Triptans and CGRP blockade - impact on the cranial vasculature

The trigeminovascular system plays a key role in the pathophysiology of migraine. The activation of the trigeminovascular system causes release of various neurotransmitters and neuropeptides, including serotonin and calcitonin gene-related peptide (CGRP), which modulate pain transmission and vascular tone. Thirty years after discovery of agonists for serotonin 5-HT1B and 5-HT1D receptors (triptans) and less than fifteen after the proof of concept of the gepant class of CGRP receptor antagonists, we are still a long way from understanding their precise site and mode of action in migraine. The effect on cranial vasculature is relevant, because all specific anti-migraine drugs and migraine pharmacological triggers may act in perivascular space. This review reports the effects of triptans and CGRP blocking molecules on cranial vasculature in humans, focusing on their specific relevance to migraine treatment

Digitization of LAr calorimeter for CSC simulations

This note describes the digitization of the LAr signals, which is the step creating RDO from Geant4 Hits, as used during the production of the CSC simulated samples with athena release 12

Framing education on headache disorders into the Global Burden of Disease Study 2010 : the European Headache Federation stands ready

Framing education on headache disorders into the Global Burden of Disease Study 2010. The European Headache Federation stands ready

Stimulus - response curves of a neuronal model for noisy subthreshold oscillations and related spike generation

We investigate the stimulus-dependent tuning properties of a noisy ionic conductance model for intrinsic subthreshold oscillations in membrane potential and associated spike generation. On depolarization by an applied current, the model exhibits subthreshold oscillatory activity with occasional spike generation when oscillations reach the spike threshold. We consider how the amount of applied current, the noise intensity, variation of maximum conductance values and scaling to different temperature ranges alter the responses of the model with respect to voltage traces, interspike intervals and their statistics and the mean spike frequency curves. We demonstrate that subthreshold oscillatory neurons in the presence of noise can sensitively and also selectively be tuned by stimulus-dependent variation of model parameters.Comment: 19 pages, 7 figure

A role for fast rhythmic bursting neurons in cortical gamma oscillations in vitro

Basic cellular and network mechanisms underlying gamma frequency oscillations (30–80 Hz) have been well characterized in the hippocampus and associated structures. In these regions, gamma rhythms are seen as an emergent property of networks of principal cells and fast-spiking interneurons. In contrast, in the neocortex a number of elegant studies have shown that specific types of principal neuron exist that are capable of generating powerful gamma frequency outputs on the basis of their intrinsic conductances alone. These fast rhythmic bursting (FRB) neurons (sometimes referred to as "chattering" cells) are activated by sensory stimuli and generate multiple action potentials per gamma period. Here, we demonstrate that FRB neurons may function by providing a large-scale input to an axon plexus consisting of gap-junctionally connected axons from both FRB neurons and their anatomically similar counterparts regular spiking neurons. The resulting network gamma oscillation shares all of the properties of gamma oscillations generated in the hippocampus but with the additional critical dependence on multiple spiking in FRB cells

Parenting ‘gifted and talented’ children in urban areas: Parents' voices

This is the author's accepted manuscript. The final published article is available from the link below. Copyright © 2014 by SAGE Publications.International evidence demonstrates the importance of engaging parents in the education of their ‘high-potential’ children, yet limited research has focused on the involvement of parents from differing economic strata/backgrounds. The current study explored the dilemmas of parenting academically high-ability children from economically deprived urban areas in the UK. Data were gathered from a sample of parents whose children attended a university-based sustained intervention programme for designated ‘gifted’ pupils aged 12–16. Parental perceptions were sought in relation to (a) the usefulness/impact of the intervention programme, (b) parents’ aspirations for their children growing up in economically deprived urban areas and (c) parents’ views on the support provided by the extended family, peer groups and the wider community. The findings have significant implications for both policy and practice and, more specifically, for engaging parents in intervention programmes offered by universities and schools to children in order to increase their access to higher education and for enhancing their life chances

Refractory Headache: One Term does Not cover All – A Statement of the European Headache Federation

[No abstract available

Initial assessment and treatment of refugees in the Mediterranean Sea (a secondary data analysis concerning the initial assessment and treatment of 2656 refugees rescued from distress at sea in support of the EUNAVFOR MED relief mission of the EU)

Excerpt of the underlying study variables with explanations and degree. (DOCX 100 kb

IL-23-mediated mononuclear phagocyte crosstalk protects mice from Citrobacter rodentium-induced colon immunopathology.

Gut homeostasis and mucosal immune defense rely on the differential contributions of dendritic cells (DC) and macrophages. Here we show that colonic CX3CR1(+) mononuclear phagocytes are critical inducers of the innate response to Citrobacter rodentium infection. Specifically, the absence of IL-23 expression in macrophages or CD11b(+) DC results in the impairment of IL-22 production and in acute lethality. Highlighting immunopathology as a death cause, infected animals are rescued by the neutralization of IL-12 or IFNγ. Moreover, mice are also protected when the CD103(+) CD11b(-) DC compartment is rendered deficient for IL-12 production. We show that IL-12 production by colonic CD103(+) CD11b(-) DC is repressed by IL-23. Collectively, in addition to its role in inducing IL-22 production, macrophage-derived or CD103(-) CD11b(+) DC-derived IL-23 is required to negatively control the otherwise deleterious production of IL-12 by CD103(+) CD11b(-) DC. Impairment of this critical mononuclear phagocyte crosstalk results in the generation of IFNγ-producing former TH17 cells and fatal immunopathology