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Prurigo nodularis (PN) or chronic prurigo of nodular type (CNPG) is a subtype of chronic prurigo with severe pruritus and neuroimmune underlying pathophysiology occurring in a plethora of dermatological, systemic, neurologic, and psychiatric conditions.We review the increasing repertoire of biologics in the treatment of CNPG focusing on those targeting interleukins 4, 13, 31, oncostatin M and IgE. Presented information is based on a database research on current clinical trials (clinicaltrials.gov, European Clinical Trials Database (EudraCT), US clinical trial registry ICH-GCP) and a PubMed search for latest publications conducted with the combinations of the terms 'chronic prurigo,' 'prurigo nodularis,' 'pathophysiology,' 'treatment,' 'therapy', and 'biologics.'CNPG gets more and more attention as new therapeutic targets have been revealed in recent years, thus allowing the use of targeted approaches. The off-label advent of dupilumab offered advanced insight into the pathogenesis of CNPG and showed an impressive relief of pruritus in the vast majority of patients. New therapies including biologics (e.g. nemolizumab, tralokinumab, lebrikizumab), small molecules (e.g. neurokinin-1 receptor antagonists, janus kinase inhibitors) as well as mu-opioid receptor antagonists and nalbuphine, a μ-antagonist/κ-agonist, are in the pipeline and offer new hope for an improved future patient care.

Chronic pruritus (duration ≥ 6 weeks) affects about 91% of patients suffering from atopic dermatitis (AD). Pruritus is often accompanied by sensations such as pain, burning, stinging, and heat, resulting in a high burden of affected patients; sleep and quality of life may be severely impaired. An important pillar of AD treatment is also to achieve sufficient control of pruritus. In addition to intensively used emollients, corticosteroids and calcineurin inhibitors have proven effective. In case of eczema affecting a large part of the body surface area (BSA), phototherapy may contribute to the healing of eczema and the relief of atopic pruritus. As to systemic therapies, several approved biologics (dupilumab, tralokinumab) and small molecules (baricitinib, upadacitinib, abrocitinib) lead to a rapid improvement of pruritus by interfering with the signal transduction of proinflammatory cytokines. While Janus kinase inhibitors initially lead to a faster relief of pruritus than biologics, the antipruritic efficacy of biologics and Janus kinase inhibitors seems to be similar in long-term use.Chronischer Pruritus (Dauer ≥ 6 Wochen) betrifft ca. 91 % der Patienten mit atopischer Dermatitis (AD). Neben reinem Jucken werden häufig Begleitsensationen wie Schmerzen, Brennen, Stechen und Hitzegefühl berichtet. Der Leidensdruck betroffener Patienten ist dadurch hoch; Schlaf und Lebensqualität können stark beeinträchtigt sein. Im Fokus der Behandlung der AD steht daher auch die suffiziente Kontrolle des Pruritus. Neben einer intensiven rückfettenden Basispflege können topisch Kortikosteroide und Calcineurininhibitoren angewendet werden. Bei ausgeprägtem Hautbefund kann Phototherapie zur Abheilung von Ekzemen und Linderung des atopischen Pruritus beitragen. Im Hinblick auf Systemtherapien stehen mehrere zugelassene Biologika (Dupilumab, Tralokinumab) und Januskinase-Inhibitoren (Baricitinib, Upadacitinib, Abrocitinib) zur Verfügung, die über die Interferenz mit der Signaltransduktion proinflammatorischer Zytokine zu einer raschen Pruritusreduktion führen. Während Januskinase-Inhibitoren zu einer initial schnelleren Prurituslinderung führen, scheinen sich Biologika und Januskinase-Inhibitoren mit zunehmender Therapiedauer hinsichtlich ihrer antipruritischen Wirksamkeit anzugleichen.

