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The baseline examinations of the German National Cohort (NAKO) : recruitment protocol, response, and weighting
Get PDFThe German National Cohort (NAKO) is the largest population-based epidemiologic cohort study in Germany and investigates the causes of the most common chronic diseases. Between 2014 and 2019, a total of 1.3 million residents aged 20–69 years from 16 German regions were randomly selected from the general population and invited to participate following a highly standardized recruitment protocol. The overall response was 15.6% and differed considerably across study centers (7.6–30.7%). Females were more likely to participate than males (17.5% vs. 14.1%) and participation increased with age (10.2% in age group “ 60 years”). Across all study regions, response was highest in rural areas (22.3%), followed by towns and suburbs (17.2%), and was lowest in cities (14.5%). Compared with the general population in the respective study regions, participants with low and medium education are underrepresented in the NAKO sample, while highly educated participants are overrepresented. Participants with non-German nationality and with a migration background are also underrepresented. Participants living in single households are underrepresented, while participants from larger households (2 or more persons) are overrepresented compared to the general population. Survey weights are made available to researchers along with the study data that account for the sampling design and adjust for differences in the distribution of age, sex, nationality (German vs. non-German), migration status, education, and household size
Seed-dispersing vertebrates and the abiotic environment shape functional diversity of the pantropical Annonaceae
Get PDFMutualistic interactions between fruiting plants and frugivorous animals are shaped by interaction-relevant functional traits. However, it is unclear whether ‘trait matching’ underlies broad-scale relationships in plant and frugivore species and their functional diversity.
We integrated novel trait data and global occurrences for c. 1900 species in a major tropical plant family (Annonaceae) with data for 7607 bird and mammal species, including 1418 frugivores, alongside data on the abiotic environment. We applied structural equation models to evaluate the direct and indirect drivers of global and continental variation in frugivory-related functional diversity in Annonaceae, and assessed frugivory-exclusive drivers through comparisons with non-frugivores.
We show that global variation in Annonaceae frugivory-related functional diversity is influenced by species richness (SRic) and trait matching with co-occurring frugivorous mammals. Frugivorous birds and mammals indirectly influenced Annonaceae functional diversity at continental scales by affecting Annonaceae SRic. We found that climate, elevation, and seed dispersers jointly shaped Annonaceae diversity globally.
Our results suggest that seed dispersal interactions with mammals are particularly important for shaping global variation in Annonaceae diversity, possibly through mutualistic co-evolutionary dynamics. However, distinct effects of frugivores on Annonaceae diversity across biogeographical realms suggest that biogeography modulates how mutualistic interactions promote diversity
Management of sacroiliac joint pain : current concepts
Get PDFIntroduction:
Managing sacroiliac joint (SIJ) pain is challenging and unpredictable. There are no internationally accepted recommendations. In light of the lack of global consensus and guidelines and the ongoing advancements in management options, a widely accepted treatment algorithm remains absent. This systematic review updates and evaluates the existing evidence on strategies for managing SIJ pain.
Methods:
This study followed the guidelines defined in the 2020 PRISMA statement. All clinical studies concerning the clinical management of SIJ pain were considered. Web of Science, PubMed, and Embase were accessed in January 2025 without additional filters or temporal constraints. The risk of bias evaluation and statistical analysis followed the guidelines described in the Cochrane Handbook for Systematic Reviews of Interventions.
Results:
Fifteen randomised controlled trials, 13 clinical trials, and 10 retrospective studies were included. Data from 2666 patients (1429 women) were retrieved. The mean length of follow-up was 14.7 ± 15.2 months. The mean age was 54.0 ± 5.8 years, and the mean BMI was 28.5 ± 2.5 kg/m2. Non-surgical options primarily focus on physical therapy to relieve discomfort. Different medications aim to decrease inflammation and pain at the SIJ. Fluoroscopically guided SIJ injections allow for directly administering steroids or mesenchymal stem cells into the joint. Radiofrequency denervation is frequently used to address SIJ pain, while surgical fusion is usually reserved for cases where conservative treatment is ineffective.
