Exploring the impact of the COVID-19 pandemic and UK lockdown on individuals with experience of eating disorders

Background The coronavirus disease 2019 (COVID-19) pandemic may raise unique challenges for individuals with experience of eating disorders. Many factors have potential for detrimental impacts on psychological wellbeing and eating disorder recovery, including: Disruption to living situations, ‘social distancing’ restrictions, difficult access to healthcare, and societal changes to food behaviours and technology usage. To date, little is known on the impact of the pandemic on this population, particularly within the UK. Method A mixed-methods online survey was developed for the purpose of this study. Data was collected from 129 individuals currently experiencing, or in recovery from, an eating disorder during the early stages of the UK pandemic lockdown. Participants were aged between 16 and 65 years, with 121 participants identifying as female, 7 male and 1 participant preferring not to disclose their gender. Results Findings suggest that the pandemic is having a profound, negative impact upon individuals with experience of eating disorders. Eight key themes were generated: Disruption to living situation, increased social isolation and reduced access to usual support networks, changes to physical activity rates, reduced access to healthcare services, disruption to routine and perceived control, changes to relationship with food, increased exposure to triggering messages, and positive outcomes. The results suggest detrimental impacts on psychological wellbeing including decreased feelings of control, increased feelings of social isolation, increased rumination about disordered eating, and low feelings of social support. Conclusions Individuals with eating disorders are at significant risk of negative impacts of the pandemic. There is a vital need for interventions to support this population. Inequalities in healthcare provision were identified, emphasising a need for a more cohesive approach to remote treatment across UK healthcare services. Positive aspects of technology use were identified but the results suggest a need to address and/or limit the potential for negative impacts of public messages around food and exercise behaviours, and to co-design technologies with end-users to facilitate effective treatment

Beyond BMI for self-estimates of body size and shape: A new method for developing stimuli correctly calibrated for body composition

Accurate self-assessment of body shape and size plays a key role in the prevention, diagnosis, and treatment of both obesity and eating disorders. These chronic conditions cause significant health problems, reduced quality of life, and represent a major problem for health services. Variation in body shape depends on two aspects of composition: adiposity and muscularity. However, most self-assessment tools are unidimensional. They depict variation in adiposity only, typically quantified by the body mass index. This can lead to substantial, and clinically meaningful, errors in estimates of body shape and size. To solve this problem, we detail a method of creating biometrically valid body stimuli. We obtained high-resolution 3D body shape scans and composition measures from 397 volunteers (aged 18–45 years) and produced a statistical mapping between the two. This allowed us to create 3D computer-generated models of bodies, correctly calibrated for body composition (i.e., muscularity and adiposity). We show how these stimuli, whose shape changes are based on change in composition in two dimensions, can be used to match the body size and shape participants believe themselves to have, to the stimulus they see. We also show how multivariate multiple regression can be used to model shape change predicted by these 2D outcomes, so that participants’ choices can be explained by their measured body composition together with other psychometric variables. Together, this approach should substantially improve the accuracy and precision with which self-assessments of body size and shape can be made in obese individuals and those suffering from eating disorders

Novel H6PDH mutations in two girls with premature adrenarche: 'apparent' and 'true' CRD can be differentiated by urinary steroid profiling.

Inactivating mutations in the enzyme hexose-6-phosphate dehydrogenase (H6PDH, encoded by H6PD) cause apparent cortisone reductase deficiency (ACRD). H6PDH generates cofactor NADPH for 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1, encoded by HSD11B1) oxo-reductase activity, converting cortisone to cortisol. Inactivating mutations in HSD11B1 cause true cortisone reductase deficiency (CRD). Both ACRD and CRD present with hypothalamic-pituitary-adrenal (HPA) axis activation and adrenal hyperandrogenism. To describe the clinical, biochemical and molecular characteristics of two additional female children with ACRD and to illustrate the diagnostic value of urinary steroid profiling in identifying and differentiating a total of six ACRD and four CRD cases. Clinical, biochemical and genetic assessment of two female patients presenting during childhood. In addition, results of urinary steroid profiling in a total of ten ACRD/CRD patients were compared to identify distinguishing characteristics. Case 1 was compound heterozygous for R109AfsX3 and a novel P146L missense mutation in H6PD. Case 2 was compound heterozygous for novel nonsense mutations Q325X and Y446X in H6PD. Mutant expression studies confirmed loss of H6PDH activity in both cases. Urinary steroid metabolite profiling by gas chromatography/mass spectrometry suggested ACRD in both cases. In addition, we were able to establish a steroid metabolite signature differentiating ACRD and CRD, providing a basis for genetic diagnosis and future individualised management. Steroid profile analysis of a 24-h urine collection provides a diagnostic method for discriminating between ACRD and CRD. This will provide a useful tool in stratifying unresolved adrenal hyperandrogenism in children with premature adrenarche and adult females with polycystic ovary syndrome (PCOS)

Structure-guided design of a domain-selective bromodomain and extra terminal N-terminal bromodomain chemical probe

Small molecule mediated disruption of the protein-protein interactions between acetylated histone tails and the tandem bromodomains of the bromodomain and extra terminal (BET) family of proteins is an important mechanism of action for the potential modulation of immuno-inflammatory and oncology disease. High quality chemical probes have proven invaluable in elucidating profound BET bromodomain biology, with seminal publications of both pan- and domain-selective BET family bromodomain inhibitors enabling academic and industrial research. To enrich the toolbox of structurally differentiated N-terminal bromodomain (BD1) BET family chemical probes, this work describes an analysis of the GSK BRD4 bromodomain dataset through a lipophilic efficiency lens, which enabled identification of a BD1 domain biased benzimidazole series. Structure guided growth targeting a key Asp/His BD1/BD2 switch enabled delivery of GSK023, a high-quality chemical probe with 300–1000-fold BET BD1 domain selectivity and a phenotypic cellular fingerprint consistent with BET bromodomain inhibition