Discovery of Small Molecule Interleukin 17A Inhibitors with Novel Binding Mode and Stoichiometry: Optimization of DNA-Encoded Chemical Library Hits to In Vivo Active Compounds.

Dysregulation of IL17A drives numerous inflammatory and autoimmune disorders with inhibition of IL17A using antibodies proven as an effective treatment. Oral anti-IL17 therapies are an attractive alternative option, and several preclinical small molecule IL17 inhibitors have previously been described. Herein, we report the discovery of a novel class of small molecule IL17A inhibitors, identified via a DNA-encoded chemical library screen, and their subsequent optimization to provide in vivo efficacious inhibitors. These new protein-protein interaction (PPI) inhibitors bind in a previously undescribed mode in the IL17A protein with two copies binding symmetrically to the central cavities of the IL17A homodimer.

Anxiety among youth with food allergy.

OBJECTIVE: Anxiety is among the major psychological concerns for children living with food allergy (FA). Yet research exploring the variables driving anxiety symptoms in FA remains sparse, and most studies still utilize homogeneous samples to assess anxiety symptoms. The current study seeks to evaluate the rates of clinically significant anxiety symptoms among a diverse sample of youth with FA and examine whether a heightened risk perception of FA outcomes and FA burden (vs. FA medical history) is associated with anxiety in youth. METHODS: 94 youth ages 10-14 and their parents were recruited from FA clinics at a mid-Atlantic children's hospital. Both youth and parents completed demographic and FA medical history questionnaires, the Screen for Child Anxiety Related Emotional Disorders, and the Food Allergy Independent Measure as part of a longitudinal study about FA adjustment and adherence. RESULTS: Over a third (37%) of youth scored above clinical cut-offs for overall anxiety symptoms. At least 25% of youth reported clinically significant scores on panic disorder, generalized anxiety, social anxiety, separation anxiety, and school avoidance subscales. Perception of risk of adverse FA outcomes and burden-but not FA medical history-were associated with total anxiety, generalized anxiety, panic disorder, and school avoidance symptoms, but not social anxiety and separation anxiety. Having more FAs was associated with higher social anxiety scores but not with other anxiety subscales. CONCLUSIONS: Youth with FA might benefit from psychosocial interventions that address FA risk perception management and promote appropriate FA vigilance to cope with anxiety symptoms.

Validation of the Sexual Discounting Task for Use in Adolescents.

The Sexual Discounting Task (SDT) was developed to evaluate the effects of delay on decision making as it relates to sexual risk-taking behaviors. Though previously validated with other populations, including urban emerging adults, the current study sought to validate the SDT with adolescents. A sample of adolescents (N = 155; 61% female) between ages 14 and 21 (Mage = 19.5 years) was recruited to complete the SDT (involving choices between immediate unprotected sex and delayed sex with a condom with hypothetical sexual partners) and the Delay Discounting Task (a delay discounting task for money outcomes). Additionally, they completed several self-report measures assessing demographics, sexual behavior, and sexual history. If the condom was readily available, respondents were more likely to use a condom for partners who were judged "most likely to have an STI" and for those that participants were "least likely to have sex with." Moreover, when a condom was not immediately available, greater self-reported sexual risk-taking was related to greater sexual discounting (i.e., greater effects of delay on decreasing condom use). Furthermore, sexual discounting was greater among partners deemed more desirable and those judged "least likely to have an STI." Differences in sexual discounting were significant after controlling for immediately available condom use. Findings from the current study suggest that the SDT is clinically meaningful for adolescents and is sensitive to factors that influence real-world decisions to use condoms. Future treatment and prevention should consider delay discounting as an important variable affecting sexual risk behavior.

A Qualitative Study to Inform Development of a Behavioral Intervention to Promote Food Allergy Self-Management and Adjustment among Early Adolescents.

Objective: Adolescence is a high-risk period for patients with food allergy (FA) as management responsibilities shift to the youth. This study used qualitative methods to explore FA experiences among a diverse pediatric FA population and inform behavioral intervention development. Methods: A total of 26 adolescents ages 9-14 years with IgE-mediated FA (M age = 11.92 years; 62% male; 42% Black, 31% White, 12% Hispanic/Latinx) and 25 primary caregivers (M age = 42.57 years; 32% annual income > $100,000) were recruited from FA clinics to complete separate qualitative interviews about FA-related experiences. Interviews were audio-recorded, transcribed, and entered into Dedoose, a qualitative software program. A grounded theory qualitative analytic approach was used to analyze data. Results: Emergent themes include: 1) FA is a chronic burden that affects daily life, 2) Families experience anxiety about FA, 3) Families find it challenging to transition FA management from parent to child, 4) FA families feel the need to be prepared, 5) FA families frequently advocate for their needs, and 6) Social experiences affect the FA experience. Conclusions: Adolescents with FA and their caregivers experience daily stress related to their chronic illness. A behavioral intervention that provides FA education, bolsters stress/anxiety management, assists parents in transitioning FA management responsibility to the youth, teaches executive functioning and advocacy skills, and fosters peer support could help adolescents successfully cope with and manage FA in their daily lives.

