A vaccine targeting resistant tumours by dual T cell plus NK cell attack.

Most cancer vaccines target peptide antigens, necessitating personalization owing to the vast inter-individual diversity in major histocompatibility complex (MHC) molecules that present peptides to T cells. Furthermore, tumours frequently escape T cell-mediated immunity through mechanisms that interfere with peptide presentation1. Here we report a cancer vaccine that induces a coordinated attack by diverse T cell and natural killer (NK) cell populations. The vaccine targets the MICA and MICB (MICA/B) stress proteins expressed by many human cancers as a result of DNA damage2. MICA/B serve as ligands for the activating NKG2D receptor on T cells and NK cells, but tumours evade immune recognition by proteolytic MICA/B cleavage3,4. Vaccine-induced antibodies increase the density of MICA/B proteins on the surface of tumour cells by inhibiting proteolytic shedding, enhance presentation of tumour antigens by dendritic cells to T cells and augment the cytotoxic function of NK cells. Notably, this vaccine maintains efficacy against MHC class I-deficient tumours resistant to cytotoxic T cells through the coordinated action of NK cells and CD4+ T cells. The vaccine is also efficacious in a clinically important setting: immunization following surgical removal of primary, highly metastatic tumours inhibits the later outgrowth of metastases. This vaccine design enables protective immunity even against tumours with common escape mutations.

High-Throughput Synthesis and Evaluation of Antiviral Copolymers for Enveloped Respiratory Viruses.

COVID-19 made apparent the devastating impact viral pandemics have had on global health and order. Development of broad-spectrum antivirals to provide early protection upon the inevitable emergence of new viral pandemics is critical. In this work, antiviral polymers are discovered using a combination of high-throughput polymer synthesis and antiviral screening, enabling diverse polymer compositions to be explored. Amphipathic polymers, with ionizable tertiary amine groups, are the most potent antivirals, effective against influenza virus and SARS-CoV-2, with minimal cytotoxicity. It is hypothesized that these polymers interact with the viral membrane as they showed no activity against a nonenveloped virus (rhinovirus). The switchable chemistry of the polymers during endosomal acidification was evaluated using lipid monolayers, indicating that a complex synergy between hydrophobicity and ionization drives polymer-membrane interactions. This new high-throughput methodology can be adapted to continue to engineer the potency of the lead candidates or develop antiviral polymers against other emerging viral classes.

Real-world experience of maralixibat in Alagille syndrome: Novel findings outside of clinical trials.

OBJECTIVE: Maralixibat, an ileal bile acid transporter inhibitor, is the first drug approved by the U.S. Food and Drug Administration for the treatment of cholestatic pruritus in patients aged ≥3 months with Alagille syndrome (ALGS). Approval was based on reductions in pruritus from the pivotal ICONIC trial, information from two additional trials (ITCH and IMAGO), and long-term extension studies. Although participants in these trials met strict inclusion and exclusion criteria, patients have received maralixibat under broader circumstances as part of an expanded access program or commercially. The expanded access and postapproval settings inform a real-world understanding of effectiveness and safety. The objective was to report on the use of maralixibat in the real-world setting in eight patients who otherwise would not have met entrance criteria for the clinical trials, providing unique insights into its effectiveness in the management of ALGS. METHODS: We reviewed records of patients with ALGS who received maralixibat but would have been excluded from trials due to surgical biliary diversion, reduction of antipruritic/cholestatic concomitant medications, administration of medication through a gastrostomy or nasogastric tube, or use in patients under consideration for transplantation. RESULTS: Maralixibat appeared to be effective with reductions in pruritus compared to baseline. Consistent with clinical trials, maralixibat was well tolerated without appreciable gastrointestinal complications. Liver enzyme elevations were observed but were interpreted as consistent with normal fluctuations observed in ALGS, with no increases in bilirubin. CONCLUSION: Maralixibat may be effective and well tolerated in patients with ALGS in broader clinical contexts than previously reported.

Frailty identification and management among Brazilian healthcare professionals: a survey.

