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Clear cell renal cell carcinoma is the most frequent malignant kidney tumor in adults. It is often associated with biallelic VHL mutations. We characterized our cell lines according to their HIF expression pattern. Cell lines RCC4, UOK-220 and CaKi-2 were assigned to subtype H1H2, cell lines 786-O and A-498 were assigned to subtype H2 and cell lines CaKi-1 and Rc-124 were assigned to subtype VHLwt.
Previous work of our group had shown, that p53 can be activated in ccRCC following irradiation but is not able to induce apoptosis. An important link to p53 activity with strong antiapoptotic qualities is the NFB pathway, which can be activated e. g. by irradiation.
We irradiated the three subtypes previously established as well as two control cell lines, SAOS-2 (p53 negative cell line) and HEK 293 (contains functioning p53) with 2 Gy and 10 Gy and analyzed several proteins of the pathway by using western blots. Several target genes with antiapoptotic qualities were analyzed by using rt-PCR.
We found, that out of the cell lines analyzed, both control cell lines (SAOS-2, HEK 293) showed the strongest response (activation of the NFB pathway) following irradiation. Among the three ccRCC subtypes the VHLwt cell lines showed the strongest response. H2 cell lines showed almost no response at all.
A connection between the missing ability of p53 to induce apoptosis and an induction of transcription factors by the NFB pathway could not be determined. We also could not determine biological differences between the subtypes.
We analyzed, whether any NFB proteins were present in the nucleus following irradiation and found, that only p50 homodimers were present in the nucleus. This might point towards p50 homodimers, which have been described to have different characteristics than heterodimers. More research is needed to analyze this important finding.
Seventeen bacterial strains able to suppress plant pathogens have been isolated from healthy Vietnamese crop plants and taxonomically assigned as members of the Bacillus cereus group. In order to prove their potential as biocontrol agents, we perform a comprehensive analysis that included the whole-genome sequencing of selected strains and the mining for genes and gene clusters involved in the synthesis of endo- and exotoxins and secondary metabolites, such as antimicrobial peptides (AMPs). Kurstakin, thumolycin, and other AMPs were detected and characterized by different mass spectrometric methods, such as MALDI-TOF-MS and LIFT-MALDI-TOF/TOF fragment analysis. Based on their whole-genome sequences, the plant-associated isolates were assigned to the following species and subspecies: B. cereus subsp. cereus (6), B. cereus subsp. bombysepticus (5), Bacillus tropicus (2), and Bacillus pacificus. These three isolates represent novel genomospecies. Genes encoding entomopathogenic crystal and vegetative proteins were detected in B. cereus subsp. bombysepticus TK1. The in vitro assays revealed that many plant-associated isolates enhanced plant growth and suppressed plant pathogens. Our findings indicate that the plant-associated representatives of the B. cereus group are a rich source of putative antimicrobial compounds with potential in sustainable agriculture. However, the presence of virulence genes might restrict their application as biologicals in agriculture.
Peatlands contribute to a wide range of ecosystem services. They play an important role as carbon sinks in their natural state, but when they are drained, they cause carbon emissions. Rewetting drained peatlands is required to reduce carbon emissions and create new carbon sinks. However, drained peatlands are commonly used as grassland or croplands; therefore, alternative agriculture schemes are required following rewetting. Paludiculture, i.e., agriculture on wet and rewetted peatlands, is an option in these areas after rewetting to produce biomass sustainably. Monitoring of peatland management is challenging, yet needed to ensure a successful rewetting and plantation of, e.g., Phragmites australis and Typha spp., two plants which are commonly used in paludiculture. Remote sensing is an excellent tool for monitoring the vegetation composition of vast rewetted peatland regions. However, because many peatland species have similar spectral characteristics, such monitoring is ideally based on high-spatial, high-temporal hyperspectral images. Data that complies with all these requirements does not exist on a regular basis. Therefore, we assessed the potential for mapping peatland vegetation communities in the Peene and Trebel river basins of the federal state of Mecklenburg-Western Pomerania, Germany, using multi-date hyperspectral (PRISMA) data. We used regression-based unmixing to map fractions of different peatland vegetation classes. Results were analyzed with regard to the contribution of multi-date observations and, in comparison, to multispectral datasets (Landsat-8/Sentinel-2). Our results showed that different classes are best mapped at different observation dates. The multi-date hyperspectral datasets produced less Mean Absolute Error (MAE = 16.4%) than the single-date hyperspectral images (ΔMAE + 1%), with high accuracies for all classes of interest. Compared to the results obtained with multispectral data from similar acquisition dates and annual spectral-temporal metrics (STM), the results from hyperspectral data were always clearly superior (ΔMAE + 4%). Besides the superior performance during comparisons, our results also indicate that information that can be derived from the hyperspectral data with the regression-based unmixing goes clearly beyond that of discrete classification. With more hyperspectral sensors coming up and an expected higher availability of multi-data hyperspectral imagery, these data can be expected to play a bigger role in the future monitoring of peatlands.
The male genitalia of pholcid spiders, which is one of the most species-rich spider families, are characterized by a procursus, which is a morphologically diverse projection of the copulatory organ. It has been shown that the procursus interacts with the female genitalia during copulation. Here, we investigate the function of the procursus in Gertschiola neuquena, a species belonging to the early branched and understudied subfamily Ninetinae, using behavioural and morphological data. Although many aspects of the copulatory behaviour of G. neuquena follow the general pattern described for the family, males use only one pedipalp during each copulation. Based on our micro-CT analysis of cryofixed mating pairs using virgin females, we can show that the long and filiform procursus is inserted deeply into the unpaired convoluted female spermatheca, and the intromittent sclerite, the embolus, is rather short and stout only reaching the most distal part of the female sperm storage organ. Histological data revealed that sperm are present in the most proximal part of the spermatheca, suggesting that the procursus is used to allocate sperm deeply into the female sperm storage organ. This represents the first case of a replacement of the sperm allocation function of the intromittent sclerite in spiders.
Background
The alignment of large numbers of protein sequences is a challenging task and its importance grows rapidly along with the size of biological datasets. State-of-the-art algorithms have a tendency to produce less accurate alignments with an increasing number of sequences. This is a fundamental problem since many downstream tasks rely on accurate alignments.
Results
We present learnMSA, a novel statistical learning approach of profile hidden Markov models (pHMMs) based on batch gradient descent. Fundamentally different from popular aligners, we fit a custom recurrent neural network architecture for (p)HMMs to potentially millions of sequences with respect to a maximum a posteriori objective and decode an alignment. We rely on automatic differentiation of the log-likelihood, and thus, our approach is different from existing HMM training algorithms like Baum–Welch. Our method does not involve progressive, regressive, or divide-and-conquer heuristics. We use uniform batch sampling to adapt to large datasets in linear time without the requirement of a tree. When tested on ultra-large protein families with up to 3.5 million sequences, learnMSA is both more accurate and faster than state-of-the-art tools. On the established benchmarks HomFam and BaliFam with smaller sequence sets, it matches state-of-the-art performance. All experiments were done on a standard workstation with a GPU.
Conclusions
Our results show that learnMSA does not share the counterintuitive drawback of many popular heuristic aligners, which can substantially lose accuracy when many additional homologs are input. LearnMSA is a future-proof framework for large alignments with many opportunities for further improvements.
Fortbildungen sind zentrale Lerngelegenheiten für die Professionalisierung pädagogischen Personals in Kindertageseinrichtungen. Inwiefern Inhalte von Fortbildungen in der alltäglichen Praxis Anwendung finden, stellt ein zentrales Qualitätskriterium von Fortbildungen dar. Daher existieren vielfältige Vorstellungen und Konzepte darüber, wie diese Anwendung – der Transfer – unterstützt werden kann. Der vorliegende Beitrag greift theoretische und empirische Erkenntnisse aus der Bildungs- und Lehr-Lernforschung auf und stellt ein Modell der Wissenstransformation von der Theorie in Handlungen und von Handlungen in die Theorie vor. Zentral an diesem Modell ist die Vorstellung, dass Wissen durch verschiedene Akteure (Fortbildner_innen sowie pädagogische Fachkräfte) transformiert wird und kontextuelle sowie individuelle Merkmale diesen Transformationsprozess beeinflussen. Implikationen für Forschung und -praxis werden diskutiert.
The multi-cell Penning–Malmberg trap concept has been proposed as a way to accumulate and confine unprecedented numbers of antiparticles, an attractive but challenging goal. We report on the commissioning and first results (using electron plasmas) of the World's second prototype of such a trap, which builds and improves on the findings of its predecessor. Reliable alignment of both ‘master’ and ‘storage’ cells with the axial magnetic field has enabled confinement of plasmas, without use of the ‘rotating wall’ (RW) compression technique, for over an hour in the master cell and tens of seconds in the storage cells. In the master cell, attachment to background neutrals is found to be the main source of charge loss, with an overall charge-confinement time of 8.6 h. Transfer to on-axis and off-axis storage cells has been demonstrated, with an off-axis transfer rate of 50% of the initial particles, and confinement times in the storage cells in the tens of seconds (again, without RW compression). This, in turn, has enabled the first simultaneous plasma confinement in two off-axis cells, a milestone for the multi-cell trap concept.
Das Zurücktreten der Erzählstimme in der Literatur der Hebräischen Bibel wurde oft benannt. Dies wurde allerdings nur selten mit der erzähltheoretischen Analysekategorie des Modus fundiert. Letzteres gilt besonders für die Darstellung von Figurenrede. Dabei ist umstritten, ob sich neben direkter und indirekter Rede auch erlebte Rede in der Hebräischen Bibel nachweisen lässt. Diese vor allem von Meir Sternberg vertretene Möglichkeit hat Cynthia L. Miller abgelehnt. Millers Einwände lassen sich aber mit einer linguistisch fundierten Erzählanalyse hinterfragen, was die grundsätzliche Möglichkeit erlebter Rede bei wᵉhinne-Phrasen begründet.
The controlled formation and adjustment of size and density of magnetic skyrmions in Ta/CoFeB/MgO trilayers with low Dzyaloshinskii–Moriya interaction is demonstrated. Close to the out-of-plane to in-plane magnetic spin reorientation transition, we find that small energy contributions enable skyrmion formation in a narrow window of 20 pm in CoFeB thickness. Zero-field stable skyrmions are established with proper magnetic field initialization within a 10 pm CoFeB thickness range. Using magneto-optical imaging with quantitative image processing, variations in skyrmion distribution and diameter are analyzed quantitatively, the latter for sizes well below the optical resolution limit. We demonstrate the controlled merging of individual skyrmions. The overall demonstrated degree of comprehension of skyrmion control aids to the development of envisioned skyrmion based magnetic memory devices.
Recent experimental campaigns in the Wendelstein 7-X stellarator, a
plasma-confining device designed to investigate the Magnetic Confinement Fusion
(MCF) approach to generating electrical power, have shown that the injection of
fuelling pellets had an unexpected and considerable impact on the performance of
the plasma. Rather than simply refuelling the device and `diluting' the plasma
energy, pellet injection is followed by a significant increase in the ratio of
the ion temperature to the electron temperature. It has been suggested that this
is not merely due to the improved confinement following the reduction of
turbulent transport after the pellet material has homogenised with the bulk
plasma, but also due to a direct transfer of energy from electrons to ions. The
proposed mechanism for this energy transfer is the ambipolar expansion of the
pellet plasmoid, the localised plasma structure produced by the
ionisation of ablated pellet material, along magnetic field lines.
Early work on pellet plasmoid expansion predicted that half the heating power
deposited in plasmoid electrons by collisions with hot ambient electrons is
transferred to plasmoid ions in the form of flow velocity as the plasmoid
expands. The complicated nature of the system of the pellet plasmoid embedded in
the ambient plasma, particularly the behaviour of electrons, which experience
many collisional and collisionless phenomena on multiple disparate timescales,
means that early models of the expansion were not wholly self-consistent, but
rather made use of strong approximations that apply in some regions of the
plasmoid but not in others. For example, only electrons and ions associated with
the plasmoid were rigorously treated, meaning that the framework was one of
`expansion into vacuum'. Combined with the assumption of Maxwellian electrons,
this led to an electric potential that was unbounded at infinity. Naturally, the
validity of the conclusions of such a model are called into question because the
approximations lose their validity far from the plasmoid and as time advances,
yet predictions about the final state of the plasma are desired. A deeper
investigation is required: careful consideration of the phenomena in question
and the timescales (and lengthscales) on which they act must be made in order to
rigorously construct a model that is valid throughout the entire expansion.
The first two papers presented in this thesis iterate on the model established
in the paper that first predicted the electron-to-ion energy transfer; their aim
was to find out how the character of the expansion changes with a more
sophisticated and accurate description of various phenomena, while remaining
within the existing framework of expansion into vacuum. Ultimately, we find that
the qualitative character is unchanged, and that approximately half the heating
power deposited in plasmoid electrons is transferred to ions.
Two other papers in this thesis address the limitations of the original model.
This is achieved by properly considering the electron kinetic problem in a
plasmoid. One paper considers the electron kinetic problem when electrons are
highly isotropised. In this case the kinetic equation can be integrated to
remove all but two independent variables, which is the maximum possible
reduction considering it is a time-dependent problem. The full nonlinear
integro-differential Landau self-collision operator is integrated exactly and
few approximations are made, leading to a rather general kinetic equation.
However, for fuelling pellets some anisotropy in the electron distribution is
expected. Another paper considers the electron kinetic problem (and the entire
plasmoid expansion) allowing for electron anisotropy. Careful consideration of
the ordering of timescales of electron phenomena in a pellet plasmoid leads to a
steady-state kinetic problem that we call collisional quasi-equilibrium (QE). QE
appears in many ways similar to the collisional steady-state characterising a
true thermal equilibrium. It was found that the time-dependent kinetic problem
of the earlier paper, with isotropic electrons, produces the QE distribution
function, corroborating the existence of the QE state. We then take moments of
the electron kinetic equation that is valid on the expansion timescale, assuming
that the electron distribution is that given as the solution to the QE kinetic
problem. This is completely analogous to what is done to obtain the Braginskii
equations or any Chapman-Enskog theory. The result is a set of equations for the
long-term evolution of the macroscopic quantities that describe the distribution
function existing in a quasi-steady-state at each point in time. It is from this
point that one may feasibly describe the plasmoid expansion with an accurate
picture of the electron kinetics and finally obtain the electron-to-ion energy
transfer so desired in a rigorous model of the expansion.
From a broader point of view, the two frameworks provided by these rigorous
investigations of the electron kinetic problem serve as a basis for the future
study of plasmoids. Such a `first-principles' approach to plasmoid dynamics is
novel and interesting in its own right, but it will be demonstrated that such an
approach is essential for pellet plasmoids owing to the fact that they are
poorly described by the `standard tools' of plasma physics.
Using the QE framework it was found that, once more, about half the heating
power experienced by plasmoid electrons is transferred to plasmoid ions. The
incredible robustness of the prediction of such an energy transfer is, in the
author's opinion, the result of the self-similar nature of the expansion found
as a solution to the original model. As a rule, the profiles of self-similar
solutions tend to be attractors for the `real', more complicated, system, and
the qualitative predictions involving no parameters, of which the
electron-to-ion energy transfer is one, tend to be very sturdy.
Aside from fuelling pellets, composed of hydrogen or deuterium, one paper in
this thesis investigates the physics of high-Z pellets that are designed to
terminate the plasma safely in the event of a `disruption', where much of the
magnetic field energy is channelled into a runaway electron beam with
potentially disastrous consequences if the beam encounters a plasma-facing
component. The paper draws on the work carried out in the paper concerning the
kinetic problem of isotropised electrons in a plasmoid.
This thesis is `cumulative'; the vast majority of the work carried out is
described within a set of Papers, labelled A-E, placed at the back of the text.
There is a preceding `wrapper text' (given in numbered Sections) tasked with
introducing the reader to the topic, guiding the reader through the papers, and
expounding some of their main results. Some amount of material not present in
the papers is also provided in the wrapper text. Naturally, the wrapper text
mainly focusses on the results of the papers which are under my first
authorship. In the course of publishing papers over an extended period of time
the nomenclature is bound to vary. Although it is mostly consistent between the
papers, a few difference do arise, and the section `Common symbols and
subscripts' is provided in the frontmatter to alleviate confusion. Particular
care should be taken with the symbols x and z; both can refer to the
coordinate parallel to the magnetic field line, but in papers where z is used
for this purpose x tends to have another definition. In the wrapper text the
choice of symbols is generally chosen to reflect those in the corresponding
paper.
Minced Cartilage Implantation in Acetabular Cartilage Defects: Case Series with 2-Year Results
(2023)
Objective
The objective was to evaluate clinical outcome and safety of arthroscopic, autologous minced cartilage implantation for acetabular cartilage lesions observed during hip arthroscopy to treat femoroacetabular impingement syndrome (FAIS).
Design
Eleven male patients, average age: 29.4 ± 5.4 years, average body mass index (BMI): 24.2 ± 2.2 kg/m2, scheduled for hip arthroscopy due to FAIS accompanied by an acetabular cartilage lesion were included in the case series. Cartilage tissue was harvested and minced from the loose cartilage flap at the chondrolabral lesion by arthroscopic shaver, augmented with autologous conditioned plasma, implanted into the defect, and fixated by autologous thrombin. Concomitant interventions were performed as indicated. The patients were evaluated preoperatively and at 24-month follow-up, using the International Hip Outcome Tool-12 (iHOT-12) and Visual Analog Scale (VAS) pain score and by magnetic resonance imaging (MRI) using the Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) grading scale at the 2-year follow-up.
Results
The defect size was on average 3.5 cm2 (1.5-4.5 cm2). From preoperatively to 2 years postoperatively, the iHOT-12 significantly improved from 50.2 ± 18 to 86.5 ± 19 (P < 0.0001), and pain score decreased from 5.6 ± 1.8 to 1.0 ± 1.5 (P < 0.0001) on the Visual Analog Scale pain score. Regarding functional outcome and pain, 10 of the 11 patients and all patients reached the minimal clinically important difference (MCID), respectively. The postoperative average MOCART score was 87.2 (± 9.2). No adverse events or reoperations were observed.
Conclusions
Arthroscopic, autologous minced cartilage implantation for treating full-thickness acetabular cartilage lesions in FAIS shows statistically and clinically significant improvement at short-term follow-up.
Background:
Minced cartilage implantation (MCI) has seen a renaissance in recent years. In this evolved technique, human articular cartilage is harvested with an arthroscopic shaver, augmented with platelet-rich plasma (PRP), and implanted with autologous thrombin. This modified technique combines the possibility of cell-based surgical cartilage repair with a minimally invasive autologous 1-step procedure. However, evidence on cell survival and preserved function after shaver-based mincing and PRP supplementation is limited.
Purpose:
To evaluate the effects of arthroscopic shaver mincing and augmentation with PRP on human cartilage tissue.
Study Design:
Controlled laboratory study.
Methods:
Standardized samples were taken from 12 donors during autologous MCI. A comparison of cell outgrowth, cell viability, proliferation capacity, and ability to produce extracellular matrix–specific proteoglycans after chondrogenic redifferentiation was made between cartilage taken by curettage from the border of the cartilage defect, cartilage tissue minced by an arthroscopic shaver, and cartilage tissue minced by an arthroscopic shaver that was additionally augmented with autologous PRP.
Results:
There was no difference between all 3 groups in terms of cell outgrowth or proliferation capacity. Metabolic activity relative to the cell number of chondrocytes isolated from shaver-minced cartilage was higher compared with chondrocytes isolated from cartilage that was derived by curettage or shaver-minced cartilage that was augmented with PRP. After chondrogenic stimulation, the normalized proteoglycan content was higher in spheroids of cells derived from shaver-minced cartilage augmented with PRP than in spheroids of cells derived from curettage. A high correlation of cell outgrowth, proliferation capacity, and viability between isolated cells from all 3 groups taken from an individual donor was observed.
Conclusion:
Chondrocytes isolated from human cartilage tissue that was harvested and minced with an arthroscopic shaver remained viable and proliferative. The augmentation of shaver-minced cartilage with PRP led to the enhanced proteoglycan production of chondrogenic spheroids in vitro, pointing toward the development of a cartilage-specific extracellular matrix. This in vitro study yields promising results regarding the use of an arthroscopic shaver and augmentation with PRP in the context of MCI.
Clinical Relevance:
Knowledge that shaver mincing and augmentation with PRP are feasible for processing articular cartilage during MCI is highly relevant for surgical cartilage repair.
