Cup positioning and its effect on polyethylene wear of vitamin E- and non-vitamin E-supplemented liners in total hip arthroplasty: radiographic outcome at 5-year follow-up.

BACKGROUND: Aseptic loosening remains a challenging problem after total hip arthroplasty. Accurate cup placement and supplementation of antioxidants in acetabular liners might reduce material failure rates. The aim of this study is to assess the effect of the cup position on the wear behaviour of UHMWPE-XE and UHMWPE-X liners in vivo using virtual radiographs. METHODS: We conducted a prospective, randomized, controlled, multicenter trial. Clinical data of 372 probands were analyzed. Anteroposterior pelvic X-rays of 324 patients immediately postoperatively and after 1 and 5 years were evaluated by the RayMatch® analysis software regarding cup position and wear behaviour. RESULTS: Mean cup anteversion was 20.3° (± 7.4) and inclination was 41.9° (± 7.0) postoperatively. 62.3% of all patients had an anteversion and inclination within the Lewinnek safe zone. Anterior and anterolateral approaches led to significantly higher cup anteversion compared to lateral approaches (27.3° ± 5.5; 20.9° ± 7.2; 17.5° ± 6.6; p < 0.001 and p = 0.001, respectively). Mean anteversion increased to 24.6° (± 8.0) after 1 year (p < 0.001). Only one revision occurred because of implant dislocation. Wear rates from UHMWPE-X and UHMWPE-XE did not differ significantly. Anteversion angles ≥ 25° correlated to increased polyethylene wear (23.7 µm/year ± 12.8 vs. 31.1 µm/year ± 22.8, p = 0.012) and this was amplified when inclination angles were ≥ 50° (23.6 µm/year ± 12.8 vs. 38.0 µm/year ± 22.7, p = 0.062). CONCLUSION: Anterior approaches lead to the highest inaccuracy of cup placement, but cup positioning outside the Lewinnek safe zone does not necessarily cause higher dislocation rates. Moreover, mean anteversion increased by approximately four degrees within the first year after operation, which is expected to be functional due to a regularization of pelvic tilt after intervention. Mid-term wear rates of UHMWPE-X and UHMWPE-XE liners are comparable, but steep cup positions lead to significantly increased polyethylene wear. In summary, a re-evaluation of target zones for intraoperative cup positioning might be considered. In the long-term reduced oxidative embrittlement could lead to superior wear behaviour of vitamin E-blended liners.

Wearable adjunct ozone and antibiotic therapy system for treatment of Gram-negative dermal bacterial infection.

The problematic combination of a rising prevalence of skin and soft tissue infections and the growing rate of life-threatening antibiotic resistant infections presents an urgent, unmet need for the healthcare industry. These evolutionary resistances originate from mutations in the bacterial cell walls which prevent effective diffusion of antibiotics. Gram-negative bacteria are of special consideration due to the natural resistance to many common antibiotics due to the unique bilayer structure of the cell wall. The system developed here provides one solution to this problem through a wearable therapy that delivers and utilizes gaseous ozone as an adjunct therapy with topical antibiotics through a novel dressing with drug-eluting nanofibers (NFs). This technology drastically increases the sensitivity of Gram-negative bacteria to common antibiotics by using oxidative ozone to bypass resistances created by the bacterial cell wall. To enable simple and effective application of adjunct therapy, ozone delivery and topical antibiotics have been integrated into a single application patch. The drug delivery NFs are generated via electrospinning in a fast-dissolve PVA mat without inducing decreasing gas permeability of the dressing. A systematic study found ozone generation at 4 mg/h provided optimal ozone levels for high antimicrobial performance with minimal cytotoxicity. This ozone treatment was used with adjunct therapy delivered by the system in vitro. Results showed complete eradication of Gram-negative bacteria with ozone and antibiotics typically used only for Gram-positive bacteria, which showed the strength of ozone as an enabling adjunct treatment option to sensitize bacteria strains to otherwise ineffective antibiotics. Furthermore, the treatment is shown through biocompatibility testing to exhibit no cytotoxic effect on human fibroblast cells.

Simulating reading acquisition: The link between reading outcome and multimodal brain signatures of letter-speech sound learning in prereaders.