BACKGROUND: National and international guidelines on frailty assessment and management recommend frailty screening in older people. This study aimed to determine how Brazilian healthcare professionals (HCPs) identify and manage frailty in practice. METHODS: An anonymous online survey on the assessment and management of frailty was circulated virtually through HCPs across Brazil. RESULTS: Most of the respondants used non-specific criteria such as gait speed (45%), handgrip strength (37.6%), and comprehensive geriatric assessment (33.2%). The use of frailty-specific criteria was lower than 50%. The most frequently used criteria were the Frailty Index (19.1%), Frailty Phenotype (13.2%), and FRAIL (12.5%). Only 43.5% felt confident, and 40% had a plan to manage frailty. In the multivariate-adjusted models, training was the most crucial factor associated with assessing frailty, confidence, and having a management plan (p < 0.001 for all). Those with fewer years of experience were more likely to evaluate frailty (p = 0.009). Being a doctor increased the chance of using a specific tool; the opposite was true for dietitians (p = 0.03). Those who assisted more older people had a higher likelihood of having a plan (p = 0.011). CONCLUSION: Frailty assessment was heterogeneous among healthcare professions groups, predominantly using non-specific criteria. Training contributed to frailty assessment, use of specific criteria, confidence, and having a management plan. This data informs the need for standardized screening criteria and management plans for frailty, in association with increasing training at the national level for all the HCPs who assist older people.

Independent associations of food addiction and binge eating measures with real-time eating behaviors and contextual factors: An exploratory ecological momentary assessment study.

Food addiction (FA) is a concept centered around the addictive potential of highly palatable processed foods, though there is debate over the discriminative validity of FA as a distinct construct from binge-eating symptomatology. This study explored how trait measures of FA and binge-eating symptoms independently and interactively predicted eating behaviors and posited correlates of FA and binge eating measured via ecological momentary assessment (EMA). Adult participants (N = 49) who met the criteria for FA and/or binge-eating disorder completed baseline measures of FA (Yale Food Addiction Scale [YFAS 2.0]) and binge-eating symptoms (Eating Pathology Symptom Inventory [EPSI] binge eating scale) followed by a 10-day EMA protocol. Generalized linear mixed models examined the independent effects of YFAS 2.0, EPSI, and their interaction predicting EMA outcomes. Higher YFAS 2.0 symptom count scores were uniquely related to greater EMA-measured overeating, loss of control eating, negative and positive affect, and impulsivity when controlling for EPSI scores. Conversely, higher EPSI scores were uniquely related to greater EMA-measured eagerness and urge to eat, and expectancies that eating would improve mood. No interaction effects were significant. These results highlight potential distinctions between phenomena captured by FA and other measures of binge eating, in that FA symptoms may be a marker of heightened binge-eating severity, emotional arousal, and impulsivity.

Associations between affect dynamics and eating regulation in daily life: a preliminary ecological momentary assessment study.

Disordered eating behaviors consistently associated with emotion regulation difficulties. However, most studies have focused on affect intensity without considering dynamic affective patterns. We examined these patterns in relation to daily overeating, loss of control eating (LOCE), dietary restraint, and food craving in young adults using ecological momentary assessment (EMA).Adults (N = 24) completed a 10-day EMA protocol during which they reported momentary affect and eating patterns. Generalized linear mixed-models examined each index in relation to eating variable.Higher PA instability (within-person) was associated with higher ratings of binge-eating symptoms (B = 0.15, SE = 0.06, p = 0.007). Lower NA differentiation (within-person) was associated with higher levels of food craving (B = -10.11, SE = 4.74, p = 0.033).Our results support previous findings suggesting that acute fluctuations in PA may increase risk of binge-eating symptoms. Further, inability to differentiate between momentary states of NA was associated with cravings. This study highlights the importance of examining multiple facets of NA and PA in relation to eating regulation.Trial registration: ClinicalTrials.gov identifier: NCT02945475.

Momentary mechanisms of binge-eating symptoms using ecological momentary assessment: The moderating role of food addiction.

