Neuronal Plasticity and the Cholinergic System Are Affected in Atopic Dermatitis and in Response to Acute Experimental Mental Stress in a Randomized Controlled Pilot Study

Rationale In mouse models for atopic dermatitis (AD) hypothalamus pituitary adrenal axis (HPA) dysfunction and neuropeptide-dependent neurogenic inflammation explain stress-aggravated flares to some extent. Lately, cholinergic signaling has emerged as a link between innate and adaptive immunity as well as stress responses in chronic inflammatory diseases. Here we aim to determine in humans the impact of acute stress on neuro-immune interaction as well as on the non-neuronal cholinergic system (NNCS). Methods Skin biopsies were obtained from 22 individuals (AD patients and matched healthy control subjects) before and after the Trier social stress test (TSST). To assess neuro-immune interaction, nerve fiber (NF)-density, NF-mast cell contacts and mast cell activation were determined by immunohistomorphometry. To evaluate NNCS effects, expression of secreted mammal Ly-6/urokinase-type plasminogen activator receptor-related protein (SLURP) 1 and 2 (endogenous nicotinic acetylcholine receptor ligands) and their main corresponding receptors were assessed by quantitative RT-PCR. Results With respect to neuro-immune interaction we found higher numbers of NGF+ dermal NF in lesional compared to non-lesional AD but lower numbers of Gap43+ growing NF at baseline. Mast cell-NF contacts correlated with SCORAD and itch in lesional skin. With respect to the NNCS, nicotinic acetylcholine receptor α7 (α7nAChR) mRNA was significantly lower in lesional AD skin at baseline. After TSST, PGP 9.5+ NF numbers dropped in lesional AD as did their contacts with mast cells. NGF+ NF now correlated with SCORAD and mast cell-NF contacts with itch in non-lesional skin. At the same time, SLURP-2 levels increased in lesional AD skin. Conclusions In humans chronic inflammatory and highly acute psycho-emotional stress interact to modulate cutaneous neuro- immune communication and NNCS marker expression. These findings may have consequences for understanding and treatment of chronic inflammatory diseases in the future

Wissensgesellschaft als Herausforderung für ländlich-periphere Regionen: Beispiele aus Nordostdeutschland

Die Heuristik einer dreidimensionalen Wissensgesellschaft wird in diesem Band aufgegriffen und weiterentwickelt. Die soziale, die ökonomische und die technische Dimension der Wissensgesellschaft werden im theoretischen Teil ausdifferenziert und anhand charakteristischer Ausprägungen strukturiert, z.B. individuelle Kompetenzen, kollektive Lernprozesse, Wirtschaftsfaktor Wissen, Zentralität, Mobilität oder Einbindung in globale Institutionensysteme. Diese strukturierenden Elemente bilden die Grundlage für die Auswahl von vertiefenden Studien im ländlichen, peripher gelegenen Raum Nordostdeutschlands im Hinblick auf Wachstumskerne in Brandenburg, Gesundheitsinfrastruktur, Mobilitätsangebote und Anschluss an Kommunikationstechnologien sowie Aus- und Weiterbildung, Bildungsnetzwerke und Bildungslandschaften. Beim Vergleich von Theorie und Praxis, von heuristischem Modell und Fallstudien, ist die Auswahl der Beispiele nicht repräsentativ und deckt nicht die ganze Vielfalt und Vielschichtigkeit der Wissensgesellschaft in ländlich- peripheren Räumen ab. Erste Konturen, wie die Wissensgesellschaft in diesen Räumen zum Ausdruck kommt, welche strategischen Herausforderungen dies mit sich bringt und welchen Anteil die räumliche Planung an den anstehenden strategischen Ansätzen haben kann, zeigen sich dennoch. Der Fachkräftemangel scheint eine zentrale Ausprägung und Herausforderung der Wissensgesellschaft in der ländlichen Peripherie zu sein. Die scharfe, theoretisch begründete Trennung der Dimensionen ist in der Praxis nicht in dieser Form aufrechtzuerhalten: So sind die für die ökonomische Dimension charakteristischen Innovationen nicht ohne soziale Lernprozesse und brückenschlagende Institutionensysteme, die hier der technischen Dimension zugerechnet werden, denkbar. Letztere wiederum funktionieren nur dann tatsächlich, wenn Menschen und Wissen mobilisiert werden und damit Wissensnetzwerke entstehen. Die peripher gelegenen ländlichen Räume sind genauso wie die Metropolräume Teil der Wissensgesellschaft. Damit sind beide Raumtypen gleichermaßen Wettbewerbs- und Selektionsprozessen ausgesetzt. Aus dieser Konstellation ergeben sich für ländlich-periphere Regionen Kernherausforderungen, die sich in zwei sich ergänzenden strategischen Ansätzen manifestieren: eine mitnehmende Basisstrategie und eine flankierende Profilierungsstrategie. Der Beitrag der räumlichen Planung zur Steuerung der wissensgesellschaftlich relevanten Veränderungsprozesse beschränkt sich weitgehend auf folgende Funktionen: Sensibilisierung für räumliche Zusammenhänge, Organisation räumlichen Wandels und Umsetzungsbegleitung sowie damit verbunden Interessenausgleich der vielen unterschiedlichen Akteure einer Region.The heuristics of a three-dimensional knowledge society has been addressed and further developed in this volume. The social, economic and technical dimensions are differentiated and structured in accordance to characteristic manifestations such as individual competences, collective learning processes, knowledge as an economic factor, centrality, mobility, or integration in global institutional systems. These structuring elements provide the basis for the choice of in-depth studies in the rural, peripherally located area of northeast Germany with regard to regional growth cores in Brandenburg, health infrastructure, mobility offerings, access to communication technologies, and educational networks and educational landscapes. Regarding the comparison of theory and practice, of the heuristic model and the case studies, the choice of examples is not representative and does not cover the entire diversity and complexity of the knowledge society in rural peripheral areas. However, the case studies do provide an initial picture of how the knowledge society finds expression in these areas, the strategic challenges it brings with it, and the role that spatial planning can play in necessary strategic approaches. The shortage of skilled workers seems to be a central feature of and a challenge for the knowledge society in the rural periphery. The sharp, theoretically founded differentiation made between the dimensions cannot be sustained in this form in practice. Thus the innovations characteristic for the economic dimension are not feasible without social learning processes and bridging institutional systems, which are here regarded as part of the technical dimension. Furthermore, these processes and systems will only actually function when people and knowledge are mobilised and knowledge networks develop. The peripherally located rural areas are just as much part of the knowledge society as the metropolitan areas. Both types of area are thus similarly subject to processes of competition and selection. This constellation gives rise to key challenges for rural peripheral regions that manifest themselves in two complementary strategic approaches: a participatory basic strategy and a flanking strategy focused on profiling. The contribution of spatial planning to the processes of change related to the knowledge society is thus mainly restricted on raising awareness of spatial interrelations, organising spatial transformation and guiding implementation while ensuring the interests of the many different regional actors

A succinate/SUCNR1-brush cell defense program in the tracheal epithelium

Host-derived succinate accumulates in the airways during bacterial infection. Here, we show that luminal succinate activates murine tracheal brush (tuft) cells through a signaling cascade involving the succinate receptor 1 (SUCNR1), phospholipase Cβ2, and the cation channel transient receptor potential channel subfamily M member 5 (TRPM5). Stimulated brush cells then trigger a long-range Ca2+ wave spreading radially over the tracheal epithelium through a sequential signaling process. First, brush cells release acetylcholine, which excites nearby cells via muscarinic acetylcholine receptors. From there, the Ca2+ wave propagates through gap junction signaling, reaching also distant ciliated and secretory cells. These effector cells translate activation into enhanced ciliary activity and Cl− secretion, which are synergistic in boosting mucociliary clearance, the major innate defense mechanism of the airways. Our data establish tracheal brush cells as a central hub in triggering a global epithelial defense program in response to a danger-associated metabolite

German S3 guideline "actinic keratosis and cutaneous squamous cell carcinoma" – long version of the update 2023

Actinic keratosis (AK) are common lesions in light-skinned individuals that can potentially progress to cutaneous squamous cell carcinoma (cSCC). Both conditions may be associated with significant morbidity and constitute a major disease burden, especially among the elderly. To establish an evidence-based framework for clinical decision making, the guideline “actinic keratosis and cutaneous squamous cell carcinoma” was updated and expanded by the topics cutanepus squamous cell carcinoma in situ (Bowen’s disease) and actinic cheilitis. This guideline was developed at the highest evidence level (S3) and is aimed at dermatologists, general practitioners, ear nose and throat specialists, surgeons, oncologists, radiologists and radiation oncologists in hospitals and office-based settings, as well as other medical specialties, policy makers and insurance funds involved in the diagnosis and treatment of patients with AK and cSCC

A worldwide survey on incidence, management and prognosis of oesophageal fistula formation following atrial fibrillation catheter ablation: The POTTER-AF study.

AIMS Oesophageal fistula represents a rare but dreadful complication of atrial fibrillation catheter ablation. Data on its incidence, management and outcome are sparse. METHODS AND RESULTS This international multicenter registry investigates the characteristics of oesophageal fistulae after treatment of atrial fibrillation by catheter ablation. A total of 553,729 catheter ablation procedures (radiofrequency: 62.9%, cryoballoon: 36.2%, other modalities: 0.9%) were performed at 214 centers in 35 countries. In 78 centers 138 patients (0.025%, radiofrequency: 0.038%, cryoballoon: 0.0015% (p<0.0001)) were diagnosed with an oesophageal fistula. Periprocedural data were available for 118 patients (85.5%). Following catheter ablation, the median time to symptoms and the median time to diagnosis were 18 (7.75, 25; range: 0-60) days and 21 (15, 29.5; range: 2-63) days, respectively. The median time from symptom onset to oesophageal fistula diagnosis was 3 (1, 9; range: 0-42) days. The most common initial symptom was fever (59.3%). The diagnosis was established by chest computed tomography in 80.2% of patients. Oesophageal surgery was performed in 47.4% and direct endoscopic treatment in 19.8%, and conservative treatment in 32.8% of patients. The overall mortality was 65.8%. Mortality following surgical (51.9%) or endoscopic treatment (56.5%) was significantly lower as compared to conservative management (89.5%) (odds ratio 7.463 (2.414, 23.072) p<0.001). CONCLUSIONS Oesophageal fistula after catheter ablation of atrial fibrillation is rare and occurs mostly with the use of radiofrequency energy rather than cryoenergy. Mortality without surgical or endoscopic intervention is exceedingly high

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events