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ZusammenfassungDeutsch: Als häufige genetisch bedingte neurodegenerative Erkrankung ist die Huntington-Krankheit eine Modellerkrankung – auch für die Gentherapie. Unter den unterschiedlichen Möglichkeiten ist die Entwicklung von Antisense-Oligonukleotiden am weitesten fortgeschritten. Als weitere Optionen auf Ebene der RNA stehen Mikro-RNAs und Modulatoren der RNA-Prozessierung (Spleißen) zur Verfügung, auf DNA-Ebene Zink-Finger-Proteine. Mehrere Produkte befinden sich in der klinischen Prüfung. Diese unterscheiden sich in Applikationsform und systemischer Verfügbarkeit, aber auch in der genauen Wirkung. Ein wichtiger Unterschied könnte darin liegen, ob alle Formen des Huntingtin-Proteins gleichermaßen von der Therapie angesprochen werden, oder ob sich die Therapie präferentiell gegen besonders toxische Formen wie das Exon1-Protein richtet. Die Ergebnisse der kürzlich abgebrochenen GENERATION HD1 Studie waren etwas ernüchternd, am ehesten aufgrund der nebenwirkungsbedingten Liquorzirkulationsstörung. Sie sind daher nur ein Schritt in der Entwicklung zu einer wirksamen Gentherapie gegen die Huntington-Krankheit.

Recently, Jennifer Saul (“Racial Figleaves, the Shifting Boundaries of the Permissible, and the Rise of Donald Trump”, 2017; “Racist and Sexist Figleaves”, 2021) has explored the use of what she calls “figleaves” in the discourse on race and gender. Following Saul, a figleaf is an utterance that, for some portion of the audience, blocks the conclusion that some other utterance, R, or the person who uttered R is racist or sexist. Such racial and gender figleaves are pernicious, says Saul, because, among other things, they can shift the boundaries of what is deemed acceptable to think or say. This paper expands on Saul’s picture in a threefold way: It is first argued that appeals to statistics can function as figleaves. It is then argued that—as far as figleaves go—there is reason to believe that statistics-as-figleaves are especially pernicious. Finally, the paper explores some strategies for counterspeech.

Zusammenfassung Martin Bräuer analysiert die Kurienreform und ihre bisherigen Auswirkungen. Er gibt einen Überblick über den bisherigen Stand der Reformen, die auf dem Dokument „Praedicate Evangelium“ fußen. Weiter wird ein Blick auf die Initiative #OutInChurch geworfen und deren konkrete Auswirkungen auf das kirchliche Arbeitsrecht – im November 2022 wurde eine neue Grundordnung dazu verabschiedet. Anschließend werden die verschiedenen Formate von Synodalität und vor allem der aktuelle Stand des deutschen Synodalen Weges analysiert. Am Ende gibt Daniel Lenski einen kurzen Überblick über den im Juni 2022 veranstalteten Katholikentag in Stuttgart.

The ligand-activated nuclear receptor peroxisome-proliferator-activated receptor-γ (PPARG or PPARγ) represents a potential target for a new generation of cancer therapeutics, especially in muscle-invasive luminal bladder cancer where PPARγ is a critical lineage driver. Here we disclose the discovery of a series of chloro-nitro-arene covalent inverse-agonists of PPARγ that exploit a benzoxazole core to improve interactions with corepressors NCOR1 and NCOR2.

ZusammenfassungBei der Beurteilung der gesundheitlichen Eignung zum Lenken eines Kraftfahrzeuges ist die öffentliche Sicherheit (Unfallprävention) das vorrangige Ziel. Der generelle Zugang zu Mobilität sollte jedoch nicht eingeschränkt werden, wenn kein besonderes Risiko für die öffentliche Sicherheit besteht. Für Menschen mit Diabetes mellitus sind im Führerscheingesetz (FSG) und in der Führerscheingesetz-Gesundheitsversorgung (FSG-GV) wichtige Aspekte zur Fahrsicherheit in Zusammenhang mit akuten und chronischen Komplikationen der Erkrankung geregelt. Zu den kritischen Komplikationen, die für die Verkehrssicherheit relevant sind, gehören schwere Hypoglykämie, ausgeprägte Hyperglykämie und Hypoglykämiewahrnehmungsstörung, sowie schwere Retinopathie und Neuropathie, weiters fortgeschrittene Nierenerkrankung und bestimmte kardiovaskuläre Manifestationen. Bei Verdacht auf Präsenz einer dieser Akutkomplikationen oder Folgeschäden ist eine genaue Evaluierung erforderlich.Darüber hinaus ist die individuelle antihyperglykämische Medikation auf vorhandenes Potenzial für Hypoglykämien zu überprüfen. Sulfonylharnstoffe, Glinide und Insulin gehören in diese Gruppe und sind daher automatisch mit der Auflage einer 5‑jährigen Befristung des Führerscheines assoziiert. Metformin, DPP-4-Hemmer (Dipeptidyl-Peptidase-4-Hemmer, Gliptine), SGLT2-Hemmer (Sodium-dependent-glucose-transporter‑2 inhibitors, Gliflozine), Glitazone und die zu injizierenden GLP-1 Analoga (GLP‑1 Rezeptor Agonisten) weisen kein Hypoglykämiepotential auf und sind daher nicht mit einer Befristung verbunden.Die FSG-GV gibt Spielraum für Interpretation, sodass im Folgenden spezifische Themen zur Fahrsicherheit für Menschen mit Diabetes mellitus aus fachärztlicher und verkehrsrelevanter Sicht aufgearbeitet wurden. Dieses Positionspapier dient zur Unterstützung von Personen, die mit dieser herausfordernden Materie befasst sind.

