The Elite-Plus stem migrates more than the flanged Charnley stem: A clinical, radiographic, and radiostereometric analysis of 114 patients with an average of 7 years follow-up

Background and purpose The Charnley Elite-Plus stem was introduced in 1993 as a presumed improvement of the flanged Charnley stem. We started this study in 1996 to investigate the migratory pattern of the Elite-Plus stem. Patients and methods We followed 114 patients with osteoarthritis and a primary total hip replacement with the Elite-Plus stem. Mean age at the time of operation was 64 (50-76) years. The mean follow-up time was 6.5 (2-7) years. Radiographs were evaluated with respect to cementing technique, migration, and wear measured by radiostereometry (RSA). Results The stem survival was 98% (CI: 96-100) at 7 years and 92% (CI: 86-97) at 10 years. Mean migration of the femoral head was 0.35 mm (SD 0.3) medially, 0.51 mm (SD 0.6) distally, and 1.1 mm (SD 1.8) in the dorsal direction. Mean total point motion was 1.7 mm (SD 1.7). The migration of the stems stabilized after 5 years in the medial and dorsal directions, but continued to subside slightly. Migration along any of the axes was higher if the cementing technique was inferior. Interpretation Patients with a Charnley Elite-Plus stem and defects in the cement mantle or other signs of inferior implantation technique should be carefully monitored

Intermediate predator naïveté and sex-skewed vulnerability predict the impact of an invasive higher predator

The spread of invasive species continues to reduce biodiversity across all regions and habitat types globally. However, invader impact prediction can be nebulous, and approaches often fail to integrate coupled direct and indirect invader effects. Here, we examine the ecological impacts of an invasive higher predator on lower trophic groups, further developing methodologies to more holistically quantify invader impact. We employ functional response (FR, resource use under different densities) and prey switching experiments to examine the trait- and density-mediated impacts of the invasive mosquitofish Gambusia affinis on an endemic intermediate predator Lovenula raynerae (Copepoda). Lovenula raynerae effectively consumed larval mosquitoes, but was naïve to mosquitofish cues, with attack rates and handling times of the intermediate predator unaffected by mosquitofish cue-treated water. Mosquitofish did not switch between male and female prey, consistently displaying a strong preference for female copepods. We thus demonstrate a lack of risk-reduction activity in the presence of invasive fish by L. raynerae and, in turn, high susceptibility of such intermediate trophic groups to invader impact. Further, we show that mosquitofish demonstrate sex-skewed predator selectivity towards intermediate predators of mosquito larvae, which may affect predator population demographics and, perversely, increase disease vector proliferations. We advocate the utility of FRs and prey switching combined to holistically quantify invasive species impact potential on native organisms at multiple trophic levels

Optimal central-place foraging by beavers: Tree-size selection in relation to defensive chemicals of quaking aspen

At a newly occupied pond, beavers preferentially felled aspen smaller than 7.5 cm in diameter and selected against larger size classes. After one year of cutting, 10% of the aspen had been cut and 14% of the living aspen exhibited the juvenile growth form. A phenolic compound which may act as a deterrent to beavers was found in low concentrations in aspen bark, and there was no significant regression of relative concentration of this compound on tree diameter. At a pond which had been intermittently occupied by beavers for over 20 years, beavers selected against aspen smaller than 4.5 cm in diameter, and selected in favor of aspen larger than 19.5 cm in diameter. After more than 28 years of cutting at this site, 51% of the aspen had been cut and 49% of the living aspen were juvenileform. The phenolic compound was found in significantly higher concentrations in aspen bark than at the newly occupied site, and there was a significant negative regression of relative concentration on tree diameter. The results of this study show that responses to browsing by trees place constraints on the predictive value of standard energy-based optimal foraging models, and limitations on the use of such models. Future models should attempt to account for inducible responses of plants to damage and increases in concentrations of secondary metabolites through time.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47775/1/442_2004_Article_BF00379963.pd

In silico pharmacodynamics, toxicity profile and biological activities of the Saharan medicinal plant Limoniastrum feei

ABSTRACT In-silico study was performed to find the pharmacodynamics, toxicity profiles and biological activities of three phytochemicals isolated from Limoniastrum feei (Plumbagenaceae). Online pharmacokinetic tools were used to estimate the potential of Quercetin, kaempferol-3-O-β-D-glucopyranoside (astragalin) and quercitin-7-O-β-D-glucopyranoside as specific drugs. Then the prediction of potential targets of these compounds were investigated using PharmMapper. Auto-Dock 4.0 software was used to investigate the different interactions of these compounds with the targets predicted earlier. The permeability of quercetin was found within the range stated by Lipinski ׳s rule of five. Hematopoietic prostaglandin (PG) D synthase (HPGDS), farnesyl diphosphate synthetase (FPPS) and the deoxycytidine kinase (DCK) were potential targets for quercetin, astragalin and quercetin 7, respectively. Quercetin showed antiallergic and anti-inflammatory activity, while astragalin and quercetin 7 were predicted to have anticancer activities. The activity of Astragalin appeared to be mediated by FPPS inhibition. The inhibition of DCK was predicted as the anticancer mechanisms of quercetin 7. The compounds showed interesting interactions and satisfactory binding energies when docked into their targets. These compounds are proposed to have activities against a variety of human aliments such as allergy, tumors, muscular dystrophy, and diabetic cataracts

