48674 research outputs found
Sort by
Clinical Management Evaluation of Infected Arterial Vascular Grafts from a 10 Year Retrospective Cohort
Get PDFArterielle Gefäßprotheseninfektionen sind ein seltenes, für die betroffenen Patient:innen jedoch bedrohliches Krankheitsbild. Das heterogene klinische Erscheinungsbild, sowie die niedrige absolute Fallzahl erschweren die Diagnose, Therapie und den Behandlungserfolg maßgeblich. Aufgrund geringer Fallzahlen besteht aktuell eine erhebliche Wissenslücke hinsichtlich einer evidenz-basierten Diagnose und Therapie.
Um zu zeigen, welche Faktoren das Outcome arterieller Gefäßprotheseninfektionen beeinflussen, präsentieren wir eine retrospektive Kohorte, bestehend aus 78 Fällen operativ implantierter und konsekutiv infizierter arterieller Gefäßprothesen, die in einem Zeitraum von zehn Jahren an den Zentren der Charité behandelt wurden. Die Beurteilung des Outcomes erfolgte hinsichtlich der Symptomatik zum Zeitpunkt der Diagnose, klinischer mikrobiologischer und apparativer Diagnostik, sowie der antimikrobiellen und operativen Therapie und in Subkohorten, die sich durch den Zeitpunkt der Diagnose, der anatomischen Lokalisation der infizierten Prothese, sowie der erfolgten antimikrobiellen und operativen Therapieregimes definierten.
Die Studienkohorte besteht aus 30 early-onset (<8 Wochen nach Implantation) und 48 late-onset Gefäßprotheseninfektionen, die sich in 29 periphere und 49 aortale Infektionen
unterteilten. Zum Zeitpunkt der Erstdiagnose präsentierten sich early-onset Infektionen klinisch apparenterer als late-onset Infektionen. Das Zeitintervall zwischen der Implantation der Gefäßprothese und deren Infektion war bei aortalen Infektionen statistisch signifikant länger als bei peripheren Infektionen (Median 363 Tage versus Median 56 Tage; p=0,018). Das Auftreten einer Wundkomplikation oder -infektion im Rahmen der initialen Prothesenimplantation war ein unabhängigen Risikofaktor für ein frühes Auftreten (early-onset) der Infektion (OR 4,33 95% KI 1,6 - 12,4; p<0,001). Das Auftreten von Wundkomplikationen oder -infektionen im Rahmen der initialen Prothesenimplantation (OR 8,21 95% KI 1,86 – 36,36; p=0,006), sowie das Vorliegen einer late-onset Infektion (OR 7,27 95% KI 1,83 - 28,92; p=0,005) waren unabhängige Risikofaktoren für ein Therapieversagen. Patient:innen, die eine operative Entfernung der infizierten Prothese erhielten, zeigten ein signifikant höheres infektionsfreies Überleben als die Kohorte mit Prothesenerhalt (Median 10,68 Monate versus Median 26,61 Monate; p=0,037). Antimikrobiell adäquat therapierte Patient:innen wiesen zudem weniger Re-infektionen (12,5% versus 28,9%; p=0,001) und neu aufgetretene Pathogene während der laufenden antimikrobiellen Behandlung auf (13,5% versus 39,4%; p=0,013).
Zusammenfassend konnten wir in dieser Studie wesentliche Charakteristika klinischer Subkohorten arterieller Gefäßprotheseninfektionen erarbeiten, die einen relevanten Einfluss auf die Diagnose, Therapie und das Outcome betroffener Patient:innen ha-ben. Unsere Ergebnisse verdeutlichen die Notwendigkeit eines strukturierten multimodalen Therapieansatzes und einer zentrumsbasierten Behandlung, die die Dichte wissenschaftlicher Daten erhöhen und somit in Zukunft zur Optimierung der Prävention und Therapie der Gefäßprotheseninfektionen beitragen kann.Arterial vascular graft infections (VGI) are a rare but an often critical medical condition. Their heterogenous clinical appearance and a low absolute number of cases make the diagnosis and treatment difficult and lead to high rates of treatment failure. Rising numbers of implanted vascular grafts increase the clinical importance to adequately treat infected vascular grafts. Due to the low absolute number of infections, there currently is a lack of scientific data to improve evidence-based diagnosis and treatment of VGI.