Die Entwicklungspsychologie beschreibt ontogenetische Prozesse, bei denen es um zeitlich überdauernde, aufeinander aufbauende Veränderungen menschlichen Erlebens und Verhaltens über die gesamte Lebensspanne geht. In diesem Artikel erläutern wir den Zusammenhang zwischen ontogenetischen und phylogenetischen Prozessen, die das zentrale Forschungsinteresse der Vergleichenden Psychologie darstellen. Untersuchungsgegenstand sind hierbei Gemeinsamkeiten und Unterschiede zwischen Menschen und verschiedenen Tierarten, die zum Beispiel Aufschluss über die Evolution von Kognition geben können. Hunde spielen dabei eine besondere Rolle: sie haben durch ihre lange Domestikationsgeschichte einzigartige Fähigkeiten in den Bereichen Kommunikation, Aufmerksamkeit und Kooperation erlangt. Durch die konvergente Entwicklung von Hund und Mensch durch den ähnlichen Selektionsdruck auf beide Spezies, kann man bei einigen dieser Eigenschaften sogar von menschenähnlichen Fähigkeiten sprechen. Developmental psychology describes ontogenetic processes that involve temporally persistent, sequential changes in human experience and behavior across the lifespan. In this article, we explain the relationship between ontogenetic and phylogenetic processes, which are the central research interest of comparative psychology. The targets of such investigations are similarities and differences between humans and various animal species, which can, for example, provide information about the evolution of cognition. Dogs play a special role in this context: Because of their long history of domestication, they have developed unique abilities in communication, attention, and cooperation. The convergent evolution of dogs and humans through similar selection pressures on both species allows us to even speak of human-like abilities in some of these characteristics.

Zusammenfassung In diesem Beitrag wird zunächst ein Blick auf die Geschichte und Entwicklung des Konfessionskundlichen Instituts von 1947 bis heute geworfen. Stand in den ersten Jahren und Jahrzehnten vor allem die römisch-katholische Kirche in Deutschland und Europa im Zentrum der Arbeit, so fächerten sich ab der zweiten Hälfte der sechziger Jahre die Aufgaben immer mehr auf. In einem zweiten Teil wird auf die Methoden der konfessionskundlichen Arbeit geschaut und dargelegt, wie heute diese Arbeit methodisch geschieht.

Von Transportaufträgen „per Zuruf„ bis zu vollständig digitalisierten Prozessen: Das Städtische Klinikum Dresden hat bei der Digitalisierung seiner Logistikprozesse einen weiten Weg zurückgelegt. Dieser war mitunter steinig, unterm Strich jedoch sehr erfolgreich – und ist noch lange nicht zu Ende.

Der Klimawandel und der hohe Grad an Automobilität ain der Stadt sind mit starken Umweltbelastungen verbunden. Ein deutliches Umsteuern mit dem Ziel einer resilienten Stadtentwicklung ist erforderlich. Das Quartier gilt hier als bedeutende räumliche Ebene für die Umsetzung einer sozial-ökologischen Transformation.

Dioxygenases catalyze stereoselective oxygen atom transfer in metabolic pathways of biological, industrial, and pharmaceutical importance, but their precise chemical principles remain controversial. The α-ketoglutarate (αKG)-dependent dioxygenase AsqJ synthesizes biomedically active quinolone alkaloids via desaturation and subsequent epoxidation of a carbon-carbon bond in the cyclopeptin substrate. Here, we combine high-resolution X-ray crystallography with enzyme engineering, quantum-classical (QM/MM) simulations, and biochemical assays to describe a peroxidic intermediate that bridges the substrate and active site metal ion in AsqJ. Homolytic cleavage of this moiety during substrate epoxidation generates an activated high-valent ferryl (Fe

