Mechanical parameter assessment of fresh human cancellous bone of the femoral head in atraumatic femoral head necrosis and primary coxarthrosis.

BACKGROUND: Atraumatic femoral head necrosis is a rare pathological change of the femoral head. It is characterized by local necrosis of the cancellous bone as a result of reduced blood supply to the bone. Even today it remains unclear how to assess the hardness of the necrosis, whether it is soft tissue that is easily removed, or hard tissue that is difficult to resect. METHODS: Femoral heads with primary coxarthrosis were selected as a comparison group. For this purpose, 49 femoral heads obtained during total hip arthroplasty surgery with either condition (23 femoral head necrosis, 26 coxarthrosis) were transferred to the testing laboratory in fresh condition. Cylindrical specimens were obtained using a tenon cutter along the main trabecular load direction in the subchondral region of the femoral head. Additionally, thin bone slices were extracted proximal and distal to the specimens for density measurements. Brass plates were glued to the circular surfaces of the specimens. After curing of the adhesive, the specimens were mounted in the testing machine and destructive uniaxial compression tests were conducted. FINDINGS: The recorded mean compressive strengths and elastic moduli were almost identical for both groups, but the necrosis group showed significantly higher data scattering and range regarding the elastic modulus. The mean density of the coxarthrosis specimens was significantly higher than that of the necrotic specimens. INTERPRETATION: The mechanical properties of cancellous bone vary considerably in the presence of femoral head necrosis. The existence of hard necrosis implies a potential challenge regarding the clinical resection of these tissues.

Mixture effects of co-formulants and two plant protection products in a liver cell line.

Plant protection products (PPPs) consist of one or more active substances and several co-formulants. Active substances provide the functionality of the PPP and are consequently evaluated according to standard test methods set by legal data requirements before approval, whereas co-formulants' toxicity is not as comprehensively assessed. However, in some cases mixture effects of active substances and co-formulants might result in increased or different forms of toxicity. In a proof-of-concept study we hence built on previously published results of Zahn et al. (2018[38]) on the mixture toxicity of Priori Xtra® and Adexar® to specifically investigate the influence of co-formulants on the toxicity of these commonly used fungicides. Products, their respective active substances in combination as well as some co-formulants were applied to human hepatoma cell line (HepaRG) in several dilutions. Cell viability analysis, mRNA expression, abundance of xenobiotic metabolizing enzymes and intracellular concentrations of active substances determined by LC-MS/MS analyses demonstrated that the toxicity of the PPPs is influenced by the presence of co-formulants in vitro. PPPs were more cytotoxic than the mix of their active substances. Gene expression profiles of cells treated with the PPPs were similar to those treated with their respective mixture combinations with marked differences. Co-formulants can cause gene expression changes on their own. LC-MS/MS analyses revealed higher intracellular concentrations of active substances in cells treated with PPPs compared to those treated with the respective active substances' mix. Proteomic data showed co-formulants can induce ABC transporters and CYP enzymes. Co-formulants can contribute to the observed increased toxicity of PPPs compared to their active substances in combination due to kinetic interactions, necessitating a more comprehensive evaluation approach.

Atraumatic femoral head necrosis: a biomechanical, histological and radiological examination compared to primary hip osteoarthritis.

