Benchmarking Visual Performance with Monofocal Intraocular Lenses with and without Enhanced Optical Properties in a Nighttime Driving Simulator Environment: A Proof-of-Concept Study. / Vergleich der Sehleistung mit monofokalen Intraokularlinsen mit und ohne verbesserte optische Eigenschaften in einem Nachtfahrsimulator: eine Proof-of-Concept-Studie.

BACKGROUND: The purpose of this study is to introduce a method for benchmarking intraocular lenses during driving activities under highly standardized conditions, specifically with regard to visual acuity (VA) and contrast sensitivity (CS). Therefore, patients with intraocular lens (IOL) implants ICB00 (Tecnis Eyhance, Johnson & Johnson, Santa Ana, CA, USA) vs. CNA0T0 (Clareon, Alcon Laboratories Inc., Fort Worth, TX, USA) were examined clinically and in a nighttime driving simulator. PATIENTS AND METHODS: Clinical tests for high (HCVA), low contrast (LCVA) distant VA, and mesopic CS were conducted in subjects at least 2 months after binocular IOL surgery (inclusion criteria: VA > 20/25, ophthalmologically normal, except cataract surgery). All patients completed a straight driving simulator route. VA, CS, and halo size were assessed binocularly during nighttime driving using eight-position Landolt Cs in four different locations and two (far and intermediate) distances. RESULTS: Results are presented as median/interquartile range: ICB00 data (corresponding CNA0T0 data are shown in brackets): 5 (6) subjects, aged 69.6/8.3 (71.1/13.0) years were enrolled. Clinical tests: logMAR HCVA 0.11/0.39 (0.00/0.51), logMAR LCVA 0.78/0.52 (0.80/0.54); logCS without glare 0.50/0.31 (0.30/0.65), logCS with glare 0.20/0.15 (0.20/0.5). Nighttime driving simulator: logMAR VA thresholds for right roadside, dashboard, navigation screen, and interior rear-view mirror were 0.50/0.06 (0.57/0.22), 0.81/0.07 (0.91/0.14), 0.80/0.17 (0.92/0.27), 0.50/0.11 (0.63/0.26); logCS thresholds were1.53/0.67 (1.00/0.81), 0.82/0.11 (0.61/0.19), 0.71/0.14 (0.50/0.15), 0.87/0.07 (0.81/0.11). Halo size: 5.40°/0.89° (5.88°/2.00°). CONCLUSIONS: Within a nighttime driving simulator environment, ICB00 exceeded CNA0T0 in median logMAR (VA) and logCS by 0.1 log unit at intermediate distances (dashboard, navigation screen). The clinical test for far and remote distances did not show a difference. These results confirm benefits of monofocal IOLs with enhanced optical properties for intermediate distances compared to conventional monofocal lenses within the target medium distance ranges.

The final implant position of a commonly used collarless straight tapered stem design (Corail®) does not correlate with femoral neck resection height in cement-free total hip arthroplasty: a retrospective computed tomography analysis.

BACKGROUND: In total hip arthroplasty, inadequate femoral component positioning can be associated with instability, impingement and component wear and subsequently with patient dissatisfaction. In this study, we investigated the influence of femoral neck resection height on the final three-dimensional position of a collarless straight tapered stem (Corail®). We asked two questions-(1) is neck resection height correlated with version, tilt, and varus/valgus alignment of the femoral component, and (2) dependent on the resection height of the femoral neck, which area of the stem comes into contact with the femoral cortical bone? MATERIALS AND METHODS: Three-dimensional computed tomography scans of 40 patients who underwent minimally invasive, cementless total hip arthroplasty were analyzed retrospectively. We analyzed the relationship between femoral neck resection height and three-dimensional alignment of the femoral implant, as well as the contact points of the implant with the femoral cortical bone. This investigation was approved by the local Ethics Commission (No.10-121-0263) and is a secondary analysis of a larger project (DRKS00000739, German Clinical Trials Register May-02-2011). RESULTS: Mean femoral neck resection height was 10.4 mm (± 4.8) (range 0-20.1 mm). Mean stem version was 8.7° (± 7.4) (range - 2° to 27.9°). Most patients had a varus alignment of the implant. The mean varus/valgus alignment was 1.5° (± 1.8). All 40 patients (100%) had anterior tilt of the implant with a mean tilt of 2.2° (± 1.6). Femoral neck resection height did not correlate with stem version, varus/valgus alignment, or tilt. Independent from femoral neck resection height, in most patients the implant had contact with the ventral and ventromedial cortical bone in the upper third (77.5%) and the middle third (52.5%). In the lower third, the majority of the implants had contact with the lateral and dorsolateral cortical bone (92.5%). CONCLUSION: Femoral neck resection height ranging between 0 and 20.1 mm does not correlate with the final position of a collarless straight tapered stem design (Corail®). LEVEL OF EVIDENCE: Level 3.