Here, to identify risk factors associated with positive or negative outcome of VGI, we present a retrospective cohort of 78 patients treated for VGI in Charité-associated centers over ten years. We evaluate outcome regarding symptoms at time of diagnosis, diagnostics, as well as antimicrobial and surgical treatment. We compare the results of subgroups defined according to onset, anatomical location of the infected graft, and surgical/antimicrobial treatment status.
We included 30 early-onset (i.e. diagnosis less than eight weeks after graft implantation) and 48 late-onset infections, which split into 49 aortic and 29 peripheral vascular grafts. Aortic infections were associated with a later onset of infection (median 363 days versus median 56 days; p=0.040) while wound complication or infection after initial graft implantation were identified as an independent risk factor for an early onset of infection (OR 4.1 95% CI 0.11-0.96; p=0.042). Wound complication or infection after initial graft implantation (OR 8.21 95% CI 1.86 – 36.36; p=0.006), as well as a late onset of VGI (OR 7.27 95% CI 1.83 – 28.92; p=0.005) were identified as independent risk factors for treatment failure. We observed a longer overall infection-free survival in cases with surgical removal of the infected graft (median 10.68 months versus median 26.61 months p=0.037).
Patients who received adequate antimicrobial treatment showed a lower number of reinfections (12.5% versus 28.9%, p=0.001) and newly detected pathogens during active treatment (13.5% versus 39.4%; p=0.013).
In this study we identified characteristics within the analyzed subcohorts that impact diagnosis, treatment, and outcome of VGI. Our results highlight the necessity of structured and multidisciplinary VGI treatment approaches. Furthermore, we highlight that managing VGI in specialized centers can not only improve this interdisciplinary approach but also increase the availability of scientific data to improve VGI prevention and treatment
Role of Polyphenols in Dermatological Diseases: Exploring Pharmacotherapeutic Mechanisms and Clinical Implications
Get PDFAlthough not frequently lethal, dermatological diseases represent a common cause of consultation worldwide. Due to the natural and non-invasive approach of phytotherapy, research for novel alternatives, such as polyphenols, to treat skin disorders is a subject of interest in modern medicine. Polyphenols, in particular, have been considered because of their anti-inflammatory, antitumoral, antimicrobial, and antioxidant properties, low molecular weight, and lipophilic nature that enables the passage of these compounds through the skin barrier. This review discusses the treatment of common dermatological diseases such as acne vulgaris, fungal infections, dermatitis, alopecia, and skin cancer, using polyphenols as therapeutic and prophylactic options. The specific molecules considered for each disorder, mechanisms of action, current clinical trials, and proposed applications are also reviewed
Quantifying salt extrusion versus surface salt flow rates at Mt. Sedom to gain insights on its mechanics and potential external atmospheric forcing
Get PDFThe study of salt tectonics is essential due to its relevance in locating hydrocarbon reserves, providing storage for fuels and waste, and offering insights into extraterrestrial geology. Despite decades of research, salt extrusion and flow rates at the surface remain poorly characterized, even with frequent confusing terminology. In our study, we aim to separate both phenomena at one of the best test sites on Earth, Mt. Sedom, a prominent salt extrusion site in a tectonically active basin. We utilized InSAR (Interferometric Synthetic Aperture Radar) techniques to measure surface salt motion with high temporal resolution, analyzing 9.5 years of Sentinel-1 data to derive both vertical and horizontal displacement components. Our approach improves previous estimates that used only line-of-sight (LOS) measurements. We are able to estimate vertical uplift rates directly above the salt extrusion channel location inferred using mechanical modeling. We propose that these estimates are a much closer representation of the actual salt extrusion rates, and largely independent of the typically overlapping surface gravity-driven flow dynamics. The InSAR time-series