The oxytocin receptor gene (OXTR) is of interest when investigating the effects of early adversity on DNA methylation. However, there is heterogeneity regarding the selection of the most promising CpG sites to target for analyses. The goal of this study was to determine functionally relevant clusters of CpG sites within the OXTR CpG island in 113 mother-infant dyads, with 58 of the mothers having experienced childhood maltreatment (CM). OXTR DNA methylation and gene expression was analyzed in peripheral/umbilical blood mononuclear cells. Different complexity reduction approaches were used to reduce the 188 CpG sites into clusters of co-methylated sites. Furthermore, associations between OXTR DNA methylation (cluster- and site-specific level) and OXTR gene expression and CM were investigated. Results showed that, first, CpG sections differed strongly regarding their statistical utility for research of individual differences in DNA methylation. Second, cluster analyses and Partial Least Squares (PLS) suggested two clusters consisting of intron1/exon2 and the protein-coding region of exon 3, respectively, as most strongly associated with outcome measures. Third, cross-validated PLS regression explained 7% of variance in CM, with low cross-validated variance explained for the prediction of gene expression. Fourth, very high mother-child correspondence was observed in correlation patterns within the identified clusters, but only modest correspondence outside these clusters. This study characterized the DNA methylation landscape of the OXTR CpG island by highlighting clusters of CpG sites that show desirable statistical properties and predictive value. We provide a Companion Web Application to guide future studies in their choice of CpG sites.

Antenatal synthetic glucocorticoid (sGC) treatment is a potent modifier of the hypothalamic-pituitary-adrenal (HPA) axis. In this context, epigenetic modifications are discussed as potential regulators explaining how prenatal exposure to GCs might translate into persistent changes of HPA axis “functioning”. The purpose of this study was to investigate whether DNA methylation and gene expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) may mediate the persistent effects of sGC on cortisol stress reactivity that have been previously observed. In addition, hair cortisol concentrations (hairC) were investigated as a valid biomarker of long-term HPA axis activity. This cross-sectional study comprised 108 term-born children and adolescents, including individuals with antenatal GC treatment and controls. From whole blood, DNA methylation was analyzed by targeted deep bisulfite sequencing. Relative mRNA expression was determined by RT-qPCR experiments and qBase analysis. Acute stress reactivity was assessed by the Trier Social Stress Test (TSST) measuring salivary cortisol by ELISA and hairC concentrations were determined from hair samples by liquid chromatography coupled with tandem mass spectrometry. First, no differences in DNA methylation and mRNA expression levels of the stress-associated genes between individuals treated with antenatal sGC compared to controls were found. Second, DNA methylation and mRNA expression levels were neither associated with cortisol stress reactivity nor with hairC. These findings do not corroborate the belief that DNA methylation and mRNA expression profiles of stress-associated genes (NR3C1; FKBP5; SLC6A4) play a key mediating role of the persistent effects of sGC on HPA axis functioning.

DNA methylation patterns can be responsive to environmental influences. This observation has sparked interest in the potential for psychological interventions to influence epigenetic processes. Recent studies have observed correlations between DNA methylation changes and therapy outcome. However, most did not control for changes in cell composition. This study had two aims: first, we sought to replicate therapy-associated changes in DNA methylation of commonly assessed candidate genes in isolated monocytes from 60 female patients with post-traumatic stress disorder (PTSD). Our second, exploratory goal was to identify novel genomic regions with substantial pre-to-post intervention DNA methylation changes by performing whole-genome bisulfite sequencing (WGBS) in two patients with PTSD. Equivalence testing and Bayesian analyses provided evidence against physiologically meaningful intervention-associated DNA methylation changes in monocytes of PTSD patients in commonly investigated target genes (NR3C1, FKBP5, SLC6A4, OXTR). Furthermore, WGBS yielded only a limited set of candidate regions with suggestive evidence of differential DNA methylation pre- to post-therapy. These differential DNA methylation patterns did not prove replicable when investigated in the entire cohort. We conclude that there is no evidence for major, recurrent intervention-associated DNA methylation changes in the investigated genes in monocytes of patients with PTSD.