Introduction: Vessel-associated retinal diseases are a major cause of blindness and severe visual impairment. The identification of appropriate biomarkers is of great importance to better anticipate disease progression and establish more targeted treatment options. MicroRNAs (miRNAs) are short, single-stranded, noncoding ribonucleic acids that are involved in the posttranscriptional regulation of gene expression through hybridization with messenger RNA. The expression of certain miRNAs can be different in patients with pathological processes and can be used for the detection and differentiation of various diseases. In this study, we investigate to what extent previously in vitro identified miRNAs are present as cell-free circulating miRNAs in the serum and vitreous of human patients with and without vessel-associated retinal diseases. Methods: Relative quantification by quantitative real-time polymerase chain reaction was used to analyze miRNA expression in patients with vessel-associated retinal diseases such as age-related macular degeneration (AMD), diabetic retinopathy (DR), and retinal vein occlusion compared with control patients. Results: In serum samples, miR-29a-3p and miR-192-5p showed increased expression in patients with neovascular AMD relative to control patients. Similarly, miR-335-5p, miR-192-5p, and miR-194-5p showed increased expression in serum from patients with proliferative DR. In vitreous samples, miR-100-5p was decreased in patients with proliferative DR. Differentially expressed miRNAs showed good diagnostic accuracy in receiver operating characteristic (ROC) and area under the ROC curve analysis. Conclusion: The miRNAs investigated in this study may have the potential to serve as biomarkers for vessel-associated retinal diseases. Combining multiple miRNAs may enhance the predictive power of the analysis.
In future fusion reactors disruptions must be avoided at all costs. Disruptions due to the density limit (DL) are typically described by the power-independent Greenwald scaling. Recently, a power dependence of the disruptive DL was predicted by several authors (Zanca et al 2019 Nucl. Fusion 59 126011; Giacomin et al 2022 Phys. Rev. Lett. 128 185003; Singh and Diamond 2022 Plasma Phys. Control. Fusion 64 084004; Stroth et al 2022 Nucl. Fusion 62 076008; Brown and Goldston 2021 Nucl. Mater. Energy 27 101002). It is investigated whether this increases the operational range of the tokamak. Increasing the heating power in the L-mode can induce an L-H transition, and therefore a power-dependent DL and the L-H transition cannot be considered independently. The different models are tested on a data base for separatrix parameters at the separatrix of ASDEX Upgrade and compared with the concept (SepOS) presented in Eich and Manz (2021 Nucl. Fusion 61 086017). The disruptive separatrix density scales with the power ne ∝ P0.38±0.08 in good agreement to all models. Also the back transition from high to low (H-L) confinement shows an approximately Greenwald scaling with an additional power dependence ne ∝ P0.4 according to the SepOS concept. For future devices operating at much higher heating power such a power scaling may allow operation at much higher separatrix densities than are common in H-mode operation. Preconditions to extrapolation for future devices are discussed.
The pulse length dependence of a reactive high power impulse magnetron sputtering (HiPIMS) discharge with a tungsten cathode in an argon+oxygen gas mixture gas was investigated. The HiPIMS discharge is operated with a variable pulse length of 20–500 µs. Discharge current measurements, optical emission spectroscopy of neutral Ar, O, and W lines, and energy-resolved ion mass spectrometry are employed. A pronounced dependence of the discharge current on pulse length is noted while the initial discharge voltage is maintained constant. Energy-resolved mass spectrometry shows that the oxygen-to-tungsten (O+/W+) and the tungsten oxide-to-tungsten (WO+/W+) ion ratio decreases with pulse length due to target cleaning. Simulation results employing the SDTrimSP program show the formation of a non-stoichiometric sub-surface compound layer of oxygen which depends on the impinging ion composition and thus on the pulse length.
Semiosis is the process in which a sign unfolds its effect—the meaning that humans ‘suddenly’ see in acts, objects or facts. The semiotic tenet is applied to the event and the question of why we narrate it. The graphics are dedicated to the author’s contribution: ‘The event and its consequences: a semiotic analysis.’
Ein wichtiges Nachsorgekonzept nach erfolgter Parodontitistherapie besteht im Angebot einer Unterstützdenden Parodontitis Therapie (UPT). Hierfür stehen herkömmliche Methoden wie Hand-, Schall- und Ultraschallinstrumente einerseits sowie Luft-Pulver-Wasserstrahlgeräte andererseits zur Verfügung.
Die vorliegende Arbeit untersucht in diesem Kontext einen spezifischen Aspekt der Luft-Pulver-Wasserstrahltechnik. Es soll betrachtet werden, welche Wirkung niedrig-abrasive Prophylaxepulver auf die Farbstabilität von Zahnschmelz haben und wie dieser Effekt sich im Vergleich zu herkömmlicher Zahnpolitur mit Polierpaste darstellt. Ein weiterer Beitrag der Studie besteht in der eigenständigen Entwicklung eines in-vitro Modells, in dem das Färbeverhalten von Zahnoberflächen reproduzierbar erfasst werden kann.
Insgesamt liegen aus dieser Untersuchung Daten von 152 extrahierten Zähnen vor, welche durch verschiedene Verfahren oberflächlich behandelt und anschließend in eine Färbelösung aus Kaffee gegeben wurden. Die Zahnfarben wurden zu verschiedenen Zeitpunkten mittels digitaler Bildanalyse bestimmt.
Im gewählten Versuchsaufbau (Durchlauf 1 und 2) ließ sich zunächst kein signifikanter Unterschied im Färbeverhalten nach Behandlung mit den Prophylaxepulvern Airflow Plus, Airflow Perio (EMS, Nyon, Schweiz) oder der Polierpaste Cleanic Prophy Paste flouride (Kerr Hawe, Bioggio, Schweiz) feststellen. Die Anwendung der verglichenen drei Produkte nach Herstellerangaben in der Studiensimulation erbrachte demnach keine signifikanten Verfärbungsunterschiede. Erst eine Modifikation des Versuchsablaufs im 3. Durchlauf, bei welchem die Zahnproben zusätzlich mit einer gesättigten Lösung aus Prophylaxemittel und Aqua Dest exponiert wurden, konnte einen signifikanten Einfluss des Prophylaxepulvers Airflow Plus auf das Färbeverhalten zeigen. Es ist von einem chemischen Einfluss des Inhaltsstoffes Chlorhexidin im Pulver Airflow Plus auszugehen, welcher in einer Konzentration von ≤0,3% im Pulver enthalten ist.
Diese Nebenwirkung ist aus der Praxis und aus der Literatur bekannt und wurde bereits in zahlreichen Untersuchungen bestätigt.
Gegenstand zukünftiger Arbeiten könnte die Untersuchung des Einflusses des Hauptbestandteils Erythritol auf das Färbeverhalten von Zahnoberflächen sein, oder der Einfluss höherer Druck- und Wassereinstellungen des Prophylaxegerätes. Des weiteren könnte ein Einfluss speziell auf das Färbeverhalten von Dentin oder Kompositrestaurationen durch das Prophylaxepulver EMS Airflow Plus und seine einzelnen Bestandteile untersucht werden.
Der Vergleich der Ernährungsgewohnheiten zweier populationsbasierter Kohorten
zeigt signifikante regionale Unterschiede in Deutschland. Anhand der in Vorpommern
ansässigen SHIP-Kohorte und der KORA-Kohorte der Region Augsburg lassen sich
sowohl Aussagen zu einem möglichen Nord-Süd-Gefälle als auch zu persistierenden
Unterschiede zwischen neuen und alten Bundesländern nach der deutschen
Wiedervereinigung treffen. In Vorpommern wird der Verzehr von Fleisch, Fisch, Obst
und Softdrinks häufiger angegeben. In der Region Augsburg dagegen ist die
Verzehrhäufigkeit von Gemüse und Cerealien höher. Mit dem ebenfalls erhobenen
Food Frequency Score lässt sich die Qualität der Ernährung messen und anhand einer
Bewertungsmatrix der einzelnen Nahrungsmittelkategorien in Beziehung zu deren
Wert gemäß den Ernährungsempfehlungen der Deutschen Gesellschaft für Ernährung
vergleichen. Die südwestdeutsche KORA-Kohorte weist einen höheren Score und
damit eine ausgewogenere Ernährung auf als die nordostdeutsche SHIP-Kohorte. Die
regionalen Unterschiede in den Ernährungsgewohnheiten bieten eine mögliche
Erklärung für die regionalen Unterschiede in der Lebenserwartung sowie in der
Prävalenz der Wohlstandserkrankungen. Die Ernährungsweisen in beiden Regionen
werden von bestimmten soziodemographischen Faktoren beeinflusst. Alter,
Geschlecht, Bildungs- und Einkommensstatus sind die Faktoren, deren Einfluss
untersucht wurden. Im Wesentlichen zeigen sich die Differenzen zwischen den
Kohorten in gleicher Ausprägung, auch unabhängig vom Geschlecht. Nur für einzelne
Lebensmittelgruppen besteht ein stärkerer Effekt. Bei Vergleich dreier Altersgruppen
ließ sich feststellen, dass die regionalen Unterschiede am deutlichsten in der Gruppe
der 60-80-jährigen sind. Das Einkommen hat in einzelnen Nahrungsmittelgruppen
keinen signifikanten Einfluss auf den Unterschied zwischen den Kohorten. Eine höhere
Schulbildung dagegen verringert die Differenz zwischen SHIP und KORA bezogen auf
den Verzehr von Sättigungsbeilagen, Fisch und Eiern. Diese Assoziation kann jedoch
nicht auf andere Lebensmittelkategorien übertragen werden. Der Food Frequency
Score liegt bei der KORA Kohorte für alle untersuchten soziodemographischen
Faktoren höher als bei der SHIP Kohorte. Für männliche Teilnehmer und Teilnehmer
mit einer Bildungsdauer über 10 Jahren ist der Effekt signifikant größer. Die Faktoren,
die mit einer ungesünderen Ernährungsweise assoziiert sind, bieten also
Angriffspunkte für Präventionsmaßnahmen für einzelne Bevölkerungsgruppen.
Der vorliegende Aufsatz untersucht aus systematisch-theologischer Sicht den von dem Heidelberger und Marburger Praktischen Theologen Friedrich Niebergall (1866–1932) zwischen ca. 1900 bis 1925 ausgeabeiteten Ansatz einer „Praktischen Dogmatik“. Niebergall wollte damit primär eine pastoraltheologisch orientierte Dogmatik entwickeln, die dem christlichen Prediger Handwerkszeug für seine „Erziehungsarbeit“ an der Gemeinde bereitstellt, mit deren Hilfe er die Gemeindeglieder zur Integration christlicher Ideale in die Pluralität ihres sozialen Alltags anleiten soll. Der Aufsatz unternimmt eine kritische Sichtung von theologischen Voraussetzungen, Inhalt, Aufbau und Folgen von Niebergalls Ansatz und stellt auch die Frage nach der Möglichkeit einer heutigen Adaption.
The current study analyzes the trajectory of the goose vowel in Received Pronunciation (RP) over ten decades (1920s-2010s). Recordings of eighty-seven RP speakers were transcribed in ELAN, and vowel tokens were extracted by FAVE, measuring F1 and F2 values at the midpoint. Showing the life-cycle of a sound change from start to (almost) completion, the results confirm that goose-fronting has been an active sound change for many decades in RP, with F2 starting to increase in the middle of the twentieth century and accelerated changes in the 1970s and the 2010s. We observe similar predictor strengths of linguistic factors as in previous studies. The results are interpreted in light of the social changes in the social composition of the RP group in the second part of the twentieth century, involving increased dialect contact.
Properties of self-excited dust acoustic waves under the influence of active compression of the dust particle system were experimentally studied in the laboratory and under microgravity conditions (parabolic flight). Ground based laboratory experiments clearly show that wave properties can be manipulated by changing the discharge volume, its aspect ratio, and thus the dust particle density. Complementary experiments under microgravity conditions, performed to exclude the effects of gravity inflicted sedimentation and anisotropic behavior, were less conclusive due to residual fluctuations in the planes acceleration indicating the need for a better microgravity environment. A theoretical model, using plasma parameters obtained from particle-in-cell simulations as input, supports the experimental findings. It shows that the waves can be described as a new observation of the dust acoustic mode, which demonstrates their generic character.
This article is the first to show that gender shapes the degree to which legislators use formal mechanisms to oversee government activities. Extensive scholarly work has analysed the use of oversight instruments, especially regarding who monitors whom. Whether, how, and why the conformity of men and women with institutional roles differs, has not yet received scholarly attention. We hypothesise that women become more active than men in overseeing the executive when in opposition while reducing their monitoring activities even more strongly than men when in government because of different social roles ascribed to men and women as well as differences in risk aversity between sexes. We analyse panel data for three oversight tools from the German Bundestag between 1949 and 2013 to test this proposition. Our findings imply that characteristics of political actors influence even a strongly institutionalised process as oversight and further clarify the gender bias in political representation.
Objective: In acute pancreatitis (AP), bacterial translocation and subsequent infection of pancreatic necrosis are the main risk factors for severe disease and late death. Understanding how immunological host defence mechanisms fail to protect the intestinal barrier is of great importance in reducing the mortality risk of the disease. Here, we studied the role of the Treg/Th17 balance for maintaining the intestinal barrier function in a mouse model of severe AP.
Design: AP was induced by partial duct ligation in C57Bl/6 or DEREG mice, in which regulatory T-cells (Treg) were depleted by intraperitoneal injection of diphtheria toxin. By flow cytometry, functional suppression assays and transcriptional profiling we analysed Treg activation and characterised T-cells of the lamina propria as well as intraepithelial lymphocytes (IELs) regarding their activation and differentiation. Microbiota composition was examined in intestinal samples as well as in murine and human pancreatic necrosis by 16S rRNA gene sequencing.
Results: The prophylactic Treg-depletion enhanced the proinflammatory response in an experimental mouse model of AP but stabilised the intestinal immunological barrier function of Th17 cells and CD8+/γδTCR+ IELs. Treg depleted animals developed less bacterial translocation to the pancreas. Duodenal overgrowth of the facultative pathogenic taxa Escherichia/Shigella which associates with severe disease and infected necrosis was diminished in Treg depleted animals.
Conclusion: Tregs play a crucial role in the counterbalance against systemic inflammatory response syndrome. In AP, Treg-activation disturbs the duodenal barrier function and permits translocation of commensal bacteria into pancreatic necrosis. Targeting Tregs in AP may help to ameliorate the disease course.
Zusammenfassung
Die Verordnung einer Stressulkusprophylaxe im Rahmen stationärer Aufenthalte ist im medizinischen Alltag weit verbreitet. Die Verschreibungspraxis einer SUP wurde bisher vor allem im Bereich der Intensivmedizin und der Inneren Medizin untersucht [33, 40, 42, 45, 46]. Allerdings konnte gezeigt werden, dass eine stressulkusbedingte gastrointestinale Blutung unter stationären Bedingungen ein sehr seltenes Ereignis darstellt [12,17]. Im Bereich chirurgischer, nicht kritisch erkrankter Patienten gibt es bislang nur wenige Studien zur aktuellen Praxis der Verschreibung einer SUP [16, 46].
Um die aktuelle Verschreibungspraxis einer SUP in einem chirurgischen Patientenkollektiv beschreiben und bezüglich des Vorliegens einer Indikation nach aktuellen Leitlinien charakterisieren zu können, wurden retrospektiv von Januar bis Juni 2016 Patientendaten an der Universitätsmedizin Greifswald erhoben und ausgewertet [49]. Des Weiteren erfolgte eine Untersuchung der landesweiten Verschreibungspraxis einer SUP auf der Basis einer Befragung der Abteilungsleiter und Mitarbeiter chirurgischer Abteilungen der Akutkliniken in Mecklenburg-Vorpommern [50].
Die Auswertung der retrospektiv erhobenen Patientendaten zeigte eindeutig, dass im weit überwiegenden Anteil der Patienten mit neu verordneter SUP keine Risikofaktoren für die Ausbildung von Stressulzera und stressulkusbedingten Blutungen vorlagen [49]. In 85.7-99.6 % der Patienten mit SUP konnte die Indikation für die Gabe nicht nachvollzogen werden [49].
Die Befragung chirurgisch tätiger Ärzte in Mecklenburg-Vorpommern zeigte, dass die Verschreibung der SUP nur in einer Minderzahl der Kliniken durch eine SOP geregelt war [50]. In den Kliniken mit vorhandener SUP war deren Inhalt nur einer Minderheit der klinisch tätigen Ärzte inhaltlich bekannt [50]. Eine kritische Reevaluation der Indikation einer SUP erfolgte nicht regelhaft bei Verlegung von Intensiv- auf die Normalstation oder bei Entlassung [50].
Die vorliegende Untersuchung zeigt, dass bei chirurgischen Patienten auch heute noch eine massive Überverschreibung einer medikamentösen Stressulkusprophylaxe zur medizinischen Routine gehört [49, 50]. Dabei scheint von den behandelnden Ärzten das Risiko eines Auftretens stressulkusbedingter Blutungen massiv überschätzt beziehungsweise den Patientengruppen nicht regelrecht zugeordnet werden zu können [49, 50]. Angesichts der Tatsache, dass den zur SUP verwendeten Medikamente eine zunehmend größere Zahl unerwünschter Nebenwirkungen (bakterielle Gastroenteritis, akute interstitielle Nephritis, Vitamin-B12-Mangel, ein erhöhtes Risiko für eine Covid-19-Infektion, ambulant und nosokomial erworbene Pneumonien, Demenzerkrankungen, Osteoporose sowie Elektrolytstörungen) zugeordnet werden kann, sollte die Verschreibung der SUP nach einem festen Indikationsschemas erfolgen und im Laufe des stationären Aufenthaltes wiederholt kritisch hinterfragt werden [23-27].
Die Entwicklung einheitlicher Empfehlungen und Richtlinien zur Handhabung von SUP und die Sensibilisierung chirurgisch tätiger Ärzte im Rahmen von Fort- und Weiterbildungen erscheint somit, angesichts der erarbeiteten Daten, dringend notwendig zu sein.
Hass im Netz findet in Deutschland zunehmend Verbreitung und ist besonders für junge Menschen mittlerweile Teil des Alltags geworden, wobei Hass ausgeübt, erlebt oder beobachtet wird. Unter Hass im Netz lassen sich Phänomene wie Cyberbullying, Hassrede und digitale Gewalt beschreiben. Dieses Gutachten betrachtet zunächst die theoretischen und empirischen Grundlagen dieser Phänomene und benennt zentrale Gemeinsamkeiten und Unterschiede, um davon ausgehend Maßnahmen zu erörtern und deren Evidenzbasierung kritisch zu reflektieren, die zur Prävention sowie zur Intervention und Reaktion bei Hass im Netz zur Verfügung stehen. Aus der Zusammenschau werden dann weiterführende Impulse für Forschung und Praxis abgeleitet. Ein besonderer Fokus der Betrachtung liegt dabei auf der Situation in Niedersachsen.
Diese Arbeit beschreibt die Konstruktion einer 3D-gedruckten modularen
Messapparatur (M3DOMA), die eine simultane Messung von Kraft und Drehmoment in allen drei Raumachsen (X, Y und Z) an drei beliebigen Zähnen des Zahnbogens erlaubt und in weiteren Ausbaustufen auf alle Zähne eines Zahnbogens erweitert werden kann. Die Messapparatur wird in Hinblick auf den Aufbau und dessen Eigenschaften, wie der Ruherausch, die Wiederholbarkeit, sowie die Verlässlichkeit der Messungen, beschrieben.
With high prevalence and mortality, myocardial infarction constitutes a social and economic burden in Germany and worldwide. Current guidelines for MI treatment require prompt reperfusion to salvage heart tissue and minimize short- and long-term complications. However, there are currently no treatments available to attenuate reperfusion injury. Ischemic as well as pharmacological post-conditioning have been identified as important clinical strategies to improve outcome. Membrane stabilizers, like Poloxamer 188 (P188), have been shown to improve myocardial ischemia reperfusion (IR) injury and mitochondrial function but have not yet been proven to directly offer mitochondrial protection. Mitochondrial function is crucial for cardiomyocyte function, and mitochondrial dysfunction plays an important role in myocardial injury.
