"My Whole World Fell Apart": Parents Discovering Their Child Has Anorexia Nervosa.

This was the first study to examine the experience of parents who discover their child was living with anorexia nervosa (AN), thus fulfilling a critical gap in the eating disorder literature. Gadamerian hermeneutic inquiry was the guiding philosophy and method used to investigate this topic. Dialogues with parents revealed the ambiguity inherent within discovery; the isolation, betrayal, and loss felt by parents; and the complicated family dynamics occurring during the process of discovering one's child has AN. As such, when discoveries are made, parents play a vital role in the development and functioning of the family's response to the situation. This research offers health care providers a better understanding of the difficult times parents and caregivers experience when discovering their child has AN.

Stay the course: practitioner reflections on implementing family-based treatment with adolescents with atypical anorexia.

BACKGROUND: Atypical anorexia nervosa (AN) has received minimal empirical attention regarding effective diagnosis and treatment. Family-based treatment (FBT) might be a promising treatment for atypical AN, yet it is unclear as to what adaptations are needed to the current manualized FBT for AN model. The objective of the current study was to identify how FBT practitioners applied FBT for atypical AN for adolescents in their clinical practice, and if there were any implementation challenges and adaptations to the model for this population. METHODS: The current study employed fundamental qualitative description, with the aim of capturing practitioners' reflections on working with adolescents with atypical AN in clinical practice. A purposeful sample of practitioners with training in FBT were recruited and each participant completed an individual, semi-structured interview. Data was analyzed using conventional content analysis. RESULTS: A total of 23 practitioners participated in this study. The results indicate that practitioners maintained some fidelity to manualized FBT in treating atypical AN, but they differed in their discussions around target weights, what constitutes weight restoration, and the dosage for FBT phases. Salient practice challenges included operationalizing the Diagnostic and Statistical Manual of Mental Disorders - 5th Edition (DSM-5) definition of atypical AN, identifying a 'goal weight' for adolescents and activating parents to take charge of the re-nourishment process. CONCLUSIONS: The results of this qualitative study demonstrate practitioner reflections on the delivery and adaptations of FBT for adolescents with atypical AN. These reflections highlight the need to establish the delivery of coherent and consistent treatment and messaging with patients and families. Further, practitioners' reflections highlight common strategies to increase the sense of urgency in parents to support their child with atypical AN.

Tackling mixed messages: Practitioner reflections on working with adolescents with atypical anorexia and their families.

The treatment of atypical anorexia nervosa (AN) poses new research and practice challenges for the field of eating disorders. The objective of this study was to describe frontline practitioners' perceptions of differences between adolescents living with atypical versus typical AN, as well as the intervention challenges they experience when working with these adolescents and their families. We followed the principles of fundamental qualitative description and recruited a purposeful sample of practitioners treating adolescent eating disorders to complete a one-on-one semi-structured interview. Conventional content analysis and the constant comparison technique were used for data analysis. A total of 23 practitioners from four countries participated in this study. Practitioners described that adolescents with atypical AN present with higher pre-morbid weights and rates of weight-based teasing compared to their AN peers. Clinical challenges perceived by practitioners to be specific to working with adolescents with atypical AN included: addressing conflicting messages about eating disorders and weight loss, empathizing with a justified fear of weight gain, and increased risk for parental and therapist collusion with the eating disorder. Findings have implications for delivering interventions to adolescents seeking care for atypical AN.

Hypoxia-inducible factor 2alpha regulates macrophage function in mouse models of acute and tumor inflammation.

Hypoxia-inducible factor 1alpha (HIF-1alpha) and HIF-2alpha display unique and sometimes opposing activities in regulating cellular energy homeostasis, cell fate decisions, and oncogenesis. Macrophages exposed to hypoxia accumulate both HIF-1alpha and HIF-2alpha, and overexpression of HIF-2alpha in tumor-associated macrophages (TAMs) is specifically correlated with high-grade human tumors and poor prognosis. However, the precise role of HIF-2alpha during macrophage-mediated inflammatory responses remains unclear. To fully characterize cellular hypoxic adaptations, distinct functions of HIF-1alpha versus HIF-2alpha must be elucidated. We demonstrate here that mice lacking HIF-2alpha in myeloid cells (Hif2aDelta/Delta mice) are resistant to lipopolysaccharide-induced endotoxemia and display a marked inability to mount inflammatory responses to cutaneous and peritoneal irritants. Furthermore, HIF-2alpha directly regulated proinflammatory cytokine/chemokine expression in macrophages activated in vitro. Hif2aDelta/Delta mice displayed reduced TAM infiltration in independent murine hepatocellular and colitis-associated colon carcinoma models, and this was associated with reduced tumor cell proliferation and progression. Notably, HIF-2alpha modulated macrophage migration by regulating the expression of the cytokine receptor M-CSFR and the chemokine receptor CXCR4, without altering intracellular ATP levels. Collectively, our data identify HIF-2alpha as an important regulator of innate immunity, suggesting it may be a useful therapeutic target for treating inflammatory disorders and cancer.

Hematopoietic cell regulation by Rac1 and Rac2 guanosine triphosphatases.

The Rho guanosine triphosphatases (GTPases) Rac1 and Rac2 are critical signaling regulators in mammalian cells. The deletion of both Rac1 and Rac2 murine alleles leads to a massive egress of hematopoietic stem/progenitor cells (HSC/Ps) into the blood from the marrow, whereas Rac1-/- but not Rac2-/- HSC/Ps fail to engraft in the bone marrow of irradiated recipient mice. In contrast, Rac2, but not Rac1, regulates superoxide production and directed migration in neutrophils, and in each cell type, the two GTPases play distinct roles in actin organization, cell survival, and proliferation. Thus, Rac1 and Rac2 regulate unique aspects of hematopoietic development and function.