INTRODUCTION: Atraumatic necrosis of the femoral head (AFHN) is a common disease with an incidence of 5000-7000 middle-aged adults in Germany. There is no uniform consensus in the literature regarding the configuration of the bone in AFHN. The clinical picture of our patients varies from very hard bone, especially in idiopathic findings, and rather soft bone in cortisone-induced necrosis. A better understanding of the underlying process could be decisive for establishing a morphology-dependent approach. The aim of this study is the closer examination of the condition of the bone in the AFHN compared to the primary hip osteo arthritis (PHOA). MATERIALS AND METHODS: The preparations were obtained as part of elective endoprosthetic treatment of the hip joint. Immediately after sample collection, thin-slice CT of the preserved femoral heads was performed to determine the exact density of the bone in the necrosis zone. Reconstruction was done in 0.8-1 mm layers in two directions, coronary and axial, starting from the femoral neck axis. Density of the femoral heads was determined by grey value analysis. The value in Hounsfield units per sample head was averaged from three individual measurements to minimize fluctuations. For biomechanical and histomorphological evaluation, the samples were extracted in the load bearing zone perpendicular to the surface of the femoral head. Group-dependent statistical evaluation was performed using single factor variance analysis (ANOVA). RESULTS: A total of 41 patients with a mean age of 64.44 years were included. The mean bone density of the AFHN samples, at 1.432 g/cm3, was about 7% higher than in the PHOA group with a mean value of 1.350 g/cm3 (p = 0.040). The biomechanical testing in the AFHN group showed a 22% higher-but not significant-mean compressive strength (20.397 MPa) than in the PHOA group (16.733 MPa). On the basis of histological analysis, no differentiation between AFHN and PHOA samples was possible. CONCLUSIONS: The present study (NCT, evidence level II) shows that AFHN has a very well detectable higher bone density compared to PHOA. However, neither biomechanical stress tests nor histomorphological evaluation did show any significant difference between the groups. The results allow the conclusion that there is no "soft" necrosis at all in the AFHN group.

Influence of the fixation technique on the mechanical properties of human cancellous bone of the femoral head.

BACKGROUND: The femoral head is of central importance for the force transmission from the suprapelvic body mass to the lower extremity. However, the condition of the subcortical bone and its mechanical properties in case of pathological changes due to coxarthrosis or femoral head necrosis differ from the healthy condition. METHODS: Fresh femoral heads were gathered during hip total endoprosthesis surgeries and cylindrical cancellous bone samples were extracted with a hollow drill. By means of a uniaxial tensile-compression test system, the compressive strength was determined for two different specimen types (fresh and 24 h storage in acetone). Exemplary tests on an exceptionally large femoral head were performed to compare properties of fresh, fresh-deep-frozen and acetone-stored samples. FINDINGS: The deformation behaviour and the material parameters determined were very heterogeneous. For most of the specimens, a destructive material test was successfully carried out, i.e. the compressive strength was determined. The average strength of fresh specimens was slightly higher than that of acetone specimens. On the other hand, the average Young's modulus of the acetone specimens was higher than that of the fresh specimens. INTERPRETATION: The lower Young's moodulus of the fresh samples compared to the acetone samples could indicate a causal effect of the degreasing influence of the acetone. The partly considerable individual differences in compressive strength and failure compression can have patient-specific influencing factors such as constitution and physical fitness as well as causes in the initial pathological condition.

Podcasts as a teaching tool in orthopaedic surgery : Is it beneficial or more an exemption card from attending lectures?

OBJECTIVE: The aim of this study was to evaluate the influence of the introduction of online podcasts as part of the main lecture series in orthopaedics on the number of lecture attendees, the examination results and the assessment of teaching by the students. Additionally, we evaluated the use of other media for examination preparation. METHODOLOGY: At the beginning and end of the lecture series questionnaires were handed out to the students to evaluate their attitudes towards attending lectures, the use of video podcasts and examination preparation. In addition, the number of lecture attendees and podcast usage during the semester were counted and the statements of the students in the evaluation assessments of orthopaedic teaching were evaluated. The examination results were correlated in a statistical analysis with the learning materials provided by the students for examination preparation. RESULTS: At the end of the lecture series, 284 students stated that they used the lecture podcast about twice as often as attending lectures; however, for the majority of the students the provision of a video podcast was no reason not to attend the lecture. For example, 37.2% stated that they never and 26.8% stated that they rarely had not attended the lecture by providing the podcasts. Of the students 91-95% considered the availability of lecture podcasts to be a rather meaningful or very meaningful supplement to the lecture visit. Students increasingly used digital media to prepare for examinations instead of using traditional analogue methods. None of the learning methods or materials examined showed a statistically significant advantage in examination results. CONCLUSION: Students in the age of digitalization use a variety of learning materials and are no longer bound to classical analog teaching methods. The use of online podcasts had no negative impact on examination performance. Most students perceived lecture podcasts as a useful supplement to lecture attendance. The students praised the expansion of the teaching curriculum to include additional digital offers with positive comments in the evaluations, but without achieving an improvement in these student evaluations.

Assessment of iron oxide nanoparticle ecotoxicity on regeneration and homeostasis in the replacement model system Schmidtea mediterranea.

