Patients' experiences of brief cognitive behavioral therapy for eating disorders: A qualitative investigation

Objective Although it is important to analyze the effectiveness of new therapies, it is also necessary to consider how patients experience them. This is particularly important if we are to maximize treatment acceptability and reduce attrition. This study examined patient experiences of a new 10‐session cognitive‐behavioral therapy (CBT‐T), using a qualitative approach. Method The sample was 17 patients with a diagnosis of bulimia nervosa who had received CBT‐T (including treatment completers and non‐completers) within the previous 2 years. Sample size was determined by saturation of the emergent themes. Responses were analyzed using a six‐step thematic analysis process. Results Rated acceptability and effectiveness of CBT‐T were high. Five themes emerged, with subthemes. The key elements of patient experience of the therapy were: the therapeutic relationship; the nature of the therapy; its challenging but beneficial aspects; ending therapy; and the overall experience of CBT‐T (including comparison with other therapies). Discussion The findings build on the effectiveness research for CBT‐T, suggesting that it is an acceptable therapy that addresses many of the same themes that matter to patients as other therapies. The findings show that patients were positive about CBT‐T relative to other therapies, and offer suggestions as to how CBT‐T might be delivered to emphasize the importance of the time‐limited nature of the therapy

Complexity in eating disorders: A case for simple or complex formulation and treatment?

© British Association for Behavioural and Cognitive Psychotherapies 2017. Eating disorders are commonly regarded as complex psychiatric conditions, although this perception might be a product of the high levels of physical and psychological co-morbidity that are present in many such cases, rather than being about complexity in the eating disorder per se. This paper will consider the reasons that eating disorders are seen as complex, and whether or not that perceived complexity should be seen as a genuine reason to deviate from existing evidence-based cognitive behavioural therapy (CBT) protocols. Case examples will be used to illustrate how complex presentations can require clinicians to work skilfully with relatively simple formulations to achieve the best outcome, rather than using unnecessarily complex formulations and treatments. The importance of clear supervision is also stressed, as it can play a role in clinicians' perception of the need for a complex or simple formulation, it can support the clinician in developing a collaborative, focused and efficient formulation, and it can keep the clinician on track with an evidence-based CBT approach

Clinicians' concerns about delivering cognitive-behavioural therapy for eating disorders

Despite research supporting the effectiveness of evidence-based interventions in the treatment of eating disorders, those interventions are under-utilised in routine clinical practice, possibly due to clinicians' concerns about delivering the relevant techniques. This study examined what elements of therapy clinicians worry about when delivering cognitive-behavioural therapy (CBT) for the eating disorders, and what clinician variables are associated with such concerns. The participants were 113 clinicians who used individual CBT with eating disorder patients. They completed a novel measure of concerns about delivering elements of CBT, as well as demographic characteristics and a standardised measure of intolerance of uncertainty. Clinicians worried most about body image work and ending treatment, but least about delivering psychoeducation. Their concerns fell into four distinct factors. Older, more experienced clinicians worried less about delivering the CBT techniques, but those with greater levels of prospective and inhibitory anxiety worried more about specific factors in the CBT techniques. Clinicians' capacity to tolerate uncertainty might impair their delivery of evidence-based CBT, and merits consideration as a target in training and supervision of CBT clinicians

Structural basis for the RING catalyzed synthesis of K63 linked ubiquitin chains

This work was supported by grants from Cancer Research UK (C434/A13067), the Wellcome Trust (098391/Z/12/Z) and Biotechnology and Biological Sciences Research Council (BB/J016004/1).The RING E3 ligase catalysed formation of lysine 63 linked ubiquitin chains by the Ube2V2–Ubc13 E2 complex is required for many important biological processes. Here we report the structure of the RING domain dimer of rat RNF4 in complex with a human Ubc13~Ub conjugate and Ube2V2. The structure has captured Ube2V2 bound to the acceptor (priming) ubiquitin with Lys63 in a position that could lead to attack on the linkage between the donor (second) ubiquitin and Ubc13 that is held in the active “folded back” conformation by the RING domain of RNF4. The interfaces identified in the structure were verified by in vitro ubiquitination assays of site directed mutants. This represents the first view of the synthesis of Lys63 linked ubiquitin chains in which both substrate ubiquitin and ubiquitin-loaded E2 are juxtaposed to allow E3 ligase mediated catalysis.PostprintPeer reviewe

Expanded Interactome of the Intrinsically Disordered Protein Dss1

Summary: Dss1 (also known as Sem1) is a conserved, intrinsically disordered protein with a remarkably broad functional diversity. It is a proteasome subunit but also associates with the BRCA2, RPA, Csn12-Thp1, and TREX-2 complexes. Accordingly, Dss1 functions in protein degradation, DNA repair, transcription, and mRNA export. Here in Schizosaccharomyces pombe, we expand its interactome further to include eIF3, the COP9 signalosome, and the mitotic septins. Within its intrinsically disordered ensemble, Dss1 forms a transiently populated C-terminal helix that dynamically interacts with and shields a central binding region. The helix interfered with the interaction to ATP-citrate lyase but was required for septin binding, and in strains lacking Dss1, ATP-citrate lyase solubility was reduced and septin rings were more persistent. Thus, even weak, transient interactions within Dss1 may dynamically rewire its interactome. : Schenstrøm et al. demonstrate that the disordered protein Dss1 forms a transient intramolecular interaction between the C-terminal helical region and a central hydrophobic region. Proteomics reveal several Dss1-binding proteins, including all PCI-domain protein complexes. The dynamic fold-back structure regulates Dss1 interactions with the mitotic septins and ATP-citrate lyase. Keywords: intrinsically disordered proteins, protein degradation, proteasome, PCI domai

