Outcome in design-specific comparisons between highly crosslinked and conventional polyethylene in total hip arthroplasty 163,368 hip replacements in the Nordic Arthroplasty Register Association database with 5-11 years of follow-up

Background and purpose - Most registry studies regarding highly crosslinked polyethylene (XLPE) have focused on the overall revision risk. We compared the risk of cup and/or liner revision for specific cup and liner designs made of either XLPE or conventional polyethylene (CPE), regarding revision for any reason and revision due to aseptic loosening and/or osteolysis.Patients and methods - Using the Nordic Arthroplasty Register Association (NARA) database, we identified cup and liner designs where either XLPE or CPE had been used in more than 500 THAs performed for primary hip osteoarthritis. We assessed risk of revision for any reason and for aseptic loosening using Cox regression adjusted for age, sex, femoral head material and size, surgical approach, stem fixation, and presence of hydroxyapatite coating (uncemented cups).Results - The CPE version of the ZCA cup had a risk of revision for any reason similar to that of the XLPE version (p = 0.09), but showed a 6-fold higher risk of revision for aseptic loosening (p < 0.001). The CPE version of the Reflection All Poly cup had an 8-fold elevated risk of revision for any reason (p < 0.001) and a 5-fold increased risk of revision for aseptic loosening (p < 0.001). The Charnley Elite Ogee/Marathon cup and the Trilogy cup did not show such differences.Interpretation Whether XLPE has any advantage over CPE regarding revision risk may depend on the properties of the polyethylene materials being compared, as well as the respective cup designs, fixation type, and follow-up times. Further research is needed to elucidate how cup design factors interact with polyethylene type to affect the risk of revision

Development of the Synarcual in the Elephant Sharks (Holocephali; Chondrichthyes): Implications for Vertebral Formation and Fusion

The synarcual is a structure incorporating multiple elements of two or more anterior vertebrae of the axial skeleton, forming immediately posterior to the cranium. It has been convergently acquired in the fossil group ‘Placodermi’, in Chondrichthyes (Holocephali, Batoidea), within the teleost group Syngnathiformes, and to varying degrees in a range of mammalian taxa. In addition, cervical vertebral fusion presents as an abnormal pathology in a variety of human disorders. Vertebrae develop from axially arranged somites, so that fusion could result from a failure of somite segmentation early in development, or from later heterotopic development of intervertebral bone or cartilage. Examination of early developmental stages indicates that in the Batoidea and the ‘Placodermi’, individual vertebrae developed normally and only later become incorporated into the synarcual, implying regular somite segmenta- tion and vertebral development. Here we show that in the holocephalan Callorhinchus milii, uniform and regular vertebral segmentation also occurs, with anterior individual vertebra developing separately with subsequent fusion into a synarcual. Vertebral elements forming directly behind the synarcual continue to be incorporated into the synarcual through growth. This appears to be a common pattern through the Vertebrata. Research into human disor- ders, presenting as cervical fusion at birth, focuses on gene misexpression studies in humans and other mammals such as the mouse. However, in chondrichthyans, vertebral fusion represents the normal morphology, moreover, taxa such Leucoraja (Batoidea) and Callorhinchus (Holocephali) are increasingly used as laboratory animals, and the Callor- hinchus genome has been sequenced and is available for study. Our observations on synarcual development in three major groups of early jawed vertebrates indicate that fusion involves heterotopic cartilage and perichondral bone/mineralised cartilage developing outside the regular skeleton. We suggest that chondrichthyans have potential as ideal extant models for identifying the genes involved in these processes, for application to human skeletal heterotopic disorders

A Yersinia Effector with Enhanced Inhibitory Activity on the NF-κB Pathway Activates the NLRP3/ASC/Caspase-1 Inflammasome in Macrophages

