Joint transcriptomic and cytometric study of children with peanut allergy reveals molecular and cellular cross talk in reaction thresholds.

BACKGROUND: Reaction thresholds in peanut allergy are highly variable. Elucidating causal relationships between molecular and cellular processes associated with variable thresholds could point to therapeutic pathways for raising thresholds. OBJECTIVE: The aim of this study was to characterize molecular and cellular systemic processes associated with reaction threshold in peanut allergy and causal relationships between them. METHODS: A total of 105 children aged 4 to 14 years with suspected peanut allergy underwent double-blind, placebo-controlled food challenge to peanut. The cumulative peanut protein quantity eliciting allergic symptoms was considered the reaction threshold for each child. Peripheral blood samples collected at 0, 2, and 4 hours after challenge start were used for RNA sequencing, whole blood staining, and cytometry. Statistical and network analyses were performed to identify associations and causal mediation between the molecular and cellular profiles and peanut reaction threshold. RESULTS: Within the cohort (N = 105), 81 children (77%) experienced allergic reactions after ingesting varying quantities of peanut, ranging from 43 to 9043 mg of cumulative peanut protein. Peripheral blood expression of transcripts (eg, IGF1R [false discovery rate (FDR) = 5.4e-5] and PADI4 [FDR = 5.4e-5]) and neutrophil abundance (FDR = 9.5e-4) were associated with peanut threshold. Coexpression network analyses revealed that the threshold-associated transcripts were enriched in modules for FcγR-mediated phagocytosis (FDR = 3.2e-3) and Toll-like receptor (FDR = 1.4e-3) signaling. Bayesian network, key driver, and causal mediation analyses identified key drivers (AP5B1, KLHL21, VASP, TPD52L2, and IGF2R) within these modules that are involved in bidirectional causal mediation relationships with neutrophil abundance. CONCLUSION: Key driver transcripts in FcγR-mediated phagocytosis and Toll-like receptor signaling interact bidirectionally with neutrophils in peripheral blood and are associated with reaction threshold in peanut allergy.

Multiscale study of the oral and gut environments in children with high- and low-threshold peanut allergy.

BACKGROUND: The oral and gut microbiomes have each been associated with food allergy status. Within food allergy, they may also influence reaction thresholds. OBJECTIVE: Our aim was to identify oral and gut microbiota associated with reaction thresholds in peanut allergy. METHODS: A total of 59 children aged 4 to 14 years with suspected peanut allergy underwent double-blind, placebo-controlled food challenge to peanut. Those children who reacted at the 300-mg or higher dose of peanut were classified as high-threshold (HT), those who reacted to lower doses were classified as low-threshold (LT), and those children who did not react were classified as not peanut allergic (NPA). Saliva and stool samples collected before challenge underwent DNA isolation followed by 16S rRNA sequencing and short-chain fatty acid measurement. RESULTS: The 59 participants included 38 HT children and 13 LT children. Saliva microbiome α-diversity (Shannon index) was higher in LT children (P = .017). We identified saliva and stool microbiota that distinguished HT children from LT children, including oral Veillonella nakazawae (amplicon sequence variant 1979), which was more abundant in the HT group than in the LT group (false discovery rate [FDR] = 0.025), and gut Bacteroides thetaiotaomicron (amplicon sequence variant 6829), which was less abundant in HT children than in LT children (FDR = 0.039). Comparison with NPA children revealed consistent ordinal trends between these discriminating species and reaction thresholds. Importantly, many of these threshold-associated species were also correlated with short-chain fatty acid levels at the respective body sites, including between oral V nakazawae and oral butyrate (r = 0.57; FDR = 0.049). CONCLUSION: Findings from this multiscale study raise the possibility of microbial therapeutics to increase reaction thresholds in children with food allergy.

Convergent and criterion validity of the CogState computerized brief battery cognitive assessment in women with and without breast cancer.