Surface thermodynamic homeostasis of salivary conditioning films through polar–apolar layering

Salivary conditioning films (SCFs) form on all surfaces exposed to the oral cavity and control diverse oral surface phenomena. Oral chemotherapeutics and dietary components present perturbations to SCFs. Here we determine the surface energetics of SCFs through contact angle measurements with various liquids on SCFs following perturbations with a variety of chemotherapeutics as well as after renewed SCF formation. Sixteen-hour SCFs on polished enamel surfaces were treated with a variety of chemotherapeutics, including toothpastes and mouthrinses. After treatment with chemotherapeutics, a SCF was applied again for 3 h. Contact angles with four different liquids on untreated and treated SCF-coated enamel surfaces were measured and surface free energies were calculated. Perturbations either caused the SCF to become more polar or more apolar, but in all cases, renewed SCF formation compensated these changes. Thus, a polar SCF attracts different salivary proteins or adsorbs proteins in a different conformation to create a more apolar SCF surface after renewed SCF formation and vice versa for apolar SCFs. This polar–apolar layering in SCF formation presents a powerful mechanism in the oral cavity to maintain surface thermodynamic homeostasis—defining oral surface properties within a narrow, biological range and influencing chemotherapeutic strategies. Surface chemical changes brought about by dietary or chemotherapeutic perturbations to SCFs make it more polar or apolar, but new SCFs are rapidly formed compensating for changes in surface energetics

Unique Structure and Stability of HmuY, a Novel Heme-Binding Protein of Porphyromonas gingivalis

Infection, survival, and proliferation of pathogenic bacteria in humans depend on their capacity to impair host responses and acquire nutrients in a hostile environment. Among such nutrients is heme, a co-factor for oxygen storage, electron transport, photosynthesis, and redox biochemistry, which is indispensable for life. Porphyromonas gingivalis is the major human bacterial pathogen responsible for severe periodontitis. It recruits heme through HmuY, which sequesters heme from host carriers and delivers it to its cognate outer-membrane transporter, the TonB-dependent receptor HmuR. Here we report that heme binding does not significantly affect the secondary structure of HmuY. The crystal structure of heme-bound HmuY reveals a new all-β fold mimicking a right hand. The thumb and fingers pinch heme iron through two apical histidine residues, giving rise to highly symmetric octahedral iron co-ordination. The tetrameric quaternary arrangement of the protein found in the crystal structure is consistent with experiments in solution. It shows that thumbs and fingertips, and, by extension, the bound heme groups, are shielded from competing heme-binding proteins from the host. This may also facilitate heme transport to HmuR for internalization. HmuY, both in its apo- and in its heme-bound forms, is resistant to proteolytic digestion by trypsin and the major secreted proteases of P. gingivalis, gingipains K and R. It is also stable against thermal and chemical denaturation. In conclusion, these studies reveal novel molecular properties of HmuY that are consistent with its role as a putative virulence factor during bacterial infection

Treatment Efficacy, Clinical Utility, and Cost-Effectiveness of Multidisciplinary Biopsychosocial Rehabilitation Treatments for Persistent Low Back Pain: A Systematic Review

Study Design: Systematic review. Objectives: To review the current literature on the treatment efficacy, clinical utility, and cost-effectiveness of multidisciplinary biopsychosocial rehabilitation (MBR) for patients suffering from persistent (nonspecific) lower back pain (LBP) in relation to pain intensity, disability, health-related quality of life, and work ability/sick leave. Methods: We carried out a systematic search of Web of Science, Cochrane Library, PubMed Central, EMBASE, and PsycINFO for English- and German-language literature published between January 2010 and July 2017. Study selection consisted of exclusion and inclusion phases. After screening for duplication, studies were excluded on the basis of criteria covering study design, number of participants, language of publication, and provision of information about the intervention. All the remaining articles dealing with the efficacy, utility, or cost-effectiveness of intensive (more than 25 hours per week) MBR encompassing at least 3 health domains and cognitive behavioral therapy–based psychological education were included. Results: The search retrieved 1199 publications of which 1116 were duplicates or met the exclusion criteria. Seventy of the remaining 83 articles did not meet the inclusion criteria; thus 13 studies were reviewed. All studies reporting changes in pain intensity or disability over 12 months after MBR reported moderate effect sizes and/or p-values for both outcomes. The effects on health-related quality of life were mixed, but MBR substantially reduced costs. Overall MBR produced an enduring improvement in work ability despite controversy and variable results. Conclusions: MBR is an effective treatment for nonspecific LBP, but there is room for improvement in cost-effectiveness and impact on sick leave, where the evidence was less compelling

p21-activated kinase signaling in breast cancer

The p21-activated kinases signal through a number of cellular pathways fundamental to growth, differentiation and apoptosis. A wealth of information has accumulated at an impressive pace in the recent past, both with regard to previously identified targets for p21-activated kinases that regulate the actin cytoskeleton and cellular stress pathways and with regard to newly identified targets and their role in cancer. Emerging data also provide new clues towards a previously unappreciated link between these various cellular processes. The present review attempts to provide a quick tutorial to the reader about the evolving significance of p21-activated kinases and small GTPases in breast cancer, using information from mouse models, tissue culture studies, and human materials