Posterior lesser trochanter line should not be used as reference for assessing femoral version in CT scans: a retrospective reliability and agreement study.

Background The estimation of femoral version in preoperative planning of total hip arthroplasty and to assess complications after total hip arthroplasty is crucial. Recent studies have recommended the posterior lesser trochanter line as an intraoperative reference for estimating femoral version. We hypothesized, that if there is a correlation, the posterior lesser trochanter line could be used to assess femoral version in computed tomography (CT) scans. Purpose To evaluate the correlation between the posterior lesser trochanter line and the posterior femoral condyle axis. Material and Methods CT scans of 126 patients after unilateral total hip arthroplasty were analyzed by means of a newly developed digital planning software for CT scans. Both hips were measured, the angle between the posterior lesser trochanter line and the posterior femoral condyle axis was determined, and the relationship between both lines was evaluated. Results We found significant differences between male and female patients ( P < 0.001) and between left and right femora ( P = 0.001). There was no significant difference between healthy hips and hips with osteoarthritis after total hip arthroplasty ( P = 0.901). Conclusion There is no reliable correlation between posterior lesser trochanter line and posterior femoral condyle axis. Therefore, posterior lesser trochanter line should not be used to assess femoral version in CT scans. As a consequence, the gold standard for measuring femoral version should still be a three-dimensional CT scan of the whole femur.

Lesser Trochanter Size on Plain Anteroposterior Radiographs Correlates With Native Femoral Anteversion.

BACKGROUND: Assessing femoral version in orthopedic surgery is important for preoperative planning of total hip arthroplasty, especially for recognizing excessive anteversion or retroversion. The present study addressed the following: (1) Is the position of the lesser trochanter correlated to the femoral neck axis? (2) If so, may femoral version be assessed by means of plain pelvic radiographs? METHODS: Three-dimensional computed tomography scans of 60 patients undergoing minimally invasive cement-free total hip arthroplasty were retrospectively analyzed, particularly with regard to the relation between the femoral neck axis and the lesser trochanter, the femoral version, and the size of the projected lesser trochanter in different rotational positions. Based on linear regression, a biomathematical formula was developed to assess femoral anteversion on plain radiographs depending on the visible part of the lesser trochanter. RESULTS: The mean difference between the location of the lesser trochanter axis and the femoral neck axis was 43.3° ± 6.2°. Eighty-seven percent of patients (52 of 60) had a deviation of <10° from the mean value of 43.3°. By virtual rotation of the femur in steps of 10°, the visible part of the lesser trochanter linearly increased with anteversion of the femur: femoral version = (lesser trochanter size - 5.57) × 4.17. There was a high correlation between the visible part of the lesser trochanter and femoral version (R2 = 0.75; P < .001). The lesser trochanter was no longer visible with femoral retroversion in each of the 60 data sets. CONCLUSION: The projected size of the lesser trochanter as available on plain pelvic AP radiographs correlates with native femoral anteversion.

Native femoral anteversion should not be used as reference in cementless total hip arthroplasty with a straight, tapered stem: a retrospective clinical study.

