Excess HB-EGF, which promotes VEGF signaling, leads to hydrocephalus

Heparin binding epidermal growth factor-like growth factor (HB-EGF) is an angiogenic factor mediating radial migration of the developing forebrain, while vascular endothelial growth factor (VEGF) is known to influence rostral migratory stream in rodents. Cell migratory defects have been identified in animal models of hydrocephalus; however, the relationship between HB-EGF and hydrocephalus is unclear. We show that mice overexpressing human HB-EGF with β-galactosidase reporter exhibit an elevated VEGF, localization of β-galactosidase outside the subventricular zone (SVZ), subarachnoid hemorrhage, and ventriculomegaly. In Wistar polycystic kidney rats with hydrocephalus, alteration of migratory trajectory is detected. Furthermore, VEGF infusions into the rats result in ventriculomegaly with an increase of SVZ neuroblast in rostral migratory stream, whereas VEGF ligand inhibition prevents it. Our results support the idea that excess HB-EGF leads to a significant elevation of VEGF and ventricular dilatation. These data suggest a potential pathophysiological mechanism that elevated HB-EGF can elicit VEGF induction and hydrocephalus

Games used with serious purposes: a systematic review of interventions in patients with cerebral palsy

The purpose of the present systematic review was to examine extant research regarding the role of games used seriously in interventions with individuals with cerebral palsy. Therefore, PubMed, PsyINFO, Web of Science, Scopus, and IEEE databases were used. Search terms included: "serious games" OR "online games" OR "video games" OR "videogame" OR "game based" OR "game" AND "intervention" AND "cerebral palsy." After the full reading and quality assessment of the papers, 16 studies met the inclusion criteria. The majority of the studies reported high levels of compliance, motivation, and engagement with game-based interventions both at home and at the clinical setting intervention. Regarding the effectiveness of the use of games, the results of the studies show both positive and negative results regarding their effectiveness. The efficacy was reported to motor function (i.e., improvements in the arm function, hand coordination, functional mobility, balance and gait function, postural control, upper-limbs function) and physical activity. Findings of this review suggest that games are used as a complement to conventional therapies and not as a substitute. Practitioners often struggle to get their patients to complete the assigned homework tasks, as patients display low motivation to engage in prescribed exercises. Data of this review indicates the use of games as tools suited to promote patients' engagement in the therapy and potentiate therapeutic gains.This study was conducted at Psychology Research Centre (UID/PSI/01662/2013), University of Minho, and supported by the Portuguese Foundation for Science and Technology and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). SL and AP were supported by a Ph.D. fellowship from the Portuguese Foundation for Science and Technology (FCT). PM was supported by a Post-Doctoral fellowship from the Psychology Research Centre (CIPsi), University of Minho. JM was supported by a research scholarship from the Psychology Research Centre (CIPsi), University of Minho

A European research agenda for somatic symptom disorders, bodily distress disorders, and functional disorders: Results of an estimate-talk-estimate delphi expert study

Background: Somatic Symptom Disorders (SSD), Bodily Distress Disorders (BDD) and functional disorders (FD) are associated with high medical and societal costs and pose a substantial challenge to the population and health policy of Europe. To meet this challenge, a specific research agenda is needed as one of the cornerstones of sustainable mental health research and health policy for SSD, BDD, and FD in Europe. Aim: To identify the main challenges and research priorities concerning SSD, BDD, and FD from a European perspective. Methods: Delphi study conducted from July 2016 until October 2017 in 3 rounds with 3 workshop meetings and 3 online surveys, involving 75 experts and 21 European countries. EURONET-SOMA and the European Association of Psychosomatic Medicine (EAPM) hosted the meetings. Results: Eight research priorities were identified: (1) Assessment of diagnostic profiles relevant to course and treatment outcome. (2) Development and evaluation of new, effective interventions. (3) Validation studies on questionnaires or semi-structured interviews that assess chronic medical conditions in this context. (4) Research into patients preferences for diagnosis and treatment. (5) Development of new methodologic designs to identify and explore mediators and moderators of clinical course and treatment outcomes (6). Translational research exploring how psychological and somatic symptoms develop from somatic conditions and biological and behavioral pathogenic factors. (7) Development of new, effective interventions to personalize treatment. (8) Implementation studies of treatment interventions in different settings, such as primary care, occupational care, general hospital and specialty mental health settings. The general public and policymakers will benefit from the development of new, effective, personalized interventions for SSD, BDD, and FD, that will be enhanced by translational research, as well as from the outcomes of research into patient involvement, GP-patient communication, consultation-liaison models and implementation. Conclusion: Funding for this research agenda, targeting these challenges in coordinated research networks such as EURONET-SOMA and EAPM, and systematically allocating resources by policymakers to this critical area in mental and physical well-being is urgently needed to improve efficacy and impact for diagnosis and treatment of SSD, BDD, and FD across Europe

