Regulation of hyphal growth and sporulation of the insect pathogenic fungus Entomophthora thripidum in vitro

Entomophthora thripidum is an obligate biotrophic insect pathogenic fungus that grows as protoplasts within the hemocoel of thrips. Prior to penetration through the insect cuticle and spore formation at the insect surface the protoplasts switch to hyphal growth. In vitro, the differentiation to hyphal growth was a prerequisite for the subsequent formation of infectious spores and was detected 10-20 days after inoculation. E. thripidum secreted a factor that autoinduced the differentiation to hyphal growth. The discovery of this activity inducing hyphal growth made possible the reliable production of spores, the infection of host insects and the consecutive re-isolation of the fungus from the infected insect

Regulation of hyphal growth and sporulation of the insect pathogenic fungus Entomophthora thripidum in vitro

Entomophthora thripidum is an obligate biotrophic insect pathogenic fungus that grows as protoplasts within the hemocoel of thrips. Prior to penetration through the insect cuticle and spore formation at the insect surface the protoplasts switch to hyphal growth. In vitro, the differentiation to hyphal growth was a prerequisite for the subsequent formation of infectious spores and was detected 10-20 days after inoculation. E. thripidum secreted a factor that autoinduced the differentiation to hyphal growth. The discovery of this activity inducing hyphal growth made possible the reliable production of spores, the infection of host insects and the consecutive re-isolation of the fungus from the infected insect

High-yielding 18F radiosynthesis of a novel oxytocin receptor tracer, a probe for nose-to-brain oxytocin uptake in vivo

A novel Al18F labelled peptide tracer for PET imaging of oxytocin receptor has been accessed through a high radiochemical yield approach. This tracer showed comparable affinity and higher selectivity and stability compared to oxytocin, and was used to demonstrate direct nose-to-brain uptake following intranasal administration, a common yet controversial delivery route for oxytocin-based therapeutics

A bedside swallowing screen for the identification of post-extubation dysphagia on the intensive care unit – validation of the Gugging Swallowing Screen (GUSS)—ICU

Purpose Screening for dysphagia at the intensive care unit (ICU) soon after extubation can prevent aspiration, pneumonia, lower mortality, and shorten re‑feeding interval. This study aimed to modify the Gugging Swallowing Screen (GUSS), which was developed for acute stroke patients, and to validate it for extubated patients in the ICU. Methods In this prospective study, forty‑five patients who had been intubated for at least 24 h were recruited consecutively at the earliest 24 h after extubation. The modified GUSS‑ICU was performed twice by two speech and language therapists independently. Concurrently, gold standard the flexible endoscopic evaluation of swallowing (FEES) was performed by an otorhinolaryngologist. Measurements were conducted within a three‑hour period; all testers were blinded to each other’s results. Results According to FEES, 36 of 45 (80%) participants were diagnosed with dysphagia; 13 of those were severe, 12 moderate, and 11 mild. Compared to FEES, the GUSS‑ICU predicted dysphagia well (area under the curve for the initial rater pair: 0.923, 95% CI 0.832–1.000 and 0.923, 95% CI 0.836 ‑1.000 for the second rater pair). The sensitivity was 91.7% (95% CI 77.5–98.3%) and 94.4% (95% CI 81.3–99.3%); the specificity was 88.9% (51.8–99.7%) and 66.7% (29.9–92.5%); the positive predictive values were 97.1% (83.8–99.5%) and 91.9% (81.7–96.6%), and the negative predictive values were 72.7% (46.8–89%) and 75% (41.9–92.6%) for the first and second rater pairs, respectively. Dysphagia severity classification according to FEES and GUSS‑ICU correlated strongly (Spearman’s rho: 0.61 for rater 1 and 0.60 for rater 2, p < 0.001). Agreement by all testers was good (Krippendorffs Alpha: 0.73). The interrater reliability showed good agreement (Cohen`s Kappa: 0.84, p < 0.001). Conclusion The GUSS‑ICU is a simple, reliable, and valid multi‑consistency bedside swallowing screen to identify post‑extubation dysphagia at the ICU

Future Skills in Forschung und Lehre in Hinblick auf digitale und soziale Transformation

Unter dem Gesichtspunkt der aktuellen digitalen, sozialen und ökologischen Transformationsprozesse strebt das Projekt TRANSFORM an, deren Auswirkungen im Kontext universitärer Lehre und Forschung zu untersuchen. Hochschulen stehen als Bildungseinrichtungen in der Verantwortung, junge Menschen bei der Entwicklung jener Fähigkeiten zu unterstützen, die ihnen dabei helfen, resilient auf zukünftige Herausforderungen zu reagieren und positive Veränderungen zu bewirken. Der Beitrag fasst die inhaltliche Stoßrichtung des laufenden Projekts zusammen und skizziert ausgewählte Umsetzungsmaßnahmen. Allen Projektarbeiten ist der Brückenschlag zwischen den Disziplinen gemein, dem in Lehre und Forschung dieselbe Bedeutung zukommt und der im Hinblick auf die nötigen „future skills“ zur Bewältigung zukünftiger Herausforderungen in Theorie und Praxis entwickelt wird

Management of swallowing disorders in ICU patients - A multinational expert opinion.

