Scientific publications of the Saarland University
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Fragility Fractures of the Pelvic Ring: Analysis of Epidemiology, Treatment Concepts, and Surgical Strategies from the Registry of the German Pelvic Multicenter Study Group
Get PDFBackground: Fragility fractures of the pelvic ring (FFPs) represent a fast-growing
entity in geriatric traumatology with increasing incidence worldwide. This study aimed
to analyze the epidemiology, treatment concepts, and surgical strategies for FFPs based
on data collected by the German Pelvic Multicenter Study Group documented in the
German Pelvic Fracture Registry. It is the largest cohort study of its kind. Methods:
This retrospective cohort study included patients aged 65 years or older after FFPs, as
classified according to the Rommens and Hofmann classification. Data were collected
from July 2018 onward and analyzed for demographics; fracture classifications; treatment
modalities (operative vs. non-operative); and details of surgery, including timing and
choice of implants. Patients after high-energy trauma were excluded. Statistical analyses
included descriptive metrics and subgroup comparisons. Results: Among 1242 patients
(84% female; median age 83.4 years), FFP Type II was the most common fracture type
(50.8%), followed by Type IV (21.1%). Non-operative management was employed in 68.8%
of cases, while 30.9% underwent surgery. Surgical intervention was more frequent in
higher-grade FFPs (e.g., 72.1% in Type IV). The most common surgical technique for the
posterior pelvic ring was percutaneous screw fixation (61.3%), with navigation used in
47.4% of cases. Conclusions: This study highlights the variability in treatment strategies for
FFPs, with conservative management predominating in lower-grade fractures and surgical
approaches increasingly utilized for more complex cases. The findings underscore the need
for standardized, evidence-based guidelines and further research to optimize treatment
and long-term outcomes for geriatric patients with FFPs
Synthesis and reactivity of low-valent group 13 compounds
No full textMixed species containing elements from both group 13 and 15 have been of interest for decades due to their potential application in the production of semiconducting materials. However, their synthesis remains challenging since they are highly reactive and tend to oligomerize. In this thesis, different approaches were followed for producing these highly reactive species. One of these approaches involves employing strong s-donating Lewis bases, namely N-heterocyclic carbenes (NHCs). Novel phosphanylgallanes have been prepared from various phosphorous sources and studied for elimination reactions to afford group 13-15 multiple bonds. Additionally, their electronic properties were investigated both experimentally and by computational methods. Another approach for stabilization of inherently instable and reactive species relies on employing sterically hindering ligand systems. Bis(silylamido)napthalene and carbazole derivatives were used for the preparation of low-valent aluminum and gallium species. Further reactivity studies were conducted including Al(II) radical addition reaction to the benzene ring and oxidative cyclization of a gallylene with a p-component. Finally, a low-valent mono-coordinated gallium (I) compound was synthesized, and its reactivity tested towards various substrates including transition metal complexes, Lewis bases, and unsaturated compounds. Moreover, its potential as a precursor to form Ga=N and Ga=P multiply bonded species was explored.Gemischte Verbindungen der Elemente der Gruppen 13 und 15 sind aufgrund ihres Potenzials in der Herstellung von Halbleitermaterialien von Interesse. Die Synthese dieser Verbindungen ist oft herausfordernd, da sie sehr reaktiv sind und zur Oligomerisierung neigen. Die vorliegende Dissertation konzentriert sich auf verschiedene Ansätze zur Herstellung dieser hochreaktiven Spezies. Im ersten Teil, N-heterozyklischer Carbene (NHC) wurden für die Synthese von neuartigen Phosphagallanen verwendet. Diese wurden auf Eliminierungsreaktionen untersucht, um Mehrfachbindungen zwischen Elementen der Gruppen 13 und 15 zu ermöglichen. Außerdem wurden ihre elektronischen Eigenschaften experimentell und mittels theoretischer Methoden untersucht. Im zweiten Teil wurden sterische anspruchsvolle Ligandensysteme, z.B. Bis(silylamido)napthalin- und Carbazol-Derivate, für die Herstellung von niedervalenten Aluminium- und Galliumspezies verwendet. Weitere Reaktivitätsstudien wurden durchgeführt, darunter die radikalische Al(II)-Additionsreaktion an Benzol und die oxidative Cyclisierung eines Gallylens mit einer p-Komponente. Schließlich wurde eine niedrigvalente monokoordinierte Gallium(I)-Verbindung synthetisiert und ihre Reaktivität gegenüber verschiedenen Verbindungen, einschließlich ungesättigter Verbindungen, Lewis-Säuren und Basen, untersucht. Außerdem wurde ihr Potenzial als Vorläufer für die Bildung von Ga=N- und Ga=P-Mehrfachbindungen untersucht
Assessing phototoxic drug properties of hydrochlorothiazide using human skin biopsies
