GP Forschungsgruppe

Neurological disorders like Alzheimer's, Parkinson's, multiple sclerosis, and primary psychiatric conditions are complex, arising from a mix of genetic and modifiable risks. Growing evidence indicates that nutrition, environment, and lifestyle significantly influence disease development, progression, and treatment response. Nutrients such as vitamins, minerals, omega-3 fatty acids, and polyphenols affect neuroinflammation, oxidative stress, mitochondrial health, and neurotransmitter function. Dietary patterns like the Mediterranean and ketogenic diets offer protective benefits in clinical and experimental contexts. Meanwhile, environmental neurotoxicants-air pollution, heavy metals, pesticides, and endocrine disruptors contribute to neurodegeneration via oxidative damage, synaptic impairment, and epigenetic alterations. Lifestyle factors, such as physical activity, sleep, stress, and substance use, affect brain plasticity, neurogenesis, and metabolic health, thereby influencing disease progression over time. These factors often share common pathways such as oxidative stress, inflammation, vascular injury, mitochondrial dysfunction, and protein misfolding, underscoring the need for a comprehensive prevention and treatment strategy. Emerging therapies now incorporate personalized nutrition, lifestyle changes, and environmental risk mitigation alongside traditional drugs, supported by advances in multi-omics, digital health, and systems biology. Public health efforts to reduce neurotoxic exposure and encourage healthy habits further strengthen these approaches. This review summarizes existing mechanistic and clinical knowledge, with a focus on the potential of nutritional, environmental, and lifestyle interventions in neurological diseases. It also outlines the future research required to enhance precision neurology and strategies for brain health prevention.

Background COVID-19, caused by SARS-CoV-2, triggers severe systemic inflammation and multiple organ dysfunction. Microvascular complications, potentially arising from endothelial cell infection and/or immunothrombosis, play a central role in the disease's pathophysiology. Upon cell activation and/or cell death, cells release cell-free DNA (cfDNA) into the circulation, and cfDNA derived specifically from endothelial cells may serve as a marker of microvascular damage severity. Objectives In this study, we aimed to develop an assay to specifically measure endothelial cell-derived DNA as a marker of microvascular damage in COVID-19 patients. Methods In this study, we developed a methylation-specific digital droplet polymerase chain reaction assay targeting the promoter of the NOS3 gene to quantify circulating endothelial cell-derived cfDNA in COVID-19 patients followed longitudinally at inclusion, day 11, and day 28. Results Total cfDNA and endothelial-specific cfDNA levels significantly increased with COVID-19 disease severity, with the highest levels in patients with severe COVID-19. Notably, patients with mild COVID-19 showed endothelial cfDNA levels comparable to those of healthy controls, and levels remained stable from inclusion through day 28. In contrast, patients with moderate disease severity showed significantly elevated endothelial cfDNA levels compared with controls, which declined over time. Patients with severe COVID-19 displayed persistently high endothelial cfDNA levels throughout the observation period. Conclusion Using a digital droplet polymerase chain reaction assay specific for cfDNA from endothelial cells, we demonstrated endothelial cell damage in patients with COVID-19 that correlated with disease severity.

While Technical Debt (TD) manifest in systems as code-related symptoms, it is often caused by management-related issues. However, existing TD visualization tools are primarily code-based, and limited in addressing organizational factors. In this context, we introduce DebtQuest: an interactive, survey-based visualization tool designed to help assess an organization’s TD management practices. DebtQuest enables stakeholders to explore insights, pinpoint issues, perform benchmarking, and compare changes across time. Complementing the capabilities of code-based tools to discover TD symptoms, DebtQuest supports the discovery of underlying organizational causes. DebtQuest’s design is grounded in task analysis and a targeted review of relevant visualization techniques. It was refined through real-world use and evaluated by industry stakeholders. The contribution of this work is an accessible and flexible visualization design that extends recent research in TD management, revealing organizational insights that are difficult to discover using code-based tools.

The field of reductive cyclization of substituted nitroarenes by CO is dominated by the use of palladium complexes with phenanthroline ligands due to their, up to now, unrivalled combination of resistance to oxidation by the nitroarene and ability to stabilize both Pd(II) and Pd(0) complexes. Recently developed pyridinium amidate and pyridinium amide (PYA) ligands are shown here to play the same role. We tested several N,N-bidentate PYAs in the reductive cyclization of methyl o-nitrocinnamate to 2- carbomethoxyindole using either phenyl formate or the formic acid/acetic anhydride combination as a suitable CO surrogate. This approach avoids high-pressure setups for CO handling, allowing the reactions to be performed in standard pressure tubes. Two of the tested ligands, viz. a quinoline-substituted parapyridinium amide and a pyridine-functionalized ortho-pyridinium amidate gave excellent results that were comparable to those achieved using phenanthroline, even at a low catalyst loading (0.25 mol%). However, the results obtained with the pyridyl-PYA ligand strongly depend on the acidity of the reaction mixture and the reason was identified as its protonation in an acidic environment. Lower activity observed with other ligands was attributed to either an ortho-palladation of the pyridinium N-Me moiety or to an insufficient stabilization of key palladium(0) intermediates.