BACKGROUND Dysphagia is common in intensive care unit (ICU) patients, yet it remains underrecognized and often unmanaged despite being associated with life-threatening complications, prolonged ICU stays and hospitalization. PURPOSE To propose an expert opinion for the diagnosis and management of dysphagia developed from evidence-based clinical recommendations and practitioner insights. METHODS A multinational group of dysphagia and critical care experts conducted a literature review using a modified ACCORD methodology. Based on a fusion of the available evidence and the panel's clinical experience, an expert opinion on best practice management was developed. RESULTS The panel recommends adopting clinical algorithms intended to promote standardized, high-quality care that triggers timely systematic dysphagia screening, assessment, and treatment of extubated and tracheostomized patients in the ICU. CONCLUSIONS Given the lack of robust scientific evidence, two clinical management algorithms are proposed for use by multidisciplinary teams to improve early systematic detection and effective management of dysphagia in ICU patients. Additionally, emerging therapeutic options such as neurostimulation have the potential to improve the quality of ICU dysphagia care

European Stroke Organization and European Society for Swallowing Disorders guideline for the diagnosis and treatment of post-stroke dysphagia

Post-stroke dysphagia (PSD) is present in more than 50% of acute stroke patients, increases the risk of complications, in particular aspiration pneumonia, malnutrition and dehydration, and is linked to poor outcome and mortality. The aim of this guideline is to assist all members of the multidisciplinary team in their management of patients with PSD. These guidelines were developed based on the European Stroke Organisation (ESO) standard operating procedure and followed the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. An interdisciplinary working group identified 20 relevant questions, performed systematic reviews and meta-analyses of the literature, assessed the quality of the available evidence and wrote evidence-based recommendations. Expert opinion was provided if not enough evidence was available to provide recommendations based on the GRADE approach. We found moderate quality of evidence to recommend dysphagia screening in all stroke patients to prevent post-stroke pneumonia and to early mortality and low quality of evidence to suggest dysphagia assessment in stroke patients having been identified at being at risk of PSD. We found low to moderate quality of evidence for a variety of treatment options to improve swallowing physiology and swallowing safety. These options include dietary interventions, behavioural swallowing treatment including acupuncture, nutritional interventions, oral health care, different pharmacological agents and different types of neurostimulation treatment. Some of the studied interventions also had an impact on other clinical endpoints such as feedings status or pneumonia. Overall, further randomized trials are needed to improve the quality of evidence for the treatment of PSD

Sustained in vivo signaling by long-lived IL-2 induces prolonged increases of regulatory T cells.

Regulatory T cells (Tregs) expressing FOXP3 are essential for the maintenance of self-tolerance and are deficient in many common autoimmune diseases. Immune tolerance is maintained in part by IL-2 and deficiencies in the IL-2 pathway cause reduced Treg function and an increased risk of autoimmunity. Recent studies expanding Tregs in vivo with low-dose IL-2 achieved major clinical successes highlighting the potential to optimize this pleiotropic cytokine for inflammatory and autoimmune disease indications. Here we compare the clinically approved IL-2 molecule, Proleukin, with two engineered IL-2 molecules with long half-lives owing to their fusion in monovalent and bivalent stoichiometry to a non-FcRγ binding human IgG1. Using nonhuman primates, we demonstrate that single ultra-low doses of IL-2 fusion proteins induce a prolonged state of in vivo activation that increases Tregs for an extended period of time similar to multiple-dose Proleukin. One of the common pleiotropic effects of high dose IL-2 treatment, eosinophilia, is eliminated at doses of the IL-2 fusion proteins that greatly expand Tregs. The long half-lives of the IL-2 fusion proteins facilitated a detailed characterization of an IL-2 dose response driving Treg expansion that correlates with increasingly sustained, suprathreshold pSTAT5a induction and subsequent sustained increases in the expression of CD25, FOXP3 and Ki-67 with retention of Treg-specific epigenetic signatures at FOXP3 and CTLA4.This work was supported by Wellcome Trust Grant 091157, JDRF International Grant 9-2011-253, the National Institute for Health Research Cambridge Biomedical Research Centre, and the Medical Research Council Cusrow Wadia Fund. The Cambridge Institute for Medical Research (CIMR) is in receipt of a Wellcome Trust Strategic Award (100140). U.M.N. was the recipient of a Hoffmann-La Roche postdoctoral fellowship.This is thefinal version. It was first published by Elsevier at http://www.sciencedirect.com/science/article/pii/S089684111400146

Selective oxytocin receptor activation prevents prefrontal circuit dysfunction and social behavioral alterations in response to chronic prefrontal cortex activation in male rats

IntroductionSocial behavioral changes are a hallmark of several neurodevelopmental and neuropsychiatric conditions, nevertheless the underlying neural substrates of such dysfunction remain poorly understood. Building evidence points to the prefrontal cortex (PFC) as one of the key brain regions that orchestrates social behavior. We used this concept with the aim to develop a translational rat model of social-circuit dysfunction, the chronic PFC activation model (CPA).MethodsChemogenetic designer receptor hM3Dq was used to induce chronic activation of the PFC over 10 days, and the behavioral and electrophysiological signatures of prolonged PFC hyperactivity were evaluated. To test the sensitivity of this model to pharmacological interventions on longer timescales, and validate its translational potential, the rats were treated with our novel highly selective oxytocin receptor (OXTR) agonist RO6958375, which is not activating the related vasopressin V1a receptor.ResultsCPA rats showed reduced sociability in the three-chamber sociability test, and a concomitant decrease in neuronal excitability and synaptic transmission within the PFC as measured by electrophysiological recordings in acute slice preparation. Sub-chronic treatment with a low dose of the novel OXTR agonist following CPA interferes with the emergence of PFC circuit dysfunction, abnormal social behavior and specific transcriptomic changes.DiscussionThese results demonstrate that sustained PFC hyperactivity modifies circuit characteristics and social behaviors in ways that can be modulated by selective OXTR activation and that this model may be used to understand the circuit recruitment of prosocial therapies in drug discovery