A type III secretion system (T3SS) in pathogenic Yersinia species functions to translocate Yop effectors, which modulate cytokine production and regulate cell death in macrophages. Distinct pathways of T3SS-dependent cell death and caspase-1 activation occur in Yersinia-infected macrophages. One pathway of cell death and caspase-1 activation in macrophages requires the effector YopJ. YopJ is an acetyltransferase that inactivates MAPK kinases and IKKβ to cause TLR4-dependent apoptosis in naïve macrophages. A YopJ isoform in Y. pestis KIM (YopJKIM) has two amino acid substitutions, F177L and K206E, not present in YopJ proteins of Y. pseudotuberculosis and Y. pestis CO92. As compared to other YopJ isoforms, YopJKIM causes increased apoptosis, caspase-1 activation, and secretion of IL-1β in Yersinia-infected macrophages. The molecular basis for increased apoptosis and activation of caspase-1 by YopJKIM in Yersinia-infected macrophages was studied. Site directed mutagenesis showed that the F177L and K206E substitutions in YopJKIM were important for enhanced apoptosis, caspase-1 activation, and IL-1β secretion. As compared to YopJCO92, YopJKIM displayed an enhanced capacity to inhibit phosphorylation of IκB-α in macrophages and to bind IKKβ in vitro. YopJKIM also showed a moderately increased ability to inhibit phosphorylation of MAPKs. Increased caspase-1 cleavage and IL-1β secretion occurred in IKKβ-deficient macrophages infected with Y. pestis expressing YopJCO92, confirming that the NF-κB pathway can negatively regulate inflammasome activation. K+ efflux, NLRP3 and ASC were important for secretion of IL-1β in response to Y. pestis KIM infection as shown using macrophages lacking inflammasome components or by the addition of exogenous KCl. These data show that caspase-1 is activated in naïve macrophages in response to infection with a pathogen that inhibits IKKβ and MAPK kinases and induces TLR4-dependent apoptosis. This pro-inflammatory form of apoptosis may represent an early innate immune response to highly virulent pathogens such as Y. pestis KIM that have evolved an enhanced ability to inhibit host signaling pathways

Inferior outcome after hip resurfacing arthroplasty than after conventional arthroplasty: Evidence from the Nordic Arthroplasty Register Association (NARA) database, 1995 to 2007

Today, total hip arthroplasty (THA) is one of the safest and most efficient surgical treatments. New materials, surgical techniques and design concepts intended to improve THA have not always been successful. Thorough preclinical and early clinical investigations can detect some aspects of under-performing, while continuing surveillance is recommended to detect and analyze reasons for any later appearing flaws. In this thesis, several ways to monitor and assess THA performance are explored and carried out, using survival analysis in registry studies, radiostereometry (RSA), radiology and clinical outcome. In Paper I, a study using the Nordic Arthroplasty Register Association (NARA) registry shows that HRA had an almost 3-fold increased early non-septic revision risk and that risk factors were found to be female sex, certain HRA designs and units having performed few HRA procedures. Papers II and III contain comparisons of highly cross-linked polyethylene (XLPE) and conventional polyethylene (PE). XLPE had a considerably lower wear rate up to 10 years but showed no obvious improvements regarding implant fixation, BMD or clinical outcome. In the NARA registry, in 2 of 4 studied cup designs the XLPE version had a lower risk of revision for aseptic loosening compared to the PE version. Paper IV describes that stem subsidence and retrotorsion measured with RSA at 2 years predicted later aseptic stem failure in an unfavorably altered, previously well-functioning cemented femoral stem. In Paper V and VI, a novel approach to measure articulation wear with RSA in radiodense hip arthroplasty articulations was presented and evaluated. Subsequently, a comparison between ceramic-on-ceramic (COC) and metal-on-conventional PE uncemented THA displayed a considerably lower wear rate, smaller periacetabular bone lesions and a relatively high squeaking rate, the latter with unknown long-term consequences, in the COC hips. Implant fixation, heterotopic ossification and clinical outcome did not differ between articulation types. In conclusion, it was confirmed that implant surveillance can be done with RSA, also in radiodense THA. Early migration predicts later aseptic implant failure. Prolonged surveillance can confirm long-term material and design performance, verify or contradict anticipated advantages as well as detect unanticipated long-term complications

Molecular dynamics of ribosomal elongation factors G and Tu

Translation on the ribosome is controlled by external factors. During polypeptide lengthening, elongation factors EF-Tu and EF-G consecutively interact with the bacterial ribosome. EF-Tu binds and delivers an aminoacyl-tRNA to the ribosomal A site and EF-G helps translocate the tRNAs between their binding sites after the peptide bond is formed. These processes occur at the expense of GTP. EF-Tu:tRNA and EF-G are of similar shape, share a common binding site, and undergo large conformational changes on interaction with the ribosome. To characterize the internal motion of these two elongation factors, we used 25 ns long all-atom molecular dynamics simulations. We observed enhanced mobility of EF-G domains III, IV, and V and of tRNA in the EF-Tu:tRNA complex. EF-Tu:GDP complex acquired a configuration different from that found in the crystal structure of EF-Tu with a GTP analogue, showing conformational changes in the switch I and II regions. The calculated electrostatic properties of elongation factors showed no global similarity even though matching electrostatic surface patches were found around the domain I that contacts the ribosome, and in the GDP/GTP binding region