In this study, hearts from 79 Sprague Dawley rats were isolated and perfused ex-vivo with oxygenated Krebs Buffer for 20 min before 30 min of no-flow ischemia. Hearts were reperfused for 10 min with Krebs buffer or 1 mM P188. Cardiac mitochondria were isolated with 1 mM P188 vs 1 mM polyethylene glycol (PEG) vs vehicle by differential centrifugation. Mitochondrial function was assessed as adenosine triphosphate (ATP) synthesis, oxygen consumption and calcium retention for complex I and II substrates of the respiratory chain.
An improvement of myocardial function with 10 min P188 post-conditioning could not be shown. Direct mitochondrial protection of P188 or PEG could not be observed in this model either. Further research is needed to ascertain whether P188 has a direct protective effect on mitochondria and, if so, on what pathways of IR injury it acts.
Die Migration von Endothelzellen unter hämodynamischen Flussbedingungen ist ein komplex regulierter Vorgang. In dieser Arbeit konnten die Aktivierung des Apelin-Rezeptors und die Zugabe von Statinen als Einflussfaktoren auf die Migration der Endothelzellen unter verschiedener Schubspannung identifiziert werden. Dabei wurden folgende Kernaussagen herausgearbeitet:
1. Der Apelin-Rezeptor reguliert die Endothelzellen-Migration in Abhängigkeit von der Schubspannung und dem Gefäßbett. In HUVEC wirkt der APLNR migrationsfördernd unter physiologischen Schubspannungen und migrationshemmend unter höheren Schubspannungen. Keinen Einfluss zeigt der APLNR auf die Migration von HCAEC.
2. Physiologische Statinkonzentrationen reduzieren die EC-Migration in HCAEC. Dies steht im Gegensatz zu der beschriebenen migrationsfördernden Wirkung von statinbehandelten HUVEC. In supraphysiologischen Konzentrationen zeigten sich Unterschiede zwischen dem lipophilen Atorvastatin und dem hydrophilen Pravastatin.
3. Die Wirkung der Statine auf die EC-Migration scheint teilweise über den APLNR zu erfolgen. Dies könnte möglicherweise abhängig von ihrer Lipophilie geschehen.
Hinsichtlich der klinischen Relevanz scheint insbesondere der Einfluss des APLNR auf die endotheliale Migration, sowie sein Zusammenspiel mit Atorvastatin von Bedeutung zu sein. In diesem experimentellen Setting konnte bei Betrachtung von arteriellen EC kein Vorteil eines der Statine bezüglich ihrer Migration herausgearbeitet werden. Inwieweit sich diese jedoch klinisch unterscheiden, müsste in in vivo Studien untersucht werden.
In Zusammenschau mit den Studien der aktuellen Literatur zeigte die hier vorliegende Arbeit besonders, wie stark zum Beispiel die Auswahl des Zellmodells die Ergebnisse beeinflusst. So lassen sich Arbeiten mit dem für Arteriosklerose oft gewählten HUVEC-Zellmodell kaum mit Experimenten an HCAEC vergleichen, obgleich es sich bei beiden um vaskuläre Endothelzellen handelt. Außerdem zeigte sich, dass die Wirkung der Statine oder der APLNR-Blockierung unter physiologischen Schubspannungen teilweise gegenteilig zu ihrer Wirkung unter höheren Schubspannungen ist.
In der individualisierten Medizin wird angestrebt für jeden einzelnen Patienten entsprechend seiner Erkrankungen, die optimalste Therapie zu finden. Wo Atorvastatin für den einen Patienten von Vorteil ist, sorgt bei einer anderen Patientin Pravastatin für mehr Sicherheit. Dass diese Wirkstoffgruppe nicht so homogen ist, zeigen die hier erhobenen Ergebnisse. Um den modernen Therapieansatz zu verfolgen, sollten auch die wissenschaftlichen Fragestellungen bezüglich der Wirkstoffgruppe der Statine konkreter abgestimmt beantworten.
In den Weltmeeren findet rund die Hälfte der jährlichen globalen Kohlenstofffixierung statt, davon ein großer Anteil in küstennahen Regionen. Hier kommt es zu wiederkehrenden saisonalen Algenblüten, die durch eine zeitlich begrenzte explosionsartige Vermehrung von Mikroalgen (hauptsächlich Diatomeen und Coccolithophoren) charakterisiert sind. Vor allem Frühjahrsblüten (März-Mai) haben aufgrund ihrer zeitlichen und räumlichen Vorhersagbarkeit einen hohen Stellenwert als Modellsysteme, anhand deren sich der Kohlenstoffkreislauf der Meere untersuchen lässt.
Mikroalgen produzieren eine große Vielfalt an Makromolekülen, die für die mit ihnen vergesellschafteten Bakterien als Nahrungsgrundlage dienen. Besonders im Fokus stehen hier die für den Kohlenstoffkreislauf relevanten Polysaccharide. Im Gegensatz zu anderen natürlichen Makromolekülen wie DNA oder Proteinen können Polysaccharide aus vielen verschiedenen Monomeren mit unterschiedlichsten Bindungen bestehen. Zusätzlich finden sich an diesen Zuckermonomeren viele Modifikationen wie Acetylierungen, Methylierungen oder Sulfatierungen, die die Komplexität weiter erhöhen. Diese Variabilität bedingt eine hohe strukturelle und funktionale Diversität. So können Polysaccharide Speicherstoffe, Zellwandbestandteile oder Teile der extrazellulären Matrix darstellen.
Komplementär hierzu besitzen Polysaccharid-verwertende Bakterien entsprechend komplexe, enzymatische Abbaumechanismen. Besonders hervorzuheben sind hier die Bakterien des Phylums Bacteroidota, die sich in verschiedensten Nischen auf den Abbau von Polysacchariden spezialisiert haben. Sie finden sich in Bodenproben, als Teil der menschlichen Darmflora, oder eben auch als bedeutende Begleiter von Algenblüten.
Bacteroidota (und in marinen Systemen hauptsächlich die zu ihnen gehörenden Flavobakterien) besitzen zum Abbau diverser Polysaccharide sogenannte Polysaccharide utilization loci (PULs), genomische Inseln, die alle notwendigen Proteine zur Aufnahme und Abbau eines bestimmten Polysaccharids codieren. Hierzu gehören hochspezifische Enzyme (Carbohydrate-active enzymes, CAZymes), transkriptionelle Regulatoren sowie Transportersysteme, die initial gespaltene Oligosaccharide über die Membran in das Bakterium transportieren, wo sie von weiteren Enzymen vollständig abgebaut werden. Diese Co-Lokalisation der benötigten Gene und deren gemeinsame Regulation stellt einen enormen Selektionsvorteil der Bacteroidota dar und ist der Grund, warum sie, ähnlich wie Algen, einer jährlich wiederkehrenden Sukzession folgen, die sich gut untersuchen lässt.Die Forschungsartikel, die Teil dieser Doktorarbeit sind, untersuchen das Zusammenspiel von Polysaccharid-produzierenden Algen mit den Bakterien, die sie abbauen, aber auch darauf basierende Beziehungen der Bakterien untereinander. Die erste Publikation beschäftigt sich mit dem weit verbreiteten Speicherpolysaccharid α-Glucan, für das der Großteil der blütenbegleitenden Bakterien einen spezifischen aktiven PUL besitzt. Eine Untersuchung der in der Blüte vorhandenen Algenarten bestätigte, dass die Blüte von β-Glucan-produzierenden Algen dominiert wird. Da Bakterien aber selbst α-Glucane als Speicherpolysaccharide verwenden, konnte gezeigt werden, dass nicht die Algen selbst, sondern die Bakterien Hauptproduzent dieser Polysaccharide während einer Phytoplanktonblüte sind. Bakterielle Proteine, die dem Abbau von Algen-β-Glucan und dem daraus folgenden Aufbau von bakteriellem α-Glucan dienen, waren in Umweltproben und in Laborkulturen unter ähnlichen Bedingungen abundant. Die Untersuchung von extrahiertem bakteriellem Polysaccharid bewies, dass dieses nicht nur α-Glucan enthält, sondern dass dieses Polysaccharid auch in der Lage war, α-Glucan PULs mariner Bakterien zu induzieren. Hier zeigte sich ein innerhalb des marinen Kohlenstoffkreislaufs bisher wenig berücksichtigter Kreislauf, indem Bakterien Polysaccharide anderer Bakterien nutzen, die z.B. durch Viren lysiert wurden.
Die anderen zwei Artikel dieser Arbeit befassen sich mit dem Abbau von Zellwandpolysacchariden durch blütenassoziierte Modellbakterien. In einer der Studien wird detailliert der Abbau eines β-Mannans (ein Polysaccharid das hauptsächlich aus dem Monosaccharid Mannose besteht) durch ein Bakterium des Genus Muricauda beschrieben. Die PUL-Struktur dieses Bakteriums kam in mehreren anderen Phytoplanktonblüten-assoziierten Bakterien vor. Diese Beobachtung wies darauf hin, dass es sich hier um ein Mannan mit zusätzlichen Galactose- und Glucose-Substitutionen handelte. Proteom-Untersuchungen bestätigten, dass das Bakterium derartige Substrate unter Induktion des β-Mannan-PULs nutzen können. β-Mannan konnte durch Antikörpermarkierung in Blütenproben sowie spezifischen Mikroalgenarten (Chaetoceros, Coscinodiscus) nachgewiesen werden. Die in dieser Publikation charakterisieren β-Mannan-PUL-codierten Enzyme waren in der Lage, dieses Signal zu löschen, was bewies, dass Muricauda sp. Mannan-basierte Zellwandpolysaccharide bestimmter Arten von Mikroalgen abbauen kann.
Die dritte Studie geht näher auf den Abbau von Xylanen (bestehend aus Xylose) durch ein blütenassoziiertes Bakterium des Genus Flavimarina ein. In diesem Bakterium wurden anhand der enthaltenen Xylanasen zwei putative Xylan-PULs annotiert. Wachstumsexperimente und Proteom-Untersuchungen zeigten, dass einer dieser PULs hauptsächlich bei Wachstum auf Glucoronoxylan induziert wird, während der andere PUL aufArabinoxylane stärker reagierte. Untersuchung der PUL-CAZymes bestätigte diese Ergebnisse durch Charakterisierung mehrerer Xylanasen sowie Glucoronidasen und Arabinofuranosidasen. Zusätzlich codierten beide PULs für Esterasen, die eine Modifikation der natürlichen Substrate durch Acetylierungen oder Methylierungen nahelegen. Da all diese Merkmale von terrestrischen Xylanen geteilt werden und in Blütenproben aus Küstennahen Regionen Xylane nachgewiesen wurden, ist es möglich, dass Bakterien aus solchen Regionen sowohl Xylane terrestrischen Ursprungs (z.B. durch Flusseinspeisung) sowie marinen Ursprungs abbauen können.
Für frühgeborene Kinder ist Muttermilch die empfohlene enterale Ernährung mit vielen bereits gut untersuchten positiven Effekten. Jedoch ist der Gehalt an Makronährstoffen zu niedrig, um die Bedürfnisse von Frühgeborenen zu decken. Zusätzlich zeigt native Muttermilch eine hohe inter- und intraindividuelle Variabilität der Makronährstoffe. Die Effizienz der allgemein verbreiteten Standardfortifizierung mit kommerziell erhältlichen Fortifiern ist durch diese Variabilität beeinträchtigt und kann so in einem Großteil der Muttermilchproben zu einer inadäquaten Nährstoffzufuhr führen, die zu niedrig, jedoch auch zu hoch ausfallen kann. Unzureichende Ernährung kann einen negativen Einfluss auf das Wachstum und die Körperzusammensetzung sowie Folgeerkrankungen im Erwachsenenalter haben.
Diese Studie zeigt anhand eines Datensatzes mit realen Messwerten zur Zusammensetzung der Muttermilch in über 3300 Proben, dass die Messung der Makronährstoffe in nativer Muttermilch und die anschließende, darauf basierende Targetfortifizierung mit der individuellen Ergänzung der fehlenden Makronährstoffen zu adäquaten Nährstoffeinträgen führt. Mit diesem Ansatz kann auf die Variabilität der nativen Muttermilch reagiert und die Variation der Makronährstoffeinfuhr signifikant verringert werden. In dieser Arbeit wurden drei verschiedene optimierte Standardfortifier entwickelt. Deren Zusammensetzung erhöht den Makronährstoffeintrag bereits unter Standardfortifizierung, aber noch mehr bei ein oder zwei Muttermilchanalysen pro Woche.
Weiterhin wurde in dieser Arbeit der Einfluss der durch die verschiedenen Fortifizierungsstrategien erzeugten Nährstoffzufuhren auf die Wachstumsraten berechnet, die für Standardfortifizierung ungenügende und für Targetfortifizierung hauptsächlich zufriedenstelle Ergebnisse zeigt.
Verschiedene Kombinationen von Pooling mit bis zu drei Proben oder von Pooling einer größeren Anzahl wie in einer Milchbank zu Verfügung stehenden Proben verringerten nicht die Variabilität der Nährstoffzufuhr. Ebenso zeigte die Gefriertrocknung keine zufriedenstellenden Ergebnisse für alle Makronährstoffkonzentrationen.
Die Ergebnisse dieser Arbeit verdeutlichen, dass standardfortifizierte Muttermilch trotz verschiedener Poolingstrategien keine adäquate Makronährstoffzufuhr für frühgeborene Kinder sicherstellt. Für den klinischen Alltag wird die Bedeutung der Targetfortifizierung deutlich, die mit regelmäßiger Muttermilchanalyse und unter Anwendung optimierter Standardfortifier zufriedenstellend gelingen kann und so zu physiologischen Wachstumsraten führen kann.
Our study examined whether potentially critical indications from depression questionnaires, interviews, and single items on suicidal ideation among partici-pants in a large prospective population-based study are related to short-term sui-cides within one year. For this purpose, we studied the association between (a) the severity of depressive symptoms according to the M-CIDI and the PHQ-9, BDI-II, and CID-S depression screening and (b) elevated scores on single sui-cidal ideation items and mortality according to claims databases.
In the baseline cohort, the frequency of depressive symptoms measured by CID-S was 12.90% (SHIP-START-0). The frequency for “Moderate” to “Severe de-pression” measured by the PHQ-9 (≥ 10 points) and BDI-II (≥ 20 points) ques-tionnaires ranged from 5.40% (SHIP-LEGENDE) to 8.80% (SHIP-TREND Morbid-ity follow-up). The 1-month prevalence of unipolar depression, measured by the M-CIDI in SHIP LEGENDE, was 2.31%.
Between 5.90% (SHIP-TREND Morbidity follow-up) and 6.60% (SHIP-LEGENDE) of respondents showed a certain degree of suicidal ideation in the two weeks preceding the assessment, according to BDI-II and PHQ-9.
Our results show the high frequency of depressive symptoms in the study region, with women being affected more frequently than men, especially in the higher categories. Furthermore, women were more frequently affected by suicidal idea-tion, although this difference was not evident in the highest categories.
There was one potential suicide in the year after a SHIP examination.
From our results, we cannot conclude that severe self-reported symptoms from depression questionnaires should be reported back to participants of an obser-vational population-based study to prevent suicide deaths within one year.
Decreased inflammatory profile in oral leukoplakia tissue exposed to cold physical plasma ex vivo
(2023)
Background
Oral leukoplakia (OL) is an unfavorable oral disease often resistant to therapy. To this end, cold physical plasma technology was explored as a novel therapeutic agent in an experimental setup.
Methods
Biopsies with a diameter of 3 mm were obtained from non-diseased and OL tissues. Subsequently, cold atmospheric pressure plasma (CAP) exposure was performed ex vivo in the laboratory. After 20 h of incubation, biopsies were cryo-conserved, and tissue sections were quantified for lymphocyte infiltrates, discriminating between naïve and memory cytotoxic and T-helper cells. In addition, the secretion pattern related to inflammation was investigated in the tissue culture supernatants by quantifying 10 chemokines and cytokines.
Results
In CAP-treated OL tissue, significantly decreased overall lymphocyte numbers were observed. In addition, reduced levels were observed when discriminating for the T-cell subpopulations but did not reach statistical significance. Moreover, CAP treatment significantly reduced levels of C-X-C motif chemokine 10 (CXCL10) and granulocyte-macrophage colony-stimulating factor in the OL biopsies' supernatants. In idiopathically inflamed tissues, ex vivo CAP exposure reduced T-cells and CXCL10 as well but also led to markedly increased interleukin-1β secretion.
Conclusion
Our findings suggest CAP to have immuno-modulatory properties, which could be of therapeutic significance in the therapy of OL. Future studies should investigate the efficacy of CAP therapy in vivo in a larger cohort.
Purpose
The significance of the underlying literature in clinical guidelines can be weakened by the risk of bias, which could negatively affect the recommendations. Especially in controversial matters, such as fluoride use for caries prevention in children, biased results may be not reliable and lead to incorrect conclusions. This study was performed to detect bias in underlying literature of the German guideline for caries prevention using fluoride in children, where no consensus was reached between paediatricians and paediatric dentists.
Methods
Three tools used for risk of bias assessments of different study designs were RoB 2 for RCTs, ROBINS-I for non-randomized studies, and ROBIS for systematic reviews. For each study cited in the guideline two independent risk of bias assessments were performed. Disagreements were resolved by consensus.
Results
Out of 58 papers, 48.3% (n = 28) showed high risk of bias, with the majority in sections regarding fluoride tablets, fluoridated toothpaste, and paediatricians’ recommendations. 9 out of 20 recommendations and statements were based on studies with high risk of bias, all of which were in these three controversial sections. 13 out of 29 RCTs showed high risk of bias (44.8%), as all 13 non-randomized trials did, while only 2 of 16 (12.5%) systematic reviews had high risk of bias.
Conclusion
Considering risk of bias of cited studies in clinical guidelines may result in substantial changes in its recommendations and aid in reaching consensus. Efforts should be made to assess risk of bias of underlying literature in future clinical guidelines.
Urbanization, industrialization, and intensification of agriculture have led to considerable heavy metal pollution across the globe, harming our ecosystems. Concentrations of arsenic (As), cadmium (Cd), copper (Cu), and lead (Pb) have been analysed in 249 eggshells collected between 2006 and 2021 from 83 female Common Cranes (Grus grus) nesting within north-eastern Germany. Information on the presence of trace elements in cranes from Europe and their potential adverse effects on the reproduction are largely missing. Only Cu and Pb were found to be present in eggshell samples. Levels of both metals did not exceed concentrations considered potentially toxic in birds and unhatched eggs did not contain higher metal concentrations compared to eggshell residues from hatched eggs. Statistical analysis revealed that trace element concentrations decreased significantly over the course of the study period. The ban of leaded gasoline in the early twenty-first century and strict limitations of heavy metal-based biocontrol products are likely responsible for this decrease over the years. However, as Cu levels gradually increase with increasing proportions of agricultural areas within the cranes’ home ranges, we suggest that considerable amounts of Cu originating from agricultural practises are still being released into the environment. We found no increase in metal concentrations in eggshells with increasing female age, suggesting that heavy metals do not accumulate in the circulatory systems of the adults over time. This study is the first to assess heavy metal contamination in Common Cranes and indicates the suitability of crane’s eggshells as bioindicator for monitoring environmental pollution.
Hintergrund:
Kardiovaskuläre Präventionsleitlinien empfehlen unterschiedliche Instrumente zur kardiovaskulären 10-Jahres-Risikobestimmung. In der hausärztlichen Praxis wird dafür häufig das arriba-Instrument verwendet und durch die Leitlinie „Hausärztliche Risikoberatung zur kardiovaskulären Prävention“ empfohlen. Ziel der Studie ist die Validierung der arriba-Risikoprädiktion auf Basis von Morbiditäts- und Mortalitätsdaten der bevölkerungsbasierten Study of Health in Pomerania.
Methoden:
In einer retrospektiven Längsschnittanalyse wurde für Probanden ohne vorheriges kardiovaskuläres Ereignis das kardiovaskuläre 10-Jahres-Gesamtrisiko (Myokardinfarkt oder Schlaganfall) zur Basisuntersuchung mit dem arriba-, SCORE-Deutschland- und PROCAM-Algorithmus (Myokardinfarkt) berechnet. Aus Daten der Folgeuntersuchungen wurden kardiovaskuläre Ereignisraten ermittelt und Diskriminierungs- und Kalibrierungsmaße für die Risikobestimmungsinstrumente berechnet.
