Treatment considerations for compulsive exercise in high-performance athletes with an eating disorder

Compulsive exercise is linked with poorer treatment outcomes in people with eating disorder (EDs). High-performance athletes represent a growing and complex subcomponent of the broader ED population, and emergent evidence indicates that different conceptualisations of compulsive exercise are needed in this population. Existing randomised controlled trials in ED populations have demonstrated small treatment effects on compulsive exercise compared with control groups; however, athletes were sparsely sampled across these studies. Thus, the extent to which current treatments for compulsive exercise in EDs are also effective in high-performance athletes is unknown. For this opinion paper, we sought representation from high-performance sports leadership, someone with lived experience of both an ED and high-performance athletics, and ED clinical experts. We discuss the utility of recommending exercise abstinence in ED treatment with athletes, as well as a number of other treatment strategies with some evidence in other contexts for further consideration and research in this population. These include using mindfulness-based interventions as an adjunct to cognitive-behavioural therapies, using wearable technologies and self-reported fatigue to inform training decisions, and incorporating greater exercise variation into training programs. We also offer practical considerations for clinicians seeking to apply foundational elements of cognitive-behavioural interventions (e.g., exposure and response prevention, cognitive restructuring, behavioural experiments) into an ED treatment program for a high-performance athlete. Future research is needed to examine characteristics of pathological compulsive exercise in athletes and whether available treatments are both feasible and effective in the treatment of compulsive exercise in athletes with an ED

Triple Bioluminescence Imaging for In Vivo Monitoring of Cellular Processes

Bioluminescence imaging (BLI) has shown to be crucial for monitoring in vivo biological processes. So far, only dual bioluminescence imaging using firefly (Fluc) and Renilla or Gaussia (Gluc) luciferase has been achieved due to the lack of availability of other efficiently expressed luciferases using different substrates. Here, we characterized a codon-optimized luciferase from Vargula hilgendorfii (Vluc) as a reporter for mammalian gene expression. We showed that Vluc can be multiplexed with Gluc and Fluc for sequential imaging of three distinct cellular phenomena in the same biological system using vargulin, coelenterazine, and D-luciferin substrates, respectively. We applied this triple imaging system to monitor the effect of soluble tumor necrosis factor-related apoptosis-inducing ligand (sTRAIL) delivered using an adeno-associated viral vector (AAV) on brain tumors in mice. Vluc imaging showed efficient sTRAIL gene delivery to the brain, while Fluc imaging revealed a robust antiglioma therapy. Further, nuclear factor-κB (NF-κB) activation in response to sTRAIL binding to glioma cells death receptors was monitored by Gluc imaging. This work is the first demonstration of trimodal in vivo bioluminescence imaging and will have a broad applicability in many different fields including immunology, oncology, virology, and neuroscience

A study of the norcaradiene-cycloheptatriene equilibrium in a series of azulenones by NMR spectroscopy; the impact of substitution on the position of equilibrium

A systematic investigation of the influence of substitution at positions C-2 and C-3 on the azulenone skeleton, based on NMR characterisation, is discussed with particular focus on the impact of the steric and electronic characteristics of substituents on the position of the norcaradiene-cycloheptatriene (NCD-CHT) equilibrium. Variable temperature (VT) NMR studies, undertaken to enable the resolution of signals for the equilibrating valence tautomers revealed, in addition, interesting shifts in the equilibrium

On the Functional Relationship Between Fluorescence and Photochemical Yields in Complex Evergreen Needleleaf Canopies

Recent advancements in understanding remotely sensed solar‐induced chlorophyll fluorescence often suggest a linear relationship with gross primary productivity at large spatial scales. However, the quantum yields of fluorescence and photochemistry are not linearly related, and this relationship is largely driven by irradiance. This raises questions about the mechanistic basis of observed linearity from complex canopies that experience heterogeneous irradiance regimes at subcanopy scales. We present empirical data from two evergreen forest sites that demonstrate a nonlinear relationship between needle‐scale observations of steady‐state fluorescence yield and photochemical yield under ambient irradiance. We show that accounting for subcanopy and diurnal patterns of irradiance can help identify the physiological constraints on needle‐scale fluorescence at 70–80% accuracy. Our findings are placed in the context of how solar‐induced chlorophyll fluorescence observations from spaceborne sensors relate to diurnal variation in canopy‐scale physiology