Core temperature monitoring is indispensable to prevent children from perioperative thermal perturbations. Although nasopharyngeal measurements are commonly used in anesthesia and considered to reflect core temperature accurately, standardized target depths for probe insertion are unknown in children.Our primary goal was to determine a target depth of nasopharyngeal temperature probe insertion in children by measuring distances on magnetic resonance imaging (MRI). Secondary aims were to correlate these measurements with biometric variables and facial landmark-distances to derive formulas estimating target depth.We conducted a prospective observational study in children ≤12 years undergoing cranial MRI with anesthesia. We documented patient characteristics and measured the landmark-distances nostril-mandible, nostril-tragus, and philtrum-tragus on patient's faces. On MRI, the target point for the probe tip was considered to be the site of the nasopharyngeal mucosa with the closest proximity to the internal carotid artery. After its determination in the transverse axis and triangulation to the sagittal axis, we measured the distance to the nostril. This distance, defined as target insertion depth, was correlated with the patient characteristics and used for univariate and multiple linear regression analysis.One hundred twenty children with a mean age of 4.5 years were included. The target insertion depth ranged from 61.8 mm in infants to 89.8 mm in 12-year-old children. Height correlated best (ρ = 0.685, 95%-CI: [0.57-0.77]). The best-fit estimation in millimeters, "40.8 + height [cm] × 0.32,″ would lead to a placement in the target position in 67% of cases. A simplified approach by categories of 50-80, 80-110, 110-130, and130 cm height with target insertion depths of 60, 70, 80, and 85 mm, respectively, achieved similar probabilities.Height-based formulas could be a valuable proxy for the insertion depth of nasopharyngeal temperature probes. Further clinical trials are necessary to investigate their measurement accuracy.

Zusammenfassung Zunächst wird die katholische Synodalität historisch betrachtet und versucht, die Entwicklungslinien bis heute nachzuzeichnen. In einem weiteren Schritt werden die aktuell gültigen kirchenrechtlichen Bestimmungen und dazu alternative Formen angeschaut. Ein eigener Blick wird auf den Synodalen Weg in Deutschland geworfen und schließlich wird die Diskussion über Synodalität unter dem gegenwärtigen Papst dargestellt und analysiert. Dabei wird auch die aktuell bis 2023 terminierte „Synode für die ganze Kirche“ in den Blick genommen.

Genetic and morphological characteristics of AML patients and healthy donors used for miR-181a/b expression and RASSF1A protein analysis.

Western blot analysis of p53 protein in puromycin and gfp sorted miR-ZIP-expressing NB4 cells. GAPDH was used as internal control. Values below the blots represent the median {plus minus} SD from three independent experiments.

Primer sequences used for mRNA applification by qPCR.

Genetic and morphological characteristics of APL patients used for miR-181a/b expression analysis.

A, Apoptosis assay in NB4 cells 24h and 48h after application of As2O3 (1 µM). B, FACS analysis for CD11b expression in As2O3 treated NB4 cells 48h after application. C, qPCR analysis for C/EBPβ mRNA expression in NB4 cells after As2O3 application. D, Apoptosis assay in NB4 cells 48h after application of doxorubicin (0.01 µg/ml) with or without cytarabine (0.05 µM). E, qPCR analys for C/EBPβ mRNA expression in NB4 cells after doxorubicin and cytarabine application. For qPCR measurement GAPDH was used as control. Bars and values in the dot blots represent the median {plus minus} SD from three independent experiments.* p-value {less than or equal to} 0.05; ** p-value {less than or equal to} 0.01.

Relying on aesthetic testimony seems problematic. For instance, it seems problematic for me to simply believe or assert that The Velvet Underground's debut album The Velvet Underground and Nico (1964) is amazing solely because you have told me so, even though I know you to be an honest and competent music critic. But why? After all, there do not seem to be similar reservations regarding testimony from many other domains. In this paper, I will argue that relying on aesthetic testimony seems problematic because we are attached to an ideal of aesthetic authenticity and feel that living up to this ideal is anathema to simply relying on aesthetic testimony.

