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The Potential of Hetero Bimetallic Systems for the Reactivity & Functionalization of Polypnictogen Ligands
No full textIn summary, this dissertation deals with the synthesis of polypnictogen ligand complexes, their subsequent functionalization and utilization in supramolecular chemistry. A successful general synthetic pathway to neutral homo- or hetero-bimetallic cage compounds or triple-decker complexes with different polypnictogen scaffolds was presented highlighting the metal-catalysed E₄ (E = P, As) activation. Furthermore, one of the obtained triple-decker complexes [(Cp*Fe)(Cp’’’Co)(µ,η⁴:⁵-P₅)] could be investigated in detail in terms of nucleophilic and subsequent electrophilic attack or oxidation. Apart from that, the general synthetic procedure could be transferred to early transition metal complexes of group 4. In a second part, the influence of different Cpᴿ ligands at the pentaphosphaferrocene [CpᴿFe(η⁵-P₅)] was demonstrated within three-component self-assembly reactions or the ligand design of novel super bulky penta-arylated Cpᴿ ligands. These Cpᴿ ligands were successfully implemented in their corresponding pentaphosphaferrocenes displaying the largest examples so far. Characterization of all intermediate products and isolation of a spherical aggregate in the reaction with CuBr emphasizes the effect of the Cpᴿ ligand design for subsequent reactivity and utilization as building block in supramolecular chemistry yielded as a proof of principle
Aussetzung des Familiennachzugs im Lichte der Rechtsprechung des EGMR
No full textMit Gesetz vom 17.7.2025 wurde der Familiennachzug zu subsidiär Schutzberechtigten für zwei Jahre ausgesetzt. Nur vordergründig hält sich dies innerhalb des Rahmens, den der EGMR in M.A./Dänemark und M.T. u.a./Schweden abgesteckt hat. Tatsächlich entstehen so lange Wartezeiten, dass über § 22 AufenthG Einzelfallgerechtigkeit herzustellen ist. Der EGMR könnte seine Rechtsprechung ändern, doch steht dafür eine tragfähige Begründung aus
Fungal biology reviews technical advances in extracellular vesicle isolation from fungi and oomycetes: Insights from plant-pathogenic species
No full textResearch on fungal extracellular vesicles (EVs) has gained a lot of attention due to their role in plant-microbe interaction and intercellular and cross-kingdom communication. However, the isolation and characterization of EVs from plant pathogenic fungi and oomycetes still face challenges. We provide a comprehensive overview of the most recent methods for EV isolation, such as density gradient, ultracentrifugation size exclusion chromatography and differential ultracentrifugation. Quality control measures, such as dynamic light scattering, nanoparticle tracking analysis and transmission electron microscopy to ensure purity and integrity, are discussed. EVs from various organisms display heterogenicity in size and cargo. To ensure reproducibility and cross-study comparisons, we highlight the importance of standardized protocols for EV isolation and characterization. Identification of pan-fungal and pan-oomycetal EV marker proteins are needed to improve our knowledge of their function in plant-pathogen interactions. This work provides a methodological framework for the comparative analysis of EVs from fungi and oomycetes based on approaches from plant pathogens and highlights their potential relevance as targets or tools in the development of innovative plant protection strategies
Generalizing Vinyl Halide Cross‐Coupling Reactions with Photoredox and Photoredox/Nickel Dual Catalysis
No full textReliable, broadly applicable cross-coupling conditions that deliver the desired products with minimal optimization are essential in pharmaceutical research, where efficient synthesis accelerates lead discovery and late-stage diversification. Although advances like high-throughput additive screening and commercial catalyst/ligand libraries improve prediction in specific systems, a general strategy for vinyl halide cross-coupling across diverse bond-forming reactions remains elusive. Herein, we report a general and highly predictable method for vinyl halide cross-coupling under photoredox conditions, employing two complementary catalytic systems. In the first, the organic photocatalyst 4CzIPN enables efficient coupling with nucleophiles such as thiols, selenols, sulfinate salts, activated alkenes, phosphorus (III), and boron compounds, affording C(sp2)─S, ─Se, ─C, ─P, and ─B bonds in high yields. In the second, a dual nickelphotoredox catalytic system facilitates coupling with less reactive nucleophiles, including phosphorus (V), nitrogen, and oxygen. This approach enables seven distinct bond-forming reactions, offering broad electrophile and nucleophile scope, high functional group tolerance, and applicability to the late-stage functionalization of complex biomolecules. The simple and consistent conditions enable one-pot, two-step bifunctional transformations by sequentially activating distinct chemical bonds involving nucleophiles and electrophiles
