Genetic and environmental interactions contribute to immune variation in rewilded mice.

The relative and synergistic contributions of genetics and environment to interindividual immune response variation remain unclear, despite implications in evolutionary biology and medicine. Here we quantify interactive effects of genotype and environment on immune traits by investigating C57BL/6, 129S1 and PWK/PhJ inbred mice, rewilded in an outdoor enclosure and infected with the parasite Trichuris muris. Whereas cellular composition was shaped by interactions between genotype and environment, cytokine response heterogeneity including IFNγ concentrations was primarily driven by genotype with consequence on worm burden. In addition, we show that other traits, such as expression of CD44, were explained mostly by genetics on T cells, whereas expression of CD44 on B cells was explained more by environment across all strains. Notably, genetic differences under laboratory conditions were decreased following rewilding. These results indicate that nonheritable influences interact with genetic factors to shape immune variation and parasite burden.

Naturalizing mouse models for immunology.

Laboratory mice have provided invaluable insight into mammalian immune systems. Yet the immune phenotypes of mice bred and maintained in conventional laboratory conditions often differ from the immune phenotypes of wild mammals. Recent work to naturalize the environmental experience of inbred laboratory mice-to take them where the wild things are (to borrow a phrase from Maurice Sendak), via approaches such as construction of exposure histories, provision of fecal transplants or surrogate mothering by wild mice, and rewilding-is poised to expand understanding, complementing genetic and phylogenetic research on how natural selection has shaped mammalian immune systems while improving the translational potential of mouse research.

The evolution of powerful yet perilous immune systems.

The mammalian immune system packs serious punch against infection but can also cause harm: for example, coronavirus disease 2019 (COVID-19) made headline news of the simultaneous power and peril of human immune responses. In principle, natural selection leads to exquisite adaptation and therefore cytokine responsiveness that optimally balances the benefits of defense against its costs (e.g., immunopathology suffered and resources expended). Here, we illustrate how evolutionary biology can predict such optima and also help to explain when/why individuals exhibit apparently maladaptive immunopathological responses. Ultimately, we argue that the evolutionary legacies of multicellularity and life-history strategy, in addition to our coevolution with symbionts and our demographic history, together explain human susceptibility to overzealous, pathology-inducing cytokine responses. Evolutionary insight thereby complements molecular/cellular mechanistic insights into immunopathology.

Impact of waning immunity against SARS-CoV-2 severity exacerbated by vaccine hesitancy.

The SARS-CoV-2 pandemic has generated a considerable number of infections and associated morbidity and mortality across the world. Recovery from these infections, combined with the onset of large-scale vaccination, have led to rapidly-changing population-level immunological landscapes. In turn, these complexities have highlighted a number of important unknowns related to the breadth and strength of immunity following recovery or vaccination. Using simple mathematical models, we investigate the medium-term impacts of waning immunity against severe disease on immuno-epidemiological dynamics. We find that uncertainties in the duration of severity-blocking immunity (imparted by either infection or vaccination) can lead to a large range of medium-term population-level outcomes (i.e. infection characteristics and immune landscapes). Furthermore, we show that epidemiological dynamics are sensitive to the strength and duration of underlying host immune responses; this implies that determining infection levels from hospitalizations requires accurate estimates of these immune parameters. More durable vaccines both reduce these uncertainties and alleviate the burden of SARS-CoV-2 in pessimistic outcomes. However, heterogeneity in vaccine uptake drastically changes immune landscapes toward larger fractions of individuals with waned severity-blocking immunity. In particular, if hesitancy is substantial, more robust vaccines have almost no effects on population-level immuno-epidemiology, even if vaccination rates are compensatorily high among vaccine-adopters. This pessimistic scenario for vaccination heterogeneity arises because those few individuals that are vaccine-adopters are so readily re-vaccinated that the duration of vaccinal immunity has no appreciable consequences on their immune status. Furthermore, we find that this effect is heightened if vaccine-hesitants have increased transmissibility (e.g. due to riskier behavior). Overall, our results illustrate the necessity to characterize both transmission-blocking and severity-blocking immune time scales. Our findings also underline the importance of developing robust next-generation vaccines with equitable mass vaccine deployment.

