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Atomic force microscopy, AFM, is a powerful tool that can produce detailed topographical images of individual nano-structures with a high signal-to-noise ratio without the need for ensemble averaging. However, the application of AFM in structural biology has been hampered by the tip-sample convolution effect, which distorts images of nano-structures, particularly those that are of similar dimensions to the cantilever probe tips used in AFM. Here we show that the tip-sample convolution results in a feature-dependent and non-uniform distribution of image resolution on AFM topographs. We show how this effect can be utilised in structural studies of nano-sized upward convex objects such as spherical or filamentous molecular assemblies deposited on a flat surface, because it causes ‘magnification’ of such objects in AFM topographs. Subsequently, this enhancement effect is harnessed through contact-point based deconvolution of AFM topographs. Here, the application of this approach is demonstrated through the 3D reconstruction of the surface envelope of individual helical amyloid filaments without the need of cross-particle averaging using the contact-deconvoluted AFM topographs. Resolving the structural variations of individual macromolecular assemblies within inherently heterogeneous populations is paramount for mechanistic understanding of many biological phenomena such as amyloid toxicity and prion strains. The approach presented here will also facilitate the use of AFM for high-resolution structural studies and integrative structural biology analysis of single molecular assemblies.

Background: Numerous studies have addressed obsessive- compulsive features in adults with anorexia nervosa (AN), but few have been conducted with younger patients. The aim of this study was to describe the frequency and severity of obsessive-compulsive disorder (OCD) symptoms and obsessive-compulsive personality (OCP) traits, and to explore the relationships between AN, OCD symptoms and OCP traits in young people.Method: Forty-nine children and adolescents with AN completed measures assessing eating disorder psychopathology, OCD symptoms, OCP traits and perfectionism.Results: Fifty-one per cent displayed clinically significant levels of OCD symptoms and 16% clinically significant OCP traits. Statistically significant positive relationships were found between AN and OCD symptoms and between OCD symptoms and OCP traits. However, no relationships were found between AN and OCP traits.Conclusion: This study suggests approximately half of young people with AN may have clinically significant OCD symptoms. Such findings indicate careful assessment for OCD is important in this group. Copyright © 2006 John Wiley & Sons, Ltd and Eating Disorders Association. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Research has suggested that a fundamental aspect of anorexia nervosa (AN) is its egosyntonic nature, the fact that it is often valued by individuals with the disorder. The current study describes the development of the P-CAN, a quantitative measure of both positive (valued) and negative aspects of AN. METHOD: Items were derived from a previous qualitative study (Serpell, Treasure, Teasdale, & Sullivan. 1999. International Journal of Eating Disorders, 25, 177-186). Data from 233 women with AN were subjected to a principal components analysis. RESULTS: Ten subscales were identified, six describing the pros of AN and four describing the cons of the illness. DISCUSSION: The P-CAN shows good psychometric properties and should prove a useful tool for the measurement of attitudes towards AN, as well as offer insights into the maintenance of the disorder. [ABSTRACT FROM AUTHOR]

Filamentous inclusions composed of the microtubule-associated protein tau are a defining characteristic of a large number of neurodegenerative diseases. Here we show that tau degradation in stably transfected and non-transfected SH-SY5Y cells is blocked by the irreversible proteasome inhibitor lactacystin. Further, we find that in vitro, natively unfolded tau can be directly processed by the 20S proteasome without a requirement for ubiquitylation, and that a highly reproducible pattern of degradation intermediates is readily detectable during this process. Analysis of these intermediates shows that 20S proteasomal processing of tau is bi-directional, proceeding from both N- and C-termini, and that populations of relatively stable intermediates arise probably because of less efficient digestion of the C-terminal repeat region. Our results are consistent with an in vivo role for the proteasome in tau degradation and support the existence of ubiquitin-independent pathways for the proteasomal degradation of unfolded proteins. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of the current study was to use a qualitative approach to investigate the attitude of people with bulimia nervosa (BN) to their illness. METHOD: Patients with BN were asked to write two letters to their bulimia, one addressing it as a friend and the other addressing it as an enemy. We used a coding scheme to classify themes in letters of people with anorexia nervosa (AN) to group together themes expressed by those with BN. We revised the coding scheme to include themes that were not present in the letters of people with AN. RESULTS: There were both similarities and differences in the themes described by AN and BN patients. Two positive themes (BN allowing the individuals to eat and not get fat and BN as a way of dealing with boredom) and two negative themes (shame or low self-esteem resulting from BN and obsessive thoughts of weight and shape) were added to the coding scheme to account for these differences. DISCUSSION: The positive and negative aspects of BN differ in some important ways from those expressed by patients with AN. The meaning of these differences is discussed with reference to the wider symptom pattern of BN compared with AN and their importance with reference to motivation for change is outlined. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study was to examine anorexics' attitudes towards anorexia nervosa. METHOD: Anorexic patients were asked to write two letters to their anorexia nervosa, one addressing it as a friend and the other addressing it as an enemy. A coding scheme was developed using a 'Grounded Theory' methodology to group recurrent themes. The scheme was used independently by three raters: the first author, a rater with extensive experience in eating disorders, and a novice in the field. Use of the coding scheme showed high interrater reliability and comprehensivess. RESULTS: Commonly expressed benefits of anorexia nervosa included feeling looked after or protected, gaining a sense of control, and feeling special. Perceived costs of the disorder included constant thoughts about food, feeling taken over, and the damage done to personal relationships. DISCUSSION: The positive themes found in the letters are important indicators of factors which may maintain anorexia nervosa. The use of the letters to examine these factors has important clinical implications which are outlined. [ABSTRACT FROM AUTHOR]

