Clinical potential of hemodynamic ramp test by simultaneous echocardiography and right heart catheterization for aortic insufficiency in a patient with continuous-flow left ventricular assist device

Journal of Artificial Organs - Aortic insufficiency (AI) is an important adverse event in patients with continuous-flow (CF) left ventricular assist device (LVAD) support. AI is often progressive,...     

Effects of idursulfase enzyme replacement therapy for Mucopolysaccharidosis type II when started in early infancy: Comparison in two siblings

Mucopolysaccharidosis type II (MPS II) is a lysosomal storage disorder that is progressive and involves multiple organs and tissues. While enzyme replacement therapy (ERT) with idursulfase has been shown to improve many somatic features of the disease, some such as dysostosis multiplex and cardiac valve disease appear irreversible once established, and little is known about the preventative effects of ERT in pre-symptomatic patients. We report on two siblings with severe MPS II caused by an inversion mutation with recombination breakpoints located within the IDS gene and its adjacent pseudogene, IDS-2. The siblings initiated treatment with idursulfase at 3.0 years (older brother) and 4 months (younger brother) of age, and we compared their outcomes following 2 years of treatment. At the start of treatment, the older brother showed typical features of MPS II, including intellectual disability. After 34 months of ERT, his somatic disease was stable or improved, but he continued to decline cognitively. By comparison, after 32 months of ERT his younger brother remained free from most of the somatic features that had already appeared in his brother at the same age, manifesting only exudative otitis media. Skeletal X-rays revealed characteristic signs of dysostosis multiplex in the older brother at the initiation of treatment that were unchanged two years later, whereas the younger brother showed only slight findings of dysostosis multiplex throughout the treatment period. The younger brother's developmental quotient trended downward over time to just below the normal range. These findings suggest that pre-symptomatic initiation of ERT may prevent or attenuate progression of the somatic features of MPS II. Follow-up in a larger number of patients is required to confirm the additive long-term benefits of ERT in pre-symptomatic patients.     

Use of puncture force measurement to investigate the conditions of blood vessel needle insertion

Central venous catheterization involves venous puncture and catheter insertion for transfusions. Quantitative conditions that facilitate insertion of the needle, such as the angle and velocity of insertion, have not been clarified. We previously developed a robotic system for guiding the needle along a specified puncture path with high precision and are currently implementing a hardware design for a robotic system to assist in blood vessel puncture. In this study, we proposed the insertion angle and velocity for stopping the needle in a blood vessel, assuming that a robotic system such as ours is used during the procedure. We inserted a needle into a segment of porcine jugular vein and obtained the puncture reaction force. Evaluation indices were the magnitude of the sudden decrease in reaction force at the point at which the needle advances and the length of time that the needle is present within the vein. Results indicated that the conditions under which it was easiest to stop the needle inside the vein were an insertion angle range of 10–20 and an insertion velocity of 3 mm/s.     

Both G3BP1 and G3BP2 contribute to stress granule formation

Upon exposure to various environmental stresses such as arsenite, hypoxia, and heat shock, cells inhibit their translation and apoptosis and then repair stress‐induced alterations, such as DNA damage and the accumulation of misfolded proteins. These types of stresses induce the formation of cytoplasmic RNA granules called stress granules (SGs). SGs are storage sites for the many mRNAs released from disassembled polysomes under these stress conditions and are essential for the selective translation of stress‐inducible genes. Ras‐GTPase‐activating protein SH3 domain‐binding protein 1 (G3BP1) is a component of SGs that initiates the assembly of SGs by forming a multimer. In this study, we examined the role of G3BP2, a close relative of G3BP1, in SG formation. Although single knockdown of either G3BP1 or G3BP2 in 293T cells partially reduced the number of SG‐positive cells induced by arsenite, the knockdowns of both genes significantly reduced the number. G3BP2 formed a homo‐multimer and a hetero‐multimer with G3BP1. Moreover, like G3BP1, the overexpression of G3BP2 induced SGs even without stress stimuli. Collectively, these results suggest that both G3BP1 and G3BP2 play a role in the formation of SGs in various human cells and thereby recovery from these cellular stresses.