A recurrent germline PAX5 mutation confers susceptibility to pre-B cell acute lymphoblastic leukemia

Somatic alterations of the lymphoid transcription factor gene PAX5 (also known as BSAP) are a hallmark of B cell precursor acute lymphoblastic leukemia (B-ALL)1–3, but inherited mutations of PAX5 have not previously been described. Here we report a new heterozygous germline variant, c.547G>A (p.Gly183Ser), affecting the octapeptide domain of PAX5 that was found to segregate with disease in two unrelated kindreds with autosomal dominant B-ALL. Leukemic cells from all affected individuals in both families exhibited 9p deletion, with loss of heterozygosity and retention of the mutant PAX5 allele at 9p13. Two additional sporadic ALL cases with 9p loss harbored somatic PAX5 substitutions affecting Gly183. Functional and gene expression analysis of the PAX5 mutation demonstrated that it had significantly reduced transcriptional activity. These data extend the role of PAX5 alterations in the pathogenesis of pre-B cell ALL and implicate PAX5 in a new syndrome of susceptibility to pre-B cell neoplasia

Divergent Macroparasite Infections in Parapatric Swiss Lake-Stream Pairs of Threespine Stickleback (Gasterosteus aculeatus).

Spatial heterogeneity in diversity and intensity of parasitism is a typical feature of most host-parasite interactions, but understanding of the evolutionary implications of such variation is limited. One possible outcome of infection heterogeneities is parasite-mediated divergent selection between host populations, ecotypes or species which may facilitate the process of ecological speciation. However, very few studies have described infections in population-pairs along the speciation continuum from low to moderate or high degree of genetic differentiation that would address the possibility of parasite-mediated divergent selection in the early stages of the speciation process. Here we provide an example of divergent parasitism in freshwater fish ecotypes by examining macroparasite infections in threespine stickleback (Gasterosteus aculeatus) of four Swiss lake systems each harbouring parapatric lake-stream ecotype pairs. We demonstrate significant differences in infections within and between the pairs that are driven particularly by the parasite taxa transmitted to fish from benthic invertebrates. The magnitude of the differences tended to correlate positively with the extent of neutral genetic differentiation between the parapatric lake and stream populations of stickleback, whereas no such correlation was found among allopatric populations from similar or contrasting habitats. This suggests that genetic differentiation is unrelated to the magnitude of parasite infection contrasts when gene flow is constrained by geographical barriers while in the absence of physical barriers, genetic differentiation and the magnitude of differences in infections tend to be positively correlated

Effects of Rater Training on the Assessment of L2 English Oral Proficiency

The main objective of this study was to examine whether a Rater Identity Development (RID)program would increase interrater reliability and improve calibration of scores againstbenchmarks in the assessment of second/foreign language English oral proficiency. Elevenprimary school teachers-as-raters participated. A pretest–intervention/RID–posttest designwas employed and data included 220 assessments of student performances. Two types ofrater-reliability analyses were conducted: first, estimates of the intraclass correlationcoefficient two-way random effects model, in order to indicate the extent to which raterswere consistent in their rankings, and second, a many-facet Rasch measurement analysis,extended through FACETS®, to explore variation regarding systematic differences of raterseverity/leniency. Results showed improvement in terms of consistency, presumably as aresult of training; simultaneously, the differences in severity became greater. Results suggestthat future rater training may draw on central components of RID, such as core concepts inlanguage assessment, individual feedback, and social moderation work.Equity in Assessment (EquA) - Likvärdig bedömnin

Introduced European smelt (Osmerus eperlanus) affects food web and fish community in a large Norwegian lake

Invasive and introduced fishes can affect recipient ecosystems and native species via altered competitive and predatory interactions, potentially leading to top-down and bottom-up cascading impacts. Here, we describe a case from a large lake in southern Norway, Storsjøen, where the illegal introduction of a small, predominantly planktivorous fish species, European smelt (Osmerus eperlanus), has led to changes in the native fish community and lake food web. Survey fishing data collected before (2007) and after (2016) the introduction indicates that smelt has become the numerically dominant fish species both in benthic and pelagic habitats, with concurrent reductions in the relative abundance of native European whitefish (Coregonus lavaretus) and Arctic charr (Salvelinus alpinus) populations. Stable isotope (d13C and d15N) data indicate minor changes in the trophic niches of native whitefish and Arctic charr despite partly overlapping niches with the introduced smelt. In contrast, brown trout (Salmo trutta) showed an earlier shift to piscivory, a more pelagic niche and increased growth rate, likely because of the smelt induced increase in pelagic prey fish abundance. The main trophic pathway supporting top predators (i.e., large brown trout) in Storsjøen has, therefore, shifted from a littoral to a more pelagic base. Our study demonstrates that small-sized introduced fishes can alter lake foodweb dynamics, with contrasting impacts on native fishes. This knowledge is vital for future evaluation and mitigation of potential impacts of smelt introductions on lake ecosystems.acceptedVersio

