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Objective: Irritability, inattention, and hyperactivity, which are common presentations of childhood psychopathology, have been associated with perturbed white matter microstructure. However, similar tracts have been implicated across these phenotypes; such non-specificity could be rooted in their high co-occurrence. To address this problem, we use a bifactor approach parsing unique and shared components of irritability, inattention, and hyperactivity, which we then relate to white matter microstructure., Method: We developed a bifactor model based on the Conners Comprehensive Behavioral Rating Scale in a sample of youth with no psychiatric diagnosis or a primary diagnosis of attention-deficit/hyperactivity disorder or disruptive mood dysregulation disorder (n = 521). We applied the model to an independent yet sociodemographically and clinically comparable sample (n = 152), in which we tested associations between latent variables and fractional anisotropy (FA)., Results: The bifactor model fit well (comparative fit index = 0.99; root mean square error of approximation = 0.07). The shared factor was positively associated with an independent measure of impulsivity (ρ S  = 0.88, p FDR  < .001) and negatively related to whole-brain FA (r = -0.20), as well as FA of the corticospinal tract (all p FWE  < .05). FA increased with age and deviation from this curve, indicating that altered white matter maturation was associated with the hyperactivity-specific factor (r = -0.16, p FWE  < .05). Inattention-specific and irritability-specific factors were not linked to FA., Conclusion: Perturbed white matter microstructure may represent a shared neurobiological mechanism of irritability, inattention, and hyperactivity related to heightened impulsivity. Furthermore, hyperactivity might be uniquely associated with a delay in white matter maturation., Plain Language Summary: In this study, researchers developed a model identifying shared aspects of key symptoms of disruptive mood dysregulation disorder (DMDD) and attention-deficit hyperactivity disorder (ADHD), more specifically irritability, inattention, and hyperactivity. In 521 participants, impulsivity emerged as a shared factor. Applied to 152 youth with brain imaging data, shared impulsivity, not specific symptoms, related to atypical brain structure. Additionally, hyperactivity was linked to delayed white matter maturation. Study findings suggest this approach might identify mechanisms of these childhood disorders that remain hidden when relying on traditional diagnostic categories., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Objective: Irritability and attention-deficit/hyperactivity disorder (ADHD) symptoms frequently co-occur in youth. Although ADHD has been associated with inhibitory control deficits, the literature on irritability and inhibitory control is mixed. Examining how irritability, ADHD symptoms, and inhibitory control interrelate both cross-sectionally and longitudinally across development could shed light on common and distinct mechanisms of youth psychopathology., Method: We utilized a cross-lagged panel model with data from 2 time points (at ages 10 and 12 years) of the Adolescent Brain and Cognitive Development (ABCD) Study (N = 7,444, or ∼63% of the baseline sample with full data at each time point) to test cross-sectional and longitudinal associations among parent-reported irritability and ADHD symptoms and behaviorally assessed inhibitory control. This was performed separately across discovery and replication subsamples, each n = 3,722., Results: As expected, irritability and ADHD symptoms exhibited strong cross-sectional and reciprocal cross-lagged associations. Higher ADHD symptoms at age 10 years were associated concurrently with poorer inhibitory control and predicted poorer inhibitory control at age 12. Contrary to predictions, inhibitory control was not significantly associated with irritability cross-sectionally, nor was it predictive of later irritability or ADHD symptoms., Conclusion: These findings highlight strong links between irritability and ADHD. Although inhibitory control deficits were linked to ADHD and predictive of its symptom course, inhibitory control had no significant associations with irritability. Future research should investigate other candidate mechanisms of the co-occurrence of irritability and ADHD symptoms and predictors of their developmental trajectories., Plain Language Summary: This study investigated how irritability, ADHD symptoms, and inhibitory control interrelate both cross-sectionally and longitudinally in a sample of youth from the Adolescent Brain and Cognitive Development (ABCD) Study (N = 7,444). Results indicate that irritability and ADHD symptoms exhibit strong reciprocal predictive relationships; however, inhibitory control does not predict later irritability or ADHD, though ADHD symptoms predicted later inhibitory control deficits. These findings corroborate the predictive relations between irritability and ADHD over development and highlight the need for continued exploration of mechanisms underlying their co-occurrence., (Copyright © 2024. Published by Elsevier Inc.)