OBJECTIVE: Food addiction (FA) shows phenotypic and diagnostic overlap with eating disorders characterised by binge eating, though it is unknown how momentary processes driving binge-eating symptoms differ by FA. The present study examined the possible moderating influence of FA severity on momentary mechanisms underlying binge-eating symptomatology using ecological momentary assessment (EMA). METHOD: Adults (N = 49, mean age = 34.9 ± 12.1, cis-gender female = 77.1%) who met criteria for FA and/or binge-eating disorder completed baseline measures including the Yale Food Addiction Scale (YFAS) followed by a 10-day EMA protocol. Generalised linear mixed models assessed main effects of YFAS, momentary antecedents (affect, impulsivity, food cue exposure, appetite, and eating expectancies) and two-way interactions between YFAS and within-person antecedents. RESULTS: FA severity moderated momentary associations between food cue exposure and subsequent binge-eating symptoms: the association was stronger among participants with lower but not higher YFAS scores. No other interactions were significant. CONCLUSIONS: Some functional associations underlying binge-eating symptoms vary based on individuals' level of FA symptoms. Future research to further understand how observed associations may differ amongst diverse populations and over course of illness may also inform future prevention and interventions.

See One, Do One, Improve One's Wellness: Resident Autonomy in US General Surgery Programs, A Mixed-methods Study.

OBJECTIVE: We sought to examine the factors associated with resident perceptions of autonomy and to characterize the relationship between resident autonomy and wellness. BACKGROUND: Concerns exist that resident autonomy is decreasing, impacting competence. METHODS: Quantitative data were collected through a cross-sectional survey administered after the 2020 ABSITE. Qualitative data were collected through interviews and focus groups with residents and faculty at 15 programs. RESULTS: Seven thousand two hundred thirty-three residents (85.5% response rate) from 324 programs completed the survey. Of 5139 residents with complete data, 4424 (82.2%) reported appropriate autonomy, and these residents were less likely to experience burnout [odds ratio (OR) 0.69; 95% CI 0.58-0.83], suicidality (OR 0.69; 95% CI 0.54-0.89), and thoughts of leaving their programs (OR 0.45; 95% CI 0.37-0.54). Women were less likely to report appropriate autonomy (OR 0.81; 95% CI 0.68-0.97). Residents were more likely to report appropriate autonomy if they also reported satisfaction with their workload (OR 1.65; 95% CI 1.28-2.11), work-life balance (OR 2.01; 95% CI 1.57-2.58), faculty engagement (OR 3.55; 95% CI 2.86-4.35), resident camaraderie (OR 2.23; 95% CI, 1.78-2.79), and efficiency and resources (OR 2.37; 95% CI 1.95-2.88). Qualitative data revealed that (1) autonomy gives meaning to the clinical experience of residency, (2) multiple factors create barriers to autonomy, and (3) autonomy is not inherent to the training paradigm, requiring residents to learn behaviors to "earn" it. CONCLUSION: Autonomy is not considered an inherent part of the training paradigm such that residents can assume that they will achieve it. Resources to function autonomously should be allocated equitably to support all residents' educational growth and wellness.

International Analgesia and Sedation Weaning and Withdrawal Practices in Critically Ill Adults: The Adult Iatrogenic Withdrawal Study in the ICU.

OBJECTIVES: Iatrogenic withdrawal syndrome (IWS) associated with opioid and sedative use for medical purposes has a reported high prevalence and associated morbidity. This study aimed to determine the prevalence, utilization, and characteristics of opioid and sedative weaning and IWS policies/protocols in the adult ICU population. DESIGN: International, multicenter, observational, point prevalence study. SETTING: Adult ICUs. PATIENTS: All patients aged 18 years and older in the ICU on the date of data collection who received parenteral opioids or sedatives in the previous 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICUs selected 1 day for data collection between June 1 and September 30, 2021. Patient demographic data, opioid and sedative medication use, and weaning and IWS assessment data were collected for the previous 24 hours. The primary outcome was the proportion of patients weaned from opioids and sedatives using an institutional policy/protocol on the data collection day. There were 2,402 patients in 229 ICUs from 11 countries screened for opioid and sedative use; 1,506 (63%) patients received parenteral opioids, and/or sedatives in the previous 24 hours. There were 90 (39%) ICUs with a weaning policy/protocol which was used in 176 (12%) patients, and 23 (10%) ICUs with an IWS policy/protocol which was used in 9 (0.6%) patients. The weaning policy/protocol for 47 (52%) ICUs did not define when to initiate weaning, and the policy/protocol for 24 (27%) ICUs did not specify the degree of weaning. A weaning policy/protocol was used in 34% (176/521) and IWS policy/protocol in 9% (9/97) of patients admitted to an ICU with such a policy/protocol. Among 485 patients eligible for weaning policy/protocol utilization based on duration of opioid/sedative use initiation criterion within individual ICU policies/protocols 176 (36%) had it used, and among 54 patients on opioids and/or sedatives ≥ 72 hours, 9 (17%) had an IWS policy/protocol used by the data collection day. CONCLUSIONS: This international observational study found that a small proportion of ICUs use policies/protocols for opioid and sedative weaning or IWS, and even when these policies/protocols are in place, they are implemented in a small percentage of patients.

