Top Ten epilepsy research priorities: A UK priority setting partnership.

Purpose: Research into epilepsy has experienced decades of chronic underfunding compared to other neurological conditions despite its prevalence and seriousness. To evidence the need for greater investment, the Epilepsy Research Institute (formerly Epilepsy Research UK) funded, led and managed a James Lind Alliance (JLA) Priority Setting Partnership (PSP). This "industry standard" methodology brings together healthcare professionals, patients, carers and patient group representatives to identify and prioritise research uncertainties within a defined area of health or care.

Why have status epilepticus trials failed: Wrong drugs or wrong trials?

Despite burgeoning interest in trials in status epilepticus over the last 20 years, outcomes have yet to improve and a number of high profile studies have failed to deliver for a range of reasons. The range of reasons a trial may fail to meet the intended outcomes are discussed. Recent well designed, adequately powered studies in established status epilepticus failed to meet primary endpoints, but are nonetheless influencing practice, reflecting the importance of interpreting results in the context of broader literature, safety and practical considerations.

A Canine Distemper Outbreak in Urban Red Foxes (Vulpes vulpes) in Brussels, Belgium, 2020.

Canine distemper has been observed infrequently in Belgian wildlife, mainly stone martens (Martes foina) and red foxes (Vulpes vulpes). This report describes an outbreak in the Brussels urban red fox population, characterized by its high density. The identified virus matched those within a cluster of viruses found previously in red foxes in Germany.

RETROSPECTIVE STUDY OF MORBIDITY AND MORTALITY OF CAPTIVE AFRICAN WILD DOGS () HELD WITHIN UNITED KINGDOM ZOOLOGICAL INSTITUTIONS BETWEEN 2000 AND 2020.

The African wild dog () is listed as Endangered by the International Union for Conservation of Nature and is part of captive breeding programs designed to support free-living populations and genetic diversity. This study's aim was to identify common causes of morbidity and mortality objectively in United Kingdom captive African wild dogs to inform management recommendations that will improve health and welfare and reduce disease prevalence. Data were gathered from 140 individual dogs housed in 10 institutions, with morbidity records for 122 individuals and 70 postmortem reports.

The α-(1,3)-glucan synthase gene agsE impacts the secretome of Aspergillus niger.

Aspergillus niger is widely used as a cell factory for the industrial production of enzymes. Previously, it was shown that deletion of α-1-3 glucan synthase genes results in smaller micro-colonies in liquid cultures of Aspergillus nidulans. Also, it has been shown that small wild-type Aspergillus niger micro-colonies secrete more protein than large mirco-colonies.

Heterogeneity in Spore Aggregation and Germination Results in Different Sized, Cooperative Microcolonies in an Aspergillus niger Culture.

The fungus Aspergillus niger is among the most abundant fungi in the world and is widely used as a cell factory for protein and metabolite production. This fungus forms asexual spores called conidia that are used for dispersal. Notably, part of the spores and germlings aggregate in an aqueous environment.

Multivalent Fucosides Targeting β-Propeller Lectins from Lung Pathogens with Promising Anti-Adhesive Properties.

Fungal and bacterial pathogens causing lung infections often use lectins to mediate adhesion to glycoconjugates at the surface of host tissues. Given the rapid emergence of resistance to the treatments in current use, β-propeller lectins such as FleA from , SapL1 from and BambL from have become appealing targets for the design of anti-adhesive agents. In search of novel and cheap anti-infectious agents, we synthesized multivalent compounds that can display up to 20 units of fucose, the natural ligand.

Probing Cell-Surface Interactions in Fungal Cell Walls by High-Resolution H-Detected Solid-State NMR Spectroscopy.

Solid-state NMR (ssNMR) spectroscopy facilitates the non-destructive characterization of structurally heterogeneous biomolecules in their native setting, for example, comprising proteins, lipids and polysaccharides. Here we demonstrate the utility of high and ultra-high field H-detected fast MAS ssNMR spectroscopy, which exhibits increased sensitivity and spectral resolution, to further elucidate the atomic-level composition and structural arrangement of the cell wall of Schizophyllum commune, a mushroom-forming fungus from the Basidiomycota phylum. These advancements allowed us to reveal that Cu(II) ions and the antifungal peptide Cathelicidin-2 mainly bind to cell wall proteins at low concentrations while glucans are targeted at high metal ion concentrations.

Novel Treatment Approach for Aspergilloses by Targeting Germination.

Germination of conidia is an essential process within the life cycle and plays a major role during the infection of hosts. Conidia are able to avoid detection by the majority of leukocytes when dormant. Germination can cause severe health problems, specifically in immunocompromised people.

Comparison of serum tryptase as a diagnostic oncological marker in canine versus human mast cell neoplasms.

Canine mast cell tumors (MCTs) are a promising translational model for human mast cell neoplasms with striking similarities such as the Darier's sign and mutations in the KIT gene. Whereas mast cell neoplasms are rare in humans, MCTs are the most frequent malignant neoplasms of the skin in dogs. In human systemic mastocytosis, serum tryptase is an important diagnostic criterion.

Growth of in Biofilms in Comparison to .

