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BACKGROUND - Mucus cytokines have been linked to baseline metrics of quality of life and olfactory function in patients with chronic rhinosinusitis (CRS). However, their potential utility in predicting postoperative outcomes has not been assessed. Therefore, in this study we evaluated the role of mucus cytokines in predicting 22-item Sino-Nasal Outcomes Test (SNOT-22) scores after endoscopic sinus surgery (ESS) in a prospective cohort of CRS patients.
METHODS - One hundred forty-seven patients with CRS electing surgical therapy were enrolled in a longitudinal cohort study. Mucus was collected intraoperatively from the middle meatus and tested for interleukin (IL)-1β, IL-2, -4, -5, -6, -7,- 8, -9, -10, -12, -13, -17A, and -21; tumor necrosis factor (TNF)-α; interferon-γ; eotaxin; and RANTES (regulated-on-activation, normal T-cell expressed and secreted) expression using a multiplex flow-cytometric bead assay. Sixty-two patients were followed postoperatively (average, 10.2 months) with baseline and follow-up SNOT-22 surveys. Stepwise multivariate linear regression was used to model relationships between baseline cytokines, phenotype, and average postoperative SNOT-22 total and domain scores. A machine learning approach using a random forest algorithm was also used to investigate potential nonlinear relationships.
RESULTS - IL-5 was an independent predictor of postoperative total SNOT-22 improvement (β = -8.8, p < 0.0001), whereas IL-2 levels predicted postoperative worsening (β = 6.97, p = 0.0015). Similar relationships were also seen for postoperative SNOT-22 domain scores. The overall model was also noted to be significant fit for the data (adjusted R = 0.398, p < 0.0001). The random forest model similarly identified IL-5, TNF-α, IL-13, and IL-2 as major predictors of postoperative SNOT-22 scores.
CONCLUSION - Mucus cytokine profiles may help identify CRS patients who are likely to obtain postoperative improvement after ESS.
© 2019 ARS-AAOA, LLC.
Purpose We examined associations between vocal communication with canonical syllables and expressive language and then examined 2 potential alternative explanations for such associations. Method Specifically, we tested whether the associations remained when excluding canonical syllables in identifiable words and controlling for the number of communication acts. Participants included 68 preverbal or low verbal children with autism spectrum disorder ( = 35.26 months). Results Vocal communication with canonical syllables and expressive language were concurrently and longitudinally associated with moderate to strong (s = .13-.70) and significant (s < .001) effect sizes. Even when excluding spoken words from the vocal predictor and controlling for the number of communication acts, vocal communication with canonical syllables predicted expressive language. Conclusions The findings provide increased support for measuring vocal communication with canonical syllables and for examining a causal relation between vocal communication with canonical syllables and expressive language in children with ASD who are preverbal or low verbal. In future studies, it may be unnecessary to eliminate identifiable words when measuring vocal communication in this population. Following replication, vocal communication with canonical syllables may be considered when making intervention- planning decisions.
Irritability is garnering increasing attention in psychiatric research as a transdiagnostic marker of both internalizing and externalizing disorders. These disorders often emerge during adolescence, highlighting the need to examine changes in the brain and in psychological functioning during this developmental period. Adolescents were recruited for a longitudinal study examining the effects of early life stress on the development of psychopathology. The 151 adolescents (73 M/78 F, average age = 11.5 years, standard deviation = 1.1) were scanned with a T1-weighted MRI sequence and parents completed reports of adolescent irritability using the Affective Reactivity Index. Of these 151 adolescents, 94 (46 M/48 F) returned for a second session (average interval = 1.9 years, SD = 0.4). We used tensor-based morphometry to examine cross-sectional and longitudinal associations between irritability and regional brain volume. Irritability was associated with brain volume across a number of regions. More irritable individuals had larger hippocampi, insula, medial orbitofrontal cortex and cingulum/cingulate cortex and smaller putamen and internal capsule. Across the brain, more irritable individuals also had larger volume and less volume contraction in a number of areas that typically decrease in volume over the developmental period studied here, suggesting delayed maturation. These structural changes may increase adolescents' vulnerability for internalizing and externalizing disorders.
© The Author(s) 2019. Published by Oxford University Press.
Psychosocial deprivation is associated with the development of socially aberrant behaviors, including signs of disinhibited social engagement disorder (DSED). In longitudinal studies, signs of DSED have been shown to decrease over time, especially as children are removed from conditions of deprivation. What is less clear is whether signs of DSED in early childhood are associated with poorer functioning in early adolescence, including among children who no longer manifest signs of DSED at this age. In a sample of 136 Romanian children from the Bucharest Early Intervention Project (BEIP), who were exposed to early psychosocial deprivation in the form of institutional care, we examined caregiver-reported (ages 30, 42, and 54 months and 12 years) and observer-rated (age 54 months) signs of DSED. Competent functioning in early adolescence (age 12 years) was assessed across seven domains (i.e., family relationships, peer relationships, academic performance, physical health, mental health, substance use, and risk-taking behavior). A diagnosis of DSED in early childhood was associated with reduced competence in early adolescence. Furthermore, this association was significant even when signs of DSED diminished by age 12 years. We conclude that signs of DSED in early life are associated with reduced likelihood of competent functioning many years later in adolescence, even if signs of the disorder remit.