Role of pathogenic oral flora in postoperative pneumonia following brain surgery

<p>Abstract</p> <p>Background</p> <p>Post-operative pulmonary infection often appears to result from aspiration of pathogens colonizing the oral cavity. It was hypothesized that impaired periodontal status and pathogenic oral bacteria significantly contribute to development of aspiration pneumonia following neurosurgical operations. Further, the prophylactic effects of a single dose preoperative cefazolin on the oral bacteria were investigated.</p> <p>Methods</p> <p>A matched cohort of 18 patients without postoperative lung complications was compared to 5 patients who developed pneumonia within 48 hours after brain surgery. Patients waiting for elective operation of a single brain tumor underwent dental examination and saliva collection before surgery. Bacteria from saliva cultures were isolated and periodontal disease was scored according to type and severity. Patients received 15 mg/kg cefazolin intravenously at the beginning of surgery. Serum, saliva and bronchial secretion were collected promptly after the operation. The minimal inhibitory concentrations of cefazolin regarding the isolated bacteria were determined. The actual antibiotic concentrations in serum, saliva and bronchial secretion were measured by capillary electrophoresis upon completion of surgery. Bacteria were isolated again from the sputum of postoperative pneumonia patients.</p> <p>Results</p> <p>The number and severity of coexisting periodontal diseases were significantly greater in patients with postoperative pneumonia in comparison to the control group (p = 0.031 and p = 0.002, respectively). The relative risk of developing postoperative pneumonia in high periodontal score patients was 3.5 greater than in patients who had low periodontal score (p < 0.0001). Cefazolin concentration in saliva and bronchial secretion remained below detectable levels in every patient.</p> <p>Conclusion</p> <p>Presence of multiple periodontal diseases and pathogenic bacteria in the saliva are important predisposing factors of postoperative aspiration pneumonia in patients after brain surgery. The low penetration rate of cefazolin into the saliva indicates that its prophylactic administration may not be sufficient to prevent postoperative aspiration pneumonia. Our study suggests that dental examination may be warranted in order to identify patients at high risk of developing postoperative respiratory infections.</p

Early Gnathostome Phylogeny Revisited: Multiple Method Consensus

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.A series of recent studies recovered consistent phylogenetic scenarios of jawed vertebrates, such as the paraphyly of placoderms with respect to crown gnathostomes, and antiarchs as the sister group of all other jawed vertebrates. However, some of the hylogenetic relationships within the group have remained controversial, such as the positions of Entelognathus, ptyctodontids, and the Guiyu-lineage that comprises Guiyu, Psarolepis and Achoania. The revision of the dataset in a recent study reveals a modified phylogenetic hypothesis, which shows that some of these phylogenetic conflicts were sourced from a few inadvertent miscodings. The interrelationships of early gnathostomes are addressed based on a combined new dataset with 103 taxa and 335 characters, which is the most comprehensive morphological dataset constructed to date. This dataset is investigated in a phylogenetic context using maximum parsimony (MP), Bayesian inference (BI) and maximum likelihood (ML) approaches in an attempt to explore the consensus and incongruence between the hypotheses of early gnathostome interrelationships recovered from different methods. Our findings consistently corroborate the paraphyly of placoderms, all `acanthodians' as a paraphyletic stem group of chondrichthyans, Entelognathus as a stem gnathostome, and the Guiyu-lineage as stem sarcopterygians. The incongruence using different methods is less significant than the consensus, and mainly relates to the positions of the placoderm Wuttagoonaspis, the stem chondrichthyan Ramirosuarezia, and the stem osteichthyan LophosteusÐthe taxa that are either poorly known or highly specialized in character complement. Given that the different performances of each phylogenetic approach, our study provides an empirical case that the multiple phylogenetic analyses of morphological data are mutually complementary rather than redundant