The Development of Age-Based Food Allergy Educational Handouts for Caregivers and Patients: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

BACKGROUND: Food allergy education is an ongoing process that must address unique safety concerns and psychosocial challenges at each developmental stage. Families require reliable information that is targeted to specific developmental stages to support the integration of food allergy management into daily life. OBJECTIVE: The purpose of this project was to develop age-specific, evidence-based patient education handouts with practical recommendations for managing and coping with food allergies at different developmental stages. METHODS: Handout content was based on: (1) practice guidelines for food allergy management; (2) literature addressing psychosocial and educational needs of patients with food allergy and their caregivers; and (3) clinical experience of the project team. Fifty-seven caregivers of patients (aged 0-21 years) with food allergy and 2 young adults with food allergy reviewed a draft of the handouts and completed an online survey to assess handout acceptability and usability and identify areas for improvement. Handouts were revised based on participant feedback. RESULTS: The majority of participants (79%) rated the amount of information in the age-specific handouts as "just right," versus "not enough" (9%) or "too much" information (12%). Sixty-three percent reported that they would be "very likely" to use the handouts as a resource and 35% "somewhat likely." Almost all participants (88%-100% by item) agreed that the handouts used elements of plain language writing and clear communication. CONCLUSION: Caregivers rated the age-based food allergy education handouts as understandable and useful. We anticipate that these handouts could be used during health care visits and directly accessed online by families.

Self-Efficacy Among Caregivers of Children With Food Allergy: A Cohort Study.

OBJECTIVE: The prevalence of pediatric food allergy (FA) is increasing and, due to early disease onset, requires significant caregiver management that is associated with psychosocial burden. Caregiver perception of how they cope and handle FA-related events (self-efficacy) has been linked to psychosocial outcomes in racially/geographically homogenous samples. This study explores FA-related caregiver self-efficacy and associations with FA-related caregiver quality of life (QoL) in a diverse cohort. METHODS: Caregivers of children, diagnosed with IgE-mediated FA who identified as non-Hispanic Black or White, were recruited from U.S. academic allergy clinics. Caregivers completed demographic and medical questionnaires, the Food Allergy Self-Efficacy Scale for Parents (FASE-P), Food Allergy Independent Measure-Parent Form (FAIM), and the Food Allergy Quality of Life-Parental Burden (FAQL-PB). Bivariate and multivariate associations estimated relationships between study variables. RESULTS: Caregivers of 365 children (Mage = 5.8 years, 62.2% male, 31.1% Black) were enrolled. Caregivers reported high FA self-efficacy (M = 82.06/100), moderate perceptions of risk/FA severity (FAIM: M = 3.9/7), and some limitations on the FAQL-PB (M = 3.9/7). Self-efficacy was related to lower perceptions of risk/FA severity across all demographic groups (r = -.42, p < .001). Caregivers who reported higher self-efficacy reported better QoL, particularly Black caregivers (r = .67). CONCLUSIONS: In this sample of caregivers of children with FA, greater self-efficacy was related to improved QoL regardless of sociodemographic factors. Caregivers' perception of risk was lower for those with greater self-efficacy. Future research into the impact of FA management on QoL among diverse caregivers is needed.

Food Allergy-Related Bullying Among Children and Adolescents.

