Inherited liver shunts in dogs elucidate pathways regulating embryonic development and clinical disorders of the portal vein

Congenital disorders of the hepatic portal vasculature are rare in man but occur frequently in certain dog breeds. In dogs, there are two main subtypes: intrahepatic portosystemic shunts, which are considered to stem from defective closure of the embryonic ductus venosus, and extrahepatic shunts, which connect the splanchnic vascular system with the vena cava or vena azygos. Both subtypes result in nearly complete bypass of the liver by the portal blood flow. In both subtypes the development of the smaller branches of the portal vein tree in the liver is impaired and terminal branches delivering portal blood to the liver lobules are often lacking. The clinical signs are due to poor liver growth, development, and function. Patency of the ductus venosus seems to be a digenic trait in Irish wolfhounds, whereas Cairn terriers with extrahepatic portosystemic shunts display a more complex inheritance. The genes involved in these disorders cannot be identified with the sporadic human cases, but in dogs, the genome-wide study of the extrahepatic form is at an advanced stage. The canine disease may lead to the identification of novel genes and pathways cooperating in growth and development of the hepatic portal vein tree. The same pathways likely regulate the development of the vascular system of regenerating livers during liver diseases such as hepatitis and cirrhosis. Therefore, the identification of these molecular pathways may provide a basis for future proregenerative intervention

Local infiltration analgesia adds no clinical benefit in pain control to peripheral nerve blocks after total knee arthroplasty.

PURPOSE: To evaluate the effect of the local infiltration of analgesics for pain after total knee arthroplasty in patients treated with femoral and sciatic peripheral nerve blocks. The secondary objective was to detect differences in analgesic consumption as well as blood loss after local infiltration of analgesics. METHODS: Prospective randomized double-blinded study in patients who underwent a TKA for knee osteoarthritis under spinal anesthesia and treated with femoral and sciatic nerve blocks. This study compared 50 patients treated with local infiltration with ropivacaine, epinephrine, ketorolac and clonidine and 50 patients treated with a placebo with the same technique. The visual analogic score was registered postoperatively at 2, 6, 12, 24, 36, 48 and 72 h after surgery. Analgesic consumption was also registered. Both groups of patients were treated with the same surgical and rehabilitation protocols. RESULTS: A significant difference of one point was found in the visual analogic pain scores 12 h after surgery (0.6 ± 1.5 vs. 1.7 ± 2.3). There were no significant differences in the visual analogic pain scores evaluated at any other time between 2 and 72 h after surgery. No significant differences were found in the required doses of tramadol or morphine in the postoperative period. Postoperative hemoglobin and blood loss were also similar in both groups. CONCLUSION: Adding local infiltration of analgesics to peripheral nerve blocks after TKA surgery only provides minimal benefit for pain control. This benefit may be considered as non-clinically relevant. Moreover, the need for additional analgesics was the same in both groups. Therefore, the use of local infiltration of analgesics treatment in TKA surgery cannot be recommended if peripheral nerve blocks are used

Electroweak parameters of the z0 resonance and the standard model

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Pangenome analyses of the wheat pathogen Zymoseptoria tritici reveal the structural basis of a highly plastic eukaryotic genome

Background: Structural variation contributes substantially to polymorphism within species. Chromosomal rearrangements that impact genes can lead to functional variation among individuals and influence the expression of phenotypic traits. Genomes of fungal pathogens show substantial chromosomal polymorphism that can drive virulence evolution on host plants. Assessing the adaptive significance of structural variation is challenging, because most studies rely on inferences based on a single reference genome sequence. Results: We constructed and analyzed the pangenome of Zymoseptoria tritici, a major pathogen of wheat that evolved host specialization by chromosomal rearrangements and gene deletions. We used single-molecule real-time sequencing and high-density genetic maps to assemble multiple genomes. We annotated the gene space based on transcriptomics data that covered the infection life cycle of each strain. Based on a total of five telomere-to-telomere genomes, we constructed a pangenome for the species and identified a core set of 9149 genes. However, an additional 6600 genes were exclusive to a subset of the isolates. The substantial accessory genome encoded on average fewer expressed genes but a larger fraction of the candidate effector genes that may interact with the host during infection. We expanded our analyses of the pangenome to a worldwide collection of 123 isolates of the same species. We confirmed that accessory genes were indeed more likely to show deletion polymorphisms and loss-of-function mutations compared to core genes. Conclusions: The pangenome construction of a highly polymorphic eukaryotic pathogen showed that a single reference genome significantly underestimates the gene space of a species. The substantial accessory genome provides a cradle for adaptive evolution