Immunological effects of probiotic Lactobacillus-supplementation in people with multiple sclerosis
No full textBackground and Objective
The rising incidence of multiple sclerosis (MS) especially in western countries, is increasingly associated with the influence of various environmental factors on the pathophysiology of MS. Besides low vitamin D levels and an early infection with the Epstein Barr virus, certain nutritional factors as well as the gut and its bacteria seem to play an important role (1). Results of recent studies have already shown a link between the gut microbiome, the so-called “Western diet” and the immune system. An essential component of the so-called “Western diet” is salt. A study in an animal model of MS, the Experimental Autoimmune Encephalomyelitis (EAE), was able to show that a high-salt diet (HSD) led to depletion of lactobacilli in the intestinal microbiome, which was accompanied by an increase in inflammatory T helper (Th) 17 cells as well as a clinical worsening of EAE (2). Supplementation of lactobacilli concurrent with a HSD prevented this effect (2). In a subsequent pilot study in healthy individuals, a HSD also led to changes in the intestinal microbiome, and lactobacilli in particular were greatly reduced (2). Many other studies also underline a connection between the gut microbiome and the immune system in various (autoimmune) diseases, such as MS, rheumatoid arthritis or high blood pressure. A modulation of the intestinal microbiome by the intake of a probiotic could therefore be positive for immune-mediated diseases such as MS. Within the framework of my doctoral thesis, the influence of Vivomixx®, a probiotic dietary supplement with a large proportion of lactobacilli, on immune cells in the blood of people with MS (pwMS) and healthy controls (HC) was investigated.
Methods
Participating pwMS and HC had four appointments each (one at baseline before starting the intake of Vivomixx®, two while taking Vivomixx® for six weeks and one as a control after ending the intake of Vivomixx®), at which blood and stool samples were taken. In addition to the routine examinations of pwMS, a medical history and clinical-neurological examination of pwMS and HC were performed during the appointments. For analysis of dietary habits of participants, a food questionnaire was filled in once during the study. The blood samples were analysed for routine blood parameters and characterised for the presence of different immune cells including B cells, natural killer cells (NK cells), monocytes, CD4+-, CD8+- and CD4+CD8+ T cells with flow cytometry (Fluorescence-activated Cell Sorting, FACS). Moreover, the effect of the probiotic supplementation on T helper cells (Th1, Th17, Th2) as well as on regulatory T cells (Treg) was investigated.
Results
Analysis of routine blood levels showed a significant reduction in cholesterol after two weeks of lactobacillus supplementation in pwMS and healthy controls.
Evaluation of the food questionnaire revealed various differences in the amount of nutrients ingested by pwMS and HC, however, this was not investigated in more detail within the scope of this work. Important for this study was the intake of dietary salt, however, there were no significant differences between pwMS and HC.
Surface staining of immune cells in whole blood before starting the intake of Vivomixx® and after two or six weeks showed no significant effects on B cells or NK cells in pwMS and HC. There have been some significant fluctuations in monocytes, CD4+, CD8+ and CD4+CD8+ T cells, whereby further studies are required to link these effects to the intake of Vivomixx®. In contrast, analysis of FoxP3+ Treg cells in pwMS showed a significant increase after Vivomixx® intake for two weeks. An increase of FoxP3+ Treg cells was also observed for HC, although not statistically significant. Th17 cells were increased significantly in pwMS when comparing timepoints with the control timepoint after stopping the intake of Vivomixx®. In HC, the comparison to control points during the intake period also showed significant effects. In pwMS and pwMS under Ocrelizumab therapy, Th1 cells were significantly decreased after two weeks of Vivomixx® intake. This effect was not visible in HC. The intake of Vivomixx® had no effect on the frequencies of Th2 cells, neither in pwMS nor in HC.