Research into the effects of calorie restriction continues to intrigue those interested in whether it may allow humans to live longer and healthier lives. Animal studies of continuous calorie restriction (CCR) and fasting have demonstrated substantial advantages to health and longevity. However, concerns remain about the impact of restricting calorie intake on human health and cognition. Given the emerging evidence of cognitive impairments in eating disorders, studies investigating restricted calorie intake in healthy humans (in an ethical way) may also have implications for understanding restrictive eating disorders. In this review, the published literature on the impact of CCR and fasting on cognitive function in healthy human participants is synthesized. Of the 33 studies of CCR and fasting in humans identified, 23 demonstrated significant changes in cognition. Despite variation across the cognitive domains, results suggest CCR benefits inhibition, processing speed, and working memory, but may lead to impairments in cognitive flexibility. The results of fasting studies suggest fasting is associated with impairments in cognitive flexibility and psychomotor abilities. Overall, the results of these studies suggest the degree (ie, the severity) of calorie restriction is what most likely predicts cognitive improvements as opposed to impairments. For individuals engaging in sustained restriction, this may have serious, irreversible consequences. However, there are mixed findings regarding the impact of CCR and fasting on this aspect of human functioning, suggesting further research is required to understand the costs and benefits of different types of calorie restriction., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute.)

Background: Many individuals perceive Anorexia Nervosa (AN) as a part of their personal identity. Externalisation of the problem is a practice that is often taken up within NICE recommended treatments for AN. Dominant understandings of externalisation are that this practice involves making the "problem" a separate entity, external to the individual. It is an attitude taken by the client and family, stimulated by the therapist to build engagement with treatment and supportive relationships around the individual. However, there is a paucity of research exploring the therapeutic effects of this approach. This research aims to address this gap by exploring the role of externalisation in treatment for AN to elicit an understanding of how this practice is experienced including how it can help and hinder recovery., Methods: Thirteen adults with a current and/or past diagnosis of AN participated in semi-structured interviews. This qualitative study used a reflexive thematic analysis., Analysis: Participants described their experience of externalisation as a journey which is depicted by four main themes. 'Separating the AN from the self' reflects the tensions inherent in learning to distinguish between one's perceived sense of "self" and "the AN". 'Making sense of the AN' describes the experience of language forms used to separate the AN from the individual's identity. 'Feeling seen, or unseen as a person beyond the AN' illustrates the helpful and harmful effects of externalising practices on relationships. 'Navigating a complex relationship with the AN' depicts the effects of one-, versus two-way externalisation on the individual's relationship to AN., Conclusions: The notion of separating one's internal dialogue from one's concept of self may initially be rejected by the individual experiencing AN. However, as the individual develops trust in the therapist and becomes socialised to common forms of externalising language, they may begin to realise two sides within them, a perceived "healthy self" and "the anorexia voice". However, social-cultural discourses around eating contribute to ambiguity during the differentiation between these two voices, thus elucidating the effects of an absence of problem deconstruction alongside externalisation within ED-focussed treatments. Externalising practices were most helpful when led by the individual using their own experience-near language and least helpful when they did not permit the individual to feel seen as a person beyond the AN. Therapists, treatment teams and family members should be cognisant of the emotional effects of language used to externalise AN. Importantly, they should ensure that externalisation is practiced within the spirit of narrative therapy from which it originates., (© 2024. The Author(s).)

