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Pediatric brain tumor survivors (PBTS) suffer from cognitive late effects, such as deteriorating executive functioning (EF). We explored the suitability of the Behavior Rating Inventory of Executive Function (BRIEF) to screen for these late effects. We assessed the relationship between the BRIEF and EF tasks, and between the BRIEF-Parent and BRIEF-Teacher, and we explored the clinical utility. Eighty-two PBTS (8-18 years) were assessed with EF tasks measuring attention, cognitive flexibility, inhibition, visual-, and working memory (WM), and with the BRIEF-Parent and BRIEF-Teacher. Pearson’s correlations between the BRIEF and EF tasks, and between the BRIEF-Parent and BRIEF-Teacher were calculated. The BRIEF-Parent related poorly to EF tasks (rs <.26, ps >.01), but of the BRIEF-Teacher the WM-scale, Monitor-scale, Behavioral-Regulation-Index, and Meta-cognition-Index, and Total-score (rs >.31, ps <.01) related significantly to some EF tasks. When controlling for age, only the WM scale and Total score related significantly to the attention task (ps <.01). The inhibit scales of the BRIEF-Parent and BRIEF-Teacher correlated significantly (r =.33, p <.01). Children with clinically elevated scores on BRIEF scales that correlated with EF tasks performed worse on all EF tasks (ds 0.56-1.23, ps <.05). The BRIEF-Teacher Total and Index scores might better screen general EF in PBTS than the BRIEF-Parent. However, the BRIEF-Teacher is also not specific enough to capture separate EFs. Solely relying on the BRIEF as a screening measure of EFs in BPTS is insufficient. Questionnaires and tasks give distinctive, valuable information. [ABSTRACT FROM AUTHOR]

The climbing fibre (CF) input controls cerebellar Purkinje cell (PC) activity as well as synaptic plasticity at parallel fibre (PF)-PC synapses. Under high activity conditions, CFs release not only glutamate, but also the neuropeptide corticotropin-releasing factor (CRF). Brief periods of such high CF activity can lead to the induction of long-term depression (LTD) at CF-PC synapses. Thus, we have examined for the first time the role of CRF in regulating excitatory postsynaptic currents (EPSCs) and long-term plasticity at this synapse. Exogenous application of CRF alone transiently mimicked three aspects of CF-LTD, causing reductions in the CF-evoked excitatory postsynaptic current, complex spike second component and complex spike afterhyperpolarization. The complex spike first component is unaffected by CF-LTD induction and was similarly unaffected by CRF. Application of a CRF receptor antagonist reduced the expression amplitude and induction probability of CF-LTD monitored at the EPSC level. Collectively, these results suggest that under particular sensorimotor conditions, co-release of CRF from climbing fibres could down-regulate excitatory transmission and facilitate LTD induction at CF-PC synapses. Inhibition of either protein kinase C (PKC) or protein kinase A (PKA) attenuated the effects of CRF upon CF-EPSCs. We have previously shown that CF-LTD induction is PKC-dependent, and here demonstrate PKA-dependence as well. These results suggest that both the acute effects of CRF on CF-EPSCs as well as the facilitating effect of CRF on CF-LTD induction can be explained by a CRF-mediated recruitment of PKC and PKA. [ABSTRACT FROM AUTHOR]

The circadian clock, located in the suprachiasmatic nuclei (SCN) of the hypothalamus not only controls the basal daily temporal organization of many neuroendocrine functions, but also its responsiveness. We studied the time-of-day influence on plasma changes in adrenocorticotropic hormone (ACTH), corticosterone, glucagon and leptin concentrations elicited by an insulin-induced hypoglycaemic event. Male Wistar rats were exposed to an insulin challenge at six different times during the light/dark cycle. The time-of-day of exposure markedly affected the responses of all four hormones studied. Generally, the magnitude of the different hormone responses correlated with their basal daily release pattern (i.e. the responses of ACTH and corticosterone were largest around lights off, and glucagon and leptin responses were most pronounced during the dark period). With regard to the hormones of the hypothalamic-pituitary-adrenal axis, the presently reported time-of-day dependent modulation is completely opposite to that previously reported for novelty or restraint. Therefore, these findings provide further support for the existence of at least two different neural pathways that are able to activate the hypothalamic-pituitary-adrenal axis, and provide different substrates for modulation by the biological clock. This observation warrants a thorough examination of possible functional explanations for the observed differences. [ABSTRACT FROM AUTHOR]

