Learning intrinsic excitability in medium spiny neurons

We present an unsupervised, local activation-dependent learning rule for intrinsic plasticity (IP) which affects the composition of ion channel conductances for single neurons in a use-dependent way. We use a single-compartment conductance-based model for medium spiny striatal neurons in order to show the effects of parametrization of individual ion channels on the neuronal activation function. We show that parameter changes within the physiological ranges are sufficient to create an ensemble of neurons with significantly different activation functions. We emphasize that the effects of intrinsic neuronal variability on spiking behavior require a distributed mode of synaptic input and can be eliminated by strongly correlated input. We show how variability and adaptivity in ion channel conductances can be utilized to store patterns without an additional contribution by synaptic plasticity (SP). The adaptation of the spike response may result in either "positive" or "negative" pattern learning. However, read-out of stored information depends on a distributed pattern of synaptic activity to let intrinsic variability determine spike response. We briefly discuss the implications of this conditional memory on learning and addiction.Comment: 20 pages, 8 figure

Phase II trial of natalizumab for the treatment of anti-Hu associated paraneoplastic neurological syndromes

BACKGROUND: Paraneoplastic neurological syndromes with anti-Hu antibodies (Hu-PNS) have a very poor prognosis: more than half of the patients become bedridden and median survival is less than 12 months. Several lines of evidence suggest a pathogenic T cell-mediated immune response. Therefore, we conducted a prospective open-label phase II trial with natalizumab. METHODS: Twenty Hu-PNS patients with progressive disease were treated with a maximum of three monthly natalizumab cycles (300 mg). The primary outcome measure was functional improvement, this was defined as at least one point decrease in modified Rankin Scale (mRS) score at the last treatment visit. In addition, treatment response was assessed wherein a mRS score ≤3 after treatment was defined as treatment responsive. RESULTS: The median age at onset was 67.8 years (SD 8.4) with a female predominance (n = 17, 85%). The median time from symptom onset to Hu-PNS diagnosis was 5 months (IQR 2–11). Most patients had subacute sensory neuronopathy (n = 15, 75%), with a median mRS of 4 at baseline. Thirteen patients had a tumor, all small cell lung cancer. After natalizumab treatment, two patients (10%) showed functional improvement. Of the remaining patients, 60% had a stable functional outcome, while 30% showed further deterioration. Treatment response was classified as positive in nine patients (45%). CONCLUSIONS: Natalizumab may ameliorate the disease course in Hu-PNS, but no superior effects above other reported immunosuppressive and immunomodulatory were observed. More effective treatment modalities are highly needed. TRIAL REGISTRATION: https://www.clinicaltrialsregister.eu/ctr-search/trial/2014-000675-13/N

Cerebroplacental ratio in predicting adverse perinatal outcome : a meta-analysis of individual participant data

Acknowledgement We would like thank Dr F. Figueras, Prof. E. Gratacos, Dr F. Crispi and Dr J. Miranda for sharing data for this project. The CPR IPD Study Group: Asma Khalil (Fetal Medi- cine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, Lon- don, UK), Basky Thilaganathan (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s Univer- sity of London, London, UK; Vascular Biology Research Centre, Molecular and Clinical Sciences Research Institute, St George’s University of London, London, UK), Ozhan M Turan (Departments of Obstetrics, Gynecology and Repro- ductive Sciences, University of Maryland School of Medi- cine, Baltimore, MD, USA), Sarah Crimmins (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Chris Harman (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Alis- son M Shannon (Departments of Obstetrics, Gynecology and Reproductive Sciences, University of Maryland School of Medicine, Baltimore, MD, USA), Sailesh Kumar (School of Medicine, The University of Queensland, Brisbane, QLD, Australia; Mater Research Institute – University of Queensland, South Brisbane, QLD, Australia), Patrick Dicker (Department of Epidemiology and Public Health, Royal College of Surgeons in Ireland), Fergal Malone (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Elizabeth C Tully (Departments of Obstetrics and Gynaecology, Royal College of Surgeons in Ireland), Julia Unterscheider (Department of Maternal Fetal Medicine, The Royal Women’s Hospital, Melbourne, VIC, Australia), Isabella Crippa (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Alessandro Ghidini (Department of Obstetrics and Gynae- cology, University of Milano-Bicocca, Monza, Italy), Nadia Roncaglia (Department of Obstetrics and Gynaecology, University of Milano-Bicocca, Monza, Italy), Patrizia Ver- gani (Department of Obstetrics and Gynaecology, Univer- sity of Milano-Bicocca, Monza, Italy), Amarnath Bhide (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK), Fran- cesco D’Antonio (Fetal Medicine Unit, St George’s Hospital Medical School and St George’s University of London, London, UK), Gianluigi Pilu (Policlinico S. Orsola-Mal- pighi, University of Bologna, Bologna, Italy), Alberto Galindo (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Ignacio Herraiz (Fetal Medicine Unit-SAMID, Department of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Com- plutense University of Madrid, Madrid, Spain), Alicia Vazquez-Sarandeses(FetalMedicineUnit-SAMID,Depart- ment of Obstetrics and Gynaecology, University Hospital 12 de Octubre, 12 de Octubre Research Institute (imas12), Complutense University of Madrid, Madrid, Spain), Cath- rine Ebbing (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Synnøve L Johnsen (Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway), Henriette O Karlsen (Research Group for Pregnancy, Fetal Develop- ment and Birth, Department of Clinical Science, University of Bergen, Bergen, Norway).Peer reviewedPublisher PD

