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PurposeLeydig-cell tumours (LCT) of the testis are poorly understood clinically. The aim of this report is to analyse the clinical characteristics of LCT in a large patient sample and to compare these findings with corresponding data of germ-cell tumours (GCT).MethodsIn a sample of 208 patients treated during 1995–2017 in 33 institutions, the following characteristics were registered: age, presenting symptoms, primary tumour size, testis-sparing surgery (TSS) or orchiectomy, malignancy, laterality, medical history, and outcome. Data analysis included descriptive statistical methods and logistic regression analysis.ResultsThe ratio LCT:GCT is 1:23 (4.4%). The findings are as follows: median age 41 years, undescended testis 8%, bilateral LCTs 3%, malignant LCT 2.5%, contralateral GCT 2.5%, incidental detection 28%, scrotal symptoms 43%, infertility 18%, elevated estradiol levels 29%. TSS was performed in 56% with no local relapse. Of the patients with malignant LCT, one was cured through surgery.ConclusionLCT is rare, with a relative frequency (relative to GCT) of 1:23. Malignancy is found in 2.5%. LCT and GCT share a number of clinical features, e.g. bilaterality, history of undescended testis, and presenting age. TSS is safe in benign LCT. Surgery is the treatment of choice in malignant LCT.

Background The Borna disease virus (BoDV-1) is an emerging zoonotic virus causing severe and mostly fatal encephalitis in humans. Methods and Results A local cluster of fatal BoDV-1 encephalitis cases was detected in the same village three years apart affecting two children. While the first case was diagnosed late in the course of disease, a very early diagnosis and treatment attempt facilitated by heightened awareness was achieved in the second case. Therapy started as early as day 12 of disease. Antiviral therapy encompassed favipiravir and ribavirin, and, after bioinformatic modelling, also remdesivir. As the disease is immunopathogenetically mediated, an intensified anti-inflammatory therapy was administered. Following initial impressive clinical improvement, the course was also fatal, although clearly prolonged. Viral RNA was detected by qPCR in tear fluid and saliva, constituting a possible transmission risk for health care professionals. Highest viral loads were found post mortem in the olfactory nerve and the limbic system, possibly reflecting the portal of entry for BoDV-1. Whole exome sequencing in both patients yielded no hint for underlying immunodeficiency. Full virus genomes belonging to the same cluster were obtained in both cases by next-generation sequencing. Sequences were not identical, indicating viral diversity in natural reservoirs. Specific transmission events or a common source of infection were not found by structured interviews. Patients lived 750m apart from each other and on the fringe of the settlement, a recently shown relevant risk factor. Conclusion Our report highlights the urgent necessity of effective treatment strategies, heightened awareness and early diagnosis. Gaps of knowledge regarding risk factors, transmission events, and tailored prevention methods become apparent. Whether this case cluster reflects endemicity or a geographical hot spot needs further investigation.

Background Numerous species, especially among rodents, are strongly affected by the availability of pulsed resources. The intermittent production of large seed crops in northern hemisphere tree species (e.g., beech Fagus spec. ,oak Quercus spec. , pine trees Pinus spec. ) are prime examples of these resource pulses. Adult edible dormice are highly dependent on high energy seeds to maximize their reproductive output. For juvenile dormice the energy rich food is important to grow and fatten in a very short time period prior to hibernation. While these erratic, often large-scale synchronized mast events provide overabundant seed availability, a total lack of seed production can be observed in so-called mast failure years. We hypothesized that dormice either switch territories between mast and non-mast years, to maximize energy availability or select habitats in which alternative food sources are also available (e.g., fleshy fruits, cones). To analyze the habitat preferences of edible dormice we performed environmental niche factor analyses (ENFA) for 9 years of capture-recapture data. Results As expected, the animals mainly used areas with high canopy closure and vertical stratification, probably to avoid predation. Surprisingly, we found that dormice avoided areas with high beech tree density, but in contrast preferred areas with a relatively high proportion of coniferous trees. Conifer cones and leaves can be an alternative food source for edible dormice and are less variable in availability. Conclusion Therefore, we conclude that edible dormice try to avoid areas with large fluctuations in food availability to be able to survive years without mast in their territory.

