Expanding the potential genes of inborn errors of immunity through protein interactions.

BACKGROUND: Inborn errors of immunity (IEI) are a group of genetic disorders that impair the immune system, with over 400 genes described so far, and hundreds more to be discovered. To facilitate the search for new genes, we need a way to prioritize among all the genes in the genome those most likely to play an important role in immunity. RESULTS: Here we identify a new list of genes by linking known IEI genes to new ones by using open-source databases of protein-protein interactions, post-translational modifications, and transcriptional regulation. We analyze this new set of 2,530 IEI-related genes for their tolerance of genetic variation and by their expression levels in various immune cell types. CONCLUSIONS: By merging genes derived from protein interactions of known IEI genes with transcriptional data, we offer a new list of candidate genes that may play a role in as-yet undiscovered IEIs.

Developing Prepare2Thrive, a community-based intervention targeting treatment engagement among African American individuals living with HIV and serious mental illness.

African American individuals living with HIV and serious mental illness (SMI) may report relatively low treatment engagement, despite treatment engagement being critical to managing both health conditions. Here, we have two aims: to describe the methodology we used to collect focus group data on treatment engagement with a sample of African American individuals living with HIV and SMI, and to describe the results of those focus groups in the context of intervention development. We conducted two focus groups (N = 15), integrating a social-ecological model for our theoretical framework, Community-Based Participatory Research for study design and execution, and group concept mapping for data analysis. Three thematic clusters relating to treatment engagement emerged from each group, with overlap across groups: Medication knowledge, Patient-provider relationships, and Barriers to treatment engagement. Items related to the Patient-provider relationship loaded onto all emergent clusters, demonstrating the pervasive impact of this variable. Findings informed the design of Prepare2Thrive, a community-based, culture-specific intervention aiming to increase treatment engagement among African American individuals living with HIV and SMI. Both our design and findings can be used in future collaborations aiming to maximize treatment engagement, and more broadly health, among individuals in this community.

Solid Cup vs Cluster Hole in Total Hip Arthroplasty: A 10-Year Randomized Control Trial.

BACKGROUND: Acetabular osteolysis is a major complication of total hip arthroplasty. It is caused in part by wear debris. It has been suggested that this debris can migrate through screw holes in the acetabular component. Solid-backed components have been used to prevent this migration and reduce osteolysis. Newer materials, however, have reduced wear debris. This study aimed to evaluate whether using solid-backed instead of cluster-hole components actually reduces osteolysis. This could open up the possibility of screws being used for greater stability where required. METHODS: This prospective trial randomized 100 patients undergoing cementless total hip arthroplasty to receive either cluster-hole or solid-backed acetabular components. A cementless cup and highly cross-linked polyethylene was used in all patients. Computed tomography, performed at 5 and 10 years after surgery, was assessed by a blinded radiologist for the presence of osteolysis. RESULTS: Of the 100 patients, 14 required screws for stability, and so were moved into a third "screw" group for per-protocol analysis. At 10 years after surgery, osteolytic lesions were discovered in 18.2% of patients. There was no difference in incidence or volume of osteolysis between patients with cluster-hole acetabular components and those with solid-backed components. CONCLUSION: This study reveals a low number of patients with osteolytic lesions 10 years after total hip arthroplasty performed with a modern cup design and highly cross-linked polyethylene liner. There was no clear benefit to using solid-backed acetabular components. Cluster-hole components, however, offer the option of screw augmentation when required.

Cluster hole versus solid cup in total hip arthroplasty: a randomized control trial.

Acetabular osteolysis has been linked to polyethylene debris that is generated in the hip migrating through screw holes in the acetabular component. Solid-backed acetabular components were designed to decrease this osteolysis. This prospective trial randomized 100 patients undergoing total hip arthroplasty to either a solid-backed or a cluster-hole acetabular component-all without screws. At 5years post-surgery, 34.4% of all patients had osteolytic lesions that were visible on CT. There was no significant difference in either presence or volume of the osteolytic lesions, cup migration or functional outcomes (OHS) between the groups. There may no longer be a detriment to using cluster-hole cups instead of solid cups in all hips. This would then give the surgeon the option to use screws for stability as required.

Neuropsychological assessment, intervention, and best practices for women with non-Central nervous system cancer: A scoping review of current standards.

Objective: Existing literature has sought to characterize the broad cognitive impact of non-central nervous system cancer and its treatment, including chemotherapy, radiation, surgery, and hormonal regulation. However, despite the frequency of women that are diagnosed with breast and gynecological cancer, there is limited research on the specific cognitive experiences of women undergoing cancer treatment. Presently, the current literature lacks concise guidance for neuropsychologists to support the cognitive health of women facing cancer, despite the acknowledged impact of cancer interventions and chronic illness on cognitive outcomes. Method: Applying scoping review criteria outlined by Peters et al. (2015) and adhering to Preferred Reporting Items for Systemic Reviews and Meta-Analysis (PRISMA) guidelines, we conducted a comprehensive examination of literature spanning multiple databases (Google Scholar, PubMed, PsychINFO) with a focus on the cognitive impact of cancer treatment on women. Conclusions: Women are subject to unique treatment-related outcomes due to the impact of hormonal alterations, differences in metabolization of certain chemotherapies, and psychosocial risk factors. Despite the known impact of cancer intervention, chronic illness, and cancer-related sequelae on cognitive outcomes, the current literature does not parsimoniously outline best practices for neuropsychologists to promote the health of women experiencing cancer. The current paper (1) provides an overview of the cognitive implications of cancer treatment with an intentional focus on cancers that are more prevalent in women versus men, (2) addresses the characteristics of this impact for women undergoing cancer intervention(s), and (3) provides possible intervention and treatment strategies for mental health providers and neuropsychologists.

Effect of processing speed and memory performance on classification accuracy of the dot counting test in a mixed neuropsychiatric sample.

OBJECTIVE: This study examined the impact of impairment in two specific cognitive abilities, processing speed and memory, on Dot Counting Test (DCT) classification accuracy by evaluating performance validity classification accuracy across cognitively unimpaired, single-domain impairment, and multidomain impairment subgroups within a mixed clinical sample. METHOD: Cross-sectional data were analyzed from 348 adult outpatients classified as valid (n = 284) or invalid (n = 64) based on four independent criterion performance validity tests (PVTs). Unimpaired (n = 164), single-domain processing speed impairment (n = 24), single-domain memory impairment (n = 53), and multidomain processing speed and memory impairment (n = 43) clinical subgroups were established among the valid group. Both the traditional DCT E-score and unrounded E-score were examined. RESULTS: Overall, the DCT demonstrated acceptable to excellent classification accuracy across the unimpaired (area under the curve [AUC] traditional E-score=.855; unrounded E-score=.855) and single-domain impairment groups (traditional E-score AUCs = .690-.754; unrounded E-score AUCs = .692-747). However, it did not reliably discriminate the multidomain processing speed and memory impairment group from the invalid performers (traditional and unrounded E-scores AUC = .557). CONCLUSIONS: Findings support the DCT as a non-memory-based freestanding PVT for use with single-domain cognitive impairment, with traditional E-score ≥17 (unrounded E-score ≥16.95) recommended for those with memory impairment and traditional E-score ≥19 (unrounded ≥18.08) with processing speed impairment. Moreover, results replicated previously established optimal cutoffs for unimpaired groups using both the traditional (≥14) and unrounded (≥13.84) E-scores. However, the DCT did not reliably discriminate between invalid performance and multidomain cognitive impairment, indicating caution is warranted when using the DCT with patients suspected of greater cognitive impairment.

Adverse childhood experiences, cognitive functioning, depression, and anxiety in adulthood.