Immunological feedback loops generate parasite persistence thresholds that explain variation in infection duration.

Infection duration affects individual host fitness and between-host transmission. Whether an infection is cleared or becomes chronic depends on the complex interaction between host immune responses and parasite growth. Empirical and theoretical studies have suggested that there are critical thresholds of parasite dose that can determine clearance versus chronicity, driven by the ability of the parasite to manipulate host immunity. However, the mammalian immune response is characterized by strong positive and negative feedback loops that could generate duration thresholds even in the absence of direct immunomodulation. Here, we derive and analyse a simple model for the interaction between T-cell subpopulations and parasite growth. We show that whether an infection is cleared or not is very sensitive to the initial immune state, parasite dose and strength of immunological feedbacks. In particular, chronic infections are possible even when parasites provoke a strong and effective immune response and lack any ability to immunomodulate. Our findings indicate that the initial immune state, which often goes unmeasured in empirical studies, is a critical determinant of infection duration. This work also has implications for epidemiological models, as it implies that infection duration will be highly variable among individuals, and dependent on each individual's infection history.

serosim: An R package for simulating serological data arising from vaccination, epidemiological and antibody kinetics processes.

serosim is an open-source R package designed to aid inference from serological studies, by simulating data arising from user-specified vaccine and antibody kinetics processes using a random effects model. Serological data are used to assess population immunity by directly measuring individuals' antibody titers. They uncover locations and/or populations which are susceptible and provide evidence of past infection or vaccination to help inform public health measures and surveillance. Both serological data and new analytical techniques used to interpret them are increasingly widespread. This creates a need for tools to simulate serological studies and the processes underlying observed titer values, as this will enable researchers to identify best practices for serological study design, and provide a standardized framework to evaluate the performance of different inference methods. serosim allows users to specify and adjust model inputs representing underlying processes responsible for generating the observed titer values like time-varying patterns of infection and vaccination, population demography, immunity and antibody kinetics, and serological sampling design in order to best represent the population and disease system(s) of interest. This package will be useful for planning sampling design of future serological studies, understanding determinants of observed serological data, and validating the accuracy and power of new statistical methods.

Timing matters in (mis)identifying moderators and mediators of digital interventions for eating disorders: Commentary on McClure et al. (2023).

This commentary addresses the challenges in identifying consistent moderators and mediators of psychological treatments for eating disorders (EDs), as highlighted by McClure et al. (International Journal of Eating Disorders, 2023) in their systematic review. Specifically, we discuss the often-overlooked importance of temporal context (when an intervention is delivered), alongside sociodemographic and symptom type (for whom an intervention is delivered), in understanding and optimizing treatment engagement and effectiveness. We outline how individuals' fluctuating levels of motivation and receptivity across different "pivotal moments" in the help-seeking process-including initial outreach and self-screening, ongoing care engagement, and post-discharge-can dynamically impact interventions' relevance and impacts. We also overview how Just-In-Time Adaptive Interventions in digital mental health interventions can be harnessed to simultaneously consider "when" and "for whom" ED interventions can exert the greatest benefits. We conclude with several recommendations for conducting ED intervention and implementation research that integrate timing into support delivery and study design, enabling a deeper understanding of not just how and for whom, but when, ED interventions can be most effective.

Partnering With Food Pantries to Disseminate and Implement Eating Disorder Interventions.

OBJECTIVE: Food insecurity is associated with eating disorder psychopathology. This Spotlight describes why food pantries could be promising partners for disseminating and implementing eating disorder interventions. METHOD: Researchers are increasingly collaborating with community-based organizations to improve access to health interventions, because community-based organizations overcome structural barriers to traditional healthcare by being embedded physically in the communities they serve, convenient to visit, regularly frequented, and led by trusted community members. RESULTS: We describe strategies we have identified with our partner to disseminate and implement our digital intervention for binge eating; we also discuss ways we support the pantry's needs to improve the mutuality of the partnership. DISCUSSION: The potential benefits of partnerships with food pantries make this an area to explore further. Future research directions include deeply engaging with food pantries to determine how pantries benefit from disseminating and implementing eating disorder interventions and how to intervene in non-stigmatizing ways, what resources they need to sustainably support these efforts, what eating disorder intervention modalities guests are willing and able to engage with, what intervention adaptations are needed so individuals with food insecurity can meaningfully engage in eating disorder intervention, and what implementation strategies facilitate uptake to intervention sustainably over time.

