This study assessed the efficacy of a 5-week, intensive working memory training program for 52 children and adolescents (ages 7-17) who had Attention-Deficit/Hyperactivity Disorder (ADHD) and other comorbid diagnoses. This study provided a treatment replication since the waitlist control group also completed training and was included in the follow-up data analyses. Parents and teachers completed paper-and-pencil measures of working memory, executive functioning, and ADHD symptoms at baseline, posttreatment, and 4-month follow-up. Parent ratings indicated that participants improved on inattention, overall number of ADHD symptoms, initiation, planning/organization, and working memory. Teacher ratings approached significance at posttreatment and at 4-month follow-up on and Initiate scale. Working memory training appears promising as an intervention in improving executive functioning and ADHD symptoms.
Our group and others have determined that immune effector cells from patients with advanced cancers exhibit reduced activation of IFN signaling pathways. We hypothesized that increases in immune regulatory cells termed myeloid derived suppressor cells (MDSC) could interfere with the host immune response to tumors by inhibiting immune cell responsiveness to interferons. The C26 murine adenocarcinoma model was employed to study immune function in advanced malignancy. C26 bearing mice had significantly elevated levels of GR1+CD11b+ MDSC as compared to control mice, and splenocytes from tumor bearing mice exhibited reduced phosphorylation of STAT1 (P-STAT1) on Tyr 701 in response to IFN alpha or IFN gamma. This inhibition was seen in splenic CD4+ and CD8+ T cells as well as NK cells. In vitro co culture experiments revealed that MDSC inhibited the IFN responsiveness of splenocytes from normal mice. Treatment of C26 bearing mice with gemcitabine or an anti-GR1 antibody led to depletion of MDSC and restored splenocyte IFN responsiveness. Spleens from C26 bearing animals displayed elevated levels of iNOS protein and nitric oxide (NO). In vitro treatment of splenocytes with a nitric oxide donor led to a decreased STAT1 IFN response. The elevation in NO in C26 bearing mice was associated with increased levels of nitration on STAT1. Finally, splenocytes from iNOS knockout mice bearing C26 tumors exhibited a significantly elevated IFN-response as compared to control C26 tumor bearing mice. These data suggest that NO produced by MDSC can lead to reduced interferon responsiveness in immune cells.
BACKGROUND: Advanced imaging techniques have allowed for earlier and more accurate detection of cerebral deep medullary vein thrombosis and infarction. Our objective was to develop an MR imaging scoring system to evaluate the severity of white matter injury in neonates with deep medullary vein thrombosis and infarction. METHODS: Retrospective study of infants born ≥32 weeks gestation (2000–2016), diagnosed with deep medullary vein thrombosis and infarction on neuroimaging in the first 30 days of life. A 102-point deep medullary vein white matter injury global severity score was developed. MR scans were scored by two pediatric radiologists. Subject clinical data, regional and global severity scores were recorded. RESULTS: 51 patients (mean gestational age 37.3±2.2 weeks; mean birth weight 3182±720g) were included with mean age at diagnosis via MR imaging postnatal day 10.1±6.1. Global severity scores ranged from 1 to 53, with median score 11 [IQR 5-25]. Lesions were more common in frontal and parietal regions and less common in occipital and temporal regions. Fifty-five percent of the group had neonatal seizures. No difference in perinatal risk factors (gestational age, birthweight, 5-minute APGAR, chorioamnionitis, delivery room resuscitation, ventilator or inotrope requirement) was observed between severity score quartiles. CONCLUSION: A MR imaging scoring system provides a comprehensive and objective classification of WM injury after deep medullary vein thrombosis and infarction in late preterm and term neonates. The global severity score is independent of gestational age and other antenatal risk factors, consistent with presentation in previously healthy appearing newborns.
Aim: To examine associations between the deep medullary vein white matter injury global severity scoring system and neurodevelopmental impairment. Methods: This is a prospective observational cohort study of infants born at ≥32 weeks, diagnosed with deep medullary vein thrombosis and infarction on neuroimaging in the first month of life. Developmental testing was performed using validated measures for early, preschool, and school-age follow-up. Results: Nineteen (37%) patients had major neurodevelopmental impairment. Global severity score was higher among patients with neurodevelopmental impairment (21.6 vs 13.4, P = .04). Overall, 78% of patients with epilepsy had neurodevelopmental impairment. A greater degree of asymmetry with right-sided injury predominance was associated with lower Bayley-III cognitive scores and presence of neurodevelopmental impairment ( P < .01). Conclusions: Results suggest a need for targeted clinical surveillance for patients with a high global severity score and/or asymmetric, predominantly right cerebral white matter injury and for those who develop epilepsy.
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