Early inhalant allergen sensitization at component level: an analysis in atopic Dutch children

BackgroundAllergic rhinitis is a common respiratory disease in children and sensitization to inhalant allergens plays a significant role in its development. However, limited knowledge exists regarding sensitization profiles of inhalant allergen components in atopic children, particularly in the very young individuals. Understanding these profiles could provide insights into the early development of allergic rhinitis. The objective of this cross-sectional retrospective study was to evaluate the IgE-sensitization profiles to multiple inhalant allergen components and their clinical relevance in Dutch atopic children, with specific focus on children under the age of 4 years.MethodsA total of 243 atopic children were included in the study and sensitization profiles were analyzed using multiplex microarray analysis (ISAC). Clinical information was obtained from records of a pediatric allergy outpatient clinic between 2011 and 2020. Specific IgE responses to inhalation allergen components from five allergen sources (grass pollen, tree pollen, house dust mite, cat and dog), were examined. The study encompassed children of different age groups and compared those with and without symptoms.ResultsThe results demonstrated that sensitization to inhalant allergen components was present in 92% of the cohort. Sensitization was already evident at a young age (87%), including infancy, with a rapid increase in prevalence after 1 year of age. House dust mite emerged as the most predominant sensitizing allergen in early childhood, followed by tree pollen in later years. Sensitization patterns were similar between symptomatic and asymptomatic children, although symptomatic children exhibited higher frequencies and values. The sensitization profiles in very young children were comparable to those of children across all age groups.ConclusionThese findings highlight the presence of sensitization to inhalant allergen components and the early onset of allergic rhinitis before the age of 4, including infancy, in Dutch atopic children. Notable allergen molecules in Dutch atopic children under the age of 4 years include Bet v 1, Fel d 1, Der f 1, Der p 1, Der p 10 and Phl p 4, with house dust mite sensitization being the most common among Dutch infants. Moreover, the prevalence of sensitization to inhalant allergens in this Dutch cohort surpassed that of general European populations, emphasizing the importance of early assessment and management of allergic rhinitis in young atopic children

Research to develop Spiritual Pedagogy, Awareness and Change

This is an Accepted Manuscript of an article published by Taylor & Francis in British Journal of Guidance and Counselling on 21-4-16, available online: http://dx.doi.org/10.1080/03069885.2016.1174976A co-operative inquiry group consisting of 8 counsellors met for 11 months to explore their experience of spirituality in their counselling training and in their work with clients (Swinton, 2010; 2015). The aim was to explore whether spirituality was absent from the process of counselling training, specifically to discover (1) how counsellors perceived and described their experience of spirituality in their training and (2) with a view to developing spiritual pedagogy; how spirituality could be incorporated into the training process of practitioner

Elevated Plasma Levels of sIL-2R in Complex Regional Pain Syndrome: A Pathogenic Role for T-Lymphocytes?

The immune system has long been thought to be involved in the pathophysiology of complex regional pain syndrome (CRPS). However, not much is known about the role of the immune system and specifically T-cells in the onset and maintenance of this disease. In this study, we aimed to evaluate T-cell activity in CRPS by comparing blood soluble interleukin-2 receptor (sIL-2R) levels between CRPS patients and healthy controls. CRPS patients had statistically significant elevated levels of sIL-2R as compared to healthy controls (median sIL-2R levels: 4151 pg/ml (Q3 − Q1 = 5731 pg/ml − 3546 pg/ml) versus 1907 pg/ml (Q3 − Q1: 2206 pg/ml − 1374 pg/ml), p < 0 001, resp.). Furthermore, sIL-2R level seems to be a good discriminator between CRPS patients and healthy controls with a high sensitivity (90%) and specificity (89.5%). Our finding indicates increased T-cell activity in patients with CRPS. This finding is of considerable relevance as it could point towards a T-cell-mediated inflammatory process in this disease. This could pave the way for new anti-inflammatory therapies in the treatment of CRPS. Furthermore, sIL-2R could be a promising new marker for determining inflammatory disease activity in CRPS