Ergebnisse:
In die Analyse wurden 2277 Proband:innen (Durchschnittsalter 53 ± 13 Jahre, 50% Männer) eingeschlossen. Nach durchschnittlich 10,2 Jahren betrug die kardiovaskuläre Ereignisrate 8,6% (196/2277). Das Verhältnis aus prädizierter und beobachteter Ereignisrate betrug für Proband:innen mit niedrigem, mittlerem und hohem kardiovaskulären Risiko 0,8, 1,5 und 1,3. Arriba unterschätzte bei Frauen und überschätzte in den Altersgruppen 30-44 und 45-59 Jahren die kardiovaskulären Ereignisraten.
Schlussfolgerung:
Diskriminierungswerte für das arriba-Instrument sind mit SCORE-Deutschland und PROCAM vergleichbar, eine individuelle Anpassung an die Zielpopulation ist jedoch nötig.
The maintenance of protein homeostasis in muscle by degradation systems, e.g. the autophagy lysosomal pathway (ALP) and the ubiquitin-proteasome system (UPS), is of great importance. It prevents the accumulation of nonfunctioning and not properly folded proteins, which can lead to protein aggregate myopathies (PAMs) and several other protein storage diseases. Degradation by the UPS depends on the transfer of ubiquitin to a target protein. This happens in a cascade of E1-E2-E3 proteins. This process is also involved in protein location and regulation of protein activity. E3 ligases are often tissue specific. Muscle RING-finger proteins (MuRFs) are a family of really interesting new gene (RING)-Finger E3 ubiquitin ligases, that are almost exclusively expressed in the striated muscle. They play a role in muscle wasting, but are also important for the maintenance of the structure of striated muscle. MuRF proteins are also involved in the regulation of the striated muscle energy metabolism. Previous work has demonstrated that MuRF1/MuRF3 DKO mice show a protein surplus myopathy characterized by an accumulation of myosin heavy chain proteins in striated muscles and a reduction in function of both heart and skeletal muscle. The aim of this study was to test the hypothesis that the myopathic phenotype of MuRF1/MuRF3 DKO mice is mediated by a disturbed energy homeostasis in the heart and skeletal muscle, with focus on mitochondrial function. Because sex-specific differences have not been investigated in these mice so far, a further aim was to investigate any differences between male and female mice.
To test these hypotheses, we measured the weight of the heart and the hindlimb muscles tibialis anterior and soleus to detect a possible hypertrophy in the DKO mice. Hematoxylin and eosin staining of histological cross sections of the tibialis anterior were performed to investigate protein accumulations. Muscle function was quantitated via grip strength and specific force measurements. Possible changes in protein amounts were detected via mass spectrometry analyses and western blot analyses. Changes in gene expression were investigated by qRT-PCR. Coimmunoprecipitation was used to determine direct interactions between proteins. Protein stability and ubiquitination were investigated by cycloheximide (CHX) and ubiquitination assays, respectively.
DKO mice showed an increase in heart and skeletal muscle weights. Grip strength assays revealed limb weakness of DKO mice. H&E staining of histological cross sections of the tibialis anterior muscle (TA) showed protein aggregates within myofibers. Mass spectrometry analyses of proteins isolated from TA and heart muscle revealed an increase of muscle stress markers and structural proteins in DKO mice, while proteins involved in the energy metabolism were reduced. Especially interesting here were the proteins of the mitochondrial electron transport chain (ETC), which play a major role in the energy production of the mitochondria by catalyzing the phosphorylation of ADP to ATP, the universal energy carrier in all living organisms. These changes were more pronounced in TA compared to heart. Western blot and qRT-PCR results of ETC subunits supported our proteome data. They also revealed a sex-specific difference, in which the reduction ETC subunits was more pronounced in females than males. In female
TA NDUFB8, SDHB, UQCRC2, MTCO1 and ATP5 were significantly reduced compared to controls, while only UQCRC2 and ATP5 were decreased in male TA compared to controls. A significant reduction in gene expression of Ndufb8, Sdhb, Mtco1 and Atp5 was detected in TA of female mice compared to controls, while only Ndufb8, Sdhb and Atp5 were decreased in male TA compared to controls. We observed the same pattern in Heart of male (protein: NDUFB8; mRNA: Mtco1) and female (protein: UQCRC2, MTCO1, ATP5; mRNA: Sdhb, Mtco1) DKO mice compared to their controls. The reduction in ETC subunits was paralleled by a reduction in complex I and complex III activity in the TA of DKO mice, but not in heart. However, this was only significant in the TA of female but not male mice. Mechanistical analyses using coimmunoprecipitation, cycloheximide chase and ubiquitination assays showed that MuRF1 physically interacted with the transcriptional repressor histone deacetylase 5 (HDAC5), mediated its ubiquitination as well as its UPS-dependent degradation. The absence of MuRF1 and MuRF3 in DKO mice let to an increase in the amounts of HDAC5 in TA. Because HDAC5 binds to PGC-1α, the master regulator of mitochondrial biogenesis (encoded by Ppargc1a), we investigated its gene expression in DKO muscle and found it to be reduced.
These data connect MuRF1 and MuRF3 directly to the striated muscle energy metabolism, by regulating mitochondrial function. The results provide insights into the development of PAMs and possibly other protein storage diseases, where a decrease of mitochondrial function has already been described.
Medieval texts reveal the normalised presence of Saami peoples in medieval Fennoscandia, suggesting close interactions involving trade, relationships, rituals, and magic. Despite growing recognition of these relations, the Saami remain overlooked in general studies of the Middle Ages, often relegated to symbolic roles or footnotes. As a result, Saami characters are typically depicted as the exotic Other within Norse society, often being stripped of agency and humanity in historical narratives. To counter these biases and distorted narratives, an essential step is analysing exclusionary structures in medieval literature and critically reviewing existing research on Saami representation. This process challenges dehumanising portrayals and confronts present-day stereotypes. The present study aims to ‘re-humanize’ (as Paulette F. C. Steeves puts it) the medieval Saami past by using decolonising frameworks and perspectives offered by the so-called ‘Indigenous turn’ of medieval studies, bridging medieval studies and Indigenous studies within a Norse context.
Comparative neuroanatomy of the central nervous system in web-building and cursorial hunting spiders
(2023)
Spiders (Araneae) include cursorial species that stalk their prey and more stationary species that use webs for prey capture. While many cursorial hunting spiders rely on visual cues, web-building spiders use vibratory cues (mechanosensation) for prey capture. We predicted that the differences in primary sensory input between the species are mirrored by differences in the morphology/architecture of the central nervous system (CNS). Here, we investigated the CNS anatomy of four spider species, two cursorial hunters Pardosa amentata (Lycosidae) and Marpissa muscosa (Salticidae), and two web-building hunters Argiope bruennichi (Araneidae) and Parasteatoda tepidariorum (Theridiidae). Their CNS was analyzed using Bodian silver impregnations, immunohistochemistry, and microCT analysis. We found that there are major differences between species in the secondary eye pathway of the brain that pertain to first-order, second-order, and higher order brain centers (mushroom bodies [MB]). While P. amentata and M. muscosa have prominent visual neuropils and MB, these are much reduced in the two web-building species. Argiope bruennichi lacks second-order visual neuropils but has specialized photoreceptors that project into two distinct visual neuropils, and P. tepidariorum lacks MB, suggesting that motion vision might be absent in this species. Interestingly, the differences in the ventral nerve cord are much less pronounced, but the web-building spiders have proportionally larger leg neuropils than the cursorial spiders. Our findings suggest that the importance of visual information is much reduced in web-building spiders, compared to cursorial spiders, while processing of mechanosensory information requires the same major circuits in both web-building and cursorial hunting spiders.
o-Hydroxyarylphosphanes are fascinating compounds by their multiple-reactivity features, attributed to the ambident hard and soft Lewis- and also Brønstedt acid-base properties, wide tuning opportunities via backbone substituents with ±mesomeric and inductive, at P and in o-position to P and O also steric effects, and in addition, the configurational stability at three-valent phosphorus. Air sensitivity may be overcome by reversible protection with BH3, but the easy oxidation to P(V)-compounds may also be used. Since the first reports on the title compounds ca. 50 years ago the multiple reactivity has led to versatile applications. This includes various P−E−O and P=C−O heterocycles, a multitude of O-substituted derivatives including acyl derivatives for traceless Staudinger couplings of biomolecules with labels or functional substituents, phosphane-phosphite ligands, which like the o-phosphanylphenols itself form a range of transition metal complexes and catalysts. Also main group metal complexes and (bi)arylphosphonium-organocatalysts are derived. Within this review the various strategies for the access of the starting materials are illuminated, including few hints to selected applications.
Aim
To investigate the medium-term associations of serum protein subfractions derived from proton nuclear magnetic resonance (1H-NMR) spectroscopy with periodontitis and tooth loss.
Materials and Methods
A total of 3031 participants of the cohort Study of Health in Pomerania (SHIP-TREND) were included. In addition to conventional serum testing, serum lipoprotein contents and subfractions were analysed by 1H-NMR spectroscopy. Confounder-adjusted associations of lipoprotein variables with periodontitis and the number of missing teeth variables were analysed using mixed-effects models with random intercepts for time across individuals, accounting for multiple testing.
Results
While only spurious associations between lipoprotein levels from conventional blood tests were found—that is, triglycerides were associated with mean clinical attachment level (CAL) and low-density lipoprotein cholesterol/high-density lipoprotein cholesterol (LDL-C/HDL-C) ratio with the number of missing teeth - several associations emerged from serum lipoprotein subfractions derived from 1H-NMR analysis. Specifically, elevated LDL triglycerides were associated with higher levels of mean probing depth (PD), mean CALs, and increased odds of having <20 teeth. HDL-4 cholesterol levels were inversely associated with mean PD. Systemic inflammation (C-reactive protein) might mediate the effects of LDL and HDL triglyceride contents on periodontitis severity.
Conclusions
Several associations between serum lipoprotein subfractions and periodontitis were observed. As the underlying biochemical mechanisms remain unclear, further research is needed.
Aim
Climate change challenges temperate forest trees by increasingly irregular precipitation and rising temperatures. Due to long generation cycles, trees cannot quickly adapt genetically. Hence, the persistence of tree populations in the face of ongoing climate change depends largely on phenotypic variation, that is the capability of a genotype to express variable phenotypes under different environmental conditions, known as plasticity. We aimed to quantify phenotypic variation of central Europe's naturally dominant forest tree across various intraspecific scales (individuals, mother trees (families), populations) to evaluate its potential to respond to changing climatic conditions.
Location
Europe.
Time Period
2016–2019.
Major Taxa Studied
European beech (Fagus sylvatica L.).
Methods
We conducted a fully reciprocal transplantation experiment with more than 9000 beech seeds from seven populations across a Europe-wide gradient. We compared morphological (Specific Leaf Area), phenological (leaf unfolding) and fitness-related (growth, survival) traits across various biological scales: within single mother trees, within populations and across different populations under the contrasting climates of the translocation sites.
Results
The experiment revealed significant phenotypic variation within the offspring of each mother tree, regardless of geographic origin. Initially, seedling height growth varied among mother trees and populations, likely due to maternal effects. However, the growth performance successively aligned after the first year. In summary, we observed a consistent growth response in different beech populations to diverse environments after initial maternal effects.
Main Conclusions
The study strikingly demonstrates the importance of considering intraspecific variation. Given the surprisingly broad spectrum of phenotypes each mother tree holds within its juvenile offspring, we conclude that Fagus sylvatica might have the potential for medium-term population persistence in face of climate change, provided that this pattern persists into later life stages. Hence, we also suggest further investigating the inclusion of passive adaptation and natural dynamics in the adaptive management of forests.
Die Untersuchung widmet sich der Analyse von Darstellungen von Erde und Kosmos in ausgewählten Drucken der Inkunabelzeit zwischen 1450 und 1500. Das Forschungskorpus umfasst verschiedene Werke, darunter das „Buch der Natur“ von Konrad von Megenberg, den „Lucidarius“, den „Schatzbehalter“ von Stephan Fridolin und die „Weltchronik“ Hartmann Schedels. Im Fokus steht die Untersuchung des Verhältnisses von Text und Bild sowie der Funktionen der Holzschnitte bei der Vermittlung von Wissen über die Welt. Bei der Analyse werden Aspekte wie Layout, Bildformeln, Kolorierung und das Zusammenspiel von Text und Bild bei der Rezeption berücksichtigt. Die Werke repräsentieren unterschiedliche Textgattungen und ermöglichen Einblicke in die sich wandelnde Rezeption von Wissen über Erde und Kosmos im Übergang von der Handschrift zum Druckmedium.
Protein engineering is essential for altering the substrate scope, catalytic activity and selectivity of enzymes for applications in biocatalysis. However, traditional approaches, such as directed evolution and rational design, encounter the challenge in dealing with the experimental screening process of a large protein mutation space. Machine learning methods allow the approximation of protein fitness landscapes and the identification of catalytic patterns using limited experimental data, thus providing a new avenue to guide protein engineering campaigns. In this concept article, we review machine learning models that have been developed to assess enzyme-substrate-catalysis performance relationships aiming to improve enzymes through data-driven protein engineering. Furthermore, we prospect the future development of this field to provide additional strategies and tools for achieving desired activities and selectivities.
Boronate esters, formed by the reaction of an oligonucleotide bearing a 5′-boronic acid moiety with the 3′-terminal cis-diol of another oligonucleotide, support the assembly of functional nucleic acid architectures. Reversible formation of boronate esters occurs in templated fashion and has been shown to restore the activity of split DNA and RNA enzymes as well as a split fluorescent light-up aptamer. Apart from their suitability for the design and application of split nucleic acid enzymes and aptamers in the field of biosensing, boronate esters may have played an important role in early life as surrogates of the natural phosphodiester bond. Their formation is reversible and thus fulfills an important requirement for biological self-assembly. Here we discuss the general concept of stimuli-dependent boronate formation and its application in biomolecules with implications for future research.
Aim
To estimate association between the use of interdental cleaning aids (IDAs) and type on 7-year follow-up levels of interdental plaque, interdental gingival inflammation, interdental periodontitis severity, the number of interdental sound surfaces and the number of missing teeth in a population-based cohort study.
Materials and Methods
We used 7-year follow-up data of 2224 participants from the Study of Health in Pomerania (SHIP-TREND). We applied generalized linear and ordinal logistic models, adjusting for confounding and selection bias using inverse probability treatment weighting and multiple imputation.
Results
Flossers were 32% less likely to have higher interdental plaque (iPlaque) levels than non-users of IDAs (odds ratio [OR] = 0.68; 95% confidence interval [CI]: 0.50–0.94); flossing resulted in 5% lower means of iPlaque. Effects on interdental bleeding on probing (iBOP), mean interdental probing depths and mean interdental clinical attachment levels were direction-consistent but statistically non-significant. Interdental brushing was associated with lower follow-up levels for interdental plaque (OR = 0.73; 95% CI: 0.57–0.93) and iBOP (OR = 0.69; 95% CI: 0.53–0.89). IDAs were more effective in reducing iPlaque in participants with periodontitis, whereas iBOP reduction was more pronounced in participants with no or mild periodontitis. The analyses did not suggest that the use of IDAs affected caries. Finally, applying change score analyses, flossing reduced tooth loss incidence (incidence rate ratio [IRR] = 0.71) compared with non-users of IDAs.
Conclusions
Recommending flossing and interdental brushing in dental practices represents an approach to the prevention of gingivitis and consequently periodontitis.
Animals face strong environmental variability even on short time scales particularly in shallow coastal habitats, forcing them to permanently adjust their metabolism. Respiration rates of aquatic ectotherms are directly influenced by water temperature, whereas ingestion rates might additionally be influenced by behavior. We aim to understand how respiration and ingestion rates of an aquatic invertebrate respond to changing temperature during a diurnal thermal fluctuation cycle and how both processes are related. We studied the benthopelagic mysid Neomysis integer as an important food web component of coastal ecosystems. Mysids were collected at the southern Baltic Sea coast and exposed in the laboratory to either constant temperature of 15°C or daily temperature fluctuation of 15 ± 5°C. Short-term (1–2 h) respiration and ingestion rates were measured at four equidistant time points within 24 h and did not differ among time points at constant temperature, but differed among time points in the fluctuating treatment. Respiration was highest at the thermal maximum and lowest at the thermal minimum. Ingestion rates showed the opposite pattern under fluctuation, likely due to differences in underlying thermal performance curves. When temperature transited the average, the direction of temperature change influenced the animals' response in respiration and ingestion rates differently. Our results suggest that respiration is not only instantaneously affected by temperature, but also influenced by the previously experienced direction of thermal change. Our experiment, using an important non-model organism, delivered new insights on the relationship between the crucial organismal processes ingestion and respiration under thermal variability.
Introduction
The number of mentally altered patients a dentist meets in practice is increasing and interaction with them can be very challenging. As a baseline for an interventional study, we want to assess the attitude of dental students and identify areas of improvement in patient communication. This work compares the attitude of dental students towards people suffering from dementia to the attitudes of trained medical caregivers and the general population. Our aim is to use the results to assess the need for training in communicating with mentally altered patients.
Materials and Methods
Fourth-year dental students attended two lectures on dementia given by a psychiatrist as part of the geriatric dentistry lecture and were questioned afterwards using the Dementia Attitude Scale. In 2016 and 2017, 73 students at the University of Greifswald were interviewed. The response rate was 84%. Using a factor analysis, the Dementia Attitude Scale's validated questions were interpreted and compared with data from nursing staff from Switzerland and the USA.
Results
The factor analysis of the data showed the same two-factor loadings as the comparative groups, and that dental students' attitude is more comparable to the general population than to medically trained nursing staff.
Conclusion
Given the results, we conclude that the implementation of a communication module can serve in improving the attitude of dental students towards patients with dementia.
Poor sleep quality or sleep deprivation may be related to decreased bone mineral density. We aimed to assess whether associations of sleep characteristics and bone turnover or strength are present in adults from the general population and whether these are independent of common risk factors such as sex, age, and obesity. A total of 1037 participants from the Study of Health in Pomerania-TREND underwent laboratory-based polysomnography and quantitative ultrasound measurements at the heel. Of these participants, 804 completed standardised questionnaires to assess daytime sleepiness, insomnia, and sleep quality. Serum concentrations of two bone turnover markers, intact amino-terminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal telopeptide of type 1 collagen (CTX) were measured. Cross-sectional associations of polysomnography variables (total sleep time, sleep efficiency, time spent wake after sleep onset, oxygen desaturation index, apnea–hypopnea index, and obstructive sleep apnea [OSA]), as well as sleep questionnaire scores with the bone turnover markers and the ultrasound-based stiffness index were assessed in linear regression models. In adjusted models, higher insomnia scores and lower sleep quality scores were related to a higher bone turnover in women but not in men. However, associations between polysomnography variables or questionnaire scores and the stiffness index were absent. Our study provides limited evidence for relationships between sleep characteristics and bone turnover and strength independent of common risk factors for OSA and osteoporosis. Nevertheless, women reporting poor sleep or insomnia in combination with risk factors for osteoporosis might benefit from an evaluation of bone health.
In der vorliegenden Arbeit wurde ein Routine-TDM auf einer Intensivstation über 3 Jahre bei Patient:innen mit Sepsis während einer kontinuierlichen Meropenemtherapie durchgeführt und auf die Umsetzung und den praktischen Nutzen hin untersucht. Da Meropenem ein Antibiotikum mit zeitabhängiger Wirkung ist, war das Ziel Konzentrationen unterhalb der 4-fachen MHK und ein dadurch bedingtes mögliches Therapieversagen zu vermeiden.
Die Patient:innen erhielten zu Beginn eine Tagesdosierung von 6 g/d mit einem initialen Bolus von 0,5 g Meropenem. Die Dosierung wurde entsprechend der erhobenen Meropenemkonzentrationen durch das Routine-TDM nach Einschätzung des ärztlichen Personals angepasst. Es wurden keine Vorgaben bzgl. eines oberen Grenzwertes oder Umsetzung der Dosisanpassungen gemacht. Das TDM ergab gerade zu Beginn erhöhte Meropenemkonzentrationen, sodass Dosissteigerungen fast ausschließlich erst nach vorheriger Dosisreduktion durchgeführt werden mussten. Konzentrationen, bei denen eine Steigerung oder eine Reduktion der Dosis beschlossen wurde, wiesen eine hohe Variabilität auf. Das Anpassungsverhalten des ärztlichen Personals kann als sehr konservativ beschrieben werden. Die Dosissteigerungen wurden bereits sehr früh und Dosisreduktionen eher spät durchgeführt.
