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Background and aims: Hereditary transthyretin amyloid (ATTRv) amyloidosis caused by the transthyretin (TTR) Val30Met (p.V50M) mutation is characterised by peripheral neuropathy, and central nervous ...

Introduction: Long-term outcomes linked to preterm (PT) births have generally found an increased amount of neuromotor-developmental delays and/or disabilities. Few studies have addressed how upper- ...

In the effort of developing new immunotherapies, the sentinel node (SN) has proven a promising source from which to harness an effective antitumour T cell response. However, tumour immune escape, a process in which regulatory T cells (Tregs) play a central role, remains a major limiting factor. Therefore, there is a clear need to increase the knowledge of Treg function and signalling in sentinel nodes. Here, we set out to explore whether the proteome in SN-resident T cells is altered by the tumour and to identify key proteins in SN T cell signalling, focusing on Tregs. Five patients with muscle-invasive urothelial bladder cancer were prospectively included. Mass spectrometry was performed on two patients, with validation and functional studies being performed on three additional patients and four healthy donors. At cystectomy, SN, non-SN lymph nodes and peripheral blood samples were collected from the patients and T cell subsets isolated through flow cytometry before downstream experiments. Proteomic analysis indicated that growth and immune signalling pathways are upregulated in SN-resident Tregs. Furthermore, centrality analysis identified the cytokine IL-16 to be central in the SN-Treg signalling network. We show that tumour-released factors, through activating caspase-3, increase Treg IL-16 processing into bioactive forms, reinforcing Treg suppressive capacity. In conclusion, we provide evidence that Tregs exposed to secreted factors from bladder tumours show increased immune and growth signalling and altered IL-16 processing which translates to enhanced Treg suppressive function, indicating altered IL-16 signalling as a novel tumour immune escape mechanism.

Altered white matter microstructure is commonly found in children born preterm (PT), especially those born at an extremely low gestational age (GA). These children also commonly show disturbed motor function. This study explores the relation between white matter alterations and upper-limb movement segmentation in 41 children born PT (19 girls), and 41 children born at term (18 girls) at 8 years. The PT group was subdivided into extremely PT (E-PT; GA = 25-27 weeks, N = 10), very PT (V-PT; GA = 28-32 weeks, N = 13), and moderately PT (M-PT; GA = 33-35 weeks, N = 18). Arm/hand preference (preferred/non-preferred) was determined through object interactions and the brain hemispheres were designated accordingly. White matter alterations were assessed using diffusion tensor imaging in nine areas, and movement segmentation of the body-parts head, shoulder, elbow, and wrist were registered during a unimanual goal-directed task. Increased movement segmentation was demonstrated consistently on the preferred side in the E-PT group compared with the term born group. Also compared with the term born peers, the E-PT group demonstrated reduced fractional anisotropy (FA) in the cerebral peduncle (targeting the corticospinal tract) in the hemisphere on the non-preferred side and in the splenium of corpus callosum. In contrast, in the anterior internal capsule on the preferred side, the E-PT group had increased FA. Lower FA in the cerebral peduncle, but higher FA in the anterior internal capsule, was associated with increased movement segmentation across body-parts in a contralateral manner. The results suggest that impaired development of sensorimotor tracts in E-PT children could explain a sub-optimal spatiotemporal organization of upper-limb movements. Hum Brain Mapp 38:5051-5068, 2017. © 2017 Wiley Periodicals, Inc.

Dopamine transporter (DaT) imaging may be supportive in the initial clinical diagnostic workup in patients with suspected parkinsonian diseases, given that the method has the potential to detect dopaminergic degeneration. We investigated the diagnostic accuracy of visual assessment of the initial DaT single‐photon emission CT (DaT‐SPECT) with 123I‐FP‐CIT in a large group of early‐stage parkinsonian patients. After inclusion in a long‐term multidisciplinary population‐based prospective study, a baseline DaT‐SPECT was done in 171 incidental, L‐dopa‐naïve, parkinsonian patients (102 men and 69 women) and 37 healthy controls (19 men and 18 women). The results of the DaT‐SPECTs were linked to criteria‐based clinical diagnoses, which were set after a mean follow‐up of 4.6 (±1.7) years. The outcome of the visual assessment was also compared with that of a semiquantitative evaluation method using regions of interest to measure uptake ratios in the caudate and putamen. We found that visual assessment of DaT‐SPECT in clinically diagnosed incidental Parkinson's disease patients had a sensitivity of 94% and a specificity of 92%, rendering a positive likelihood ratio of 11.75 and a negative likelihood ratio of 0.07. The proportion of false positives was 1.4% and false negatives 4.8% at baseline. These figures were comparable to those of the semiquantitative method. This study demonstrates that visual interpretation of presynaptic dopamine imaging with 123I‐FP‐CIT offers reliable support in the diagnostic procedure of early parkinsonian diseases.

Study Type - Therapy (case series) Level of Evidence 4 What's known on the subject? and What does the study add? This is the first presented results and second publication on detection of tumour-dr ...

This study reports the effect of an affect-focused intervention program, the Affect School, on stress, psychological symptoms, cognitive functioning and neural activity. Fifty employees in social service and education, with high levels of chronic stress, were randomly divided into a treatment (N= 27) and control (N= 23) group. Complete sets of data were available in 20 participants in the treatment group and 17 in the control group. The Perceived Stress Questionnaire assessed stress and the Symptom Check List-90 psychological symptoms before and after treatment. Episodic-memory functioning under focused and divided attention conditions was also assessed. Prior and after the Affect School, seven participants in the treatment group were studied with functional magnetic resonance imaging (fMRI) during episodic memory processing. After the Affect School there was a reduction in stress and psychological symptoms for the treatment group but not in the control group. The controls showed a reduction in episodic memory functioning whereas the performance of the treatment group remained intact. The fMRI scanning indicated a qualitative change in the neural network subserving episodic memory. These preliminary results suggest that the Affect School is effective on individuals with high stress.

Background: Children born preterm have a high prevalence of long-term cognitive and behavioral disturbances. Still, studies of how preterm-twin-births may effect brain maturation and thus, contribu ...