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Sacral neuromodulation (SNM) is an established, highly relevant, surgical therapy for faecal incontinence (FI). The spectrum of indications has evolved over time. Currently, these include a wide variety of pathophysiological and pathomorphological causes. However, they can extend beyond the exclusively faecal to include complex conditions such combined faecal and urinary dysfunction and low anterior resection syndrome (LARS). To improve the outcome of SNM further, crucial elements of the therapy such as electrode placement have been refined and standardized. This article addresses the scope of indications, highlights the results and the role of SNM in the treatment armamentarium of FI, and touches upon current trends.

Hemophilia A (HA) is a rare bleeding disorder caused by deficiency/dysfunction of the FVIII protein. As current therapies based on frequent FVIII infusions are not a definitive cure, long-term expression of FVIII in endothelial cells through lentiviral vector (LV)-mediated gene transfer holds the promise of a one-time treatment. Thus, here we sought to determine whether LV-corrected blood outgrowth endothelial cells (BOECs) implanted through a prevascularized medical device (Cell Pouch) would rescue the bleeding phenotype of HA mice. To this end, BOECs from HA patients and healthy donors were isolated, expanded, and transduced with an LV carrying FVIII driven by an endothelial-specific promoter employing GMP-like procedures. FVIII-corrected HA BOECs were either directly transplanted into the peritoneal cavity or injected into a Cell Pouch implanted subcutaneously in NSG-HA mice. In both cases, FVIII secretion was sufficient to improve the mouse bleeding phenotype. Indeed, FVIII-corrected HA BOECs reached a relatively short-term clinically relevant engraftment being detected up to 16 weeks after transplantation, and their genomic integration profile did not show enrichment for oncogenes, confirming the process safety. Overall, this is the first preclinical study showing the safety and feasibility of transplantation of GMP-like produced LV-corrected BOECs within an implantable device for the long-term treatment of HA.

Biologically, effectively regulated light with a wavelength of about 485 nm can support physiological processes in the body and has a positive impact on the human sleep–wake rhythm. However, the application of common light therapy devices is not always practicable and sometimes difficult to integrate into everyday life. Here, miniaturization of therapy devices, for example, in the form of contact lenses, can reduce the handling disadvantages. Especially, contact lenses modified with phosphorescence materials offer this benefit. Herein, a method to prepare phosphorescent Eu2+, Dy3+‐doped strontium aluminate nanoparticles (NPs) by laser vaporization of macroscopic Eu2+, Dy3+‐doped Sr4Al14O25 particle powder and their integration into polymer‐based contact lenses is provided. NPs with a diameter of about 34 nm emit light in the desired therapeutic wavelength region. These novel NPs are biocompatible and do not show any negative effects during the testing of eye irritation safety in a 3D in vitro cornea model.

The investigation of the biodistribution profile of a cell-based medicinal product is a pivotal prerequisite to allow a factual benefit-risk assessment within the non-clinical to clinical translation in product development. Here, a qPCR-based method to determine the amount of human DNA in mouse DNA was validated according to the guidelines of the European Medicines Agency and the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use. Furthermore, a preclinical worst-case scenario study was performed in which this method was applied to investigate the biodistribution of 2 × 106 intravenously administered, genetically modified, blood outgrowth endothelial cells from hemophilia A patients after 24 h and 7 days. The validation of the qPCR method demonstrated high accuracy, precision, and linearity for the concentration interval of 1:1 × 103 to 1:1 × 106 human to mouse DNA. The application of this method in the biodistribution study resulted in the detection of human genomes in four out of the eight investigated organs after 24 h. After 7 days, no human DNA was detected in the eight organs analyzed. This biodistribution study provides mandatory data on the toxicokinetic safety profile of an actual candidate cell-based medicinal product. The extensive evaluation of the required validation parameters confirms the applicability of the qPCR method for non-clinical biodistribution studies.