Objective: Neighborhoods provide essential resources (eg, education, safe housing, green space) that influence neurodevelopment and mental health. However, we need a clearer understanding of the mechanisms mediating these relationships. Limited access to neighborhood resources may hinder youths from achieving their goals and, over time, shape their behavioral and neurobiological response to negatively biased environments blocking goals and rewards., Method: To test this hypothesis, 211 youths (aged ∼13.0 years, 48% boys, 62% identifying as White, 75% with a psychiatric disorder diagnosis) performed a task during functional magnetic resonance imaging. Initially, rewards depended on performance (unbiased condition); but later, rewards were randomly withheld under the pretense that youths did not perform adequately (negatively biased condition), a manipulation that elicits frustration, sadness, and a broad response in neural networks. We investigated associations between the Childhood Opportunity Index (COI), which quantifies access to youth-relevant neighborhood features in 1 metric, and the multimodal response to the negatively biased condition, controlling for age, sex, medication, and psychopathology., Results: Youths from less-resourced neighborhoods responded with less anger (p < .001, marginal R 2  = 0.42) and more sadness (p < .001, marginal R 2  = 0.46) to the negatively biased condition than youths from well-resourced neighborhoods. On the neurobiological level, lower COI scores were associated with a more localized processing mode (p = .039, marginal R 2  = 0.076), reduced connectivity between the somatic-motor-salience and the control network (p = .041, marginal R 2  = 0.040), and fewer provincial hubs in the somatic-motor-salience, control, and default mode networks (all p FWE  < .05)., Conclusion: The present study adds to a growing literature documenting how inequity may affect the brain and emotions in youths. Future work should test whether findings generalize to more diverse samples and should explore effects on neurodevelopmental trajectories and emerging mood disorders during adolescence., Diversity & Inclusion Statement: One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented racial and/or ethnic groups in science. One or more of the authors of this paper self-identifies as a member of one or more historically underrepresented sexual and/or gender groups in science. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group., (Copyright © 2024 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

Introduction: Lowering kidney stone risk and urine calcium oxalate supersaturation is a primary clinical focus for kidney stone prevention and can be achieved with multiple strategies. Common strategies include advice to increase fluid intake, restrict dietary sodium, or prescribing a thiazide-type diuretic. We investigated how physicians make these decisions in real-world practice and evaluate their efficacy based on 24-h urine collections., Methods: We reviewed medical charts for 203 kidney stone formers with idiopathic calcium stones from University of Chicago Kidney Stone Clinic between 2005 and 2020. Patients had three 24-h urines before an initial pre-treatment clinic visit and one follow-up 24-h urine. We analyzed changes in urine composition based on treatment advice using t tests and ANOVA., Results: Patients who received advice to increase fluid intake had lower urine volume at baseline (1.5 vs. 2.5 L/day, p < 0.001) and larger increase in urine volume at follow-up (0.6 vs. 0.1 L/day, p < 0.001) compared to those who did not receive the advice. Patients who were advised to restrict dietary sodium had a higher urine sodium at baseline (208 vs. 139 mEq/day, p < 0.001), a larger reduction in urine sodium (-28 vs. 13 mEq/day, p = 0.002), and larger reduction in urine calcium (-74 vs. -28 mg/day, p = 0.005) compared with those not advised to restrict dietary sodium. Patients started on a thiazide had a higher baseline urine calcium (281 vs. 213 mg/day) and larger reduction in urine calcium (-83 vs. -9 mg/day, p < 0.001) compared with patients not started on a thiazide. In combination, thiazide prescriptions with dietary sodium restriction reduced urine calcium by 99 mg/day and reduced calcium oxalate supersaturation from 8.0 to 5.5 and calcium phosphate supersaturation from 1.4 to 1.0., Conclusion: Providers use 24-h urine data to guide treatment strategy decisions. These strategies achieved the intended effects on urine composition and lowered kidney stone risk., (© 2022 S. Karger AG, Basel.)

Objective: Neurocognitive differences in pediatric obesity may be underpinned by cortical structural alterations. Differences in cortical thickness associated with severe obesity were examined, and preliminary evidence was sought for changes following vertical sleeve gastrectomy (VSG)., Methods: A total of 18 adolescents with severe obesity (OB) and 17 without obesity (nOB), aged 14 to 21, underwent T1-weighted structural magnetic resonance imaging. A subset was scanned twice 5 months apart to compare cortical thickness following VSG (n = 6) with two control groups: wait-listed (n = 9) and nOB (n = 12)., Results: At baseline, OB had a thinner cortex than nOB in motor and superior parietal cortices. At follow-up, VSG adolescents lost weight, the wait-listed group gained weight, and nOB did not change. Group × Time interactions indicated that VSG had cortical thinning in orbitofrontal, primary sensorimotor, superior, and middle temporal cortices and thickening in lingual, fusiform, and lateral occipital cortices. Wait-listed and nOB groups largely did not change., Conclusions: Severe obesity is associated with a thinner cortex in motor and attentional function-associated regions. VSG resulted in cortical thinning in reward valuation, sensory, and perceptual regions and thickening in visual regions. Surgery-related changes in regions distinct from those associated with obesity suggest compensation, rather than normalization. These results provide preliminary evidence supporting structural neural alterations following sleeve gastrectomy., (© 2021 The Obesity Society.)

