Targeted Skipping of Human Dystrophin Exons in Transgenic Mouse Model Systemically for Antisense Drug Development

Antisense therapy has recently been demonstrated with great potential for targeted exon skipping and restoration of dystrophin production in cultured muscle cells and in muscles of Duchenne Muscular Dystrophy (DMD) patients. Therapeutic values of exon skipping critically depend on efficacy of the drugs, antisense oligomers (AOs). However, no animal model has been established to test AO targeting human dystrophin exon in vivo systemically. In this study, we applied Vivo-Morpholino to the hDMD/mdx mouse, a transgenic model carrying the full-length human dystrophin gene with mdx background, and achieved for the first time more than 70% efficiency of targeted human dystrophin exon skipping in vivo systemically. We also established a GFP-reporter myoblast culture to screen AOs targeting human dystrophin exon 50. Antisense efficiency for most AOs is consistent between the reporter cells, human myoblasts and in the hDMD/mdx mice in vivo. However, variation in efficiency was also clearly observed. A combination of in vitro cell culture and a Vivo-Morpholino based evaluation in vivo systemically in the hDMD/mdx mice therefore may represent a prudent approach for selecting AO drug and to meet the regulatory requirement

The L-proline modified Zr-based MOF (Basu-proline) catalyst for the one‐pot synthesis of dihydropyrano[3,2-c]chromenes

Abstract A novel, reusable, and efficient L-proline-modified Zr-based metal–organic framework (Basu-proline) was designed, synthesized, and characterized by Fourier Transform-Infrared spectroscopy (FT-IR), Energy-Dispersive X-ray spectroscopy (EDX), elemental mapping, Field Emission Scanning Electron Microscopy (FE-SEM), X-ray Diffraction analysis (XRD), Thermo-Gravimetric-Differential Thermal Analysis (TGA-DTA), and N2 adsorption–desorption isotherms. Then, its catalytic performance was assessed in the synthesis of dihydropyrano[3,2-c]chromenes via the one-pot, three‐component tandem condensation reaction of 4-hydroxycoumarin, aromatic aldehydes and malononitrile. The Basu-proline catalyst exhibited a better efficiency than some reported protocols regarding higher yields, lower reaction times, and simple separation

Total laparoscopic retrieval of inferior vena cava filter

While there is some local variability in the use of inferior vena cava filters and there has been some evolution in the indications for filter placement over time, inferior vena cava filters remain a standard option for pulmonary embolism prophylaxis. Indications are clear in certain subpopulations of patients, particularly those with deep venous thrombosis and absolute contraindications to anticoagulation. There are, however, a variety of reported inferior vena cava filter complications in the short and long term, making retrieval of the filter desirable in most cases. Here, we present the case of a morbidly obese patient complaining of chronic abdominal pain after inferior vena cava filter placement and malposition of the filter with extensive protrusion outside the inferior vena cava. She underwent successful laparoscopic retrieval of her malpositioned inferior vena cava filters after failure of a conventional endovascular approach