👤 Jan Spillner

IntroductionPulmonary artery (PA) cannulation is emerging as a method for concurrent cardiac and respiratory failure, but limited data exists on how cannula positioning, particularly cannula tip angle, affects perfusion symmetry. Due to varying pulmonary bifurcation geometry between patients, ensuring even distribution of oxygen-saturated blood becomes critical. This computational fluid dynamics (CFD) study investigated the effects of cannula positioning and angles on oxygen delivery within the PA using 6 different configurations.MethodAn idealized PA geometry based on a CT scan was constructed including the 6 different cannula configurations: two straight (short and long) and four angled (5° and 10° toward either pulmonary branch). Simulations assumed laminar, steady-state flow at 6 L/min total (50% ECMO contribution). Oxygen transport was modeled as a passive scalar with 75% saturation from the heart and 100% from the cannula. Perfusion symmetry was quantified using the absolute difference in mean oxygen saturation (ΔSaO Show less

Nucleoporins build the nuclear pore complex (NPC), which, as sole gate for nuclear-cytoplasmic exchange, is of outmost importance for normal cell function. Defects in the process of nucleocytoplasmic transport or in its machinery have been frequently described in human diseases, such as cancer and neurodegenerative disorders, but only in a few cases of developmental disorders. Here we report biallelic mutations in the nucleoporin NUP88 as a novel cause of lethal fetal akinesia deformation sequence (FADS) in two families. FADS comprises a spectrum of clinically and genetically heterogeneous disorders with congenital malformations related to impaired fetal movement. We show that genetic disruption of nup88 in zebrafish results in pleiotropic developmental defects reminiscent of those seen in affected human fetuses, including locomotor defects as well as defects at neuromuscular junctions. Phenotypic alterations become visible at distinct developmental stages, both in affected human fetuses and in zebrafish, whereas early stages of development are apparently normal. The zebrafish phenotypes caused by nup88 deficiency are rescued by expressing wild-type Nup88 but not the disease-linked mutant forms of Nup88. Furthermore, using human and mouse cell lines as well as immunohistochemistry on fetal muscle tissue, we demonstrate that NUP88 depletion affects rapsyn, a key regulator of the muscle nicotinic acetylcholine receptor at the neuromuscular junction. Together, our studies provide the first characterization of NUP88 in vertebrate development, expand our understanding of the molecular events causing FADS, and suggest that variants in NUP88 should be investigated in cases of FADS. Show less