BACKGROUND: Evidence suggests that adverse childhood experiences (ACEs) predict cognitive dysfunction, possibly through direct (e.g., brain structure/function changes) and indirect (e.g., increased psychopathology risk) pathways. However, extant studies have focused on young and older adults, with limited understanding of how ACEs affect cognitive health in midadulthood. OBJECTIVE: This study compared psychiatric and cognitive differences between adults at high- and low-risk of adverse health outcomes based on the ACE risk classification scheme. PARTICIPANTS AND SETTING: Adult patients (N = 211; 46.9% female; Mage = 44.1, SD = 17.1; Meducation = 13.8, SD = 3.0) consecutively referred for outpatient neuropsychological evaluation within a large, Midwestern academic medical center. METHOD: Patients were divided into high and low ACE groups based on the number of ACEs endorsed. Subsequently, a series of one-way analyses of variances were conducted to compare high versus low ACE groups on the Test of Premorbid Functioning, Wechsler Adult Intelligence Scale-Fourth Edition Digit Span Test, Trail Making Test-Parts A and B, Rey Auditory Verbal Learning Test, Beck Depression Inventory-II, and Beck Anxiety Inventory scores. RESULTS: Significant group differences were detected for anxiety and depression with the high ACE group endorsing significantly greater depression and anxiety symptoms relative to the low ACE group. High and low ACE groups did not significantly differ on any cognitive measures. CONCLUSIONS: Results indicate that an individual's psychological health, but not cognitive functioning, is impacted by the level of ACE exposure. Study findings highlight the importance of including ACE measures in neuropsychological evaluations, as it will aid in case conceptualization and tailoring treatment recommendations. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Social Determinants of Health: Associations Between Dichotomous Versus Dimensional Scores, Neuropsychological Test Performance, and Psychiatric Symptoms.

This study examined the utility of dichotomous versus dimensional scores across two measures of social determinants of health (SDOH) regarding their associations with cognitive performance and psychiatric symptoms in a mixed clinical sample of 215 adults referred for neuropsychological evaluation (Mage = 43.91, 53.5% male, 44.2% non-Hispanic White). Both dimensional and dichotomous health literacy scores accounted for substantial variance in all cognitive outcomes assessed, whereas dimensional and dichotomous adverse childhood experience scores were significantly associated with psychiatric symptoms. Tests of differences between correlated correlations indicated that correlations with cognitive and psychiatric outcomes were not significantly different across dimensional versus dichotomous scores, suggesting that these operationalizations of SDOH roughly equivalently characterize risk of poorer cognitive performance and increased psychiatric symptoms. Results highlight the necessity of measuring multiple SDOH, as different SDOH appear to be differentially associated with cognitive performance versus psychiatric symptoms. Furthermore, results suggest that clinicians can use cut-scores when characterizing patients' risk of poor cognitive or psychiatric outcomes based on SDOH.

Does Far Cortical Locking Improve Fracture Healing in Distal Femur Fractures: A Randomised, Controlled, Prospective Multicentre Study.

(1) Background: Bone healing is influenced by various mechanical factors, such as stability, interfragmentary motion, strain rate, and direction of loading. Far cortical locking (FCL) is a novel screw design that promotes bone healing through controlled fracture motion. (2) Methods: This study compared the outcome of distal femur fractures treated with FCL or SL (standard locking) screws and an NCB plate in a randomised controlled prospective multicentre trial. The radiographic union scale (RUST) and healing time was used to quantify bone healing on follow-up imaging. (3) Results: The study included 21 patients with distal femur fractures, 7 treated with SL and 14 treated with FCL screws. The mean working length for patients with SL screws was 6.1, whereas for FCL screws, it was 3.9. The mean RUST score at 6 months post fracture was 8.0 for patients with SL plates and 7.3 for patients with FCL plates (p value > 0.05). The mean healing time was 6.5 months for patients with SL plates and 9.9 months for patients with FCL plates (p value < 0.05). (4) Conclusions: Fractures fixed with SL plates had longer working lengths and faster healing times when compared to FCL constructs, suggesting that an adequate working length is important for fracture healing regardless of screw choice.

A Neighborhood-level analysis of mental health distress and income inequality as quasi-longitudinal risk of reported COVID-19 infection and mortality outcomes in Chicago.

Extant literature investigates the impact of COVID-19 on mental health outcomes, however there is a paucity of work examining mental health distress as a risk factor for COVID-19 outcomes. While systemic variables like income inequality relate to both mental health and COVID-19, more work is needed to test theoretically informed models including such variables. Using a social-ecological framework, we aimed to address these gaps in the literature by conducting a neighborhood-level analysis of potential mental health distress and systemic- (income inequality) level predictors of reported COVID-19 infection and mortality over time in Chicago. Neighborhood-level comparisons revealed differences in mental health distress, income inequality, and reported COVID-19 mortality, but not reported COVID-19 infection. Specifically, Westside and Southside neighborhoods generally reported higher levels of mental health distress and greater concentration of poverty. The Central neighborhood showed a decline in reported mortality rates over time. Multi-level negative binomial models established that Zip-codes with greater mental health distress were at increased reported COVID-19 infection risk, yet lower mortality risk; Zip-codes with more poverty were at increased reported COVID-19 infection risk, yet lower mortality risk; and Zip-codes with the highest percentage of People of Color were at decreased risk of reported COVID-19 mortality. Taken together, these findings substantiate Chicago neighborhood-level disparities in mental health distress, income inequality, and reported COVID-19 mortality; identify unique differential associations of mental health distress and income inequality to reported COVID-19 infection and reported mortality risk; and, offer an alternative lens towards understanding COVID-19 outcomes in terms of race/ethnicity.

