The Adolescent Adjustment Profile (AAP) in comparisons of patients with obesity,phenylketonuria or neurobehavioural disorders

Psychosocial development in children with chronic disease is a key issue in paediatrics. This study investigated whether psychosocial adjustment could be reliably assessed with the 42-item Adolescent Adjustment Profile (AAP) instrument. The study mainly focused on adjustment-to-obesity measurement, although it compared three patient groups with chronic conditions. All phenylketonuria (PKU) patients in Sweden between ages 9 and 18 and their parents and teachers were invited to participate. Patients with neurobehavioural syndromes and obesity were age- and gender-matched with PKU patients. Healthy children constituted a reference group. Psychosocial adjustment was measured using the AAP, which is a multi-informant questionnaire that contains four domains. Information concerning parents’ socio-economic and civil status was requested separately. Respondents to the three questionnaires judged the PKU patients to be normal in all four domains. Patients with neurobehavioural syndromes demonstrated less competence and the most problems compared with the other three groups. According to the self-rating, the parent rating and the teacher rating questionnaires, obese patients had internalizing problems. The parent rating and the teacher rating questionnaire scored obese patients as having a lower work capacity than the reference group. Compared with the reference group, not only families with obese children but also families with children with neurobehavioural syndromes had significantly higher divorce rates. Obese patients were also investigated with the Strength and Difficulties Questionnaire (SDQ), another instrument that enables comparison between two measures of adjustment. The AAP had good psychometric properties; it was judged a useful instrument in research on adolescents with chronic diseases.     

In vivo imaging of system xc- as a novel approach to monitor multiple sclerosis

Purpose

Glutamate excitotoxicity contributes to oligodendroglial and axonal damage in multiple sclerosis pathology. Extracellular glutamate concentration in the brain is controlled by cystine/glutamate antiporter (system xc-), a membrane antiporter that imports cystine and releases glutamate. Despite this, the system xc^? activity and its connection to the inflammatory reaction in multiple sclerosis (MS) is largely unknown.

Methods

Longitudinal in vivo magnetic resonance (MRI) and positron emission tomography (PET) imaging studies with 2-[¹⁸F]Fluoro-2-deoxy-D-glucose ([¹⁸F]FDG), [¹¹C]-(R)-(1-(2-chlorophenyl)-N-methyl-N-1(1-methylpropyl)-3-isoquinolinecarboxamide ([¹¹C]PK11195) and (4S)-4-(3-¹⁸F-fluoropropyl)-L-glutamate ([¹⁸F]FSPG) were carried out during the course of experimental autoimmune encephalomyelitis (EAE) induction in rats.

Results

[¹⁸F]FSPG showed a significant increase of system xc^? function in the lumbar section of the spinal cord at 14 days post immunization (dpi) that stands in agreement with the neurological symptoms and ventricle edema formation at this time point. Likewise, [¹⁸F]FDG did not show significant changes in glucose metabolism throughout central nervous system and [¹¹C]PK11195 evidenced a significant increase of microglial/macrophage activation in spinal cord and cerebellum 2 weeks after EAE induction. Therefore, [¹⁸F]FSPG showed a major capacity to discriminate regions of the central nervous system affected by the MS in comparison to [¹⁸F]FDG and [¹¹C]PK11195. Additionally, clodronate-treated rats showed a depletion in microglial population and [¹⁸F]FSPG PET signal in spinal cord confirming a link between neuroinflammatory reaction and cystine/glutamate antiporter activity in EAE rats.

Conclusions

Altogether, these results suggest that in vivo PET imaging of system xc^? could become a valuable tool for the diagnosis and treatment evaluation of MS.

     

Pitch Discrimination in Musicians and Non-Musicians: Effects of Harmonic Resolvability and Processing Effort

Musicians typically show enhanced pitch discrimination abilities compared to non-musicians. The present study investigated this perceptual enhancement behaviorally and objectively for resolved and unresolved complex tones to clarify whether the enhanced performance in musicians can be ascribed to increased peripheral frequency selectivity and/or to a different processing effort in performing the task. In a first experiment, pitch discrimination thresholds were obtained for harmonic complex tones with fundamental frequencies (F0s) between 100 and 500 Hz, filtered in either a low- or a high-frequency region, leading to variations in the resolvability of audible harmonics. The results showed that pitch discrimination performance in musicians was enhanced for resolved and unresolved complexes to a similar extent. Additionally, the harmonics became resolved at a similar F0 in musicians and non-musicians, suggesting similar peripheral frequency selectivity in the two groups of listeners. In a follow-up experiment, listeners’ pupil dilations were measured as an indicator of the required effort in performing the same pitch discrimination task for conditions of varying resolvability and task difficulty. Pupillometry responses indicated a lower processing effort in the musicians versus the non-musicians, although the processing demand imposed by the pitch discrimination task was individually adjusted according to the behavioral thresholds. Overall, these findings indicate that the enhanced pitch discrimination abilities in musicians are unlikely to be related to higher peripheral frequency selectivity and may suggest an enhanced pitch representation at more central stages of the auditory system in musically trained listeners.     