BACKROUND: Improper femoral and acetabular component positioning can be associated with instability, impingement, component wear and finally patient dissatisfaction in total hip arthroplasty (THA). The concept of "femur first"/"combined anteversion", incorporates various aspects of performing a functional optimization of the prosthetic stem and cup position of the stem relative to the cup intraoperatively. In the present study we asked two questions: (1) Do native femoral anteversion and anteversion of the implant correlate? (2) Do anteversion of the final broach and implant anteversion correlate? METHODS: In a secondary analysis of a prospective controlled trial, a subgroup of 55 patients, who underwent computer-assisted, cementless THA with a straight, tapered stem through an anterolateral, minimally invasive (MIS) approach in a lateral decubitus position were examined retrospectivly. Intraoperative fluoroscopy was used to verify a "best-fit" position of the final broach. An image-free navigation system was used for measurement of the native femoral version, version of the final broach and the final implant. Femoral neck resection height was measured in postoperative CT-scans. This investigation was approved by the local Ethics Commission (No.10-121-0263) and is a secondary analysis of a larger project (DRKS00000739, German Clinical Trials Register May-02-2011). RESULTS: The mean difference between native femoral version and final implant was 1.9° (+/- 9.5), with a range from -20.7° to 21.5° and a Spearman's correlation coefficient of 0.39 (p < 0.003). In contrast, we observed a mean difference between final broach and implant version of -1.9° (+/- 3.5), with a range from -12.7° to 8.7° and a Spearman's correlation coefficient of 0.89 (p < 0.001). In 83.6 % (46/55) final stem version was outside the normal range as defined by Tönnis (15-20°). The mean femoral neck resection height was 7.3 mm (+/- 5.6). There was no correlation between resection height and version of the implant (Spearman's correlation coefficient 0.14). CONCLUSION: Native femoral version significantly differs from the final anteversion of a cementless, straight, tapered stem and therefore is not a reliable reference in cementless THA. Measuring anteversion of the final "fit and fill" broach is a feasible assistance in order to predict final stem anteversion intraoperatively. There is no correlation between femoral neck resection height and version of the implant.

Treatment With Erythropoietin for Patients With Optic Neuritis: Long-term Follow-up.

BACKGROUND AND OBJECTIVE: Erythropoietin (EPO) is a candidate neuroprotective drug. We assessed its long-term safety and efficacy as an adjunct to methylprednisolone in patients with optic neuritis and focused on conversions to multiple sclerosis (MS). METHODS: The TONE trial randomized 108 patients with acute optic neuritis but without previously known MS to either 33,000 IU EPO or placebo in conjunction with 1,000 mg methylprednisolone daily for 3 days. After reaching the primary end point at 6 months, we conducted an open-label follow-up 2 years after randomization. RESULTS: The follow-up was attended by 83 of 103 initially analyzed patients (81%). There were no previously unreported adverse events. The adjusted treatment difference of peripapillary retinal nerve fiber layer atrophy in relation to the fellow eye at baseline was 1.27 µm (95% CI -6.45 to 8.98, p = 0.74). The adjusted treatment difference in low-contrast letter acuity was 2.87 on the 2.5% Sloan chart score (95% CI -7.92 to 13.65). Vision-related quality of life was similar in both treatment arms (National Eye Institute Visual Functioning Questionnaire median score [IQR]: 94.0 [88.0 to 96.9] in the EPO and 93.4 [89.5 to 97.4] in the placebo group). The rate of multiple sclerosis-free survival was 38% in the placebo and 53% in the EPO group (hazard ratio: 1.67, 95% CI 0.96 to 2.88, p = 0.068). DISCUSSION: In line with the results at 6 months, we found neither structural nor functional benefits in the visual system of patients with optic neuritis as a clinically isolated syndrome, 2 years after EPO administration. Although there were fewer early conversions to MS in the EPO group, the difference across the 2-year window was not statistically significant. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute optic neuritis, EPO as an adjunct to methylprednisolone is well tolerated and does not improve long-term visual outcomes. TRIAL REGISTRATION INFORMATION: The trial was preregistered before commencement at clinicaltrials.gov (NCT01962571).

Formation of hydrogen peroxide by VUV-photolysis of water and aqueous solutions with methanol.

The hydrogen peroxide production upon vacuum ultraviolet (VUV) irradiation of water is reviewed, because published results from the last 10 years lead to conflicting mechanistic interpretations. This work confirms that in pure water, hydrogen peroxide is only produced in the presence of molecular oxygen. Mechanistic schemes explain these findings and confirm earlier statements that recombination of hydroxyl radicals is kinetically disfavoured. In agreement with other recent publications, this work confirms that enhanced hydrogen peroxide production takes place upon VUV irradiation of aqueous solutions of organic compounds. For these investigations, methanol was chosen as an organic model compound. During photolyses, hydrogen peroxide, dissolved molecular oxygen, pH-value of the reaction system, methanol and its products of oxidative degradation were analyzed, and kinetic studies were undertaken to explain the evolution of the concentrations of these components.

Synthesis of Spherical Nanoparticle Hybrids via Aerosol Thiol-Ene Photopolymerization and Their Bioconjugation.