Using the Grooved Pegboard Test as an Embedded Validity Indicator in a Mixed Neuropsychiatric Sample with Varying Cognitive Impairment: Cross-Validation Problems.

Embedded validity indicators (EVIs) derived from motor tests have received less empirical attention than those derived from tests of other neuropsychological abilities, particularly memory. Preliminary evidence suggests that the Grooved Pegboard Test (GPB) may function as an EVI, but existing studies were largely conducted using simulators and population samples without cognitive impairment. In this study we aimed to evaluate the GPB's classification accuracy as an EVI among a mixed clinical neuropsychiatric sample with and without cognitive impairment. This cross-sectional study comprised 223 patients clinically referred for neuropsychological testing. GPB raw and T-scores for both dominant and nondominant hands were examined as EVIs. A known-groups design, based on ≤1 failure on a battery of validated, independent criterion PVTs, showed that GPB performance differed significantly by validity group. Within the valid group, receiver operating characteristic curve analyses revealed that only the dominant hand raw score displayed acceptable classification accuracy for detecting invalid performance (area under curve [AUC] = .72), with an optimal cut-score of ≥106 seconds (33% sensitivity/88% specificity). All other scores had marginally lower classification accuracy (AUCs = .65-.68) for differentiating valid from invalid performers. Therefore, the GPB demonstrated limited utility as an EVI in a clinical sample containing patients with bona fide cognitive impairment.

Does comorbid depression impact executive functioning (EF) in adults diagnosed with ADHD?: a comparison of EF across diagnoses in clinically-referred individuals.

INTRODUCTION: Executive functioning (EF) is a salient factor in both ADHD as well as depressive disorders. However, sparse literature has examined whether depression severity impacts EF concurrently among adults with ADHD. The goal of this study was to examine differences in EF between adult patients diagnosed with ADHD and those diagnosed with a non-ADHD primary psychopathological condition, as a function of both ADHD presentation and depression severity in a diverse clinical sample. METHOD: This crosssectional study included 404 adult patients clinically referred for neuropsychological evaluation to assist with differential diagnosis and/or treatment planning related to known or suspected ADHD. Various EF tasks and a measure of depression severity were administered. One-way MANOVA analyses were conducted to compare EF performance between individuals diagnosed with ADHD or a non-ADHD primary psychopathological condition, with additional analyses examining group differences based on ADHD presentation and depression severity. Regression analyses also examined the potential contribution of depression severity to each EF measure within each group. RESULTS: No significant EF performance differences were found when comparing individuals diagnosed with ADHD and those with a non-ADHD primary psychopathological condition, nor based on ADHD presentation. When comparing across groups using cut-offs for high or low depression, only one EF measure showed significant differences between groups. Further, depression severity generally did not predict reduced EF performances with the exception of verbal fluency and working memory performances in select groups. CONCLUSIONS: This study demonstrated that individuals with ADHD generally perform comparably on EF measures regardless of the presence or absence of comorbid depression. These results suggest further examination of EF deficits when they emerge for adults with ADHD, especially beyond comorbid depression severity.

Ondansetron-induced pseudoallergy with non-ischemic myocardial injury: A rare case report of Kounis syndrome.

Ondansetron is an FDA-approved selective serotonin 5-HT3 receptor commonly indicated as an anti-emetic agent for nausea and vomiting. It is rare to observe fatal reactions from ondansetron despite having no allergies or previous exposure. We report a case of anaphylactoid reaction with spontaneous coronary vasospasms in response to intravenous ondansetron.

A scoping review of stereotype threat for BIPOC: Cognitive effects and intervention strategies for the field of neuropsychology.

