A retrospective multi‐center study of treatment, outcome, and prognostic factors in 34 dogs with disseminated aspergillosis in Australia

Background Disseminated aspergillosis (DA) in dogs has a guarded prognosis and there is a lack of a gold standard treatment protocol. Objective To retrospectively assess survival times and factors influencing survival times. Animals Dogs diagnosed with DA from January 2007 to June 2017. Methods Disseminated aspergillosis case data were retrieved from 13 Australian veterinary referral centers, with a diagnosis confirmed with culture or PCR. Factors influencing survival time after diagnosis were quantified using a Cox proportional hazards regression model. Results Thirty-four dogs met the study inclusion criteria. Twenty-two dogs were treated with antifungal treatment and 12 dogs received no antifungal treatment. Accounting for censoring of dogs that were either still alive on the date of data collection or were loss to follow-up, dogs treated with itraconazole alone (n = 8) had a median survival time (MST) of 63 (95% CI: 20−272) days compared to 830 (95% CI: 267-1259) days for the n = 14 dogs that received multimodal antifungal therapy

Multi-Level Interactions between the Nuclear Receptor TRα1 and the WNT Effectors β-Catenin/Tcf4 in the Intestinal Epithelium

Intestinal homeostasis results from complex cross-regulation of signaling pathways; their alteration induces intestinal tumorigenesis. Previously, we found that the thyroid hormone nuclear receptor TRα1 activates and synergizes with the WNT pathway, inducing crypt cell proliferation and promoting tumorigenesis. Here, we investigated the mechanisms and implications of the cross-regulation between these two pathways in gut tumorigenesis in vivo and in vitro. We analyzed TRα1 and WNT target gene expression in healthy mucosae and tumors from mice overexpressing TRα1 in the intestinal epithelium in a WNT-activated genetic background (vil-TRα1/Apc mice). Interestingly, increased levels of β-catenin/Tcf4 complex in tumors from vil-TRα1/Apc mice blocked TRα1 transcriptional activity. This observation was confirmed in Caco2 cells, in which TRα1 functionality on a luciferase reporter-assay was reduced by the overexpression of β-catenin/Tcf4. Moreover, TRα1 physically interacted with β-catenin/Tcf4 in the nuclei of these cells. Using molecular approaches, we demonstrated that the binding of TRα1 to its DNA target sequences within the tumors was impaired, while it was newly recruited to WNT target genes. In conclusion, our observations strongly suggest that increased β-catenin/Tcf4 levels i) correlated with reduced TRα1 transcriptional activity on its target genes and, ii) were likely responsible for the shift of TRα1 binding on WNT targets. Together, these data suggest a novel mechanism for the tumor-promoting activity of the TRα1 nuclear receptor

A Histologic Scoring System for Prognosis of Patients With Alcoholic Hepatitis

There is no histologic classification system to determine prognoses of patients with alcoholic hepatitis (AH). We identified histologic features associated with disease severity and created a histologic scoring system to predict short-term (90 day) mortality

Sarcocystis infection in red deer (Cervus elaphus) with eosinophilic myositis/fasciitis in Switzerland and involvement of red foxes (Vulpes vulpes) and hunting dogs in the transmission

Red deer (Cervus elaphus) carcasses showing grey-greenish discolouration have been increasingly observed in the canton of Grisons, Switzerland. We investigated whether Sarcocystis infections were associated with this pathology, and whether wild and domestic canids were involved in their transmission. Meat from affected red deer (n = 26), faeces and intestines from red foxes (Vulpes vulpes) (n = 126), and faeces from hunting dogs (n = 12) from the region, were analysed. Eosinophilic myositis and/or fasciitis were diagnosed in 69% of the deer, and sarcocysts were observed in 89% of the animals. Molecular typing targeting a ~700bp variable region of the 18S rRNA gene revealed Sarcocystis hjorti in 73%, S. venatoria/S. iberica in 54%, S. linearis/S. taeniata in 12%, S. pilosa in 8% and S. ovalis in 4% of the deer samples. No inflammatory changes were observed in red deer carcasses with normal appearance (n = 8); however, sarcocysts were observed in one sample, and S. hjorti, S. venatoria/S. iberica or S. silva DNA was detected in five samples. Sarcocystis oocysts/sporocysts were observed in 11/106 faecal and 6/20 intestinal fox samples, and in 2/12 canine samples. Sarcocystis tenella (n = 8), S. hjorti (n = 2), S. gracilis (n = 2), and S. miescheriana (n = 1) were identified in foxes, and S. gracilis (n = 2), S. capreolicanis (n = 1) and S. linearis/S. taeniata (n = 1) in dogs. This study provides first molecular evidence of S. pilosa and S. silva infection in red deer and S. linearis/S. taeniata in dogs and represents the first record of S. ovalis transmitted by corvids in Central Europe. Although Sarcocystis species infecting red deer are not regarded as zoonotic, the affected carcasses can be declared as unfit for human consumption due to the extensive pathological changes