suggests that thermal expansion is a first-order driver of the observed seasonal uplift and subsidence patterns. Moreover, for the first time in Mt. Sedom, displacement changes in response to weather (rainfall) were inferred to be statistically significant. We conclude that any rainfall event, regardless of its magnitude, might be sufficient to enhance salt flow rate. This can be explained as a result of salt dissolution and increased gravity-driven downslope movement in the salt glacier as the salt becomes wet, due to increased surface load or reduced viscous/frictional forces. By integrating InSAR measurements, mechanical modeling, and meteorological data, this study provides new constraints on surface salt motion at Mt. Sedom, improving our understanding of its driving mechanisms. Most importantly, our results reveal an immediate response of salt motion to rainfall, providing new insights into interactions between atmospheric and crustal processes
Tensor network analysis of the maple-leaf antiferromagnet spangolite
Get PDFSpangolite (Cu6Al(SO4)(OH)12Cl ⋅ 3H2O) is a hydroxy-hydrated copper sulfate mineral with a one-seventh depleted triangular lattice of Cu2+ ions in each layer. Experimental measurements revealed a non-magnetic ground state at T ~ 8 K with magnetic properties dominated by dimerization. We propose a spatially anisotropic Heisenberg model for the Cu2+ spin-1/2 degrees of freedom on this geometrically frustrated and effectively two-dimensional maple-leaf lattice, featuring five symmetry inequivalent couplings with ferromagnetic bonds on hexagons and antiferromagnetic triangular bonds. The validity of the proposed Hamiltonian is demonstrated by state-of-the-art tensor network calculations, which can assess both the nature of the ground state as well as low-temperature thermodynamics, including the effects of a magnetic field. We provide theoretical support for a picture of a non-trivially correlated dimer ground state, which accounts for the appreciable reduction of the magnetic moment at high temperatures observed in experiment, thereby resolving a long-standing puzzle. We predict the static spin structure factor as well as the emergence of magnetisation plateaus at high values of an external magnetic field, explore the nature of the quantum states in them, and study their melting with increasing temperature
De Novo Glycan Annotation of Mass Spectrometry Data
Get PDFCarbohydrates are fundamental molecules of life that are involved in virtually all biological processes. The chemical diversity of glycanscarbohydrate chainsenables diverse functions but also challenges analytics. Annotation of glycans in mass spectrometry (MS) data relies heavily on experimental databases or manual calculations, hindering the discovery of novel glycan compositions and structures. Here, we introduce GlycoAnnotateRa package in the open-source programming language Rfor de novo annotation of glycan compositions in MS data. GlycoAnnotateR calculates all possible monomer and modification combinations, which are then filtered against a defined set of chemical rules to provide biologically relevant compositions. The “glycoPredict” function can return compositions for oligosaccharides ranging from 1 to 22 monomers in length while accounting for four different modifications in under 10 min with less than 4 GB of random-access memory (RAM). Here, three case studies demonstrate the efficacy and versatility of GlycoAnnotateR: (1) accurate identification of mono- and oligosaccharide standards, (2) characterization of sulfated fucan oligosaccharides obtained by enzymatic digestion of fucoidan, a complex algal glycan, and (3) reproduction and expansion of glycan annotations for a published mouse lung MALDI-MS imaging data set previously annotated by NGlycDB. GlycoAnnotateR rapidly provides accurate annotations and complements existing R packages for MS data processing, enabling metabolomic and glycomic data integration. This combinatorial, rule-based approach enhances glycan annotation capabilities and supports hypothesis generation in glycoscience, expanding our ability to explore the chemical space of glycan diversity
Ist die Zeiß-Wollnysche Refraktometrie eine exakte Methode zur Fettgehaltbestimmung der Milch, und kann sie den wissenschaftlichen Methoden gleichwertig zur Seite gestellt werden?
