Amyloid beta and its naturally occurring N-terminal variants are potent activators of human and mouse formyl peptide receptor 1.

Formyl peptide receptors (FPRs) may contribute to inflammation in Alzheimer's disease through interactions with neuropathological Amyloid beta (Aß) peptides. Previous studies reported activation of FPR2 by Aß1-42, but further investigation of other FPRs and Aß variants is needed. This study provides a comprehensive overview of the interactions of mouse and human FPRs with different physiologically relevant Aß-peptides using transiently transfected cells in combination with calcium imaging. We observed that, in addition to hFPR2, all other hFPRs also responded to Aß1-42, Aß1-40, and the naturally occurring variants Aß11-40 and Aß17-40. Notably, Aß11-40 and Aß17-40 are very potent activators of mouse and human FPR1, acting at nanomolar concentrations. Buffer composition and aggregation state are extremely crucial factors that critically affect the interaction of Aß with different FPR subtypes. To investigate the physiological relevance of these findings, we examined the effects of Aß11-40 and Aß17-40 on the human glial cell line U87. Both peptides induced a strong calcium flux at concentrations that are very similar to those obtained in experiments for hFPR1 in HEK cells. Further immunocytochemistry, qPCR, and pharmacological experiments verified that these responses were primarily mediated through hFPR1. Chemotaxis experiments revealed that Aß11-40 but not Aß17-40 evoked cell migration, which argues for a functional selectivity of different Aß peptides. Together, these findings provide the first evidence that not only hFPR2 but also hFPR1 and hFPR3 may contribute to neuroinflammation in Alzheimer's disease through an interaction with different Aß variants.

Towards Recognition of Human Actions in Collaborative Tasks with Robots: Extending Action Recognition with Tool Recognition Methods.

This paper presents a novel method for online tool recognition in manual assembly processes. The goal was to develop and implement a method that can be integrated with existing Human Action Recognition (HAR) methods in collaborative tasks. We examined the state-of-the-art for progress detection in manual assembly via HAR-based methods, as well as visual tool-recognition approaches. A novel online tool-recognition pipeline for handheld tools is introduced, utilizing a two-stage approach. First, a Region Of Interest (ROI) was extracted by determining the wrist position using skeletal data. Afterward, this ROI was cropped, and the tool located within this ROI was classified. This pipeline enabled several algorithms for object recognition and demonstrated the generalizability of our approach. An extensive training dataset for tool-recognition purposes is presented, which was evaluated with two image-classification approaches. An offline pipeline evaluation was performed with twelve tool classes. Additionally, various online tests were conducted covering different aspects of this vision application, such as two assembly scenarios, unknown instances of known classes, as well as challenging backgrounds. The introduced pipeline was competitive with other approaches regarding prediction accuracy, robustness, diversity, extendability/flexibility, and online capability.

Emerging contributions of formyl peptide receptors to neurodegenerative diseases.

Inflammation is a central element of many neurodegenerative diseases. Formyl peptide receptors (FPRs) can trigger several receptor-dependent signal transduction pathways that play a key role in neuroinflammation and neurodegeneration. They are chemotactic receptors that help to regulate pro- and anti-inflammatory responses in most mammals. FPRs are primarily expressed in the immune and nervous systems where they interact with a complex pattern of pathogen-derived and host-endogenous molecules. Mounting evidence points towards a contribution of FPRs - via neuropathological ligands such as Amyloid beta, and neuroprotective ligands such as Humanin, Lipoxin A4, and Annexin A1 - to multiple pathological aspects of neurodegenerative diseases. In this review, we aim to summarize the interplay of FPRs with neuropathological and neuroprotective ligands. Next, we depict their capability to trigger a number of ligand-dependent cell signaling pathways and their potential to interact with additional intracellular cofactors. Moreover, we highlight first studies, demonstrating that a pharmacological inhibition of FPRs helps to ameliorate neuroinflammation, which may pave the way towards novel therapeutic strategies.