The demand for novel antimicrobial compounds is rapidly growing due to the rising appearance of antibiotic resistance in bacteria; accordingly, alternative approaches are urgently needed. Antimicrobial peptides (AMPs) are promising since they are a naturally occurring part of the innate immune system and display remarkable broad-spectrum activity and high selectivity against various microbes. Marine invertebrates are a primary resource of natural AMPs. Consequently, cDNA expression (EST) libraries from the Cnidarian moon jellyfishAurelia auritaand the Ctenophore comb jellyMnemiopsis leidyiwere constructed inEscherichia coli. Cell-free size-fractionated cell extracts (< 3 kDa) of the two libraries (each with 29,952 clones) were consecutively screened for peptides preventing the biofilm formation of opportunistic pathogens using the crystal violet assay. The 3 kDa fraction of ten individual clones demonstrated promising biofilm-preventing activities againstKlebsiella oxytocaandStaphylococcus epidermidis. Sequencing the respective activity-conferring inserts allowed the identification of small ORFs encoding peptides (10 – 22 aa), which were subsequently chemically synthesized to validate their inhibitory potential. Biofilm-preventing effects againstK. oxytoca, Pseudomonas aeruginosa, S. epidermidis, andS. aureuswere verified for five synthetic peptides in a concentration-dependent manner, with peptide BiP_Aa_5 showing the strongest effects. The impact of BiP_Aa_2, BiP_Aa_5, and BiP_Aa_6 on dynamic biofilm formation ofK. oxytocawas further validated in microfluidic flow cells, demonstrating a significant reduction in biofilm thickness and volume by BiP_Aa_2 and BiP_Aa_5. Overall, the structural characteristics of the marine invertebrate-derived AMPs, their physicochemical properties, and promising anti-biofilm effects highlight them as attractive candidates for discovering new antimicrobials.

The associated diverse microbiome contributes to the overall fitness ofAurelia aurita, particularly to asexual reproduction. However, howA. auritamaintains this specific microbiome or reacts to manipulations is unknown. In this report, the response ofA. auritato manipulations of its native microbiome was studied by a transcriptomics approach. Microbiome-manipulated polyps were generated by antibiotic treatment and challenging polyps with a non-native, native, and potentially pathogenic bacterium. Total RNA extraction followed by RNAseq resulted in over 155 million reads used for ade novoassembly. The transcriptome analysis showed that the antibiotic-induced change and resulting reduction of the microbiome significantly affected the host transcriptome, e.g., genes involved in processes related to immune response and defense mechanisms were highly upregulated. Similarly, manipulating the microbiome by challenging the polyp with a high load of bacteria (2 × 107cells/polyp) resulted in induced transcription of apoptosis-, defense-, and immune response genes. A second focus was on host-derived quorum sensing interference as a potential defense strategy. Quorum Quenching (QQ) activities and the respective encoding QQ-ORFs ofA. auritawere identified by functional screening a cDNA-based expression library generated inEscherichia coli. Corresponding sequences were identified in the transcriptome assembly. Moreover, gene expression analysis revealed differential expression of QQ genes depending on the treatment, strongly suggesting QQ as an additional defense strategy. Overall, this study allows first insights intoA. aurita’sresponse to manipulating its microbiome, thus paving the way for an in-depth analysis of the basal immune system and additional fundamental defense strategies.

Climate change globally endangers certain marine species, but at the same time, such changes may promote species that can tolerate and adapt to varying environmental conditions. Such acclimatization can be accompanied or possibly even be enabled by a host’s microbiome; however, few studies have so far directly addressed this process. Here we show that acute, individual rises in seawater temperature and salinity to sub-lethal levels diminished host fitness of the benthicAurelia auritapolyp, demonstrated by up to 34 % reduced survival rate, shrinking of the animals, and almost halted asexual reproduction. Changes in the fitness of the polyps to environmental stressors coincided with microbiome changes, mainly within the phyla Proteobacteria and Bacteroidota. The absence of bacteria amplified these effects, pointing to the crucial importance of a balanced microbiota to cope with a changing environment. In a future ocean scenario, mimicked by a combined but milder rise of temperature and salinity, the fitness of polyps was severely less impaired, together with condition-specific changes in the microbiome composition. Our results show that the effects on host fitness correlate with the strength of environmental stress, while salt-conveyed thermotolerance might be involved. Further, a specific, balanced microbiome ofA. auritapolyps is essential for the host’s acclimatization. Microbiomes may provide a means for acclimatization, and microbiome flexibility can be a fundamental strategy for marine animals to adapt to future ocean scenarios and maintain biodiversity and ecosystem functioning.

The Cnidarian Aurelia aurita undergoes a complex life cycle alternating between the benthic polyp to the pelagic medusa. In absence of its natural microbiome, the asexual reproduction of this jellyfish is severely comprised, with limited strobilation and ephyrae release, whereas the recolonization of sterile polyps can restore this defect. Yet, the timing and molecular consequences of the microbiome during the strobilation process had not been investigated. Here, we demonstrate that a microbiota must be present at the polyp stage, before strobilation is initiated, to ensure normal asexual reproduction and a successful polyp-to-jellyfish transition. Addition of a microbiota at later stages of sterile animals failed to restore the defected process. Absence of a microbiome was accompanied with reduced transcription of developmental and strobilation genes. The transcription of strobilation genes was exclusively observed for native and recolonized polyps, pointing to the microbiome's impact on the strobilation process at the molecular level. Moreover, direct cell contact between the host and the bacteria was required for the generation of normal offspring. Overall, this study demonstrates that the timing of the host-microbe interaction in this developmental animal model is crucial, with the microbial impact being essential at the polyp stage, to ensure normal polyp-to-jellyfish transition.

