Extrakorporale Stoßwellentherapie eines komplizierten chronischen Ulcus cruris venosum

Zusammenfassung: Extrakorporale Stoßwellen werden definiert als eine Sequenz von akustischen Schallimpulsen, die einen charakteristisch schnellen Druckanstieg auf über 100MPa mit Abfall auf Normaldruck in wenigen Mikrosekunden aufweisen. In den 1980er-Jahren wurde die extrakorporale Stoßwellenlithotripsie (ESWL) erstmals zur Behandlung der Urolithiasis angewandt. Orthopäden setzten anschließend die extrakorporale Stoßwellentherapie (ESWT) zur Behandlung von nicht heilenden Frakturen, Tendinopathien und Osteonekrose ein. Die erste Anwendung von ESWT in der Dermatologie erfolgte zur Behandlung des chronischen Ulcus cruris. Verschiedene Studien der letzten 10Jahre zeigten, dass die ESWT die Angiogenese stimuliert und die Perfusion im ischämischen Gewebe verbessert, die Entzündungsreaktion mindert, die Zelldifferenzierung unterstützt und hiermit die Wundheilung deutlich verbessern kann. Wir setzten die ESWT erfolgreich zur Behandlung eines komplizierten chronischen venösen Ulcus cruris ein. Weiter konnten wir eine Verbesserung des lymphatischen Abflusses nach Applikation von ESWT beobachten. Die ESWT stellt somit eine nebenwirkungsarme und effiziente physikalische Therapiemodalität zur Behandlung von therapieresistenten chronischen Wunden da

Physical topography is associated with human personality.

Regional differences in personality are associated with a range of consequential outcomes. But which factors are responsible for these differences? Frontier settlement theory suggests that physical topography is a crucial factor shaping the psychological landscape of regions. Hence, we investigated whether topography is associated with regional variation in personality across the United States (n = 3,387,014). Consistent with frontier settlement theory, results from multilevel modelling revealed that mountainous areas were lower on agreeableness, extraversion, neuroticism and conscientiousness but higher on openness to experience. Conditional random forest algorithms confirmed mountainousness as a meaningful predictor of personality when tested against a conservative set of controls. East-west comparisons highlighted potential differences between ecological (driven by physical features) and sociocultural (driven by social norms) effects of mountainous terrain.N

The Effect of wake Turbulence Intensity on Transition in a Compressor Cascade

Direct numerical simulations of separating flow along a section at midspan of a low-pressure V103 compressor cascade with periodically incoming wakes were performed. By varying the strength of the wake, its influence on both boundary layer separation and bypass transition were examined. Due to the presence of small-scale three-dimensional fluctuations in the wakes, the flow along the pressure surface undergoes bypass transition. Only in the weak-wake case, the boundary layer reaches a nearly-separated state between impinging wakes. In all simulations, the flow along the suction surface was found to separate. In the simulation with the strong wakes, separation is intermittently suppressed as the periodically passing wakes managed to trigger turbulent spots upstream of the location of separation. As these turbulent spots convect downstream, they locally suppress separation. © 2014 Springer Science+Business Media Dordrecht

Toward genome editing in X-linked RP-development of a mouse model with specific treatment relevant features

Genome editing represents a powerful tool to treat inherited disorders. Highly specific endonucleases induce a DNA double strand break near the mutant site, which is subsequently repaired by cellular DNA repair mechanisms that involve the presence of a wild type template DNA. In vivo applications of this strategy are still rare, in part due to the absence of appropriate animal models carrying human disease mutations and knowledge of the efficient targeting of endonucleases. Here we report the generation and characterization of a new mouse model for X-linked retinitis pigmentosa (XLRP) carrying a point mutation in the mutational hotspot exon ORF15 of the RPGR gene as well as a recognition site for the homing endonuclease I-SceI. Presence of the genomic modifications was verified at the RNA and protein levels. The mutant protein was observed at low levels. Optical coherence tomography studies revealed a slowly progressive retinal degeneration with photoreceptor loss starting at 9 months of age, paralleling the onset of functional deficits as seen in the electroretinogram. Early changes to the outer retinal bands can be used as biomarker during treatment applications. We further show for the first time efficient targeting using the I-SceI enzyme at the genomic locus in a proof of concept in photoreceptors following adeno-associated virus mediated gene transfer in vivo. Taken together, our studies not only provide a human-XLRP disease model but also act as a platform to design genome editing technology for retinal degenerative diseases using the currently available endonucleases

Validation of farm-scale methane emissions using nocturnal boundary layer budgets

This study provides the first experimental validation of Swiss agricultural methane emission estimates at the farm scale. We measured CH4 concentrations at a Swiss farmstead during two intensive field campaigns in August 2011 and July 2012 to (1) quantify the source strength of livestock methane emissions using a tethered balloon system and (2) to validate inventory emission estimates via nocturnal boundary layer (NBL) budgets. Field measurements were performed at a distance of 150m from the nearest farm buildings with a tethered balloon system in combination with gradient measurements at eight heights on a 10m tower to better resolve the near-surface concentrations. Vertical profiles of air temperature, relative humidity, CH4 concentration, wind speed, and wind direction showed that the NBL was strongly influenced by local transport processes and by the valley wind system. Methane concentrations showed a pronounced time course, with highest concentrations in the second half of the night. NBL budget flux estimates were obtained via a time–space kriging approach. Main uncertainties of NBL budget flux estimates were associated with nonstationary atmospheric conditions and the estimate of the inversion height zi (top of volume integration). The mean NBL budget fluxes of 1:60$\pm$0:31 μgCH$_{4}$m$^{-2}$ s$^{-1}$ (1:40$\pm$0:50 and 1:66$\pm$0:20 μgCH$_{4}$m$^{-2}$ s$^{-1}$ in 2011 and 2012 respectively) were in good agreement with local inventory estimates based on current livestock number and default emission factors, with 1:29$\pm$0:47 and 1:74$\pm$0:63 μgCH$_{4}$m$^{-2}$ s$^{-1}$ for 2011 and 2012 respectively. This indicates that emission factors used for the national inventory reports are adequate, and we conclude that the NBL budget approach is a useful tool to validate emission inventory estimates