OBJECTIVE: Computerized tests have increasingly garnered interest for assessing cognitive functioning due to their potential logistical and financial advantages over traditional 'pencil and-paper' neuropsychological tests. However, psychometric information is necessary to guide decisions about their clinical and research utility with varied populations. We explored the convergent construct validity and criterion validity of the CogState computerized tests in breast cancer survivors, a group known to present with mostly mild, subtle cognitive dysfunction. METHOD: Fifty-three post-menopausal women (26 breast cancer survivors, 27 healthy controls) completed the CogState Brief Battery tests with passed performance checks, conceptually matched traditional neuropsychological tests, and a self-report measure of daily functioning, the Functional Activities Questionnaire. RESULTS: Significant positive correlations were found between the CogState Brief Battery tests and traditional neuropsychological tests, although the traditional tests specifically hypothesized to correlate with CogState tests did not reach statistical significance. Analysis of Covariance results showed preliminary support for criterion validity, as the patient and control groups differed on the traditional test of working memory (Digits Backwards, p = .01), with a trend towards significance for the CogState test of working memory (One Back, p = .02), controlled for age, race, and mood. CONCLUSIONS: The results provide preliminary support for further research to determine if the CogState tests are viable as screening tools to detect subtle cognitive differences between breast cancer survivors and healthy women. Our study was limited by the low base rate of cognitive impairment and small sample size. We recommend further research employing sufficiently powered sample sizes and a longitudinal, repeated measures study design.

Parent-directed intervention for children with cancer-related neurobehavioral late effects: a randomized pilot study.

OBJECTIVE : To evaluate feasibility and preliminary efficacy of an intervention directed at parents of childhood cancer survivors (CCSs) with neurobehavioral late effects to improve targeted parenting skills, and thus to indirectly benefit the child's educational functioning. METHODS : 44 CCSs and their parents were randomized. Intervention-arm parents participated in eight individual training sessions augmented by a 3-month telephone support period. Pre- and postparent measures and child performance on Wechsler Individual Achievement Test-II and School Motivation and Learning Strategies Inventory assessed intervention effects. RESULTS : 90% of intervention parents completed the program with high adherence/perceived benefit. Between-group effect sizes ranged from d = 0.77 to d = 1.45 for parent knowledge, efficacy, frequency of pro-learning behaviors, and d = 0.21 to d = 0.76 for child academic scores. Parental time spent in intervention activities was associated with academic change. CONCLUSIONS : A parent-directed intervention to indirectly promote academic functioning in CCSs appears feasible and effective in improving targeted parenting outcomes and for selected child academic outcomes.

Effectiveness of the Comalli Stroop Test as a measure of negative response bias.

Practice guidelines recommend the use of multiple performance validity tests (PVTs) to detect noncredible performance during neuropsychological evaluations, and PVTs embedded in standard cognitive tests achieve this goal most efficiently. The present study examined the utility of the Comalli version of the Stroop Test as a measure of response bias in a large sample of "real world" noncredible patients (n = 129) as compared with credible neuropsychology clinic patients (n=233). The credible group performed significantly better than the noncredible group on all trials, but particularly on word-reading (Stroop A) and color-naming (Stroop B); cut-scores for Stroop A and Stroop B trials were associated with moderate sensitivity (49-53%) as compared to the low sensitivity found for the color interference trial (29%). Some types of diagnoses (including learning disability, severe traumatic brain injury, psychosis, and depression), very advanced age (⩾80), and lowered IQ were associated with increased rates of false positive identifications, suggesting the need for some adjustments to cut-offs in these subgroups. Despite some previous reports of an inverted Stroop effect (i.e., color-naming worse than color interference) in noncredible subjects, individual Stroop word reading and color naming trials were much more effective in identifying response bias.

Neurocognitive and behavioral outcomes in Latino childhood cancer survivors.