In visual conflict tasks (e.g., Stroop or flanker), response times (RTs) are generally longer on incongruent trials relative to congruent ones. Two event-related-potential (ERP) components classically associated with the processing of stimulus conflict are the fronto-central, incongruency-related negativity (N inc ) and the posterior late-positive complex (LPC), which are derived from the ERP difference waves for incongruent minus congruent trials. It has been questioned, however, whether these effects, or other neural measures of incongruency (e.g., fMRI responses in the anterior cingulate), reflect true conflict processing, or whether such effects derive mainly from differential time-on-task. To address this question, we leveraged high-temporal-resolution ERP measures of brain activity during two behavioral tasks. The first task, a modified Erikson flanker paradigm (with congruent and incongruent trials), was used to evoke the classic RT and ERP effects associated with conflict. The second was a non-conflict control task in which, participants visually discriminated a single stimulus (with easy and hard discrimination conditions). Behaviorally, the parameters were titrated to yield similar RT effects of conflict and difficulty (27ms). Neurally, both within-task contrasts showed an initial fronto-central negative-polarity wave (N2-latency effect), but they then diverged. In the difficulty difference wave, the initial negativity led directly into the posterior LPC, whereas in the incongruency contrast the initial negativity was followed a by a second fronto-central negative peak (N inc ), which was then followed by a considerably longer-latency LPC. These results provide clear evidence that the longer processing for incongruent stimulus inputs do not just reflect time-on-task or difficulty, but include a true conflict-processing component., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Both stimulus and response conflict can disrupt behavior by slowing response times and decreasing accuracy. Although several neural activations have been associated with conflict processing, it is unclear how specific any of these are to the type of stimulus conflict or the amount of response conflict. Here, we recorded electrical brain activity, while manipulating the type of stimulus conflict in the task (spatial [Flanker] versus semantic [Stroop]) and the amount of response conflict (two versus four response choices). Behaviorally, responses were slower to incongruent versus congruent stimuli across all task and response types, along with overall slowing for higher response-mapping complexity. The earliest incongruency-related neural effect was a short-duration frontally-distributed negativity at ~200 ms that was only present in the Flanker spatial-conflict task. At longer latencies, the classic fronto-central incongruency-related negativity 'N(inc)' was observed for all conditions, but was larger and ~100 ms longer in duration with more response options. Further, the onset of the motor-related lateralized readiness potential (LRP) was earlier for the two vs. four response sets, indicating that smaller response sets enabled faster motor-response preparation. The late positive complex (LPC) was present in all conditions except the two-response Stroop task, suggesting this late conflict-related activity is not specifically related to task type or response-mapping complexity. Importantly, across tasks and conditions, the LRP onset at or before the conflict-related N(inc), indicating that motor preparation is a rapid, automatic process that interacts with the conflict-detection processes after it has begun. Together, these data highlight how different conflict-related processes operate in parallel and depend on both the cognitive demands of the task and the number of response options., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Issue Addressed: Flipcharts are widely used as education tools in Indigenous health but there is no published quantitative data on their use. As respiratory illness is the most frequent reason for hospitalisation of young children, we developed culturally sensitive flipcharts to educate carers of children on the 3 most common serious respiratory illness (bronchiolitis, pneumonia and bronchiectasis) affecting Indigenous children in the Northern Territory. In this study, we aimed to determine if use of these flipcharts improved the knowledge of these respiratory conditions among carers of Indigenous children admitted to the Royal Darwin Hospital., Methods: We assessed the knowledge of 60 carers pre- and post-flipchart education using a questionnaire. Pre- and post-flipchart education scores for the three illnesses were combined and were compared using non-parametric analyses., Results: Most carers were mothers (n = 43, 72%) aged between 20-40 years (n = 54, 90%) and lived in a remote community (n = 53, 88%). Knowledge of all respiratory conditions improved post education: median scores pre = 8 (Interquartile range 6, 10); post = 12 (10, 14), P = < 0.0001., Conclusions: The use of culturally appropriate educational flipcharts improves the knowledge of respiratory conditions among carers of Indigenous children hospitalised with common serious respiratory illness. SO WHAT? In the first paediatric quantitative study on the use of flipcharts as a means of providing health education to Indigenous Australians, we have shown that the use of culturally-appropriate flipcharts is an effective method of providing health education.

