A preliminary investigation of the long-term outcome of the Unified Protocol for Transdiagnostic Treatment of Emotional Disorders

Objective

The aim of this study is to conduct a preliminary examination of long-term outcomes on a broad range of affective disorder symptoms treated with a newly developed intervention: The Unified Protocol for Transdiagnostic Treatment of Emotional Disorders (UP).

Method

Maintenance of treatment gains at long-term follow-up (LTFU) were explored in patients (N = 15, mean age = 32.27; 60% female) who completed a clinical trial of the UP.

Results

Treatment gains observed at 6-month follow-up (6MFU) on measures of clinical severity, general symptoms of depression and anxiety, and a measure of symptom interference in daily functioning were largely maintained 12 months later (at an average of 18 months posttreatment), and any significant changes from 6MFU to LTFU reflected small increases in symptoms that remained, on average, in the subclinical range.

Conclusions

These findings provide the first initial support for the durability of broad treatment gains following transdiagnostic treatment.     

Regulation of the Fanconi anemia pathway by a CUE ubiquitin-binding domain in the FANCD2 protein

The Fanconi anemia (FA)-BRCA pathway is critical for the repair of DNA interstrand crosslinks (ICLs) and the maintenance of chromosome stability. A key step in FA-BRCA pathway activation is the covalent attachment of monoubiquitin to FANCD2 and FANCI. Monoubiquitinated FANCD2 and FANCI localize in chromatin-associated nuclear foci where they interact with several well-characterized DNA repair proteins. Importantly, very little is known about the structure, function, and regulation of FANCD2. Herein, we describe the identification and characterization of a CUE (coupling of ubiquitin conjugation to endoplasmic reticulum degradation) ubiquitin-binding domain (UBD) in FANCD2, and demonstrate that the CUE domain mediates noncovalent binding to ubiquitin in vitro. We show that although mutation of the CUE domain destabilizes FANCD2, the protein remains competent for DNA damage-inducible monoubiquitination and phosphorylation. Importantly, we demonstrate that the CUE domain is required for interaction with FANCI, retention of monoubiquitinated FANCD2, and FANCI in chromatin, and for efficient ICL repair. Our results suggest a model by which heterodimerization of monoubiquitinated FANCD2 and FANCI in chromatin is mediated in part through a noncovalent interaction between the FANCD2 CUE domain and monoubiquitin covalently attached to FANCI, and that this interaction shields monoubiquitinated FANCD2 from polyubiquitination and proteasomal degradation.     

Patterns of gaze behavior during an eye-tracking measure of joint attention in typically developing children and children with autism spectrum disorder

This study evaluated whether diagnostic classifications or features of ASD were associated with individual differences in children's gaze pattern during an eye-tracking measure of joint attention. The sample included 21 children with ASD (mean age, 7.3 ± 1.5 years) and 24 typically developing children (mean age, 6.8 ± 1.6 years), matched on receptive language abilities. Results revealed no significant group differences on global measures of gaze allocation (total gaze time allocation). However, significant group differences emerged using a measure evaluating a microstructure of children's gaze (duration of first fixation). In addition, individual differences in children's gaze pattern were reliably predicted by parent report measures of children's social abilities. The majority of children in this sample (including all typically developing children and those children with ASD who scored lowest on the SRS Social Awareness subscale) showed significant modulation in eye-gaze between the two experimental conditions. In contrast, children with ASD who also scored the highest on the SRS Social Awareness subscale consistently failed to modulate their eye gaze in accordance with the experimental condition. This failure to flexibly modulate gaze in the context of a joint attention eye-tracking paradigm may reveal children's limited awareness of social cues that may further limit social learning.     

Alagille syndrome and Wilson disease in siblings: a diagnostic conundrum

The authors describe two siblings, each with a different, rare genetic condition that affects liver function. The index case, the 18-year-old asymptomatic brother of a young man recently diagnosed with Wilson disease, presented for Wilson disease screening and was also found to have abnormal liver function suggestive of cholestasis. However, ceruloplasmin level, 24 h urine copper concentration and liver synthetic function were normal. Further hepatic investigations and genetic mutation analysis were performed, ultimately leading to a diagnosis of Alagille syndrome. He was treated with ursodiol, which resulted in normalization of his liver function tests. Subsequently, he was found to be a carrier for a mutation in the Wilson disease gene, ATP7B. In the present report, the potential implications of being a heterozygote for Wilson disease in the context of Alagille syndrome are discussed. Also stressed is that care must be exercised by the clinician when diagnosing family members who may present with two different disorders closely mimicking one another.     

Late evening snack: exploiting a period of anabolic opportunity in cirrhosis

Background and Aim: Cirrhosis is a state of accelerated starvation with impaired protein synthesis. Increased rate of gluconeogenesis and alterations in skeletal muscle signaling pathways result in anabolic resistance and consequent loss of muscle mass or sarcopenia in cirrhosis. Late evening snack (LES) is an intervention to reduce the postabsorptive (fasting) phase with the potential to improve substrate utilization and reverse sarcopenia. Published reports were evaluated to examine the effect of LES on regulation of substrate utilization (short‐term studies) and nutritional outcomes (long‐term studies). Methods: PubMed, EMBASE, Google scholar and OVID databases were searched. All studies published on LES in cirrhosis were included. Studies that included few (n < 3) subjects and patients with hepatocellular carcinoma were excluded. Results: Late evening snack decreased lipid oxidation and improved nitrogen balance, irrespective of the composition or type of formulation used. Daytime isocaloric isonitrogenous snacks did not have the metabolic or clinical benefit of LES. LES decreased skeletal muscle proteolysis. No studies have examined its effect on muscle protein synthesis. There was inconsistent translation into an increase in lean body or skeletal muscle mass. Improved quality of life occurs but decreased mortality or need for transplantation has not been reported. The optimal composition of LES has not been defined, but based on mechanistic considerations, a branched chain supplemented LES holds most promise. Conclusions: Late evening snack holds the most promise as an intervention to reverse anabolic resistance and sarcopenia of cirrhosis with improved quality of life in patients with cirrhosis. Long term benefit and improved survival need critical evaluation.