Bei knapp 46 % der Patient:innen wurde die Dosis gar nicht angepasst und bei 46 % der Patient:innen wurde insgesamt eine Dosisreduktion durchgeführt. Dies war zu 96 % eine Halbierung der Tagesdosis auf 3 g/d. Die gemessenen Wirkkonzentrationen unterschieden sich bei Patient:innen die 6 g/d und bei Patient:innen die 3 g/d Meropenem erhielten letztendlich nicht signifikant voneinander. Dies zeigt, dass die Dosisanpassungen genutzt wurden um andere Einflussfaktoren auf die Konzentration auszugleichen.
In einer multivarianten Regressionsanalyse zeigten die Nierenfunktion, die Körpergröße und das Körpergewicht einen signifikanten Einfluss auf die Antibiotikumkonzentration. Dennoch zeigte die Regressionsanalyse sich in den Extrembereichen ungenau, weshalb ein TDM sehr sinnvoll ist. Gerade bei einer veränderten Nierenfunktion oder bei Patient:innen mit RRT zeigte sich ein TDM als sehr hilfreich. Patient:innen mit ARC zeigten sich in der vorliegenden Arbeit signifikant häufiger unterdosiert und Patient:innen mit RRT wiesen eine höhere Variabilität der gemessenen Konzentrationen auf. Tools zur Anpassung der Dosierung anhand der Nierenfunktion wurden in Studien bisher überwiegend als unzureichend beschrieben. Bei Patient:innen mit RRT werden verschiedenste Dosierungsoptionen aktuell diskutiert. Insgesamt wurde bei knapp 5,8 % der Patient:innen eine Unterdosierung detektiert. Daraufhin wurde vom ärztlichen Personal inkonsequent reagiert. Einen Einfluss auf das klinische Outcome konnte durch das TDM oder durch die Unterdosierungen nicht ausgemacht werden. Lediglich die Schwere der Sepsisart zeigte einen signifikanten Einfluss auf die Mortalität.
Neurologische Auffälligkeiten, wie Krampfanfälle konnten nur selten detektiert werden. Patient:innen, bei denen diese auffielen, zeigten zwar signifikant höhere Meropenemkonzentrationen, allerdings ließen sich die Symptome nicht mit Sicherheit auf die Antibiotikatherapie zurückführen, da diese Patient:innen zusätzlich eine neurologische Grunderkrankung hatten. In gezielten Studien zu neurotoxischen Nebenwirkungen bei Betalaktamen wird der Zusammenhang mit supratherapeutischen Konzentrationen aber immer öfter beschrieben.
Zusammenfassend zeigt sich, dass das TDM einen maßgeblichen Einfluss auf die Therapieentscheidungen hatte. Unterdosierungen sind unter der gewählten Dosierungsform nur selten aufgetreten und Dosissteigerungen waren kaum nötig. Gerade bei Patient:innen mit RRT oder erhöhter Nierenfunktion zeigte sich das TDM als nützlich. Die Grenzen für Anpassungen variierten sehr stark und wurden eher konservativ gewählt. Ein genau definierter Zielbereich der angestrebten Meropenemkonzentration und festgelegte Optionen zur Dosisanpassung könnten den Nutzen des TDMs weiter erhöhen. Weitere prospektive Studien sind nötig, um eine Obergrenze zu definieren und Toxizität zu vermeiden.
Empfehlungen für die Praxis:
• Fortsetzung des TDMs bei kritisch kranken Patient:innen
• Etablierung einer SOP zur Dosisanpassung sowie Reduzierung der Startdosierung auf 3 g Meropenem/d mit Initialbolus von 0,5 g
• Hinweise bei Patientengruppen mit Gefahr für Unter- oder Überdosierungen.
Changes in the microcirculation of the skin are a frequently observed accompanying phenomenon of many diseases, far beyond the spectrum of dermatological diseases. Not all of these changes are pathological, many are transient and have no serious consequences. This is true for many inflammatory diseases such as psoriasis vulgaris or atopic eczema.
However, there are also diseases in which functionally and morphologically recognizable microangiopathies lead to severe disease consequences. One of the most important diseases in this context is systemic sclerosis, an autoimmune systemic disease with multiple organ manifestations. Investigations of the cutaneous microcirculation are of great importance for the initial diagnosis as well as for prognosis and assessment of disease progression.
In peripheral hemodynamic disorders such as peripheral arterial disease (PAD) and chronic venous insufficiency (CVI), understanding microcirculatory disturbances also plays an important role in therapy and in monitoring the success of therapeutic interventions.
In this article, we address the transition of the Kolbe electrolysis of valeric acid (VA) to n-octane as an exemplary electrosynthesis process from a batch reaction to a continuous, self-regulated process. Based on a systematic assessment of chemical boundary conditions and sustainability aspects, we propose a continuous electrosynthesis including a simple product separation and electrolyte recirculation, as well as an online-pH-controlled VA feeding. We demonstrate how essential performance parameters such as product selectivity (S) and coulombic efficiency (CE) are significantly improved by the transition from batch to a continuous process. Thus, the continuous and pH-controlled electrolysis of a 1 M valeric acid, starting pH 6.0, allowed a constantly high selectivity of around 47 % and an average Coulomb efficiency about 52 % throughout the entire experimental duration. Under otherwise identical conditions, the conventional batch operation suffered from lower and strongly decreasing performance values (Sn-octane, 60min=10.4 %, Sn-octane, 240min=1.3 %; CEn-octane, 60min=7.1 %, CEn-octane, 240min=0.5 %). At the same time, electrolyte recirculation significantly reduces wastes and limits the use of electrolyte components.
Aims
To investigate factors that influence the willingness of inactive nurses to return to nursing in a crisis situation and to identify aspects that need to be considered with regard to a possible deployment.
Design
A deductive and inductive qualitative content analysis of semi-structured focus group interviews.
Methods
Semi-structured focus group interviews with inactive or marginally employed nurses, nurses who have been inactive for some time and nursing home managers in October and November 2021. The participating inactive nurses had declared their willingness for a deployment during the COVID-19 pandemic or not. Data were analysed using qualitative content analysis.
Results
Communication was seen as essential by the participants for an informed decision for or against a temporary return to nursing and to potential or actual deployments. To make them feel safe, inactive nurses need to know what to expect and what is expected of them, for example, regarding required training and responsibilities. Considering their current employment status, some flexibility in terms of deployment conditions is needed.
A remaining attachment to care can trigger a sense of duty. Knowledge of (regular) working conditions in nursing can lead to both a desire to support former colleagues and a refusal to be exposed to these conditions again.
Conclusion
Past working experiences and the current employment situation play a major role in the willingness of inactive nurses to return to nursing in a crisis situation. Unbureaucratic arrangements must be provided for those who are willing to return.
Summary Statement
What already is known - In crisis situations, not every inactive nurse is willing or able to return to nursing and therefore, the ‘silent reserve’ may not be as large as suspected.
What this paper adds - Inactive nurses need to know what to expect and what is expected of them for their decision regarding a return to active patient care during a crisis situation.
Implications for practice/policy – Inactive nurses need to be informed and should be offered free training and refresher courses to ensure patient safety.
Impact
This research shows that the group of inactive nurses are not a silent workforce which can be activated anytime. Those who are able and willing to return to direct patient care in crisis situations need the best possible support – during and between crises.
Reporting Method
This study adhered to COREQ guidelines.
No Patient or Public Contribution
The involvement of patients or members of the public did not apply for the study, as the aim was to gain insight into the motivations and attitudes of the group of inactive nurses.
Enzymatic degradation and recycling can reduce the environmental impact of plastics. Despite decades of research, no enzymes for the efficient hydrolysis of polyurethanes have been reported. Whereas the hydrolysis of the ester bonds in polyester‐polyurethanes by cutinases is known, the urethane bonds in polyether‐polyurethanes have remained inaccessible to biocatalytic hydrolysis. Here we report the discovery of urethanases from a metagenome library constructed from soil that had been exposed to polyurethane waste for many years. We then demonstrate the use of a urethanase in a chemoenzymatic process for polyurethane foam recycling. The urethanase hydrolyses low molecular weight dicarbamates resulting from chemical glycolysis of polyether‐polyurethane foam, making this strategy broadly applicable to diverse polyether‐polyurethane wastes.
Aim
To determine the long-term effects of the use of powered tooth brush (PTB) in comparison to manual tooth brush (MTB) on periodontitis severity, coronal caries experience, and the number of missing teeth using in a population-based cohort study.
Materials and Methods
Using 7-year follow-up data of 2214 participants of the Study of Health in Pomerania (SHIP-TREND), comprehensively adjusted linear models using generalized least squares and ordinal regression models estimated the effects of PTB usage on dental outcomes in complete case and imputed data.
Results
At follow-up, PTB users had lower medians for mean probing depth (PD; 2.21 mm) and mean clinical attachment levels (1.73 mm) than MTB users (2.30 and 1.96 mm, respectively). Adjusted models revealed the beneficial effects of PTB usage on follow-up levels of plaque, bleeding on probing, mean PD, percentage of sites with PDs ≥4 mm, mean clinical attachment levels (all, interdental, and non-interdental sites, respectively), and the number of missing teeth. For the number of missing teeth, the effects were more pronounced in participants aged ≥50 years. No significant effects of PTB usage on the number of decayed or filled surfaces (all and interdental sites) were found.
Conclusions
A recommendation of PTB usage in dental practice could contribute to the long-term promotion of oral health.
Aim
The aim of this study was to evaluate whether extraction thresholds in persons with severe periodontitis have changed between 2000 and 2010 and whether potential shifts have contributed to the reported decrease in tooth extractions in German adults over the last decades.
Materials and Methods
Data from two German population-based cohort studies in Northeast Germany (Studies of Health in Pomerania; SHIP-START [baseline 1997–2001; 11-year follow-up] and SHIP-TREND [baseline 2008–2012; 7-year follow-up]) were used. In SHIP-START (SHIP-TREND), 522 (478) participants with severe periodontitis according to the CDC/AAP case definition were included. Patterns of maximum probing depth (PD) and maximum clinical attachment level (CAL) for retained and extracted teeth were compared between SHIP-START and SHIP-TREND participants.
Results
No major differences in patterns of baseline maximum CAL of retained or extracted teeth were detected between SHIP-START and SHIP-TREND. Extraction thresholds were identified at the baseline at maximum CAL ≥6 and ≥9 mm. Tooth-level incidence rates for extraction for baseline maximum CAL of 6 mm were comparable between SHIP-START and SHIP-TREND (17.1 vs. 15.9 events per 1000 person-years).
Conclusions
After a decade, teeth in persons with severe periodontitis were still undergoing extraction with minor or moderate attachment loss. A change in extraction pattern did not contribute to the higher tooth retention rate.
Poly(vinyl alcohol) (PVA) is a water‐soluble synthetic vinyl polymer with remarkable physical properties including thermostability and viscosity. Its biodegradability, however, is low even though a large amount of PVA is released into the environment. Established physical‐chemical degradation methods for PVA have several disadvantages such as high price, low efficiency, and secondary pollution. Biodegradation of PVA by microorganisms is slow and frequently involves pyrroloquinoline quinone (PQQ)‐dependent enzymes, making it expensive due to the costly cofactor and hence unattractive for industrial applications. In this study, we present a modified PVA film with improved properties as well as a PQQ‐independent novel enzymatic cascade for the degradation of modified and unmodified PVA. The cascade consists of four steps catalyzed by three enzymes with in situ cofactor recycling technology making this cascade suitable for industrial applications.
For the characterization of Kv7.2/3 channel activators, several analytical methods are available that vary in effort and cost. In addition to the technically elaborate patch-clamp method, which serves as a reference method, there exist several medium to high-throughput screening methods including a rubidium efflux flame-atomic absorption spectrometry (F-AAS) assay and a commercial thallium uptake fluorescence-based assay. In this study, the general suitability of a graphite furnace atomic absorption spectrometry (GF-AAS)-based rubidium efflux assay as a screening method for Kv7.2/3 channel activators was demonstrated. With flupirtine serving as a reference compound, 16 newly synthesizedcompounds and the known Kv7.2/3 activator retigabine were first classified as either active or inactive by using the GF-AAS-based rubidium (Rb) efflux assay. Then, the results were compared with a thallium (Tl) uptake fluorescence-based fluorometric imaging plate reader (FLIPR) potassium assay. Overall, 16 of 17 compounds were classified by the GF-AAS-based assay in agreement with their channel-activating properties determined by the more expensive Tl uptake, fluorescence-based assay. Thus, the performance of the GF-AAS-based Rb assay for primary drug screening of Kv7.2/3-activating compounds was clearly demonstrated, as documented by the calculated Z’-factor of the GF-AAS-based method. Moreover, method development included optimization of the coating of the microtiter plates and the washing procedure, which extended the range of this assay to poorly adherent cells such as the HEK293 cells used in this study.
In temperate regions, climate warming alters temperature and precipitation regimes. During winter, a decline in insulating snow cover changes the soil environment, where especially frost exposure can have severe implications for soil microorganisms and subsequently for soil nutrient dynamics. Here, we investigated winter climate change responses in European beech forests soil microbiome. Nine study sites with each three treatments (snow exclusion, insolation, and ambient) were investigated. Long-term adaptation to average climate was explored by comparing across sites. Triplicated treatment plots were used to evaluate short-term (one single winter) responses. Community profiles of bacteria, archaea and fungi were created using amplicon sequencing. Correlations between the microbiome, vegetation and soil physicochemical properties were found. We identify core members of the forest-microbiome and link them to key processes, for example, mycorrhizal symbiont and specialized beech wood degraders (fungi) and nitrogen cycling (bacteria, archaea). For bacteria, the shift of the microbiome composition due to short-term soil temperature manipulations in winter was similar to the community differences observed between long-term relatively cold to warm conditions. The results suggest a strong link between the changes in the microbiomes and changes in environmental processes, for example, nitrogen dynamics, driven by variations in winter climate.
Being a master of metaphors
(2023)
Combining solid acid catalysts with enzyme reactions in aqueous environments is challenging because either very acidic conditions inactivate the enzymes, or the solid acid catalyst is neutralized. In this study, Amberlyst-15 encapsulated in polydimethylsiloxane (Amb-15@PDMS) is used to deprotect the lignin depolymerization product G−C2 dioxolane phenol in a buffered system at pH 6.0. This reaction is directly coupled with the biocatalytic reduction of the released homovanillin to homovanillyl alcohol by recombinant horse liver alcohol dehydrogenase, which is subsequently acylated by the promiscuous acyltransferase/hydrolase PestE_I208A_L209F_N288A in a one-pot system. The deprotection catalyzed with Amb-15@PDMS attains up to 97 % conversion. Overall, this cascade enables conversions of up to 57 %.
Baeyer-Villiger monooxygenases (BVMOs) are important flavin-dependent enzymes which perform oxygen insertion reactions leading to valuable products. As reported in many studies, BVMOs are usually unstable during application, preventing a wider usage in biocatalysis. Here, we discovered a novel NADPH-dependent BVMO which originates from Halopolyspora algeriensis using sequence similarity networks (SSNs). The enzyme is stable at temperatures between 10 °C to 30 °C up to five days after the purification, and yields the normal ester product. In this study, the substrate scope was investigated for a broad range of aliphatic ketones and the enzyme was biochemically characterized to identify optimum reaction conditions. The best substrate (86 % conversion) was 2-dodecanone using purified enzyme. This novel BVMO could potentially be applied as part of an enzymatic cascade or in bioprocesses which utilize aliphatic alkanes as feedstock.
In mandibulate arthropods, the primary olfactory centers, termed olfactory lobes in crustaceans, are typically organized in distinct fields of dense synaptic neuropils called olfactory glomeruli. In addition to olfactory sensory neuron terminals and their postsynaptic efferents, the glomeruli are innervated by diverse neurochemically distinctive interneurons. The functional morphology of the olfactory glomeruli is understudied in crustaceans compared with insects and even less well understood and described in a particular crustacean subgroup, the Peracarida, which embrace, for example, Amphipoda and Isopoda. Using immunohistochemistry combined with confocal laser scanning microscopy, we analyzed the neurochemistry of the olfactory pathway in the amphipod Parhyale hawaiensis. We localized the biogenic amines serotonin and histamine as well as the neuropeptides RFamide, allatostatin, orcokinin, and SIFamide. As for other classical neurotransmitters, we stained for γ-aminobutyric acid and glutamate decarboxylase and used choline acetyltransferase as indicator for acetylcholine. Our study is another step in understanding principles of olfactory processing in crustaceans and can serve as a basis for understanding evolutionary transformations of crustacean olfactory systems.
Boronate esters formed by reaction of an oligonucleotide carrying a 5′-boronic acid moiety with the 3′-terminal cis-diol of another have been shown previously to assist assembly of fragmented DNAzymes. Here we demonstrate that boronate esters replacing the natural phosphodiester linkage at selected sites of two functional RNAs, the hairpin ribozyme and the Mango aptamer, allow assembly of functional structures. The hairpin ribozyme, a small naturally occurring RNA that supports the reversible cleavage of appropriate RNA substrates, is very sensitive to fragmentation. Splitting the ribozyme at four different sites led to a significant decrease or even loss of cleavage and ligation activity. Ribozymes assembled from fragments capable of boronate ester formation showed restoration of cleavage activity in some but not all cases, dependent on the split site. Ligation proved to be more challenging, no supportive effect of the boronate ester was observed. Split variants of the Mango aptamer also showed a dramatic loss of functionality, which however, was restored when 5′-boronic acid modified fragments were used for assembly. These studies show for the first time that boronate esters as internucleoside linkages can act as surrogates of natural phosphodiesters in functional RNA molecules.
Amine transaminases (ATAs) are powerful biocatalysts for the stereoselective synthesis of chiral amines. Machine learning provides a promising approach for protein engineering, but activity prediction models for ATAs remain elusive due to the difficulty of obtaining high-quality training data. Thus, we first created variants of the ATA from Ruegeria sp. (3FCR) with improved catalytic activity (up to 2000-fold) as well as reversed stereoselectivity by a structure-dependent rational design and collected a high-quality dataset in this process. Subsequently, we designed a modified one-hot code to describe steric and electronic effects of substrates and residues within ATAs. Finally, we built a gradient boosting regression tree predictor for catalytic activity and stereoselectivity, and applied this for the data-driven design of optimized variants which then showed improved activity (up to 3-fold compared to the best variants previously identified). We also demonstrated that the model can predict the catalytic activity for ATA variants of another origin by retraining with a small set of additional data.
In der Klinik wird eine inter- und intraindividuelle Variabilität in Wirkung und Nebenwirkung von Opioiden beobachtet [5,6]. Ursächlich hierfür könnte unter anderem eine individuelle Ausstattung mit Transportproteinen sein, welche pharmakologische Substanzen wie zum Beispiel Opioide über körpereigene Barrieren zu ihren Wirkorten transportieren. Mit dieser Arbeit sollte die Affinität der Opioide Fentanyl und Sufentanil zu ausgewählten organic anion transporting polypeptides (OATP) untersucht werden. Ein weiteres Ziel war die Generierung eines neuen OATP1A2-Transportmodells. Im Vergleich zum bisherig verwendeten Modell mit pQCXIN::OATP1A2 sollte eine Zelllinie mit definiert integriertem Transportprotein-Gen für eine reproduzierbarere OATP1A2-Überexpression generiert werden.
Eine Affinität von Fentanyl zu OATP1A2 konnte in Kompetitionsversuchen
(IC50 14,17 µM) belegt werden. Für die Kombination Fentanyl/ OATP1B1 war keine Inhibition des Transporters nachweisbar. Sufentanil inhibierte OATP1A2 geringfügig, konnte aber herstellerbedingt nicht in vergleichbaren Konzentrationen untersucht werden. Es zeigte sich kein Transport von Fentanyl durch OATP1A2.