A pilot study evaluating online training for therapist delivery of interpersonal psychotherapy for eating disorders.

OBJECTIVE: Individuals with eating disorders (EDs) often do not receive evidence-based care, such as interpersonal psychotherapy (IPT), partly due to lack of accessible training in these treatments. The standard method of training (i.e., in-person workshops) is expensive and time consuming, prompting a need for more scalable training tools. The primary aim of this pilot and open trial was to examine the effects of an IPT online training platform on training outcomes (i.e., IPT fidelity, knowledge, and acceptance) and, secondarily, whether online training was different from in-person training (using a comparative sample from a separate study) in terms of training outcomes and patient symptoms. METHOD: Participants were therapists (N = 60) and student patients (N = 42) at 38 college counseling centers. Therapists completed baseline questionnaires and collected data from a student patient with ED symptoms. Therapists then participated in an IPT online training program and completed post-training assessments. RESULTS: Following online training, acceptance of evidence-based treatments, therapist knowledge of IPT, therapist acceptance of IPT, and treatment fidelity increased; acceptance of online training was high at baseline and remained stable after training. Using the 90% confidence interval on outcome effect sizes, results suggested IPT online training was not different from in-person training on most outcomes. Results are based on 60% of therapists who originally enrolled due to high dropout rate of therapist participants. CONCLUSIONS: Findings from this preliminary pilot study support the use of IPT online training, which could increase access to evidence-based ED treatment and improve patient care. PUBLIC SIGNIFICANCE: Lack of accessible therapist training has contributed to many therapists not delivering, and therefore many patients not receiving, evidence-based treatment. This study evaluated a highly disseminable online training and compared outcomes to traditional in-person training and found that training and patient outcomes were not different. Online training has the potential to enhance access to evidence-base care, which could in turn optimize patient outcomes.

Nurturing innovation, catalyzing change: Honoring the legacy of Dr. C. Barr Taylor in the eating disorders field.

This Virtual Issue of the International Journal of Eating Disorders honors the legacy of the late Dr. C. Barr Taylor in the eating disorders (EDs) field. For decades, Dr. Taylor led the way in not only conducting the research needed to achieve the ultimate goal of making affordable, accessible, and evidence-based care for EDs available to all, but also nurturing the next generation of scientific leaders and innovators. Articles included in this Virtual Issue are a selection of Dr. Taylor's published works in the Journal in the past decade, spanning original research, ideas worth researching, commentaries, and a systematic review. We hope this Virtual Issue will inspire the next generation of research in EDs, and equally, if not more importantly, the next generation of young investigators in the field. We urge the field to continue and build upon Dr. Taylor's vision-to increase access to targeted prevention and intervention for EDs in innovative and forward-thinking ways-while embracing his unique and powerful mentorship style to lift up early career investigators and create a community of leaders to address and solve our field's biggest challenges.

Immune response of the Almaco jack (Seriola rivoliana) against the infestation with Neobenedenia sp. in three cultivated temperatures.

The Almaco jack (Seriola rivoliana) is a marine fish maintained in mariculture systems and frequently infested by monogenean parasites like Neobenedenia sp. Severe infestations can lead to high mortalities and economic losses for farmers. This study evaluated the effects of temperature on the immune response on Almaco jack infested with Neobenedenia sp. We exposed infested fishes at temperatures of 20 °C, 24 °C, and 30 °C for 20 days and took samples of different tissues at the beginning of the experiment, and after 3 and 20 days. The tissues considered were the skin, thymus, cephalic kidney, and spleen to evaluate the relative gene expression of different genes: Hsp70, IgM, IL-1ß, IL-10, and MyD88. Our results showed an increase in IL-1ß gene expression in the skin after 20 days of infestation but no significant effect of temperature on gene expression, despite increases in infestation rates with temperature. Therefore, relative genetic expression was controlled by the number of parasites and the days post-infestation. These results show that the parasite infestation induced a local response in the skin, but that temperature has an indirect effect on the immune system of Almaco jack.