Hybrid nanomaterials possess the properties of both organic and inorganic components and find applications in various fields of research and technology. In this study, aerosol photopolymerization is used in combination with thiol-ene chemistry to produce silver poly(thio-ether) hybrid nanospheres. In aerosol photopolymerization, a spray solution of monomers is atomized, forming a droplet aerosol, which then polymerizes, producing spherical polymer nanoparticles. To produce silver poly(thio-ether) hybrids, silver nanoparticles were introduced to the spray solution. Diverse methods of stabilization were used to produce stable dispersions of silver nanoparticles to prevent their agglomeration before the photopolymerization process. Successfully stabilized silver nanoparticle dispersion in the spray solution subsequently formed nanocomposites with non-agglomerated silver nanoparticles inside the polymer matrix. Nanocomposite particles were analyzed via scanning and transmission electron microscopy to study the degree of agglomeration of silver nanoparticles and their location inside the polymer spheres. The nanoparticle hybrids were then introduced onto various biofunctionalization reactions. A two-step bioconjugation process was developed involving the hybrid nanoparticles: (1) conjugation of (biotin)-maleimide to thiol-groups on the polymer network of the hybrids, and (2) biotin-streptavidin binding. The biofunctionalization with gold-nanoparticle-conjugates was carried out to confirm the reactivity of -SH groups on each conjugation step. Fluorescence-labeled biomolecules were conjugated to the spherical nanoparticle hybrids (applying the two-step bioconjugation process) verified by Fluorescence Spectroscopy and Fluorescence Microscopy. The presented research offers an effective method of synthesis of smart systems that can further be used in biosensors and various other biomedical applications.

Does intraocular straylight predict night driving visual performance? Correlations between straylight levels and contrast sensitivity, halo size, and hazard recognition distance with and without glare.

Purpose: To evaluate the relationship between intraocular straylight perception and: (i) contrast sensitivity (CS), (ii) halo size, and (iii) hazard recognition distance, in the presence and absence of glare. Subjects and methods: Participants were 15 (5 female) ophthalmologically healthy adults, aged 54.6-80.6 (median: 67.2) years. Intraocular straylight (log s) was measured using a straylight meter (C-Quant; Oculus GmbH, Wetzlar, Germany). CS with glare was measured clinically using the Optovist I device (Vistec Inc., Olching, Germany) and also within a driving simulator using Landolt Cs. These were presented under both static or dynamic viewing conditions, and either with or without glare. Hazard detection distance was measured for simulated obstacles of varying contrast. For this, the participant was required to maintain a speed of 60 km/h within a custom-built nighttime driving simulator. Glare was simulated by LED arrays, moved by cable robots to mimic an oncoming car's headlights. Halo size ("halometry") was measured by moving Landolt Cs outward originating from the center of a static glare source. The outcome measure from "halometry" was the radius of the halo (angular extent, in degrees visual angle). Results: The correlation between intraocular straylight perception, log s, and hazard recognition distance under glare was poor for the low contrast obstacles (leading/subdominant eye: r = 0.27/r = 0.34). Conversely, log CS measured with glare strongly predicted hazard recognition distances under glare. This was true both when log CS was measured using a clinical device (Optovist I: r = 0.93) and within the driving simulator, under static (r = 0.69) and dynamic (r = 0.61) conditions, and also with "halometry" (r = 0.70). Glare reduced log CS and hazard recognition distance for almost all visual function parameters. Conclusion: Intraocular straylight was a poor predictor of visual function and driving performance within this experiment. Conversely, CS was a strong predictor of both hazard recognition and halo extent. The presence of glare and motion lead to a degradation of CS in a driving simulator. Future studies are necessary to evaluate the effectiveness of all above-mentioned vision-related parameters for predicting fitness to drive under real-life conditions.

Contrast Sensitivity and Night Driving in Older People: Quantifying the Relationship Between Visual Acuity, Contrast Sensitivity, and Hazard Detection Distance in a Night-Time Driving Simulator.

