Altered interregional molecular associations of the serotonin transporter in attention deficit/hyperactivity disorder assessed with PET

Altered serotonergic neurotransmission has been found to cause impulsive and aggressive behavior, as well as increased motor activity, all exemplifying key symptoms of ADHD. The main objectives of this positron emission tomography (PET) study were to investigate the serotonin transporter binding potential (SERT BP_ND) in patients with ADHD and to assess associations of SERT BP_ND between the brain regions. 25 medication‐free patients with ADHD (age ± SD; 32.39 ± 10.15; 10 females) without any psychiatric comorbidity and 25 age and sex matched healthy control subjects (33.74 ± 10.20) were measured once with PET and the highly selective and specific radioligand [¹¹C]DASB. SERT BP_ND maps in nine a priori defined ROIs exhibiting high SERT binding were compared between groups by means of a linear mixed model. Finally, adopted from structural and functional connectivity analyses, we performed correlational analyses using regional SERT binding potentials to examine molecular interregional associations between all selected ROIs. We observed significant differences in the interregional correlations between the precuneus and the hippocampus in patients with ADHD compared to healthy controls, using SERT BP_ND of the investigated ROIs (P < 0.05; Bonferroni corrected). When correlating SERT BP_ND and age in the ADHD and the healthy control group, we confirmed an age‐related decline in brain SERT binding in the thalamus and insula (R² = 0.284, R² = 0.167, Ps < 0.05; Bonferroni corrected). The results show significantly different interregional molecular associations of the SERT expression for the precuneus with hippocampus in patients with ADHD, indicating presumably altered functional coupling. Altered interregional coupling between brain regions might be a sensitive approach to demonstrate functional and molecular alterations in psychiatric conditions. Hum Brain Mapp 38:792–802, 2017. © 2016 Wiley Periodicals, Inc.     

Carotid intima–media thickness value distributions in The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Objective

Carotid intima–media thickness (IMT) is a noninvasive measurement of early atherosclerosis. Most IMT studies have involved populations with low rates of racial blending. The aim of the present article is to describe IMT value distributions and analyze the influence of sex and race on IMT values in a large Brazilian sample, a setting with a high rate of racial admixture.

Methods

The Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) is a multicenter cohort of 15,105 adult (aged 35–74 years) civil servants in six Brazilian cities. Baseline assessment included IMT measurements in both common carotid arteries. Race was self-reported. We studied the association between sex and race with IMT values using multiple linear regression models. We conducted analyses in all and low-risk individuals, defined as those without classical cardiovascular risk factors.

Results

We analyzed complete IMT data from 10,405 ELSA-Brasil participants. We present nomograms by age for all and low-risk individuals, stratified by sex and race. We found that men had significantly higher maximal IMT values compared with women (β = 0.058; P < 0.001). This association remained for low-risk individuals (β = 0.027; P = 0.001). In addition, Brown and White individuals had lower maximal IMT values compared with Black individuals for all (β = −0.034 and β = −0.054, respectively; P < 0.001) and low-risk individuals (β = −0.027; P = 0.013 and β = −0.035; P < 0.001, respectively).

Conclusion

We found significantly higher IMT values in men. We found significantly higher IMT values in Black individuals than White and Brown individuals. These results persisted when analyses were restricted to low-risk individuals.     

Predictors of Outcome for Cognitive Behaviour Therapy in Binge Eating Disorder

The aim of this naturalistic study was to identify pretreatment predictors of response to cognitive behaviour therapy in treatment‐seeking patients with binge eating disorder (BED; N = 304). Furthermore, we examined end‐of‐treatment factors that predict treatment outcome 6 months later (N = 190). We assessed eating disorder psychopathology, general psychopathology, personality characteristics and demographic variables using self‐report questionnaires. Treatment outcome was measured using the bulimia subscale of the Eating Disorder Inventory 1. Predictors were determined using hierarchical linear regression analyses. Several variables significantly predicted outcome, four of which were found to be both baseline predictors of treatment outcome and end‐of‐treatment predictors of follow‐up: Higher levels of drive for thinness, higher levels of interoceptive awareness, lower levels of binge eating pathology and, in women, lower levels of body dissatisfaction predicted better outcome in the short and longer term. Based on these results, several suggestions are made to improve treatment outcome for BED patients. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.     

Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia

Minimal residual disease (MRD) during early chemotherapy is a powerful predictor of relapse in acute lymphoblastic leukaemia (ALL) and is used in children to determine eligibility for allogeneic haematopoietic stem cell transplantation (HSCT) in first (CR1) or later complete remission (CR2/CR3). Variables affecting HSCT outcome were analysed in 81 children from the ANZCHOG ALL8 trial. The major cause of treatment failure was relapse, with a cumulative incidence of relapse at 5 years (CIR) of 32% and treatment‐related mortality of 8%. Leukaemia‐free survival (LFS) and overall survival (OS) were similar for HSCT in CR1 (LFS 62%, OS 83%, n = 41) or CR2/CR3 (LFS 60%, OS 72%, n = 40). Patients achieving bone marrow MRD negativity pre‐HSCT had better outcomes (LFS 83%, OS 92%) than those with persistent MRD pre‐HSCT (LFS 41%, OS 64%, P < 0·0001) or post‐HSCT (LFS 35%, OS 55%, P < 0·0001). Patients with B‐other ALL had more relapses (CIR 50%, LFS 41%) than T‐ALL and the main precursor‐B subtypes including BCR‐ABL1, KMT2A (MLL), ETV6‐RUNX1 (TEL‐AML1) and hyperdiploidy >50. A Cox multivariate regression model for LFS retained both B‐other ALL subtype (hazard ratio 4·1, P = 0·0062) and MRD persistence post‐HSCT (hazard ratio 3·9, P = 0·0070) as independent adverse prognostic variables. Persistent MRD could be used to direct post‐HSCT therapy.     

Effectiveness of collagen/oxidised regenerated cellulose/silver‐containing composite wound dressing for the treatment of medium‐depth split‐thickness skin graft donor site wounds in multi‐morbid patients: a prospective,non‐comparative,single‐centre study

Split‐thickness skin grafting (STSG) is a widely used method in reconstructive surgery, but donor site wounds (DSWs) are often slow healing and painful. This prospective study evaluated the performance of a composite wound dressing containing collagen/oxidised regenerated cellulose in the treatment of medium‐depth (0·4 mm) DSWs in 25 multi‐morbid patients with chronic leg ulcers requiring STSG. The range of patients' ages was 44–84 years (mean 71·6 years) with DSW sizes ranging between 12 and 162 cm² (mean 78 cm²). Comorbidities included anticoagulation therapy (15 patients), anaemia (11 patients), diabetes (6 patients) and methicillin‐resistant Staphylococcus aureus (MRSA) ulcer colonisation (6 patients). The first dressing change was performed after 10 days. Complete reepithelialisation was observed between the 10th and 34th day (mean 17·2, median 14 days). Postoperative medium to strong bleeding occurred in only five patients (four with anticoagulation). Wound pain levels one day after harvesting were only moderate (range 0–1·5, mean 0·5, median 0·5 on a six‐item scale). No wound infection was observed during the first dressing. The composite dressing used allowed for the fast healing of medium‐depth DSWs with minimal or no postoperative pain and bleeding in older multi‐morbid patients under anticoagulation treatment.     

The predictive validity of the Dutch Restrained Eating Scale

The present study aims to determine the predictive validity of the 10-item Dutch Restrained Eating Scale. The ultimate criterion of restrained eating is the degree to which an individual eats less than he or she actually would like to eat. Since a study on both actual food consumption and restriction of food intake is very complicated, if not impossible, the difference between actual and desired intake of energy was studied indirectly, that is, from estimates of deviations from the required energy intake. The relationships were studied between restrained eating scores and the magnitude of the deviation from energy requirement, and between restrained eating scores and intake of fat and sugar, because restriction in intake of these may also reflect dietary restraint. About 20% of the variance of scores on the Restrained Eating Scale could be explained from these measures of food intake, which suggests that the Dutch Restrained Eating Scale has moderate to good predictive validity.     

Three C-terminal phosphorylation sites in the Abutilon mosaic virus movement protein affect symptom development and viral DNA accumulation

The Abutilon mosaic virus (AbMV, Geminiviridae) DNA B component encodes a movement protein (MP), which facilitates viral transport within plants and affects pathogenicity. The presence of phosphorylated serine and threonine residues was confirmed for MP expressed in yeast and Nicotiana benthamiana by comparative Western blot analysis using phospho-amino acid- and MP-specific immunodetection. Mass spectrometry of yeast-derived MP identified three phosphorylation sites located in the C-terminal domain (Thr-221, Ser-223 and Ser-250). To assess their functional relevance in plants, several point mutations were generated in the MP gene of DNA B, which replace Thr-221, Ser-223 and Ser-250, either singly or in combinations, with either an uncharged alanine or a phosphorylation-mimicking aspartate residue. When co-inoculated with DNA A, all mutants were infectious. In systemically infected plants the symptoms and/or viral DNA accumulation were significantly altered for several of the mutants.