Exploring Alcohol-Related Behaviours in an Adult Sample with Anorexia Nervosa and Those in Recovery.

While individuals with Bulimia Nervosa (BN) and Binge Eating Disorder (BED) often present with a higher rate of Alcohol Use Disorder (AUD) than the general population, it is unclear whether this extends to AN. This cross-sectional study examined differences in alcohol-related behaviours, measured using the Alcohol Use Identification Test (AUDIT), between AN participants (n = 58), recovered AN (rec-AN) participants (n = 25), and healthy controls (n = 57). Statistical models controlled for age and ethnicity. The relationship between alcohol-related behaviours with ED psychopathology and with depression was also assessed. The findings indicated that acute AN participants were not at greater risk of AUD than healthy controls. However, rec-AN participants displayed greater total audit scores than those with acute AN, and more alcohol-related behaviours than healthy controls. Acute AN participants consumed significantly less alcohol than both the healthy control group and rec-AN group. No associations were found between ED psychopathology and alcohol-related behaviours in the AN group or rec-AN. This highlights alcohol as a potential coping mechanism following AN recovery. Clinicians should consider assessments for AUD and targeted interventions aimed at encouraging healthy coping mechanisms in this group. Future studies should look at alcohol use as a moderating factor for AN recovery.

Co-producing an inclusive-care model for young people transitioning from adolescent eating disorder services to adult care: A qualitative study protocol for Transition for Eating Disorder Youth intervention.

Eating disorders (EDs) present a chronic issue to child paediatric mental health services due to their high mortality and relapse rates. The transition from Child and Adolescent Mental Health Services to Adult Mental Health Services is a particularly high-risk period for young people with EDs given their high vulnerability to change, which can negatively impact treatment outcomes. However, there is lack of evidence on the feasibility of inclusive and youth-specific interventions that address the multiple and complex needs of this group during their transition to adult care. This proposed study aims to develop a newly introduced model of care called Transition for Eating Disorder Youth intervention (TEDYi) for young people aged 16-18 years with EDs transitioning from adolescent ED services to adult care. TEDYi will be co-produced with young people, carers, and staff targeting interpersonal and psychosocial needs during the transition process. The first phase of the study involves interviews with young people (N = 15) and carers (N = 15) as well as focus groups with mental health professionals (N = 15) across four ED adolescent and adult specialist services to explore their transition experiences. The second phase, consists of four Experience-Based Co-Design workshops, aimed at collaboratively developing and refining TEDYi.

Pharmacological activation of the EDA/EDAR signaling pathway restores salivary gland function following radiation-induced damage.

Radiotherapy of head and neck cancers often results in collateral damage to adjacent salivary glands associated with clinically significant hyposalivation and xerostomia. Due to the reduced capacity of salivary glands to regenerate, hyposalivation is treated by substitution with artificial saliva, rather than through functional restoration of the glands. During embryogenesis, the ectodysplasin/ectodysplasin receptor (EDA/EDAR) signaling pathway is a critical element in the development and growth of salivary glands. We have assessed the effects of pharmacological activation of this pathway in a mouse model of radiation-induced salivary gland dysfunction. We report that post-irradiation administration of an EDAR-agonist monoclonal antibody (mAbEDAR1) normalizes function of radiation damaged adult salivary glands as determined by stimulated salivary flow rates. In addition, salivary gland structure and homeostasis is restored to pre-irradiation levels. These results suggest that transient activation of pathways involved in salivary gland development could facilitate regeneration and restoration of function following damage.

Autophagy correlates with maintenance of salivary gland function following radiation.

The current standard of care for head and neck cancer includes surgical resection of the tumor followed by targeted head and neck radiation. This radiotherapy results in a multitude of negative side effects in adjacent normal tissues. Autophagy is a cellular mechanism that could be targeted to ameliorate these side effects based on its role in cellular homeostasis. In this study, we utilized Atg5(f/f);Aqp5-Cre mice which harbor a conditional knockout of Atg5, in salivary acinar cells. These autophagy-deficient mice display increased radiosensitivity. Treatment of wild-type mice with radiation did not robustly induce autophagy following radiotherapy, however, using a model of preserved salivary gland function by IGF-1-treatment prior to irradiation, we demonstrate increased autophagosome formation 6-8 hours following radiation. Additionally, administration of IGF-1 to Atg5(f/f);Aqp5-Cre mice did not preserve physiological function. Thus, autophagy appears to play a beneficial role in salivary glands following radiation and pharmacological induction of autophagy could alleviate the negative side effects associated with therapy for head and neck cancer.

Fhit delocalizes annexin a4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel.

Fhit protein is lost or reduced in a large fraction of human tumors, and its restoration triggers apoptosis and suppresses tumor formation or progression in preclinical models. Here, we describe the identification of candidate Fhit-interacting proteins with cytosolic and plasma membrane localization. Among these, Annexin 4 (ANXA4) was validated by co-immunoprecipitation and confocal microscopy as a partner of this novel Fhit protein complex. Here we report that overexpression of Fhit prevents Annexin A4 translocation from cytosol to plasma membrane in A549 lung cancer cells treated with paclitaxel. Moreover, paclitaxel administration in combination with AdFHIT acts synergistically to increase the apoptotic rate of tumor cells both in vitro and in vivo experiments.

Prevention of radiation-induced salivary gland dysfunction utilizing a CDK inhibitor in a mouse model.

BACKGROUND: Treatment of head and neck cancer with radiation often results in damage to surrounding normal tissues such as salivary glands. Permanent loss of function in the salivary glands often leads patients to discontinue treatment due to incapacitating side effects. It has previously been shown that IGF-1 suppresses radiation-induced apoptosis and enhances G2/M arrest leading to preservation of salivary gland function. In an effort to recapitulate the effects of IGF-1, as well as increase the likelihood of translating these findings to the clinic, the small molecule therapeutic Roscovitine, is being tested. Roscovitine is a cyclin-dependent kinase inhibitor that acts to transiently inhibit cell cycle progression and allow for DNA repair in damaged tissues. METHODOLOGY/PRINCIPAL FINDINGS: Treatment with Roscovitine prior to irradiation induced a significant increase in the percentage of cells in the G(2)/M phase, as demonstrated by flow cytometry. In contrast, mice treated with radiation exhibit no differences in the percentage of cells in G(2)/M when compared to unirradiated controls. Similar to previous studies utilizing IGF-1, pretreatment with Roscovitine leads to a significant up-regulation of p21 expression and a significant decrease in the number of PCNA positive cells. Radiation treatment leads to a significant increase in activated caspase-3 positive salivary acinar cells, which is suppressed by pretreatment with Roscovitine. Administration of Roscovitine prior to targeted head and neck irradiation preserves normal tissue function in mouse parotid salivary glands, both acutely and chronically, as measured by salivary output. CONCLUSIONS/SIGNIFICANCE: These studies suggest that induction of transient G(2)/M cell cycle arrest by Roscovitine allows for suppression of apoptosis, thus preserving normal salivary function following targeted head and neck irradiation. This could have an important clinical impact by preventing the negative side effects of radiation therapy in surrounding normal tissues.