Addressing the psychosocial aspects of transition to adult care in patients with cystinosis.

Cystinosis is a rare autosomal-recessive lysosomal storage disease that progressively affects multiple organs beginning with the kidneys. Patients require lifelong multidisciplinary care for the management of kidney disease and progressive extra-renal manifestations, and thus, they are especially fragile and vulnerable during transition from pediatric to adult care. Previous documents have provided guidance to help the medical transition of these highly burdened patients. Patients and their families often experience great psychological distress and face significant social challenges; for these reasons, they often need help from psychologists, social workers, and other psychosocial professionals. Due to the rarity of the disease, most psychosocial professionals have no expertise in this disorder and require advice. To this end, a steering committee (SC) composed of six experts, including pediatric nephrologists, psychologists, and social workers with experience in the care for patients with cystinosis, have identified and addressed seven key questions related to psychosocial challenges of the disease and the burden of treatment. Ten additional international experts (the extended faculty, EF) were invited to answer these questions. Since robust evidence is lacking, as in many rare diseases, conclusions were based on collective agreement between members of the SC and the EF, and the consolidated answers were summarized into expert opinion statements. The present document contains information on the concerns and psychosocial burden of patients with cystinosis and of their caregivers, and provides practical advice for timely and appropriate support to facilitate the transition to adult care.

Weighing the Evidence: A Systematic Review on Long-Term Neurocognitive Effects of Cannabis Use in Abstinent Adolescents and Adults.

Findings on neurocognitive effects of sustained cannabis use are heterogeneous. Previous work has rarely taken time of abstinence into account. In this review, we focus on understanding sustained effects of cannabis, which begin when clinical symptoms of the drug have worn off after at least 14 days. We conducted a search between 2004 and 2015 and found 38 studies with such a prolonged abstinence phase. Study-design quality in terms of evidence-based medicine is similar among studies. Studies found some attention or concentration deficits in cannabis users (CU). There is evidence that chronic CU might experience sustained deficits in memory function. Findings are mixed regarding impairments in inhibition, impulsivity and decision making for CU, but there is a trend towards worse performance. Three out of four studies found evidence that motor function remains impaired even after a time of abstinence, while no impairments in visual spatial functioning can be concluded. Functional imaging demonstrates clear differences in activation patterns between CU and controls especially in hippocampal, prefrontal and cerebellar areas. Structural differences are found in cortical areas, especially the orbitofrontal region and the hippocampus. Twenty studies (57 %) reported data on outcome effects, leading to an overall effect size of r mean = .378 (CI 95 % = [.342; .453]). Heavy use is found to be more consistently associated with effects in diverse domains than early age of onset. Questions of causality-in view of scarce longitudinal studies, especially those targeting co-occurring psychiatric disorders-are discussed.

Visual Attention and Saccadic Oculomotor Control in Parkinson's Disease.

BACKGROUND: In patients with Parkinson's disease (PD) we aimed at differentiating the relation between selective visual attention, deficits of programming and dynamics of saccadic eye movements while searching for a target and hand-reaction time as well as hand-movement time. Visual attention is crucial for concentrating selectively on one aspect of the visual field while ignoring other aspects. Eye movements are anatomically and functionally related to mechanisms of visual attention. Saccadic dysfunction might confound selective visual attention in PD. METHODS: We studied visual selective attention in 22 medicated PD patients (clinical ON status, mild to moderate disease severity) and 22 age matched controls. We looked for possible interferences through oculomotor deficits. Two tasks were compared: free viewing of photographs and time optimal visual search of a hidden target. Visual search times (VST), task related dynamics of saccades, and hand-reaction and hand-movement times were analyzed. RESULTS: In the free viewing task mild to moderately affected PD patients did not differ statistically from healthy subjects with respect to saccade dynamics. However, patients differed significantly from healthy subjects in the time optimal visual search task with 25% lower rates of successful searches. Hand movement reaction time did not differ in both groups, whereas hand movement execution time was significantly prolonged in PD patients. CONCLUSION: Saccadic oculomotor control and hand movement reaction times were intact, whereas in our less severely affected treated PD patients, visual selective attention was not. The highly reduced successful search rate might be related to disturbed programming and delayed execution of saccades during time optimal visual search due to decreased execution of serial-order sequential generation of saccades.

On why left events are the right ones: neural mechanisms underlying the left-hemifield advantage in rapid serial visual presentation.

When simultaneous series of stimuli are rapidly presented left and right, containing two target stimuli T1 and T2, T2 is much better identified when presented in the left than in the right hemifield. Here, this effect was replicated, even when shifts of gaze were controlled, and was only partially compensated when T1 side provided the cue where to expect T2. Electrophysiological measurement revealed earlier latencies of T1- and T2-evoked N2(pc) peaks at the right than at the left visual cortex, and larger right-hemisphere T2-evoked N2(pc) amplitudes when T2 closely followed T1. These findings suggest that the right hemisphere was better able to single out the targets in time. Further, sustained contralateral slow shifts remained active after T1 for longer time at the right than at the left visual cortex, and developed more consistently at the right visual cortex when expecting T2 on the contralateral side. These findings might reflect better capacity of right-hemisphere visual working memory. These findings about the neurophysiological underpinnings of the large right-hemisphere advantage in this complex visual task might help elucidating the mechanisms responsible for the severe disturbance of hemineglect following damage to the right hemisphere.

Deficiency of brain 5-HT synthesis but serotonergic neuron formation in Tph2 knockout mice.

The relative contribution of the two tryptophan hydroxylase (TPH) isoforms, TPH1 and TPH2, to brain serotonergic system function is controversial. To investigate the respective role of TPH2 in neuron serotonin (5-HT) synthesis and the role of 5-HT in brain development, mice with a targeted disruption of Tph2 were generated. The preliminary results indicate that in Tph2 knockout mice raphe neurons are completely devoid of 5-HT, whereas no obvious alteration in morphology and fiber distribution are observed. The findings confirm the exclusive specificity of Tph2 in brain 5-HT synthesis and suggest that Tph2-synthesized 5-HT is not required for serotonergic neuron formation.

Changes in connectivity profiles as a mechanism for strategic control over interfering subliminal information.

Human behavior can be influenced by information that is not consciously perceived. Recent behavioral and electrophysiological evidence suggests, however, that the processing of subliminal stimuli is not completely beyond an observer's conscious control. The present study aimed to characterize the cortical network that implements strategic control over interfering subliminal information at multiple stages. Fourteen participants underwent functional magnetic resonance imaging (fMRI) scanning while performing a metacontrast masking paradigm. We systematically varied the amount of conflicting versus non-conflicting trials across experimental blocks, and behavioral performance demonstrated strategic effects whenever a high proportion of subliminal prime stimuli induced response competition. A psychophysiological interaction analysis revealed the pre-supplementary motor area (pre-SMA) to exhibit context-dependent covariation with activation in the lateral occipital complex (LOC) and the putamen. The pre-SMA thereby appears to fulfill a superordinate function in the control of processing subliminal information by simultaneously modulating perceptual analysis and motor selection.