Ludwig-Maximilians-Universität München
Open Access LMU ( Ludwig-Maximilians-Univ. München)Not a member yet
40914 research outputs found
Sort by
Online learning for crisis response: evaluating reach and perceived knowledge gains from the MOOC “Infection, Prevention, and Control of Acute Respiratory Infections for Healthcare Workers in Low- and Middle-Income Countries (IPC MOOC)”
Full text linkThe COVID-19 pandemic had challenged healthcare systems worldwide, significantly affecting healthcare workers (HWs), particularly in low- and middle-income countries (LMICs). To address the urgent need for infection prevention and control (IPC) training among diverse healthcare roles, the Massive Open Online Course (MOOC) titled "Infection, Prevention, and Control of Acute Respiratory Infections for Healthcare Workers in Low- and Middle-Income Countries (IPC MOOC)" was developed and implemented in Ecuador. This study aimed to evaluate reach and perceived knowledge gains from the IPC MOOC, focusing on whether successful course completion was influenced by sociodemographic factors or occupational roles (manual vs. intellectual work) and whether satisfaction and perceived learning outcomes differed between these groups. The IPC MOOC was developed through an interdisciplinary collaboration involving experts from the Center for International Health at the LMU Munich University Hospital (CIHLMU) and their partners in Latin America. It utilized problem-based learning and interactive scenarios to teach IPC principles in the context of COVID-19. The course was offered to all Ecuadorian healthcare workers between August and December 2021, with a total of 3498 participants enrolling. Data were collected through registration and post-MOOC surveys and analysed using Chi-squared and Mann-Whitney U tests to assess the influence of sociodemographic and occupational factors on course completion and satisfaction, and to compare perceived learning outcomes between manual and intellectual workers. Of the enrolled participants, 75% completed the IPC MOOC successfully, with no significant differences in completion rates based on gender, region, or occupation. Among the 809 participants who completed the post-course survey, 80% reported high satisfaction (on a scale from 0 to 100%) with the course, and 95% would recommend it to colleagues. There was a small but statistically significant difference in perceived knowledge before the course between manual and intellectual workers (3.41 vs. 3.57 on a 5-point Likert scale; p=0.02), but post-course perceived knowledge was similar for both groups (4.08 vs. 4.14 on the same Likert scale; p=0.41). The IPC MOOC demonstrated to be an effective and accessible training tool, bridging knowledge gaps across diverse healthcare roles and promoting equitable access to IPC education. The high completion and satisfaction rates indicate its potential as a scalable educational intervention in health crisis
Aneuploidy-induced proteostasis disruption impairs mitochondrial functions and mediates aggregation of mitochondrial precursor proteins through SQSTM1/p62
Full text linkAneuploidy, or aberrant chromosomal content, disrupts cellular proteostasis through altered expression of numerous proteins. Aneuploid cells accumulate SQSTM1/p62-positive cytosolic bodies, exhibit impaired protein folding, and show altered proteasomal and lysosomal activity. Here, we employ p62 proximity- and affinity-based proteomics to elucidate p62 interactors in aneuploid cells and observe an enrichment of mitochondrial proteins. Increased protein aggregation and colocalization of p62 with both novel interactors and mitochondrial proteins is further confirmed by microscopy. Compared to parental diploids, aneuploid cells suffer from mitochondrial defects, including perinuclearly-clustered mitochondrial networks, elevated reactive oxygen species levels, reduced mitochondrial DNA abundance, and impaired protein import, leading to cytosolic accumulation of mitochondrial precursor proteins. Overexpression of heat shock proteins in aneuploid cells mitigates protein aggregation and decreases the colocalization of p62 with the mitochondrial protein TOMM20. Thus, proteotoxic stress caused by chromosome gains results in the sequestration of mitochondrial precursor proteins into cytosolic p62-bodies, thereby compromising mitochondrial function
Barriers on the path to inclusion. The development of special needs education in Germany over time
Full text linkSpecial education is a school-based construct intended to to provide specific help and more resources to individual children. This textbook provides a historical overview of the development of special education in Germany, outlines key concepts and theories that underpin this field of study, and identifies fundamental questions posed by scholars and practitioners alike. The different perspectives on disability and the special educational needs for support are presented and discussed, especially for children with learning diffi-culties (special needs in the area of learning). This book serves as an introductory work in the field of inclusive education. It serves as the basis and basic knowledge for the teaching profession of special education. This book is a translation of a German open textbook (Gebhardt, 2024) that provides international students with better access to international courses in special education at German universities
The immunoproteasome disturbs neuronal metabolism and drives neurodegeneration in multiple sclerosis
No full textAn Exploratory Analysis of Differential Tear Fluid miRNAs in Patients with Parkinson’s Disease and Atypical Parkinsonian Syndromes