Get PDFThe diuretic drug hydrochlorothiazide (HCT) is associated with an increased risk of non-melanoma
skin cancer upon UV exposure. The underlying cellular and molecular mechanisms behind this
association remain elusive. Herein, a human skin model to assess the photocarcinogenic effects of
HCT is established. Skin biopsies collected from human body donors are treated with HCT and
irradiated with 300 mJ/cm2 low dose UVA or UVB or with 5 J/cm2 high dose UVA. In HCT-treated
biopsies but not in control, low dose UVA irradiation results in activation and nuclear translocation of
the tumor-suppressor protein p53 accompanied by an upregulated gene expression of p53-negative
regulator MDM2. High dose UVA additionally provokes DNA damage and initiation of proinflammatory gene expression. In contrast, UVB induces pronounced DNA damage, p53 protein
activation, gene expression of MDM2 and inflammatory marker genes in both HCT-treated biopsies
and untreated control. In summary, in HCT-treated skin biopsies, activation of the p53-MDM2 axis,
induction of DNA damage, and inflammatory response depends on UVA-dosage and may influence
skin carcinogenesis over time. This human model eliminates the need for animal testing and mitigates
species difference, offering a valuable tool for future drug development and safety testing
Simulation of a Custom-Made Temporomandibular Joint—An Academic View on an Industrial Workflow
Get PDFTemporomandibular joint replacement is a critical intervention for severe temporomandibular joint disorders, enhancing pain levels, jaw function and overall quality of
life. In this study, we compare two finite element method-based simulation workflows from
both academic and industrial perspectives, focusing on a patient-specific case involving a
custom-made temporomandibular joint prosthesis. Using computed tomography data and
computer-aided design data, we generated different 3D models and performed mechanical
testing, including wear and static compression tests. Our results indicate that the academic
workflow, which is retrospective, purely image-based and applied post-operatively, produced peak stress values within 9–20% of those obtained from the industrial workflow.
The industrial workflow is prospective, pre-operative, computer-aided design-based and
guided by stringent regulatory standards and approval protocols. Observed differences
between workflows were attributed primarily to distinct modelling assumptions, simplifications and constraints inherent in each method. To explicitly quantify these differences,
multiple additional models were generated within the academic workflow using partial
data from the industrial process, revealing specific sources of variation in stress distribution
and implant performance. The findings underscore the potential of patient-specific simulations not only to refine temporomandibular joint prosthesis design and enhance patient
outcomes, but also to highlight the interplay between academic research methodologies
and industrial standards in the development of medical devices
Connecting image inpainting with denoising in the homogeneous diffusion setting
Get PDFWhile local methods for image denoising and inpainting may use similar concepts,
their connections have hardly been investigated so far. The goal of this work is to
establish links between the two by focusing on the most foundational scenario on
both sides – the homogeneous diffusion setting. To this end, we study a denoising by
inpainting (DbI) framework. It averages multiple inpainting results from different
noisy subsets. We derive equivalence results between DbI on shifted regular grids and
homogeneous diffusion filtering in 1D via an explicit relation between the density
and the diffusion time. We also provide an empirical extension to the 2D case. We
present experiments that confirm our theory and suggest that it can also be
generalized to diffusions with nonhomogeneous data or nonhomogeneous
diffusivities. More generally, our work demonstrates that the hardly explored idea of
data adaptivity deserves more attention – it can be as powerful as some popular
models with operator adaptivity
Unraveling the molecular basis of substrate specificity and halogen activation in vanadium-dependent haloperoxidases
Get PDFVanadium-dependent haloperoxidases (VHPOs) are biotechnologically valuable and operationally versatile biocatalysts. VHPOs share remarkable activesite structural similarities yet display variable reactivity and selectivity. The
factors dictating substrate specificity and, thus, a general understanding of
VHPO reaction control still need to be discovered. This work’s strategic singlepoint mutation in the cyanobacterial bromoperoxidase AmVHPO facilitates a
selectivity switch to allow aryl chlorination. This mutation induces loop formation that interacts with the neighboring protein monomer, creating a tunnel
to the active sites. Structural analysis of the substrate-R425S-mutant complex
reveals a substrate-binding site at the interface of two adjacent units. There,
residues Glu139 and Phe401 interact with arenes, extending the substrate
residence time close to the vanadate cofactor and stabilizing intermediates.
