Metal-on-metal total hip arthroplasty: is there still a role in 2016?

The use of metal-on-metal (MoM) bearings in total hip arthroplasty (THA) was popularized due to its enhanced wear profile and the ability to use large femoral heads to reduce post-operative instability. However, enthusiasm for the bearing declined following serious complications encountered at the primary articulation. This review discusses the development of MoM and the subsequent unexpected downstream challenges, most notably elevated serum metal ion levels, aseptic lymphocyte-dominated vasculitis-associated lesions (ALVAL), pseudotumor formation, and subsequent soft tissue and bone destruction. Both patient centered risk factors as well as component design led to high early failure rates resulting in product recalls and an overall decline in the use of MoM. In 2016, there is not a role for large-head MoM bearing in THA. Alternatively, the bearing has shown promise in hip resurfacing procedures for carefully selected patients.

The effect of viscosity on cement penetration in total knee arthroplasty, an application of the squeeze film effect.

The authors present a prospective randomized blinded cadaver study designed to evaluate the engineering concept of a squeeze film effect and the effect of cement viscosity on cement penetration in total knee arthroplasty. This was done in response to an earlier clinical study demonstrating inferior tibial cement penetration using early, often liquid, phase cement. Paired cadaver tibias were implanted with the tibial component using either liquid or dough phase cement. Based on an AP fluoroscopic image, the dough phase cement penetrated deeper than liquid in all four zones. This was statistically significant in zones 1, 2 and 3. Deeper cement penetration has been shown to provide a stronger cement-bone interphase. As a result dough phase cement is recommended to obtain optimal cement penetration.

Scientific collaboration networks using biomedical text.

The combination of scientific knowledge and experience is the key success for biomedical research. This chapter demonstrates some of the strategies used to help in identifying key opinion leaders with the expertise you need, thus enabling an effort to increase collaborative biomedical research.

Regulation of synaptic Pumilio function by an aggregation-prone domain.

We identified Pumilio (Pum), a Drosophila translational repressor, in a computational search for metazoan proteins whose activities might be regulated by assembly into ordered aggregates. The search algorithm was based on evolutionary sequence conservation patterns observed for yeast prion proteins, which contain aggregation-prone glutamine/asparagine (Q/N)-rich domains attached to functional domains of normal amino acid composition. We examined aggregation of Pum and its nematode ortholog PUF-9 by expression in yeast. A domain of Pum containing the Q/N-rich sequence, denoted as NQ1, the entire Pum N terminus, and the complete PUF-9 protein localize to macroscopic aggregates (foci) in yeast. NQ1 and PUF-9 can generate the yeast Pin+ trait, which is transmitted by a heritable aggregate. NQ1 also assembles into amyloid fibrils in vitro. In Drosophila, Pum regulates postsynaptic translation at neuromuscular junctions (NMJs). To assess whether NQ1 affects synaptic Pum activity in vivo, we expressed it in muscles. We found that it negatively regulates endogenous Pum, producing gene dosage-dependent pum loss-of-function NMJ phenotypes. NQ1 coexpression also suppresses lethality and NMJ phenotypes caused by overexpression of Pum in muscles. The Q/N block of NQ1 is required for these phenotypic effects. Negative regulation of Pum by NQ1 might be explained by formation of inactive aggregates, but we have been unable to demonstrate that NQ1 aggregates in Drosophila. NQ1 could also regulate Pum by a "dominant-negative" effect, in which it would block Q/N-mediated interactions of Pum with itself or with cofactors required for translational repression.

Interaction between a G-patch protein and a spliceosomal DEXD/H-box ATPase that is critical for splicing.

Prp2 is an RNA-dependent ATPase that activates the spliceosome before the first transesterification reaction of pre-mRNA splicing. Prp2 has extensive homology throughout the helicase domain characteristic of DEXD/H-box helicases and a conserved carboxyl-terminal domain also found in the spliceosomal helicases Prp16, Prp22, and Prp43. Despite the extensive homology shared by these helicases, each has a distinct, sequential role in splicing; thus, uncovering the determinants of specificity becomes crucial to the understanding of Prp2 and the other DEAH-splicing helicases. Mutations in an 11-mer near the C-terminal end of Prp2 eliminate its spliceosome binding and splicing activity. Here we show that a helicase-associated protein interacts with this domain and that this interaction contributes to the splicing process. First, a genome-wide yeast two-hybrid screen using Prp2 as bait identified Spp2, which contained a motif with glycine residues found in a number of RNA binding proteins. SPP2 was originally isolated as a genetic suppressor of a prp2 mutant. In a reciprocal screen, Spp2 specifically pulled out the C-terminal half of Prp2. Mutations in the Prp2 C-terminal 11-mer that disrupted function or spliceosome binding also disrupted Spp2 interaction. A screen of randomly mutagenized SPP2 clones identified an Spp2 protein with a mutation in the G patch that could restore interaction with Prp2 and enhanced splicing in a prp2 mutant strain. The study identifies a potential mechanism for Prp2 specificity mediated through a unique interaction with Spp2 and elucidates a role for a helicase-associated protein in the binding of a DEXD/H-box protein to the spliceosome.