Closing the gap between science and management of cold-water refuges in rivers and streams.

Human activities and climate change threaten coldwater organisms in freshwater ecosystems by causing rivers and streams to warm, increasing the intensity and frequency of warm temperature events, and reducing thermal heterogeneity. Cold-water refuges are discrete patches of relatively cool water that are used by coldwater organisms for thermal relief and short-term survival. Globally, cohesive management approaches are needed that consider interlinked physical, biological, and social factors of cold-water refuges. We review current understanding of cold-water refuges, identify gaps between science and management, and evaluate policies aimed at protecting thermally sensitive species. Existing policies include designating cold-water habitats, restricting fishing during warm periods, and implementing threshold temperature standards or guidelines. However, these policies are rare and uncoordinated across spatial scales and often do not consider input from Indigenous peoples. We propose that cold-water refuges be managed as distinct operational landscape units, which provide a social and ecological context that is relevant at the watershed scale. These operational landscape units provide the foundation for an integrated framework that links science and management by (1) mapping and characterizing cold-water refuges to prioritize management and conservation actions, (2) leveraging existing and new policies, (3) improving coordination across jurisdictions, and (4) implementing adaptive management practices across scales. Our findings show that while there are many opportunities for scientific advancement, the current state of the sciences is sufficient to inform policy and management. Our proposed framework provides a path forward for managing and protecting cold-water refuges using existing and new policies to protect coldwater organisms in the face of global change.

Simple and Efficient Synthesis of 3-Aryl-2-oxazolidinone Scaffolds Enabling Increased Potency toward Biofilms.

Infectious diseases caused by bacterial pathogens are a leading cause of mortality worldwide. In particular, recalcitrant bacterial communities known as biofilms are implicated in persistent and difficult to treat infections. With a diminishing antibiotic pipeline, new treatments are urgently required to combat biofilm infections. An emerging strategy to develop new treatments is the hybridization of antibiotics. The benefit of this approach is the extension of the useful lifetime of existing antibiotics. The oxazolidinones, which include the last resort antibiotic linezolid, are an attractive target for improving antibiofilm efficacy as they present one of the most recently discovered classes of antibiotics. A key step in the synthesis of new 3-aryl-2-oxazolidinone derivatives is the challenging formation of the oxazolidinone ring. Herein we report a direct synthetic route to the piperazinyl functionalized 3-aryl-2-oxazolidinone 17. We also demonstrate an application of these piperazine molecules by functionalizing them with a nitroxide moiety as a strategy to extend the useful lifetime of oxazolidinones and improve their potency against Methicillin-resistant Staphylococcus aureus (MRSA) biofilms. The antimicrobial susceptibility of the linezolid-nitroxide conjugate 11 and its corresponding methoxyamine derivative 12 (a control for biofilm dispersal) was assessed against planktonic cells and biofilms of MRSA. In comparison to linezolid and our lead compound 10 (a piperazinyl oxazolidinone derivative), the linezolid-nitroxide conjugate 11 displayed a minimum inhibitory concentration that was 4-16-fold higher. The opposite effect was seen in biofilms where the linezolid-nitroxide hybrid 11 was >2-fold more effective (160 µg/mL versus >320 µg/mL) in eradicating MRSA biofilms. The methoxyamine derivative 12 performed on par with linezolid. The drug-likeness of the compounds was also assessed, and all compounds were predicted to have good oral bioavailability. Our piperazinyl oxazolidinone derivative 10 was confirmed to be lead-like and would be a good lead candidate for future functionalized oxazolidinones. The modification of antibiotics with a dispersal agent appears to be a promising approach for eradicating MRSA biofilms and overcoming the antibiotic resistance associated with the biofilm mode of growth.