Elevated Thyroxine Concentration and Lithium Intoxication - An Analysis Based on the LiSIE Retrospective Cohort Study

(1) Background: It has been suggested that hyperthyroxinaemia is a risk factor for lithium intoxication by altering tubular renal function. (2) Methods: We determined the relevance of hyperthyroxinaemia as a risk factor for lithium intoxication in patients with bipolar or schizoaffective disorder in the framework of the LiSIE (Lithium-Study into Effects and Side Effects) retrospective cohort study. Of 1562 patients included in the study, 897 patients had been exposed to lithium at any time between 1997 and 2017 with 6684 person-years of observation. (3) Results: There were 65 episodes of unintentional lithium intoxication in 53 patients. There were nine episodes with hyperthyroxinaemia at the time of lithium intoxication, yielding an incidence of 1.3 episodes/1000 person-years. For all nine episodes, we could identify alternative, more plausible, explanations for the observed lithium intoxications. (4) Conclusions: We conclude that hyperthyroxinaemia-associated unintentional lithium intoxication is an uncommon event. A direct causal link between hyperthyroxinaemia and altered tubular renal function remains elusive. Increasing the frequency of routine thyroid function tests seems unlikely to decrease the risk of lithium intoxication

Self-injurious behaviour in patients with bipolar disorder and attention deficit hyperactivity disorder after central stimulant start : a retrospective study based on the lisie cohort

INTRODUCTION: Currently, our understanding remains limited of how co-occurring bipolar disorder and attention deficit hyperactivity disorder (ADHD) should be treated. OBJECTIVES: To evaluate the impact of central stimulant treatment on self-injurious behaviour in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD. METHODS: Retrospective cohort study (LiSIE) into effects and side-effects of lithium as compared to other mood stabilisers. Here, using a mirror-image design, we compared suicide attempts and non-suicidal self-injury events within 6 months and 2 years before and after central stimulant treatment start. RESULTS: Of 1564 eligible patients, 206 patients met inclusion criteria; having a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD at first central stimulant initiation. In these, suicide attempts and non-suicidal self-injury events decreased significantly within both 6 months (p = 0.004) and 2 years (p = 0.028) after central stimulant start. After multiple adjustments, this effect was preserved 2 years after central stimulant start (OR 0.63, 95% CI; 0.40 – 0.98, p = 0.041). CONCLUSIONS: Central stimulant treatment may reduce the risk of self-injurious behavior in patients with a dual diagnosis of bipolar disorder or schizoaffective disorder and ADHD. However, to reduce the risk of manic switches, concomitant mood stabilising treatment remains warranted. DISCLOSURE: Michael Ott has been a scientific advisory board member of Astra Zeneca Sweden, Ursula Werneke has received funding for educational activities on behalf of Norrbotten Region (Masterclass Psychiatry Programme 2014–2018 and EAPM 2016, Luleå, Sweden): Astr

Suicidal and non-suicidal self-injurious behaviour in patients with bipolar disorder and comorbid attention deficit hyperactivity disorder after initiation of central stimulant treatment : a mirror-image study based on the LiSIE retrospective cohort

Background: Currently, our understanding regarding treatment of adult attention deficit hyperactivity disorder (ADHD) co-occurring with bipolar disorder (BD) remains limited. The aim of this study was to evaluate the impact of central stimulant (CS) treatment on suicidal and non-suicidal self-injurious behaviour in patients with a pre-existing diagnosis of BD or schizoaffective disorder (SZD). Specifically, we tested the hypothesis that CS treatment significantly decreased the number of suicide attempts and non-suicidal self-injury events. Methods: A mirror-image study in patients with a dual diagnosis of BD or SZD and ADHD, comparing suicide attempts and non-suicidal self-injury events within 6 months and 2 years before and after CS initiation. This study was part of a retrospective cohort study (LiSIE) into effects and side-effects of lithium for maintenance treatment of BD as compared with other mood stabilisers. Results: Of 1564 eligible patients, 206 patients met the inclusion criteria. Within the 6 months after CS initiation, suicide attempts and non-suicidal self-injury events decreased significantly, both in terms of numbers of patients having such events (p = 0.013) and numbers of events experienced (p = 0.004). These effects were preserved 2 years after CS initiation. Conclusions: CS treatment may reduce the risk of suicide attempts and non-suicidal self-injury events in patients with a dual diagnosis of BD or SZD and ADHD. Based on our findings, clinicians should not withhold CS treatment from patients with concomitant ADHD for fear of deterioration of the underlying BD. However, to minimise the risk of manic episodes concomitant mood stabiliser treatment and close monitoring remains warranted.Originally included in thesis in manuscript form with title: "Suicidal and other deliberate self-injurious behaviour in patients with bipolar disorder and comorbid attention deficit hyperactivity disorder after initiation of central stimulant treatment: a mirror-image study based on the LiSIE retrospective cohort".</p