Performance of the resurfaced hip. Part 2: the influence of prosthesis stem design on remodelling and fracture of the femoral neck

Hip resurfacing is a popular treatment for osteoarthritis in young, active patients. Previous studies have shown that occasional failures – femoral neck fracture and implant loosening, possibly associated with bone adaptation – are affected by prosthesis sizing and positioning, in addition to patient and surgical factors. With the aim of improving tolerance to surgical variation, finite element modelling was used to indicate the effects of prosthesis metaphyseal stem design on bone remodelling and femoral neck fracture, with a range of implant orientations. The analysis suggested that the intact femoral neck strength in trauma could be maintained across a wider range of varus–valgus orientations for short-stemmed and stemless prostheses. Furthermore, the extent of periprosthetic bone remodelling was lower for the short-stemmed implant, with slightly reduced stress shielding and considerably reduced densification around the stem, potentially preventing further progressive proximal stress shielding. The study suggests that a short-stemmed resurfacing head offers improved tolerance to misalignment and remodelling stimulus over traditional designs. While femoral neck fracture and implant loosening are multifactorial, biomechanical factors are of clear importance to the clinical outcome, so this may reduce the risk for patients at the edge of the indications for hip resurfacing, or shorten the surgical learning curve.<br/

Mathematical evaluation of jumping distance in total hip arthroplasty: Influence of abduction angle, femoral head offset, and head diameter

Background and purpose The jumping distance (JD) is the degree of lateral translation of the femoral head center required before dislocation occurs. The smaller the distance, the higher the theoretical risk of dislocation. The aim of our study was to evaluate this jumping distance and its variation according to the characteristics of the implant, and also the theoretical gain in using large head diameters of above 38 mm

Catalysis of water oxidation in acetonitrile by iridium oxide nanoparticles

Water oxidation catalysed by iridium oxide nanoparticles (IrO2 NPs) in water–acetonitrile mixtures using [RuIII(bpy)3]3+ as oxidant was studied as a function of the water content, the acidity of the reaction media and the catalyst concentration. It was observed that under acidic conditions (HClO4) and at high water contents (80% (v/v)) the reaction is slow, but its rate increases as the water content decreases, reaching a maximum at approximately equimolar proportions (≈25% H2O (v/v)). The results can be rationalized based on the structure of water in water–acetonitrile mixtures. At high water fractions, water is present in highly hydrogen-bonded arrangements and is less reactive. As the water content decreases, water clustering gives rise to the formation of water-rich micro-domains, and the number of bonded water molecules decreases monotonically. The results presented herein indicate that non-bonded water present in the water micro-domains is considerably more reactive towards oxygen production. Finally, long term electrolysis of water–acetonitrile mixtures containing [RuII(bpy)3]2+ and IrO2 NPs in solution show that the amount of oxygen produced is constant with time demonstrating that the redox mediator is stable under these experimental conditions

Healing Multiculturalism: Middle-Ground Liberal Forgiveness in a Diverse Public Realm

This article examines debates about political forgiveness in liberal, pluralist societies. Although the concept of forgiveness is not usually taken up by liberals, I outline a plausible conception by exploring two recent approaches. The first, ‘unattached articulation’, concept requires no real emotional change on the forgiver’s part, but rather a form of civic restraint. In contrast, the second version highlights a strong form of empathy for perpetrators. In spite of their advantages, each concept proves too extreme. The problems are revealed by focusing on the case of the Harkis, who fought for the French during the Algerian war. Often still marginalised in French society, their case helps to highlight the conceivability of a ‘middle-ground’ or moderate concept of political forgiveness. Its core rests on the forgiver’s care for the social world. While this concept brings considerable challenges also, and is not inevitable in any particular case, it entails a more plausible combination of emotional and rational shifts in the forgiver’s world-view. Although the article does not recommend forgiveness by any person or group, it observes, recalling Arendt’s idea of amor mundi or ‘love of the world’, that political forgiveness may sustain a viable connection between diverse citizens’ public and non-public lives

Selection of Diethylstilbestrol-Specific Single-Chain Antibodies from a Non-Immunized Mouse Ribosome Display Library

Single chain variable fragments (scFvs) against diethylstilbestrol (DES) were selected from the splenocytes of non-immunized mice by ribosome display technology. A naive library was constructed and engineered to allow in vitro transcription and translation using an E. coli lysate system. Alternating selection in solution and immobilization in microtiter wells was used to pan mRNA-ribosome-antibody (ARM) complexes. After seven rounds of ribosome display, the expression vector pTIG-TRX containing the selected specific scFv DNAs were transformed into Escherichia coli BL21 (DE3) for expression. Twenty-six positive clones were screened and five clones had high antibody affinity and specificity to DES as evidenced by indirect competitive ELISA. Sequence analysis showed that these five DES-specific scFvs had different amino acid sequences, but the CDRs were highly similar. Surface plasmon resonance (SPR) analysis was used to determine binding kinetics of one clone (30-1). The measured KD was 3.79 µM. These results indicate that ribosome display technology can be used to efficiently isolate hapten-specific antibody (Ab) fragments from a naive library; this study provides a methodological framework for the development of novel immunoassays for multiple environmental pollutants with low molecular weight detection using recombinant antibodies

Clinical Practice Recommendations on Genetic Testing of CYP2C9 and VKORC1 Variants in Warfarin Therapy

