Molecular characterization of a lizard adenovirus reveals the first atadenovirus with two fiber genes and the first adenovirus with either one short or three long fibers per penton

Although adenoviruses (AdVs) have been found in a wide variety of reptiles, including numerous squamate species, turtles, and crocodiles, the number of reptilian adenovirus isolates is still scarce. The only fully sequenced reptilian adenovirus, snake adenovirus 1 (SnAdV-1), belongs to the Atadenovirus genus. Recently, two new atadenoviruses were isolated from a captive Gila monster (Heloderma suspectum) and Mexican beaded lizards (Heloderma horridum). Here we report the full genomic and proteomic characterization of the latter, designated lizard adenovirus 2 (LAdV-2). The double-stranded DNA (dsDNA) genome of LAdV-2 is 32,965 bp long, with an average G+C content of 44.16%. The overall arrangement and gene content of the LAdV-2 genome were largely concordant with those in other atadenoviruses, except for four novel open reading frames (ORFs) at the right end of the genome. Phylogeny reconstructions and plesiomorphic traits shared with SnAdV-1 further supported the assignment of LAdV-2 to the Atadenovirus genus. Surprisingly, two fiber genes were found for the first time in an atadenovirus. After optimizing the production of LAdV-2 in cell culture, we determined the protein compositions of the virions. The two fiber genes produce two fiber proteins of different sizes that are incorporated into the viral particles. Interestingly, the two different fiber proteins assemble as either one short or three long fiber projections per vertex. Stoichiometry estimations indicate that the long fiber triplet is present at only one or two vertices per virion. Neither triple fibers nor a mixed number of fibers per vertex had previously been reported for adenoviruses or any other virus

The management of acute venous thromboembolism in clinical practice. Results from the European PREFER in VTE Registry

Venous thromboembolism (VTE) is a significant cause of morbidity and mortality in Europe. Data from real-world registries are necessary, as clinical trials do not represent the full spectrum of VTE patients seen in clinical practice. We aimed to document the epidemiology, management and outcomes of VTE using data from a large, observational database. PREFER in VTE was an international, non-interventional disease registry conducted between January 2013 and July 2015 in primary and secondary care across seven European countries. Consecutive patients with acute VTE were documented and followed up over 12 months. PREFER in VTE included 3,455 patients with a mean age of 60.8 ± 17.0 years. Overall, 53.0 % were male. The majority of patients were assessed in the hospital setting as inpatients or outpatients (78.5 %). The diagnosis was deep-vein thrombosis (DVT) in 59.5 % and pulmonary embolism (PE) in 40.5 %. The most common comorbidities were the various types of cardiovascular disease (excluding hypertension; 45.5 %), hypertension (42.3 %) and dyslipidaemia (21.1 %). Following the index VTE, a large proportion of patients received initial therapy with heparin (73.2 %), almost half received a vitamin K antagonist (48.7 %) and nearly a quarter received a DOAC (24.5 %). Almost a quarter of all presentations were for recurrent VTE, with >80 % of previous episodes having occurred more than 12 months prior to baseline. In conclusion, PREFER in VTE has provided contemporary insights into VTE patients and their real-world management, including their baseline characteristics, risk factors, disease history, symptoms and signs, initial therapy and outcomes

Effect of benzylpenicillin on intravenous pharmacokinetics of acyclovir in red‐eared slider turtles ( Trachemys scripta elegans

The aim of this study was to determine the effect of benzylpenicillin on the pharmacokinetics of acyclovir in red-eared slider turtles (Trachemys scripta elegans). Six clinically healthy red-eared slider turtles weighing 400 and 580 g were used for the study. Acyclovir (40 mg/kg) and benzylpenicillin (30 mg/kg) were administered intravenously to turtles. In the study, the cross-pharmacokinetic design (2 x 2) with a 30-day washout period was performed in two periods. Plasma concentrations of acyclovir were assayed using the high-performance liquid chromatography with fluorescence detection. Pharmacokinetic parameters were calculated by two-compartment open pharmacokinetic model. Following the administration of acyclovir alone, elimination half-life (t(1/2)(beta)), area under the plasma concentration-time curve (AUC), total clearance (Cl-T), and volume of distribution at steady-state (V-dss) were 20.12 hr, 1,372 hr * mu g/mL, 0.03 L hr(-1) kg(-1), and 0.84 L/kg, respectively. Benzylpenicillin administration increased t(1/2)(beta), AUC, and V-dss while decreased Cl-T of acyclovir. These results showed that benzylpenicillin changed the pharmacokinetics of acyclovir following simultaneous administration in turtles. However, further research is needed to determine molecular mechanism of interaction in turtle