Background: Bronchiolitis is a major health burden in infants globally, particularly among Indigenous populations. It is unknown if 3 weeks of azithromycin improve clinical outcomes beyond the hospitalization period. In an international, double-blind randomized controlled trial, we determined if 3 weeks of azithromycin improved clinical outcomes in Indigenous infants hospitalized with bronchiolitis., Methods: Infants aged ≤24 months were enrolled from three centers and randomized to receive three once-weekly doses of either azithromycin (30 mg/kg) or placebo. Nasopharyngeal swabs were collected at baseline and 48 h later. Primary endpoints were hospital length of stay (LOS) and duration of oxygen supplementation monitored every 12 h until judged ready for discharge. Secondary outcomes were: day-21 symptom/signs, respiratory rehospitalizations within 6 months post-discharge and impact upon nasopharyngeal bacteria and virus shedding at 48 h., Results: Two hundred nineteen infants were randomized (n = 106 azithromycin, n = 113 placebo). No significant between-group differences were found for LOS (median 54 h for each group, difference = 0 h, 95% CI: -6, 8; p = 0.8), time receiving oxygen (azithromycin = 40 h, placebo = 35 h, group difference = 5 h, 95% CI: -8, 11; p = 0.7), day-21 symptom/signs, or rehospitalization within 6 months (azithromycin n = 31, placebo n = 25 infants, p = 0.2). Azithromycin reduced nasopharyngeal bacterial carriage (between-group difference 0.4 bacteria/child, 95% CI: 0.2, 0.6; p < 0.001), but had no significant effect upon virus detection rates., Conclusion: Despite reducing nasopharyngeal bacterial carriage, three large once-weekly doses of azithromycin did not confer any benefit over placebo during the bronchiolitis illness or 6 months post hospitalization. Azithromycin should not be used routinely to treat infants hospitalized with bronchiolitis., Clinical Trial Registration: The trial was registered with the Australian and New Zealand Clinical Trials Register: Clinical trials number: ACTRN1261000036099.

Background: Ensuring adherence to treatment and retention is important in clinical trials, particularly in remote areas and minority groups. We describe a novel approach to improve adherence, retention and clinical review rates of Indigenous children., Methods: This descriptive study was nested within a placebo-controlled, randomised trial (RCT) on weekly azithromycin (or placebo) for 3-weeks. Indigenous children aged ≤24-months hospitalised with acute bronchiolitis were recruited from two tertiary hospitals in northern Australia (Darwin and Townsville). Using mobile phones embedded within a culturally-sensitive approach and framework, we report our strategies used and results obtained. Our main outcome measure was rates of adherence to medications, retention in the RCT and self-presentation (with child) to clinic for a clinical review on day-21., Results: Of 301 eligible children, 76 (21%) families declined participation and 39 (13%) did not have access to a mobile phone. 186 Indigenous children were randomised and received dose one under supervision in hospital. Subsequently, 182 (99%) children received dose two (day-7), 169 (93%) dose three (day-14) and 180 (97%) attended their clinical review (day-21). A median of 2 calls (IQR 1-3) were needed to verify adherence. Importantly, over 97% of children remained in the RCT until their clinical endpoint at day-21., Conclusions: In our setting, the use of mobile phones within an Indigenous-appropriate framework has been an effective strategy to support a clinical trial involving Australian Indigenous children in urban and remote Australia. Further research is required to explore other applications of this approach, including the impact on clinical outcomes., Trial Registration: ACTRN12608000150347 (RCT component).

The hypothesis was tested that vitamin E protects chickens from a lethal Escherichia coli infection by inhibiting the biosynthesis of prostaglandins, thereby activating humoral immunity and phagocytosis. When chickens were fed supplement vitamin E at the level of 300 mg/kg diet, which is six times the presently used dietary level, endogenous PGE1, PGE2, and PGF2 alpha levels decreased in the immunopoietic organs, bursa, and spleen. Antibody titers to E. coli lipopolysaccharide and phagocytosis increased at the same time. Infection slightly increased prostaglandin levels and vitamin E appeared to compensate for this increase. Aspirin, a known prostaglandin inhibitor acted synergistically with vitamin E in depressing endogenous PG levels in bursa and decreasing mortality from E. coli infection.