Purpose: (i) To assess how well contrast sensitivity (CS) predicts night-time hazard detection distance (a key component of night driving ability), in normally sighted older drivers, relative to a conventional measure of high contrast visual acuity (VA); (ii) To evaluate whether CS can be accurately quantified within a night driving simulator. Materials and Methods: Participants were 15 (five female) ophthalmologically healthy adults, aged 55-81 years. CS was measured in a driving simulator using Landolt Cs, presented under static or dynamic driving conditions, and with or without glare. In the dynamic driving conditions, the participant was asked to simultaneously maintain a (virtual) speed of 60 km/h on a country road. In the with glare conditions, two calibrated LED arrays, moved by cable robots, simulated the trajectories and luminance characteristics of the (low beam) headlights of an approaching car. For comparison, CS was also measured clinically (with and without glare) using a Optovist I instrument (Vistec Inc., Olching, Germany). Visual acuity (VA) thresholds were also assessed at high and low contrast using the Freiburg Visual Acuity Test (FrACT) under photopic conditions. As a measure of driving performance, median hazard detection distance (MHDD) was computed, in meters, across three kinds of simulated obstacles of varying contrast. Results: Contrast sensitivity and low contrast VA were both significantly associated with driving performance (both P < 0.01), whereas conventional high contrast acuity was not (P = 0.10). There was good correlation (P < 0.01) between CS measured in the driving simulator and a conventional clinical instrument (Optovist I). As expected, CS was shown to decrease in the presence of glare, in dynamic driving conditions, and as a function of age (all P < 0.01). Conclusion: Contrast sensitivity and low contrast VA predict night-time hazard detection ability in a manner that conventional high contrast VA does not. Either may therefore provide a useful metric for assessing fitness to drive at night, particularly in older individuals. CS measurements can be made within a driving simulator, and the data are in good agreement with conventional clinical methods (Optovist I).

Accuracy of acetabular cup placement in computer-assisted, minimally-invasive THR in a lateral decubitus position.

In a prospective and randomised clinical study, we implanted acetabular cups either by means of an image-free computer-navigation system (navigated group, n = 32) or by free-hand technique (freehand group n = 32, two drop-outs). Total hip replacement was conducted in the lateral position and through a minimally invasive anterior approach (MicroHip). The position of the component was determined postoperatively on CT scans of the pelvis using CT-planning software. We found an average inclination of 42.3° (range 32.7-50.6°; SD ± 3.8°) and an average anteversion of 24.5° (range 12.0-33.3°; SD ± 6.0°) in the computer-assisted study group and an average inclination of 37.9° (range 25.6-50.2°; SD ± 6.3°) and an average anteversion of 23.8° (range 5.6-46.9°; SD ± 10.1°) in the freehand group. The higher precision of computer navigation was indicated by the lower standard deviations. For both measurements we found a significant heterogeneity of variances (p < 0.05, Levene's test). The mean difference between the cup inclination/anteversion values displayed by computer navigation and the true cup position (CT control) was 0.37° (SD 3.26) and -5.61° (SD 6.48), respectively. We found a bias (underestimation) with regard to anteversion determined by the imageless computer navigation system. A bias for inclination was not found. Registration of the landmarks of the anterior pelvic plane in lateral position with undraped percutaneous methods leads to an error in cup anteversion, but not to an error in cup inclination. The bias we found is consistent with a correct registration of the anterosuperior iliac spine (ASIS) and with a registration of the symphysis 1 cm above the bone, corresponding to the less compressible overlying soft tissue in this region. There was no significant correlation between the bias and the thickness of soft tissue above the pubic tubercles. We suggest use of a percutaneous registration of ASIS and an invasive registration above the pubic tubercles when computer-assisted navigation is performed in minimally invasive THR in a lateral position.

Dissociation between red and white stimulus perception: A perimetric quantification of protanopic color vision deficiencies.