Advanced Therapy Medicinal Products (ATMP) provide promising treatment options particularly for unmet clinical needs, such as progressive and chronic diseases where currently no satisfying treatment exists. Especially from the ATMP subclass of Tissue Engineered Products (TEPs), only a few have yet been translated from an academic setting to clinic and beyond. A reason for low numbers of TEPs in current clinical trials and one main key hurdle for TEPs is the cost and labor-intensive manufacturing process. Manual production steps require experienced personnel, are challenging to standardize and to scale up. Automated manufacturing has the potential to overcome these challenges, toward an increasing cost-effectiveness. One major obstacle for automation is the control and risk prevention of cross contaminations, especially when handling parallel production lines of different patient material. These critical steps necessitate validated effective and efficient cleaning procedures in an automated system. In this perspective, possible technologies, concepts and solutions to existing ATMP manufacturing hurdles are discussed on the example of a late clinical phase II trial TEP. In compliance to Good Manufacturing Practice (GMP) guidelines, we propose a dual arm robot based isolator approach. Our novel concept enables complete process automation for adherent cell culture, and the translation of all manual process steps with standard laboratory equipment. Moreover, we discuss novel solutions for automated cleaning, without the need for human intervention. Consequently, our automation concept offers the unique chance to scale up production while becoming more cost-effective, which will ultimately increase TEP availability to a broader number of patients.

Die Förderung von wissens- und fähigkeitsbezogenen Aspekten der Diagnose von individuellen fachlichen Lernendenvorstellungen ist ein wichtiger Bestandteil vieler universitärer Fachdidaktiken. Unter Anwendung des Planungsrahmens der Didaktischen Rekonstruktion wurde daher eine Seminarkonzeption exemplarisch für die chemiedidaktische Lehre entwickelt und durchgeführt. In diesem Beitrag werden entsprechend zwei Ziele verfolgt: Einerseits wird eine Seminarkonzeption vorgestellt, welche zur Förderung der Diagnosefähigkeiten angehender Lehrkräfte beitragen soll und welche auch von weiteren Fachberei-chen verwendet werden kann, in denen Lernendenvorstellungen eine zentrale Rolle spielen. Andererseits wird die konkrete Anwendung der Didaktischen Rekonstruktion zur Planung dieses Seminars exemplarisch vorgestellt. Im Rahmen dieses Beitrags werden außerdem Evaluationsergebnisse aus zwei Umsetzungen des Seminars präsentiert. Diese zeigen, dass die Studierenden ihr diagnostisches Wissen sowie ihre diagnostischen Fähigkeiten im Rahmen des Seminars verbessern können. Auch ihre Perspektive hinsichtlich der Bedeutung von Lernendenvorstellungen für ihren späteren Unterricht entwickelt sich hin zu einer wertschätzenden Variante. Durch die Konfrontation mit alternativen Lernendenvorstellungen beginnen die Studierenden, kritisch ihr eigenes Fachwissen zu reflektieren, und ziehen Parallelen zwischen ihren persönlichen Lernprozessen und denen der Schüler*innen. In einem Ausblick werden Anknüpfungspunkte für kommende Lehrveranstaltungen skizziert.

Team-based design courses are offered in the majority of engineering programs. While teams are critically important for successfully completing design projects, the relationship between team characteristics and team performance are not fully understood. This paper presents an approach for identifying the characteristics of student design teams in the middle of a design course that significantly and positively correlate with the teams' performance at the end of the course. in this paper, we illustrate the approach in a two-semester capstone design course in which some team characteristics that significantly correlated with team performance were different in the middle and at the end of the course. For example, team characteristics that significantly correlated with team performance were team composition m both semesters, supportiveness oforganization context and teampsychological safety only in the first semester, and clear direction only in the second semester. By knowing such team characteristics, course instructors may be able to survey teams in the middle of a design course to find teams that have higher risks of performing poorly at the end of the course, take an early action to help those teams, and possibly improve their performance. [ABSTRACT FROM AUTHOR]