OBJECTIVE: Food allergy (FA) management requires youth to avoid allergens and carry emergency medication which can impact participation in social activities. Previous research indicates that some youth experience FA-related bullying, but many studies are limited by single-item assessment methods and a narrow definition of bullying. This study describes FA-related bullying among a diverse cohort of youth with FA and evaluates parent-child disagreement and bullying assessment methods. METHODS: Youth ages 9-15 years (n = 121) diagnosed with an IgE-mediated FA and their primary caregivers were recruited from pediatric FA clinics to complete surveys about their FA-related bullying experiences. Descriptive statistics were conducted to assess overall FA-related bullying and McNemar tests were utilized to assess disagreement among parent-child report and between multi-item and single-item assessment methods. RESULTS: Seventeen percent and 31% of youth reported FA-related bullying on single-item and multi-item assessments, respectively. Twelve percent of parents reported their child had experienced FA-related bullying. Youth reported overt physical (51%), overt non-physical (66%), and relational FA-related bullying (20%). FA-related bullying was most common among classmates. Assessment method significantly affected the rates of FA-related bullying reported by youth, and parents and youth only agreed on FA-bullying experiences when assessed via the single-item measure. CONCLUSIONS: A subset of a diverse sample of youth with FA reported FA-related bullying. Clinicians should use multi-item assessment methods and ask both parents and children about their experiences to fully capture the experiences of families managing FA. School policies that facilitate FA safety and social inclusion should be promoted. CLINICAL TRIAL REGISTRATION: N/A.

Food Insecurity in the Food Allergic Population: A Work Group Report of the AAAAI Adverse Reactions to Foods Committee.

Food allergies affect 32 million Americans. Restricted diets due to food allergies can be difficult to maintain especially when the household is food insecure. Food insecurity is defined as the inability to acquire food for household members due to insufficient money or resources for food. The COVID-19 pandemic has caused many people to face food insecurity for the first time with Latinx, Native American, and Black communities disproportionately affected. Because of the increase in food insecurity, this work group developed a survey regarding food insecurity screening. This survey was sent out to a random sample of American Academy of Allergy Asthma & Immunology members to assess food insecurity knowledge and practices. The majority of survey participants did not routinely screen their patients for food insecurity. The biggest barrier identified to screening was lack of knowledge of how to perform a screen and resources available when a patient screened positive. This work group report provides guidance on how to implement and perform a food insecurity screen, including federal resources and assistance programs.

Assessing daily food allergy self-management among adolescents using a 24-hour recall interview.

BACKGROUND: Severe food allergic reactions can be life-threatening or fatal and are experienced by up to 40% of children with food allergies, with adolescents at greatest risk. There are no comprehensive measures to assess food allergy management behaviors that could prevent allergic reactions. OBJECTIVE: To describe food allergy self-management behaviors as reported by adolescents on a 24-hour recall measure and identify related factors. METHODS: Adolescents aged 10 to 14 years with immunoglobulin E-mediated food allergy completed the Food Allergy Management 24-Hour Recall as an interview. Participants answered questions on each food they ate on the previous day and food allergy self-management behaviors. RESULTS: Participants were a diverse sample (28% White) of 101 adolescents (mean age = 11.80 years; 53% male sex). Most meals and snacks (76%) were observed by adults. Epinephrine autoinjectors (EAIs) were reportedly available for almost all meals and snacks (93%). Almost all foods had been eaten before (95%) and were verified as allergen free (92%). Furthermore, 35% of the time, past experience with the food was the only method used to verify safety. Child age, number of food allergies, or time since allergic reaction was not related to self-management behavior. EAI availability and ingredient verification were most common at home and in school; adult observation was least likely in the home. CONCLUSION: Adolescents reported that EAIs were frequently available, but they relied on past experience with food to determine safety. Appropriate assessment of food safety should be a primary intervention target. The Food Allergy Management 24-Hour Recall may be a useful tool to assess and track food allergy self-management.

The Food Allergy Parent Mentoring Program: A Pilot Intervention.

OBJECTIVE: Parents of young children with newly diagnosed food allergy (FA) are at risk for poor psychosocial outcomes due to FA's life-threatening nature and demanding management routines. Presently, there are no interventions to support FA parents during this adjustment phase. This single-arm pilot study explores the feasibility, acceptability, and preliminary efficacy of a novel intervention using peer mentorship to improve psychosocial functioning in parents of young children with newly diagnosed FA. METHODS: Parent mentors were trained in mentorship and ethics and then matched with a mentee for a 6-month intervention period. Mentees, parents of children (under age 5 years) diagnosed with FA within 1 year, completed baseline and follow-up questionnaires to assess demographic and medical characteristics, FA knowledge, quality of life, self-efficacy, and social support and a program evaluation. Follow-up focus groups with mentors and individual interviews with mentees were conducted. RESULTS: Participants were 8 mentors and 10 mentees (Mage = 36.60 years, 80% Caucasian) of children ages 0-3 years (Mage = 16.15 months; 60% male). Mentees reported high acceptability for the intervention in program evaluation and interviews, noting improvements in their social support, FA-related stress, confidence in FA management, and positive changes in FA parenting behaviors. CONCLUSION: This study supports the use of a peer mentorship program to support parents of children with newly diagnosed FA. Future research is needed to determine how to scale this intervention to meet the needs of a large medical division.