Background: Autistic women are at high risk of developing restrictive eating disorders (REDs), such as anorexia nervosa., Aims: This study provides an overview of the clinical characteristics of autistic women with REDs to (i) enhance understanding of increased risk, and (ii) support the identification of autistic women in eating disorder services., Method: We compared self-reported autistic and disordered eating characteristics of: autistic participants with REDs (Autism + REDs; n = 57); autistic participants without REDs (Autism; n = 69); and women with REDs who are not autistic (REDs; n = 80). We also included a group of women with high autistic traits (HATs) and REDs, but no formal autism diagnosis (HATs + REDs; n = 38)., Results: Autism + REDs participants scored similarly to Autism participants in terms of autistic characteristics and to REDs participants in terms of experiencing traditional disordered eating symptoms. Autism + REDs participants were distinguished from both groups by having more restricted and repetitive behaviours and autism-specific eating behaviours related to sensory processing, flexibility and social differences. HATs + REDs participants showed a similar pattern of scores to Autism + REDs participants, and both also presented with high levels of co-occurring mental health difficulties, particularly social anxiety., Conclusion: The presentation of autistic women with REDs is complex, including both traditional disordered eating symptoms and autism-related needs, as well as high levels of co-occurring mental health difficulties. In eating disorder services, the REDs presentation of autistic women and those with HATs should be formulated with reference to autism-specific eating behaviours and co-occurring difficulties. Treatment adaptations should be offered to accommodate autistic characteristics and related needs.

Objective: To synthesise young person and family member perspectives on processes of change in family therapy for anorexia nervosa (AN), including systemic family therapy and manualised family-based treatments, to obtain an understanding of what helps and hinders positive change., Method: A systematic search of the literature was conducted to identify qualitative studies focussing on experiences of therapeutic change within family therapies for AN from the perspectives of young people and their families. Fifteen studies met inclusion criteria and underwent quality appraisal following which they were synthesised using a meta-synthesis approach., Results: Six overarching themes were generated: "A holistic focus on the young person's overall development"; "The therapeutic relationship as a vehicle for change"; "The therapist's confinement to a script and its impact on emotional attunement"; "A disempowering therapeutic context"; "Externalisation of the eating disorder (ED)"; and "The importance of family involvement". Positive change was helped by understanding and support given to the young person's overall development including their psychological, emotional, social and physical wellbeing, positive therapeutic relationships, relational containment within the family system and externalising conversations in which young people felt seen and heard. Positive change was hindered by inflexibility in the treatment approach, counter-effects of externalisation, negative experiences of the therapist, a narrow focus on food-intake and weight, as well as the neglect of family difficulties, emotional experiences, and psychological factors., Conclusions: Positive change regarding the young person's eating-related difficulties ensued in the context of positive relational changes between the young person, their family members, the therapist and treatment team, highlighting the significance of secure and trusting relationships. The findings of this review can be utilised by ED services to consider how they may adapt to the needs of young people and their families in order to improve treatment satisfaction, treatment outcomes, and in turn reduce risk for chronicity in AN., (© 2024. The Author(s).)

Coronavirus disease 2019 (COVID-19) was initially considered a primarily respiratory disease but is now known to affect other organs including the heart and brain. A major route by which COVID-19 impacts different organs is via the vascular system. We studied the impact of apolipoprotein E (APOE) genotype and inflammation on vascular infectivity by pseudo-typed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viruses in mouse and human cultured endothelial cells and pericytes. Possessing the APOE4 allele or having existing systemic inflammation is known to enhance the severity of COVID-19. Using targeted replacement human APOE3 and APOE4 mice and inflammation induced by bacterial lipopolysaccharide (LPS), we investigated infection by SARS-CoV-2. Here, we show that infectivity was higher in murine cerebrovascular pericytes compared to endothelial cells and higher in cultures expressing APOE4. Furthermore, increasing the inflammatory state of the cells by prior incubation with LPS increased infectivity into human and mouse pericytes and human endothelial cells. Our findings provide insights into the mechanisms underlying severe COVID-19 infection, highlighting how risk factors such as APOE4 genotype and prior inflammation may exacerbate disease severity by augmenting the virus's ability to infect vascular cells.

Background: Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse., Methods: STORY follows 720 young people aged 16-25 with EDs and 120 healthy controls for 12 months. Online self-report questionnaires regularly assess ED symptoms, psychiatric comorbidities, quality of life, and socioeconomic environment. Additional ongoing monitoring using multi-parametric RMT via smartphones and wearable smart rings ('Ōura ring') unobtrusively measures individuals' daily behaviour and physiology (e.g., Bluetooth connections, sleep, autonomic arousal). A subgroup of participants completes additional in-person cognitive and neuroimaging assessments at study-baseline and after 12 months., Discussion: By leveraging these large-scale longitudinal data from participants across ED diagnoses and illness durations, the STORY study seeks to elucidate potential biopsychosocial predictors of outcome, their interplay with developmental and socioemotional changes, and barriers and facilitators of recovery. STORY holds the promise of providing actionable findings that can be translated into clinical practice by informing the development of both early intervention and personalised treatment that is tailored to illness stage and individual circumstances, ultimately disrupting the long-term burden of EDs on individuals and their families., (© 2024. The Author(s).)