An intranuclear virus identical with or closely related to that of verruca vulgaris was demonstrated previously by the authors in epidermodysplasia verruciformis. The behavior of the virus in malignant degeneration of these skin lesions was studied by electron microscopy. Virus-containing cells could be demonstrated in intra-epidermal carcinomas, probably originating from the original cutaneous lesion. In contrast with these findings no virus-containing cells could be demonstrated after careful examination of an invasive "bowenoid" squamous cell carcinoma which histologically showed some features of an original e.v. lesion (epithelioma epidermodysplasique). A similar behavior of virus is known in malignant changes induced by polyoma virus in animals. The establishment of a possible relationship between virus and carcinogenesis was not within the scope of the investigations reported. [ABSTRACT FROM AUTHOR]

Leptin injections into the lateral, third or fourth ventricles decrease 24h food intake and body weight gain. When we injected leptin into either the fourth or lateral ventricles on three consecutive days, 24h food intake and body weight were markedly reduced by comparable amounts in association with both routes of administration. As expected, reductions of food intake by lateral ventricle leptin were associated with decreased meal size. However, fourth ventricle leptin unexpectedly caused a reduction in meal number, but not meal size. We hypothesized that the two routes of administration might influence distinct but interconnected ingestive control circuits. In order to evaluate this hypothesis, we analyzed STAT3 phosphorylation in the dorsal hindbrain and in the hypothalamus after leptin injection into either fourth or lateral cerebral ventricle. Leptin increased phospho-STAT3 in hindbrain and hypothalamus, regardless of its site of injection. Because our ventricular injection volumes were relatively large (3μl), we also injected low doses of leptin (200ng) in relatively small volumes (200nl) directly into the nucleus of the solitary tract (NTS). NTS leptin induced increased phosphorylated STAT3 in the hypothalamus as well as the hindbrain. These results suggest that local leptin administration evokes STAT3 phosphorylation both near the site of injection and at remote sites, such as the hypothalamus. The mechanisms by which NTS leptin evokes hypothalamic STAT3 phosphorylation are under investigation. Supported by NIH Grant NS20561 and Netherlands Organisation of Scientific Research (NWO Rubicon). [Copyright &y& Elsevier]

Systemic gene therapies in Duchenne muscular dystrophy are complicated by relatively low yield and risks, especially in the older, non-ambulant population where a large part of muscle tissue is replaced by fat. Alternatively, local intramuscular (IM) therapy can be promising to increase therapeutic efficacy. We aimed to establish an optimal injection technique and tissue distribution by investigating the relation between injection volume, tissue volume, and fluid distribution in muscle using ultrasound-guided IM delivery in a preclinical setting in preparation for clinical trials. Fluid distribution was assessed by dose escalation (n=4) and repeatability (n=4) in 8 in-situ porcine extensor digitorum brevis muscles (EDBM) using an ink solution (dilution 1/10). Ischemia time of the limbs was kept minimal with fast transportation to preserve tissue integrity. A 20G Chiba needle was used for 4 longitudinal injections from 4 directions to target the entire muscle. Ink distribution was evaluated quantitatively with ImageJ in 2cm cross-sections (ratio-stained vs total muscle). Muscle volume was determined of each cross-section. Repeatability was assessed with the intraclass correlation coefficient (ICC). EDBM volumes were 26.9±4.1cm3. The injection to volume ratio was 0,1; 0,2; 0,3 and 0,3 (2.5ml; 5ml; 7.6ml and 10ml respectively). Higher injection volumes showed increased fluid distribution, and repeatability experiments improved distribution (2.5ml injection 54.8% and 65.4%; 5ml 77.4% and 81.5%; 7,6ml 94.3% and 99%; 10ml 93.9% and 99.4%) with an ICC of 0.99 (0.88-1.0 - 95%CI). At higher injection volumes, we observed increased fluid leakage into adjacent surrounding tissue. Ultrasound-guided longitudinal IM administration using 4 injections provided up to 100% distribution of ink solution, and excellent consistency between the measurements. Future experiments will investigate fluid distribution in muscle and adjacent tissue on MRI. [ABSTRACT FROM AUTHOR]