Da Funktionskontrollen mit den vorhandenen HEK-pQCXIN::OATP-Zelllinien mit zunehmender Passagennummer fluktuierende oder abnehmende Aktivitäten zeigten, sollten stabile Zelllinien mit definierter vorzugsweise singulärer Integration des Zielgens in HEK-293-Zellen generiert werden. Mittels Flp-In™-System wurden über drei verschiedene Klonierungsstrategien Klone von T-REx™-pcDNA5/FRT::OATP1A2 hergestellt. Auf RNA- und DNA-Ebene konnte die korrekte Integration der OATP1A2-Sequenz nachgewiesen werden. In der Funktionskontrolle zeigte sich aber nur eine maximal 1,7 fache erhöhte Aktivität gegenüber Kontrollzellen. Mit keiner der drei gewählten Klonierungsstrategien konnten ausreichend funktionelle OATP1A2 überexprimierende Zellen generiert werden, trotz intakt integrierter OATP1A2-Sequenz sowie korrekter Übergänge, Startcodon und Kozak-Sequenz, bestätigt durch Sequenzierung des Genoms der T-REx™-pcDNA5/FRT::OATP1A2 (Variante 3). In stabil transfizierten Zellen ließ sich durch Immunfluoreszenz keine Expression, ordnungsgemäße Lokalisation und Überexpression von OATP1A2 darstellen. Ob dies an einer Proteinfehlfaltung oder einer zu niedrigen Proteinexpression liegt, konnte nicht zweifelsfrei bestimmt werden.
Insgesamt trägt diese Arbeit zur Beantwortung der Frage bei, inwiefern Fentanyl die Aufnahmetransporter der OATP-Familie beeinflusst und somit durch pharmakologische Hemmung die Wirkungen und Nebenwirkungen anderer Arzneimittel verändern kann. Obwohl die Generierung OATP1A2-überexprimierender T-REx™-pcDNA5/FRT::OATP mit dem Flp-In™-System im Rahmen dieser Arbeit nicht erfolgreich verlief, konnten weitere Erfahrungen zum Flp-In™-System gesammelt werden.
Chronic kidney disease is a major public health burden associated with a drastically reduced quality of living and life span that lacks suitable, individualized therapeutic strategies. Here we present a human induced pluripotent stem cell line (iPSC, UMGACBi001-A) reprogrammed from urine cells of an acute septic dialysis patient suffering from chronic kidney disease using non-integrating administration of RNAs. The generated iPSCs were positively characterized for typical morphology, pluripotency marker expression, directed differentiation potential, non-contamination, chromosomal consistency and donor identity. This iPSC-line can be a useful source for in vitro disease modelling and individualized therapeutic approaches.
Background and Aims
Hepatocellular ballooning is a common finding in chronic liver disease, mainly characterized by rarefied cytoplasm that often contains Mallory-Denk bodies (MDB). Ballooning has mostly been attributed to degeneration but its striking resemblance to glycogenotic/steatotic changes characterizing preneoplastic hepatocellular lesions in animal models and chronic human liver diseases prompts the question whether ballooned hepatocytes (BH) are damaged cells on the path to death or rather viable cells, possibly involved in neoplastic development.
Methods
Using specimens from 96 cirrhotic human livers, BH characteristics were assessed for their glycogen/lipid stores, enzyme activities, and proto-oncogenic signaling cascades by enzyme- and immunohistochemical approaches with serial paraffin and cryostat sections.
Results
BH were present in 43.8% of cirrhotic livers. Particularly pronounced excess glycogen storage of (glycogenosis) and/or lipids (steatosis) were characteristic, ground glass features and MDB were often observed. Decreased glucose-6-phosphatase, increased glucose-6-phosphate dehydrogenase activity and altered immunoreactivity of enzymes involved in glycolysis, lipid metabolism, and cholesterol biosynthesis were discovered. Furthermore, components of the insulin signaling cascade were upregulated along with insulin dependent glucose transporter glucose transporter 4 and the v-akt murine thymoma viral oncogene homolog/mammalian target of rapamycin signaling pathway associated with de novo lipogenesis.
Conclusions
BH are hallmarked by particularly pronounced glycogenosis with facultative steatosis, many of their features being reminiscent of metabolic aberrations documented in preneoplastic hepatocellular lesions in experimental animals and chronic human liver diseases. Hence, BH are not damaged entities facing death but rather viable cells featuring metabolic reprogramming, indicative of a preneoplastic nature.
Global and even national genome surveillance approaches do not provide the resolution necessary for rapid and accurate direct response by local public health authorities. Hence, a regional network of microbiological laboratories in collaboration with the health departments of all districts of the German federal state of Mecklenburg-Western Pomerania (M-V) was formed to investigate the regional molecular epidemiology of circulating SARS-CoV-2 lineages between 11/2020 and 03/2022. More than 4750 samples from all M-V counties were sequenced using Illumina and Nanopore technologies. Overall, 3493 (73.5%) sequences fulfilled quality criteria for time-resolved and/or spatially-resolved maximum likelihood phylogenic analyses and k-mean/ median clustering (KMC). We identified 116 different Pangolin virus lineages that can be assigned to 16 Nextstrain clades. The ten most frequently detected virus lineages belonged to B.1.1.7, AY.122, AY.43, BA.1, B.1.617.2, BA.1.1, AY.9.2, AY.4, P.1 and AY.126. Time-resolved phylogenetic analyses showed the occurrence of virus clades as determined worldwide, but with a substantial delay of one to two months. Further spatio-temporal phylogenetic analyses revealed a regional outbreak of a Gamma variant limited to western M-V counties. Finally, KMC elucidated a successive introduction of the various virus lineages into M-V, possibly triggered by vacation periods with increased (inter-) national travel activities. The COVID-19 pandemic in M-V was shaped by a combination of several SARS-CoV-2 introductions, lockdown measures, restrictive quarantine of patients and the lineage specific replication rate. Complementing global and national surveillance, regional surveillance adds value by providing a higher level of surveillance resolution tailored to local health authorities.
Counting of microbial colonies is a common technique employed in research and diagnostics. To simplify this tedious and time-consuming process, automated systems have been proposed. This study aimed to elucidate the reliability of automated colony counting. We evaluated a commercially available instrument (UVP ColonyDoc-It Imaging Station) in regard to its accuracy and potential time savings. Suspensions of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterococcus faecium, and Candida albicans (n = 20 each) were adjusted to achieve growth of approximately 1,000, 100, 10, and 1 colony per plate, respectively, after overnight incubation on different solid media. Compared with manual counting, each plate was automatically counted by the UVP ColonyDoc-It with and without visual adjustment on a computer display. For all bacterial species and concentrations automatically counted without visual correction, an overall mean difference from manual counts of 59.7%, a proportion of isolates with overestimation/underestimation of colony numbers of 29%/45%, respectively, and only a moderate relationship (R2 = 0.77) with the manual counting were shown. Applying visual correction, the overall mean difference from manual counts was 1.8%, the proportion of isolates with overestimation/underestimation of colony numbers amounted to 2%/42%, respectively, and a strong relationship (R2 = 0.99) with the manual counting was observed. The mean time needed for manual counting compared with automated counting without and with visual correction was 70 s, 30 s, and 104 s, respectively, for bacterial colonies through all concentrations tested. Generally, similar performance regarding accuracy and counting time was observed with C. albicans. In conclusion, fully automatic counting showed low accuracy, especially for plates with very high or very low colony numbers. After visual correction of the automatically generated results, the concordance with manual counts was high; however, there was no advantage in reading time.
IMPORTANCE Colony counting is a widely utilized technique in the field of microbiology. The accuracy and convenience of automated colony counters are essential for research and diagnostics. However, there is only sparse evidence on performance and usefulness of such instruments. This study examined the current state of reliability and practicality of the automated colony counting with an advanced modern system. For this, we thoroughly evaluated a commercially available instrument in terms of its accuracy and counting time required. Our findings indicate that fully automatic counting resulted in low accuracy, particularly for plates with very high or very low colony numbers. Visual correction of the automated results on a computer screen improved concordance with manual counts, but there was no benefit in counting time.
Ecological Impacts and Phenotypic Plasticity of a Global Invasive Cactus, Opuntia ficus-indica
(2023)
Biological invasions by non-native species pose one of the major threats to biodiversity, the way ecosystems function, and the well-being of humans. These invasions can occur through various means, including accidental or intentional introductions by humans, natural dispersal, and climate change. Non-native species can harm the native species and ecosystems, by homogenizing plant communities, competing for resources, changing how the ecosystem operates, and eventually causing native species to go extinct. Even though not all non-native species become invasive, changes in climate and ecosystems can cause the successful establishment and spread of non-native species. Despite the advancements in our understanding of biological invasions in recent years, research has been biased towards temperate regions, whereas arid and semi-arid regions that are highly impacted by climate change are underrepresented. Thus, particularly focusing on the impacts of biological invasions in subtropical arid and semi-arid regions, the goal of this PhD project was to explore the effects of an invasive cactus on the local native communities and investigate the mechanisms of its successful invasion. Certain species are found to take advantage of the ever-drying climates in the arid/ semi-arid regions of the world. Opuntia ficus-indica, native to Mexico, is an exceptionally successful drought-tolerant invasive cactus that successfully grows in these regions. O. ficus-indica, a most widespread invasive cactus, is considered an ecosystem engineer as it modifies the habitats of indigenous plant species and dependent animals. This project aimed to identify the ecological impacts of O. ficus-indica in the highlands of Eritrea, the competitive potential of O. ficus-indica and the plastic changes that enabled its spread and invasion (Chapters I-III). For this purpose, field observations and common garden experiments were carried out throughout the project.
We investigated the effects of Opuntia ficus-indica on the spatial diversity of native plant communities (Chapter I), its competitive ability against native species (Chapter II) and the phenotypic plasticity of O. ficus-indica (Chapter III). To investigate the main ecological effects of O. ficus-indica on the native community, field data was collected from the highlands of Eritrea and comparisons were made between O. ficus-indica invaded and noninvaded areas (Chapter I). The study aimed to understand the effects of O. ficus-indica by examining species composition, richness, and diversity across vegetation layers and revealed that O. ficus-indica homogenises the species composition of the native ecosystem. This provides evidence that the presence of O. ficus-indica reduces landscape-level heterogeneity or spatial diversity. However, O. ficus-indica did not influence the species richness and diversity of the local communities. The mechanisms of the successful homogenisation of the local communities by O. ficus-indica were attributed to the potential competitive abilities of O. ficus-indica against the native species, and the plastic and adaptive traits it developed in the non-native ranges. The first assumption was tested by setting up a common garden competition experiment between two native Eritrean species, Ricinus communis and Solanum marginatum (Chapter II). The experiment used two water availability treatments, wet and dry, and categorized plants into intraspecific (native or invasive only) and interspecific (native and invasive) competition. The study evaluated the impacts by comparing the growth of O. ficus-indica alone to the growth alongside native species which revealed the weak competitive potential of O. ficus-indica. However, O. ficus-indica was observed to outgrow the native species in several folds which can be attributed to its successful invasion. The second assumption of the successful spread of O. ficus-indica was attributed to the phenotypic plastic traits adapted by O. ficus-indica in the non-native ranges (Chapter III). The phenotypic plasticity of O. ficus-indica was assessed by exposing it to water stress across dry and wet environments. The species were cultivated from a diverse set of 12 populations, encompassing its native range in Mexico with three cultivars and nonnative ranges in Africa (Algeria, Eritrea, Ethiopia), the island of Madeira off the coast of Africa, and in Europe, Italy with two cultivars and in Portugal from three sites. In Mexico and Italy, we collected various cultivars to ensure a wide representation of genotypes. We found that the species originating from the native range of O. ficus-indica exhibited lower plasticity to conditions of elevated water availability. Furthermore, a trial gradient experiment on O. ficus-indica was conducted to determine the appropriate watering levels for the species and the experiment revealed not only the species' capacity to endure a lack of water for nine months but also its ability to withstand prolonged waterlogged conditions.
This thesis illustrates the fact that invasive species are a major threat to biodiversity and ecosystem functioning worldwide, especially in rarely studied regions with dry climates and limited resources. How can invasive plants spread and cause negative impacts on native ecosystems (Chapter I), despite their weak competitive abilities (Chapter II)? This thesis explored these questions by examining the case of O. ficus-indica, an invasive species in arid/ semi-arid climates (Chapter I). It showed that O. ficus-indica has a high growth potential that allows it to overcome resource limitations, that its growth is not affected by competition from native species (Chapter II), and that it exhibits adaptive plasticity that enhances its invasion success in different environments (Chapter III). This thesis revealed the complex mechanisms and consequences of biological invasions in dry climates and contributes to the understanding of invasive species. It also suggests that more research is needed in understudied regions to assess the impacts of O. ficus-indica or invasive species in general on native biodiversity and ecosystem services and to identify the factors that influence the competitive and adaptive potentials.
Neuroblastoma is the most common extracranial, malignant, solid tumor found in children. In more than one-third of cases, the tumor is in an advanced stage, with limited resectability. The treatment options include resection, with or without (neo-/) adjuvant therapy, and conservative therapy, the latter even with curative intent. Contrast-enhanced MRI is used for staging and therapy monitoring. Diffusion-weighted imaging (DWI) is often included. DWI allows for a calculation of the apparent diffusion coefficient (ADC) for quantitative assessment. Histological tumor characteristics can be derived from ADC maps. Monitoring the response to treatment is possible using ADC maps, with an increase in ADC values in cases of a response to therapy. Changes in the ADC value precede volume reduction. The usual criteria for determining the response to therapy can therefore be supplemented by ADC values. While these changes have been observed in neuroblastoma, early changes in the ADC value in response to therapy are less well described. In this study, we evaluated whether there is an early change in the ADC values in neuroblastoma under therapy; if this change depends on the form of therapy; and whether this change may serve as a prognostic marker. We retrospectively evaluated neuroblastoma cases treated in our institution between June 2007 and August 2014. The examinations were grouped as ‘prestaging’; ‘intermediate staging’; ‘final staging’; and ‘follow-up’. A classification of “progress”, “stable disease”, or “regress” was made. For the determination of ADC values, regions of interest were drawn along the borders of all tumor manifestations. To calculate ADC changes (∆ADC), the respective MRI of the prestaging was used as a reference point or, in the case of therapies that took place directly after previous therapies, the associated previous staging. In the follow-up examinations, the previous examination was used as a reference point. The ∆ADC were grouped into ∆ADCregress for regressive disease, ∆ADCstable for stable disease, and ∆ADC for progressive disease. In addition, examinations at 60 to 120 days from the baseline were grouped as er∆ADCregress, er∆ADCstable, and er∆ADCprogress. Any differences were tested for significance using the Mann–Whitney test (level of significance: p < 0.05). In total, 34 patients with 40 evaluable tumor manifestations and 121 diffusion-weighted MRI examinations were finally included. Twenty-seven patients had INSS stage IV neuroblastoma, and seven had INSS stage III neuroblastoma. A positive N-Myc expression was found in 11 tumor diseases, and 17 patients tested negative for N-Myc (with six cases having no information). 26 patients were assigned to the high-risk group according to INRG and eight patients to the intermediate-risk group. There was a significant difference in mean ADC values from the high-risk group compared to those from the intermediate-risk group, according to INRG. The differences between the mean ∆ADC values (absolute and percentage) according to the course of the disease were significant: between ∆ADCregress and ∆ADCstable, between ∆ADCprogress and ∆ADCstable, as well as between ∆ADCregress and ∆ADCprogress. The differences between the mean er∆ADC values (absolute and percentage) according to the course of the disease were significant: between er∆ADCregress and er∆ADCstable, as well as between er∆ADCregress and er∆ADCprogress. Forms of therapy, N-Myc status, and risk groups showed no further significant differences in mean ADC values and ∆ADC/er∆ADC. A clear connection between the ADC changes and the response to therapy could be demonstrated. This held true even within the first 120 days after the start of therapy: an increase in the ADC value corresponds to a probable response to therapy, while a decrease predicts progression. Minimal or no changes were seen in cases of stable disease.
Background
Understanding how SARS-CoV-2 affects respiratory centres in the brainstem may help to preclude assisted ventilation for patients in intensive care setting. Viral invasion appears unlikely, although autoimmunity has been implicated, the responsible antigens remain unknown. We previously predicted the involvement of three epitopes within distinct brainstem proteins: disabled homolog 1 (DAB1), apoptosis-inducing-factor-1 (AIFM1), and surfeit-locus-protein-1 (SURF1).
Methods
Here, we used microarrays to screen serum from COVID-19 patients admitted to intensive care and compared those with controls who experienced mild course of the disease.
Findings
The results confirm the occurrence of IgG and IgM antibodies against the hypothesised epitopes in COVID-19 patients. Importantly, while IgM levels were similar in both groups, IgG levels were significantly elevated in severely ill patients compared to controls, suggesting a pathogenic role of IgG.
Interpretation
The newly discovered anti-neuronal antibodies might be promising markers of severe disease and the targeted peptide epitopes might be used for targeted immunomodulation. Further work is needed to determine whether these antibodies may play a role in long-COVID.
Funding
AF, CF and PR received support from the German Research Foundation (grants FL 379/22-1, 327654276-SFB 1315, FR 4479/1-1, PR 1274/8-1). SH, DR, and DB received support from the Ministry of Economy, State of Mecklenburg Western Pomerania, Germany (grant COVIDPROTECT: “Optimisation of diagnostic and therapeutic pathways for COVID-19 patients in MV”). SH received support from the Research Group Molecular Medicine University of Greifswald (FVMM, seed funding FOVB-2021-01). AV received support from the Else Kröner Fresenius Foundation and the Alzheimer Research Initiative.
The cortical silent period (CSP), assessed with transcranial magnetic stimulation (TMS), provides insights into motor cortex excitability. Alterations in the CSP have been observed in multiple sclerosis (MS), although a comparison of the sometimes contradictory results is difficult due to methodological differences. The aim of this study is to provide a more profound neurophysiological understanding of fatigue’s pathophysiology and its relationship to the CSP. Twenty-three patients with MS, along with a matched control group, underwent comprehensive CSP measurements at four intensities (125, 150, 175, and 200% resting motor threshold), while their fatigue levels were assessed using the Fatigue Scale for Motor and Cognitive Functions (FSMC) and its motor and cognitive subscore. MS patients exhibited a significantly increased CSP duration compared to controls (p = 0.02), but CSP duration was not associated with the total FSMC, or the motor or cognitive subscore. Our data suggest a systematic difference in MS patients compared to healthy controls in the CSP but no association with fatigue when measured with the FSMC. Based on these results, and considering the heterogeneous literature in the field, our study highlights the need for a more standardized approach to neurophysiological data collection and validation. This standardization is crucial for exploring the link between TMS and clinical impairments in diseases like MS.
Immunotherapies against high-risk neuroblastoma (NB), using the anti-GD2 antibody (Ab) dinutuximab beta (DB), significantly improved patient survival. Ab-dependent cellular cytotoxicity (ADCC) is one of the main mechanisms of action and it is primarily mediated by NK cells. To further improve antitumor efficacy, we investigated here a combinatorial immunotherapy with DB and the double immune checkpoint blockade of T-cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) and programmed cell death ligand-1 (PD-L1). The effects of ADCC, mediated by DB against NB cells on NK-cell activity, and the expression of TIGIT and CD226 and their ligands CD112 and CD155, as well as of PD-1 and PD-L1 on NB and effector cells, were investigated using flow cytometry. ADCC was assessed with a calcein-AM-based cytotoxicity assay. The efficacy of a combinatorial immunotherapy with DB, given as a long-term treatment, and the double immune checkpoint blockade of TIGIT and PD-L1 was shown using a resistant murine model of NB, followed by an analysis of the tumor tissue. We detected both TIGIT ligands, CD112 and CD155, on all NB cell lines analyzed. Although ADCC by DB resulted in a strong activation of NK cells leading to an effective tumor cell lysis, a remarkable induction of PD-L1 expression on NB cells, and of TIGIT and PD-1 on effector cells, especially on NK cells, was observed. Additional anti-TIGIT or anti-PD-L1 treatments effectively inhibited tumor growth and improved survival of the mice treated with DB. The superior antitumor effects were observed in the “DB + double immune checkpoint blockade” group, showing an almost complete eradication of the tumors and the highest OS, even under resistant conditions. An analysis of tumor tissue revealed both TIGIT and TIGIT ligand expression on myeloid-derived suppressor cells (MDSCs), suggesting additional mechanisms of protumoral effects in NB. Our data show that the targeting of TIGIT and PD-L1 significantly improves the antitumor efficacy of anti-GD2 immunotherapy, with DB presenting a new effective combinatorial treatment strategy against high-risk tumors.