Iron oxide nanoparticles (IONs) are used in a number of applications, from food to cosmetics, from medical applications to magnetic storage. In spite of the 550 tons produced each year in Europe alone, no effective dose limit recommendations are established and the overall risks connected to IONs are still debated. The incorporation of IONs in daily life raises a concern about their effects on the environment, on living organisms, and on human health. In this study, we used freshwater planarians to assess the nanoecotoxicity of IONs. Planarians are free-living invertebrates known for their astonishing regenerative ability. Because of their sensitivity to toxicants, they are often used to determine the effects of toxic, genotoxic and carcinogenic environmental compounds with an approach in line with the 3Rs (Reduce, Refine, Replace) principle. Planarians were exposed to IONs at concentrations up to 1 mg/mL and their effects were evaluated at the behavioral, morphofunctional and molecular levels, with a special emphasis on the regeneration process. Our results indicate that IONs did not affect the stem cell population dynamics, nor did they induce substantial changes in either homeostatic or regenerating planarians. As positive controls, gold nanoparticles coated with the pro-apoptotic anti-cancer drug hexadecylmethylammonium bromide, silver nanoparticles and highly concentrated polystyrene nanoparticles were used. These all elicited toxic effects. Therefore, we conclude that IONs at environmental concentrations are safe for planarians, and that the planarian is a powerful model system that can replace vertebrate animal models in nanoecotoxicology research and for nanoecotoxicology studies.

Poly(amidoamine)-alginate hydrogels: directing the behavior of mesenchymal stem cells with charged hydrogel surfaces.

The surface charge of a biomaterial represents a promising tool to direct cellular behavior, which is crucial for therapeutic approaches in regenerative medicine. To expand the understanding of how the material surface charge affects protein adsorption and mesenchymal stem cell behavior, differently charged surfaces with zeta potentials spanning from -25 mV to +15 mV were fabricated by the conjugation of poly(amidoamine) to alginate-based hydrogels. We showed that the increase of the biomaterials surface charge resulted in enhanced quantities of biologically available, surface-attached proteins. Since different surface charges were equalized after protein adsorption, mesenchymal stem cells interacted rather with diverse protein compositions instead of different surface features. Besides an enhanced cell attachment to increasingly positively charged surfaces, the cell spreading area and the expression of adhesion-related genes integrin α5 and tensin 1 were found to be increased after adhesion. Moreover, first results indicate a potential impact of the surface charge on mesenchymal stem cell differentiation towards bone and fat cells. The improved understanding of surface charge-related cell behavior has significant impact on the design of biomedical devices and artificial organs.

First metatarsophalangeal joint arthrodesis versus proximal phalanx hemiarthroplasty for hallux rigidus: feasibility study for a randomised controlled trial.

BACKGROUND: Osteoarthritis of the first metatarsophalangeal joint (hallux rigidus) leads to pain and poor function and mobility. Arthrodesis is the gold standard treatment for end-stage disease. Total joint arthroplasties have been attempted, but early loosening has been attributed to dorsally directed shear forces on the metatarsal component. Metallic proximal phalangeal hemiarthroplasty theoretically avoids this. Whilst early results are promising, no comparative trials exist comparing this to arthrodesis. METHODS/DESIGN: The primary objectives are to determine the range of outcome scores between the two treatment arms (to inform a power calculation). Outcome measures will include the MOXFQ, AOFAS-Hallux and EuroQol EQ-5D-5 L. Secondary objectives are to determine the accrual rate, dropout rate and trial acceptability to both patients and surgeons. These data will allow the development of a larger trial with longer follow-up.This is a prospective randomised controlled single-centre study comparing proximal phalanx hemiarthroplasty (AnaToemic, Arthrex Ltd., Sheffield, UK) with arthrodesis (15 patients in each arm). Randomisation will be performed using a 1:1 allocation ratio in blocks of six.Patients meeting the eligibility criteria will be recruited from three foot and ankle consultant surgeon's clinics (East Lancashire Hospitals NHS Trust). If agreeable, informed consent will be obtained before patients are randomised.The outcome measure scores will be completed pre-operatively and repeated at 6 weeks, 3 months and 12 months. A radiological review will be performed at 6 weeks and 12 months to determine rates of loosening (hemiarthroplasty) and union (arthrodesis). Data on length of stay, return to work, complications and re-operation rates will also be collected.The analysis will compare the change in outcome scores between treatment groups at all follow-up time points. Scores will be compared using a Student t-test, adjusting for scores at baseline.This study will be conducted in accordance with the current revision of the Declaration of Helsinki (1996) and the ICH-GCP Guideline (International Conference on Harmonisation, Good Clinical Practice, E6(R1), 1996). This study has been approved by the sponsor, the Trust Research & Development office. Ethical approval has been received from the National Research Ethics Service (North East: 12/NE/0385 for protocol version 5.3 dated 3 June 2013). TRIAL REGISTRATION: Current Controlled Trials ISRCTN88273654.