OBJECTIVE: Abundant evidence documents stereotype threat's (ST) detrimental effect on test performance across identities and contexts (i.e., eliciting underperformance). Review of the literature shows varied aspects of both stereotyped identities and cognition are inconsistently explored across studies. Only a portion of the literature focuses on ST's impact on Black, Indigenous, and People of Color (BIPOC). It is important to understand and learn to mitigate ST, particularly for historically marginalized and systemically oppressed BIPOC patients. Relevance exists for neuropsychologists, who engage in activities (i.e., assessments) that may activate ST, and should be aware of additional factors impacting testing results and clinical decision making. METHOD: Using scoping review criteria (Peters et al., 2015) and Preferred Reporting Item for Systemic Reviews and Meta-Analysis (PRISMA) guidelines, we reviewed literature across multiple databases (Google Scholar, PubMed, PsychINFO) on ST and cognition with a focus on BIPOC. RESULTS: The current literature suggests that race-based ST may be implicated in underperformance for executive functioning and separately working memory. There is limited research on the effects of ST for memory, language, attention, and visuospatial skills. CONCLUSION: Research on ST requires additional attention to establish interventions to mitigate negative effects in practice. These results provide 1) an overview of the cognitive implications of ST, 2) address the scope of this impact for BIPOC, and 3) provide possible intervention and training strategies for neuropsychologists and other clinicians to work to mitigate the effects of ST on BIPOC.

Something new and something blue: Responses to novelty in a rodent model of depression and epilepsy comorbidity.

A bidirectional comorbidity exists between depression and epilepsy such that patients with epilepsy are at higher risk for developing depression, and vice versa. Each of these conditions individually can be complicated by behavioral effects that worsen quality of life, but less is known about these interactions within the comorbidity of depression and epilepsy. The SwLo rat has been selectively bred for depression-relevant behaviors and exhibits enhanced limbic seizure susceptibility. This study sought to characterize the effects of novelty and stress on the SwLo rodent model of this comorbidity. It was hypothesized that SwLo rats would exhibit altered responses to novelty, reflected in hyperactivity-, anxiety-, sensation seeking-, and/or compulsive behaviors, and that this would be exacerbated with stress. Compared to the SwHi rat (their depression- and epilepsy-resistant counterparts), SwLo rats showed increased entries in all areas of the Open Field Test and spent significantly more time in the light compartment of the Light-Dark Box. SwLo rats also had a significantly higher number of rearing behaviors in the inner squares of the Open Field Test, the closed arms of the Elevated Plus Maze, and both areas of the Light-Dark Box. They demonstrated increased Nestlet shredding but showed no difference in a marble burying task or in latency to consume food in a novelty suppressed feeding task. Interestingly, restraint stress showed little effect on these behaviors, despite increasing corticosterone levels. Combined, these results suggest an increase in exploratory sensation seeking and hypervigilant information-gathering behaviors in the SwLo rat that are not dependent on corticosterone levels. This shows the utility of this model for studying behavioral effects of comorbid depression and epilepsy and allows for their use in identifying underlying mechanisms or screening treatment strategies for this complex comorbidity.

Assessing performance validity during attention-deficit/hyperactivity disorder evaluations: Cross-validation of non-memory embedded validity indicators.

Embedded performance validity tests (PVTs) are key components of neuropsychological evaluations. However, most are memory-based and may be less useful in the assessment of attention-deficit/hyperactivity disorder (ADHD). Four non-memory-based validity indices derived from processing speed and executive functioning measures commonly included in ADHD evaluations, namely Verbal Fluency (VF) and the Trail Making Test (TMT), were cross-validated using the Rey 15-Item Test (RFIT) Recall and Recall/Recognition as memory-based comparison measures. This consecutive case series included data from 416 demographically-diverse adults who underwent outpatient neuropsychological evaluation for ADHD. Validity classifications were established, with ≤1 PVT failure of five independent criterion PVTs as indicative of valid performance (374 valid performers/42 invalid performers). Among the statistically significant validity indicators, TMT-A and TMT-B T-scores (AUCs = .707-.723) had acceptable classification accuracy ranges and sensitivities ranging from 29%-36% (≥89% specificity). RFIT Recall/Recognition produced similar results as TMT-B T-score with 42% sensitivity/90% specificity, but with lower classification accuracy. In evaluating adult ADHD, VF and TMT embedded PVTs demonstrated comparable sensitivity and specificity values to those found in other clinical populations but necessitated alternate cut-scores. Results also support use of RFIT Recall/Recognition over the standard RFIT Recall as a PVT for adult ADHD evaluations.