Purpose The purpose of this study was to evaluate if higher quantity, diversity, and grammatical informativeness of verb phrases in parent follow-in utterances (i.e., utterances that mapped onto child attentional leads) were significantly related to later expressive verb vocabulary in children with autism spectrum disorder (ASD). Method We examined these associations in a sample of 31 toddlers with ASD and their parents in a longitudinal correlational study. Key aspects of parents' verb input were measured in 2 video-recorded 15-min parent-child free-play sessions. Child expressive verb vocabulary was measured using parent report. Results An aggregate variable composed of the quantity, diversity, and grammatical informativeness of parent verb input in follow-in utterances across the 2 parent-child sessions strongly and positively predicted later child expressive verb vocabulary, total R = .25, even when early child expressive verb vocabulary was controlled, R change = .17. Parent follow-in utterances without verbs were not significantly related to later child expressive verb vocabulary, R = .001. Conclusions These correlational findings are initial steps toward developing a knowledge base for how strong verb vocabulary skills might be facilitated in children with ASD.
OBJECTIVE - To cross-sectionally relate multiple small vessel disease (SVD) neuroimaging markers to cognition among older adults.
METHODS - Vanderbilt Memory & Aging Project participants free of clinical dementia and stroke (n = 327, age 73 ± 7 years, 59% male, 40% with mild cognitive impairment) completed neuropsychological assessment and 3T MRI to measure white matter hyperintensities (WMH), perivascular spaces (PVS), cerebral microbleeds (CMBs), and lacunes. Linear regressions related each SVD marker to neuropsychological performances and adjusted for age, sex, race/ethnicity, education, cognitive diagnosis, ε4 presence, Framingham Stroke Risk Profile, and intracranial volume.
RESULTS - WMH related to the most neuropsychological measures, including the Boston Naming Test, Animal Naming, Coding, Number Sequencing, Executive Function Composite, and Hooper Visual Organization Test performances ( ≤ 0.01). PVS related to multiple information processing and executive function performances ( ≤ 0.02). Lacunes and CMBs related to fewer measures than expected. Combined models simultaneously testing multiple statistically significant SVD predictors suggested that WMH, PVS, and CMBs each independently related to information processing and executive function performances; however, compared to other SVD markers, PVS remained statistically significant in models related to information processing and executive functioning performances.
CONCLUSIONS - As expected, increased WMH corresponded to poorer performances across multiple cognitive domains. PVS, previously considered a benign neuroimaging feature in older adults, may have important clinical implications because PVS was related to information processing and executive function performances even in combined models. On the basis of models with multiple SVD predictors, WMH, PVS, and CMBs may each reflect a separate pathway of small vessel injury.
© 2019 American Academy of Neurology.
Obtaining stable estimates of caregiver-child joint engagement states is of interest for researchers who study development and early intervention in young children with autism spectrum disorder (ASD). However, studies to date have offered little guidance on the numbers of sessions and coders necessary to obtain sufficiently stable estimates of these constructs. We used procedures derived from G theory to carry out a generalizability study, in which we partitioned error variance between two facets of our system for measuring joint engagement states: session and coder. A decision study was then conducted to determine the number of sessions and coders required to obtain g coefficients of 0.80, an a priori threshold set for acceptable stability. This process was conducted separately for 10 infant siblings of children with ASD (Sibs-ASD) and 10 infants whose older sibling did not have ASD (Sibs-TD), and for two different joint engagement states; lower- and higher-order supported joint engagement (LSJE and HSJE, respectively). Results indicated that, in the Sibs-ASD group, four sessions and one coder was required to obtain acceptably stable estimates for HSJE; only one session and one coder were required for LSJE. In the Sibs-TD group, two sessions and one coder were required for HSJE; seven sessions and two coders were required for LSJE. Implications for measurement in future research are discussed. Autism Res 2019, 12: 495-504 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: This study offers guidance for researchers who measure joint engagement between caregivers and infants who have an older sibling with ASD, and who have older siblings who are TD.
© 2019 International Society for Autism Research, Wiley Periodicals, Inc.
BACKGROUND - Blood transfusions are administered to children and adults with sickle cell anemia (SCA) for secondary stroke prevention, or as treatment for recurrent pain crises or acute anemia, but transfusion effects on cerebral hemodynamics and metabolism are not well-characterized.
PURPOSE - To compare blood transfusion-induced changes in hemometabolic parameters, including oxygen extraction fraction (OEF) and cerebral blood flow (CBF), within and between adults and children with SCA.