Designing Digital Interventions for Eating Disorders.

PURPOSE OF REVIEW: Digital (i.e., online, mobile) interventions have potential to increase access to care for people with eating disorders, but engagement with digital interventions has been challenging. Human-centered design is a methodology that centralizes the design of technologies on the people who will be using them and the settings in which they will be implemented, to yield solutions with high engagement and clinical impact. The paper presents an overview of the human-centered design process, followed by a review of publications that have applied design methods to digital interventions for eating disorders. RECENT FINDINGS: Design research has been conducted via needs assessments, prototyping and usability studies, and during ongoing delivery of digital eating disorder interventions. There has been growing research applying design methods to digital interventions for eating disorders. Additional opportunities include designing for implementation, designing for equity, and designing for the optimization of digital interventions over time.

Digital guided self-help for eating disorders: thematic analysis of participant text messages to coaches.

Digital guided self-help for eating disorders (GSH-ED) can reduce treatment disparities. Understanding program participants' interests throughout the program can help adapt programs to the service users' needs. Participants were 383 college students receiving a digital GSH-ED, who were each assigned a coach to help them better utilize the intervention through text correspondence. A thematic and affective analysis of the texts participants had sent found they primarily focused on: strategies for changing their ED-related cognitions, behaviors, and relationships; describing symptoms without expressing an active endeavor to change; and participants' relationship with their coach. Most texts also expressed affect, demonstrating emotional engagement with the intervention. Findings suggest that participants in GSH-ED demonstrate high involvement with the intervention, and discuss topics that are similar to those reported in clinician-facilitated interventions. The themes discussed by digital program participants can inform future iterations of GSH-ED, thereby increasing scalability and accessibility of digital evidence-based ED interventions.

Disentangling the dynamical underpinnings of differences in SARS-CoV-2 pathology using within-host ecological models.

Health outcomes following infection with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are remarkably variable. The way the virus spreads inside hosts, and how this spread interacts with host immunity and physiology, is likely to determine variation in health outcomes. Decades of data and dynamical analyses of how other viruses spread and interact with host cells could shed light on SARS-CoV-2 within-host trajectories. We review how common axes of variation in within-host dynamics and emergent pathology (such as age and sex) might be combined with ecological principles to understand the case of SARS-CoV-2. We highlight pitfalls in application of existing theoretical frameworks relevant to the complexity of the within-host context and frame the discussion in terms of growing knowledge of the biology of SARS-CoV-2. Viewing health outcomes for SARS-CoV-2 through the lens of ecological models underscores the value of repeated measures on individuals, especially since many lines of evidence suggest important contingence on trajectory.

Optimal immune specificity at the intersection of host life history and parasite epidemiology.

Hosts diverge widely in how, and how well, they defend themselves against infection and immunopathology. Why are hosts so heterogeneous? Both epidemiology and life history are commonly hypothesized to influence host immune strategy, but the relationship between immune strategy and each factor has commonly been investigated in isolation. Here, we show that interactions between life history and epidemiology are crucial for determining optimal immune specificity and sensitivity. We propose a demographically-structured population dynamics model, in which we explore sensitivity and specificity of immune responses when epidemiological risks vary with age. We find that variation in life history traits associated with both reproduction and longevity alters optimal immune strategies-but the magnitude and sometimes even direction of these effects depends on how epidemiological risks vary across life. An especially compelling example that explains previously-puzzling empirical observations is that depending on whether infection risk declines or rises at reproductive maturity, later reproductive maturity can select for either greater or lower immune specificity, potentially illustrating why studies of lifespan and immune variation across taxa have been inconclusive. Thus, the sign of selection on the life history-immune specificity relationship can be reversed in different epidemiological contexts. Drawing on published life history data from a variety of chordate taxa, we generate testable predictions for this facet of the optimal immune strategy. Our results shed light on the causes of the heterogeneity found in immune defenses both within and among species and the ultimate variability of the relationship between life history and immune specificity.

