Four months ago, he underwent endovascular treatment for disabling claudication, which included placement of overlapping polytetrafluoroethylene-coated stents in the left superficial femoral and popliteal arteries. His popliteal and pedal pulses are absent, and the foot is cool and mottled. Angiography reveals complete occlusion of the stent, with thrombosis extending distally into the popliteal and tibial arteries below the knee. How should his case be managed?”
“Mutations

in the MYH9 gene, coding for the non-muscle myosin heavy chain IIA (NMHC-IIA), are responsible for syndromes characterized by macrothrombocytopenia associated with deafness, cataracts, and severe glomerular disease. Electron microscopy of renal biopsies from these patients found glomerular abnormalities characterized by alterations in mesangial cells, podocytes, and thickening of the glomerular basement membrane. Knockout of NMHC-IIA in mice is lethal, and therefore little is known about the glomerular-related functions of Myh9. Here, we use zebrafish as a model to study the role and

function of zNMHC-IIA in the glomerulus. Knockdown of zNMHC-IIA resulted in malformation of the glomerular capillary tuft characterized by few and dilated capillaries of the pronephros. In zNMHC-IIA morphants, endothelial cells failed to develop fenestrations, mesangial cells were absent or reduced, and the glomerular basement membrane appeared nonuniformly thickened. Knockdown of zNMHC-IIA did not impair the formation of podocyte foot processes or slit diaphragms; however, podocyte processes were less uniform in these morphants compared to controls. In vivo clearance of fluorescent dextran indicated that the glomerular barrier function was not 1 compromised by zNMHC-IIA knockdown; however, glomerular filtration was significantly

reduced. Thus, our results demonstrate an important role of zNMHC-IIA for the proper formation and function of the glomerulus in zebrafish. Kidney International (2011) 80, 1055-1063; doi:10.1038/ki.2011.256; published online 17 August 2011″
“In vitro fertilization has provided a unique window into the metabolic processes that drive embryonic growth and development from a fertilized ovum to a competent blastocyst. Post-fertilization development is dependent upon a dramatic reshuffling of the parental genomes during meiosis, as well as epigenetic changes that provide a new and autonomous set of instructions to guide cellular differentiation both in the embryo and beyond. Although early literature focused simply on the substrates and culture conditions required for progress through embryonic development, more recent insights lead us to suggest that the surrounding environment can alter the epigenome, which can, in turn, impact upon embryonic metabolism and developmental competence.”
“The CXCR1 receptor and chemokine CXCL8 (IL-8) support neutrophil-dependent clearance of uropathogenic Escherichia coli from the urinary tract.