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.

Supporting Teams with Designing for Dissemination and Sustainability: the Design, Development, and Usability of a Digital Interactive Platform.

Background: The use of Designing for Dissemination and Sustainability (D4DS) principles and methods can support the development of research products (interventions, tools, findings) to match well with the needs and context of the intended audience and setting. D4DS principles and methods are not well-known or used during clinical and public health research; research teams would benefit from applying D4DS. This paper presents the development of a new digital platform for teams to learn and apply a D4DS process to their work. Methods: A user-centered design (UCD) approach engaged users (n=14) and an expert panel (n=6) in an iterative design process from discovery to prototyping and testing. We led five design sessions using Zoom and Figma software over a 5-month period. Users (71% academics; 29% practitioners) participated in at least 2 sessions. Following design sessions, feedback from users were summarized and discussed to generate design decisions. A prototype was then built and heuristically tested with 11 users who were asked to complete multiple tasks within the platform while verbalizing their decision-making using the 'think aloud' procedure. The System Usability Scale (SUS) was administered at the end of each testing session. After refinements to the platform were made, usability was reassessed with 7 of 11 same users to examine changes. Results: The interactive digital platform (the D4DS Planner) has two main components: 1) the Education Hub (e.g., searchable platform with literature, videos, websites) and 2) the Action Planner. The Action Planner includes 7 interactive steps that walk users through a set of activities to generate a downloadable D4DS action plan for their project. Participants reported that the prototype tool was moderately usable (SUS=66) but improved following refinements (SUS=71). Conclusions: This is a first of its kind tool that supports research teams in learning about and explicitly applying D4DS to their work. The use of this publicly available tool may increase the adoption, impact, and sustainment of a wide range of research products. The use of UCD yielded a tool that is easy to use. The future use and impact of this tool will be evaluated, and the tool will continue to be refined and improved.

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.

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.

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.

Spatiotemporal-social association predicts immunological similarity in rewilded mice.

Environmental influences on immune phenotypes are well-documented, but our understanding of which elements of the environment affect immune systems, and how, remains vague. Behaviors, including socializing with others, are central to an individual's interaction with its environment. We therefore tracked behavior of rewilded laboratory mice of three inbred strains in outdoor enclosures and examined contributions of behavior, including associations measured from spatiotemporal co-occurrences, to immune phenotypes. We found extensive variation in individual and social behavior among and within mouse strains upon rewilding. In addition, we found that the more associated two individuals were, the more similar their immune phenotypes were. Spatiotemporal association was particularly predictive of similar memory T and B cell profiles and was more influential than sibling relationships or shared infection status. These results highlight the importance of shared spatiotemporal activity patterns and/or social networks for immune phenotype and suggest potential immunological correlates of social life.

From formative design to service-ready therapeutic: A pragmatic approach to designing digital mental health interventions across domains.

As digital mental health interventions (DMHIs) proliferate, there is a growing need to understand the complexities of moving these tools from concept and design to service-ready products. We highlight five case studies from a center that specializes in the design and evaluation of digital mental health interventions to illustrate pragmatic approaches to the development of digital mental health interventions, and to make transparent some of the key decision points researchers encounter along the design-to-product pipeline. Case studies cover different key points in the design process and focus on partnership building, understanding the problem or opportunity, prototyping the product or service, and testing the product or service. We illustrate lessons learned and offer a series of questions researchers can use to navigate key decision points in the digital mental health intervention (DMHI) development process.

Reach and uptake of digital mental health interventions based on cognitive-behavioral therapy for college students: A systematic review.

Background: Mental health problems are increasing in prevalence among college students, yet few students receive treatment due to barriers such as insufficient resources in college counseling centers. Digital mental health interventions (DMHIs) have potential to overcome barriers and offer accessible, evidence-based care to college students. However, to evaluate the true public health impact of evidence-based DMHIs, it is important to assess the reach and uptake rates of DMHIs on college campuses. Objectives: We conducted a systematic review to examine the reach (i.e., % of invited students who express interest) and uptake (i.e., % of enrolled participants who initiate an intervention) of DMHIs based on cognitive-behavioral therapy (CBT) for college students. Methods: Eight databases were searched. Inclusion criteria included: (1) college population; (2) experimental design; (3) CBT-based intervention; (4) intervention targeting specific mental health conditions; and (5) digital intervention. Reach and uptake rates were calculated from data reported. A systematic narrative review framework was used to synthesize results. Results: Of 10,315 articles screened, 90 were included. Seventeen studies (19%) reported sufficient data to calculate reach; 35 studies (39%) reported uptake rates. Of studies that reported reach or uptake, most evaluated unguided (n = 20) or guided (n = 16) self-help programs. Measurement methods varied widely. Overall reach was low, whereas uptake was high among enrolled participants. Discussion: Despite evidence that improving reach and uptake can increase the public health impact of DMHIs, most studies did not report on either outcome. Suggested practices to improve these outcomes, and their reporting, are discussed.