Is the rate of re-operation after primary lumbar microdiscectomy affected by surgeon grade or intra-operative lavage of the disc space?

STUDY DESIGN. Retrospective audit of consecutive patients. OBJECTIve. To investigate the re-operation rate following elective primary lumbar microdiscectomy and to determine whether principal surgeon grade and/or disc space lavage is a factor in recurrence. SUMMARY OF BACKGROUND DATA. Recurrent herniation of disc material following lumbar microdiscecomy surgery is one of the commonest complications of the procedure. Any reduction in the number of revision microdiscectomies performed per year would have a significant impact on patients' lives and on the health service economy. We undertook this study to ascertain whether principal surgeon grade and/or disc space lavage has an impact in reducing the re-operation rate. METHODS. We undertook a retrospective audit of patients who underwent elective primary lumbar microdiscectomy, over a 3-year period (n = 971). RESULTS. The overall re-operation rate for primary elective microdiscectomy was 3.8%, consistent with the published literature. The relative risk of re-operation in patients primarily operated by registrar surgeons was 1.2 fold the risk in patients operated by consultants (95% CI: 0.62, 2.35) although not statistically significant (p = 0.568). The risk of re-operation in the 'non lavage' group was 2.15 times the risk in the 'lavage' group (95% CI: 0.63, 7.34), but it did not reach significance (p = 0.222). CONCLUSIONS. Principal surgeon grade and intervertebral disc lavage have not been found conclusively to be factors in the rate of recurrence. This information is useful to reassure patients that their outcome from such surgery is not dependent on the grade of surgeon performing the operation. There is a possible trend towards intervertebral disc lavage reducing the rate of recurrence.

Aire-dependent thymic development of tumor-associated regulatory T cells.

Despite considerable interest in the modulation of tumor-associated Foxp3(+) regulatory T cells (T(regs)) for therapeutic benefit, little is known about the developmental origins of these cells and the nature of the antigens that they recognize. We identified an endogenous population of antigen-specific T(regs) (termed MJ23 T(regs)) found recurrently enriched in the tumors of mice with oncogene-driven prostate cancer. MJ23 T(regs) were not reactive to a tumor-specific antigen but instead recognized a prostate-associated antigen that was present in tumor-free mice. MJ23 T(regs) underwent autoimmune regulator (Aire)-dependent thymic development in both male and female mice. Thus, Aire-mediated expression of peripheral tissue antigens drives the thymic development of a subset of organ-specific T(regs), which are likely coopted by tumors developing within the associated organ.

An organizing region in metamorphosing hydrozoan planula larvae--stimulation of axis formation in both larval and in adult tissue.

A novel wingless gene was isolated from the marine colonial hydroid Hydractinia echinata. Alignments and Bayesian inference analysis clearly assign the gene to the Wnt5A group. In line with data found for the brachyury ortholog of Hydractinia, He-wnt5A is expressed during metamorphosis in the posterior tip of the spindle-shaped planula larva, suggesting that the tip functions as a putative organizer during metamorphosis. Additionally, the outermost cells of the posterior tip are omitted from apoptosis during metamorphosis. In order to investigate this putative organizer function, we transplanted the posterior tip of metamorphosing animals into non-induced larvae and into primary polyps 24 h and 48 h of age. In larvae, the tip induced formation of a secondary axis. In polyps the building of ectopic head structures was induced. Based on our data on axis formation, on gene expression similar to the organizers of other species, and the absence of regular apoptosis, we conclude that the posterior tip of the Hydractinia larva has organizing activity during metamorphosis.

