Metastatic cornual melanoma in a Valesian copperneck goat

A 10-year-old, neutered, male Valesian copperneck goat was presented to the Clinic for Ruminants, Vetsuisse Faculty, University of Bern for a chronic wound at the base of the right horn first noticed 3 weeks before presentation. Clinical examination revealed a firm mass with ulcerations and malodorous discharge at the base of the right horn, and a duller sound on percussion of the right frontal sinus. Radiography revealed a soft tissue opacity filling the right cornual diverticulum of the frontal sinus. Upon wound debridement, tissue of grey to black discolorationwas noticed and sent in for histopathological examination, which confirmed the presence of a melanoma. Subsequent ultrasonography of the liver and radiography of the thorax revealed no sign of metastatic disease. Given the poor prognosis, the goat was euthanased, and postmortem examination revealed the presence of multiple metastatic lesions in the regional lymph nodes

Revision der Gattung Dichodontium (Musci, Dicranaceae)

The eight species so far comprised in the genus Dichodondium are reduced to three. Dichodontium verrucosum Card. is regarded as conspecific with D. pellucidum ( Hedw.) Schimp. Dichodontium opacifolium Dix. is regarded as conspecific with D. brasiliense Broth. The placement of this species in the genus Dichodontium is doubtful. Dichodontium nelsonii Kindb. proved to be Bartramia pomiformis Hedw. Dichodontium debile Broth. and D. integrum Sak. remain dubious species because of a lack of type material and references. Dichodontium pellucidum (Hedw.) Schimp. is lectotypified.Die 8 bisher in der Gattung Dichodontium eingeschlossenen Arten werden auf 3 reduziert. Dichodontium verrucosum Card. ist synonym mit D. pellucidum (Hedw.) Schimp. Dichodontium opacifolium Dix. ist synonym mit D. brasiliense Broth., wobei die Zugehörigkeit dieser Art zur Gattung Dichodontium nicht vollkommen geklärt ist. Dichodontium nelsonii Kindb. stellte sich als Bartramia pomiformis Hedw. heraus. Dichodontium debile Broth. und D. integrum Sak. bleiben aufgrund von fehlendem Typusmaterial unrevidiert. Dichodontium pellucidum (Hedw.) Schimp. wird lektotypifiziert

Detection of Spirocerca lupi and an unknown Trichinella-like nematode in raccoon (Procyon lotor).

The raccoon Procyon lotor (Carnivora: Procyonidae) is an invasive species of growing importance for the introduction of alien pathogens or as additional hosts for autochthonous pathogens in Europe, including zoonotic parasites. As the population is steadily increasing and outcompeting the red fox (Vulpes vulpes) in Germany, the consumption of raccoon meat raises concerns about pathogens they may transmit. Therefore the presence of Trichinella larvae was here investigated in muscle samples (n = 904) of raccoons from northern Germany. No Trichinella larvae were found, thus confirming the general low occurrence of this parasite in Germany. However, Spirocerca lupi (n = 12) and an unidentified Trichinella-like nematode (n = 1) were accidently detected in the examined samples. The first is not a zoonotic parasite but has a high veterinary relevance as it can cause severe diseases in dogs. It is the first documented autochthonous infection of this nematode in Germany. The larvae of an unidentified Trichinella-like nematode were found in high abundance in all examined muscles of one raccoon, though they could not be identified to species level. Histological investigation revealed intramuscular cystic structures. This is the largest study investigating muscular parasites of raccoons in Europe so far, which suggests that this invasive animal species is infected by S. lupi and by a yet unknown Trichinella -like parasite

Assessment of treatment response in cardiac sarcoidosis based on myocardial 18^{18}F-FDG uptake

OBJECTIVE Immunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by $^{18}$F-fluorodeoxyglucose positron emission tomography/computed tomography ($^{18}$F-FDG PET/CT) of the heart. METHODS We conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020. RESULTS We identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial $^{18}$F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed. CONCLUSION TNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF

Instability results for the wave equation in the interior of Kerr black holes

We prove that a large class of smooth solutions $\psi$ to the linear wave equation $\Box_g\psi=0$ on subextremal rotating Kerr spacetimes which are regular and decaying along the event horizon become singular at the Cauchy horizon. More precisely, we show that assuming appropriate upper and lower bounds on the energy along the event horizon, the solution has infinite (non-degenerate) energy on any spacelike hypersurfaces intersecting the Cauchy horizon transversally. Extrapolating from known results in the Reissner--Nordstr\"om case, the assumed upper and lower bounds required for our theorem are conjectured to hold for solutions arising from generic smooth and compactly supported initial data on a Cauchy hypersurface. This result is motivated by the strong cosmic censorship conjecture in general relativity

Searching for a Stochastic Background of Gravitational Waves with LIGO

The Laser Interferometer Gravitational-wave Observatory (LIGO) has performed the fourth science run, S4, with significantly improved interferometer sensitivities with respect to previous runs. Using data acquired during this science run, we place a limit on the amplitude of a stochastic background of gravitational waves. For a frequency independent spectrum, the new limit is $\Omega_{\rm GW} < 6.5 \times 10^{-5}$. This is currently the most sensitive result in the frequency range 51-150 Hz, with a factor of 13 improvement over the previous LIGO result. We discuss complementarity of the new result with other constraints on a stochastic background of gravitational waves, and we investigate implications of the new result for different models of this background.Comment: 37 pages, 16 figure