Conclusion:
Managing SIJ pain is challenging due to limited and inconsistent evidence. Treatment progresses from conservative options, physiotherapy, lifestyle changes, and non-steroidal anti-inflammatory drugs to more invasive approaches like injections, radiofrequency denervation, and, in severe cases, surgical management. Research limitations include small sample sizes, short follow-ups, and inconsistent methodologies. Future high-quality studies are needed to establish clear diagnostic and treatment guidelines, compare techniques, and explore new therapies like regenerative medicine
Boosting the host–guest binding by programming the curvature in geodesic nanoribbons
Get PDFThe curvature of an aromatic system is an essential parameter that can be used to program the self-assembly and host–guest complementarity in geodesic polyarenes. However, the challenging synthesis of curved aromatics impedes exploration of the related effects on the binding properties. The design and synthesis of a polyarene with programmed curvature fitting to C60 by a stepwise introduction of five-membered rings are presented to solve this challenge. Among several methods explored, the route utilizing cyclodehydrofluorination proved to be the most successful, in terms of the highest product yield. The binding studies suggest that fine-tuning the curvature in acyclic systems leads to a dramatic increase in affinity, embedding specific binding modes and selectivity, as revealed from the comparative studies with C60 and C70. Experimental and theoretical investigations with curved polyarenes of different sizes show that the buried surface area upon binding has a linear correlation with the binding energies. The curvature complementarity appeared to play a decisive role in achieving selective recognition of C70 via the formation of a 2:1 complex along the major axis with an overall constant of 108 M–2 and positive cooperativity. The developed nanoribbons bearing the curvature of C60 is the first all-carbon host showing binding affinities for fullerenes that are comparable with macrocyclic [10]CPP. The obtained data pave the way for understanding the properties of geodesic polyarenes and the design of new self-assembled materials based on fullerenes, nanotubes, and other curved structures
Development of a 19 F/1 H coil for a 7 T human magnetic resonance Imaging system with first results of non-invasive temperature measurements
Get PDFFluorinated substances have attracted increasing attention in recent decades due to their
interesting properties and potential uses in various research projects. 19 F is an ecellent
substance in magnetic resonance imaging (MRI) as it has a nuclear spin of 1
⁄ 2, a theoretically
similar MR sensitivity to protons and no natural occurence in the human body. Therefore,
fluorinated substances may be ideal for the development of contrast agents. However, the
construction of MRI coils is challenging due to the rather close Larmor frequencies of 1 H
and 19 F, which in turn complicates the decoupling of double-tuned coils.
To address this issue, an MRI coil was developed in the present work that allows 19 F
imaging to be performed with a 7 T MRI scanner. Due to broadband characteristics of
the 19 F coil, 1 H imaging was additionally enabled without the need for custom tuning of
additional coil elements. First, simulations for the coil design were carried out, effects with
different phantom types inside the developed four-element phased-array coil were discussed,
and a coil was constructed which provided a homogeneous B +
1 field within the phantoms.
The optimized simulated coil was finally built with 3D printing support and tested in the 7 T
whole body MRI. Various fluorinated substances were measured in aqueous solution, mostly
using trifluoroethanol (TFE) and heptafluorobutyric acid (HFBA). It was shown that both
19 F and 1 H imaging is possible with the constructed coil. Additionally, series of experiments
were carried out to measure different concentrations. Here, concentrations as low as 700 μ M
of TFE could be detected by imaging with a signal-to-noise ratio of 2.5. This concentra-
tion in the used resolution corresponds to the detection of 5. 7 · 10 16 fluorine nuclei per voxel.
In addition to the imaging experiments, spectroscopic investigations were also carried
out at the 7 T MRI, which provided information about the structure as well as about
intermolecular interactions or general changes in the environment of the nucleus under
consideration. These results were confirmed by complementary measurements at a wide
bore 7 T nuclear magnetic resonance (NMR) spectrometer (300 MHz proton frequency).