This study investigated, if a mixed electroactive bacterial (EAB) culture cultivated heterotrophically at a positive applied potential could be adapted from oxidative to reductive or bidirectional extracellular electron transfer (EET). To this end, a periodic potential reversal regime between − 0.5 and 0.2 V vs. Ag/AgCl was applied. This yielded biofilm detachment and mediated electroautotrophic EET in combination with carbonate, i.e., dissolved CO2, as the sole carbon source, whereby the emerged mixed culture (S1) contained previously unknown EAB. Using acetate (S2) as well as a mixture of acetate and carbonate (S3) as the main carbon sources yielded primarily alternating electrogenic organoheterotropic metabolism with the higher maximum oxidation current densities recorded for mixed carbon media, exceeding on average 1 mA cm−2. More frequent periodic polarization reversal resulted in the increase of maximum oxidative current densities by about 50% for S2-BES and 80% for S3-BES, in comparison to half-batch polarization. The EAB mixed cultures developed accordingly, with S1 represented by mostly aerobes (84.8%) and being very different in composition to S2 and S3, dominated by anaerobes (96.9 and 96.5%, respectively). S2 and S3 biofilms remained attached to the electrodes. There was only minor evidence of fully reversible bidirectional EET. In conclusion the three triplicates fed with organic and/or inorganic carbon sources demonstrated two forms of diauxie: Firstly, S1-BES showed a preference for the electrode as the electron donor via mediated EET. Secondly, S2-BES and S3-BES showed a preference for acetate as electron donor and c-source, as long as this was available, switching to CO2 reduction, when acetate was depleted.
The impact of the COVID-19 pandemic on social-emotional developmental risks (SE-DR) of preschool children is largely unknown. Therefore, the aim of this prospective longitudinal dynamic cohort study was to assess changes in preschoolers’ SE-DR from before the pandemic to after the first COVID-19 wave. SE-DR were assessed annually with the instrument “Dortmund Developmental Screening for Preschools” (DESK). Longitudinal DESK data from 3- to 4-year-old children who participated both in survey wave (SW) three (DESK-SW3, 2019) and SW four (DESK-SW4, 2020) from August 1 to November 30 were used, respectively. Additionally, data from previous pre-pandemic SW were analyzed to contextualize the observed changes (SW1: 2017; SW2: 2018). A total of N = 786 children were included in the analysis. In the pre-pandemic DESK-SW3, the proportion of children with SE-DR was 18.2%, whereas in DESK-SW4 after the first COVID-19 wave, the proportion decreased to 12.4% (p = 0.001). Thus, the prevalence rate ratio (PRR) was 0.68. Compared to data from previous SW (SW1-SW2: PRR = 0.88; SW2-SW3: PRR = 0.82), this result represents a notable improvement. However, only short-term effects were described, and the study region had one of the highest preschool return rates in Germany. Further studies are needed to examine long-term effects of the pandemic on preschoolers’ SE-DR.
Background
The ‘wallflower’ hypothesis proposes females mate indiscriminately to avoid reproductive delays. Post-copulatory mechanisms may then allow ‘trading up’, favouring paternity of future mates. We tested links between pre- and post-copulatory choice in Latrodectus geometricus female spiders paired sequentially with two males. These females copulate as adults or as subadults and store sperm in paired spermathecae. Choosy adults have a higher risk of delays to reproduction than subadults.
Results
We predicted low pre-copulatory, but high post-copulatory choice at first matings for adults and the opposite for subadults. At second matings, we expected all females would prefer males superior to their first. We found all females mated indiscriminately at their first pairing, but in contrast to subadults, adults usually allowed only a single insertion (leaving one of their paired spermatheca empty); a mechanism of post-copulatory choosiness. Adult-mated females were more likely to remate than subadult-mated females when they became adults, showing a preference for larger males, while subadult-mated females tended to prefer males of greater size-corrected mass.
Conclusions
Our results show that the ‘wallflower’ effect and ‘trading up’ tactics can be utilized at different life stages, allowing females to employ choice even if rejecting males is costly.
This dynamic cohort was established to evaluate the targeted individual promotion of children affected by developmental risks as part of the German federal state law for child day-care and preschools in Mecklenburg-Western Pomerania. The project has been conducted in preschools in regions with a low socio-economic profile since 2011. Since 2017, the revision of the standardized Dortmund Developmental Screening for Preschools (DESK 3–6 R) has been applied. Developmental risks of 3 to 6-year-old children in the domains of motor, linguistic, cognitive and social competencies are monitored. The cohort is followed up annually. In 2020, n = 7,678 children from n = 152 preschools participated. At the baseline (2017), n = 8,439 children participated. Due to the defined age range of this screening, 3,000 to 4,000 5-6-year-old children leave the cohort annually. Simultaneously, an approximately equal number of 3-year-old children enters the cohort per survey wave. N = 702 children participated in all 4 survey waves. On the basis of DESK 3–6 R scores available from survey waves 2017 to 2019 it is possible to compute expected values for the survey wave 2020 and to compare those with the measured values to evaluate the effects of the COVID-19 pandemic (i.e. parental home care due to restrictions related to COVID-19).
Background
Only about half the people with depression seek professional health care services. To constitute the different predictors and associating variables of health care utilisation, we model the process and aim to test our hypothesised Seeking Mental Health Care Model. The model includes empirical influences on the help-seeking process to predict actual behaviour and incorporates superordinate (stigma, treatment experiences) as well as intermediate attitudinal variables (continuum and causal beliefs, depression literacy and self-efficacy).
Method
All variables are examined in an online study (baseline, three- and six-month follow-up). The sample consisted of adults with depressive symptoms (PHQ-9 sum score ≥ 8), currently not receiving mental health care treatment. To examine the prediction of variables explaining help-seeking behaviour, a path model analysis was carried out (lavaan package, software R).
Results
Altogether, 1368 participants (Mage = 42.38, SDage = 15.22, 65.6% female) were included, 983 participating in at least one follow-up. Model fit was excellent (i.e., RMSEA = 0.059, CFI = 0.989), and the model confirmed most of the hypothesised predictions. Intermediary variables were significantly associated with stigma and experiences. Depression literacy (ß = .28), continuum beliefs (ß = .11) and openness to a balanced biopsychosocial causal model (ß = .21) significantly influenced self-identification (R2 = .35), which among the causal beliefs and self-efficacy influenced help-seeking intention (R2 = .10). Intention (ß = .40) prospectively predicted help-seeking behaviour (R2 = .16).
Conclusion
The Seeking Mental Health Care Model provides an empirically validated conceptualisation of the help-seeking process of people with untreated depressive symptoms as a comprehensive approach considering internal influences. Implications and open questions are discussed, e.g., regarding differentiated assessment of self-efficacy, usefulness of continuum beliefs and causal beliefs in anti-stigma work, and replication of the model for other mental illnesses.
Trial registration
German Clinical Trials Register: DRKS00023557. Registered 11 December 2020. World Health Organization, Universal Trial Number: U1111–1264-9954. Registered 16 February 2021.
Although serious accidents remain the leading cause of pediatric mortality, protocols to orient diagnostic procedures towards a certain type of initial imaging are widely needed. Since 2007, we have performed whole-body magnetic resonance imaging (WBMR) and whole-body computed tomography (WBCT) for diagnoses of severely injured children. We retrospectively reviewed 134 WBMR and 158 WBCT in patients younger than 16 years that were performed at two trauma centers between 2007 and 2018. A higher Injury Severity Score (ISS) was found in WBCT vs. WBMR (10.6 vs. 5.8; p = 0.001), but without any significant difference in mortality. The WBMR was significantly preferred at younger ages (9.6 vs. 12.8 years; p < 0.001). The time between patient’s arrival until diagnosis was 2.5 times longer for WBCT (92.1 vs. 37.1 min; p < 0.001). More patients in the CT group received analgesic sedation and/or intubation at 37.3% vs. 21.6% in the MRI group. Of these patients, 86.4% (CT) and 27.6% (MRI) were already preclinically sedated (p < 0.001). Correspondingly, 72.4% of the patients were first sedated in-hospital for MRIs. In conclusion, WBMR is an alternative and radiation-free imaging method for high-energy-traumatized children. Although the selected diagnostics seemed appropriate, limitations regarding longer duration or additional analgesic sedation are present, and further studies are needed.
Treatment of high-risk neuroblastoma (NB) patients with the anti-GD2 antibody (Ab) dinutuximab beta (DB) improves survival by 15%. Ab-dependent cellular cytotoxicity (ADCC) is the major mechanism of action and is primarily mediated by NK cells. Since IL-2 co-treatment did not show a therapeutic benefit but strongly induced Treg, we investigated here a DB-based immunotherapy combined with the immunocytokine FAP-IL-2v, which comprises a fibroblast activation protein α (FAP)-specific Ab linked to a mutated IL-2 variant (IL-2v) with abolished binding to the high-affinity IL-2 receptor, thus stimulating NK cells without induction of Treg. Effects of FAP-IL-2v on NK cells, Treg and ADCC mediated by DB, as well as FAP expression in NB, were investigated by flow cytometry, calcein-AM-based cytotoxicity assay and RT-PCR analysis. Moreover, the impact of soluble factors released from tumor cells on FAP expression by primary fibroblasts was assessed. Finally, a combined immunotherapy with DB and FAP-IL-2v was evaluated using a resistant syngeneic murine NB model. Incubation of leukocytes with FAP-IL-2v enhanced DB-specific ADCC without induction of Treg. FAP expression on NB cells and myeloid-derived suppressor cells (MDCS) in tumor tissue was identified. A tumor-cell-dependent enhancement in FAP expression by primary fibroblasts was demonstrated. Combination with DB and FAP-IL-2v resulted in reduced tumor growth and improved survival. Analysis of tumor tissue revealed increased NK and cytotoxic T cell numbers and reduced Treg compared to controls. Our data show that FAP-IL-2v is a potent immunocytokine that augments the efficacy of DB against NB, providing a promising alternative to IL-2.
Platelet adhesion and spreading at the sites of vascular injury is vital to hemostasis. As an integral part of the innate immune system, platelets interact with opsonized bacterial pathogens through FcγRIIA and contribute to host defense. As mechanoscavangers, platelets actively migrate and capture bacteria via cytoskeleton-rich, dynamic structures, such as filopodia and lamellipodia. However, the role of human platelet FcγRIIA in cytoskeleton-dependent interaction with opsonized bacteria is not well understood. To decipher this, we used a reductionist approach with well-defined micropatterns functionalized with immunoglobulins mimicking immune complexes at planar interfaces and bacteriamimetic microbeads. By specifically blocking of FcγRIIA and selective disruption of the platelet cytoskeleton, we show that both functional FcγRIIA and cytoskeleton are necessary for human platelet adhesion and haptotaxis. The direct link between FcγRIIA and the cytoskeleton is further explored by single-particle tracking. We then demonstrate the relevance of cytoskeleton-dependent differential mobilities of FcγRIIA on bacteria opsonized with the chemokine platelet factor 4 (PF4) and patient-derived anti-PF4/polyanion IgG. Our data suggest that efficient capture of opsonized bacteria during host-defense is governed by mobility dynamics of FcγRIIA on filopodia and lamellipodia, and the cytoskeleton plays an essential role in platelet morphodynamics at biological interfaces that display immune complexes.
A Brief History of APIs
(2021)
Online platforms such as Facebook, YouTube and Twitter offer a wide range of data for scientific research. Since many of the social media providers have set up application programming interfaces (APIs), extensive volumes of data can be collected automatically (Jünger, 2018; Keyling & Jünger, 2016). Social media data are attractive, inter alia, because they not only include already available communication, such as that from public media, but they also make organisational and interpersonal communication visible (Ledford, 2020). In addition, these data are process-generated (Baur, 2011, p. 1234), meaning that they are generated independently of scientific research and thus promise an authentic insight into human behaviour. 1 A wide range of studies in the social sciences exploit APIs for data collection and analysis. Thus, the establishment and development of APIs has significant implications for science.
Einführung in die Ethik
(2021)
Das Open Access-Lehrbuch bietet eine allgemeinverständliche, aber wissenschaftlichen Ansprüchen genügende Einführung in die philosophische Ethik. Es erläutert den Begriff der Ethik, ihre zentralen Probleme, ihre geschichtliche Entwicklung, die einflussreichsten ethischen Grundpositionen und ihre aktuelle Relevanz in verschiedenen Praxisfeldern. Dabei erleichtert der historisch-systematische Zugang das Verständnis des Zusammenhangs von ethischer Theorie und gesellschaftlicher Praxis.
Soziale Eingebundenheit
(2021)
Der Schul- und Unterrichtsalltag wird maßgeblich durch soziale Interaktionen geprägt. Sowohl Beziehungen mit Lehrer*innen als auch mit Schülern und Schülerinnen (Peers) tragen zentral zu Lehr-/Lernprozessen und persönlicher Entwicklung der Heranwachsenden bei. Bei Lehrkräften entscheiden sie über Erfolg und Misserfolg beruflichen Handelns und finden dementsprechend zunehmend auch in der Lehrer*innenbildung Berücksichtigung. Was lange Zeit als „Kuschelpädagogik“ belächelt wurde, entpuppt sich – auch durch aktuelle Befunde aus der Hirnforschung – als einer der wichtigsten Bausteine für erfolgreiche Lehr-Lernprozesse: die Qualität der sozialen Beziehungen – subsumiert unter dem Begriff der sozialen Eingebundenheit.
In diesem Band werden sowohl theoretische Beiträge als auch aktuelle empirische Befunde zu Lehrer*innen-Schüler*innen-Beziehungen, Schüler*innen-Schüler*innen-Beziehungen und Beziehungen in der Lehrer*innenbildung vereint.
Der Band richtet sich an Personen, die sich mit sozialen Beziehungen im Bereich Schule und Lehrer*innenbildung beschäftigen, sei es durch eigene Forschungstätigkeiten, das Studium oder eine Tätigkeit in ebendieser Praxis.
The interdisciplinary study investigates the relationship between Norse and Saami peoples in the medieval period and focuses on the multifaceted portrayal of Saami peoples in medieval texts. The investigative analysis is anchored in postcolonial methodologies and argues for the inherent need to decolonise the medieval source-material as well as recent historiography. This is achieved by presenting the historiographic and political background of research into Norse-Saami relations, before introducing an overview of textual sources discussing Saami peoples from the classical period to the late 1400s, an analysis of the textual motifs associated with the Saami in medieval literature (their relevance and prevalence), geo-political affairs, trading relations, personal relations and Saami presence in the south. By using decolonising tools to read Norse-Saami relations in medieval texts, influenced by archaeological material and postcolonial frameworks, the study challenges lingering colonial assumptions about the role of the Saami in Norse society. The current research episteme is re-adjusted to offer alternative readings of Saami characters and emphasis is put on agency, fluidity and the dynamic realities of the Saami medieval pasts.
Bei einem Herz-Kreislauf-Stillstand können Leitstellendisponenten mit Hilfe eines Telefonreanimationsprotokolls medizinische Laien in Wiederbelebungsmaßnahmen anleiten. Durch die Anwendung von Automatisierten Externen Defibrillatoren (AED) durch hinzukommende qualifizierte Ersthelfer (Community-First-Responder) kann die Überlebenswahrscheinlichkeit weiter gesteigert werden. Im Rahmen des Pilotprojektes MVLIFEDRONE wurde die Umsetzung eines Telefonreanimationsprotokolls, sowie die Reanimationsqualität und AED-Anwendung von Laienhelfenden und Community-First-Respondern in 48 Simulationsszenarien untersucht. Die Datenanalyse basierte auf Videoaufzeichnungen der Simulationen und Daten des Reanimationssimulators.
Die Forschungshypothese, dass bei dem aktuell in der Untersuchungsregion angewendeten Telefonreanimationsprotokolls Teilschritte in der Umsetzung durch die Laienhelfende nicht korrekt erfolgen, konnte nachgewiesen werden. Nur 64% der Laienhelfenden führten eine suffiziente Atemkontrolle durch. Bei Verwendung einer konkretisierten Atemkontrollanweisung mit Handlungsbeschreibung führten signifikant mehr Laienhelfende (92%) eine leitlinienkonforme Atemkontrolle durch, p <0,05. Verglichen zu Laienhelfenden (99 bpm), führten Community-First-Responder die Reanimation mit einer leitlinienkonformen Frequenz (109 bpm) und korrekter Handposition durch, wobei das Erreichen der Kompressionstiefe für beide Gruppen keine Herausforderung darstellte. Lautes Mitzählen der Laienhelfenden kann die Frequenz der Thoraxkompressionen verbessern. Eine Aufforderung zur Nutzung dieser Methode im Protokoll wird empfohlen. Andere Aufforderungen, wie Bewusstseinskontrolle, Entkleidung oder die Aktivierung der Freisprechfunktion, wurden von fast 100% der Laienhelfenden suffizient umgesetzt. Damit zeigen sich diese Formulierungen als verständlich und gut umsetzbar. Die vollständige Entlastung des Thoraxes wurde von beiden Helfergruppen unzureichend durchgeführt und sollte in der Ausbildung der Community-First-Responder explizit behandelt werden. In der AED-Anwendung fand sich kein signifikanter qualitativer Unterschied zwischen den Helfergruppen, wenngleich die Community-First-Responder im Mittel 20 Sekunden schneller waren. Die Hypothese der höheren Reanimationsqualität und schnelleren AED-Anwendung der Community-First-Respondern konnte bestätigt werden. Abschließend lässt sich feststellen, dass jedes Telefonreanimationsprotokoll auf seine Umsetzbarkeit und Qualität evaluiert werden sollte.
In diesem Open-Access-Buch wird die Aussteuerung von Zielkonflikten bei der Gestaltung des Luftrettungssystems in Deutschland erarbeitet, indem ein Modell zur Bewertung von Luftrettungsleistungen entwickelt wird. Der hubschraubergestützten Luftrettung kommt seit Jahren eine zunehmende Bedeutung in der notfallmedizinischen Versorgung zu. Als auffälliges und leistungsfähiges, aber auch teures Rettungsmittel unterliegt die Luftrettung äußerst vielen Ansprüchen, die von unterschiedlichsten Interessensgruppen an das Luftrettungssystem gestellt werden. Diese Partikularinteressen implizieren Zielkonflikte bei der Gestaltung des Luftrettungssystems.
Mit dem Kostenmodell werden verschiedene Szenarien modelliert, welche auf einem exemplarischen Erfahrungsobjekt basieren. Abgebildet werden unter anderem der Status Quo, Kritikpunkte am deutschen Luftrettungssystem sowie verschiedene Innovationen, die sich auch aus einem Vergleich ausgewählter internationaler Luftrettungssysteme ergeben. Die Ergebnisse der Arbeit werden genutzt, um Handlungsempfehlungen zur Gestaltung von Luftrettungssystemen auszuarbeiten.
Der interdisziplinäre Band postuliert eine Macht des Kontextes und erklärt, was darunter verstanden wird. Die Beiträge beleuchten und hinterfragen die Macht des Kontextes in dessen Relationen zu Sprache(n), Gesellschaft(en) und Medien. Dies geschieht teils aus philologischem, teils aus sozialwissenschaftlich-kommunikationswissenschaftlichem Blickwinkel und schließt jeweils mit Thesen zur Macht des Kontextes. Der Fokus in den Beiträgen lässt sich entlang der sozialwissenschaftlichen Ebenen (Mikroebene, Mesoebene, Makroebene) differenzieren. Mit Blick auf die gewonnenen Erkenntnisse eröffnet sich die Perspektive einer breit verstandenen Kontextlinguistik, und es werden Impulse und Anknüpfungspunkte für weitere Forschung in den Einzeldisziplinen sowie für disziplinenverbindende Forschung geboten.
Osteoporosis, a complex chronic disease with increasing prevalence, is characterised by reduced bone mineral density (BMD) and increased fracture risk. The high heritability of BMD suggests substantial impact of the individual genetic disposition on bone phenotypes and the development of osteoporosis. In the past years, genome-wide association studies (GWAS) identified hundreds of genetic variants associated with BMD or osteoporosis. Here, we analysed 1103 single nucleotide polymorphisms (SNPs), previously identified as associated with estimated BMD (eBMD) in the UK Biobank. We assessed whether these SNPs are related to heel stiffness index obtained by quantitative ultrasound in 5665 adult participants of the Study of Health in Pomerania (SHIP). We confirmed 45 significant associations after correction for multiple testing. Next, we analysed six selected SNPs in 631 patients evaluated for osteoporosis [rs2707518 (CPED1/WNT16), rs3779381 (WNT16), rs115242848 (LOC101927709/EN1), rs10239787 (JAZF1), rs603424 (PKD2L1) and rs6968704 (JAZF1)]. Differences in minor allele frequencies (MAF) of rs2707518 and rs3779381 between SHIP participants (higher MAF) and patients evaluated for osteoporosis (lower MAF) indicated a protective effect of the minor allele on bone integrity. In contrast, differences in MAF of rs603424 indicated a harmful effect. Co-localisation analyses indicated that the rs603424 effect may be mediated via stearoyl-CoA desaturase (SCD) expression, an enzyme highly expressed in adipose tissue with a crucial role in lipogenesis. Taken together, our results support the role of the WNT16 pathway in the regulation of bone properties and indicate a novel causal role of SCD expression in adipose tissue on bone integrity.