Medium-term scenarios of COVID-19 as a function of immune uncertainties and chronic disease.

As the SARS-CoV-2 trajectory continues, the longer-term immuno-epidemiology of COVID-19, the dynamics of Long COVID, and the impact of escape variants are important outstanding questions. We examine these remaining uncertainties with a simple modelling framework that accounts for multiple (antigenic) exposures via infection or vaccination. If immunity (to infection or Long COVID) accumulates rapidly with the valency of exposure, we find that infection levels and the burden of Long COVID are markedly reduced in the medium term. More pessimistic assumptions on host adaptive immune responses illustrate that the longer-term burden of COVID-19 may be elevated for years to come. However, we also find that these outcomes could be mitigated by the eventual introduction of a vaccine eliciting robust (i.e. durable, transmission-blocking and/or 'evolution-proof') immunity. Overall, our work stresses the wide range of future scenarios that still remain, the importance of collecting real-world epidemiological data to identify likely outcomes, and the crucial need for the development of a highly effective transmission-blocking, durable and broadly protective vaccine.

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.

Demographic, environmental and physiological predictors of gastrointestinal parasites in urban raccoons.

Raccoons are host to diverse gastrointestinal parasites, but little is known about the ecology of these parasites in terms of their interactions with each other during coinfections, their interactions with host physiology and environmental factors, and their impact on raccoon health and survival. As a first step, we investigated the patterns of parasite infection and their demographic distribution in an urban-suburban population of raccoons trapped in the summers and autumns of 2018 and 2019. We collected faecal samples, demographic data, morphometric measurements, and blood smears, and used GPS data to classify trapping location by land cover type. Faecal floats were performed to detect and quantify gastrointestinal nematode eggs and coccidia oocysts, and white blood cell differentials were performed on blood smears to characterise white blood cell distributions. Data were analysed cross-sectionally and, where possible, longitudinally, using generalised linear models. Overall, 62.6% of sampled raccoons were infected with gastrointestinal nematodes, and 82.2% were infected with gastrointestinal coccidia. We analysed predictors of infection status and faecal egg count for three different morphotypes of nematode-Baylisascaris, strongyle, and capillariid nematodes-and found that infection status and egg count varied with Year, Month, Age class, Land cover, and coinfection status, though the significance of these predictors varied between nematode types. Gastrointestinal coccidia prevalence varied with Year, Month, Age class, strongyle infection status, and capillariid infection status. Coccidia oocyst counts were lower in adults and in October, but higher in females and in raccoons trapped in areas with natural land cover; furthermore, coccidia oocysts were positively associated with capillariid faecal egg counts. We found no evidence that gastrointestinal parasites influenced raccoon body condition or overwinter mortality, and so conclude that raccoons, though harbouring diverse and abundant gastrointestinal parasites, may be relatively tolerant of these parasites.

The relation of food insecurity to eating disorder characteristics and treatment-seeking among adult respondents to the National Eating Disorders Association online screen.

BACKGROUND: Food insecurity (FI), characterized by limited or uncertain access to adequate food, has been associated with eating disorders (EDs). This study explored whether FI was associated with ED behaviors, ED diagnosis, current treatment status, and treatment-seeking intentions among adults who completed an online ED screen. METHODS: Respondents to the National Eating Disorders Association online screening tool self-reported demographics, FI, height and weight, past 3-month ED behaviors, and current treatment status. Respondents were also asked an optional question about treatment-seeking intentions. Hierarchical regressions evaluated relations between FI and ED behaviors, treatment status, and treatment-seeking intentions. Logistic regressions explored differences in probable ED diagnosis by FI status. RESULTS: Of 8714 respondents, 25 % screened at risk for FI. FI was associated with greater binge eating (R2Change = 0.006), laxative use (R2Change = 0.001), and presence of dietary restriction (R2Change = 0.001, OR: 1.32) (ps < .05). Having FI was associated with greater odds of screening positive for a probable ED or as high risk for an ED (ps < .05). FI was not associated with current treatment status or treatment-seeking intentions (ps > .05). CONCLUSIONS: Findings add to existing literature supporting a relation between FI and EDs. Implications include a need to disseminate EDs screening and treatment resources to populations affected by FI and to tailor treatments to account for barriers caused by FI.

Positive affect dysregulation and its relation to binge eating size and frequency.