We explored the suitability of perceptual and acoustic outcome measures to prepare E-learning based Speech Therapy (EST) efficacy tests regarding speech intelligibility in dysarthric speakers. Eight speakers with stroke ( n = 3), Parkinson's disease ( n = 4) and traumatic brain injury ( n = 1) participated in a 4 weeks EST trial. A repeated measures design was employed. Perceptual measures were (a) scale ratings for 'ease of intelligibility' and 'pleasantness' in continuous speech and (b) orthographic transcription scores of semantically unpredictable sentences. Acoustic measures were (c) 'intensity during closure' (ΔIDC) in the occlusion phase of voiceless plosives, (d) changes in the vowel space of /a/, /e/ and /o/ and (e) the F0 variability in semantically unpredictable sentences. The only consistent finding concerned an increased (instead of the expected decreased) ΔIDC after EST, possibly caused by increased speech intensity without articulatory adjustments. The importance of suitable perceptual and acoustic measures for efficacy research is discussed. [ABSTRACT FROM AUTHOR]

Patients with HDR syndrome suffer from hypoparathyroidism, deafness, and renal dysplasia due to a heterozygous deletion of the transcription factor GATA3. Since GATA3 is prominently expressed in both the inner ear and different parts of the auditory nervous system, it is not clear whether the deafness in HDR patients is caused by peripheral and/or central deficits. Therefore, we have created and examined heterozygous Gata3 knockout mice. Auditory brainstem response (ABR) thresholds of alert heterozygous Gata3 mice, analyzed from 1 to 19 months of age, showed a hearing loss of 30 dB compared to wild-type littermates. Neither physiological nor morphological abnormalities were found in the brainstem, cerebral cortex, the outer or the middle ear. In contrast, cochleae of heterozygous Gata3 mice showed significant progressive morphological degeneration starting with the outer hair cells (OHCs) at the apex and ultimately affecting all hair cells and supporting cells in the entire cochlea. Together, these findings indicate that hearing loss following Gata3 haploinsufficiency is peripheral in origin and that this defect is detectable from early postnatal development and maintains through adulthood. [Copyright &y& Elsevier]

Objectives: To evaluate whether (1) first‐trimester prognostic models for gestational diabetes mellitus (GDM) outperform the currently used single risk factor approach, and (2) a first‐trimester random venous glucose measurement improves model performance. Design: Prospective population‐based multicentre cohort. Setting: Thirty‐one independent midwifery practices and six hospitals in the Netherlands. Population: Women recruited before 14 weeks of gestation without pre‐existing diabetes. Methods: The single risk factor approach (presence of at least one risk factor: BMI ≥30 kg/m2, previous macrosomia, history of GDM, positive first‐degree family history of diabetes, non‐western ethnicity) was compared with the four best performing models in our previously published external validation study (Gabbay‐Benziv 2014, Nanda 2011, Teede 2011, van Leeuwen 2010) with and without the addition of glucose. Main outcome measures: Discrimination was assessed by c‐statistics, calibration by calibration plots, added value of glucose by the likelihood ratio chi‐square test, net benefit by decision curve analysis and reclassification by reclassification plots. Results: Of the 3723 women included, a total of 181 (4.9%) developed GDM. The c‐statistics of the prognostic models were higher, ranging from 0.74 to 0.78 without glucose and from 0.78 to 0.80 with glucose, compared with the single risk factor approach (0.72). Models showed adequate calibration, and yielded a higher net benefit than the single risk factor approach for most threshold probabilities. Teede 2011 performed best in the reclassification analysis. Conclusions: First‐trimester prognostic models seem to outperform the currently used single risk factor approach in screening for GDM, particularly when glucose was added as a predictor. Prognostic models seem to outperform the currently used single risk factor approach in screening for gestational diabetes. Prognostic models seem to outperform the currently used single risk factor approach in screening for gestational diabetes. [ABSTRACT FROM AUTHOR]