Sarah von Spiczak, Holger Lerche and colleagues identify mutations in GRIN2A that cause idiopathic focal epilepsy with rolandic spikes. Idiopathic focal epilepsy (IFE) with rolandic spikes is the most common childhood epilepsy, comprising a phenotypic spectrum from rolandic epilepsy (also benign epilepsy with centrotemporal spikes, BECTS) to atypical benign partial epilepsy (ABPE), Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike and waves during slow-wave sleep (CSWS) 1 , 2 . The genetic basis is largely unknown. We detected new heterozygous mutations in GRIN2A in 27 of 359 affected individuals from 2 independent cohorts with IFE (7.5%; P = 4.83 × 10 −18 , Fisher's exact test). Mutations occurred significantly more frequently in the more severe phenotypes, with mutation detection rates ranging from 12/245 (4.9%) in individuals with BECTS to 9/51 (17.6%) in individuals with CSWS ( P = 0.009, Cochran-Armitage test for trend). In addition, exon-disrupting microdeletions were found in 3 of 286 individuals (1.0%; P = 0.004, Fisher's exact test). These results establish alterations of the gene encoding the NMDA receptor NR2A subunit as a major genetic risk factor for IFE.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are important regulators of inflammation. The exact impact of ROS/RNS on cutaneous delayed-type hypersensitivity reaction (DTHR) is controversial. The aim of our study was to identify the dominant sources of ROS/RNS during acute and chronic trinitrochlorobenzene (TNCB)-induced cutaneous DTHR in mice with differently impaired ROS/RNS production. TNCB-sensitized wild-type, NADPH oxidase 2 (NOX2)- deficient (gp91 ), myeloperoxidase-deficient (MPO ), and inducible nitric oxide synthase-deficient (iNOS ) mice were challenged with TNCB on the right ear once to elicit acute DTHR and repetitively up to five times to induce chronic DTHR. We measured ear swelling responses and noninvasively assessed ROS/RNS production by employing the chemiluminescence optical imaging (OI) probe L-012. Additionally, we conducted extensive analyses of inflamed ears focusing on ROS/RNS production and the biochemical and morphological consequences. The L-012 OI of acute and chronic DTHR revealed completely abrogated ROS/RNS production in the ears of gp91 mice, up to 90 % decreased ROS/RNS production in the ears of MPO mice and unaffected ROS/RNS production in the ears of iNOS mice. The DHR flow cytometry analysis of leukocytes derived from the ears with acute DTHR confirmed our L-012 OI results. Nevertheless, we observed no significant differences in the ear swelling responses among all the experimental groups. The histopathological analysis of the ears of gp91 mice with acute DTHRs revealed slightly enhanced inflammation. In contrast, we observed a moderately reduced inflammatory immune response in the ears of gp91 mice with chronic DTHR, while the inflamed ears of MPO mice exhibited the strongest inflammation. Analyses of lipid peroxidation, 8-hydroxy-2'deoxyguanosine levels, redox related metabolites and genomic expression of antioxidant proteins revealed similar oxidative stress in all experimental groups. Furthermore, inflamed ears of wild-type and gp91 mice displayed neutrophil extracellular trap (NET) formation exclusively in acute but not chronic DTHR. MPO and NOX2 are the dominant sources of ROS/RNS in acute and chronic DTHR. Nevertheless, depletion of one primary source of ROS/RNS exhibited only marginal but conflicting impact on acute and chronic cutaneous DTHR. Thus, ROS/RNS are not a single entity, and each species has different properties at certain stages of the disease, resulting in different outcomes.

Background The aim was to compare the return-to-sports-time (RTST) following stress fractures on the basis of site and severity of injury. This retrospective study was set up at a single institution. Diagnosis was confirmed by an interdisciplinary adjudication panel and images were rated in a blinded-read setting. Methods 52 athletes (female, n = 30; male, n = 22; mean age, 22.8 years) with stress fracture (SFX) who had undergone at least one examination, either MRI or bone scintigraphy, were included. Magnetic resonance images (MRI) and/or bone scintigraphy (BS) of SFX were classified as either low- or high-grade SFX, according to existing grading systems. For MRI, high-grade SFX was defined as visibility of a fracture line or bone marrow edema in T1-, T2-weighted and short tau inversion recovery (STIR) sequences, with low-grade SFX showing no fracture line and bone marrow edema only in STIR and/or T2-weighted sequences. In BS images, a mild and poorly defined focal tracer uptake represented a low-grade lesion, whereas an intense and sharply marginated uptake marked a high-grade SFX. In addition, all injuries were categorized by location as high- or low-risk stress fractures. RTST was obtained from the clinical records. All patients were treated according to a non-weight-bearing treatment plan and comprehensive follow-up data was complete until full recovery. Two-sided Wilcoxon’s rank sum test was used for group comparisons. Results High-risk SFX had a mean RTST of 132 days (d) [IQR 64d – 132d] compared to 119d [IQR 50d – 110d] for low-risk sites (p = 0.19). RTST was significantly longer (p = 0.01) in high-grade lesions [mean, 143d; IQR 66d – 134d] than in low-grade [mean, 95d; IQR 42d – 94d]. Analysis of high-risk SFX showed no difference in RTST (p = 0.45) between high- and low-grade [mean, 131d; IQR 72d – 123d vs. mean, 135d; IQR 63d – 132d]. In contrast, the difference was significant for low-risk SFX (p = 0.005) [low-grade; mean, 61d; IQR 35d – 78d vs. high-grade; mean, 153d; IQR 64d – 164d]. Conclusion For SFX at low-risk sites, the significant difference in RTST between low- and high-grade lesions allows more accurate estimation of RTST by this approach. Both location of the injury and severity determined by imaging should therefore be considered for prediction of RTST.