In high mountain environments with harsh weather conditions, soil development and its limitations strongly depend on topography and morphodynamics, both leading to heterogeneous landscape patterns of different geological substrate, vegetation, (micro)relief, and (micro)climate. In addition, as glaciers currently are retreating disproportionately strong, a large area is exposed to initial soil development, enabling to study time related issues of soil formation.These mosaic-like patterns are particularly intensified within the high-alpine and nival zone, due to the dominating influence of cryospheric elements, such as ice (e.g. retreating glaciers), snow (e.g. snowbeds; shallow self-deepening sinks with snow accumulation at altitudes above 2500 m a.s.l.), and frost (e.g. causing solifluction, controlling physical weathering, changing permafrost dynamics, increasing the probability mass movements and sediment transport). The high-alpine environment with its site diversity therefore represents a perfect study area to analyze soil-vegetation-interactions at various microsites within a single catchment.To study the influence of time, the glacier foreland of Zufall- and Fürkeleferner (Martelltal, South Tyrol) was found to be excellent for an interdisciplinary chronosequence study. Large amounts of historical maps, aerial orthophotos, and remote sensing data are available, enabling reconstructed glacier retreat with a high spatial and temporal accuracy. Study sites of different soil age were chosen for the analysis of various soil and vegetation parameters. The influence of temperature and soil water availability were determined by installing temperature and soil matric potential data loggers.Furthermore, to study soil development as a function of geological substrate, microrelief, altitude, slope, and microclimate, an additional transect along an altitudinal gradient (Martelltal, South Tyrol, within the maximum extent of Egesen) was sampled and analyzed regarding central soil properties, vegetation, and microclimate. Directly bordering to those sites, heterogeneous and morphodynamically active microsites were investigated. These special sites were characterized by different morphological features, in particularly: soil sinks of different genesis, hilltops, and scree-dominated sites with initial soil development after primary plant succession.As expected, we found clear trends of soil development with changing altitude and/or time. However, the small-scaled special sites differed distinctly from the reference sites regarding basic soil properties such as soil pH or soil organic matter content, and also remarkably in plant-available NH4-N, microbial activity, and microbial biomass. This was especially true where the water regime was strongly affected by the microrelief.The observed distinct changes in soil properties within small scales of sometimes only several meters help to better understand and predict soil formation and diversity as well as soil-plant-interactions in high alpine environments of the European Alps.

Glacier forelands are perfect for analysing the development of plant communities from zero onward. According to Matthews (1992), the chronosequence can act as a spatial representation of the temporal sequence. Therefore, it is ideal to analyse changes in landscape and land cover in time slices. Development of plant communities does not only depend on the age of the deposits, but also on topography, microclimate, soil development, and geomorphological processes as well as on biotic interactions. In the long term, permanent plots represent an adequate method to follow the colonisation on differently aged terrain throughout time.The main research question of the study is: Do cryospheric changes influence plant community development in time and space? During the first study year we were focused on the following questions: i) How fast does a plant community evolve? ii) How many species do occur on different moraine stages? iii) How do soil parameters correlate with primary succession stages?The study site is located in the southern part of the Central European Alps, Martell Valley (South Tyrol, Italy). We established 12 permanent plot clusters of 2 x 5 m on areas deglaciated between 1985 and 2018, two per retreat area. In each square meter of these clusters, species composition, cover, and number of individuals were sampled. On the ground moraines of the glacier stages 1911 and approximately 1850 we recorded species composition and cover on 10 x 10 m plots (four plots in total). In all plot clusters and plots on the old moraines, soil temperature and soil water potential as well as relevant soil parameters were measured.We found up to two vascular plant species per square meter on areas ice free for one year and up to 16 vascular plant species per square meter on areas ice free since 1985.On the moraines of 1911 were up to 39 vascular plant species per plot with a mean cover of 52.5 %. On the moraines of 1850 we found up to 43 vascular plant species with a mean cover of 40 %.In the next step we will analyse the effects of pioneer, early and late successional species on morphodynamic processes and their response to these processes using functional traits.Matthews, J.A. (1992): The ecology of recently-deglaciated terrain: a geoecological approach to glacier forelands and primary succession. Cambridge University Press, Cambridge.