Get PDFDigitalisat der Ausgabe von 1914, erschienen 202
Daphnia-associated bacterial communities correlate with diet quantity, environmental conditions, and epidemic size across natural outbreaks
Get PDFZooplankton-associated microbiomes play an important role for host health, and contribute to ecosystem processes such as nutrient cycling. Yet, few studies have assessed how environmental gradients and biotic interactions, including parasitism and diet, may shape the microbiome composition of wild zooplankton. Here, we analyzed the microbiomes of water fleas from the Daphnia longispina species complex using 16S rRNA gene sequencing and a long-term field dataset spanning six sampling events over 13 years. Sampling coincided with outbreaks of the virulent eukaryotic gut parasite Caullerya mesnili. Additionally, we explored how microbiome structure varied in relation to water parameters, phytoplankton density (i.e., Daphnia diet), and zooplankton density and community structure. Daphnia microbiomes displayed strong temporal variation and comparatively small differences based on host infection status. Microbiome beta diversity correlated with phytoplankton density but not with its community composition, including green algae, protists, and cyanobacteria. Environmental conditions, including temperature, dissolved oxygen, and cyanobacterial abundance—previously found to drive Caullerya epidemics—were also associated with distinct microbiome structures. Importantly, microbiome beta diversity co-varied with infection prevalence, suggesting a link between microbiome shifts, epidemic size, and environmental conditions driving large epidemics. Dominant bacterial taxa correlated with Daphnia density, whereas the phylogenetic composition of rare taxa was associated with total zooplankton density. These findings demonstrate the dynamic nature of Daphnia microbiomes and suggest potential mechanisms by which they may mediate disease dynamics, particularly through associations with diet quantity, temperature, and host population density
The Design of Current Replication Studies: A Systematic Literature Review on the Variation of Study Characteristics
Get PDFIn what aspects do replication studies differ from their primary studies? This question is central for providing insights into the reasons for the nonreplicability of psychological effects. So far, research on potential explanations for the nonreplicability of effects has mainly focused on publication bias and methodological challenges related to measurement error or statistical inference. The recently developed causal-replication framework directs attention toward controlling for differences in study characteristics, including variations in treatment conditions, outcome measures, recruitment, causal estimates, time, location, population, and setting. To contribute to this aim, we conducted a systematic literature review to investigate the design practices of current replication studies. We preregistered the assessment of study characteristics in a detailed review protocol and investigated the available information and intended or unintended variations across primary and replication studies. To do this, we compiled a database of studies that aimed to replicate a causal effect of a clearly stated primary study and that were published in impactful social- and cognitive-psychological journals between January 2017 and August 2022. Our review results highlight that compared with the primary study, authors of replication studies predominantly focus on controlling specific study characteristics in (i.e., methods, procedures, analysis) while often neglecting other study characteristics, such as population or setting. Furthermore, the results indicate that in most replication studies, multiple study characteristics are varied in the study comparison or are insufficiently reported. Accordingly, we discuss prevalent variations, reporting standards, and strategies for planning future replication studies
Entwicklung eines rekonstruierten, aus induzierten pluripotenten Stammzellen gewonnenen immunkompetenten Hautmodells
No full textThe assessment of skin sensitization is a crucial aspect of toxicology and regulatory safety testing, particularly for industries involving pharmaceuticals, chemicals, and cosmetics. Traditional animal-based assays, such as the Local Lymph Node Assay have been widely used for this purpose. However, these models face ethical concerns, regulatory restrictions, and limited predictive accuracy due to interspecies differences. To address these challenges, in vitro and in silico assays have been developed, but current methods only assess individual key events in the Adverse Outcome Pathway for skin sensitization, lacking a comprehensive evaluation of the sensitization process.
This thesis aimed to develop a fully immunocompetent human skin model derived entirely from induced pluripotent stem cells (iPSC) to provide a more physiologically relevant and scalable alternative for skin sensitization assessment. The skin model was built using iPSC-derived fibroblasts, keratinocytes, and dendritic cells (iPSC-FB, iPSC-KC and iPSC-DC), integrated into a three-dimensional skin structure. This innovation allows for the simultaneous evaluation of multiple key events in the sensitization process, including keratinocyte activation, dendritic cell maturation, and cytokine secretion, making it a more robust and mechanistically relevant tool for the detection of skin sensitizing substances.
