Effekte lokal applizierter mikrovaskulärer Fragmente mittels thermoresponsivem Hydrogel auf die Frakturheilung

Eine defizitäre Vaskularisation ist ein vorrangiger Grund für eine verzögerte Frakturheilung bzw. die Entwicklung von Pseudarthrosen. Um dieses Problem zu lösen, können mikrovaskuläre Gefäßfragmente (MVF) aus Fettgewebe als Vaskularisationseinheiten dienen. Jedoch benötigt es zur präzisen Applikation von MVF in einen Knochendefekt eine geeignete Trägersubstanz. In dieser Studie wurde untersucht, ob dies durch ein thermoresponsives Hydrogel (TRH) erreicht werden kann. MVF wurden aus CD-1 Mäusen isoliert und in TRH inkorporiert, während nicht inkorporierte MVF als Kontrolle dienten. Die Viabilität von MVF wurde immunhistochemisch über einen Zeitraum von bis zu 7 Tagen untersucht. Zusätzlich wurde in Femora von CD-1 Mäusen eine Osteotomie induziert. Der Osteotomiespalt wurde mit MVF-beladenem TRH (TRH+MVF), unbeladenem TRH (TRH) oder ohne Material (Kontrolle) aufgefüllt. Die Knochenheilung wurde 14 und 35 Tage postoperativ untersucht. In TRH eingebettete MVF zeigten weniger apoptotische Zellen und eine stabile Gefäßmorphologie im Vergleich zu Kontrollen. Im Tiermodell zeigte die Mikrocomputertomographie weniger Knochenvolumen in TRH+MVF Femora. Die Histomorphometrie ergab weniger Knochen- und mehr Bindegewebe 35 Tage postoperativ in TRH+MVF Femora verglichen mit Kontrollen. Dementsprechend war der ossäre Überbrückungsscore und die Biegesteifigkeit in Femora der Gruppe TRH+MVF reduziert. Die Histologie und der Western Blot zeigten eine verbesserte Vaskularisierung und erhöhte CD31 Expression, wohingegen die Expression von vascular endothelial growth factor (VEGF) in TRH+MVF Femora reduziert war. Zudem zeigte der Kallus von TRH+MVF Femora eine höhere Expression von Rezeptor-aktiviertem NF-κB Liganden (RANKL) und eine größere Anzahl an Osteoklasten. Diese Ergebnisse weisen darauf hin, dass TRH eine geeignete Trägersubstanz für MVF darstellt. Die Applikation von TRH+MVF verbessert die Vaskularisation in Knochendefekten. Jedoch stört dies die Knochenheilung, am ehesten durch eine geringere VEGF Expression in der frühen Phase der Knochenheilung.Insufficient vascularization is a major cause for the development of non-unions. To overcome this problem, adipose tissue-derived microvascular fragments (MVF) may serve as 2 vascularization units. However, their application into bone defects needs a carrier system. Herein, we analyzed whether this is achieved by a thermoresponsive hydrogel (TRH). MVF were isolated from CD-1 mice and cultivated after incorporation into TRH, while non-incorporated MVF served as controls. Viability of MVF was assessed immunohistochemically over a 7-day period. Moreover, osteotomies were induced in femurs of CD-1 mice. The osteotomy gaps were filled with MVF-loaded TRH (TRH+MVF), unloaded TRH (TRH) or no material (control). Bone healing was evaluated 14 and 35 days postoperatively. MVF incorporated into TRH exhibited less apoptotic cells and showed a stable vessel morphology compared to controls. In the animal model, micro-computed tomography revealed a reduced bone volume in TRH+MVF femurs. Histomorphometry showed less bone and more fibrous tissue after 35 days in TRH+MVF femurs compared to controls. Accordingly, TRH+MVF femurs exhibited a lower osseous bridging score and a reduced bending stiffness. Histology and Western blot analysis revealed an increased vascularization and CD31 expression, whereas vascular endothelial growth factor (VEGF) expression was reduced in TRH+MVF femurs. Furthermore, the callus of TRH+MVF femurs showed increased receptor activator of NF-κB ligand expression and higher numbers of osteoclasts. These findings indicate that TRH is an appropriate carrier system for MVF. Application of TRH+MVF increases the vascularization of bone defects. However, this impairs bone healing, most likely due to lower VEGF expression during the early course of bone healing

Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil

The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27%) in contrast to the DC coil (about 15%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil

Orometric methods in bounded metric data

A large amount of data accommodated in knowledge graphs (KG) is metric. For example, the Wikidata KG contains a plenitude of metric facts about geographic entities like cities or celestial objects. In this paper, we propose a novel approach that transfers orometric (topographic) measures to bounded metric spaces. While these methods were originally designed to identify relevant mountain peaks on the surface of the earth, we demonstrate a notion to use them for metric data sets in general. Notably, metric sets of items enclosed in knowledge graphs. Based on this we present a method for identifying outstanding items using the transferred valuations functions isolation and prominence. Building up on this we imagine an item recommendation process. To demonstrate the relevance of the valuations for such processes, we evaluate the usefulness of isolation and prominence empirically in a machine learning setting. In particular, we find structurally relevant items in the geographic population distributions of Germany and France. © 2020, The Author(s)

Non-Precious Metal Alloy Double Crown-Retained Removable Partial Dentures: A Cross-Sectional In Vivo Investigation.

(1) Background: An alternative material to precious metal alloys are non-precious metal alloys. The material properties of these are different and, therefore, their clinical, biological and mechanical behaviors may also differ. Hence, the purpose of this in vivo investigation was to analyze the clinical and patient-reported outcomes of patients restored with non-precious metal alloy double crown-retained removable partial dentures (NP-D-RPDs). (2) Methods: Partially edentulous patients were restored with non-precious metal alloy partially veneered NP-D-RPDs. Survival rates, success rates, failures and patient-reported outcomes were investigated and statistically evaluated. (3) Results: A total of 61 patients (65.6 ± 10.8 years) were included and clinically and radiographically examined. The mean follow-up time was 25.2 ± 16.5 months. In total, 82 NP-D-RPDs and 268 abutment teeth were examined. The overall survival rate of the NP-D-RPDs was 100% after a mean follow-up time of 2.1 years. The overall success rate was 68.3%. The overall satisfaction with the NP-D-RPDs was 94.3%. (4) Conclusions: Non-precious metal alloy partially veneered NP-D-RPDs seem to be an efficient alternative to precious metal alloy RPDs with excellent patient-reported outcomes

Eddies: Fluid Dynamical Niches or Transporters?–A Case Study in the Western Baltic Sea

Fluid flows in the ocean have a strong impact on the growth and distribution of planktonic communities. In this case study, we applied a Lagrangian eddy detection and tracking tool and a transfer operator approach to data from a coupled hydrodynamical-chemical-biological model of the Western Baltic Sea and studied the effects of eddies on plankton in the blooming period March to October 2010. We investigated the residence times of water bodies inside these eddies, using a tracer analysis and found that eddies can act in two different ways: They can be transporters of an enclosed water body that embodies nutrients and the plankton community and export them from the coast to the open sea; and they can act as fluid dynamical niches that enhance the growth of certain species or functional groups by providing optimal temperature and nutrient composition

Virtual Axle Detector Based on Analysis of Bridge Acceleration Measurements by Fully Convolutional Network

In the practical application of the Bridge Weigh-In-Motion (BWIM) methods, the position of the wheels or axles during the passage of a vehicle is a prerequisite in most cases. To avoid the use of conventional axle detectors and bridge type-specific methods, we propose a novel method for axle detection using accelerometers placed arbitrarily on a bridge. In order to develop a model that is as simple and comprehensible as possible, the axle detection task is implemented as a binary classification problem instead of a regression problem. The model is implemented as a Fully Convolutional Network to process signals in the form of Continuous Wavelet Transforms. This allows passages of any length to be processed in a single step with maximum efficiency while utilising multiple scales in a single evaluation. This allows our method to use acceleration signals from any location on the bridge structure and act as Virtual Axle Detectors (VADs) without being limited to specific structural types of bridges. To test the proposed method, we analysed 3787 train passages recorded on a steel trough railway bridge of a long-distance traffic line. Results of the measurement data show that our model detects 95% of the axles, which means that 128,599 out of 134,800 previously unseen axles were correctly detected. In total, 90% of the axles were detected with a maximum spatial error of 20 cm, at a maximum velocity of vmax=56.3m/s. The analysis shows that our developed model can use accelerometers as VADs even under real operating conditions

Long‐term validation of virtual sensing of a railway bridge with ballasted superstructure