Negative affect is an established predictor of binge eating, yet less is known about positive affect. Low positive affect has been theorized to increase binge eating, but a better understanding is needed on the relationship between positive affect and binge eating frequency and size. Participants were 182 treatment-seeking adults (76% self-identified as female; 45% self-identified their race as Black and 40% as White; and 25% self-identified their ethnicity as Hispanic/Latino) with self-reported recurrent binge eating (≥12 binge episodes in the past 3 months). Participants completed the positive and negative affect schedule (PANAS) survey and the eating disorder examination to assess frequency of objective binge episodes (OBEs) and subjective binge episodes (SBEs) over the past 3 months. OBEs and SBEs also were combined to yield total binge episodes over the past 3 months. Independent t-tests and linear regression analyses were used to test associations between positive affect scores and binge episode size and frequencies, and to compare low versus higher positive affect on binge frequency. Additional exploratory models were conducted controlling for negative affect, identity characteristics, and socio-demographic variables. Lower positive affect was significantly associated with more frequent total binge episodes, but not OBEs and SBEs when assessed independently. Findings remained consistent when controlling for covariates and when comparing individuals with the lowest versus higher positive affect levels. Overall, results lend support to the theory that low positive affect is associated with binge eating. Increasing positive affect may be an important treatment consideration for those with recurrent binge eating.

A budget impact analysis of cost to implement a whole child health focused, family-based intervention in primary care for children with elevated BMI.

BACKGROUND: Although the cost of implementing evidence-based interventions (EBIs) is a key determinant of adoption, lack of cost information is widespread. We previously evaluated the cost of preparing to implement Family Check-Up 4 Health (FCU4Health), an individually tailored, evidence-based parenting program that takes a whole child approach, with effects on both behavioral health and health behavior outcomes, in primary care settings. This study estimates the cost of implementation, including preparation. METHODS: We assessed the cost of FCU4Health across the preparation and implementation phases spanning 32 months and 1 week (October 1, 2016-June 13, 2019) in a type 2 hybrid effectiveness-implementation study. This family-level randomized controlled trial took place in Arizona with n = 113 predominantly low-income, Latino families with children ages > 5.5 to < 13 years. Using electronic cost capture and time-based activity-driven methods, budget impact analysis from the perspective of a future FCU4Health adopting entity-namely, ambulatory pediatric care clinicians-was used to estimate the cost of implementation. Labor costs were based on 2021 Bureau of Labor Statistics Occupational Employment Statistics, NIH-directed salary cap levels or known salaries, plus fringe benefits at a standard rate of 30%. Non-labor costs were based on actual amounts spent from receipts and invoices. RESULTS: The cost of FCU4Health implementation to 113 families was $268,886 ($2380 per family). Actual per family cost varied widely, as individual tailoring resulted in families receiving a range of 1-15 sessions. The estimated cost of replicating implementation for future sites ranged from $37,636-$72,372 ($333-$641 per family). Using our previously reported preparation costs (i.e., $174,489; $1544 per family), with estimated replication costs of $18,524-$21,836 ($164-$193 per family), the total cost of delivering FCU4Health was $443,375 ($3924 per family), with total estimated replication costs of $56,160-$94,208 ($497-$834 per family). CONCLUSIONS: This study provides a baseline for costs associated with implementation of an individually tailored parenting program. Results provide critical information for decision makers and a model for future economic analysis and can be used to inform optimization thresholds for implementation and, when necessary, benchmarks for program adaptation to promote scale-up. TRIAL REGISTRATION: This trial was prospectively registered on January 6, 2017, at ClinicalTrials.gov (NCT03013309).

Challenges in cybersecurity: Lessons from biological defense systems.

Defending against novel, repeated, or unpredictable attacks, while avoiding attacks on the 'self', are the central problems of both mammalian immune systems and computer systems. Both systems have been studied in great detail, but with little exchange of information across the different disciplines. Here, we present a conceptual framework for structured comparisons across the fields of biological immunity and cybersecurity, by framing the context of defense, considering different (combinations of) defensive strategies, and evaluating defensive performance. Throughout this paper, we pose open questions for further exploration. We hope to spark the interdisciplinary discovery of general principles of optimal defense, which can be understood and applied in biological immunity, cybersecurity, and other defensive realms.

Rewilding of laboratory mice enhances granulopoiesis and immunity through intestinal fungal colonization.

The paucity of blood granulocyte populations such as neutrophils in laboratory mice is a notable difference between this model organism and humans, but the cause of this species-specific difference is unclear. We previously demonstrated that laboratory mice released into a seminatural environment, referred to as rewilding, display an increase in blood granulocytes that is associated with expansion of fungi in the gut microbiota. Here, we find that tonic signals from fungal colonization induce sustained granulopoiesis through a mechanism distinct from emergency granulopoiesis, leading to a prolonged expansion of circulating neutrophils that promotes immunity. Fungal colonization after either rewilding or oral inoculation of laboratory mice with Candida albicans induced persistent expansion of myeloid progenitors in the bone marrow. This increase in granulopoiesis conferred greater long-term protection from bloodstream infection by gram-positive bacteria than by the trained immune response evoked by transient exposure to the fungal cell wall component ß-glucan. Consequently, introducing fungi into laboratory mice may restore aspects of leukocyte development and provide a better model for humans and free-living mammals that are constantly exposed to environmental fungi.

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.