Background Advances in diagnostic and therapeutic strategies in oncology have significantly increased the chance of survival of cancer patients, even those with metastatic disease. However, cancer-related cognitive impairment (CRCI) is frequently reported in patients treated for non-central nervous system cancers, particularly during and after chemotherapy. Design This review provides an update of the state of the art based on PubMed searches between 2012 and March 2019 on 'cognition', 'cancer', 'antineoplastic agents' or 'chemotherapy'. It includes the most recent clinical, imaging and pre-clinical data and reports management strategies of CRCI. Results Evidence obtained primarily from studies on breast cancer patients highlight memory, processing speed, attention and executive functions as the most cognitive domains impaired post-chemotherapy. Recent investigations established that other cancer treatments, such as hormone therapies and targeted therapies, can also induce cognitive deficits. Knowledge regarding predisposing factors, biological markers or brain functions associated with CRCI has improved. Factors such as age and genetic polymorphisms of apolipoprotein E, catechol-O-methyltransferase and BDNF may predispose individuals to a higher risk of cognitive impairment. Poor performance on neuropsychological tests were associated with volume reduction in grey matter, less connectivity and activation after chemotherapy. In animals, hippocampus-based memory and executive functions, mediated by the frontal lobes, were shown to be particularly susceptible to the effects of chemotherapy. It involves altered neurogenesis, mitochondrial dysfunction or brain cytokine response. An important next step is to identify strategies for managing cognitive difficulties, with primary studies to assess cognitive training and physical exercise regimens. Conclusions CRCI is not limited to chemotherapy. A multidisciplinary approach has improved our knowledge of the complex mechanisms involved. Nowadays, studies evaluating cognitive rehabilitation programmes are encouraged to help patients cope with cognitive difficulties and improve quality of life during and after cancer. [ABSTRACT FROM AUTHOR]

Abstract: Background: Decreased sensation of urge to defecate is often reported by children with functional constipation (FC) and functional nonretentive fecal incontinence (FNRFI). The aim of this cross‐sectional study was to evaluate cerebral activity in response to rectal distension in adolescents with FC and FNRFI compared with healthy controls (HCs). Methods: We included 15 adolescents with FC, 10 adolescents with FNRFI, and 15 young adult HCs. Rectal barostat was performed prior to functional magnetic resonance imaging (fMRI) to determine individual pressure thresholds for urge sensation. Subjects received 2 sessions of 5 × 30 seconds of barostat stimulation during the acquisition of blood oxygenation level‐dependent fMRI. Functional magnetic resonance imaging signal differences were analyzed using SPM8 in Matlab. Key Results: Functional constipation and FNRFI patients had higher thresholds for urgency than HCs (P < .001). During rectal distension, FC patients showed activation in the anterior cingulate cortex, dorsolateral prefrontal cortex, inferior parietal lobule, and putamen. No activations were observed in controls and FNRFI patients. Functional nonretentive fecal incontinence patients showed deactivation in the hippocampus, parahippocampal gyrus, fusiform gyrus (FFG), lingual gyrus, posterior parietal cortex, and precentral gyrus. In HCs, deactivated areas were detected in the hippocampus, amygdala, FFG, insula, thalamus, precuneus, and primary somatosensory cortex. In contrast, no regions with significant deactivation were detected in FC patients. Conclusions & Inferences: Children with FC differ from children with FNRFI and HCs with respect to patterns of cerebral activation and deactivation during rectal distension. Functional nonretentive fecal incontinence patients seem to resemble HCs when it comes to brain processing of rectal distension. [ABSTRACT FROM AUTHOR]

An abstract of the article "Added value of second-trimester uterine artery Doppler in predicting pre-eclampsia and small-for-gestational age neonates in the general population" by A. J. Landman and colleagues is presented.