STUDY TYPE - Prospective, longitudinal study.
SUBJECTS - Adults with SCA (n = 16) receiving simple (n = 7) or exchange (n = 9) transfusions and children with SCA (n = 11) receiving exchange transfusions were scanned once when hematocrit was near nadir and again within 7 days of transfusion. Adult controls without SCA or sickle trait (n = 7) were scanned twice on separate days.
FIELD STRENGTH/SEQUENCE - 3.0T T -weighted, T -weighted, and T -relaxation-under-spin-tagging (TRUST) imaging, and phase contrast angiography.
ASSESSMENT - Global OEF was computed as the relative difference between venous oxygenation (from TRUST) and arterial oxygenation (from pulse oximetry). Global CBF was computed as total blood flow to the brain normalized by intracranial tissue volume.
STATISTICAL TESTS - Hemometabolic variables were compared using two-sided Wilcoxon signed-rank tests; associations were analyzed using two-sided Spearman's correlation testing.
RESULTS - In adults with SCA, posttransfusion OEF = 0.38 ± 0.05 was lower (P = 0.001) than pretransfusion OEF = 0.45 ± 0.09. A change in OEF was correlated with increases in hematocrit (P = 0.02; rho = -0.62) and with pretransfusion hematocrit (P = 0.02; rho = 0.65). OEF changes after transfusion were greater (P = 0.002) in adults receiving simple versus exchange transfusions. Posttransfusion CBF = 77.7 ± 26.4 ml/100g/min was not different (P = 0.27) from pretransfusion CBF = 82.3 ± 30.2 ml/100g/min. In children with SCA, both posttransfusion OEF = 0.28 ± 0.04 and CBF = 76.4 ± 26.4 were lower than pretransfusion OEF = 0.36 ± 0.06 (P = 0.004) and CBF = 96.4 ± 16.5 (P = 0.004).
DATA CONCLUSION - Cerebral OEF reduces following transfusions in adults and children with SCA. CBF reduces following transfusions more often in children compared to adults, indicating that vascular reserve capacity may remain near exhaustion posttransfusion in many adults.
LEVEL OF EVIDENCE - 2 Technical Efficacy Stage 5 J. Magn. Reson. Imaging 2019;49:466-477.
© 2018 International Society for Magnetic Resonance in Medicine.
Models of the neural basis of arithmetic argue that left inferior frontal cortex is involved in cognitive control of verbal representations of math facts in left lateral temporal cortex, whereas bilateral intra-parietal cortex is involved in numerical calculation. Lower levels of math competence for multiplications is associated with greater effortful retrieval because of less robust verbal representations and the engagement of numerical operations as a back-up strategy. Previous studies on multiplication have focused on brain activation in isolated nodes of the network, so we do not know how functional connectivity between these nodes is related to competence. Moreover, previous studies have not employed longitudinal designs, so we do not know how changes in multiplication performance over time is related to changes in its neural basis. The objective of this study was to investigate how changes in multiplication task performance is associated with changes in functional connectivity of temporal cortex with frontal and parietal cortices. Longitudinal data was collected from 45 children, with an average 2.2-year interval between the two sessions, when they were about 11 years old at time 1 (T1) and 13 years old at time 2 (T2). A Psychophysiological Interaction (PPI) analysis was carried out by defining the seed in the temporal cortex (i.e. posterior superior and middle temporal gyri) and examining changes in connectivity with frontal cortex (i.e. left inferior frontal gyrus) as well as parietal cortex (i.e. left and right inferior and superior parietal lobules). We found that children who did not improve in a multiplication task showed greater levels of functional connectivity of left temporal cortex with left inferior frontal gyrus (IFG) and left intraparietal sulcus (IPS) at T2, as compared to their peers who improved. The cluster showing greater levels of connectivity in the left IFG at T2 for the Non-improvers overlapped a cluster independently identified by a verbal localizer task and the cluster showing greater levels of connectivity in the left IPS Non-improvers overlapped a cluster independently identified by a numerosity localizer task. These results suggest that lack of improvement in multiplications are associated with greater cognitive control of verbal representations and greater engagement of numerical operations.
Copyright © 2018 Elsevier Inc. All rights reserved.
Although the study of reactive attachment disorder (RAD) in early childhood has received considerable attention, there is emerging interest in RAD that presents in school age children and adolescents. We examined the course of RAD signs from early childhood to early adolescence using both variable-centered (linear mixed modeling) and person-centered (growth mixture modeling) approaches. One-hundred twenty-four children with a history of institutional care from the Bucharest Early Intervention Project, a randomized controlled trial of foster care as an alternative to institutional care, as well as 69 community comparison children were included in the study. While foster care was associated with steep reductions in RAD signs across development, person-centered approaches indicated that later age of placement into families and greater percent time in institutional care were each associated with prolonged elevated RAD signs. Findings suggest the course of RAD is variable but substantially influenced by early experiences.