Identifying factors which influence eating disorder risk during behavioral weight management: A consensus study

This study aimed to understand clinician, researcher and consumer views regarding factors which influence eating disorder (ED) risk during behavioral weight management, including individual risk factors, intervention strategies and delivery features. Eighty-seven participants were recruited internationally through professional and consumer organizations and social media and completed an online survey. Individual characteristics, intervention strategies (5-point scale) and delivery features (important/unimportant/unsure) were rated. Participants were mostly women (n = 81), aged 35-49 y, from Australia or United States, were clinicians and/or reported lived experience of overweight/obesity and/or ED. There was agreement (64% to 99%) that individual characteristics were relevant to ED risk, with history of ED, weight-based teasing/stigma and weight bias internalization having the highest agreement. Intervention strategies most frequently rated as likely to increase ED risk included those with a focus on weight, prescription (structured diets, exercise plans) and monitoring strategies, e.g., calorie counting. Strategies most frequently rated as likely to decrease ED risk included having a health focus, flexibility and inclusion of psychosocial support. Delivery features considered most important were who delivered the intervention (profession, qualifications) and support (frequency, duration). Findings will inform future research to quantitatively assess which of these factors predict eating disorder risk, to inform screening and monitoring protocols

Efficacy, Safety, and Durability of Voretigene Neparvovec-rzyl in RPE65 Mutation–Associated Inherited Retinal Dystrophy: Results of Phase 1 and 3 Trials

Purpose: To report the durability of voretigene neparvovec-rzyl (VN) adeno-associated viral vector–based gene therapy for RPE65 mutation–associated inherited retinal dystrophy (IRD), including results of a phase 1 follow-on study at year 4 and phase 3 study at year 2. Design: Open-label phase 1 follow-on clinical trial and open-label, randomized, controlled phase 3 clinical trial. Participants: Forty subjects who received 1.5×1011 vector genomes (vg) of VN per eye in at least 1 eye during the trials, including 11 phase 1 follow-on subjects and 29 phase 3 subjects (20 original intervention [OI] and 9 control/intervention [CI]). Methods: Subretinal injection of VN in the second eye of phase 1 follow-on subjects and in both eyes of phase 3 subjects. Main Outcome Measures: End points common to the phase 1 and phase 3 studies included change in performance on the Multi-Luminance Mobility Test (MLMT) within the illuminance range evaluated, full-field light sensitivity threshold (FST) testing, and best-corrected visual acuity (BCVA). Safety end points included adverse event reporting, ophthalmic examination, physical examination, and laboratory testing. Results: Mean (standard deviation) MLMT lux score change was 2.4 (1.3) at 4 years compared with 2.6 (1.6) at 1 year after administration in phase 1 follow-on subjects (n = 8), 1.9 (1.1) at 2 years, and 1.9 (1.0) at 1 year post-administration in OI subjects (n = 20), and 2.1 (1.6) at 1 year post-administration in CI subjects (n = 9). All 3 groups maintained an average improvement in FST, reflecting more than a 2 log10(cd.s/m2) improvement in light sensitivity at 1 year and subsequent available follow-up visits. The safety profile was consistent with vitrectomy and the subretinal injection procedure, and no deleterious immune responses occurred. Conclusions: After VN gene augmentation therapy, there was a favorable benefit-to-risk profile with similar improvement demonstrated in navigational ability and light sensitivity among 3 groups of subjects with RPE65 mutation–associated IRD, a degenerative disease that progresses to complete blindness. The safety profile is consistent with the administration procedure. These data suggest that this effect, which is nearly maximal by 30 days after VN administration, is durable for 4 years, with observation ongoing