SIGNIFICANCE: Horizontal visual field extension was assessed for red and white stimuli in subjects with protanopia using semi-automated kinetic perimetry. In contrast to a conventional anomaloscope, the "red/white dissociation ratio" (RWR) allows to describe protanopia numerically. For the majority of subjects with protanopia a restriction for faint red stimuli was found. PURPOSE: Comparing the horizontal visual field extensions for red and white stimuli in subjects with protanopia and those with normal trichromacy and assessing the related intra-subject intra-session repeatability. METHODS: The subjects were divided into groups with protanopia and with normal trichromacy, based on color vision testing (HMC anomaloscope, Oculus, Wetzlar/FRG). Two stimulus characteristics, III4e and III1e, according to the Goldmann-classification, were presented with semi-automated kinetic perimetry (Octopus 900 perimeter, Haag-Streit, Köniz/CH). They moved along the horizontal meridian, with an angular velocity of 3°/s towards the visual field center, starting from either the temporal or nasal periphery. If necessary, a 20° nasal fixation point offset was chosen to capture the temporal periphery of the visual field. For each condition the red/white dissociation ratio (RWR); Pat Appl. DPMA DRN 43200082D) between the extent of the isopter for red (RG610, Schott, Mainz/ FRG) and white stimuli along the horizontal meridian was determined. RESULTS: All data are listed as median/interquartile range: Five males with protanopia (age 22.1/4.5 years) and six males with normal trichromacy (control group, age 30.5/15.2 years) were enrolled. The RWR is listed for the right eye, as no clinically relevant difference between right and left eye occurred. Protanopes' RWR for mark III4e (in brackets: control group) was 0.941/0.013 (0.977/0.019) and for mark III1e 0.496/0.062 (0.805/0.051), respectively. CONCLUSIONS: In this exploratory "proof-of-concept study" red/white dissociation ratio perimetry is introduced as a novel technique aiming at assessing and quantifying the severity of protanopia. Further effort is needed to understand the magnitude of the observed red-/white dissociation and to extend this methodology to a wider age range of the sample and to anomalous trichromacies (protanomalia) with varying magnitude.

Thiol-Functional Polymer Nanoparticles via Aerosol Photopolymerization.

Spherical, individual polymer nanoparticles with functional -SH groups were synthesized via aerosol photopolymerization (APP) employing radically initiated thiol-ene chemistry. A series of various thiol and alkene monomer combinations were investigated based on di-, tri-, and tetrafunctional thiols with difunctional allyl and vinyl ethers, and di- and trifunctional acrylates. Only thiol and alkene monomer combinations able to build cross-linked poly(thio-ether) networks were compatible with APP, which requires fast polymerization of the generated droplet aerosol during the photoreactor passage within a residence time of half-minute. Higher monomer functionalities and equal overall stoichiometry of functional groups resulted in the best nanoparticles being spherical and individual, proven by scanning electron microscopy (SEM). The presence of reactive -SH groups in the synthesized nanoparticles as a basis for post-polymerization modifications was verified by Ellman's test.

Immobilization of ß-Galactosidase by Encapsulation of Enzyme-Conjugated Polymer Nanoparticles Inside Hydrogel Microparticles.

Increasing the shelf life of enzymes and making them reusable is a prominent topic in biotechnology. The encapsulation inside hydrogel microparticles (HMPs) can enhance the enzyme's stability by preserving its native conformation and facilitating continuous biocatalytic processes and enzyme recovery. In this study, we present a method to immobilize ß-galactosidase by, first, conjugating the enzyme onto the surface of polymer nanoparticles, and then encapsulating these enzyme-conjugated nanoparticles (ENPs) inside HMPs using microfluidic device paired with UV-LEDs. Polymer nanoparticles act as anchors for enzyme molecules, potentially preventing their leaching through the hydrogel network especially during swelling. The affinity binding (through streptavidin-biotin interaction) was used as an immobilization technique of ß-galactosidase on the surface of polymer nanoparticles. The hydrogel microparticles of roughly 400 µm in size (swollen state) containing unbound enzyme and ENPs were produced. The effects of encapsulation and storage in different conditions were evaluated. It was discovered that the encapsulation in acrylamide (AcAm) microparticles caused an almost complete loss of enzymatic activity. Encapsulation in poly(ethylene glycol) (PEG)-diacrylate microparticles, on the other hand, showed a residual activity of 15-25%, presumably due to a protective effect of PEG during polymerization. One of the major factors that affected the enzyme activity was presence of photoinitiator exposed to UV-irradiation. Storage studies were carried out at room temperature, in the fridge and in the freezer throughout 1, 7 and 28 days. The polymer nanoparticles showcased excellent immobilization properties and preserved the activity of the conjugated enzyme at room temperature (115% residual activity after 28 days), while a slight decrease was observed for the unbound enzyme (94% after 28 days). Similar trends were observed for encapsulated ENPs and unbound enzyme. Nevertheless, storage at -26°C resulted in an almost complete loss of enzymatic activity for all samples.

Safety and efficacy of erythropoietin for the treatment of patients with optic neuritis (TONE): a randomised, double-blind, multicentre, placebo-controlled study.