During reading acquisition, neural reorganization of the human brain facilitates the integration of letters and speech sounds, which enables successful reading. Neuroimaging and behavioural studies have established that impaired audiovisual integration of letters and speech sounds is a core deficit in individuals with developmental dyslexia. This longitudinal study aimed to identify neural and behavioural markers of audiovisual integration that are related to future reading fluency. We simulated the first step of reading acquisition by performing artificial-letter training with prereading children at risk for dyslexia. Multiple logistic regressions revealed that our training provides new precursors of reading fluency at the beginning of reading acquisition. In addition, an event-related potential around 400 ms and functional magnetic resonance imaging activation patterns in the left planum temporale to audiovisual correspondences improved cross-validated prediction of future poor readers. Finally, an exploratory analysis combining simultaneously acquired electroencephalography and hemodynamic data suggested that modulation of temporoparietal brain regions depended on future reading skills. The multimodal approach demonstrates neural adaptations to audiovisual integration in the developing brain that are related to reading outcome. Despite potential limitations arising from the restricted sample size, our results may have promising implications both for identifying poor-reading children and for monitoring early interventions.

Isoflavone supplementation in postmenopausal women does not affect leukocyte LDL receptor and scavenger receptor CD36 expression: A double-blind, randomized, placebo-controlled trial.

SCOPE: Isoflavones are discussed to improve serum lipoproteins and body composition and to reduce cardiovascular disease risk in postmenopausal women (PMW). LDL receptors (LDLR) and scavenger receptor CD36 (CD36) play a pivotal role in the regulation of plasma LDL-cholesterol concentrations (LDL-chol). We investigated the impact of isoflavones on the receptor expression of both receptors in leukocytes of PMW. METHODS AND RESULTS: A randomized, double-blind, placebo-controlled trial in parallel design was conducted to assess the effects of an isoflavone-enriched soy extract (117.4 mg/day isoflavone aglycone equivalents) for 12 weeks on serum LDL-chol, LDLR, and CD36 expression on leukocytes in 170 healthy PMW. Baseline and after 12 weeks, blood lipid concentrations, anthropometric data and body composition were determined. Receptor expression on leukocytes was measured by means of flow cytometry. After the intervention, no significant differences were found for LDLR and CD36 expression on leukocytes. A significant increase of serum LDL-chol was shown for the isoflavone group (p = 0.03) after 12 weeks. Body fat content and VAT were not affected. CONCLUSION: Isoflavone supplementation for 12 weeks did not change LDLR and CD36 expression on leukocytes of PMW and did not affect body fat content and visceral adipose tissue (VAT), but slightly increased serum LDL-chol.

Effects of a dietary intervention with conjugated linoleic acid on immunological and metabolic parameters in children and adolescents with allergic asthma--a placebo-controlled pilot trial.

BACKGROUND: Circumstantial evidence suggests that conjugated linoleic acid (CLA) beneficially modulates immune function in allergic subjects. C9,t11-CLA, naturally occurring in ruminant fats, is suggested to be the effective isomer. In contrast, for the t10,c12-CLA isomer, which is naturally found only in traces but usually constitutes a relevant part in commercial CLA mixtures, adverse effects have been reported. Aim of this study was to assess putative immunomodulatory effects of highly enriched c9,t11-CLA in allergic subjects. To our best knowledge, our study is the first in that a CLA preparation was used for such purpose which was free of t10,c12-CLA. DESIGN: Twenty-nine asthmatic children and adolescents (age 6-18 y) with diagnosed allergic sensitization against grass pollen, house dust mite, or cat hair/epithelia consumed daily a portion of yoghurt containing either 3 g CLA (75 % c9,t11-CLA, 87 % purity) or placebo (safflower oil) over a period of 12 weeks. At study start and end, lung function parameters, specific IgE, in vitro allergen-induced cytokine production in peripheral blood mononuclear cells (PBMC), plasma ECP, urinary 8-oxodG as marker of oxidation, fatty acid profiles of erythrocytes, and routine haematological parameters were determined. Prior to blood samplings, 3-days dietary records were requested. Throughout the study, the participants documented daily their peak expiratory flow and kept protocol about their allergy symptoms and usage of demand medication. RESULTS: In contrast to the CLA group, PBMC-produced IFN-γ and IL-4 increased significantly and by trend, respectively, in the placebo group. Moreover, plasma ECP tended to increase in the placebo group. In the pollen subgroup, FEV1 improved upon both CLA and placebo oil supplementation. In both intervention groups, the n-6/n-3 PUFA ratio in red blood cells decreased, mainly due to an increase in n-3 PUFA. Moreover, 8-oxodG excretion increased in both groups. No changes occurred regarding specific IgE concentrations, allergy symptoms, and volume parameters. CONCLUSION: Our results indicate that CLA modestly dampens the inflammatory response on the cellular level. A clinically relevant amelioration of the symptoms could not be proved in atopic manifest patients. TRIAL REGISTRATION: NCT01026506.