Objective: To systematically review evidence on genetic variants influencing outcomes during warfarin therapy and provide practice recommendations addressing the key questions: (1) Should genetic testing be performed in patients with an indication for warfarin therapy to improve achievement of stable anticoagulation and reduce adverse effects? (2) Are there subgroups of patients who may benefit more from genetic testing compared with others? (3) How should patients with an indication for warfarin therapy be managed based on their genetic test results? Methods: A systematic literature search was performed for VKORC1 and CYP2C9 and their association with warfarin therapy. Evidence was critically appraised, and clinical practice recommendations were developed based on expert group consensus. Results: Testing of VKORC1 (-1639G\u3eA), CYP2C92, and CYP2C93 should be considered for all patients, including pediatric patients, within the first 2 weeks of therapy or after a bleeding event. Testing for CYP2C95, 6, 8, or 11 and CYP4F2 (V433M) is currently not recommended. Testing should also be considered for all patients who are at increased risk of bleeding complications, who consistently show out-of-range international normalized ratios, or suffer adverse events while receiving warfarin. Genotyping results should be interpreted using a pharmacogenetic dosing algorithm to estimate the required dose. Significance: This review provides the latest update on genetic markers for warfarin therapy, clinical practice recommendations as a basis for informed decision making regarding the use of genotype-guided dosing in patients with an indication for warfarin therapy, and identifies knowledge gaps to guide future research.

Clinical Practice Recommendations for the Management and Prevention of Cisplatin-Induced Hearing Loss Using Pharmacogenetic Markers

Currently no pharmacogenomics-based criteria exist to guide clinicians in identifying individuals who are at risk of hearing loss from cisplatin-based chemotherapy. This review summarizes findings from pharmacogenomic studies that report genetic polymorphisms associated with cisplatin-induced hearing loss and aims to (1) provide up-to-date information on new developments in the field, (2) provide recommendations for the use of pharmacogenetic testing in the prevention, assessment, and management of cisplatin-induced hearing loss in children and adults, and (3) identify knowledge gaps to direct and prioritize future research. These practice recommendations for pharmacogenetic testing in the context of cisplatin-induced hearing loss reflect a review and evaluation of recent literature, and are designed to assist clinicians in providing optimal clinical care for patients receiving cisplatin-based chemotherapy

Practicing Imperfect Forgiveness

Forgiveness is typically regarded as a good thing - even a virtue - but acts of forgiveness can vary widely in value, depending on their context and motivation. Faced with this variation, philosophers have tended to reinforce everyday concepts of forgiveness with strict sets of conditions, creating ideals or paradigms of forgiveness. These are meant to distinguish good or praiseworthy instances of forgiveness from problematic instances and, in particular, to protect the self-respect of would-be forgivers. But paradigmatic forgiveness is problematic for a number of reasons, including its inattention to forgiveness as a gendered trait. We can account for the values and the risks associated with forgiving far better if we treat it as a moral practice and not an ideal

Promoter methylation and large intragenic rearrangements of DPYD are not implicated in severe toxicity to 5-fluorouracil-based chemotherapy in gastrointestinal cancer patients

<p>Abstract</p> <p>Background</p> <p>Severe toxicity to 5-fluorouracil (5-FU) based chemotherapy in gastrointestinal cancer has been associated with constitutional genetic alterations of the dihydropyrimidine dehydrogenase gene (<it>DPYD</it>).</p> <p>Methods</p> <p>In this study, we evaluated <it>DPYD </it>promoter methylation through quantitative methylation-specific PCR and screened <it>DPYD </it>for large intragenic rearrangements in peripheral blood from 45 patients with gastrointestinal cancers who developed severe 5-FU toxicity. <it>DPYD </it>promoter methylation was also assessed in tumor tissue from 29 patients</p> <p>Results</p> <p>Two cases with the IVS14+1G > A exon 14 skipping mutation (c.1905+1G > A), and one case carrying the 1845 G > T missense mutation (c.1845G > T) in the DPYD gene were identified. However, <it>DPYD </it>promoter methylation and large <it>DPYD </it>intragenic rearrangements were absent in all cases analyzed.</p> <p>Conclusions</p> <p>Our results indicate that <it>DPYD </it>promoter methylation and large intragenic rearrangements do not contribute significantly to the development of 5-FU severe toxicity in gastrointestinal cancer patients, supporting the need for additional studies on the mechanisms underlying genetic susceptibility to severe 5-FU toxicity.</p

Role of Cellular Heparan Sulfate Proteoglycans in Infection of Human Adenovirus Serotype 3 and 35

Species B human adenoviruses (Ads) are increasingly associated with outbreaks of acute respiratory disease in U.S. military personnel and civil population. The initial interaction of Ads with cellular attachment receptors on host cells is via Ad fiber knob protein. Our previous studies showed that one species B Ad receptor is the complement receptor CD46 that is used by serotypes 11, 16, 21, 35, and 50 but not by serotypes 3, 7, and 14. In this study, we attempted to identify yet-unknown species B cellular receptors. For this purpose we used recombinant Ad3 and Ad35 fiber knobs in high-throughput receptor screening methods including mass spectrometry analysis and glycan arrays. Surprisingly, we found that the main interacting surface molecules of Ad3 fiber knob are cellular heparan sulfate proteoglycans (HSPGs). We subsequently found that HSPGs acted as low-affinity co-receptors for Ad3 but did not represent the main receptor of this serotype. Our study also revealed a new CD46-independent infection pathway of Ad35. This Ad35 infection mechanism is mediated by cellular HSPGs. The interaction of Ad35 with HSPGs is not via fiber knob, whereas Ad3 interacts with HSPGs via fiber knob. Both Ad3 and Ad35 interacted specifically with the sulfated regions within HSPGs that have also been implicated in binding physiologic ligands. In conclusion, our findings show that Ad3 and Ad35 directly utilize HSPGs as co-receptors for infection. Our data suggest that adenoviruses evolved to simulate the presence of physiologic HSPG ligands in order to increase infection