DFT‐Guided Discovery of Ethynyl‐Triazolyl‐Phosphinates as Modular Electrophiles for Chemoselective Cysteine Bioconjugation and Profiling

We report the density functional theory (DFT) guided discovery of ethynyl‐triazolyl‐phosphinates (ETPs) as a new class of electrophilic warheads for cysteine selective bioconjugation. By using CuI‐catalysed azide alkyne cycloaddition (CuAAC) in aqueous buffer, we were able to access a variety of functional electrophilic building blocks, including proteins, from diethynyl‐phosphinate. ETP‐reagents were used to obtain fluorescent peptide‐conjugates for receptor labelling on live cells and a stable and a biologically active antibody‐drug‐conjugate. Moreover, we were able to incorporate ETP‐electrophiles into an azide‐containing ubiquitin under native conditions and demonstrate their potential in protein–protein conjugation. Finally, we showcase the excellent cysteine‐selectivity of this new class of electrophile in mass spectrometry based, proteome‐wide cysteine profiling, underscoring the applicability in homogeneous bioconjugation strategies to connect two complex biomolecules.By means of density functional theory calculations, ethynyl‐triazolyl‐phosphinates (ETPs) were discovered as modular and cysteine‐selective electrophiles for bioconjugation. Using CuI‐click chemistry in aqueous buffers, this functional group can be easily introduced into azide‐containing (bio‐)molecules. These reagents can be used for proteome‐wide cysteine profiling and to obtain functional peptide‐ and protein conjugates, as well as protein–protein conjugates . imageDeutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Leibniz-Gemeinschaft http://dx.doi.org/10.13039/501100001664Studienstiftung des Deutschen Volkes http://dx.doi.org/10.13039/501100004350Alexander von Humboldt-Stiftung http://dx.doi.org/10.13039/100005156Institute for Basic Science in KoreaPeer Reviewe

Development of an auditory implant manipulator for minimally invasive surgical insertion of implantable hearing devices

Abstract Objective: To present the auditory implant manipulator, a navigation-controlled mechanical and electronic system which enables minimally invasive (‘keyhole') transmastoid access to the tympanic cavity. Materials and methods: The auditory implant manipulator is a miniaturised robotic system with five axes of movement and an integrated drill. It can be mounted on the operating table. We evaluated the surgical work field provided by the system, and the work sequence involved, using an anatomical whole head specimen. Results: The work field provided by the auditory implant manipulator is considerably greater than required for conventional mastoidectomy. The work sequence for a keyhole procedure included pre-operative planning, arrangement of equipment, the procedure itself and post-operative analysis. Conclusion: Although system improvements are necessary, our preliminary results indicate that the auditory implant manipulator has the potential to perform keyhole insertion of implantable hearing device

Assessment of thermal and hydrolytic stabilities and aqueous solubility of artesunate for formulation studies

For the purpose of establishing the optimum processing parameters and storage conditions associated with nanolipid formulations of the artemisinin derivative artesunate, it was necessary to evaluate the thermal stability and solubility profiles of artesunate in aqueous solutions at various temperatures and pH. The effect of increased temperature and humidity on artesunate was determined by storing samples of the raw material in a climate chamber for 3 months and analyzing these by an established HPLC metho

DFT‐basierte Entdeckung von Ethynyl‐Triazolyl‐Phosphinaten als modulare Elektrophile für die chemoselektive Cystein‐Biokonjugation und Profilierung

Wir berichten über eine Dichtefunktionaltheorie (DFT)-basierte Entdeckung von Ethinyl-Triazolyl-Phosphinaten (ETP) als eine neue Klasse elektrophiler Verbindungen für die selektive Biokonjugation von Cystein. Mit Hilfe der CuI-katalysierten Azid-Alkin-Cycloaddition (CuAAC) in wässrigem Puffer konnten wir eine Vielzahl funktioneller elektrophiler Bausteine, darunter auch Proteine, aus Diethynylphosphinat herstellen. Wir verwendeten diese ETP-Reagenzien, um fluoreszierende Peptid-Konjugate für die Markierung von Rezeptoren auf lebenden Zellen sowie ein stabiles und biologisch aktives Antikörper-Wirkstoff-Konjugat zu erhalten. Darüber hinaus konnten wir ETP-Elektrophile unter nativen Bedingungen in ein Azid-haltiges Ubiquitin einbauen und ihr Potenzial für die Protein-Protein-Konjugation demonstrieren. Schließlich zeigen wir die exzellente Cystein-Selektivität dieser neuen Klasse von Elektrophilen in Massenspektrometrie basierten, proteomweiten Reaktivitätsstudien und unterstreichen damit die generelle Anwendbarkeit in homogenen Biokonjugationsstrategien zur Verknüpfung zweier komplexer Biomoleküle.Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659Leibniz-Gemeinschaft http://dx.doi.org/10.13039/501100001664Studienstiftung des Deutschen Volkes http://dx.doi.org/10.13039/501100004350Alexander von Humboldt-Stiftung http://dx.doi.org/10.13039/100005156Institute for Basic Science in KoreaPeer Reviewe