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Lagovirus europaeus GI.2, also known as RHDV2 or RHDVb, is an emerging virus that causes rabbit haemorrhagic disease (RHD) in European rabbits ( Oryctolagus cuniculus ). In contrast to L. europaeus GI.1 (or RHDV/RHDVa) viruses that are only pathogenic for adults, GI.2 causes clinical disease in both adults and kittens. However, detailed descriptions of the pathology of this virus that may provide insight into its pathogenicity and emergence are lacking. Using an Australian GI.2 field strain isolated in 2015, we provide the first detailed description of pathology, viral antigen distribution and tissue load of GI.2 in adult and 5-week old New Zealand white rabbits using histology, immunohistochemistry and RT-qPCR. Liver was the target organ, but in contrast to GI.1 viruses, lesions and inflammatory responses did not differ between adults and kittens. Lymphocytic inflammation, proposed to be protective in kittens infected with GI.1, was notably absent. We also present the first descriptions of bone marrow changes in RHD, including decreased myeloid-to-erythroid ratio. Consistent with other pathogenic lagoviruses, intracellular viral antigen was demonstrated in hepatocytes and cells of the mononuclear phagocytic system. In terminal stages of disease, viral loads were highest in liver, serum and spleen. Despite the small sample size, our data suggest that unlike early European GI.2 strains, the pathogenicity of the Australian GI.2 virus is similar to GI.1 viruses. Additionally, GI.2 was fatal for all ( n  = 5) inoculated kittens in this study. This may significantly alter RHD epidemiology in the field, and may impact biocontrol programs for invasive rabbits in Australia where GI.1 viruses are intentionally released.

Background Prior to 2010, the lagoviruses that cause rabbit hemorrhagic disease (RHD) in European rabbits ( Oryctolagus cuniculus ) and European brown hare syndrome (EBHS) in hares ( Lepus spp . ) were generally genus-specific. However, in 2010, rabbit hemorrhagic disease virus 2 (RHDV2), also known as Lagovirus europaeus GI.2, emerged and had the distinguishing ability to cause disease in both rabbits and certain hare species. The mountain hare ( Lepus timidus ) is native to Sweden and is susceptible to European brown hare syndrome virus (EBHSV), also called Lagovirus europaeus GII.1. While most mountain hare populations are found on the mainland, isolated populations also exist on islands. Here we investigate a mortality event in mountain hares on the small island of Hallands Väderö where other leporid species, including rabbits, are absent. Results Post-mortem and microscopic examination of three mountain hare carcasses collected from early November 2016 to mid-March 2017 revealed acute hepatic necrosis consistent with pathogenic lagovirus infection. Using immunohistochemistry, lagoviral capsid antigen was visualized within lesions, both in hepatocytes and macrophages. Genotyping and immunotyping of the virus independently confirmed infection with L. europaeus GI.2, not GII.1. Phylogenetic analyses of the vp60 gene grouped mountain hare strains together with a rabbit strain from an outbreak of GI.2 in July 2016, collected approximately 50 km away on the mainland. Conclusions This is the first documented infection of GI.2 in mountain hares and further expands the host range of GI.2. Lesions and tissue distribution mimic those of GII.1 in mountain hares. The virus was most likely initially introduced from a concurrent, large-scale GI.2 outbreak in rabbits on the adjacent mainland, providing another example of how readily this virus can spread. The mortality event in mountain hares lasted for at least 4.5 months in the absence of rabbits, which would have required virus circulation among mountain hares, environmental persistence and/or multiple introductions. This marks the fourth Lepus species that can succumb to GI.2 infection, suggesting that susceptibility to GI.2 may be common in Lepus species. Measures to minimize the spread of GI.2 to vulnerable Lepus populations therefore are prudent.

BackgroundCurrent sepsis screening tools are predominantly based on vital signs. However, patients with serious infections frequently present with normal vital signs and there has been an increased interest to include other variables such as symptoms in screening tools to detect sepsis. The majority of patients with sepsis arrive to the emergency department by emergency medical services. Our hypothesis was that the presentation of sepsis, including symptoms, may differ between patients arriving to the emergency department by emergency medical services and patients arriving by other means. This information is of interest to adapt future sepsis screening tools to the population in which they will be implemented. The aim of the current study was to compare the prevalence of keywords reflecting the clinical presentation of sepsis based on mode of arrival among septic patients presenting to the emergency department.MethodsRetrospective cross-sectional study of 479 adult septic patients. Keywords reflecting sepsis presentation upon emergency department arrival were quantified and analyzed based on mode of arrival, i.e., by emergency medical services or by other means. We adjusted for multiple comparisons by applying Bonferroni-adjusted significance levels for all comparisons. Adjustments for age, gender, and sepsis severity were performed by stratification. All patients were admitted to the emergency department of Södersjukhuset, Stockholm, and discharged with an ICD-10 code compatible with sepsis between January 1, and December 31, 2013.Results“Abnormal breathing” (51.8% vs 20.5%, p value < 0.001), “abnormal circulation” (38.4% vs 21.3%, p value < 0.001), “acute altered mental status” (31.1% vs 13.1%, p value < 0.001), and “decreased mobility” (26.1% vs 10.7%, p value < 0.001) were more common among patients arriving by emergency medical services, while “pain” (71.3% vs 40.1%, p value < 0.001) and “risk factors for sepsis” (50.8% vs 30.8%, p value < 0.001) were more common among patients arriving by other means.ConclusionsThe distribution of most keywords related to sepsis presentation was similar irrespective of mode of arrival; however, some differences were present. This information may be useful in clinical decision tools or sepsis screening tools.

Objective: To identify molecular markers useful for the diagnostic discrimination of benign and malignant follicular thyroid tumors. Methods: A panel of thyroid tumors was characterized with expression profiling using cDNA microarrays. A robust algorithm for gene selection was developed to identify molecular markers useful for the classification of heterogeneous tumor classes. The study included tumor tissue specimens from 10 patients with benign follicular adenomas and from 10 with malignant tumors. The malignant tumors mainly consisted of clinically relevant minimally invasive follicular carcinomas. The mRNA expression level of a candidate gene, FHL1, was evaluated in an independent series of 61 tumors. Results: 22 gene expression markers were identified as differentially expressed. Several of the identified genes, for example DIO1, CITED1, CA12 and FN1, have previously been observed as differentially expressed in various thyroid tumors. FHL1 was significantly underexpressed in carcinomas compared to adenomas in the independent panel of tumors. The results indicate that a small number of genes can be useful to distinguish follicular adenomas from follicular carcinomas. Conclusions: Our findings clearly corroborate previous studies and identify novel candidate molecular markers. These genes have the potential for molecular classification of follicular thyroid tumors and for providing improved understanding of the molecular mechanisms involved in thyroid malignancies.