Facets of impulsivity and reward in relation to binge-eating disorder course of illness among children: findings from the Adolescent Brain Cognitive Development study.

BACKGROUND: The present study examined facets of impulsivity and reward sensitivity [as measured by the UPPS-P Impulsive Behavior Scale and Behavioral Activation and Behavioral Inhibition Scales (BIS/BAS)] as multivariable predictors of subsequent binge-eating disorder (BED) course of illness in middle childhood. METHODS: The current sample included children aged 9-10 years (N = 9,438) who took part in the baseline and 1-year follow-up assessments of the Adolescent Brain Cognitive Development (ABCD) study. BED course was operationalized as those who never developed BED or subthreshold BED (SBED) ('control'), were diagnosed with BED/SBED at year 1 but not baseline ('developers'), were diagnosed with BED/SBED at baseline but not year 1 ('remitters'), or were diagnosed with BED/SBED at both times ('maintainers'). RESULTS: Higher baseline BIS/BAS reward responsivity scores were related to the greater likelihood of belonging to the maintainer group relative to the control and remitter groups (ORs1.12-1.19). Regarding covariates, higher baseline body mass index percentile and internalizing symptoms were related to the greater likelihood of BED development, remittance, and maintenance compared to the control group (ORs = 1.04-1.14); no variables were uniquely related to BED development. Exploratory analyses showed that the likelihood of belonging to the maintainer group compared to the control group was greatest at higher levels of negative urgency in combination with high reward responsivity. CONCLUSIONS: Heightened reward responsivity may convey risk for poorer BED course in children, while emotional disorder symptomatology may act as a more general risk and maintenance factor for BED.

Multiscale Spatial Variability and Stability in the Structure and Diversity of Bacterial Communities Associated with the Kelp Eisenia cokeri in Peru.

Ecological communities are structured by a range of processes that operate over a range of spatial scales. While our understanding of such biodiversity patterns in macro-communities is well studied, our understanding at the microbial level is still lacking. Bacteria can be free living or associated with host eukaryotes, forming part of a wider "microbiome," which is fundamental for host performance and health. For habitat forming foundation-species, host-bacteria relationships likely play disproportionate roles in mediating processes for the wider ecosystem. Here, we describe host-bacteria communities across multiple spatial scales (i.e., from 10s of m to 100s of km) in the understudied kelp, Eisenia cokeri, in Peru. We found that E. cokeri supports a distinct bacterial community compared to the surrounding seawater, but the structure of these communities varied markedly at the regional (~480 km), site (1-10 km), and individual (10s of m) scale. The marked regional-scale differences we observed may be driven by a range of processes, including temperature, upwelling intensity, or regional connectivity patterns. However, despite this variability, we observed consistency in the form of a persistent core community at the genus level. Here, the genera Arenicella, Blastopirellula, Granulosicoccus, and Litorimonas were found in >80% of samples and comprised ~53% of total sample abundance. These genera have been documented within bacterial communities associated with kelps and other seaweed species from around the world and may be important for host function and wider ecosystem health in general.

Synergistic or antagonistic antioxidant combinations - a case study exploring flavonoid-nitroxide hybrids.

