Challenges in Medicine: The Odyssey of a Patient with Isolated IgG4-Related Eosinophilic Angiocentric Fibrosis Presenting as a Locally Destructive Sinonasal Mass

Eosinophilic angiocentric fibrosis (EAF) is an exceeding rare clinical entity and is considered a part of the spectrum of IgG4-related disease (IgG4RD). We hereby present such an unusual case of a 60-year-old female who presented to us with recurrent sinonasal mass, after a decade long haul of multiple clinical evaluations, biopsies, and debulking surgery without a definitive diagnosis. Over this period, the mass eroded through the ethmoid cells along with nasal septal destruction leading to saddle nose deformity, extended superiorly through the cribriform plates to right frontal lobe, and compressed the optic nerve leading to visual loss. Although initial biopsy was negative, repeat biopsy was performed owing to high clinical suspicion due to all the classic histopathological findings compatible with the diagnosis of eosinophilic angiocentric fibrosis IgG4-related disease (EAF-IgG4RD). Steroids are the recommended first-line therapy; however, our case was resistant to steroids needing rituximab to halt the disease progression. Our case interestingly also had T-cell clonality and isolated isocitrate dehydrogenase 2 enzyme mutation on next-generation sequencing, suggesting a possible role of novel molecular-targeted therapies in this rare disease. This case highlights the clinical challenges physicians face towards diagnosing and treating EAF-IgG4RD, emphasizing the need for high clinical suspicion and the possible role of targeted therapies for this rare disease

Inhibition of RNA Recruitment and Replication of an RNA Virus by Acridine Derivatives with Known Anti-Prion Activities

Small molecule inhibitors of RNA virus replication are potent antiviral drugs and useful to dissect selected steps in the replication process. To identify antiviral compounds against Tomato bushy stunt virus (TBSV), a model positive stranded RNA virus, we tested acridine derivatives, such as chlorpromazine (CPZ) and quinacrine (QC), which are active against prion-based diseases.Here, we report that CPZ and QC compounds inhibited TBSV RNA accumulation in plants and in protoplasts. In vitro assays revealed that the inhibitory effects of these compounds were manifested at different steps of TBSV replication. QC was shown to have an effect on multiple steps, including: (i) inhibition of the selective binding of the p33 replication protein to the viral RNA template, which is required for recruitment of viral RNA for replication; (ii) reduction of minus-strand synthesis by the tombusvirus replicase; and (iii) inhibition of translation of the uncapped TBSV genomic RNA. In contrast, CPZ was shown to inhibit the in vitro assembly of the TBSV replicase, likely due to binding of CPZ to intracellular membranes, which are important for RNA virus replication.Since we found that CPZ was also an effective inhibitor of other plant viruses, including Tobacco mosaic virus and Turnip crinkle virus, it seems likely that CPZ has a broad range of antiviral activity. Thus, these inhibitors constitute effective tools to study similarities in replication strategies of various RNA viruses

Compilation and traits of Australian bird species killed by cats

House cats Felis catus have contributed to the extinction of many bird species on islands, but their impact on continental bird faunas is less well resolved. Here, we compile and analyse a comprehensive record of all bird species known to be killed by feral cats at a continental scale. From published studies and unpublished data, we document predation by feral and pet cats on 357 bird species in Australia, including 338 Australian (nonvagrant) native bird species (=45.6% of the 741 Australian native bird species, excluding vagrants). This tally included 24 species listed as threatened or extinct by the IUCN (40% of the 58 non-vagrant Australian species listed as threatened), and 71 of the 117 bird species (61%) listed as threatened under Australian legislation (or species with one or more subspecies so listed). These tallies are substantially larger than reported in previous reviews. We provide the first continental-scale attempt to model bird species' traits that are associated with likelihood of being killed by cats, and use such modelling to attempt to redress some inevitable biases in compilation of predation records on birds. We conclude that the likelihood of being killed by a cat was highest for bird species that are restricted to islands, are of intermediate body mass (ca. 60–300 g), and nest and forage on the ground, and least likely for bird species occurring mostly in rainforests and wetlands. We also identify a set of bird species most likely to be threatened by cat-predation and hence most likely to benefit from enhanced management of cats. This study does not specifically evaluate the impact of cats on bird populations or on the conservation of Australian birds, but our results suggest that such impact may be much more pervasive than previously documented

How many birds are killed by cats in Australia?

From analysis of results from 93 studies on the frequency of occurrence of birds in cat dietary samples, and a recently published assessment of the population size of feral cats in largely natural landscapes, we estimate and map the number of birds killed annually in Australia by feral cats. We show that average rates of predation on birds by cats on islands are ca. 10 times higher than for comparable mainland areas. Predation rates on birds are also relatively high in hot, arid regions. Across Australia's natural landscapes, feral cats typically consume 272 million birds yr−1 (95% confidence interval [CI]: 169–508 million). However, there is substantial inter-annual variation, depending on changes in the cat population that are driven by rainfall conditions: ranging between 161 million birds yr−1 (95% CI: 114–284 million) following dry periods and 757 million birds yr−1 (95% CI: 334–1580 million) following wet periods. On average, feral cats kill 35.6 birds km−2 yr−1 (95% CI: 22.2–66.6). About 99% of these mortalities are native bird species. With a much sparser evidence base, we also estimate that a further 44 million birds are killed annually by feral cats in highly modified landscapes, and 61 million birds are killed annually by pet cats, summing to 377 million birds killed yr−1 (i.e., just over 1 million birds per day) by all cats. Feral cats include a significantly higher proportion of birds in their diet than do other main mammalian predators. The national tally of birds killed by cats in Australia is broadly comparable to recent assessments for Canada, but less than that reported for the United States (because the cat population is much higher there). However, it remains challenging to interpret this mortality tally in terms of population viability or conservation concern for Australian birds