Zusammenfassung Dieser Bericht wirft Schlaglichter auf die katholischen Kirchen, so auf die Enzyklika „Fratelli Tutti“, auf den weltweiten Synodalen Prozess und den deutschen Synodalen Weg als auch auf die versuchten Bischofsrücktritte in Deutschland und die „ökumenische Haftungsgemeinschaft“ aus der Sicht der Alt-Katholischen Kirche.

Mit Dünnschichtsensoren werden die Temperaturen, Kräfte und der Werkzeugverschleiß in Zerspanungsprozessen in unmittelbarer Nähe zur Wirkzone erfasst. Dadurch können zum einen analytische Modelle zur Beschreibung von Randschichtzuständen präzise kalibriert werden. Zum anderen kann mit den in-process erfassten Kenngrößen ein sogenannter Softsensor zur Regelung der Prozessstellgrößen implementiert werden, um gezielt Randzoneneigenschaften des Werkstücks einzustellen. Thin film sensors are used to record temperatures, forces and tool wear in machining processes in the immediate vicinity of the contact zone between tool and workpiece. On the one hand, this makes it possible to precisely calibrate analytical models for describing boundary layer conditions. On the other hand, the parameters recorded in-process can be used to implement a so-called soft sensor for controlling the process parameters in order to specifically adjust the properties of the subsurface layer of the workpiece.

Peripheral T-cell lymphomas (PTCL) - especially angioimmunoblastic (AITL) and follicular TCL - have a dismal prognosis due to lack of efficient therapies, and patients` symptoms are often dominated by an inflammatory phenotype including fever, night sweats, weight loss and skin rash. In this study, we investigated the role of inflammatory granulocytes and activated cytokine signaling on PTCL-TFH (T-follicular helper type) disease progression and symptoms. We show, that ITK-SYK driven murine PTCLs and primary human PTCL-TFH xenografts both induce inflammation in mice including murine neutrophil expansion and massive cytokine release. Granulocyte/lymphoma interactions were mediated by positive autoregulatory cytokine loops involving INF-γ (CD4+malignant T-cells) and IL-6 (activated granulocytes), ultimately inducing broad JAK kinase activation (Jak1/2/3, Tyk2) in both cell types. Depletion of inflammatory granulocytes via antibodies (Ly6G), genetic granulocyte depletion (LyzM-Cre/MCL1flox/flox) or the deletion of IL-6 within microenvironmental cells blocked inflammatory symptoms, reduced lymphoma infiltration and enhanced mouse survival. Furthermore, unselective JAK kinase inhibitors (ruxolitinib) inhibited both, TCL progression and granulocyte activation in various PTCL mouse models. Our results support the important role of granulocyte-driven inflammation, cytokine-induced granulocyte/CD4+ TCL interactions and the requirement of an intact JAK/STAT signaling pathway for PTCL-TFH development, and support broad JAK kinase inhibition as an effective treatment strategy in early disease stages.

Background Even though mandibular condyle fractures have a high clinical relevance, their treatment remains somewhat challenging. Open reduction and internal fixation are difficult due to narrow surgical approaches, poor overview during reduction, and a possible risk of facial nerve damage. In times of technical endeavors in surgery, there is a trend towards the usage of stable CAD-CAM-implants from additive manufacturing or titanium laser sintering. Up until now, there have not been any reports of fracture treatment of the mandibular condyle using this technique. Results and conclusion We present a workflow for virtual repositioning of the fractured mandibular condyle, to manufacture patient-specific implants for osteosynthesis with the intention of use of resorbable metal alloys in the future.

Monitoring peri-operative body temperature in children is currently mainly achieved through invasive devices. The Temple Touch Pro Temperature Monitoring System estimates core temperature noninvasively based on heat flux thermometry.To investigate the agreement of this noninvasive sensor against standard oesophageal core temperature.A prospective observational study.University hospital recruiting between April and July 2021.One hundred children (32 girls) aged 6 years or younger scheduled for noncardiac surgery, resulting in 6766 data pairs. Exclusion criteria were contraindication for the insertion of an oesophageal temperature probe, and procedures in which one of the measurement methods would interfere with the surgical field.Primary outcome was the agreement analysis by a Bland-Altman comparison with multiple measurements. Posthoc, we performed another agreement analysis after exclusion of a statistically determined equilibration time. Secondary outcomes were the temperature differences over time and subgroup analysis of hypothermic, normothermic and hyperthermic temperature ranges, age, sex and sensor's side by type III analysis of variance. Further, we correlated the sonographically determined depth of the artery with trueness.The mean difference was -0.07°C (95% CI -0.15 to +0.05) with limits of agreement of -1.00 and +0.85°C. After adjusting for an equilibration time of 13 min, the mean difference improved to -0.04°C (95% CI -0.08 to +0.01) with limits of agreement of -0.68 and +0.60°C. Concordance correlation coefficient was 0.83 (95% CI 0.82 to 0.84). Differences between the skin sensor and oesophageal reference increased over time by -0.05°C per hour. Subgroup analysis showed no clinically relevant differences. Depth of artery negatively correlated with trueness by 0.03°C per millimetre.Although the Temple Touch Pro sensor showed acceptable accuracy after allowing for an equilibration time, it still needs further investigation for routine use in children. This particularly affects accuracy in hypothermic ranges, imprecise positioning and applicability in children with immature or vulnerable skin.German Clinical Trials Register, identifier: DRKS00024703.