Discussion and conclusion
These results suggest a potential benefit of probiotic Vivomixx® intake on the immune system, especially concerning the increase of FoxP3+ Treg cells as well as the decrease of Th1 cells. On the other hand, Th17 cells did not show any decrease. Yet, this pilot study is one of the first that deals with the effects of probiotics on immune cells in pwMS and not only in HC or mice. Therefore, it may serve as a basis for future research in this field. In view of previous research and the results of the current study, there may be a connection between diet, the gut microbiome and the immune system. It remains interesting, how strong this connection actually is and how it may contribute to treat autoimmune diseases like MS through probiotic modulations
Cross‐Sectional Observational Study of the Differences in Cephalometric Parameters in German Class I/II Orthodontic Patients
No full textObjectives: The correct classification of orthodontic patients is essential in individualized diagnostics and treatment planning. However, due to the complexity of the craniofacial skeleton and differences related to gender, age, and ethnicity, cephalometric analysis can be prone to errors. This multicenter, cross-sectional study aimed to compare cephalometric measurements between skeletal class I and II in German orthodontic patients and analyze the effect of gender/age subgroups.
Materials and Methods: In total, 556 German orthodontic patients were included and stratified into skeletal class I (n = 210) and II (n = 346), based on the individualized ANB of Panagiotidis and Witt (Calculated_ANB). Both classes presented a mean age of 13 with a range of 6.6–41 years and 5.4–53 years in classes I and II, respectively. Regarding the gender variations, most participants were females, n = 194 (56%) among class I, and n = 125 (60%) among class II. Cephalometric parameters were compared between classes and among age and gender-specific subgroups, followed by identifying correlations and performing principal component analysis (PCA).
Results: Class II patients presented a more considerable sagittal discrepancy between jaw bases than class I cases (Calculated_ANB 2.8° vs. 0.025°), a more horizontal growth pattern (Gonion angle 119° vs. 123°), and compensated inclinations of the incisors in the upper (+ 1/NL 71° vs. 68°) and lower jaw (−1/ML 84° vs. 80°). Correlations were found between sagittal, vertical, and dental cephalometric parameters, which were strongest in adult class II males. Finally, ML-NSL angle, SNPg angle, PFH/AFH ratio, and SNB angle are related to the variations of the first four components.
Conclusions: The differences in cephalometric parameters between skeletal class I and II demonstrate certain configurations in vertical, sagittal, and dental parameters, and identifying these marks precisely will enable accurate diagnosis. In addition, the variations concerning gender and age highlight the possible influence of these factors on orthodontic diagnostics and treatment planning. Future studies with equal sample sizes among subgroups must validate these findings. Finally, the PCA results highlighted that the mandible’s vertical and sagittal position has a strong influence on the diagnosis of skeletal class I/II, which highlights the importance of identifying the corresponding reference marks
Seamless monotherapy-combination phase I dose-escalation model-based design
No full textPhase I dose-escalation studies for a single-agent and combination of anti-cancer agents have explored various model-based designs to guide identification of a maximum tolerated dose and recommended phase II dose. This work describes a parallel approach to dose escalation to expedite identification of maximum tolerated doses both for an anti-cancer agent as monotherapy and in combination with another agent. We develop a three-parameter Bayesian logistic regression model that allows for more efficient use of information between monotherapy and combination parts of the study. The model allows the monotherapy and combination data to drive dose escalation of the combination of treatments, reflecting the known dose-toxicity relationship between the monotherapy and combination setting. Through a thorough simulation study in which the proposed model is compared to two comparative approaches, the three-parameter Bayesian logistic regression model is shown to accurately select doses in the target toxicity interval, performing similar to comparative approaches in terms of proportion of target dose/combination selection, while more than halving the proportion of doses selected that were greater than the target toxicity, thereby improving safety concerns
An adaptive multiarm randomised trial of biomedical and psychosocial interventions to improve convalescence following severe acute malnutrition in sub-Saharan Africa: Co-SAM trial protocol
No full textIntroduction:
Children discharged from hospital following management of complicated severe acute malnutrition (SAM) have a high risk of mortality, readmission and failed nutritional recovery. Current management approaches fail to sufficiently promote convalescence after inpatient nutritional rehabilitation. Novel interventions during the post-discharge period could enhance convalescence to help children survive and thrive.