Examining weight concern and delay discounting in adolescent females.

OBJECTIVE: Pediatric obesity is a growing public health concern that contributes to high rates of negative long-term physical and mental health outcomes. Research focused on identifying risk for pediatric obesity has linked delay discounting, or an inclination for immediate rewards, as well as weight concern to individuals with greater Body Mass Index (BMI). The current study seeks to fill a void in the literature by examining how these two variables interact to promote higher BMI in female adolescents. METHOD: Adolescent (n=60) females between the ages of 13-19years (mage=17.45, SD=1.74) of age completed the Eating Disorder Examination Questionnaire (EDE-Q) and the Delay Discounting Questionnaire. RESULTS: A mediation model examined whether delay discounting accounted for the relationship between weight concern and BMI. Results indicate that in the current study weight concern was negatively related to delay discounting and delay discounting was negatively related to BMI. The overall model revealed that a partial mediation occurred [b=1.28, t(60)=4.92, p<0.01]. DISCUSSION: These results suggest that while impulsivity is an important factor to consider, other constructs may also be influential in how weight concerns contribute to greater BMI. Nevertheless, the results indicate that prevention and interventions should identify females with high levels of both weight concern and impulsivity as an increased risk for experiencing pediatric obesity and long-term negative health outcomes.

The Role of Counterfactual Thinking on Attitudes Toward ADHD Medication Use.

OBJECTIVE: Despite serious health risks, attitudes toward Attention-Deficit Hyperactivity Disorder (ADHD) medication use in college students remain favorable. Given the robust link between attitudes and behavior (e.g., the Theory of Planned Behavior), it is important to understand how these attitudes are developed and maintained. The current study examined the role of counterfactual, or "what if'" thinking as a mechanism for the development of attitudes toward ADHD medications. METHOD: All participants (n = 190) were asked to read either a positive or negative scenario regarding ADHD medication misuse and rate their attitudes toward the behavior; half of the participants were also asked to generate counterfactuals prior to rating their attitudes. RESULTS: Results suggest that scenario valence influenced the direction of counterfactual statements. Further, through the generation of upward counterfactuals, the negative scenario elicited more positive attitudes toward ADHD medication misuse. CONCLUSIONS: Based on limited prior research, it is suggested that upward counterfactuals may allow individuals to explain away the misuse of ADHD medication and avoid negative emotions such as guilt and shame related to current or prior ADHD medication misuse. In sum, additional research is needed to confirm preliminary findings that suggest counterfactual thinking could be a precursor to ADHD medication misuse.

Effects of weight and gender on a task of inattention.

OBJECTIVE: Previous studies have established that obese adolescents possess a stronger tendency to behave more impulsively and be more inattentive than healthy-weight children. Additionally, gender difference in inattention and impulsivity has also been substantiated by previous researchers. The current study examined the relationship between gender, body weight, and inattention and impulsivity in adolescents. It was hypothesized that obese males and females would have more inattentive and impulsive responses than their healthy-weight peers. METHOD: Participants were 113 adolescents between the ages of 14 and 19; all participants completed the CPT-II, a measure of inattentive and impulsive response styles. RESULTS: Findings indicated that males who were classified as overweight or obese scored higher on inattention than did obese females, healthy-weight males, and healthy-weight females. Additionally, females committed a greater number of commission errors and were less able to distinguish the target stimuli, suggestive of impulsive responding. CONCLUSION: These findings indicate a gender difference in regard to impulsive responding, and also reveal an interaction of weight status and gender on inattention. Implications for prevention and treatment are discussed.

The relationship between stress and delay discounting: a meta-analytic review.

The objective of the present meta-analytic review was two-fold: (a) to address the mixed findings of previous research by determining the relationship between stress and impulsivity; and (b) to examine age differences in this relationship. A total of 16 articles fulfilled the inclusion criteria for the present meta-analysis for a total sample size of 2189 participants (k=22) ranging in age from 36 months to 71 years. Using the statistical software, Comprehensive Meta-Analysis, Version 2.0 - Hedges's g was computed to estimate the effect size. Results showed that impulsivity was related to stress with a moderate-large effect size (g=0.590). Significant moderating effects were found for the type of stress measure (g=0.592) and the type of discounting measure (g=0.696) used. The current study emphasizes the need for further research on the relationship between stress and discounting as additional findings may aid in improving future prevention and intervention programs for health-risk behaviors.