We propose heat machines that are nonlinear, coherent, and closed systems composed of few field (oscillator) modes. Their thermal-state input is transformed by nonlinear Kerr interactions into nonthermal (non-Gaussian) output with controlled quantum fluctuations and the capacity to deliver work in a chosen mode. These machines can provide an output with strongly reduced phase and amplitude uncertainty that may be useful for sensing or communications in the quantum domain. They are experimentally realizable in optomechanical cavities where photonic and phononic modes are coupled by a Josephson qubit or in cold gases where interactions between photons are transformed into dipole-dipole interacting Rydberg atom polaritons. This proposed approach is a step toward the bridging of quantum and classical coherent and thermodynamic descriptions.

Molecularly imprinted polymers (MIPs) are widely used as robust biomimetic recognition layers in sensing devices targeting a wide variety of analytes including microorganisms such as bacteria. Assessment of imprinting success and selectivity toward the target is of great importance in MIP quality control. We generated Escherichia coli-imprinted poly(styrene-co-DVB) as a model system for bacteria-imprinted polymers via surface imprinting using a glass stamp with covalently immobilized E. coli. Confocal Raman Microscopy was successfully employed to visualize bacteria, imprints, and polymer and to distinguish them from each other. The method has proven highly feasible for assessing if imprinting had been successful. In addition, we developed a method for selectivity investigation of bacteria MIPs based on combining Confocal Raman Microscopy and Partial Least Squares Discriminant Analysis (PLS-DA). The Raman spectra of E. coli and Bacillus cereus were acquired on E. coli-imprinted poly(styrene-co-DVB) and used to establish a PLS-DA model for differentiating between the bacteria species. Model validation demonstrated a correct classification of 95% of Raman spectra, indicating sufficient accuracy of the model for future use in MIP selectivity studies. Simultaneous differentiation of 3 bacteria species (E. coli, B. cereus, and Lactococcus lactis) on E. coli-imprinted poly(styrene-co-DVB) proved more difficult, which might be due to the limited depth resolution of the confocal Raman microscope resulting in the presence of interfering signals from the polymer substrate. It might be possible to overcome this obstacle by selective enhancement of the Raman signals originating from bacteria surfaces, such as tip enhanced Raman spectroscopy.

S1P is a pleotropic sphingolipid signalling molecule that acts through binding to five high-affinity G-protein coupled receptors. S1P-signaling affects cell fate in a multitude of ways, e.g. influencing cell differentiation, proliferation, and apoptosis, as well as playing an important role in immune cell trafficking. Though many effects of S1P-signaling in the human body have been discovered, the full range of functions is yet to be understood. For inflammatory skin diseases such as atopic dermatitis and psoriasis, evidence is emerging that dysfunction and imbalance of the S1P-axis is a contributing factor. Multiple studies investigating the efficacy of S1PR modulators in alleviating the severity and symptoms of skin conditions in various animal models and human clinical trials have shown promising results and validated the interest in the S1P-axis as a potential therapeutic target. Even though the involvement of S1P-signalling in inflammatory skin diseases still requires further clarification, the implications of the recent findings may prompt expansion of research to additional skin conditions and more S1P-axis modulatory pharmaceuticals.

Im Automobil- und Maschinenbau werden massivumgeformte Bauteile in vielen Anwendungen eingesetzt. Die Gesenke für die Bauteile erfahren während der Umformung aufgrund von hohen Umformkräften und Temperaturen einen hohen Verschleiß. Um einen wirtschaftlichen Produktionsbetrieb zu ermöglichen, wurden Methoden zur Verminderung des Verschleißes bei der Halbwarmumformung untersucht. Eine vielversprechende Methode ist der Einsatz von Diamondlike-Carbon (DLC)-Verschleißschutzschichten.