Generalized arterial calcification of infancy (GACI), is characterized by calcification of the internal elastic lamina of large and medium‐sized arteries and stenosis due to myointimal proliferation. Although survival to adulthood has been reported, most patients die within the first six months of life. Recently, we found mutations of ENPP1 coding for ecto‐nucleotide pyrophosphatase/phosphodiesterase 1 to be associated with GACI in 8 of 11 families. In this study, we analyzed ENPP1 in affected individuals of another 12 unrelated families. We identified 11 novel homozygous or compound heterozygous mutations in 10 of the 12 new families. The mutations (1 nonsense, 7 missense, 1 single amino acid deletion, and 2 frame shift mutations) were scattered over the whole coding region with a slightly more condensed distribution within the catalytic and nuclease‐like domain as compared to the first survey. In this study, three mutations were found repeatedly in apparently unrelated patients, 7 x c.913C>A (p.Pro305Thr) and c.2680C>T (p.Arg888Trp) as well as c.2320C>T (p.Arg774Cys) each twice. However, haplotype analysis suggested a founder effect of British extraction for mutation c.913C>A (p.Pro305Thr). The fact that the two other mutations c.2680C>T (p.Arg888Trp) and c.2320C>T (p.Arg774Cys) occurred twice within a single allele also suggests a single founder. This study confirms the role of ENPP1 mutations as the main cause of GACI and adds considerably to the mutational spectrum of ENPP1. © 2004 Wiley‐Liss, Inc.

Edible dormice (Glis glis) are exposed temporally and spatially to a tremendous variation in food resources. This variation strongly influences reproduction; in edible dormice reproduction is tightly linked to the availability of energy-rich seeds. Although most dormice reproduce in full mast years of beech or oak, entire populations skip reproduction in years without seed production; however, nearly 50% of all years are intermediate mast years, during which only part of the dormouse population reproduces. We investigated how the beech mast pattern, local habitat characteristics, and individual traits (body mass and age class) influence whether individual female edible dormice invest in reproduction in intermediate mast years. Our field study, conducted during 2006–2009 in the Vienna Woods, revealed that in intermediate mast years the probability of females reproducing increased with the age of trees but not with the proportion of beech trees within their home ranges. Mean litter size was larger in years with higher seed availability and also increased with the mean age of trees within the home range of the dormice. More adult than yearling females reproduced, but this effect was modulated by yearly and local variation in food availability. Whether a female edible dormouse reproduces in an intermediate mast year depends mainly on the local food availability and age of the individual.

Kurt Schwitters (1887−1948) gehört zu den Protagonisten der Avantgarden nach dem Ersten Weltkrieg. Obwohl sein bildkünstlerisches Werk mittlerweile kanonisiert ist und seine literarischen Texte seit über dreißig Jahren in einer Leseausgabe ediert vorliegen, stagniert die literaturwissenschaftliche Forschung zu Schwitters seit Längerem. Die Beiträge des Bandes nehmen die notwendige Diskussion um den Status und die Wirkung der Avantgarden und der Moderne zu Schwitters‘ Zeit auf. Sie verbinden diese Diskussion mit den bisher weitgehend unbekannten Materialien, die durch die im Jahr 2010 gestartete Neuedition von Schwitters‘ Texten der wissenschaftlichen Öffentlichkeit erstmalig zugänglich gemacht werden. Hinzu kommt die Intensivierung der Schwitters- und Avantgarde-Forschung unter literaturwissenschaftlichen Gesichtspunkten, die aktuelle kultur-, kunst- und medienwissenschaftliche Perspektiven berücksichtigt. Die Beiträge gehen auf eine Tagung im Sprengel Museum Hannover 2011 zurück.