Functional properties of feed-forward inhibition

ISBN : 978-2-9532965-0-1Neurons receive a large number of excitatory and inhibitory synaptic inputs whose temporal interplay determines the spiking behavior. On average, excitation and inhibition balance each other, such that spikes are elicited by fluctuations. In addition, it has been shown in vivo that excitation and inhibition are correlated, with inhibition lagging excitation only by few milliseconds (~6 ms), creating a small temporal integration window. This correlation structure could be induced by feed-forward inhibition (FFI), which has been shown to be present at many sites in the central nervous system. To characterize the functional properties of feed-forward inhibition, we constructed a simple circuit using spiking neurons with conductance based synapses and applied spike pulse packets with defined strength and width. We found that the small temporal integration window, induced by the FFI, changes the integrative properties of the neuron. Only transient stimuli could produce a response when the FFI was active, whereas without FFI the neuron responded to both steady and transient stimuli. In addition, the FFI increased the trial-by-trial precision

Unmet Medical Needs in Ulcerative Colitis: An Expert Group Consensus

BACKGROUND The authors aimed to conduct an extensive literature review and consensus meeting to identify unmet needs in ulcerative colitis (UC) and ways to overcome them. UC is a relapsing and remitting inflammatory bowel disease with varied, and changing, incidence rates worldwide. UC has an unpredictable disease course and is associated with a high health economic burden. During 2016 and 2017, a panel of experts was convened to identify, discuss and address areas of unmet need in UC. METHODS PubMed and Cochrane Library databases were searched for relevant articles describing studies performed in patients with UC. These findings were used to generate a set of statements relating to unmet needs in UC. Consensus on these statements was then sought from a panel of 9 expert gastroenterologists using a modified Delphi review process that consisted of anonymous surveys followed by live meetings. RESULTS In 2 literature reviews, over 5,000 unique records were identified and a total of 138 articles were fully reviewed. These were used to consider 26 areas of unmet need, which were explored in 2 face-to-face meetings, in which the statements were debated and amended, resulting in consensus on 30 final statements. The unmet needs identified were categorised into 7 areas: impact of UC on patients' daily life; importance of early diagnosis and treatment; drawbacks of existing treatments; urgent need for new treatments; and disease-, practice- or patient-focused unmet needs. CONCLUSIONS These expert group meetings found a number of areas of unmet needs in UC, which is an important first step in tackling them in the future. Future research and development should be focused in these areas for the management of patients with UC

A New Crocodylian from the Late Maastrichtian of Spain: Implications for the Initial Radiation of Crocodyloids

The earliest crocodylians are known primarily from the Late Cretaceous of North America and Europe. The representatives of Gavialoidea and Alligatoroidea are known in the Late Cretaceous of both continents, yet the biogeographic origins of Crocodyloidea are poorly understood. Up to now, only one representative of this clade has been known from the Late Cretaceous, the basal crocodyloid Prodiplocynodon from the Maastrichtian of North America.The fossil studied is a skull collected from sandstones in the lower part of the Tremp Formation, in Chron C30n, dated at -67.6 to 65.5 Ma (late Maastrichtian), in Arén (Huesca, Spain). It is located in a continuous section that contains the K/P boundary, in which the dinosaur faunas closest to the K/P boundary in Europe have been described, including Arenysaurus ardevoli and Blasisaurus canudoi. Phylogenetic analysis places the new taxon, Arenysuchus gascabadiolorum, at the base of Crocodyloidea.The new taxon is the oldest crocodyloid representative in Eurasia. Crocodyloidea had previously only been known from the Palaeogene onwards in this part of Laurasia. Phylogenetically, Arenysuchus gascabadiolorum is situated at the base of the first radiation of crocodyloids that occurred in the late Maastrichtian, shedding light on this part of the cladogram. The presence of basal crocodyloids at the end of the Cretaceous both in North America and Europe provides new evidence of the faunal exchange via the Thulean Land Bridge during the Maastrichtian

Crucial Ignored Parameters on Nanotoxicology: The Importance of Toxicity Assay Modifications and “Cell Vision”

Until now, the results of nanotoxicology research have shown that the interactions between nanoparticles (NPs) and cells are remarkably complex. In order to get a deep understanding of the NP-cell interactions, scientists have focused on the physicochemical effects. However, there are still considerable debates about the regulation of nanomaterials and the reported results are usually in contradictions. Here, we are going to introduce the potential key reasons for these conflicts. In this case, modification of conventional in vitro toxicity assays, is one of the crucial ignored matter in nanotoxicological sciences. More specifically, the conventional methods neglect important factors such as the sedimentation of NPs and absorption of proteins and other essential biomolecules onto the surface of NPs. Another ignored matter in nanotoxicological sciences is the effect of cell “vision” (i.e., cell type). In order to show the effects of these ignored subjects, we probed the effect of superparamagnetic iron oxide NPs (SPIONs), with various surface chemistries, on various cell lines. We found thatthe modification of conventional toxicity assays and the consideration of the “cell vision” concept are crucial matters to obtain reliable, and reproducible nanotoxicology data. These new concepts offer a suitable way to obtain a deep understanding on the cell-NP interactions. In addition, by consideration of these ignored factors, the conflict of future toxicological reports would be significantly decreased