Purpose Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The aetiology and pathogenesis are multifactorial, multifaceted, and not yet fully understood. The present study is intended to provide deeper insights into possible triggering factors and correlating comorbidities. Materials and Methods In German ophthalmological practices, 306 persons (174 women, 132 men, age: 18 – 87 years) were interviewed by questionnaire on concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the chi-squared test (SPSS statistical software). Results DES occurred with significantly (p Conclusion Some of the known comorbidities and DES risk factors, e.g., computer work or depression, were confirmed. In contrast, the higher prevalence of hyperlipidaemia, hyperuricaemia, osteoporosis, nephrolithiasis, and fibroids among DES patients has not previously been reported. Additional studies should be performed on causal connections between DES and specific comorbidities.

Dry eye syndrome (DES) is one of the most common diseases of the ocular surface. Affected persons suffer from different subjective complaints, with sometimes severe impairment in the quality of life. The etiology and pathogenesis is multifactorial, multifaceted and not yet fully understood. The present work should provide deeper insights into possible triggering factors and correlating comorbidities.In German ophthalmological practices 306 persons (174 women, 132 men, age: 18-87 years) were interviewed by questionnaire regarding concomitant diseases and possible further triggering factors. DES was diagnosed by an ophthalmologist in 170 cases. The statistical comparative analysis between persons with and without DES was carried out using the Chi-square test (SPSS statistical software).DES occurred with a significantly (p0.05) increased frequency in women over 40 years of age, as well as in persons exposed to screen work, air conditioning, persons with chronic ocular inflammation, myomas (hysterectomy), dry skin, arterial hypertonicity in need of medication, cardiac arrhythmias, fatty liver, gastric ulcer, appendicitis, cholecystectomy, depression, hyperlipidemia, hyperuricemia, osteoporosis and nephrolithiasis.Some of the known comorbidities and DES-risk factors, e.g. computer work or depression were confirmed. In contrast, the higher prevalence of hyperlipidemia, hyperuricemia, osteoporosis, nephrolithiasis, and fibroids among DES-patients was described for the first time in this work. Causal connections between DES and certain comorbidities should constitute the subject of further investigation in the future. Zusammenfassung Zielsetzung: Das Trockene Auge (TA) ist eine der häufigsten Erkrankungen der Augenoberfläche. Betroffene leiden unter verschiedenen subjektiven Beschwerden, die die Lebensqualität mitunter stark beeinträchtigen. Die Ätiologie und Pathogenese sind multifaktoriell, vielschichtig und noch nicht vollständig geklärt. Die vorliegende Arbeit soll tiefere Einblicke in mögliche auslösende Faktoren und korrelierende Komorbiditäten geben.In deutschen Augenarztpraxen wurden 306 Personen (174 Frauen, 132 Männer, Alter: 18-87 Jahre) per Fragebogen zu Begleiterkrankungen und möglichen weiteren auslösenden Faktoren befragt. In 170 Fällen wurde ein TA durch einen Augenarzt diagnostiziert. Die statistische Vergleichsanalyse zwischen Personen mit und ohne TA wurde mit dem Chi-Quadrat-Test (Statistiksoftware SPSS) durchgeführt. Ergebnisse: TA traten signifikant (p0,05) häufiger bei Frauen über 40 Jahren auf sowie bei Personen, die Bildschirmarbeit und Klimaanlagen ausgesetzt waren, bei Personen mit chronischen Augenentzündungen, Myomen (Hysterektomie), trockener Haut, arterieller Hypertonie, die medikamentös behandelt werden musste, Herzrhythmusstörungen, Fettleber, Magengeschwür, Blinddarmentzündung, Cholezystektomie, Depression, Hyperlipidämie, Hyperurikämie, Osteoporose und Nephrolithiasis. Schlussfolgerung: Einige der bekannten Komorbiditäten und TA-Risikofaktoren, z. B. Bildschirmarbeit oder Depression, wurden bestätigt. Die höhere Prävalenz von Hyperlipidämie, Hyperurikämie, Osteoporose, Nephrolithiasis und Myomen bei TA-Patientinnen wurde dagegen in dieser Arbeit erstmals beschrieben. Kausale Zusammenhänge zwischen TA und bestimmten Komorbiditäten sollten in Zukunft Gegenstand weiterer Untersuchungen sein.

The identification of material parameters accurately describing the region-dependent mechanical behavior of human brain tissue is crucial for computational models used to assist, e.g., the development of safety equipment like helmets or the planning and execution of brain surgery. While the division of the human brain into different anatomical regions is well established, knowledge about regions with distinct mechanical properties remains limited. Here, we establish an inverse parameter identification scheme using a hyperelastic Ogden model and experimental data from multi-modal testing of tissue from 19 anatomical human brain regions to identify mechanically distinct regions and provide the corresponding material parameters. We assign the 19 anatomical regions to nine governing regions based on similar parameters and microstructures. Statistical analyses confirm differences between the regions and indicate that at least the corpus callosum and the corona radiata should be assigned different material parameters in computational models of the human brain. We provide a total of four parameter sets based on the two initial Poisson’s ratios of 0.45 and 0.49 as well as the pre- and unconditioned experimental responses, respectively. Our results highlight the close interrelation between the Poisson’s ratio and the remaining model parameters.The identified parameters will contribute to more precise computational models enabling spatially resolved predictions of the stress and strain states in human brains under complex mechanical loading conditions.

