Mathewsgoode8482

Enterovirus 71 (EV71) is a major pathogen that causes hand, foot and mouth disease (HFMD), which is a life threatening disease in certain children. The pathogenesis of EV71-caused HFMD is poorly defined due to the lack of simple and robust animal models with severe phenotypes that recapitulate symptoms observed in humans. Here, we generated the infectious clone of a clinical isolate from a severe HFMD patient. Virus rescued from the cDNA clone was infectious in cell lines. When administrated intraperitoneally to neonatal ICR, BALB/c and C57 immune competent mice at a dosage of1.4 × 104 pfu per mouse, the virus caused weight loss, paralysis and death in the infected mice after 4-5 days of infection. In the infected mice, detectable viral replication was detected in various tissues such as heart, liver, brain, lung, kidney, small intestine, leg skeletal muscle and medulla oblongata. DW71177 order The histology of the infected mice included massive myolysis, glomerular atrophy, villous blunting in small intestine, widened alveolar septum, diminished alveolar spaces and lymphocytes infiltration into the lung. By using the UV-inactivated virus as a control, we elucidated that the virus first amplified in the leg skeletal muscle tissue and the muscle tissue served as a primary viral replication site. In summary, we generated a stable EV71 infectious clone that is capable of infecting neonatal immune competent mice without adaptive mutations and provide a simple, valuable animal model for the studies of EV71pathogenesis and therapy.Bicuspid aortic valve (BAV) is the most common human congenital cardiac malformation. Although the etiology is unknown for most patients, formation of the 2 main BAV anatomic types (A and B) has been shown to rely on distinct morphogenetic mechanisms. Animal models of BAV include 2 spontaneous hamster strains and 27 genetically modified mouse strains. To assess the value of these models for extrapolation to humans, we examined the aortic valve anatomy of 4340 hamsters and 1823 mice from 8 and 7 unmodified strains, respectively. In addition, we reviewed the literature describing BAV in nonhuman mammals. The incidences of BAV types A and B were 2.3% and 0.03% in control hamsters and 0% and 0.3% in control mice, respectively. Hamsters from the spontaneous model had BAV type A only, whereas mice from 2 of 27 genetically modified strains had BAV type A, 23 of 27 had BAV type B, and 2 of 27 had both BAV types. In both species, BAV incidence was dependent on genetic background. Unlike mice, hamsters had a wide spectrum of aortic valve morphologies. We showed interspecific differences in the occurrence of BAV between humans, hamsters, and mice that should be considered when studying aortic valve disease using animal models. Our results suggest that genetic modifiers play a significant role in both the morphology and incidence of BAV. We propose that mutations causing anomalies in specific cardiac morphogenetic processes or cell lineages may lead to BAV types A, B, or both, depending on additional genetic, environmental, and epigenetic factors.OBJECTIVES Infrapopliteal arterial pseudoaneurysms (IAP) following blunt trauma with associated orthopedic injuries are uncommon, often present in a delayed fashion, and encompass a diagnostic and therapeutic dilemma. Herein, we present a series of IAPs that were diagnosed following blunt trauma and their management. METHODS Case series consisting of 3 patients and a review of the international literature. RESULTS Our case series included 3 patients presenting with IAPs following blunt trauma with associated orthopedic injuries. They were all identified in a delayed manner (>3 weeks) after the orthopedic injuries were treated. All patients presented with pain and a pulsatile mass while one concurrently had neurologic deficits. The pseudoaneurysms were diagnosed by duplex ultrasound and confirmed by angiography to be originating from the tibioperoneal trunk, anterior tibial, and posterior tibial arteries respectively. Two patients were treated with surgical excision. Of these, one required an arterial bypass procedure while the other underwent direct ligation only. The third patient was treated by endovascular coiling. A literature review from 1950 to the present found 51 reported cases of IAP resulting from blunt trauma. Ninety percent of trauma-related infrapopliteal injuries occurred in men with a mean delay in diagnosis of 5.6 months (median 1.8 months) after injury. Since 1950, management has shifted from primarily ligation to incorporating minimally invasive endovascular techniques when appropriate. CONCLUSIONS Infrapopliteal artery pseudoaneurysms are rare following blunt skeletal trauma. A delay in diagnosis often occurs and can result in major morbidity and extensive surgical intervention. We recommend a high index of suspicion and a thorough vascular examination in patients with lower extremity skeletal trauma to help identify and treat these injuries early and effectively.Insects are a highly successful group of animals that inhabit almost every habitat and environment on Earth. Part of their success is due to a rapid and highly effective immune response that identifies, inactivates, and eliminates pathogens. Insects possess an immune system that shows many similarities to the innate immune system of vertebrates, but they do not possess an equivalent system to the antibody-mediated adaptive immune response of vertebrates. However, some insect do display a process known as immune priming in which prior exposure to a sublethal dose of a pathogen, or pathogen-derived material, leads to an elevation in the immune response rendering the insect resistant to a subsequent lethal infection a short time later. This process is mediated by an increase in the density of circulating hemocytes and increased production of antimicrobial peptides. Immune priming is an important survival strategy for certain insects while other insects that do not show this response may have colony-level behaviors that may serve to limit the success of pathogens. Insects are now widely used as in vivo models for studying microbial pathogens of humans and for assessing the in vivo efficacy of antimicrobial agents. Knowledge of the process of immune priming in insects is essential in these applications as it may operate and augment the perceived in vivo antimicrobial activity of novel compounds.Abbreviations 1,3-dibenzyl-4,5-diphenyl-imidazol-2-ylidene silver(I) acetate; SBC3 antimicrobial peptides; AMPs dorsal-related immunity factor; DIF Down syndrome cell adhesion molecule; Dscam Lipopolysaccharide; LPS Pathogen-associated molecular patterns; PAMPS Patterns recognition receptors; PRR Prophenoloxidase; PO Toll-like receptors; TLRs Toll/IL-1R; TIR, Transgenerational Immune Priming; TgIP Tumor necrosis factor-α; TNF-α.