BACKGROUND: The human cytokine erythropoietin conveys neuroprotection in animal models but has shown ambiguous results in phase 2 clinical trials in patients with optic neuritis. We assessed the safety and efficacy of erythropoietin in patients with optic neuritis as a clinically isolated syndrome in a multicentre, prospective, randomised clinical trial. METHODS: This randomised, placebo-controlled, double-blind phase 3 trial, conducted at 12 tertiary referral centres in Germany, included participants aged 18-50 years, within 10 days of onset of unilateral optic neuritis, with visual acuity of 0·5 or less, and without a previous diagnosis of multiple sclerosis. Participants were randomly assigned (1:1) to receive either 33 000 IU erythropoietin or placebo intravenously for 3 days as an adjunct to high-dose intravenous methylprednisolone (1000 mg per day). Block randomisation was performed by the trial statistician using an SAS code that generated randomly varying block sizes, stratified by study site and distributed using sealed envelopes. All trial participants and all study staff were masked to treatment assignment, except the trial pharmacist. The first primary outcome was atrophy of the peripapillary retinal nerve fibre layer (pRNFL), measured by optic coherence tomography (OCT) as the difference in pRNFL thickness between the affected eye at week 26 and the unaffected eye at baseline. The second primary outcome was low contrast letter acuity at week 26, measured as the 2·5% Sloan chart score of the affected eye. Analysis was performed in the full analysis set of all randomised participants for whom treatment was started and at least one follow-up OCT measurement was available. Safety was analysed in all patients who received at least one dose of the trial medication. This trial is registered at ClinicalTrials.gov, NCT01962571. FINDINGS: 108 participants were enrolled between Nov 25, 2014, and Oct 9, 2017, of whom 55 were assigned to erythropoietin and 53 to placebo. Five patients were excluded from the primary analysis due to not receiving the allocated medication, withdrawn consent, revised diagnosis, or loss to follow-up, yielding a full analysis set of 52 patients in the erythropoietin group and 51 in the placebo group. Mean pRNFL atrophy was 15·93 µm (SD 14·91) in the erythropoietin group and 14·65 µm (15·60) in the placebo group (adjusted mean treatment difference 1·02 µm; 95% CI -5·51 to 7·55; p=0·76). Mean low contrast letter acuity scores were 49·60 (21·31) in the erythropoietin group and 49·06 (21·93) in the placebo group (adjusted mean treatment difference -4·03; -13·06 to 5·01). Adverse events occurred in 43 (81%) participants in the erythropoietin group and in 42 (81%) in the placebo group. The most common adverse event was headache, occuring in 15 (28%) patients in the erythropoietin group and 13 (25%) patients in the placebo group. Serious adverse events occurred in eight (15%) participants in the erythropoietin and in four (8%) in the placebo group. One patient (2%) in the erythropoietin group developed a venous sinus thrombosis, which was treated with anticoagulants and resolved without sequelae. INTERPRETATION: Erythropoietin as an adjunct to corticosteroids conveyed neither functional nor structural neuroprotection in the visual pathways after optic neuritis. Future research could focus on modified erythropoietin administration, assess its efficacy independent of corticosteroids, and investigate whether it affects the conversion of optic neuritis to multiple sclerosis. FUNDING: German Federal Ministry of Education and Research (BMBF).

Stem torsion in total hip replacement.

BACKGROUND AND PURPOSE: The clinical results of THR may be improved by correct femoral torsion. We evaluated the stem position by postoperative CT examination in 60 patients. METHODS: 60 patients requiring total hip arthroplasty were prospectively enrolled in this study. Minimally invasive THR was performed (anterior approach) in a lateral decubitus position and each patient underwent a postoperative CT examination. The position of the stem was evaluated by an independent external institution. RESULTS: Stem torsion ranged from ­ 19° retrotorsion to 33° antetorsion. Normal antetorsion (i.e 10­15° according to Tönnis) was present in 5 of 60 patients, so the prevalence of abnormal stem antetorsion was 92% (95% CI: 82­97). We found a stem antetorsion outside the range of 0­25° in 21 of 60 hips. Women had a higher mean stem antetorsion (8.0° (SD 11)) than men (1.5° (SD 10)). INTERPRETATION: Postoperative stem antetorsion shows a high variability and is gender-related. We suggest precise assessment of stem antetorsion intraoperatively by means of computer navigation, preparing the femur first. In abnormal stem antetorsion, the cup position can be adjusted using a combined anteversion concept; alternatively, modular femoral components or stems with retroverted or anteverted necks ("retrostem") could be used.