Neurodegenerative diseases impose a considerable medical and public health burden on populations throughout the world. Oxidative stress, an imbalance in pro-oxidant/antioxidant homeostasis that leads to the generation of reactive oxygen species (ROS), has been implicated in the progression of a number of neurodegenerative diseases. The manipulation of ROS levels may represent a promising treatment option to slow down neurodegeneration, although adequate potency of treatments has not yet been achieved. Using a hybrid pharmacology approach, free radical nitroxide antioxidants were hybridised with a class of natural antioxidants, flavonoids, to form a potential multitargeted antioxidant. Modification of the Baker-Venkataraman reaction achieved the flavonoid-nitroxide hybrids (6-9) in modest yields. Antioxidant evaluation of the hybrids by cyclic voltammetry showed both redox functionalities were still active, with little influence on oxidation potential. Assessment of the peroxyl radical scavenging ability through an ORAC assay showed reduced antioxidant activity of the hybrids compared to their individual components. It was hypothesized that the presence of the phenol in the hybrids creates a more acidic medium which does not favour regeneration of the nitroxide from the corresponding oxammonium cation, disturbing the typical catalytic cycle of peroxyl radical scavenging by nitroxides. This work highlights the potential intricacies involved with drug hybridization as a strategy for new therapeutic development.

Using Nitroxides to Enhance Carbon Fiber Interfacial Adhesion and as an Anchor for "Graft to" Surface Modification Strategies.

Nitroxide groups covalently grafted to carbon fibers are used as anchoring sites for TEMPO-terminated polymers (poly-n-butylacrylate and polystyrene) in a "graft to" surface modification strategy. All surface-modified fibers are evaluated for their physical properties, showing that several treatments have enhanced the tensile strength and Young's modulus compared to the control fibers. Up to an 18% increase in tensile strength and 12% in Young's modulus are observed. Similarly, the evaluation of interfacial shear strength in an epoxy polymer shows improvements of up to 144% relative to the control sample. Interestingly, the polymer-grafted surfaces show smaller increases in interfacial shear strength compared to surfaces modified with a small molecule only. This counterintuitive result is attributed to the incompatibility, both chemical and physical, of the grafted polymers to the surrounding epoxy matrix. Molecular dynamics simulations of the interface suggest that the diminished increase in mechanical shear strength observed for the polymer grafted surfaces may be due to the lack of exposed chain ends, whereas the small molecule grafted interface exclusively presents chain ends to the resin interface, resulting in good improvements in mechanical properties.

Marine heatwaves and decreased light availability interact to erode the ecophysiological performance of habitat-forming kelp species.

Coastal marine ecosystems are threatened by a range of anthropogenic stressors, operating at global, local, and temporal scales. We investigated the impact of marine heatwaves (MHWs) combined with decreased light availability over two seasons on the ecophysiological responses of three kelp species (Laminaria digitata, L. hyperborea, and L. ochroleuca). These species function as important habitat-forming foundation organisms in the northeast Atlantic and have distinct but overlapping latitudinal distributions and thermal niches. Under low-light conditions, summertime MHWs induced significant declines in biomass, blade surface area, and Fv/Fm values (a measure of photosynthetic efficiency) in the cool-water kelps L. digitata and L. hyperborea, albeit to varying degrees. Under high-light conditions, all species were largely resistant to simulated MHW activity. In springtime, MHWs had minimal impacts and in some cases promoted kelp performance, while reduced light availability resulted in lower growth rates. While some species were negatively affected by summer MHWs under low-light conditions (particularly L. digitata), they were generally resilient to MHWs under high-light conditions. As such, maintaining good environmental quality and water clarity may increase resilience of populations to summertime MHWs. Our study informs predictions of how habitat-forming foundation kelp species will be affected by interacting, concurrent stressors, typical of compound events that are intensifying under anthropogenic climate change.

Education and employment as young adults living with spina bifida transition to adulthood in the USA: A study of the National Spina Bifida Patient Registry.