Assessment of treatment response in cardiac sarcoidosis based on myocardial 18F-FDG uptake

ObjectiveImmunosuppressive therapy for cardiac sarcoidosis (CS) still largely consists of corticosteroid monotherapy. However, high relapse rates after tapering and insufficient efficacy are significant problems. The objective of this study was to investigate the efficacy and safety of non-biological and biological disease-modifying anti-rheumatic drugs (nb/bDMARDs) considering control of myocardial inflammation assessed by 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) of the heart.MethodsWe conducted a retrospective analysis of treatment response to nb/bDMARDs of all CS patients seen in the sarcoidosis center of the University Hospital Zurich between January 2016 and December 2020.ResultsWe identified 50 patients with CS. Forty-five patients with at least one follow-up PET/CT scan were followed up for a mean of 20.5 ± 12.8 months. Most of the patients were treated with prednisone and concomitant nb/bDMARDs. At the first follow-up PET/CT scan after approximately 6.7 ± 3 months, only adalimumab showed a significant reduction in cardiac metabolic activity. Furthermore, comparing all serial follow-up PET/CT scans (143), tumor necrosis factor inhibitor (TNFi)-based therapies showed statistically significant better suppression of myocardial 18F-FDG uptake compared to other treatment regimens. On the last follow-up, most adalimumab-treated patients were inactive (n = 15, 48%) or remitting (n = 11, 35%), and only five patients (16%) were progressive. TNFi was safe even in patients with severely reduced left ventricular ejection fraction (LVEF), and a significant improvement in LVEF under TNFi treatment was observed.ConclusionTNFi shows better control of myocardial inflammation compared to nbDMARDs and corticosteroid monotherapies in patients with CS. TNFi was efficient and safe even in patients with severely reduced LVEF

In Silico Ascription of Gene Expression Differences to Tumor and Stromal Cells in a Model to Study Impact on Breast Cancer Outcome

Breast tumors consist of several different tissue components. Despite the heterogeneity, most gene expression analyses have traditionally been performed without prior microdissection of the tissue sample. Thus, the gene expression profiles obtained reflect the mRNA contribution from the various tissue components. We utilized histopathological estimations of area fractions of tumor and stromal tissue components in 198 fresh-frozen breast tumor tissue samples for a cell type-associated gene expression analysis associated with distant metastasis. Sets of differentially expressed gene-probes were identified in tumors from patients who developed distant metastasis compared with those who did not, by weighing the contribution from each tumor with the relative content of stromal and tumor epithelial cells in their individual tumor specimen. The analyses were performed under various assumptions of mRNA transcription level from tumor epithelial cells compared with stromal cells. A set of 30 differentially expressed gene-probes was ascribed solely to carcinoma cells. Furthermore, two sets of 38 and five differentially expressed gene-probes were mostly associated to tumor epithelial and stromal cells, respectively. Finally, a set of 26 differentially expressed gene-probes was identified independently of cell type focus. The differentially expressed genes were validated in independent gene expression data from a set of laser capture microdissected invasive ductal carcinomas. We present a method for identifying and ascribing differentially expressed genes to tumor epithelial and/or stromal cells, by utilizing pathologic information and weighted t-statistics. Although a transcriptional contribution from the stromal cell fraction is detectable in microarray experiments performed on bulk tumor, the gene expression differences between the distant metastasis and no distant metastasis group were mostly ascribed to the tumor epithelial cells of the primary breast tumors. However, the gene PIP5K2A was found significantly elevated in stroma cells in distant metastasis group, compared to stroma in no distant metastasis group. These findings were confirmed in gene expression data from the representative compartments from microdissected breast tissue. The method described was also found to be robust to different histopathological procedures

Mitoxantrone Induces Natural Killer Cell Maturation in Patients with Secondary Progressive Multiple Sclerosis

Mitoxantrone is one of the few drugs approved for the treatment of progressive multiple sclerosis (MS). However, the prolonged use of this potent immunosuppressive agent is limited by the appearance of severe side effects. Apart from its general cytotoxic effect, the mode of action of mitoxantrone on the immune system is poorly understood. Thus, to develop safe therapeutic approaches for patients with progressive MS, it is essential to elucidate how mitoxantrone exerts it benefits. Accordingly, we initiated a prospective single-arm open-label study with 19 secondary progressive MS patients. We investigated long-term effects of mitoxantrone on patient peripheral immune subsets using flow cytometry. While we corroborate that mitoxantrone persistently suppresses B cells in vivo, we show for the first time that treatment led to an enrichment of neutrophils and immunomodulatory CD8low T cells. Moreover, sustained mitoxantrone applications promoted not only persistent NK cell enrichment but also NK cell maturation. Importantly, this mitoxantrone-induced NK cell maturation was seen only in patients that showed a clinical response to treatment. Our data emphasize the complex immunomodulatory role of mitoxantrone, which may account for its benefit in MS. In particular, these results highlight the contribution of NK cells to mitoxantrone efficacy in progressive MS