SUMO chain formation is required for response to replication arrest in S. pombe

SUMO is a ubiquitin-like protein that is post-translationally attached to one or more lysine residues on target proteins. Despite having only 18% sequence identity with ubiquitin, SUMO contains the conserved betabetaalphabetabetaalphabeta fold present in ubiquitin. However, SUMO differs from ubiquitin in having an extended N-terminus. In S. pombe the N-terminus of SUMO/Pmt3 is significantly longer than those of SUMO in S. cerevisiae, human and Drosophila. Here we investigate the role of this N-terminal region. We have used two dimensional gel electrophoresis to demonstrate that S. pombe SUMO/Pmt3 is phosphorylated, and that this occurs on serine residues at the extreme N-terminus of the protein. Mutation of these residues (in pmt3-1) results in a dramatic reduction in both the levels of high Mr SUMO-containing species and of total SUMO/Pmt3, indicating that phosphorylation of SUMO/Pmt3 is required for its stability. Despite the significant reduction in high Mr SUMO-containing species, pmt3-1 cells do not display an aberrant cell morphology or sensitivity to genotoxins or stress. Additionally, we demonstrate that two lysine residues in the N-terminus of S. pombe SUMO/Pmt3 (K14 and K30) can act as acceptor sites for SUMO chain formation in vitro. Inability to form SUMO chains results in aberrant cell and nuclear morphologies, including stretched and fragmented chromatin. SUMO chain mutants are sensitive to the DNA synthesis inhibitor, hydroxyurea (HU), but not to other genotoxins, such as UV, MMS or CPT. This implies a role for SUMO chains in the response to replication arrest in S. pomb

Operationalising learning from rare events: framework for middle humanitarian operations managers

The purpose of this paper is to investigate the learning from rare events and the knowledge management processinvolved, which presents a significant challenge to many organizations. This is primarily attributed to the inability tointerpret these events in a systematic and “rich” manner, which this paper seeks to address. We start by summarizing therelevant literature on humanitarian operations management (HOM), outlining the evolution of the socio-technical disasterlifecycle and its relationship with humanitarian operations, using a supply chain resilience theoretical lens. We then out-line theories of organizational learning (and unlearning) from disasters and the impact on humanitarian operations. Subse-quently, we theorize the role of middle managers in humanitarian operations, which is the main focus of our paper. Themain methodology incorporates a hybrid of two techniques for root cause analysis, applied to two related case studies.The cases were specifically selected as, despite occurring twenty years apart, there are many similarities in the chain ofcausation and supporting factors, potentially suggesting that adequate learning from experience and failures is not occur-ring. This provides a novel learning experience within the HOM paradigm. Hence, the proposed approach is based on amultilevel structure that facilitates the operationalization of learning from rare events in humanitarian operations. Theresults show that we are able to provide an environment for multiple interpretations and effective learning, with emphasison middle managers within a humanitarian operations and crisis/disaster management context

Global Reprogramming of Host SUMOylation during Influenza Virus Infection

Dynamic nuclear SUMO modifications play essential roles in orchestrating cellular responses to proteotoxic stress, DNA damage, and DNA virus infection. Here,we describe a non-canonical host SUMOylation response to the nuclear-replicating RNA pathogen, influenza virus, and identify viral RNA polymerase activity as a major contributor to SUMO proteome re-modeling. Using quantitative proteomics to compare stress-induced SUMOylation responses, we reveal that influenza virus infection triggers unique re-targeting of SUMO to 63 host proteins involved in transcription, mRNA processing, RNA quality control, and DNA damage repair. This is paralleled by widespread host deSUMOylation. Depletion screening identified ten virus-induced SUMO targets as potential antiviral factors, including C18orf25 and the SMC5/6 and PAF1 complexes. Mechanistic studies further uncovered a role for SUMOylation of the PAF1 complex component, parafibromin (CDC73), in potentiating antiviral gene expression. Our global characterization of influenza virus-triggered SUMO redistribution provides a proteomic resource to understand host nuclear SUMOylation responses to infection

Structural insight into SUMO chain recognition and manipulation by the ubiquitin ligase RNF4

The small ubiquitin-like modifier (SUMO) can form polymeric chains that are important signals in cellular processes such as meiosis, genome maintenance and stress response. The SUMO-targeted ubiquitin ligase RNF4 engages with SUMO chains on linked substrates and catalyses their ubiquitination, which targets substrates for proteasomal degradation. Here we use a segmental labelling approach combined with solution nuclear magnetic resonance (NMR) spectroscopy and biochemical characterization to reveal how RNF4 manipulates the conformation of the SUMO chain, thereby facilitating optimal delivery of the distal SUMO domain for ubiquitin transfer