Accelerating the research-to-practice translation of eating disorder apps and other digital interventions: Commentary on O'Leary and Torous (2022).

Smartphone apps are increasingly being developed to address mental health problems, including eating disorders. Yet a review by O'Leary and Torous (2022) revealed the dearth of publicly available evidence-based apps for eating disorders, despite growing research in this area in recent years. The lack of publicly available evidence-based apps is problematic for society and reflects a gap in the research-to-practice translation of the advances that have been made through academic research in this area. We detail barriers that academic researchers face to such translation, including the lack of incentives and pathways for making these interventions available beyond the academic institutions in which they are often created. The effective translation of eating disorder apps, and other digital approaches, from research to practice will require new approaches, including bolstering successful and sustainable translation through partnerships across sectors, being more proactive toward research-to-practice translation, and designing more sustainable digital interventions. Harnessing such approaches can improve the availability of evidence-based eating disorder apps and other digital approaches. Additionally, academic researchers are encouraged to be advocates within their institutions and with funding agencies to find ways to better incentivize and fund these efforts.

Understanding self-monitoring to inform a mobile intervention for binge eating and weight management: A proof-of-concept randomized trial.

OBJECTIVE: This study explored consumers' perspectives on self-monitoring, a common feature in behavioral interventions that helps inform consumers' progress and answer their questions, to learn what outcome metrics matter to consumers and whether self-selection of these metrics leads to greater engagement (i.e., compliance, satisfaction) in self-monitoring than monitoring only default options. METHODS: In a proof-of-concept randomized trial, 48 adult participants were randomly assigned to "clinician-determined monitoring" or "clinician + self-determined monitoring" conditions. Before starting monitoring, all participants shared outcomes that would matter to them in a mobile intervention for binge eating and weight management. Then, for 3 weeks, participants in the "clinician-determined" condition monitored their weight and binge-eating episodes, and participants in the "clinician + self-determined" condition monitored these and another metric of their choosing. After, satisfaction and compliance were assessed. RESULTS: Participants identified 116 metrics, grouped into 12 themes, that mattered to them. During monitoring, participants in the "clinician + self-determined" condition monitored 41 metrics. Surprisingly, participants in the "clinician-determined" condition also monitored metrics besides weight and binge eating. This resulted in a failure of our experimental manipulation, which represents a significant limitation of this research. No significant differences emerged in satisfaction or compliance between conditions. DISCUSSION: Although our proof-of-concept trial yielded null quantitative results, findings also suggested binge eating and weight management interventions may benefit from including an individually customizable monitoring option in addition to default metrics, warranting testing in future research. PUBLIC SIGNIFICANCE: Examining consumers' self-monitoring preferences for a mobile intervention for binge eating and weight management revealed a variety of metrics that matter to consumers, although binge eating and weight were still most valued. Findings from our proof-of-concept trial suggest design implications of encouraging an individually customizable monitoring option, in addition to default metrics, which needs to be tested in future research over a longer period and during actual mobile intervention delivery.

Eating to cope: Advancing our understanding of the effects of exposure to racial discrimination on maladaptive eating behaviors.