Difficulties in assessing cytomegalovirus-associated gastric perforation in an HIV-infected patient

BACKGROUND: Active Cytomegalovirus (CMV) infection is a common complication in advanced symptomatic Human Immunodeficiency Virus (HIV) infection. CMV-induced intestinal perforations are hard to diagnose and may be observed throughout the gastrointestinal tract. Isolated stomach perforation is exceptional. CASE PRESENTATION: A 47-year-old man was admitted to our intensive care unit with multiorgan failure. Gastrointestinal endoscopic examination showed erythematous gastritis but normal duodenum and colon. CMV blood culture was positive. Histologic examination of a gastric biopsy showed inflammatory infiltrate and immunostaining typical intranuclear CMV inclusion bodies. Concomitant abdominal CT scan disclosed large peripancreatic hypodensities without pneumoperitoneum. The patient died despite supportive therapies and ganciclovir infusion. Postmortem examination showed a 4-cm gastric perforation adhering to the transverse colon and liver, with a thick necrotic inflammatory coating around the pancreas. The whole GI tract, except the stomach, was normal. As other causes, especially Helicobacter pylori infection could be ruled out, a causal relationship between CMV and gastric disease was assumed. CONCLUSION: CMV may be responsible for gastric perforations, with difficulties in assessing the diagnosis. Early diagnosis based on cautious endoscopy and histopathologic examination is needed to make a favorable outcome possible

Glucosamine increases hyaluronic acid production in human osteoarthritic synovium explants

Background. Glucosamine (GlcN) used by patients with osteoarthritis was demonstrated to reduce pain, but the working mechanism is still not clear. Viscosupplementation with hyaluronic acid (HA) is also described to reduce pain in osteoarthritis. The synthesis of HA requires GlcN as one of its main building blocks. We therefore hypothesized that addition of GlcN might increase HA production by synovium tissue. Methods. Human osteoarthritic synovium explants were obtained at total knee surgery and pre-cultured for 1 day. The experimental conditions consisted of a 2 days continuation of the culture with addition of N-Acetyl-glucosamine (GlcN-Ac; 5 mM), glucosamine-hydrochloride (GlcN-HCl; 0.5 and 5 mM), glucose (Gluc; 0.5 and 5 mM). Hereafter HA production was measured in culture medium supernatant using an enzyme-linked binding protein assay. Real time RT-PCR was performed for hyaluronic acid synthase (HAS) 1, 2 and 3 on RNA isolated from the explants. Results. 0.5 mM

Detecting spatio-temporal mortality clusters of European countries by sex and ag

[EN] Background: Mortality decreased in European Union (EU) countries during the last century. Despite these similar trends, there are still considerable differences in the levels of mortality between Eastern and Western European countries. Sub-group analysis of mortality in Europe for different age and sex groups is common, however to our knowledge a spatio-temporal methodology as in this study has not been applied to detect significant spatial dependence and interaction with time. Thus, the objective of this paper is to quantify the dynamics of mortality in Europe and detect significant clusters of mortality between European countries, applying spatio-temporal methodology. In addition, the joint evolution between the mortality of European countries and their neighbours over time was studied. Methods: The spatio-temporal methodology used in this study takes into account two factors: time and the geographical location of countries and, consequently, the neighbourhood relationships between them. This methodology was applied to 26 European countries for the period 1990-2012. Results: Principally, for people older than 64 years two significant clusters were obtained: one of high mortality formed by Eastern European countries and the other of low mortality composed of Western countries. In contrast, for ages below or equal to 64 years only the significant cluster of high mortality formed by Eastern European countries was observed. In addition, the joint evolution between the 26 European countries and their neighbours during the period 1990-2012 was confirmed. For this reason, it can be said that mortality in EU not only depends on differences in the health systems, which are a subject to national discretion, but also on supra-national developments. Conclusions: This paper proposes statistical tools which provide a clear framework for the successful implementation of development public policies to help the UE meet the challenge of rethinking its social model (Social Security and health care) and make it sustainable in the medium term.The authors are grateful for the financial support provided by the Ministry of Economy and Competitiveness, project MTM2013-45381-P. Adina Iftimi gratefully acknowledges financial support from the MECyD (Ministerio de Educacion, Cultura y Deporte, Spain) Grant FPU12/04531. Francisco Montes is grateful for the financial support provided by the Spanish Ministry of Economy and Competitiveness, project MTM2016-78917-R. The research by Patricia Carracedo and Ana Debon has been supported by a grant from the Mapfre Foundation.Carracedo-Garnateo, P.; Debón Aucejo, AM.; Iftimi, A.; Montes-Suay, F. (2018). Detecting spatio-temporal mortality clusters of European countries by sex and ag. 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