Background
Short-term infusions of dinutuximab beta plus isotretinoin and cytokines administered in previous immunotherapy studies in neuroblastoma were associated with severe pain. Here, long-term, continuous infusion of single-agent dinutuximab beta was evaluated in patients with relapsed/refractory neuroblastoma.
Methods
In this open-label, single-arm, Phase 2 study, patients with either refractory or relapsed high-risk neuroblastoma received dinutuximab beta by continuous infusion over 10 days of each cycle, for up to five cycles. The primary endpoint was objective response rate 24 weeks after the end of cycle 5. Secondary endpoints included adverse events, intravenous morphine use, best response, duration of response, and three-year progression-free and overall survival.
Results
Of the 40 patients included, 38 had evaluable response. Objective response rate was 26% and best response rate 37%. Median duration of response was 238 days (IQR 108–290). Three-year progression-free and overall survival rates were 31% (95% CI 17–47) and 66% (95% CI 47–79), respectively. Prophylactic intravenous morphine use and duration of use decreased with increasing cycles. The most common grade 3 treatment-related adverse events were pain, diarrhea, and hypokalemia.
Conclusion
Long-term continuous infusion of single-agent dinutuximab beta is tolerable and associated with clinically meaningful responses in patients with relapsed/refractory high-risk neuroblastoma.
Clinical trial registration
The study is registered with ClinicalTrials.gov (NCT02743429) and EudraCT (2014-000588-42).
In dem Maß, in dem Gegenwartsliteratur gängige Auffassungen von Literatur wie von Gegenwart irritieren kann, kann sie auch als Impulsgeber und Korrektiv für eine Literaturwissenschaft fungieren, die nicht immer schon voraussetzt zu wissen, was Literatur ist. Sichtbar geworden ist dies zuletzt in Auseinandersetzungen mit Sozialen Medien, bei denen in Experimenten mit digitalen Tools wie im Rahmen konventionellerer Formen von Literatur und korrespondierender Theoriediskurse literarische und zeitdiagnostische Schreibweisen aneinanderrücken und auf je verschiedene Weise das hervorbringen, was als »Gegenwartsvergegenwärtigung« bezeichnet werden kann.
Der Nationale Kompetenzbasierte Lernzielkatalog Zahnmedizin (NKLZ) wurde 2015 verabschiedet und definiert die Lernziele für die zahnmedizinische Ausbildung in Deutschland. Er legt fest, welche Kompetenzen Studierende erwerben sollen, und dient als Grundlage für die curriculare Gestaltung des Studiums, der Prüfungen und der Unterrichtsmaterialien. Der NKLZ fördert eine umfassende Ausbildung, die neben fachlichem Wissen auch klinische Fähigkeiten und Fertigkeiten, professionelles Verhalten und kommunikative Kompetenzen einschließt. Er trägt zur Vorbereitung angehender Zahnmediziner:innen auf ihren Beruf bei und standardisiert die Ausbildung, um Qualität und Vergleichbarkeit sicherzustellen.
Der vorliegende Artikel beschreibt Hintergründe, Geschichte, Aufbau und die Weiterentwicklung des NKLZ. Derzeit wird der NKLZ zur Version 2.0 in einem mehrstufigen Prozess weiterentwickelt. Seine Struktur orientiert sich am NKLM 2.0, dem Nationalen Kompetenzbasierten Lernzielkatalog Medizin. Ziel ist es, die Anforderungen für die Zahnärztliche Approbationsordnung umfassend abzubilden.
Eine wichtige Voraussetzung für die offizielle Anerkennung des NKLZ als grundlegender Leitfaden für die Ausbildung von Zahnmediziner:innen ist die Verankerung in einer zeitnah zu reformierenden Approbationsordnung Zahnmedizin. Dadurch werden Klarheit und Verbindlichkeit für Lehrende und Studierende geschaffen. Eine solche Verankerung ermöglicht zudem eine bessere Abstimmung zwischen Ausbildungszielen und den Anforderungen der Berufspraxis. Da die Approbationsordnung weniger häufig angepasst wird, bietet die Einbindung des NKLZ die Möglichkeit, Aktualisierungen und Anpassungen des Lernzielkatalogs strukturiert und reguliert vorzunehmen. Dies gewährleistet, dass die Ausbildung den aktuellen Standards und Entwicklungen entspricht.
Numerous insertions of mitochondrial DNA in the genome of the northern mole vole, Ellobius talpinus
(2024)
Background
Ellobius talpinus is a subterranean rodent representing an attractive model in population ecology studies due to its highly special lifestyle and sociality. In such studies, mitochondrial DNA (mtDNA) is widely used. However, if nuclear copies of mtDNA, aka NUMTs, are present, they may co-amplify with the target mtDNA fragment, generating misleading results. The aim of this study was to determine whether NUMTs are present in E. talpinus.
Methods and results
PCR amplification of the putative mtDNA CytB-D-loop fragment using ‘universal’ primers from 56 E. talpinus samples produced multiple double peaks in 90% of the sequencing chromatograms. To reveal NUMTs, molecular cloning and sequencing of PCR products of three specimens was conducted, followed by phylogenetic analysis. The pseudogene nature of three out of the seven detected haplotypes was confirmed by their basal positions in relation to other Ellobius haplotypes in the phylogenetic tree. Additionally, ‘haplotype B’ was basal in relation to other E. talpinus haplotypes and found present in very distant sampling sites. BLASTN search revealed 195 NUMTs in the E. talpinus nuclear genome, including fragments of all four PCR amplified pseudogenes. Although the majority of the NUMTs studied were short, the entire mtDNA had copies in the nuclear genome. The most numerous NUMTs were found for rrnL, COXI, and D-loop.
Conclusions
Numerous NUMTs are present in E. talpinus and can be difficult to discriminate against mtDNA sequences. Thus, in future population or phylogenetic studies in E. talpinus, the possibility of cryptic NUMTs amplification should always be taken into account.
Objective
To conduct a systematic review of the published scientific evidence to evaluate the efficacy of nonsurgical periodontal therapy (NSPT) in treating periodontitis in patients with concurrent systemic conditions (diabetes, CVD, erectile dysfunction, chronic kidney disease, rheumatoid arthritis, polycystic ovarian syndrome, obesity, pregnancy). We hypothesised that NSPT results in better periodontal outcomes when compared to untreated controls after follow-up.
Materials and methods
A systematic search (PUBMED/EMBASE) was conducted from 1995 to 2023 to identify randomised controlled trials (RCTs) with a minimum follow-up of 3 months. The primary outcome was the difference in mean probing depth (PD), and the secondary outcomes were mean clinical attachment loss (CAL), percentage of sites with PD ≤ 3 mm (%PD ≤ 3 mm) and percentage of sites with bleeding on probing (%BOP) between the treated and untreated control group in patients with comorbidities.
Results
The electronic search resulted in 2,403 hits. After removing duplicates, 1,565 titles and abstracts were screened according to the eligibility criteria, resulting in 126 articles for full-text screening. Following this, 44 studies were analysed. Restricting to studies with low bias or some concerns, NSPT group demonstrated a 0.55 mm lower mean PD (95%CI: −0.69; −0.41) after 3 months compared to the control group.
Conclusion
Compared to the untreated controls, NSPT notably reduced mean PD, mean CAL, and %BOP while increasing %PD ≤ 3 mm in patients with concurrent systemic conditions. These findings suggest that NSPT is also an effective procedure in managing periodontitis in patients with concurrent systemic conditions.
Trial registration
This systematic review was registered under the protocol registration number CRD42021241517/PROSPERO.
Das vorliegende Essay gibt einen Überblick zum Standortauswahlprozess für die Endlagerung des hochradioaktiven Abfalls in der Bundesrepublik Deutschland. Dieses Verfahren stellt einen Paradigmenwechsel gegenüber dem früheren Versuch der Ausweisung eines Standortes dar, indem zunächst einzig geologische Kriterien hinsichtlich der Sicherheit der Einlagerung und nicht politisch-wirtschaftliche Einzelinteressen von Regionen entscheidend sein sollen. Der aktuelle Stand der Forschung bildet weitergehende Wissensbedarfe gut ab. Derzeit besonders diskutierte Aspekte im Rahmen der Einengung der großen Teilgebiete auf Standortregionen zur übertägigen Erkundung werden angesprochen.
Begrenzte Knorpelschäden sind ein häufiger Befund im Rahmen von Arthroskopien des Kniegelenkes. Neben Gelenkschmerzen und Funktionsverlust sind diese mit erhöhter Inzidenz einer Gonarthrose vergesellschaftet. Es stehen eine Reihe von Therapieansätzen für Knorpelschäden des Kniegelenkes zur Verfügung. Neben oraler Medikation mit Chondroitin oder Vitamin D, sind dies Analgetika und intraartikuläre Injektionen mit Hyaluronsäure oder platelet-rich Plasma (PRP). Weiterhin stehen verschiedene operative Verfahren zur chirurgischen Therapie von begrenzten Knorpelschäden des Kniegelenkes zur Verfügung. Die Indikationsstellung und Wahl des Verfahrens wird vor dem Hintergrund der aktuellen Evidenz regelmäßig in Handlungsempfehlungen der Fachgesellschaften zusammengefasst. Zunächst wurde die Indikation zu knorpelregenerativen Verfahren auf begrenzte traumatische Knorpeldefekte bei jungen Patienten eingeschränkt, in den vergangenen Jahren zeigt sich jedoch ein Trend zur Ausweitung der Indikation. Die Handlungsempfehlungen zur Wahl des geeigneten Therapieverfahrens orientieren sich an der Größe des Defektes. Für kleinere Defekte sind in erster Linie knochenmarkstimulierende Verfahren wie Mikro- oder Nanofrakturierungen vorgesehen, die um den Einsatz einer Kollagenmembran zur temporären Fixierung der eingewanderten Zellen aus dem Knochenmark erweitert werden können. Für größere Knorpeldefekte wird die autologe Chondrozytentransplantation (ACT) empfohlen. Die ACT ist das am besten wissenschaftlich untersuchte Verfahren. Weitere chirurgische, knorpelregenerative Therapiemethoden sind das Débridement, die Thermochondroplastik (TCP) und die osteochondrale Transplantation (OCT). Im Deutschen KnorpelRegister werden seit dem Jahr 2013 chirurgische Knorpeltherapieverfahren gemonitort. Die vorliegende Arbeit ist eine Auswertung zur Indikationsstellung und Auswahl des geeigneten Therapieverfahrens in Abhängigkeit von patientenspezifischen und verletzungsspezifischen Faktoren.
Bezüglich der Indikationsstellung zeigte sich, dass das Durchschnittsalter behandelter Patienten bei 37 Jahren lag und ein Viertel der behandelten Patienten älter als 47 Jahre war. Bei 60 % der behandelten Patienten wurde Übergewicht festgestellt, bei einem Drittel der Übergewichtigen lag ein starkes Übergewicht mit einem BMI über 30 kg/m² vor. Der Großteil der behandelten Knorpelschäden war degenerativer Genese (54,7 %), im Vergleich dazu lagen seltener traumatische Knorpelschäden (21,4 %) vor. Während in 59,0 % der Behandlungen der korrespondierende Knorpel intakt war, wurde in 31,9 % der Fälle eine Schädigung Grad I oder II nach ICRS und in 6,6 % der Fälle eine höhergradige Knorpelschädigung toleriert. Intakte Menisken lagen in 53,8 % der Fälle vor, in 17,9 % der Fälle lag eine Teilresektion von weniger als einem Drittel und in 7,6 % von mehr als einem Drittel der Meniskussubstanz vor.
Die Auswertung bezüglich der Wahl des geeigneten Therapieverfahrens ergab, dass das am häufigsten registrierte Verfahren im Deutschen KnorpelRegister die ACT war (52,4 %). Weitere registrierte Verfahren waren BMS (18,4 %), ACT mit Spongiosaplastik (10,0 %), Matrix-BMS (8,3 %), Débridement (4,7 %), TCP (4,2 %) und OCT (2,0 %). Bezüglich der Wahl des geeigneten Verfahrens zeigte sich, dass prinzipiell die ACT bei größeren- (Mittelwert ± Standardabweichung: 4,4 ± 2,3 cm²) und die BMS-Verfahren bei kleineren (2,1 ± 2,0 cm²) Knorpeldefekten eingesetzt wurden, jedoch gab es eine große Varianz. Innerhalb des Mittelwertes ± der zweifachen Standardabweichung für BMS-Verfahren lagen Defekte von 0,25 bis 7,5 cm², gleichzeitig wurde bei 21,2 % der Defekte mit einer Größe von weniger als 2,0 cm² entgegen der Handlungsempfehlung eine ACT durchgeführt. Unabhängige Variablen, die zum Einsatz einer ACT bei kleinen Knorpeldefekten führten, waren Voroperationen und Defekte an Patella oder Trochlea. Unabhängige Faktoren, die bei kleinen Defekten den Einsatz eines BMS-Verfahrens begünstigten, waren höheres Patientenalter, korrespondierende Knorpelschäden und bestimmte Begleitoperationen wie Bandplastiken, Meniskustherapien und Osteotomien. Für ältere Patienten fiel eine veränderte Verteilung der häufig angewendeten Therapieverfahren auf. Während die ACT bei Patienten über 47 Jahren deutlich seltener eingesetzt wurde, wurden BMS-Verfahren, Débridement und TCP vor allem in dieser Altersgruppe eingesetzt.
Im Unterschied zu den ersten Handlungsempfehlungen zum Einsatz von chirurgischen, knorpelregenerativen Eingriffen zeigte diese aktuelle Analyse, dass die Indikation auf degenerative Defekte ausgeweitet wurde. Übergewicht stellt ebenso wie höheres Alter keine Kontraindikation für einen knorpelregenerativen Eingriff dar. Während leichtgradige korrespondierende Knorpelschäden und partieller Meniskusverlust toleriert werden, stellen auch Kissing-Lesions und subtotaler Meniskusverlust keine strikte Kontraindikation für eine operative Therapie des Knorpels dar. Es fällt jedoch auf, dass fortschreitende degenerative Veränderungen des Gelenkes den Einsatz von BMS-Verfahren wahrscheinlicher, und den Einsatz einer ACT weniger wahrscheinlich machen. Ebenso werden ältere Patienten häufiger mit, gemäß der aktuellen Literatur, im Vergleich weniger potenten, aber günstigeren Methoden wie BMS, Débridement oder TCP behandelt als jüngere Patienten, welche verhältnismäßig häufiger eine ACT erhalten. Bezüglich der Wahl des geeigneten Therapieverfahrens für einen Knorpeldefekt ist die Indikationsgrenze für eine ACT zuletzt auf 2 cm² reduziert worden. Durch die vorliegende Analyse der Daten aus dem Deutschen KnorpelRegister konnte gezeigt werden, dass die ACT regelmäßig auch bei Defekten unter 2,0 cm² angewendet wurde. Es entsteht der Eindruck, dass BMS-Verfahren häufig im Rahmen von bereits geschädigten Gelenken und bei älteren Patienten eingesetzt wurden, und eine ACT bei diesen Patienten zurückhaltend eingesetzt wurde. In Zukunft muss geprüft werden, ob die Zurückhaltung bei der Indikation zur ACT bei älteren Patienten und degenerativen Veränderungen gerechtfertigt ist, ob die Matrix-BMS auch im klinischen Alltag eine Alternative zur ACT bei mittelgroßen Knorpelschäden wird, ob das Tolerieren von Übergewicht bei der Indikationsstellung gerechtfertigt ist, ob weitere Kriterien neben der Defektgröße die Wahl des Therapieverfahrens beeinflussen sollten und welche Rolle die zuletzt vermehrt eingesetzte Minced-Cartilage Implantation in Zukunft spielen wird.
Binding of general transcription factors TFIID and TFIIA to basal promoters is rate-limiting for transcriptional initiation of eukaryotic protein-coding genes. Consequently, activator proteins interacting with subunits of TFIID and/or TFIIA can drastically increase the rate of initiation events. Yeast transcriptional activator Ino2 interacts with several Taf subunits of TFIID, among them the multifunctional Taf1 protein. In contrast to mammalian Taf1, yeast Taf1 lacks bromodomains which are instead encoded by separate proteins Bdf1 and Bdf2. In this work, we show that Bdf1 not only binds to acetylated histone H4 but can also be recruited by Ino2 and unrelated activators such as Gal4, Rap1, Leu3 and Flo8. An activator-binding domain was mapped in the N-terminus of Bdf1. Subunits Toa1 and Toa2 of yeast TFIIA directly contact sequences of basal promoters and TFIID subunit TBP but may also mediate the influence of activators. Indeed, Ino2 efficiently binds to two separate structural domains of Toa1, specifically with its N-terminal four-helix bundle structure required for dimerization with Toa2 and its C-terminal β-barrel domain contacting TBP and sequences of the TATA element. These findings complete the functional analysis of yeast general transcription factors Bdf1 and Toa1 and identify them as targets of activator proteins.
Neutron scattering is a very high-performance method for studying the structure and dynamics of condensed matter with similar approaches in wide ranges of space and time, matching dimensions in space from single atoms to macromolecules and in time from atomic vibrations over crystal phonons to low-lying transitions in the microwave range, and to motions of large molecular units. Concerning the number and depth of physical concepts, neutron scattering may be compared to modern nuclear magnetic resonance. Neutrons have contributed essential results to the understanding of atomic and molecular processes and are, in this respect, complementary to other materials science probes. Among others, three properties of thermal neutrons make them especially appropriate for such work: the neutron mass is similar to atomic masses, and both neutron energies and the wavelengths of the neutron material wave match typical values for condensed matter. A further important feature of neutron scattering, making it especially valuable in biochemistry and polymer sciences, is that hydrogen and deuterium atoms very significantly and specifically contribute to the signal in both diffraction and spectroscopy. Additionally, neutrons are scattered at the nuclei and directly reflect the nuclear structure and motions. Results from neutron scattering are of great general interest. This paper aims to provide an introduction for chemists on a level understandable also to students and researchers who are not going to become part of the neutron community and will not be involved in the experiments, but shall be able to understand the basic concepts of the method and its relevance to modern chemistry. The paper focuses on basic theory, typical experiments, and some examples demonstrating the applications. As for many modern experimental techniques, the interpretation of the results of neutron scattering is based on theoretical models and requires a significant mathematical overhead. Most results are only meaningful when compared with computer simulations. For understanding this, in this paper, the theory of scattering is developed, starting with intuitive models and presenting typical concepts such as the scattering triangle, energy and momentum transfer, and the relation of inelastic and elastic scattering to space- and time-dependent information. The interaction of neutrons with matter, scattering cross sections, beam attenuation, and coherent versus incoherent scattering are explained in detail. Two further typical concepts that are not generally familiar to scientists outside the community are the use of wave and particle equivalence, and of handling results as a scattering function that depends simultaneously on momentum and energy transfers. The possibility of obtaining neutron beams for scattering experiments at a few research centers around high-performance sources is explained, and experimentally relevant features of research reactors and spallation sources are mentioned. As neutron experiments always have to deal with small flux and extended beams and shielding, experimental conditions are very far away from laboratory methods where handling of samples and instruments is concerned. Experimental details are given for making experiments more understandable and familiarizing the reader with the method. Related to this are extended possibilities for handling samples in a large variety of different environments. In a further part of the manuscript, a variety of techniques and typical instruments are presented, together with some characteristic applications bringing alive the theory developed so far. This covers powder diffraction and structure of liquid water, triple-axis spectrometers and lattice phonons, backscattering spectrometry and rotational tunneling, time-of-flight spectrometry, and simultaneously probing the energy and shape of low lying vibrations and diffusion, filter spectrometer and vibrational spectroscopy without selection rules, small-angle neutron scattering and protein unfolding, as well as micelles, neutron spin echo spectroscopy, and polymer dynamics.