Basophils are key effector cells in atopic diseases, and the signaling sphingolipid Sphigosine-1-phosphate (S1P) is emerging as an important mediator in these conditions. The possible interaction of S1P and basophils and the resulting biological effects have not yet been studied. We hypothesize that S1P influences the function of basophils in atopy and aim to elucidate the modes of interaction. S1P receptor (S1PR) expression in human peripheral blood basophils from atopic and non-atopic patients was assessed through qRT-PCR and flow cytometry analysis. Functional effects of S1P were assessed through a basophil activation test (BAT), calcium flux, apoptosis, and chemotaxis assays. Immunofluorescence staining was performed to visualize intracellular S1P. Human basophils express S1PR1, S1PR2, S1PR3, and S1PR4 on the mRNA level. 0.1 µM S1P have anti-apoptotic, while 10 µM exhibits apoptotic effects on basophils. Basophils from atopic patients show less chemotactic activity in response to S1P than those from healthy donors. Protein expression of S1PR1 is downregulated in atopic patients, and basophils in lesional AD skin possess intracellular S1P. These findings suggest that the interaction of S1P and basophils might be an important factor in the pathophysiology of atopy.

Purpose Following the introduction of the Regulation (EU) 2017/745 by the European Parliament, any bioactive substance or surgical implant introduced into the human body must be documented. The regulation requires any implant to be traced back to the manufacturer. Lot numbers need to be available for every single medical implant. Also, the manufacturer is required by law to provide implants individually packaged and sterilized. Previously, model tray systems (MOS tray) were used for osteosynthesis in oral and maxillofacial surgery, in which the individual implants could not be registered separately. The new regulation made it impossible to use such processes during surgery anymore and a need for a change in the medical practice surged. We examined a possible solution for the new legislation. The aim of this prospective cohort study is to analyze the MOS tray systems to osteosynthesis materials prepackaged in sets. We record and evaluate parameters such as surgical time and documentation time. We perform a short cost analysis of our clinic. The primary aim is to determine how much time is gained or lost by the mandatory increased patient safety. The secondary aim is to describe change in costs. Methods Patients that underwent standard surgical procedures in the clinic of oral and maxillofacial surgery of the faculty hospital Carl Gustav Carus in Dresden were included. We chose open reduction and internal fixation (ORIF) of anterior mandibular corpus fractures as well as mandibular advancement by means of bilateral sagittal split osteotomies (BSSO) as standardized procedures. Both of these procedures require two osteosynthesis plates and at least four screws for each plate. MOS trays were compared to prepackaged sterilized sets. The sets include a drill bit, two plates, and eight 5-mm screws. A total number of 40 patients were examined. We allocated 20 patients to the ORIF group and the other 20 patients to the BSSO group. Each group was evenly subdivided into a MOS tray group and a prepackaged group. Parameters such as the incision-suture time (IST) as well as the documentation time (DT) by the operating room (OR) staff to complete documentation for the implants are the main focus of investigation. Results For open reduction, the incision-suture time was significantly different in favor of the MOS tray (p p Conclusions By law, a change in the method of approaching surgery is necessary. For standardized procedures, the right choice of implants can lead to a reduction of documentation time and costs for implant material, sterilization, as well as utilizing less instruments. This in turn leads to lower costs for perioperative processing as well as provision of state-of-the-art implant quality implementing higher patient security.

Monoplanar microbeam irradiation (MBI) and pencilbeam irradiation (PBI) are two new concepts of high dose rate radiotherapy, combined with spatial dose fractionation at the micrometre range. In a small animal model, we have explored the concept of integrating MBI or PBI as a simultaneously integrated boost (SIB), either at the beginning or at the end of a conventional, low-dose rate schedule of 5x4 Gy broad beam (BB) whole brain radiotherapy (WBRT). MBI was administered as array of 50 µm wide, quasi-parallel microbeams. For PBI, the target was covered with an array of 50 µm × 50 µm pencilbeams. In both techniques, the centre-to-centre distance was 400 µm. To assure that the entire brain received a dose of at least 4 Gy in all irradiated animals, the peak doses were calculated based on the daily BB fraction to approximate the valley dose. The results of our study have shown that the sequence of the BB irradiation fractions and the microbeam SIB is important to limit the risk of acute adverse effects, including epileptic seizures and death. The microbeam SIB should be integrated early rather than late in the irradiation schedule.