From assistance towards restoration with epidural brain-computer interfacing.

PURPOSE: Today's implanted brain-computer interfaces make direct contact with the brain or even penetrate the tissue, bearing additional risks with regard to safety and stability. What is more, these approaches aim to control prosthetic devices as assistive tools and do not yet strive to become rehabilitative tools for restoring lost motor function. METHODS: We introduced a less invasive, implantable interface by applying epidural electrocorticography in a chronic stroke survivor with a persistent motor deficit. He was trained to modulate his natural motor-related oscillatory brain activity by receiving online feedback. RESULTS: Epidural recordings of field potentials in the beta-frequency band projecting onto the anatomical hand knob proved most successful in discriminating between the attempt to move the paralyzed hand and to rest. These spectral features allowed for fast and reliable control of the feedback device in an online closed-loop paradigm. Only seven training sessions were required to significantly improve maximum wrist extension. CONCLUSIONS: For patients suffering from severe motor deficits, epidural implants may decode and train the brain activity generated during attempts to move with high spatial resolution, thus facilitating specific and high-intensity practice even in the absence of motor control. This would thus transform them from pure assistive devices to restorative tools in the context of reinforcement learning and neurorehabilitation.

Limited Applicability of GW9662 to Elucidate PPARγ-Mediated Fatty Acid Effects in Primary Human T-Helper Cells.

Synthetic antagonists of the nuclear receptor PPARγ such as GW9662 are widely used to elucidate receptor-mediated ligand effects. In addition and complementary to recent work, we examined whether GW9662 is suitable to serve for mechanistic investigation in T-helper cells. Human peripheral blood mononuclear cells (PBMC) were preincubated with increasing concentrations of GW9662 (0, 0.4, 2, and 10 µmol/L) 30 min before adding the c9,t11-isomer of conjugated linoleic acid (c9,t11-CLA) as representative of PPARγ-activating fatty acids with immunomodulatory properties. Corresponding cultures were incubated with GW9662 in the absence of the fatty acid. After 19 h, cells were mitogen stimulated for further 5 h. Subsequently, intracellular IL-2 was measured in CD3(+)CD4(+) lymphocytes by means of flow cytometry. 100 µmol/L c9,t11-CLA reduced the number of T-helper cells expressing IL-2 by 68%. GW9662 failed to abrogate this fatty acid effect, likely due to the fact that the compound exerted an own inhibitory effect on IL-2 production. Moreover, GW9662 dose-dependently induced cell death in human leukocytes. These results suggest that application of GW9662 is not conducive in this experimental setting.

Degradation of folic acid in fortified vitamin juices during long term storage.

Folic acid (FA) concentrations of nine fortified vitamin juices were determined with the aim to study the FA degradation and to investigate the deviation from the declared label value. The juices were received shortly after bottling and were analyzed monthly during controlled storage conditions (light and dark) over one year. The analyses were performed by HPLC-MS/MS, which included a fast "dilute and shoot" sample preparation. Average decreases in FA concentration of 46% were observed after one year. Fresh juices (shortly after bottling) showed the highest deviations from the declared label value (up to+89%). Label values did not reflect the actual concentration of FA in these products, making it difficult to determine the intake of this vitamin.

Dietary walnut oil modulates liver steatosis in the obese Zucker rat.

