Vascular endothelial growth factor (VEGF)-A is differentially spliced to give two functionally different isoform families; pro-angiogenic, pro-permeability VEGF-Axxx and anti-angiogenic, anti-permeability VEGF-Axxxb. VEGF-A splicing is dysregulated in several pathologies, including cancer, diabetes, and peripheral arterial disease. The bichromatic VEGF-A splicing-sensitive fluorescent reporter harboured in a transgenic mouse is a novel approach to investigate the splicing patterns of VEGF-A in vivo. We generated a transgenic mouse harbouring a splicing-sensitive fluorescent reporter designed to mimic VEGF-A terminal exon splicing (VEGF8ab) by insertion into the ROSA26 genomic locus. dsRED expression denotes proximal splice site selection (VEGF-Axxx) and eGFP expression denotes distal splice site selection (VEGF-Axxxb). We investigated the tissue-specific expression patterns in the eye, skeletal muscle, cardiac muscle, kidney, and pancreas, and determined whether the splicing pattern could be manipulated in the same manner as endogenous VEGF-A by treatment with the SRPK1 inhibitor SPHINX 31. We confirmed expression of both dsRED and eGFP in the eye, skeletal muscle, cardiac muscle, kidney, and pancreas, with the highest expression of both fluorescent proteins observed in the exocrine pancreas. The ratio of dsRED and eGFP matched that of endogenous VEGF-Axxx and VEGF-Axxxb. Treatment of the VEGF8ab mice with SPHINX 31 increased the mRNA and protein eGFP/dsRED ratio in the exocrine pancreas, mimicking endogenous VEGF-A splicing. The VEGF-A exon 8 splicing-sensitive fluorescent reporter mouse is a novel tool to assess splicing regulation in the individual cell-types and tissues, which provides a useful screening process for potentially therapeutic splicing regulatory compounds in vivo

In total hip arthroplasty 32 mm heads are often used as the greater diameter is thought to contribute to improved stability. However, greater head diameter can also lead to greater volumetric wear. We compared polyethylene wear between patients with 32 mm heads and those with smaller heads. All patients who had Harris Galante1 metal-backed, uncemented cups inserted between 1986 and 1996 at our institute were annually reviewed clinically and radiographically. Accelerated polyethylene wear was noted between the fifth and seventh postoperative year in 17 out of 165 total hip replacements with 32 mm heads, but only in 21 out of 961 total hip arthroplasties with smaller femoral heads. In all 17 THRs, accelerated wear was also associated with thin polyethylene (<6 mm). This paper highlights a potentially serious problem. When 32 mm metal heads are used with uncemented cups and polyethylene liners, there is a risk of accelerated acetabular wear in patients with thin polyethylene.

In total hip arthroplasty 32 mm heads are often used as the greater diameter is thought to contribute to improved stability. However, greater head diameter can also lead to greater volumetric wear. We compared polyethylene wear between patients with 32 mm heads and those with smaller heads. All patients who had Harris Galante1 metal-backed, uncemented cups inserted between 1986 and 1996 at our institute were annually reviewed clinically and radiographically. Accelerated polyethylene wear was noted between the fifth and seventh postoperative year in 17 out of 165 total hip replacements with 32 mm heads, but only in 21 out of 961 total hip arthroplasties with smaller femoral heads. In all 17 THRs, accelerated wear was also associated with thin polyethylene (<6 mm). This paper highlights a potentially serious problem. When 32 mm metal heads are used with uncemented cups and polyethylene liners, there is a risk of accelerated acetabular wear in patients with thin polyethylene.