To achieve this, hair follicle-derived keratinocytes were reprogrammed into iPSC using non-integrative Sendai virus vectors, ensuring genomic stability and ethical sourcing. These iPSC were then efficiently differentiated into functional skin-resident cells, including fibroblasts, keratinocytes, and dendritic cells. The differentiated cells exhibited characteristics comparable to their primary cell counterparts, with iPSC-FB demonstrating robust collagen secretion and extracellular matrix formation, and iPSC-KC expressing key epidermal differentiation markers. Additionally, iPSC-DC displayed antigen-presenting capabilities, as confirmed by the expression of CD86, HLA-DR, and CD209, and were able to induce allogeneic T-cell proliferation, confirming their immune functionality.
The developed iPSC-derived immunocompetent skin models were functionally evaluated using a Lucifer Yellow permeability assay to confirm epidermal barrier integrity, as well as assays evaluating the cell viability. Furthermore, a skin sensitization assay was conducted, where the model was exposed to sensitizers of varying potencies, including dinitrochlorobenzene, p-phenylenediamine, isoeugenol, resorcinol and the non-sensitizer glycerol. The results demonstrated increased dendritic cell maturation and cytokine secretion (IL-8, IL-1β, MIP-1β, IL-18, TSLP, and TGF-β1) in response to sensitizers, confirming the model’s ability to distinguish between sensitizing and non-sensitizing compounds. Notably, the immunocompetent skin model outperformed conventional skin models by integrating both key event 2 (keratinocyte activation) and key event 3 (dendritic cell activation), aligning with the Adverse Outcome Pathway framework and improving predictive accuracy.
This thesis represents a significant advancement in skin model development by creating a fully human, reproducible, and scalable system that eliminates the need for primary cell sourcing and animal testing. The iPSC-derived immunocompetent skin model holds broad applications in toxicology, the assessment of skin sensitizers, and disease modeling, offering a powerful platform for studying inflammatory skin conditions such as atopic dermatitis and psoriasis. Furthermore, the ability to generate patient-specific iPSC lines enables the development of personalized in vitro models for precision medicine and drug screening in the future.
By providing an ethically responsible and human-relevant alternative to current testing models, this study contributes to the ongoing efforts to replace, reduce, and refine (3R principles) the use of animal testing in toxicology. The fully integrated iPSC-derived skin model presents a scalable and standardized approach for evaluating chemical sensitization, advancing both scientific research and regulatory safety assessment. Future research should focus on further refining the model for clinical applications, integrating additional immune components, and expanding its use in genetic disease modeling and personalized therapeutic testing
Global Impacts Dataset of Invasive Alien Species (GIDIAS)
Get PDFInvasive alien species are a major driver of global change, impacting biodiversity, ecosystem services, and human livelihoods. To document these impacts, we present the Global Impacts Dataset of Invasive Alien Species (GIDIAS), a dataset on the positive, negative and neutral impacts of invasive alien species on nature, nature’s contributions to people, and good quality of life. This dataset arises from the Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services’ (IPBES) thematic assessment report of this topic. Data were compiled from published sources, including grey literature, reporting a direct observation of an invasive alien species’ impact. All impact records contain up to 52 fields of contextual information and attempt to link impacts to the global standard “environmental impact classification for alien taxa” (EICAT) and “socio-economic impact classification for alien taxa” (SEICAT). GIDIAS includes more than 22000 records of impacts caused by 3353 invasive alien species (plants, vertebrates, invertebrates, microorganisms) from all continents and realms (terrestrial, freshwater, marine), extracted from over 6700 sources. We intend GIDIAS to be a global resource for investigating and managing the variety of impacts of invasive alien species across taxa and regions