Wear predictions for reverse total shoulder replacements

Reverse total shoulder arthroplasty (RTSA) has become the gold standard to treat rotator cuff tear arthropathy. RTSA is performed by substituting the humeral head and the glenoid cavity by a plastic cup in UHMWPE and a metallic head, respectively, in a geometrical reversed configuration with respect to the anatomical one. Major complications affect 27% of cases and mainly regard scapular notching due to cup-bone impingement and wear debris. Unfortunately, wear in shoulder prosthesis has not been largely studied as for hip and knee implants. Indeed, no wear test standards or even shoulder simulators exist, also because of a limited knowledge on shoulder/RTSA dynamics. Additionally, only a few numerical wear models for RTSA can be found in the literature, mainly focused on the comparison between anatomical and reverse solutions, and which often simulates simplified conditions, such as planar unloaded motions even neglecting fundamental aspects of wear process, i.e. cross-shearing (CS). The aim of the present study is to numerically investigate wear in RTSAs analysing the effect of: a) wear factor and wear law; a) implant geometry; b) inversion of bearing materials, i.e. plastic head + metallic cup, which should reduce the risks associated to scapular notching

Comparative analysis of tunisian sheep-like virus, bungowannah virus and border disease virus infection in the porcine host

Apart from the established pestivirus species Pestivirus A to Pestivirus K novel species emerged. Pigs represent not only hosts for porcine pestiviruses, but are also susceptible to bovine viral diarrhea virus, border disease virus (BDV) and other ruminant pestiviruses. The present study focused on the characterization of the ovine Tunisian sheep-like virus (TSV) as well as Bungowannah virus (BuPV) and BDV strain Frijters, which were isolated from pigs. For this purpose, we performed genetic characterization based on complete coding sequences, studies on virus replication in cell culture and in domestic pigs, and cross-neutralization assays using experimentally derived sera. TSV forms a distinct phylogenetic group more closely related to Pestivirus C (classical swine fever virus, CSFV) than to Pestivirus D (BDV). In contrast to BDV and BuPV, TSV replicates by far more efficiently on ovine than on porcine cells. Nevertheless, pigs were susceptible to TSV. As a consequence of close antigenic relatedness of TSV to CSFV, cross-reactivity was detected in CSFV-specific antibody assays. In conclusion, TSV is genetically closely related to CSFV and can replicate in domestic pigs. Due to close antigenic relatedness, field infections of pigs with TSV and other ruminant pestiviruses can interfere with serological diagnosis of classical swine fever

Targeting Cullin-RING E3 ubiquitin ligases for drug discovery: Structure, assembly and small-molecule modulation

© The Authors Journal compilation © 2015 Biochemical Society. In the last decade, the ubiquitin-proteasome system has emerged as a valid target for the development of novel therapeutics. E3 ubiquitin ligases are particularly attractive targets because they confer substrate specificity on the ubiquitin system. CRLs [Cullin-RING (really interesting new gene) E3 ubiquitin ligases] draw particular attention, being the largest family of E3s. The CRLs assemble into functional multisubunit complexes using a repertoire of substrate receptors, adaptors, Cullin scaffolds and RING-box proteins. Drug discovery targeting CRLs is growing in importance due to mounting evidence pointing to significant roles of these enzymes in diverse biological processes and human diseases, including cancer, where CRLs and their substrates often function as tumour suppressors or oncogenes. In the present review, we provide an account of the assembly and structure of CRL complexes, and outline the current state of the field in terms of available knowledge of small-molecule inhibitors and modulators of CRL activity. A comprehensive overview of the reported crystal structures of CRL subunits, components and full-size complexes, alone or with bound small molecules and substrate peptides, is included. This information is providing increasing opportunities to aid the rational structure-based design of chemical probes and potential small-molecule therapeutics targeting CRLs

Disseminated phaeohyphomycosis in a beluga sturgeon (Huso huso)

Phaeohyphomycosis is a fungal infection caused by dematiaceous or melanised fungi (Seyedmousavi, Guillot, and de Hoog 2013). Although considered ubiquitous residents of plant material, soil, and wood, melanised fungi are likely adapted to specific niches that facilitate variable opportunistic or true pathogenic potentials. Exposure is typically associated with inoculation by minor trauma or inhalation. In mammals, infections are commonly cutaneous, subcutaneous, upper respiratory or primary cerebral, but in cold-blooded vertebrates are often disseminated and accompanied by severe tissue necrosis (Revankar, Sutton, and Rinaldi 2004; Seyedmousavi, Guillot, and de Hoog 2013)

Viral nervous necrosis outbreaks caused by the RGNNV/SJNNV reassortant betanodavirus in gilthead sea bream (Sparus aurata) and European sea bass (Dicentrarchus labrax)

Mediterranean marine aquaculture has suffered significant economic losses due to viral nervous necrosis (VNN) outbreaks mainly caused by different RGNNV betanodavirus strains. In recent years, the marine aquaculture sector has experienced the emergence of the RGNNV/SJNNV reassortant betanodavirus, harbouring the RNA1 segment of RGNNV genotype and the RNA2 segment of SJNNV genotype. So far, the reassortant strains caused massive mortality outbreaks in gilthead sea bream (Sparus aurata) larvae sparing the European sea bass (Dicentrarchus labrax). In this study, multiple mortality outbreaks occurred in one Italian marine hatchery involving both European sea bass and gilthead sea bream at different life stages were investigated through a complete microbiological and molecular analysis. Gilthead sea bream larvae and juveniles have recorded the highest mortality rates, however, both European sea bass and gilthead sea bream incurred a RGNNV/SJNNV reassortant betanodavirus persistent infection, able to act as asymptomatic carriers and viral source for susceptible fish. These new epidemiological data on nervous necrosis virus (NNV) reassortant infection provide precious advice on how to manage fish to reduce VNN spread in Mediterranean aquaculture. Evidence of interspecies transmission of RGNNV/SJNNV reassortant strains and the persistent infection in both European sea bass and gilthead sea bream, point out the importance to enforce a wide surveillance and a strict biosecurity programme addressing both RGNNV and reassortant RGNNV/SJNNV betanodaviruses in Mediterranean European sea bass and gilthead sea bream farms. Furthermore, the presence assessment of betanoviruses in all newly-introduced fish batches in the farm, regardless of the species and a strict segregation between European sea bass and gilthead sea bream batches within farms can significantly reduce the risk of NNV transmission. Finally, surviving fish can act as carrier fish, and thereby must be segregated from other batches and protected from stress conditions that could trigger a new clinical phase