An atypical presentation of hallucial sesamoid avascular necrosis: a case report.

UNLABELLED: Sesamoid bone disorders are a rare cause of metatarsal pain and can be difficult to diagnose. This article describes an atypical case of avascular necrosis of the fibular sesamoid in a 62-year-old male. Avascular necrosis of the sesamoid is an infrequent and incompletely defined process. The case described in this report is somewhat atypical as this condition is usually associated with female sex, adolescence, or a precipitating factor of minor trauma. LEVEL OF CLINICAL EVIDENCE: 4.

Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement.

OBJECTIVES: Our prospective study tested the hypothesis that the 30-day clinical outcome of elective percutaneous catheter intervention (PCI) differs between strata defined by quartiles of platelet aggregation after loading with 600 mg clopidogrel. BACKGROUND: Platelet responses after loading with clopidogrel are highly variable. The impact of this variability on the peri-interventional risk of patients undergoing PCI has not been investigated prospectively. METHODS: Our study included 802 consecutive patients undergoing elective coronary stent placement. Before PCI, patients received a loading dose of 600 mg clopidogrel followed by 75 mg daily. Primary end point was the 30-day composite of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events [MACE]). Platelet aggregation was assessed immediately before PCI by optical aggregometry (5 micromol/l adenosine diphosphate). RESULTS: During 30-day follow-up, 15 patients (1.9%) incurred MACE (3 deaths, 8 myocardial infarctions, 8 target lesion revascularizations). Quartiles of platelet aggregation were <4%, 4% to 14%, 15% to 32%, and >32%. Thirty-day MACE differed significantly (p = 0.034) between quartiles of platelet aggregation. It was 0.5% in the first quartile, 0.5% in the second, 3.1% in the third, and 3.5% in the fourth. Platelet aggregation above the median carried a 6.7-fold risk (95% confidence interval 1.52 to 29.41; p = 0.003) of 30-day MACE. Multivariable logistic regression analysis, including pertinent covariables, confirmed platelet aggregation as a significant independent predictor of 30-day MACE (adjusted odds ratio per 10% increase in platelet aggregation 1.32, 95% confidence interval 1.04 to 1.61; p = 0.026). CONCLUSIONS: The level of platelet aggregation immediately before elective coronary stenting in patients pre-treated with a high loading dose of clopidogrel is correlated with early outcome after the procedure.

Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention.

BACKGROUND: Pretreatment with clopidogrel can reduce the risks associated with percutaneous coronary intervention (PCI). To shorten the time for clopidogrel to become effective, a 600-mg loading dose has been used. We sought to validate this regimen in a large cohort and investigated the time dependence of the antiplatelet effect of 600 mg of clopidogrel. METHODS AND RESULTS: Our study included 1001 patients who were scheduled for cardiac catheterization as potential candidates for PCI. We obtained blood samples before administration of 600 mg of clopidogrel and at the time of catheterization, which varied according to logistic needs. We assessed platelet aggregation by optical aggregometry and surface expression of P-selectin and activated glycoprotein IIb/IIIa by flow cytometry. Platelet aggregation induced by 5 micromol/L ADP was 51+/-14% when catheterization was performed at <1 hour, 41+/-14% at 1 to <2 hours, 37+/-15% at 2 to <4 hours, 36+/-13% at 4 to <6 hours, and 35+/-14% at > or =6 hours after clopidogrel administration. After 2 hours (n=718), the level of platelet aggregation and the surface expression of P-selectin and activated glycoprotein IIb/IIIa did not change significantly with time after clopidogrel (P>0.24 by univariate or multivariate regression). Comedication with CYP3A4 metabolized statins did not significantly affect platelet aggregation after clopidogrel (P=0.62). Among the 428 patients undergoing PCI, the 30-day composite rate of major adverse cardiac events was 1.9%, with no significant difference between patients undergoing PCI within 2 hours after clopidogrel loading and those undergoing PCI at a later time point. CONCLUSIONS: After loading with 600 mg of clopidogrel, the full antiplatelet effect of the drug is achieved after 2 hours. Statins do not interfere with the level of platelet inhibition after this dose.