Furthermore, the temperature-dependence of TFE and HFBA was determined using chemi-
cal shift imaging sequences proving that spatial resolution of spectroscopic measurements
is possible. The various fluorinated groups exhibit characteristic chemical shift differences
when the temperature changes. Using HFBA with its three fluorinated groups, a method
was developed that allows the temperature to be determined without an additional reference
substance to be recorded.
Concluding, this work was able to demonstrate that the developed 19 F MRI coil for 7 T MRI
showed a quality high enough to allow 19 F/ 1 H imaging, spatially resolved spectroscopy and
due to that temperature determination. It shows that further developments are promising
for subsequent studies.Fluorierte Substanzen haben in den letzten Jahrzehnten aufgrund ihrer interessanten Eigen-
schaften und potenziellen Verwendungsmöglichkeiten in verschiedenen Forschungsprojekten
zunehmend Aufmerksamkeit auf sich gezogen. In der Magnetresonanztomographie (MRT)
ist 19 F eine ausgezeichnete Substanz, da es einen Kernspin von 1
⁄ 2, eine theoretisch ähn-
liche MR-Empfindlichkeit wie Protonen hat und kein natürliches Fluor-Hintergrundsignal
im menschlichen Körper aufweist, was es ideal für die Entwicklung von Kontrastmit-
teln erscheinen lässt. Der Bau von MRT-Spulen ist jedoch aufgrund der relativ nahen
Larmor-Frequenzen von 1 H und 19 F, was eine Entkopplung der Elemente erschwert, eine
Herausforderung.
In der vorliegenden Arbeit wurde eine MRT-Spule entwickelt, die die Durchführung einer
19 F-Bildgebung mit einem 7 T-MRT ermöglicht. Aufgrund der Breitbandeigenschaften
der 19 F-Spule wurde zusätzlich die 1 H-Bildgebung ermöglicht, ohne dass eine individuelle
Abstimmung zusätzlicher Spulenelemente erforderlich war. Zunächst wurden Simulationen
für das Spulendesign durchgeführt, Effekte mit verschiedenen Phantomtypen innerhalb der
entwickelten 4-Element-Phased-Array-Spule diskutiert und schließlich eine Spule konstruiert,
die ein homogenes B +
1 -Feld innerhalb der Phantome erzeugte.
Die optimierte simulierte Spule wurde anschließend mit Unterstützung eines 3D-Drucks
gebaut und im 7 T-Ganzkörper-MRT getestet. Es wurden verschiedene fluorierte Sub-
stanzen, hauptsächlich Trifluorethanol (TFE) und Heptafluorbuttersäure (HFBA), in wäss-
riger Lösung gemessen und die Möglichkeit von 19 F- als auch 1 H-Bildgebung nachgewiesen.
Zusätzlich wurden Versuchsreihen zur Messung verschiedener Konzentrationen durchgeführt.
Dabei konnten Konzentrationen von nur 700 μ M TFE durch Bildgebung mit einem Signal-
Rausch-Verhältnis von 2,5 nachgewiesen werden. Diese Konzentration in der verwendeten
Auflösung entspricht dem Nachweis von 5.7 · 1016 Fluor-Kernen pro Voxel.
Zusätzlich zu den Bildgebungsexperimenten wurden auch spektroskopische Untersuchungen
am 7 T-MRT durchgeführt, die Informationen über die Struktur sowie über intermoleku-
lare Wechselwirkungen oder allgemeine Veränderungen in der Umgebung des betrachteten
Kerns lieferten. Diese Ergebnisse wurden durch ergänzende Messungen an einem 7 T-
Kernspinresonanz Spektrometer mit breiter Bohrung bestätigt. Darüber hinaus wurde
die Temperaturabhängigkeit von TFE und HFBA mithilfe von Chemical-Shift-Imaging-
Sequenzen, welche räumlich aufgelöste spektroskopische Messungen erlauben, untersucht.