OBJECTIVE: Racial discrimination is a stressor for young Black women that leads to poor health outcomes, including maladaptive eating. This study presents findings on racial discrimination and maladaptive eating behaviors (overeating, LOC eating) using ecological momentary assessment (EMA). METHODS: Black emerging adult women (N = 27) with overweight or obesity participated in a 14-day EMA study examining exposure to racial discrimination, eating behaviors, and racial identity. Frequencies and chi-square tests were used to characterize the type of racial discrimination experienced and frequency of overeating. Mixed effect ordinal logistic regression models were used to assess the relation between racial discrimination and maladaptive eating. Moderation analysis was conducted by creating interaction terms for discrimination and racial identity variables. RESULTS: 81.5% of participants reported experiencing racial discrimination. Young Black women reporting exposure to racial discrimination were more likely to endorse higher levels of both overeating and LOC eating compared to times when discrimination was not experienced (p < .0001). Racial identity moderated the link between racial discrimination and maladaptive eating (overeating, LOC) such that reporting greater levels of private regard buffered the deleterious effect of racial discrimination. Higher levels of public regard exacerbated the association between racial discrimination and both overeating, and LOC. Higher centrality worsened the relation between racial discrimination and LOC. CONCLUSION: Young Black women might use maladaptive eating to cope with exposure to racial discrimination, which underscores the importance of examining the link between racism and disordered eating, particularly among Black women submerged in a society that continuously exposes them to racial discrimination. PUBLIC SIGNIFICANCE: Emerging adult Black women are exposed to racial discrimination daily. In theory, exposure to racial discrimination could contribute to overeating and loss of control eating in this population. Using ecological momentary assessment, to capture experiences and eating behaviors in the moment they occur, this project quantified the magnitude of racial discrimination and how it was associated with maladaptive eating behaviors. Further, it examined ways in which racial identity was linked to this association.

Accountability in promoting representation of historically marginalized racial and ethnic populations in the eating disorders field: A call to action.

Promoting representation of historically marginalized racial and ethnic populations in the eating disorders (EDs) field among professionals and the populations studied and served has long been discussed, with limited progress. This may be due to a reinforcing feedback loop in which individuals from dominant cultures conduct research and deliver treatment, participate in research, and receive diagnoses and treatment. This insularity maintains underrepresentation: EDs in historically marginalized populations are understudied, undetected, and undertreated. An Early Career Investigators Workshop generated recommendations for change that were not inherently novel but made apparent that accountability is missing. This paper serves as a call to action to spearhead a paradigm shift from equality to equity in the ED field. We provide a theoretical framework, suggest ways to disrupt the feedback loop, and summarize actionable steps to increase accountability in ED leadership and research toward enhancing racial/ethnic justice, equity, diversity, and inclusion (JEDI). These actionable steps are outlined in the service of challenging our field to reflect the diversity of our global community. We must develop and implement measurable metrics to assess our progress toward increasing diversity of underrepresented racial/ethnic groups and to address JEDI issues in our providers, patients, and research participants.

Predictors of treatment seeking and uptake among respondents to a widely disseminated online eating disorders screen in the United States.

OBJECTIVE: To explore predictors of treatment seeking and uptake among individuals following an online eating disorders (EDs) screen in the U.S. disseminated by the National Eating Disorders Association. METHOD: Respondents who screened at risk or positive for a probable ED from 04/2019 to 05/2021 (N = 263,530) were eligible to complete a 2-month follow-up survey that assessed treatment seeking and uptake after being offered referral options following screening. Analyses were conducted using chi-square tests or logistic regressions. RESULTS: Sixty thousand thirty-four respondents (22.8%) opted-in to the follow-up survey, of whom 2276 (3.8%) completed it. Of the final analytic sample (n = 1922), 35.7% of respondents reported seeking and 22.4% reported receiving treatment. Treatment seeking and uptake were more common among respondents who were female, White, or >24 years of age; uptake was more common among respondents who were non-Hispanic or higher income. Elevated shape/weight concerns were significantly, albeit modestly, associated with reduced likelihood to receive treatment. DISCUSSION: Demographic differences in treatment seeking and uptake highlight the need to optimize ED screening tools/feedback to meet the needs of underserved groups and to address stereotypes and structural barriers that may interfere. Research is also needed to identify barriers to uptake among those with elevated shape/weight concerns. PUBLIC SIGNIFICANCE: Relatively low rates of treatment seeking and uptake were observed, particularly among underserved groups, 2 months following a widely disseminated online eating disorders screen. Optimization of online eating disorder screening tools and delivery of feedback and referral information may be needed to increase health care utilization.