LRP1b shows restricted expression in human tissues and binds to several extracellular ligands, including fibrinogen and apoE – carrying lipoproteins

AbstractObjectiveTo investigate low-density lipoprotein receptor-related protein 1b (LRP1b) expression in human tissues and to identify circulating ligands of LRP1b.Methods and resultsUsing two independent RT-PCR assays, LRP1b mRNA was detected in human brain, thyroid gland, skeletal muscle, and to a lesser amount in testis but absent in other tissues, including heart, kidney, liver, lung, and placenta. Circulating ligands were purified from human plasma by affinity chromatography using FLAG-tagged recombinant LRP1b ectodomains and identified by mass spectrometry. Using this technique, several potential ligands (fibrinogen, clusterin, vitronectin, histidine rich glycoprotein, serum amyloid P-component, and immunoglobulins) were identified. Direct binding of LRP1b ectodomains to fibrinogen was verified by co-immunoprecipitation. ApoE – carrying lipoproteins were shown to bind to LRP1b ectodomains in a lipoprotein binding assay. Furthermore, binding as well as internalization of very low density lipoproteins by cells expressing an LRP1b minireceptor was demonstrated.DiscussionLRP1b expression in humans appears to be confined to few tissues, which could point out to specialized functions of LRP1b in certain organs. Most of the newly identified LRP1b ligands are well-known factors in blood coagulation and lipoprotein metabolism, suggesting a possible role of LRP1b in atherosclerosis

Sunshine virus in Australian pythons

Sunshine virus is a recently discovered novel paramyxovirus that is associated with illness in snakes. It does not phylogenetically cluster within either of the two currently accepted paramyxoviral subfamilies. It is therefore only distantly related to the only other known genus of reptilian paramyxoviruses, Ferlavirus, which clusters within the Paramyxovirinae subfamily. Clinical and diagnostic aspects associated with Sunshine virus are as yet undescribed. The objective of this paper was to report the clinical presentation, virus isolation, PCR testing and pathology associated with Sunshine virus infection. Clinical records and samples from naturally occurring cases were obtained from two captive snake collections and the archives of a veterinary diagnostic laboratory. The clinical signs that are associated with Sunshine virus infection are localised to the neurorespiratory systems or are non-specific (e.g. lethargy, inappetence). Out of 15 snakes that were infected with Sunshine virus (detected in any organ by either virus isolation or PCR), the virus was isolated from four out of ten (4/10) sampled brains, 3/10 sampled lungs and 2/7 pooled samples of kidney and liver. In these same 15 snakes, PCR was able to successfully detect Sunshine virus in fresh-frozen brain (11/11), kidney (7/8), lung (8/11) and liver (5/8); and various formalin-fixed paraffin-embedded tissues (7/8). During a natural outbreak of Sunshine virus in a collection of 32 snakes, the virus could be detected in five out of 39 combined oral-cloacal swabs that were collected from 23 of these snakes over a 105 day period. All snakes that were infected with Sunshine virus were negative for reovirus and ferlavirus by PCR. Snakes infected with Sunshine virus reliably exhibited hindbrain white matter spongiosis and gliosis with extension to the surrounding grey matter and neuronal necrosis evident in severe cases. Five out of eight infected snakes also exhibited mild bronchointerstitial pneumonia. Infection with Sunshine virus should be considered by veterinarians investigating disease outbreaks in snakes, particularly those that are associated with neurorespiratory disease