acute myeloid leukemia (CN-AML) represents nearly 50% of human AML. Co-occurring mutations in the de novo DNA methyltransferase DNMT3A and the FMS related tyrosine kinase 3 (FLT3) are common in CN-AML and confer a poorer prognosis. We demonstrate that mice with Flt3-internal tandem duplication (Flt3(ITD)) and inducible deletion of Dnmt3a spontaneously develop a rapidly lethal, completely penetrant, and transplantable AML of normal karyotype. AML cells retain a single Dnmt3a floxed allele, revealing the oncogenic potential of Dnmt3a haploinsufficiency. FLT3(ITD)/DNMT3A-mutant primary human and murine AML exhibit a similar pattern of global DNA methylation associated with changes in the expression of nearby genes. In the murine model, rescuing Dnmt3a expression was accompanied by DNA remethylation and loss of clonogenic potential, suggesting that Dnmt3a-mutant oncogenic effects are reversible. Dissection of the cellular architecture of the AML model using single-cell assays, including single-cell RNA sequencing, identified clonogenic subpopulations that express genes sensitive to the methylation of nearby genomic loci and responsive to DNMT3A levels. Thus, Dnmt3a haploinsufficiency transforms Flt3(ITD) myeloproliferative disease by modulating methylation-sensitive gene expression within a clonogenic AML subpopulation. SIGNIFICANCE: DNMT3A haploinsufficiency results in reversible epigenetic alterations that transform FLT3(ITD)-mutant myeloproliferative neoplasm into AML. Cancer Discov; 6(5); 501-15. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 461.

The influence of carer fear and self-blame when supporting a loved one with an eating disorder.

Carers often feel disempowered and engage in behaviours that inadvertently enable their loved one's ED symptoms and yet little is known regarding these processes. This study examined the relationships among fear, self-blame, self-efficacy, and accommodating and enabling behaviours in 137 carers of adolescents and adults with ED. The results revealed that fear and self-blame predicted low carer self-efficacy in supporting their loved one's recovery as well as the extent to which carers reported engaging in recovery-interfering behaviours. The relevance of these findings are discussed in the context of family-oriented ED therapies and highlight the importance for clinicians to attend to and help to process strong emotions in carers, in order to improve their supportive efforts and, ultimately, ED outcomes.

Measuring Subtypes of Emotion Regulation: From Broad Behavioural Skills to Idiosyncratic Meaning-making.

UNLABELLED: The current paper introduces the notion of clinically relevant subtypes of emotion regulation behaviours. A new measure of emotion regulation, the Complexity of Emotional Regulation Scale (CERS), was established as psychometrically sound. It was positively correlated with a measure of emotional awareness (r = 0.28, p < 0.001) and negatively correlated with measures of self-criticism (r = -0.28, p < 0.001) and depression (r = -0.35, p = 0.025), among others. Participants were drawn from two samples: clients from a university counselling centre and a non-clinical student sample. Comparisons were conducted between non-clinical and clinical samples to determine the effects of depression and other symptoms of psychopathology on participant's generation of strategies for emotion regulation. Participants in the clinical sample more often identified an intention to soothe but did not follow through as compared with the non-clinical group, F(1, 198) = 4.662, p < 0.04. Furthermore, individuals in the non-clinical sample were more likely to engage in specific, meaning-making strategies when compared with the clinical group, F(1, 198) = 5.875, p < 0.02. Implications from the current studies suggest the possible applicability of the CERS to clinical settings using an interview rather than questionnaire format. Copyright © 2015 John Wiley & Sons, Ltd. KEY PRACTITIONER MESSAGE: Emotion regulation should be thought of as being on a continuum of complexity, where strategies range from general ('one size fits all') action to specific ('personal and idiosyncratic') meaning. The best emotion regulation strategy depends on a client's presenting difficulty and level of distress.

Executive function in pathological gamblers and healthy controls.

Executive function (EF) deficits may underlie some of the impulse control problems seen in pathological gambling. Pathological gamblers (PGs, n = 45) and controls (n = 45) were compared on several measures of EF (including measures of response inhibition, working memory, cognitive flexibility and perseveration, planning and decision-making), as well as memory and intelligence tests to examine whether PGs evidence EF dysfunction. Compared with controls, PGs exhibited specific deficits on measures of planning and decision-making. PGs also exhibited relative deficits on a measure of perseveration, but this deficit was no longer significant after controlling for group differences in intelligence. These results suggest that PGs may experience deficits on specific components of EF.

Affective and cognitive correlates of gambling behavior in university students.

The purpose of the following study was to explore certain affective and cognitive components and their relationships to gambling behavior in an undergraduate population. Specifically, the aim was to predict gambling severity using depression scores on the BDI-II, the dependency and self-criticism subscales on the DEQ, emotional awareness scores on the LEAS, cognitive flexibility scores from the STROOP, and a creativity subtests from the TTCT. Participants were 200 undergraduate students and 3.5-7.5% of individuals reported some level of problematic gambling behavior. Multiple regression analysis indicated that self-criticism and creative originality were significant predictors of gambling behavior, explaining 7.6% of the variance. Further analyses reveal a non-linear trend in the creative originality of those who gamble; only the at-risk gamblers were high in creativity whereas abstainers and problematic gamblers display similarly lower levels of creativity. Results are discussed in regards to Blaszczynski and Nower's Addiction 97:487-499 (2002) subtypes of gambling vulnerability.

The influence of shyness on the use of Facebook in an undergraduate sample.

Researchers have suggested that individual differences will help to determine which online communication tools appeal to and are used by different individuals. With respect to the domain of computer-mediated communication, shyness is a particular personality trait of interest, as forums provide opportunities for social interactions that shy individuals might otherwise avoid. The present study investigated the personality trait of shyness and its relation with certain features of an online communication tool (Facebook). We hypothesized that shyness would be significantly related to the quantity of time spent on Facebook, the number of contacts added to one's Facebook profile, and attitudes toward Facebook. Our findings supported that shyness was significantly positively correlated with the time spent on Facebook and having favorable attitudes toward the social networking site. Furthermore, shyness was significantly negatively correlated with the number of Facebook "Friends.'' Limitations of the present study and suggestions for future research are addressed.