Biofilm formation during infections with the opportunistic pathogen can be very problematic in clinical settings, since it provides the fungal cells with a protective environment. Resistance against drug treatments, immune recognition as well as adaptation to the host environment allows fungal survival in the host. The exact molecular mechanisms behind most processes in the formation of biofilms are unclear.

Management of status epilepticus: a narrative review.

Status epilepticus causes prolonged or repetitive seizures that, if left untreated, can lead to neuronal injury, severe disability, coma and death in paediatric and adult populations. While convulsive status epilepticus can be diagnosed using clinical features alone, non-convulsive status epilepticus requires confirmation by electroencephalogram. Early seizure control remains key in preventing the complications of status epilepticus.

The Protective Role of 1,8-Dihydroxynaphthalene-Melanin on Conidia of the Opportunistic Human Pathogen Aspergillus fumigatus Revisited: No Role in Protection against Hydrogen Peroxide and Superoxides.

Previously, 1,8-dihydroxynaphthalene (DHN)-melanin was described to protect Aspergillus fumigatus against hydrogen peroxide (HO), thereby protecting this opportunistic human pathogen from reactive oxygen species generated by the immune system. This was based on the finding that the ATCC 46645 mutant with mutations in the gene of the DHN-melanin synthesis pathway showed increased sensitivity to reactive oxygen species compared to the wild type. Here, it is shown that deletion of the gene in A.

Correction: Variation of virulence of five Aspergillus fumigatus isolates in four different infection models.

[This corrects the article DOI: 10.1371/journal.pone.

Variation of virulence of five Aspergillus fumigatus isolates in four different infection models.

Conidia of Aspergillus fumigatus are inhaled by humans on daily basis. As a consequence, these conidia can cause infections that differ in severity ranging from allergic bronchopulmonary aspergillosis to invasive aspergillosis. In this study we compared virulence of five A.

Back to the Basics: Two Approaches for the Identification and Extraction of Lipid Droplets from Malassezia pachydermatis CBS1879 and Malassezia globosa CBS7966.

Malassezia spp. are lipid-dependent yeasts that have been related to skin mycobiota and dermatological and systemic diseases. Study of lipid droplets (LDs) is relevant to elucidate the unknown role of these organelles in Malassezia and to gain a broader overview of lipid metabolism in Malassezia.

Host defence peptides identified in human apolipoprotein B as promising antifungal agents.

Therapeutic options to treat invasive fungal infections are still limited. This makes the development of novel antifungal agents highly desirable. Naturally occurring antifungal peptides represent valid candidates, since they are not harmful for human cells and are endowed with a wide range of activities and their mechanism of action is different from that of conventional antifungal drugs.

Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial.

Objective: This study was undertaken to describe patterns of benzodiazepine use as first-line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second-line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT).

Methods: Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second-line agent, route of administration, setting, and patient weight were characterized.

Early Exposure of Fosphenytoin, Levetiracetam, and Valproic Acid After High-Dose Intravenous Administration in Young Children With Benzodiazepine-Refractory Status Epilepticus.

Fosphenytoin (FOS) and its active form, phenytoin (PHT), levetiracetam (LEV), and valproic acid (VPA) are commonly used second-line treatments of status epilepticus. However, limited information is available regarding LEV and VPA concentrations following high intravenous doses, particularly in young children. The Established Status Epilepticus Treatment Trial, a blinded, comparative effectiveness study of FOS, LEV, and VPA for benzodiazepine-refractory status epilepticus provided an opportunity to investigate early drug concentrations.

The sino-nasal warzone: transcriptomic and genomic studies on sino-nasal aspergillosis in dogs.

We previously showed that each dog with chronic non-invasive sino-nasal aspergillosis (SNA) was infected with a single genotype of Aspergillus fumigatus. Here, we studied the transcriptome of this fungal pathogen and the canine host within the biofilm resulting from the infection. We describe here transcriptomes resulting from natural infections in animal species with A.

EphA2-Dependent Internalization of Conidia in A549 Lung Cells Is Modulated by DHN-Melanin.

Dectin-1 and ephrin type-A receptor 2 (EphA2) receptors recognize β-glucan present in the fungal cell wall. Inhibition of Dectin-1 with the monoclonal 2a11 antibody was shown to reduce internalization of conidia of the human pathogen into epithelial cells. In this study, we investigated the role of the EphA2 receptor present on A549 epithelial type II lung cells in the interaction with conidia.

In Vitro or In Vivo Models, the Next Frontier for Unraveling Interactions between spp. and Hosts. How Much Do We Know?

is a lipid-dependent genus of yeasts known for being an important part of the skin mycobiota. These yeasts have been associated with the development of skin disorders and cataloged as a causal agent of systemic infections under specific conditions, making them opportunistic pathogens. Little is known about the host-microbe interactions of spp.

Testing blood and CSF in people with epilepsy: a practical guide.

Laboratory investigations, whilst not essential to the diagnosis of seizures or of epilepsy, can be fundamental to determining the cause and guiding management. Over 50% of first seizures have an acute symptomatic cause, including a range of metabolic, toxic or infectious cause. The same triggers can precipitate status epilepticus, either de novo or as part of a deterioration in control in individuals with established epilepsy.