Unter Verwendung von HFBA mit ihren drei fluorierten Gruppen, welche bei Temperaturän-
derung charakteristische Unterschiede in der chemischen Verschiebung aufweise, wurde eine
Methode entwickelt, mit der die Temperatur ohne zusätzliche Referenzsubstanz bestimmt
werden kann.
Zusammenfassend konnte diese Arbeit die Möglichkeit der 19 F/ 1 H-Bildgebung, der orts-
aufgelösten Spektroskopie und damit der Temperaturbestimmung mit der entwickelten
MRT-Spule aufzeigen. Sie zeigt, dass weitere Entwicklungen für nachfolgende Studien
vielversprechend sind.Literaturverzeichnis: Seite 82-9
Naphthalimide-buckybowl tweezer for selective recognition of fullerene C70
Get PDFSupramolecular tweezers-like receptors represent a simple and efficient approach for the molecular recognition of fullerenes. Straightforward synthesis and easy fine-tuning of their geometry are the advantages that allow one to achieve strong binding and specific selectivity. However, the use of buckybowls in constructing tweezers and incorporating fluorescent dyes is still underexplored. To achieve this goal, we have designed mono- and di-substituted receptors by attaching indacenopicene to a naphthalimide dye. The tweezers-like receptor shows the highest selectivity for C70 with an affinity of 2150 M−1, which is about 50-fold stronger than the recognition of C60. DFT and NMR data indicate that the preferred binding mode involves the ellipsoidal C70 molecule coordinating with buckybowls at its poles. In this arrangement, the naphthalimide core establishes two CH–π interactions with the fullerene. The results indicate that conjugating buckybowls with naphthalimides in a suitable design presents a promising method for selective binding and fine-tuning photoinduced electron transfer in the host–guest complex.70 in C70 im Titel tiefgestell
WildPosh : pan-European assessment, monitoring, and mitigation of chemical stressors on the health of wild pollinators
Get PDFWild fauna and flora are facing variable and challenging environmental disturbances. One of the animal groups that is most impacted by this, concerns pollinators. Pollinators face multiple threats, but the spread of anthropogenic chemicals (i.e. pesticides) form a major potential driver of these threats. WildPosh is a multi-actor, transdisciplinary project whose overarching mission and ambition are to significantly improve the evaluation of risk to pesticide exposure of wild pollinators, and enhance the sustainable health of pollinators and pollination services in Europe. As chemical exposure varies geographically, across cropping systems, inside the crop system and among pollinators, we will characterise exposure by doing fieldwork in 4 countries representing the four main climatic European regions, Mediterranean, Atlantic, Continental and Boreal climate in Germany, England, Estonia and Spain. We will also develop experiments in controlled conditions on different species of bees, syrphid flies, moths and butterflies, and collect in silico data on their traits and on toxicity of pesticides. With WildPosh, we aim to achieve the following objectives: 1. Determining the real-world agrochemical exposure profile of wild pollinators at landscape level, within and among sites;
2. Using integrated and controlled laboratory and semi-field experiments to characterise causal relationships between pesticides and pollinator health;
3. Building an open database on pollinator traits/distribution and chemicals to define exposure and toxicity scenarios by developing databases on ecological traits and the spatial distribution of pollinators in relation to their potential exposure to pesticide;
4. Proposing integrated systems-based risk assessment tools for risk assessment for wild pollinators; and
5. Driving policy and practice through interactive innovation, meeting the need for monitoring tools, novel and innovative screening protocols for practice and policymaker use
High-throughput assessment of anemophilous pollen size and variability using imaging cytometry
Get PDFPollen grain size relates to plant community structure via pollen dispersal, plant resource allocation into regenerative processes, plant phylogeny and plant genetics (ploidy), or it can be used as a decisive trait for pollen species distinction. However, the availability of pollen size data is limited because of labor- and time-consuming methodological constraints and is classically based on fewer than 50 measured pollen grains per species, thus restricting our knowledge of the temporal and spatial variability of pollen size in response to biotic and abiotic conditions.
We addressed this data gap by using imaging flow cytometry (IFC), which allows for high-throughput assessment of pollen size and measured > 500 000 single pollen from 100 anemophilous species that were sampled between 2018 and 2022.