BACKGROUND: Children with brain tumors and leukemia are at risk for neurocognitive and behavioral late effects due to central nervous system-directed therapies. Few studies have examined these outcomes in ethnic minority samples, despite speculation that socio-demographic factors may increase vulnerability for adverse neurobehavioral outcomes. We evaluated the neurocognitive and behavioral outcomes and their impact on the health-related quality of life in survivors of childhood cancer drawn from Latino families in the Los Angeles region. PROCEDURE: Using culturally-relevant recruitment strategies, 73 predominantly Spanish-speaking parents of pediatric brain tumor or leukemia survivors completed standardized questionnaires, including the Conners parent-report and the Bidimensional Acculturation Scales. Clinical and socio-demographic factors influencing the development of neurocognitive and behavioral dysfunction were examined. RESULTS: Approximately 50% of the children placed at or above the "elevated" level for difficulties with attention, school-based learning, and peer relations. Younger age at diagnosis significantly predicted dysfunction in inattention, learning problems, and hyperactivity/impulsivity. Children whose parents were less adherent to the non-Hispanic white culture were more likely to have problems with peer relations and executive functioning. HRQL was significantly lower in survivors with neurocognitive and behavioral dysfunction relative to those with normal range scores on the Conners scale. CONCLUSIONS: In addition to the child's age at diagnosis, acculturation appears to predict select neurocognitive and behavioral outcomes in this socio-demographically homogeneous sample of Latino families. Further research is needed to understand the interaction of ethnic and cultural factors with therapeutic exposures in determining the adverse neurobehavioral outcomes, so as to optimally design interventions.

Outcomes of couples with infidelity in a community-based sample of couple therapy.

Infidelity is an often cited problem for couples seeking therapy, but the research literature to date is very limited on couple therapy outcomes when infidelity is a problem. The current study is a secondary analysis of a community-based sample of couple therapy in Germany and Austria. Outcomes for 145 couples who reported infidelity as a problem in their relationship were compared with 385 couples who sought therapy for other reasons. Analyses based on hierarchical linear modeling revealed that infidelity couples were significantly more distressed and reported more depressive symptoms at the start of therapy but continued improving through the end of therapy and to 6 months posttherapy. At the follow-up assessment, infidelity couples were not statistically distinguishable from non-infidelity couples, replicating previous research. Sexual dissatisfaction did not depend on infidelity status. Although there was substantial missing data, sensitivity analyses suggested that the primary findings were not due to missing data. The current findings based on a large community sample replicated previous work from an efficacy trial and show generally optimistic results for couples in which there has been an affair.

Difficulties regulating emotions: Do binge eaters have fewer strategies to modulate and tolerate negative affect?

The current study evaluated whether difficulties regulating emotions explained unique variance in binge eating and examined which types of emotion regulation difficulties are most strongly associated with binge eating. The Eating Disorders Diagnostic Scale and the Difficulties in Emotion Regulation Scale were completed by 695 undergraduates. Hierarchical regression results indicated that difficulties regulating emotions accounted for a significant amount of the variance in binge eating over and above sex, food restriction, and over-evaluation of weight and shape. Results also indicated that greater difficulty identifying and making sense of emotional states, and limited access to emotion regulation strategies were primarily responsible for the link between emotion regulation difficulties and binge eating. This supports a model of binge eating that includes emotional vulnerability and a deficit of skills to functionally modulate negative moods.

Sexually transmitted disease rates and high-risk sexual behaviors in borderline personality disorder versus borderline personality disorder with substance use disorder.

We examined the rates of sexually transmitted diseases (STDs) in women with borderline personality disorder (BPD) (using PDE and SCID-II) and substance abuse or dependence (SCID-I) (BPD-SUD) (N=82) compared with those with BPD-only (N=102), exploring mediators of this relationship. Participants were interviewed about STD history (gonorrhea, genital herpes, syphilis, trichomonas, human papillomavirus, and HIV), condom use, number of sexual partners, poverty, and prostitution. BPD-SUD appeared to be particularly at high risk for STDs, reporting significantly more STDs than BPD (F[1,172]=11.74, p=0.001, d=.27), particularly for gonorrhea, trichomonas, and human papillomavirus. The relationship between BPD-SUD and STDs is mediated by poverty, prostitution in the last year, recent unprotected sex with two or more partners, and >20 lifetime partners (z=-2.16 which is p=0.03), with prostitution alone making a significant contribution to this relationship (z=-2.49, p=0.01).