No full textParkinson’s disease (PD), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) are neurodegenerative disorders diagnosed by clinical criteria with limited diagnostic specificity in early stages. Diagnostic biomarkers facilitating early and precise diagnosis are needed. Tear fluid (TF) is an easily accessible body fluid reflecting pathophysiological changes in ocular and systemic diseases. In this exploratory study, we investigate TF as a non-invasive source of disease-specific miRNAs for PD, MSA, and PSP. We demonstrate reduced TF production in PD patients. Using a real-time quantitative PCR-based array targeting 1113 miRNAs, we identified 55 exclusively expressed in PD, 35 in PSP, and 14 in MSA, respectively. Several of these have previously been identified in other biofluids. Overrepresentation analysis of target genes showed apoptotic and cell differentiation pathways as common targets. While these findings suggest that miRNA alterations in TF might reflect disease mechanisms in PD and atypical Parkinsonian syndromes, the exploratory character of the study combined with the use of pooled samples, indicates the need for further validation. The small sample size highlights the importance of follow-up studies with larger, more definitive cohorts to confirm the potential of these miRNAs as reliable biomarkers
Human Genetics Informing Drug Development in Cardiovascular Disease: Interleukin-6 Signaling as a Case Study
No full textCardiovascular disease remains the leading cause of death worldwide, calling for the development of novel therapeutics. Over the past 3 decades, substantial investments in human genetic research have unveiled the genetic architecture of cardiovascular disease, offering promising novel therapeutic targets. These discoveries have been instrumental in the development of several cardiovascular drug development programs, such as those targeting proprotein convertase subtilisin/kexin type 9, lipoprotein (a), apo C3, and angiopoietin-like 3. Large-scale resources such as population-based biobanks and data repositories, now enable human genetic data to be leveraged at scale and inform not only target selection, but also clinical drug development. This review highlights the transformative potential of human genetics in cardiovascular drug development, focusing on IL (interleukin)-6 signaling as a case study. Specifically, we discuss how IL-6 signaling was pinpointed as a key causal mediator of atherosclerosis by genetic data, shaping the current development landscape for anti–IL-6 therapeutics in cardiovascular disease. Recent genetic studies employing innovative methodologies have provided key insights into prioritizing indications for clinical testing, informing repurposing strategies, optimizing clinical trial design for population selection, and assessing safety signals. Despite this progress, methodological challenges, such as pleiotropic effects of genetic variants, extrapolation of small genetic associations to large interventional effects, and the predominance of European-derived data, highlight the need for careful interpretation. Continued methodological advances, coupled with the emergence of high-throughput omics data and detailed cardiovascular phenotyping, promise unprecedented opportunities to refine drug discovery and development
Comment by European Alzheimer’s Disease Consortium (EADC) investigators on the negative recommendation of the CHMP on the marketing authorization of donanemab for early Alzheimer’ s disease
No full textThe role of submarine volcanism in atmospheric chemistry
No full textSubmarine volcanic eruptions can form subaerial plumes that reach the stratosphere. Despite this, the impact of submarine eruptions on climate remains unclear due to a lack of clear geological record, with the recent large-scale Hunga eruption on 15 January 2022 being considered as an isolated case. Here, we review the impact of submarine and subaerial volcanoes in island or coastal settings (i.e., near seawater) on volatile/aerosol loading in the stratosphere. Isotopic δ34S signatures of the Hunga ash suggest that CaSO4 salts on the ash surface are dominantly formed by the evaporation of seawater during the eruption. We infer that SO2 scavenging on volcanic ash did not play a major role in the lower-than-expected SO2 detected in the volcanic cloud. Chlorine isotopic compositions (δ37Cl) also argue in favor of a seawater-derived origin of the chlorides from ash leachates. Combining petrological, leachate, isotopic and thermal analysis data, we demonstrate a near-absence of halogen degassing from the Hunga magma prior to and during the eruption, and conclude that the chlorine and bromine contents of tropospheric and stratospheric volatile species very dominantly derive from seawater/sea salts. We generalize our findings to all submarine eruptions, and large-scale, non-submarine eruptions in island or coastal settings, and propose that these may commonly form volcanic clouds that incorporate seawater thereby leading to the injection of related components (water vapor, sea salts, halogens) into the stratosphere. This makes seawater inputs a serious consideration when evaluating the long-term impact of volcanoes on climate
Development of Trastuzumab-coupled, siRNA encapsulating mPolyplexes targeting HER2 overexpressing cancer cells
No full textOver the past decades, significant advancements have been made in various medical fields; however, ovarian cancer (OC) remains inadequately addressed, predominantly relying on relatively toxic cytostatic treatments. In this study, we applied newly developed poly(β-amino) esters (PBAEs) for siRNA delivery. As recent literature has shown, the introduction of a hydrophobic, unsaturated fatty acid together with polycationic spermines as the PBAE side chains are leading to a favourable transfection efficiency, and the resulting materials form a unique class of micelleplexes, termed micelle-embedded polyplexes (mPolyplexes). Here, such mPolyplexes were modified post-particle formation with the approved monoclonal antibody Trastuzumab for HER2 targeting, as supported by a receptor binding analysis through fluorescence shift assay. Physicochemical analysis revealed suitable hydrodynamic diameters of modified mPolyplexes, as determined by dynamic light scattering. Improved cellular uptake when targeted with Trastuzumab was optimized by applying Design of Experiment (DoE). We demonstrated superior gene silencing efficiency of EGFR as well as PLK1, both involved in OC progression, with knockdown values exceeding 82% and 70%, respectively. These findings were corroborated by a relevant cell migration assay. The macroscopic impact after PLK1 silencing on epithelial-mesenchymal transition (EMT) was visualized using confocal microscopy. This work addresses critical questions in the field of ovarian cancer therapy and confirms the suitability of siRNA encapsulating PBAE nanocarriers as promising non-viral vectors