We present a workflow for high-throughput data analysis, show the agreement of IFC estimates with literature size estimates and assess pollen size variability in the context of plant phylogeny.
Our approach allows us to make statistically robust measurements of pollen size that are not limited by sampling effort and sample throughput to answer broad ecological questions at large temporal and spatial scales
Digital participation with the help of participatively developed information and counselling concepts : a qualitative study with the elderly
Get PDFHintergrund: Mit der zunehmenden Digitalisierung ländlicher Versorgungsstrukturen gewinnt die Vermittlung von digitalen Kompetenzen für Senior:innen an Bedeutung. Telemedizinische Angebote bieten bspw. das Potenzial, fehlende Zugänge zu fachmedizinischer Versorgung auszugleichen. Dem stehen fehlende Informationsangebote entgegen, die Zugänge ermöglichen und digitale Anwendungskompetenzen älterer Menschen unterstützen. Das Ziel der Studie ist es, die Perspektiven von Senior:innen zu Informations-und Beratungsangeboten zum Thema Digitalisierung in der Gesundheits-und Pflegeversorgung zu explorieren und somit einen Startpunkt in ein partizipatives Forschungsprojekt zu initiieren.
Methode: Es wurden explorierende, leitfadengestützte Fokusgruppen mit Senior:innen in ausgewählten ländlichen Kommunen durchgeführt. Die Auswertung erfolgte mithilfe der Inhaltsanalyse nach Gläser und Laudel (2010) im Rahmen eines iterierenden Erhebungsprozesses.
Ergebnisse: Es nahmen n = 21 Personen an den Fokusgruppen teil. Die Senior:innen nehmen eine deutliche Rückbildung der kommunalen Infrastruktur wahr, welche die gesundheitliche Versorgungssicherheit beeinflusst. Die Digitalisierung in der Gesundheits-und Pflegeversorgung nehmen sie als problematisch wahr und haben Sorgen, digital abgehängt zu werden. Es mangelt an praktischen Erfahrungen im Alltag sowie an Zugängen zu Informationen. Die Informationsgewinnung zu versorgungsrelevanten Themen sollte in direktionaler Form, durch persönliche Begegnungen, ermöglicht werden.
Schlussfolgerung: Es mangelt an erlebbaren Zugängen zur Digitalisierung in der Gesundheits-und Pflegeversorgung für Senior:innen in ländlichen Regionen. Daher werden Aspekte der digitalen Transformation häufig negativ konnotiert. Dabei könnten positive Alltagserfahrungen sowie kontinuierliche Angebote zur digital-unterstützenden Versorgung das vorhandene Interesse weiter ausbauen
Identification and characterization of the RNA modifying factors PUS7 and WTAP as key components for the control of tumor biological processes in renal cell carcinomas
Get PDFCurrent research discusses the putative importance of RNA modification in tumor diseases. These RNA modifications include predominantly pseudouridinylation, ortho-methylations on the ribose residues, as well as methylations on the organic bases. Such chemical modifications directly influence fundamental properties such as transcript stability, alternative splicing, and translation efficiency, all of which are basic requirements for (tumor) cell proliferation, cell metabolism, cell migration, apoptosis resistance, etc. In this comparative study, the two RNA-modifying factors, pseudouridine synthase 7 (PUS7, RNA pseudouridinylation) and WT1-associated protein (WTAP, m6A RNA methylation), were identified using data from human renal cell carcinoma (RCC) tumors. PUS7 and WTAP showed a statistically significant correlation with relevant proliferation and prognosis markers such as CXCR4, TP53, PTEN, and NRAS, as well as with the two tumor immune checkpoints HLA-G and LGALS9 and were directly associated with a statistically significant effect on overall survival. Furthermore, comparative analyses also identified further putative target mRNAs of importance for tumor biology of PUS7 and WTAP. In particular, components with direct relevance for mitosis, the cell cycle, and cell division, as well as the WNT pathway, were identified