AIM: To describe the education and employment transition experience of young adults with spina bifida (YASB) and investigate factors associated with employment. METHOD: We queried education and employment data from the US National Spina Bifida Patient Registry from 2009 to 2019. We applied generalized estimating equations models to analyze sociodemographic and disease-related factors associated with employment. RESULTS: A total of 1909 participants (850 males, 1059 females) aged 18 to 26 years contributed 4379 annual visits. Nearly 84% had myelomeningocele and, at last visit, the median age was 21 years (mean 21 years 5 months, SD 2 years 10 months). A total of 41.8% had at least some post-high school education, and 23.9% were employed. In a multivariable regression model, employment was significantly associated with education level, lower extremity functional level, bowel continence, insurance, and history of non-shunt surgery. This large, national sample of YASB demonstrated low rates of post-secondary education attainment and employment and several potentially modifiable factors associated with employment. INTERPRETATION: Specific sociodemographic, medical, and functional factors associated with employment are important for clinicians to consider when facilitating transition for YASB into adulthood. Additional research is needed to understand the impact of cognitive functioning and social determinants of health on transition success in YASB. WHAT THIS PAPER ADDS: There were low education attainment and employment rates in a large sample of young adults with spina bifida. Specific sociodemographic, medical, and functional factors are associated with employment. Some employment-associated factors, such as continence and self-management skills, are modifiable.

Cognitive rigidity and restrictive eating disorders: Delineating the impact of low weight, low fat, weight suppression, acute negative energy balance, and chronic restriction.

Restrictive eating disorders such as anorexia nervosa (AN) are characterized by extremely rigid cognitive and behavioral patterns, understood to underpin the chronic nature of these disorders. Interrogating the mechanisms contributing to and maintaining the rigid cognitive styles and limited behavioral repertoires, particularly in terms of restrictive eating and excessive exercise is of critical importance. Dietary restriction is overall understood to underpin this rigidity to a large extent, however, to date little is understood regarding the relative contributions of different aspects of restriction including low body weight, low fat mass, weight suppression, acute negative energy balance, and chronic restriction. Clarifying the respective roles of these different factors would be useful for both the better targeting intervention efforts in AN. Extending research to other disorders such as muscle dysmorphia, avoidant restrictive food intake disorders, or atypical AN, that may present similar features to AN but differ from it on other critical dimensions, may offer unique opportunities to identify clinical elements specific to these cognitive patterns. Doing so may inform interventions and pave the way towards more effective treatment approaches.

Divergent trajectories of positive affect following maladaptive and non-maladaptive exercise among individuals with binge-spectrum eating disorders.

OBJECTIVE: Individuals with eating disorders (EDs) often engage in maladaptive exercise (e.g., feeling driven, or to "compensate" for eating) which maintains eating pathology. Maladaptive exercise has been theorized to help individuals with EDs regulate emotions by enhancing positive affect (PA) and reducing negative affect (NA) associated with binge episodes and poor body image. However, no research has considered the presence of non-maladaptive exercise or evaluated this theory in binge-spectrum EDs. METHODS: This study evaluated affective trajectories pre- and post-exercise and examined exercise type (maladaptive or non-maladaptive) as a moderator. We recruited adults with binge-spectrum EDs (N = 107; n = 84 endorsed exercise) to complete a 7- to 14-day ecological momentary assessment protocol assessing NA (anxiety, guilt, and sadness), PA (excitement and cheerfulness), and exercise. RESULTS: There was a significant quadratic trajectory of PA pre-exercise, suggesting that the upward trajectory of PA leveled out as it moved closer to an exercise episode. Exercise type significantly moderated the cubic trajectory of PA post-exercise, such that the upward trajectory of PA accelerated in the hours following non-maladaptive exercise episodes while the downward trajectory of PA accelerated in the hours following maladaptive exercise episodes. No trajectories of NA demonstrated significant effects. CONCLUSIONS: Pre-exercise trajectories of PA may reflect positive expectancies around exercise. Post-exercise trajectories of PA suggest that non-maladaptive exercise promotes increased PA. Future research should evaluate when, and for whom, exercise serves to regulate affect and examine other momentary risk factors of exercise in EDs. PUBLIC SIGNIFICANCE: Individuals with EDs often engage in maladaptive exercise (e.g., feeling driven, or to "compensate" for eating). Maladaptive exercise has been theorized to help individuals with EDs regulate emotions. This study evaluated affective trajectories pre- and post-exercise and examined whether exercise type (maladaptive or non-maladaptive) changed these trajectories. Pre-exercise trajectories of PA may reflect positive expectancies around exercise. Post-exercise trajectories of PA suggest that non-maladaptive exercise promotes increased PA.