Background. Functional neuroimaging studies have shown increased Stroop interference coupled with altered anterior cingulate cortex (ACC) and insula activation in post-traumatic stress disorder (PTSD). These brain areas are associated with error detection and emotional arousal. There is some evidence that treatment can normalize these activation patterns. Method. At baseline, we compared classic and emotional Stroop performance and blood oxygenation level- dependent responses (functional magnetic resonance imaging) of 29 child abuse-related complex PTSD patients with 22 non-trauma-exposed healthy controls. In 16 of these patients, we studied treatment effects of psycho-educational and cognitive behavioural stabilizing group treatment (experimental treatment; EXP) added to treatment as usual (TAU) versus TAU only, and correlations with clinical improvement. Results. At baseline, complex PTSD patients showed a trend for increased left anterior insula and dorsal ACC activation in the classic Stroop task. Only EXP patients showed decreased dorsal ACC and left anterior insula activation after treatment. In the emotional Stroop contrasts, clinical improvement was associated with decreased dorsal ACC activation and decreased left anterior insula activation. Conclusions. We found further evidence that successful treatment in child abuse-related complex PTSD is associated with functional changes in the ACC and insula, which may be due to improved selective attention and lower emotional arousal, indicating greater cognitive control over PTSD symptoms. [ABSTRACT FROM AUTHOR]

We present the design and development of the electronic multi-beam radio astronomy concept (EMBRACE), a demonstrator that is part of the European contribution towards the square kilometre array, which is currently being designed by the global radio astronomical community. One of the design goals of EMBRACE is to demonstrate the applicability of phased array technology for use in future radio telescopes. The EMBRACE system will ultimately consist of two stations, the largest of which comprises over 20,000 elements and has a physical area of about 160 m2 . The antenna system, covering the 500-1500 MHz frequency range, is designed as a dual polarized system, however only the signals for one polarization are processed. To obtain a cost effective design, RF analog beam-forming is performed on tile level close to the radiators. The demonstrator is designed to provide two independent beams such that different parts of the sky can be observed simultaneously. First results from part of the array are presented and discussed. The results show that the complete data path is functional. Since the design resembles a large regular contiguous array, all coupling can be taken into account in the embedded element patterns. The array factor therefore suffices to describe the scanning of the array reducing significantly calibration complexity compared to, e.g. sparse, random or more irregular arrays. This is confirmed by the first array factor measurements, that were done using a novel technique that does not require calibration of the array. The first measurements on an astronomical source, the Sun, indicate that the system noise temperature lies between 104 and 118 K, which is reassuringly close to the design target of 100 K. [ABSTRACT FROM AUTHOR]

Poster: Physics track: Quantitative functional and biological imaging PO-1676: Blood biomarkers for cognitive damage after PCI; an exploratory analysis of the HA-PCI phase 3 trial I. Compter, E. Oldoni, R. Houben, L. Van der Weijst, M. De Ruiter, A. Goris, M. Holt, S. Deprez, M. Lambrecht, Y. Lievens, J.P. Van Meerbeeck, S.B. Schagen, J.S.A. Belderbos, D.K.M. De Ruysscher. [Extracted from the article]

The circadian clock in the suprachiasmatic nucleus (SCN) is composed of thousands of oscillator neurons, each dependent on the cell-autonomous action of a defined set of circadian clock genes. Still, the major question remains how these individual oscillators are organized into a biological clock producing a coherent output able to time all the different daily changes in behavior and physiology. In the present review, the authors discuss the anatomical connections and neurotransmitters used by the SCN to control the daily rhythms in hormone release. The efferent SCN projections mainly target neurons in the medial hypothalamus surrounding the SCN. The activity of these preautonomic and neuroendocrine target neurons is controlled by differentially timed waves of, among others, vasopressin, GABA, and glutamate release from SCN terminals. Together, the data on the SCN control of neuroendocrine rhythms provide clear evidence not only that the SCN consists of phenotypically (i.e., according to neurotransmitter content) different subpopulations of neurons but also that subpopulations should be distinguished (within phenotypically similar groups of neurons) based on the acrophase of their (electrical) activity. Moreover, the specialization of the SCN may go as far as a single body structure, that is, the SCN seems to contain neurons that specifically target the liver, pineal, and adrenal. [ABSTRACT FROM AUTHOR]