We compared synchrotron-based C near-edge X-ray absorption fine structure (NEXAFS) and CPMAS 13C nuclear magnetic resonance (NMR) spectroscopy with respect to their precision and accuracy to quantify different organic carbon (OC) species in defined mixtures of soil organic matter source compounds. We also used both methods to quantify different OC species in organic surface horizons of a Histic Leptosol as well as in mineral topsoil and subsoil horizons of two soils with different parent material, stage of pedogenesis, and OC content (Cambisol: 15–30 OC mg g−1, Podzol: 0.9–7 OC mg g−1). CPMAS 13C NMR spectroscopy was more accurate and precise (mean recovery of different C functional groups 96–103%) than C NEXAFS spectroscopy (mean recovery 92–113%). For organic surface and topsoil samples, NMR spectroscopy consistently yielded larger O-alkyl C percentages and smaller alkyl C percentages than C NEXAFS spectroscopy. For the Cambisol subsoil samples both methods performed well and showed similar C speciation results. NEXAFS spectroscopy yielded excellent spectra with a high signal-to-noise ratio also for OC-poor Podzol subsoil samples, whereas this was not the case for CPMAS 13C NMR spectroscopy even after sample treatment with HF. Our results confirm the analytical power of CPMAS 13C NMR spectroscopy for a reliable quantitative OC speciation in soils with >10 mg OC g−1. Moreover, they highlight the potential of synchrotron-based C NEXAFS spectroscopy as fast, non-invasive method to semi-quantify different C functional groups in soils with low C content (0.9–10 mg g−1).

Particularly on sites with shallow, nutrient-poor soils, forest soil organic surface layers (O layers) are important for the storage of plant-available nutrients and water, and thus for forest vitality and productivity. O layers can contain up to 70 mass percent of inorganic compounds (minerals) which may be spatially separated from or closely associated with soil organic matter (SOM). O layer SOM may differ in biochemical properties and resistance against mineralization, depending on the extent of organo-mineral association. Moreover, type and intensity of SOM-mineral mixing in O layers conveys information about biological activity. Here, for the first time we present detailed density fractionation results to distinguish SOM constituents in O layers with different chemical properties and likely also different degrees of organo-mineral association. Additionally, we characterized spatial association patterns of the SOM fractions. We investigated samples of Of (Oe) and Oh (Oa) horizons of temperate forest soils with different parent materials (basalt, gneiss, andesite, Pleistocene gravel, dolomite). The samples were distinguished into six density fractions (ρ 1.6 g cm−3) by sequential treatment with deionized H2O (ρ = 1.0 g cm−3), 1-propanol (ρ = 0.8 g cm−3), and sodium polytungstate (SPT) solution of increasing density (ρ = 1.2, 1.4, 1.6 g cm−3). The procedure is characterized by a mass recovery of 93 ± 5% and an organic carbon (OC) recovery of 90 ± 9%. In each fraction, we analyzed the concentrations of C, N, metal cations (Fe, Al, Ca, Mg), C speciation (13C NMR spectroscopy), as well as abundances of 13C and 15N. For selected fractions, we additionally determined the radiocarbon age and acquired microscopic images. From the Of to the Oh horizons, the contribution of heavy fractions (>1.4 g cm−3) to total soil mass and total SOC increased, indicating augmented organo–mineral association with progressive SOM decomposition state. Compared to bulk soil, heavier fractions >1.4 g cm−3 were characterized by smaller SOC concentrations, whereas concentrations of Al and Fe were increased for fractions >1.4 g cm−3 in the of and >1.6 g cm−3 in the Oh horizon. The SOM in the heavy fractions was enriched in N, carboxyl C, and alkyl C, but depleted in O/N-alkyl C and aryl C. Smaller mean particle sizes and C/N ratios as well as increased alkyl C / O/N-alkyl C ratios and 13C and 15N abundances indicate an advanced SOM decomposition state and enrichment of microbial-derived SOM in heavier fractions. However, according to its 14C signature, in contrast to high-density (ρ > 1.6 g cm−3) SOM in the mineral soil, forest floor SOM with high density is a rapidly cycling SOM pool with a turnover time

We compared synchrotron-based C near-edge X-ray absorption fine structure (NEXAFS) and CPMAS

For the direct steam generation in solar fields, the recirculation concept has been demonstrated in several installations. Water masses in the solar field vary during transient phases, such as passing clouds. The volume of the steam drum can serve as a buffer during such transients by taking in excess water and providing water storage. The saturated steam mass flow to the superheating section or the consumer can be maintained almost constant during short transients; therefore the steam drum plays a key role for constant steam supply. Its buffer effect depends on the right sizing of the steam drum for the prevailing situations. Due to missing experiences, steam drums have been sized under conservative assumptions and are thereby usually oversized. With this paper, experiences on the steam drum of the 5 MWel TSE1 power plant are discussed for optimized future plant design. The results are also of relevance for process heat installations, in which saturated steam is produced by the solar field.