Our findings validate the long-debated existence of direct substrate binding
and provide a detailed VHPO mechanistic understanding. This work will pave
the way for a broader application of VHPOs in diverse chemical processes
A spatio-temporal brain miRNA expression atlas identifies sex-independent age-related microglial driven miR-155-5p increase
Get PDFAn in-depth understanding of the molecular processes composing aging is crucial to develop therapeutic approaches that decrease aging as a key risk factor for cognitive decline. Herein, we present a spatio-temporal brain atlas (15 different regions) of microRNA expression across the mouse lifespan (7 time points) and two aging interventions. MicroRNAs are promising therapeutic targets, as they silence genes by complementary base-pair binding of messenger RNAs and mediate aging speed. We first established sex- and brain-region-specific microRNA expression patterns in young adult samples. Then we focused on sex-dependent and independent brain-region-specific microRNA expression changes during aging. We identified three sex-independent brain aging microRNAs (miR-146a-5p, miR-155-5p, and miR-5100). For miR-155-5p, we showed that these expression changes are driven by aging microglia and target mTOR signaling pathway components and other cellular communication pathways. In this work, we identify strong sex-brain-region-specific aging microRNAs and microglial miR-155-5p as a promising therapeutic target
Prognostic Significance of Macrophage Phenotypes in Peri-Tumoral Normal Tissue of Early-Stage Breast Cancer
Get PDFIn recent years, tumor-infiltrating inflammatory cells within the tumor microenvi ronment have been extensively studied. However, much less is known about inflammatory
cells in the normal tissue surrounding tumors. In this study, we assess the prognostic signif icance of tumor-associated macrophages (TAMs) in relation to disease-free survival (DFS)
in patients with early-stage breast cancer. Our cohorts included patients from the APBI and
BBCC trials, with eligible tumors being small in size and showing no signs of metastasis. We
analyzed eight distinct inflammatory cell types in the normal tissue surrounding tumors,
with a particular focus on the various macrophage subsets. There were clear differences
in the frequencies of the different inflammatory cells, with a higher abundance of cells
being found in the intraepithelial compartment compared to the stromal compartment.
Notably, we found that M2-type macrophages located in the stromal compartment of tumor
distant normal tissue exhibited a positive prognostic impact, in contrast to the M2-type
macrophages found within the tumor itself. In the normal tissue surrounding tumors, there
are surprisingly clear prognostic predictions for DFS. Normal tissue surrounding breast
cancer tumors is clearly influenced by the tumor and could also influence the tumor in
terms of growth and metastasis. Tumor-influenced inflammatory cells in the surrounding
normal tissue could prevent the immune system from acting against the tumor and promote
tumor growth through inflammation
Log File Times as Indicators of Structured Figural Matrix Processing
Get PDFPrevious research has shown individual differences in (a) time on task (ToT)
and (b) the degree of structuredness in processing figural matrices. The goal of this article
was to integrate these two lines of research by analyzing log files from a computer-based
assessment (N = 198) to examine the role of three ToT sub-components: onset times (before
engaging with the first matrix rule), interrule times (between the rules), and intrarule
times (within a single rule). We tested three clues that support the assumptions that the
interrule times reflect the cognitive construction of a rule-specific solution plan, while
the onset times represent a global orientation reaction, and the intrarule times capture
the behavioral execution of the plan: (1) based on the interrule times, we identified two
clusters of participants, of which one processed the matrices in a more structured fashion;
(2) only the accelerating effect of the interrule times across the test was associated with
test performance, indicating higher reasoning saturation; (3) a mediated path analysis
revealed that faster interrule times propagate in faster intrarule times and more structured
processing of matrix rules, resulting in better performance. Confirming internal validity,
the three log file times accounted for an incremental 24.30% of test performance variance
beyond the traditional ToT. Confirming external validity, two clusters were also identified
based on the interrule times from the first test and performance scores from a second
matrix test
Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease: Insights into Pathophysiology and Treatment
Get PDFBackground: Alzheimer’s disease (AD) is a progressive neurodegenerative disor der characterized by cognitive decline and memory loss. Increasing evidence highlights
oxidative stress as a pivotal contributor to AD pathogenesis, closely associated with hall mark features such as amyloid-β (Aβ) plaque accumulation, tau hyperphosphorylation,
and synaptic dysfunction. This review aims to elucidate the mechanisms by which ox idative stress contributes to AD and to evaluate emerging therapeutic strategies targeting
oxidative damage. Methods: We conducted an extensive literature search using PubMed
and Google Scholar for studies published between 1994 and 2024. This narrative review
integrates findings from in vitro, in vivo, and clinical studies focusing on oxidative stress,
mitochondrial dysfunction, and their roles in AD to provide a comprehensive overview
of the current research landscape. Results: ROS and RNS levels are significantly elevated
in aging and AD-affected brains, leading to oxidative damage to lipids, proteins, and
DNA, which compromises neuronal function and structure. Mitochondrial dysfunction
plays a key role by amplifying ROS production, impairing ATP synthesis, and accelerating
neurodegeneration. Oxidative stress also interacts with central AD pathologies, including
Aβ aggregation, tau hyperphosphorylation, and synaptic dysfunction, creating a vicious
cycle of neuronal injury. Although traditional antioxidant therapies have shown limited
efficacy in clinical settings, often due to poor bioavailability, limited BBB penetration, and
systemic distribution, novel strategies such as mitochondrial-targeted antioxidants and
combination therapies have demonstrated improved outcomes in preclinical models. Con clusions: Oxidative stress plays a multifaceted role in the progression of AD, necessitating
comprehensive therapeutic approaches. Future treatments should focus on targeting multi ple aspects of oxidative stress, particularly mitochondrial dysfunction, to enhance clinical
outcomes and slow neurodegeneration in AD patients