Placebokontrollierte klinische Studie zum Effekt von Knoblauchtrockenpulver auf die Durchblutung bei gesunden Kontrollpersonen und Patienten mit systemischer Sklerodermie

Die biologischen Grundlagen der Wirkphysiologie von Knoblauch (Allium sativum) auf Blutrheologie und Vasomotion sind bisher weitgehend unbekannt. In einer randomisierten, doppelblinden Studie erhielten 20 Patientinnen mit systemischer Sklerodermie und 12 Probanden für 7 Tage je 900 mg Knoblauchtrockenpulver (Kwai, N oder Placebo / d als Add-on Medikation) zur Standardherapie. Rheologische Parameter wurden zu Beginn, nach 1 Tag, sowie nach 7 Tagen Therapiedauer bestimmt. Eine Beurteilung der Vasomotion erfolgte mittels NIRP, einem Verfahren zur Beurteilung der Mikrozirkulation, sowie mittels Messung der akralen Hauttemperatur. 7 Tage Knoblauch- bzw. Placebotherapie ergaben nur bei den Verum-behandelten Patienten eine signifikante Abnahme der Erythrozytenaggregation und ADP-induzierter Thrombozytenaggregation. Signifikante Effekte auf die Gefäßregulation ergaben sich nicht, die akrale Hauttemperatur wurde durch die Knoblauch gesteigert

Peculiarities of structural-phase state of multi-layer coatings based on Zr-Y-O

Using high-resolution transmission electron microscopy it was established that the Zr-Y-O-based coating layers have a ZrO[2] phase in the tetragonal and monoclinic modifications in the initial state. When it is heated up to 900°C, the ZrO[2] phase in the cubic modification appears in the layer of the coating. With an annealing time of 20 minutes, the grains are crushed to a size of about 15-20 nm. The microdiffraction pattern is modified, the number of reflexes of the tetragonal and monoclinic phases first increases, and then changes without systemic

MODELLING TECHNICAL SYSTEMS IN THE EARLY PHASE: PROPOSING A FORMAL DEFINITION FOR THE SYSTEM CONCEPT

The task of developing “concepts” is common in all fields of engineering, especially in the early phases of product development. However, an in-depth literature analysis showed that authors - often depending on different contexts in design research, education, and industry - define the term “concept” in differing ways. The aspect of reference-based development is rarely addressed in existing definitions. This indicates that there is a need for an updated and concise concept definition. In this paper, the authors propose a new definition of the term “system concept” within the context of SGE - System Generation Engineering that incorporates the findings from the literature analysis. The definition was reflected on in two case-studies. The first one contained the system concept for automotive display and operating systems, the second one the system concept for a kinesthetic-haptic VR interface. The proposed definition contains the relevant characteristics identified from the literature review and supports both current activity-based process models and reference-based development, as practical application has shown

Inhibition of lysyl oxidases synergizes with 5-azacytidine to restore erythropoiesis in myelodysplastic and myeloid malignancies

Limited response rates and frequent relapses during standard of care with hypomethylating agents in myelodysplastic neoplasms (MN) require urgent improvement of this treatment indication. Here, by combining 5-azacytidine (5-AZA) with the pan-lysyl oxidase inhibitor PXS-5505, we demonstrate superior restoration of erythroid differentiation in hematopoietic stem and progenitor cells (HSPCs) of MN patients in 20/31 cases (65%) versus 9/31 cases (29%) treated with 5-AZA alone. This effect requires direct contact of HSPCs with bone marrow stroma components and is dependent on integrin signaling. We further confirm these results in vivo using a bone marrow niche-dependent MN xenograft model in female NSG mice, in which we additionally demonstrate an enforced reduction of dominant clones as well as significant attenuation of disease expansion and normalization of spleen sizes. Overall, these results lay out a strong pre-clinical rationale for efficacy of combination treatment of 5-AZA with PXS-5505 especially for anemic MN

Addiction Research Consortium: Losing and regaining control over drug intake (ReCoDe)—From trajectories to mechanisms and interventions

One of the major risk factors for global death and disability is alcohol, tobacco, and illicit drug use. While there is increasing knowledge with respect to individual factors promoting the initiation and maintenance of substance use disorders (SUDs), disease trajectories involved in losing and regaining control over drug intake (ReCoDe) are still not well described. Our newly formed German Collaborative Research Centre (CRC) on ReCoDe has an interdisciplinary approach funded by the German Research Foundation (DFG) with a 12-year perspective. The main goals of our research consortium are (i) to identify triggers and modifying factors that longitudinally modulate the trajectories of losing and regaining control over drug consumption in real life, (ii) to study underlying behavioral, cognitive, and neurobiological mechanisms, and (iii) to implicate mechanism-based interventions. These goals will be achieved by: (i) using mobile health (m-health) tools to longitudinally monitor the effects of triggers (drug cues, stressors, and priming doses) and modify factors (eg, age, gender, physical activity, and cognitive control) on drug consumption patterns in real-life conditions and in animal models of addiction; (ii) the identification and computational modeling of key mechanisms mediating the effects of such triggers and modifying factors on goal-directed, habitual, and compulsive aspects of behavior from human studies and animal models; and (iii) developing and testing interventions that specifically target the underlying mechanisms for regaining control over drug intake

Definitions and methods of measuring and reporting on injurious falls in randomised controlled fall prevention trials: a systematic review

<p>Abstract</p> <p>Background</p> <p>The standardisation of the assessment methodology and case definition represents a major precondition for the comparison of study results and the conduction of meta-analyses. International guidelines provide recommendations for the standardisation of falls methodology; however, injurious falls have not been targeted. The aim of the present article was to review systematically the range of case definitions and methods used to measure and report on injurious falls in randomised controlled trials (RCTs) on fall prevention.</p> <p>Methods</p> <p>An electronic literature search of selected comprehensive databases was performed to identify injurious falls definitions in published trials. Inclusion criteria were: RCTs on falls prevention published in English, study population ≥ 65 years, definition of injurious falls as a study endpoint by using the terms "injuries" and "falls".</p> <p>Results</p> <p>The search yielded 2089 articles, 2048 were excluded according to defined inclusion criteria. Forty-one articles were included. The systematic analysis of the methodology applied in RCTs disclosed substantial variations in the definition and methods used to measure and document injurious falls. The limited standardisation hampered comparability of study results. Our results also highlight that studies which used a similar, standardised definition of injurious falls showed comparable outcomes.</p> <p>Conclusions</p> <p>No standard for defining, measuring, and documenting injurious falls could be identified among published RCTs. A standardised injurious falls definition enhances the comparability of study results as demonstrated by a subgroup of RCTs used a similar definition. Recommendations for standardising the methodology are given in the present review.</p

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure