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

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

A Polyclonal Aptamer Library for the Specific Binding of the Gut Bacterium Roseburia intestinalis in Mixtures with Other Gut Microbiome Bacteria and Human Stool Samples

Roseburia intestinalis has received attention as a potential probiotic bacterium. Recent studies have demonstrated that changes in its intestinal abundance can cause various diseases, such as obesity, enteritis and atherosclerosis. Probiotic administration or fecal transplantation alter the structure of the intestinal flora, offering possibilities for the prevention and treatment of these diseases. However, current monitoring methods, such as 16S rRNA sequencing, are complex and costly and require specialized personnel to perform the tests, making it difficult to continuously monitor patients during treatment. Hence, the rapid and cost-effective quantification of intestinal bacteria has become an urgent problem to be solved. Aptamers are of emerging interest because their stability, low immunogenicity and ease of modification are attractive properties for a variety of applications. We report a FluCell-SELEX polyclonal aptamer library specific for R. intestinalis isolated after seven evolution rounds, that can bind and label this organism for fluorescence microscopy and binding assays. Moreover, R. intestinalis can be distinguished from other major intestinal bacteria in complex defined mixtures and in human stool samples. We believe that this preliminary evidence opens new avenues towards aptamer-based electronic biosensors as new powerful and inexpensive diagnostic tools for the relative quantitative monitoring of R. intestinalis in gut microbiomes

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

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

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