Aims and Method: In response to recommendations for improving the quality and coordination of care delivered by eating disorder services, a whole-team training programme was commissioned by Health Education England in 2020. This paper describes the development and evaluation of the Eating Disorder Services for Adults (EDSA) whole-team training course, delivered to National Health Service adult eating disorder community teams in England. Course participants ( n = 561) in the first two EDSA training cohorts (2021 and 2022) were asked to complete questionnaires at intake and after each session, asking about their views on the training., Results: All course aspects were rated as highly enjoyable, meeting participants' training needs and fostering reflective practice. Thematic analysis identified themes relating to key innovative features of the course and suggestions for improvements., Clinical Implications: Preliminary evaluation suggests that EDSA is valued by clinicians to enhance their knowledge, skills and ability to improve eating disorder patient care.

Objective: There is a lack of reliable and valid parent-report measures assessing eating disorder (ED) pathology in children and adolescents. This study aimed to develop and provide preliminary validation of a new parent-report measure, the 12-item Eating Disorder Examination Questionnaire-Short Parent Version (EDE-QS-P)., Method: The EDE-QS-P was completed by 296 parents seeking treatment for their child at an ED clinic. Children (ages 6-18, N  = 296) completed the Eating Disorder Examination-Questionnaire (EDE-Q), the seven-item Generalized Anxiety Disorder Questionnaire (GAD-7), and the nine-item Patient Health Questionnaire (PHQ-9)., Results: After removing item 10, the 11-item version of the EDE-QS-P showed borderline adequate fit to the one factor solution and strong internal consistency (α = 0.91). This measure also demonstrated strong convergent validity with child scores on the EDE-Q ( r  = .69), and moderate convergent validity with child scores on the GAD-7 ( r  = .37) and PHQ-9 ( r  = .46). The EDE-QS-P was able to differentiate children with EDs characterized by body image disturbances (e.g. anorexia nervosa) from those with avoidant/restrictive food intake disorder, who do not experience shape or weight concerns., Discussion: The 11-item EDE-QS-P may be a promising parent-report measure of ED pathology in children and adolescents.

Anorexia nervosa-focussed family therapy (FT-AN) is the first-line treatment for adolescent anorexia nervosa (AN), but the predictors of poor treatment response are not well understood. The main aim of this study was to investigate the role of attachment and mentalization in predicting treatment outcome. The secondary aims of the study were to investigate therapeutic alliance at 1 month as a predictor of outcome, and to test the associations between alliance and baseline attachment and mentalization. 192 adolescents with AN and their parents were recruited as they began family therapy in out-patient specialist eating disorder services. Self-report measures of attachment, mentalization, and emotion regulation were completed at the start of treatment by adolescent patients and one of their parents. Self-reported alliance scores were collected at one month. Higher scores on the Certainty Scale of the Reflective Functioning Questionnaire, completed by parents, which indicate over-certainty about mental states, were the strongest predictor of poor outcome (Odds Ratio: 0.42, CI: 0.20-0.87). Similarly, for adolescents, higher Lack of Clarity scores on the Difficulties in Emotion Regulation Scale, representing being unclear about one's feelings, were predictive of positive treatment outcome (OR: 1.10, CI: 1.00-1.21). Higher alliance scores at 1 month predicted positive outcome, and were associated with attachment security and mentalization. These novel findings suggest that, particularly in parents, a tendency towards excessive certainty about mental states in others may predict poor outcome in FT-AN. Further research is warranted to replicate the finding and characterise families at risk of poor outcome., (© 2021. The Author(s).)

Objective: This paper outlines the evidence base for early intervention for eating disorders; provides a global overview of how early intervention for eating disorders is provided in different regions and settings; and proposes policy, service, clinician and research recommendations to progress early intervention for eating disorders., Method and Results: Currently, access to eating disorder treatment often takes many years or does not occur at all. This is despite neurobiological, clinical and socioeconomic evidence showing that early intervention may improve outcomes and facilitate full sustained recovery from an eating disorder. There is also considerable variation worldwide in how eating disorder care is provided, with marked inequalities in treatment provision. Despite these barriers, there are existing evidence-based approaches to early intervention for eating disorders and progress is being made in scaling these., Conclusions: We propose action steps for the field that will transform eating disorder service provision and facilitate early detection, treatment and recovery for everyone affected by eating disorders, regardless of age, socioeconomic status and personal characteristics., (© 2022 The Authors. European Eating Disorders Review published by Eating Disorders Association and John Wiley & Sons Ltd.)