Methods and analysis:
The Co-SAM trial is an adaptive, multicountry, phase III, individually randomised clinical trial, based on the principles that (i) interacting biological and social factors drive multimorbidity in children with SAM, and (ii) both medical and psychosocial interventions may therefore ameliorate underlying causal pathways to reduce morbidity and mortality and improve recovery. Children aged 6–59 months with complicated SAM, who have stabilised and started the transition to ready-to-use therapeutic food (RUTF), will be enrolled and randomised to one of five trial arms (standard-of-care alone; antimicrobials; reformulated RUTF; psychosocial support; or a combination of all strategies). Standard-of-care, which is provided in all trial arms, includes RUTF until nutritional recovery (defined as weight-for-height Z-score >−2, mid-upper arm circumference >12.5 cm and oedema-free since the last study visit), and other management recommended in WHO guidelines. The 12-week antimicrobial package provides daily co-formulated rifampicin and isoniazid (with pyridoxine) and 3 days of azithromycin monthly. The reformulated RUTF, which incorporates medium-chain triglycerides and hydrolysed protein to increase nutrient bioavailability and reduce metabolic stress, is provided at the same dose and duration as standard RUTF. The 12-week psychosocial package includes caregiver problem-solving therapy, educational modules, peer support groups and child play. The combined arm includes all interventions. Children start their intervention package prior to hospital discharge, with follow-up data collection in study clinics at 2, 4, 6, 8, 12 and 24 weeks. The primary composite outcome is death, hospitalisation or failed nutritional recovery within 24 weeks post-randomisation. An interim analysis will allow unpromising arms to be dropped, while the final analysis will be conducted when 1266 children have completed the study. Embedded process evaluation and laboratory substudies will explore the mechanisms of action of the interventions
A Highly Reduced Magnesium Dicobalt Complex for the Hydrogenation of Tri- and Tetra-Substituted Alkenes
No full textThe reaction of [K(thf)0.33][Co(η4-cod)2] (E; cod = 1,5-cyclooctadiene) with 0.5 equiv of MgCl2 led to the isolation of the magnesium dicobalt complex Mg[Co(η4-cod)2]2 (1). Complex 1 forms a tight ionic complex in the solid state and in toluene solution due to electrostatic interactions between the Mg2+ cation and the [Co(η4-cod)2]− anions. The complex is a successful precatalyst for the hydrogenation of sterically challenging tri- and tetra-substituted alkenes, surpassing the catalytic capabilities of related alkali metal and β-diketiminate magnesium complexes
Distinct Plasma LPC Signatures Differentiate COVID-19 Sepsis from Other Sepsis Aetiologies
Get PDFBackground/Objectives: Low levels of lysophosphatidylcholine (LPC) in the blood can be used as a diagnostic marker for sepsis. SARS-CoV-2 infection, a more recent cause of sepsis, shares similarities with non-SARS-CoV-2 sepsis but also exhibits distinct features. We have recently shown that plasma cholesteryl ester levels are higher in patients with SARS-CoV-2 infection than in patients without, and this study analysed whether this may extend to differences in LPC, a bioactive constituent of lipoproteins. Methods: The plasma levels of 13 LPC species were measured by flow injection analysis tandem mass spectrometry (FIA-MS/MS) in 157 patients with systemic inflammatory response syndrome (SIRS), sepsis or septic shock. Of these patients, 24 had SARS-CoV-2 infection. Results: Patients with SIRS exhibited higher plasma levels of the minor LPC species LPC 15:0 and 22:4 compared to those with sepsis or septic shock. Five LPC species were also reduced in the plasma of 31 patients with liver cirrhosis; therefore, patients with cirrhosis or SIRS were excluded from subsequent analyses. Compared to 76 non-COVID-19 patients with sepsis or septic shock, SARS-CoV-2 infection in 21 patients was associated with significantly higher plasma levels of ten individual LPC species and total LPC concentration. In patients with sepsis/septic shock, LPC species showed negative correlations with procalcitonin and interleukin-6, and positive correlations with gamma-glutamyltransferase and cholesteryl ester levels. In contrast, no significant associations were observed between LPC levels and C-reactive protein, aminotransferases, or free cholesterol. Conclusions: Differential LPC levels, despite comparable disease severity, may serve as metabolic biomarkers to distinguish SARS-CoV-2 sepsis from other causes of sepsis and inform targeted therapeutic approaches