Railway bridges have a long lifespan, which is challenged by the constant development of vehicles leading to increased loads that they were not originally designed for. To ensure the longest possible use of existing structures, a sensor‐based structural health monitoring system can make a significant contribution. However, due to economic reasons and the inaccessibility of many points of interest, sensors cannot be installed everywhere. Therefore, in most cases, only a few sensors are available at a few points of interest, and methods that aim to reconstruct structural responses at unmeasured points from these measurements are referred to as virtual sensing. In this paper, we have analyzed 19,075 passages recorded on a steel trough bridge with a ballast superstructure and a span of 16.4 m, together with weather data. Our findings show that the influence of train type and speed has a significantly higher impact on the results than environmental factors. The investigation revealed that the model‐based analysis produced similar results to the data‐driven analysis concerning acceleration signals. However, when analyzing strain signals, the two approaches yielded distinctly different results

Linagliptin and its effects on hyperglycaemia and albuminuria in patients with type 2 diabetes and renal dysfunction : the randomized MARLINA-T2D trial

Aims: The MARLINA-T2D study (ClinicalTrials. gov, NCT01792518) was designed to investigate the glycaemic and renal effects of linagliptin added to standard-of-care in individuals with type 2 diabetes and albuminuria. Methods: A total of 360 individuals with type 2 diabetes, HbA1c 6.5% to 10.0% (48-86 mmol/ mol), estimated glomerular filtration rate (eGFR) >= 30 mL/min/1.73 m(2) and urinary albumin-tocreatinine ratio (UACR) 30-3000 mg/g despite single agent renin-angiotensin-system blockade were randomized to double-blind linagliptin (n = 182) or placebo (n = 178) for 24 weeks. The primary and key secondary endpoints were change from baseline in HbA1c at week 24 and time-weighted average of percentage change from baseline in UACR over 24 weeks, respectively. Results: Baseline mean HbA1c and geometric mean (gMean) UACR were 7.8% +/- 0.9% (62.2 +/- 9.6 mmol/mol) and 126 mg/g, respectively; 73.7% and 20.3% of participants had microalbuminuria or macroalbuminuria, respectively. After 24 weeks, the placebo-adjusted mean change in HbA1c from baseline was -0.60% (-6.6 mmol/mol) (95% confidence interval [CI], -0.78 to -0.43 [-8.5 to -4.7 mmol/mol]; P Conclusions: In individuals at early stages of diabetic kidney disease, linagliptin significantly improved glycaemic control but did not significantly lower albuminuria. There was no significant change in placebo-adjusted eGFR. Detection of clinically relevant renal effects of linagliptin may require longer treatment, as its main experimental effects in animal studies have been to reduce interstitial fibrosis rather than alter glomerular haemodynamics.Peer reviewe

Hemodynamic effects of the dipeptidyl peptidase-4 inhibitor linagliptin with renin-angiotensin system inhibitors in type 2 diabetic patients with albuminuria

Objective: Concomitant treatment with angiotensin-converting enzyme (ACE) inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors is increasingly common. Pharmacological studies have suggested a potential adverse drug interaction between ACE inhibitors and DPP-4 inhibitors resulting in unfavorable hemodynamic changes; very few studies have examined such an interaction between angiotensin II receptor blockers (ARBs) and DPP-4 inhibitors. We investigated blood pressure (BP) and heart rate (HR) during treatment with the DPP-4 inhibitor linagliptin in individuals receiving either ACE inhibitors or ARBs in the MARLINA-T2D trial. Methods: In this study, 360 individuals with type 2 diabetes and albuminuria receiving unchanged doses of ACE inhibitors or ARBs were randomized to linagliptin or placebo. Twenty-four-hour ambulatory BP monitoring, an exploratory endpoint, was conducted at baseline and after 24 weeks. Results: Ambulatory BP monitoring data were available for 208 individuals (linagliptin: n = 111; placebo: n = 97). Baseline mean +/- SD 24-h SBP and DBP were 132.5 +/- 12.4 mmHg and 75.9 +/- 9.4 mmHg, respectively; mean 24-h HR was 76.3 +/- 10.1 bpm. At week 24, no overall effect of the DPP-4 inhibitor versus placebo was seen on mean 24-h SBP, DBP, or HR. Furthermore, in the subgroups receiving either an ACE inhibitor or an ARB, no effect on these hemodynamic parameters was seen as a result of concomitant DPP-4 inhibitor treatment. Conclusion: Adding linagliptin to treatment with ACE inhibitors or ARBs was not associated with any hemodynamic changes, supporting their concomitant use in individuals with type 2 diabetes and albuminuria.Peer reviewe