Initial clinical experience with the novel POLARx FIT cryoballoon system for pulmonary vein isolation in patients with atrial fibrillation.

Background: The POLARx FIT system (Boston Scientific, MA, USA) is a novel cryoballoon (CB) ablation technology in which the balloon diameter can be expanded from 28 to 31 mm. The aim of this study was to compare the benefits and safety of the new POLARx FIT system to those of the existing POLARx system currently in use for pulmonary vein (PV) isolation (PVI) in patients with atrial fibrillation. Methods: The first 70 consecutive patients who underwent CB-based PVI with the POLARx FIT system were retrospectively compared with 200 consecutive patients treated with the POLARx system at Sakakibara Heart Institute from October 2021 to May 2023. Results: The POLARx FIT system yielded a higher mean ± standard deviation nadir temperature in the right inferior PV (-59.2 ± 5.29 °C vs. - 62.0 ± 5.08 °C, p = 0.006), but this required a balloon size reduction to 28 mm in 30 % of cases. No significant differences were detected in the time to isolation and thaw time of any PV between the two groups. After the CB-based PVI procedure, no residual PV carina potentials were observed with the POLARx FIT system, whereas 4/20 were with the POLARx system (p = 0.04). Conclusions: The POLARx FIT system had comparable effectiveness and safety to the basic POLARx system. This technology may improve the ablation area, including the PV carina. However, the 31-mm balloon alone was not sufficient to isolate certain PVs.

Ribosomal Synthesis of Peptides Bearing Noncanonical Backbone Structures via Chemical Posttranslational Modifications.

Noncanonical peptide backbone structures, such as heterocycles and non-α-amino acids, are characteristic building blocks present in peptidic natural products. To achieve ribosomal synthesis of designer peptides bearing such noncanonical backbone structures, we have devised translation-compatible precursor residues and their chemical posttranslational modification processes. In this chapter, we describe the detailed procedures for the in vitro translation of peptides containing the precursor residues by means of genetic code reprogramming technology and posttranslational generation of objective noncanonical backbone structures.

In Vitro Selection of Thioether-Closed Macrocyclic Peptide Ligands by Means of the RaPID System.

The Random nonstandard Peptides Integrated Discovery (RaPID) system enables efficient screening of macrocyclic peptides with high affinities against target molecules. Random peptide libraries are prepared by in vitro translation using the Flexible In vitro Translation (FIT) system, which allows for incorporation of diverse nonproteinogenic amino acids into peptides by genetic code reprogramming. By introducing an N-chloroacetyl amino acid at the N-terminus and a Cys at the downstream, macrocyclic peptide libraries can be readily generated via posttranslational thioether formation. Here, we describe how to prepare a thioether-closed macrocyclic peptide library, and its application to the RaPID screening.

Clinical evaluation of a novel press-fit acetabular cup using "Ein-Bild-Roentgen-Analysis" (EBRA): A positive short-term prognosis.

INTRODUCTION: Demographic change and demand for high quality of life lead to increasing implantation numbers. Aim of this study was to compare the Plasmafit® cup to Allofit® and Plasmacup®. METHODS: The study included 174 patients who had received 33 Plasmacup®, 68 Allofit® and 73 Plasmafit® cup implants. These were reviewed postoperatively, after 6 months control and after 12 months. RESULTS: No significant progressive migration could be discovered in any of the cup systems. At each follow-up the cups showed nearly constant values. CONCLUSIONS: All examined acetabular cups showed excellent migration behavior within the first 12 postoperative months.

Discovery of Functional Macrocyclic Peptides by Means of the RaPID System.

Flexizymes, highly flexible tRNA aminoacylation ribozymes, have enabled charging of virtually any amino acid (including non-proteogenic ones) onto tRNA molecules. Coupling to a custom-made in vitro translation system, namely the flexible in vitro translation (FIT) system, has unveiled the remarkable tolerance of the ribosome toward molecules, remote from what nature has selected to carry out its elaborate functions. Among the very diverse molecules and chemistries that have been ribosomally incorporated, a plethora of entities capable of mediating intramolecular cyclization have revolutionized the design and discovery of macrocyclic peptides. These macrocyclization reactions (which can be spontaneous, chemical, or enzymatic) have all served as tools for the discovery of peptides with natural-like structures and properties. Coupling of the FIT system and mRNA display techniques, known as the random non-standard peptide integrated discovery (RaPID) system, has in turn allowed for the simultaneous screening of trillions of macrocyclic peptides against challenging biological targets. The macrocyclization methodologies are chosen depending on the structural and functional characteristics of the desired molecule. Thus, they can emanate from the peptide's N-terminus or its side chains, attributing flexibility or rigidity, or even result in the installation of fluorescent probes.