A comparison of embedded validity indicators from the Stroop Color and Word Test among adults referred for clinical evaluation of suspected or confirmed attention-deficit/hyperactivity disorder.

This study investigated the utility of four Stroop Color and Word Test (SCWT) indices, including the raw score and T score for the word reading (WR) and color naming (CN) trials, as embedded performance validity tests (PVTs) within a sample referred for evaluation of suspected or known attention-deficit/hyperactivity disorder (ADHD). Data were analyzed from a final sample of 317 patients consecutively referred for ADHD evaluation, which was divided into groups with invalid (n = 43; 14%) and valid neuropsychological test performance (n = 274; 86%). A subset of the valid group with confirmed ADHD diagnoses (n = 226; 71%) were also analyzed separately. Classification accuracy for the overall valid sample was in the acceptable range (AUCs = .757-.794), with optimal cut scores of WR raw ≤75 (54% sensitivity/90% specificity), WR T score ≤ 28 (54% sensitivity/88% specificity), CN raw ≤57 (42% sensitivity/90% specificity), and CN T score ≤ 30 (40% sensitivity/90% specificity). Classification accuracy was also in the acceptable range for the ADHD-confirmed subgroup (AUCs = .750-.790), with optimal cut scores of WR Raw ≤ 75 (54% sensitivity/89% specificity), WR T score ≤ 28 (54% sensitivity/87% specificity), CN Raw ≤ 57 (42% sensitivity/90% specificity), and CN T score ≤ 30 (40% sensitivity/90% specificity). These findings indicate that embedded PVTs derived from the SCWT, particularly those derived from the WR trial, are effective measures for determining validity status in samples with suspected or confirmed ADHD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Mentorship in clinical neuropsychology: Survey of current practices, cultural responsiveness, and untapped potential.

INTRODUCTION: Neuropsychology trainees have identified mentorship as an important factor in their training. Limited past work has been conducted on mentorship within neuropsychology, and there is a need to better understand the experiences and perspectives of neuropsychology mentors. METHOD: Self-identified mentors in clinical neuropsychology completed a survey about their mentorship practices, including culturally responsive mentorship, as well as perceived barriers and challenges to providing effective mentorship. Themes were derived using qualitative analyses for free response questions, and descriptive statistics were calculated for quantitative variables. RESULTS: Mentors identified assessment, professionalism, and ethics as top priorities in mentorship, which may reflect the overlap within neuropsychology of assessment supervision and mentoring. Reported best practices included being self-aware and engaging in a personalized approach to mentorship relationships that varies depending upon the needs of the mentee. A majority reported that their training program is not diverse and they themselves do not mentor trainees from diverse backgrounds which provides a clear area for targeted efforts to recruit and retain diversity in the discipline. Mentors described practices related to discussing diversity-related differences with their trainees including self-disclosure, creating a safe space for conversations, and tailoring discussions to the individual trainee. They reported an interest in more training on how to engage in culturally competent mentorship. Two barriers to providing effective mentorship identified most by mentors were time constraints and a lack of training. CONCLUSIONS: These results highlight a variety of perspectives and approaches to mentorship, which may be beneficial for mentors to consider as they reflect on their mentorship practices and/or for trainees as part of their professional development toward becoming future mentors themselves. These results also highlight the need for a greater emphasis on mentorship training within neuropsychology, including training in culturally responsive mentorship practices.

The Actin-Capping Protein Alpha-Adducin Is Required for T-Cell Costimulation.

Alpha-adducin (Add1) is a critical component of the actin-spectrin network in erythrocytes, acting to cap the fast-growing, barbed ends of actin filaments, and recruiting spectrin to these junctions. Add1 is highly expressed in T cells, but its role in T-cell activation has not been examined. Using a conditional knockout model, we show that Add1 is necessary for complete activation of CD4+ T cells in response to low levels of antigen but is dispensable for CD8+ T cell activation and response to infection. Surprisingly, costimulatory signals through CD28 were completely abrogated in the absence of Add1. This study is the first to examine the role of actin-capping in T cells, and it reveals a previously unappreciated role for the actin cytoskeleton in regulating costimulation.