3D-Printable and Enzymatically Active Composite Materials Based on Hydrogel-Filled High Internal Phase Emulsions.

The immobilization of enzymes in biocatalytic flow reactors is a common strategy to increase enzyme reusability and improve biocatalytic performance. Extrusion-based 3D bioprinting has recently emerged as a versatile tool for the fabrication of perfusable hydrogel grids containing entrapped enzymes for the use in such reactors. This study demonstrates the suitability of water-in-oil high internal phase emulsions (HIPEs) as 3D-printable bioinks for the fabrication of composite materials with a porous polymeric scaffold (polyHIPE) filled with enzyme-laden hydrogel. The prepared HIPEs exhibited excellent printability and are shown to be suitable for the printing of complex three-dimensional structures without the need for sacrificial support material. An automated activity assay method for the systematic screening of different material compositions in small-scale batch experiments is presented. The monomer mass fraction in the aqueous phase and the thickness of printed objects were found to be the most important parameters determining the apparent activity of the immobilized enzyme. Mass transfer limitations and enzyme inactivation were identified as probable factors reducing the apparent activity. The presented HIPE-based bioinks enable the fabrication of flow-optimized and more efficient biocatalytic reactors while the automated activity assay method allows the rapid screening of materials to optimize the biocatalytic efficiency further without time-consuming flow-through experiments involving whole printed reactors.

Electrochemical reduction of the iodinated contrast medium iomeprol: iodine mass balance and identification of transformation products.

Potentiostatic-controlled electrochemical reduction of iomeprol was used to deiodinate iomeprol (IMP), a representative of the iodinated X-ray contrast media. The reduction process was followed by product analysis with liquid chromatography-electrospray ionization-tandem mass spectrometry and ion chromatography-inductively coupled plasma-mass spectrometry. The identification is mainly based on the interpretation of the mass fragmentation. The product analysis showed a rather selective deiodination process with the successive occurrence of IMP-I, IMP-2I, IMP-3I, and a transformation product (TP), respectively. The TP was formed from IMP-3I by a further cleavage of an amide bond and release of a (C=O)CHOH group from the side chain of IMP. The iodine mass balance on the basis of IMP and iodide showed a gap of about 26% at the beginning of the electrolysis process which could be completely closed by taking the intermediates IMP-I and IMP-2I into consideration. This means that the major intermediates and the TPs were considered and that the reduction process is a rather selective one to remove organically bound iodine from X-ray contrast media. An attractive application area would be the electrochemical deiodination of X-ray contrast media in urine of patients or hospital effluents.

Characterization of nanostructured surfaces generated by reconstitution of the porin MspA from Mycobacterium smegmatis.

Nanostructures with long-term stability at the surface of gold electrodes are generated by reconstituting the porin MspA from Mycobacterium smegmatis into a specially designed monolayer of long-chain lipid surfactant on gold. Tailored surface coverage of gold electrodes with long-chain surfactants is achieved by electrochemically assisted deposition of organic thiosulfates (Bunte salts). The subsequent reconstitution of the octameric-pore MspA is guided by its extraordinary self-assembling properties. Importantly, electrochemical reduction of copper(II) yields copper nanoparticles within the MspA nanopores. Electrochemical impedance spectroscopy, reflection electron microscopy, and atomic force microscopy (AFM) show that: 1) the MspA pores within the self-assembled monolayer (SAM) are monodisperse and electrochemically active, 2) MspA reconstitutes in SAMs and with a 10-nm thickness, 3) AFM is a suitable method to detect pores within SAMs, and 4) the electrochemical reduction of Cu2+ to Cu0 under overpotential conditions starts within the MspA pores.

A cockspur for the DSS cells: Erythrina crista-galli sensitizers.

Dye sensitized solar cells were assembled employing a mixture of anthocyanins extracted from red ceibo's flowers. At the literature different extraction procedures are reported to extract anthocyanins from natural products and sensitize the cells. In order to compare them, different methods were followed to set the cells under the same conditions. Assembled cells showed very interesting conversion efficiency values, reaching a 0.73% value for extracts purified using C18 column, in open cells under illumination using a solar light simulator, 1 sun, 1.5 AM. Data reported herein prove that anthocyanins obtained from ceibo's flower, after simple further purification, might represent an excellent, cheap and clean alternative for the development of DSS cells.