The HLA 8.1 ancestral haplotype is strongly linked to the C allele of -429T>C promoter polymorphism of receptor of the advanced glycation endproduct (RAGE) gene. Haplotype-independent association of the -429C allele with high hemoglobinA1C levels in diabetic patients

Previously we reported on strong linkage disequilibrium (LD) between the mono-S-C4B-RCCX module (mono-S) and the TNF2 allele (both known constituents of the 8.1 ancestral haplotype (8.1 AH)) in two Caucasian populations. The gene for the receptor of advanced glycation endproducts (RAGE) is encoded between the RCCX module and the HLA class II genes in the central MHC region. In order to assess the relationship between the promoter polymorphisms of the RAGE gene and the 8.1 AH, we performed a family study in eight informative families affected with type 1 diabetes mellitus; haplotypes of a RAGE promoter SNP (-429T>C) with the HLA-DQ2, -DR-3(17) and TNF2 alleles, as well as the mono-S genotype were determined. A similar analysis was performed in 82 unrelated patients with type 1 diabetes mellitus, and in unrelated healthy individuals of three different Caucasian populations (Hungarians, Ohioian females, Icelandics). In the diabetic patients clinical correlations were also investigated. Out of the 32 paternal and maternal chromosome 6 from the eight families, 15 different MHC haplotypes were found. Haplotypes containing at least three of the known constituents of the 8.1 AH (HLA-DQ2, -DR17, mono-S, TNF2) were always linked to the RAGE -429C allele. The RAGE -429C allele exhibited highly significant (p<0.0001) LD coefficients to known constituents of the 8.1 AH both in healthy persons and patients with type 1 diabetes. In the group of patients with diabetes we found significantly (p=0.013) higher maximal hemoglobinA1C concentration in the carriers of the RAGE -429C allele, this trait, however was not linked to the 8.1 AH. Our present findings indicate that the RAGE -429C allele can be considered as a candidate member of the 8.1 AH. The results also reveal a spectrum of recombinant MHC haplotypes in addition to the conserved ancestral haplotypes.     

Effects of high-dose baclofen on cue reactivity in alcohol dependence: A randomized,placebo-controlled pharmaco-fMRI study

Increased functional brain response towards alcohol-associated stimuli is a neural hallmark of alcohol dependence and a promising target for pharmacotherapy. For the first time, we assessed the effects of individually titrated high-dose baclofen on cue reactivity and functional connectivity in alcohol-dependent (AD) patients in a randomized controlled trial (RCT).We investigated 23 recently detoxified AD patients and 23 matched healthy controls (HC) with a cue reactivity functional magnetic resonance imaging task. Patients were further scanned at baseline without medication and during treatment with high-dose baclofen/placebo (30–270 mg/d). Analyses were conducted for alcohol cue-elicited brain response, alcohol cue-modulated and stimulus-independent functional connectivity with left ventral tegmental area (VTA) as seed region.At baseline, AD patients (N?=?23) showed increased cue-elicited brain activation in the ventral striatum (VS) compared to HC (N?=?23), which was decreased at the second scanning session compared to baseline. Patients receiving baclofen (N?=?10) showed a significant stronger decrease in cue-elicited brain activation in left orbitofrontal cortex (OFC), bilateral amygdala and left VTA than patients receiving placebo (N?=?13). Treatment with baclofen further led to a decrease in alcohol cue-modulated functional connectivity between left VTA and left anterior cingulate cortex (ACC) as well as left medial prefrontal cortex (MPFC). Regarding clinical outcome, significantly more patients of the baclofen group remained abstinent during the high-dose period.Baclofen specifically decreased cue-elicited brain responses in areas known to be involved in the processing of salient (appetitive and aversive) stimuli. Treatment with high-dose baclofen seems to provide a pharmacological relief of this neural “warning signal” evoked by alcohol-related cues, thereby possibly supporting patients in remaining abstinent.Trial Registration Identifier of the main trial [BACLAD study] at clinicaltrials.gov: NCT01266655.     

A widening gap? Static and dynamic performance differences between specialist and general hospitals

This paper develops and tests a dynamic model of hospital focus. It does so by tracing the performance trajectories of specialist and general hospitals to identify whether a performance gap exists and whether it widens or shrinks over time. Our longitudinal analyses of all hospital organizations within the English National Health Service (NHS) reveal not only a notable performance gap between specialist and general hospitals in particular with regards to patient satisfaction that widens over time, but also the emergence of a gap especially with regards to hospital staff job satisfaction. These findings reflect the considerable potential of specialization as a means to enhance hospital effectiveness. However, they also alert health policy makers to the threat of a widening performance gap between specialist and general hospitals with potential negative repercussions at the patient and health system level.