PURPOSE: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome. We aimed to clarify the impact of dietary walnut oil versus animal fat on hepatic steatosis, representing the initial step of multistage pathogenesis of NAFLD, in Zucker obese rats. METHODS: Zucker lean ad libitum (a.l.), Zucker obese a.l. or Zucker obese pair fed (p.f.) to the lean received isocaloric diets containing 8% walnut oil (W8), W14 or 14% lard (L14) (n = 10/group). Body weight, clinical serology, liver weight, lipid content and fatty acid composition and hepatic lipid metabolism-related transcripts were evaluated. RESULTS: Compared to lean, Zucker obese a.l. and p.f. showed hepatic triacylglyceride (TAG) accumulation. In Zucker obese p.f., W14 compared to W8 and L14 reduced liver lipids, TAG as well as hepatic omega-6 (n-6)/n-3 ratio and SCD activity index [(C18:0 + C18:1)/C18:0 ratio] paralleled by decreased lipoprotein lipase mRNA in obese p.f. and elevated microsomal triglyceride transfer protein mRNA in lean and obese. Further, W14 elevated the fasting blood TAG and reduced cholesterol levels in obese. CONCLUSIONS: In our model, consumption of W14 inhibited hepatic lipid accumulation along with modulated hepatic gene expression implicated in hepatic fatty acid influx or lipoprotein assembly. These results provide first indication that dietary lipids from walnut oil are modulators of hepatic steatosis as the initial step of progressive NAFLD pathogenesis.

Treatment of paroxysmal nocturnal hemoglobinuria in the era of eculizumab.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening and debilitating clonal blood disorder caused by an acquired mutation in the phosphatidylinositol glycan (PIG)-A gene. In pluripotent hematopoietic stem cells, this leads to a deficiency of glycosylphosphatidylinositol (GPI)-anchors and GPI-anchored proteins, including the complement regulators CD55 and CD59, on the surface of affected blood cells. PNH red blood cells are highly vulnerable to activation of complement and the formation of the membrane attack complex (MAC). The resulting chronic intravascular hemolysis is the underlying cause of PNH morbidities and mortality. Until recently, the treatment of PNH has been largely empirical and symptomatic with blood transfusions, anticoagulation, and supplementation with folic acid or iron. The only potentially curative treatment is allogeneic stem cell transplantation, but this has severe complications and high mortality and morbidity rates. A new targeted and disease-modifying treatment strategy is the inhibition of the terminal complement cascade with the humanized monoclonal anti-C5 antibody, eculizumab. This effectively inhibits MAC formation and intravascular hemolysis. Eculizumab has shown significant efficacy in controlled studies, with a marked decrease in anemia, fatigue, transfusion requirements, renal impairment, pulmonary hypertension, and risk of severe thromboembolic events, ultimately resulting in improving quality of life and survival.

Chronic treatment of paroxysmal nocturnal hemoglobinuria patients with eculizumab: safety, efficacy, and unexpected laboratory phenomena.

The terminal complement inhibitor eculizumab has become the standard of treatment in patients with symptomatic paroxysmal nocturnal hemoglobinuria (PNH). In this retrospective study, 19 PNH patients received chronic therapy with eculizumab with a median duration of 16 months (range 6-46 months). Parameters of hemolysis, transfusion requirements, and serum iron parameters were analyzed. Lactate dehydrogenase levels were significantly decreased by 85% from a median of 1897 U/l (range 293-3360) to 283 U/l (range 143-667), with an 86% reduction of transfusion requirements, whereas other parameters of hemolysis remained abnormal. Six patients (31.6%) became completely transfusion independent. A significant increase in ferritin levels from a median of 104 µg/l before to a median of 528 µg/l (p = 0.011) during treatment with eculizumab was observed. This was more pronounced in patients with low reticulocyte production index and/or requiring blood transfusions. Monospecific direct Coombs test was positive in most PNH patients, indicating a shift to extravascular hemolysis. Positive immunofixation for IgG kappa was observed, due to the presence of eculizumab in the serum. Eculizumab was safe and well tolerated long term in our study population. Iron should not be routinely supplemented in PNH patients treated with eculizumab without close monitoring of iron parameters, and iron depletion therapy should be considered in the case of overload.

Increased event-related potential latency and amplitude variability in schizophrenia detected through wavelet-based single trial analysis.

Analysis of single-trial event-related potentials can potentially yield important information about the underlying brain dynamics. We were specifically interested in latency and amplitude variability of the P3 component in patients with schizophrenia. For this purpose we developed a method for analyzing single-trial ERPs based on a wavelet smoothing algorithm, which is presented in detail. This method was applied to data from schizophrenic patients and healthy controls in an auditory Go/Nogo task. We found a significant increase of latency variability in the schizophrenic group at electrode Fz (frontal midline) and increased amplitude variability at electrode Pz (parietal midline). These results support the concept of increased cortical noise in patients with schizophrenia.