The Hidden Role of Non-Canonical Amyloid ß Isoforms in Alzheimer's Disease.

Recent advances have placed the pro-inflammatory activity of amyloid ß (Aß) on microglia cells as the focus of research on Alzheimer's Disease (AD). Researchers are confronted with an astonishing spectrum of over 100 different Aß variants with variable length and chemical modifications. With the exception of Aß1-42 and Aß1-40, the biological significance of most peptides for AD is as yet insufficiently understood. We therefore aim to provide a comprehensive overview of the contributions of these neglected Aß variants to microglia activation. First, the impact of Aß receptors, signaling cascades, scavenger mechanisms, and genetic variations on the physiological responses towards various Aß species is described. Furthermore, we discuss the importance of different types of amyloid precursor protein processing for the generation of these Aß variants in microglia, astrocytes, oligodendrocytes, and neurons, and highlight how alterations in secondary structures and oligomerization affect Aß neurotoxicity. In sum, the data indicate that gene polymorphisms in Aß-driven signaling pathways in combination with the production and activity of different Aß variants might be crucial factors for the initiation and progression of different forms of AD. A deeper assessment of their interplay with glial cells may pave the way towards novel therapeutic strategies for individualized medicine.

Evaluation of Patients' Preferences for Skin Grafting in Plastic-Surgical Defect Coverage.

BACKGROUND: Grafting split-thickness (STSGs) and full-thickness skin grafts (FTSGs) are common techniques to replace missing skin and to restore the skin barrier in burn, trauma and remaining skin defects after tumor resections. The defect coverage with skin grafts offer many advantages, but also disadvantages such as donor site morbidity like possible sensory disturbances, scarring, risk of infection, contour changes and pigment disorders. We aimed to assess the preferred distribution of donor site for STSGs and FTSGs in patient's skin grafting for plastic-surgical defect coverage. METHODS: Patients and their accompany persons referred to the Department of Plastic Surgery were interviewed for defect coverage with STSGs or FTSGs, the preference in donor site was investigated and the detailed advantages and disadvantages were clarified. RESULTS: We evaluated 85 participants (male=43, female=42) with a median age of 42 years (mean=46 years). The definition of the donor site (n=188 markings) was mainly based on the physicians recommendation (32.98%), mobility (23.40%), aesthetic results (22.34%) and pain (21.28%). Feared complications (n=152) were mainly wound healing disorders (32.24%), circulation disorders (28.29%), scars (20.39%) and bleeding risks (19.08%). Among all participants, 79 split-skin graft preferences were specified, while 32% favored the scalp as a donor site, as well as 29% the frontal part of the left thigh and 10% the frontal part of the right thigh. CONCLUSION: There were preferred anatomical donor sites for skin grafting. Nevertheless, in conscious patients, the donor site has to be selected in a consent talk and joint approval, preoperatively. The options of taking STSGs from the occipital region with all its advantages should be discussed intensively as it is an attractive graft donor site.

How to become a medical professor - a comparative analysis of academic requirements in Germany and the United States.

BACKGROUND: The acquisition of a medical professorship represents a significant step in a physician's academic career. The responsibility as well as the honor and the associated obligations are significant; however, the requirements to become a medical professor vary in Germany. OBJECTIVE: We analyzed the variable requirements for prospective medical professors in Germany, with special focus on the tenure track concept and the U.S. system. METHODS: Based on an online research, we queried German medical faculty regulations to obtain a medical professorship within Germany. RESULTS: We analyzed 35 German universities. On average, 11 publications are required after "venia legendi" to meet professorship (apl) prerequisites (median x̅ = 10, max = 24, min = 6, n = 16), whereas 6 publications with first or last authorship are required on average (x̅ = 6, max = 16, min = 4, n = 26). In most German universities, it takes an average of 4 years after gaining habilitation to apply for a professorship (x̅ = 5 years, max = 6 years, min = 2 years). Candidates for university chair positions, however, can shorten this period by an average of 38%. DISCUSSION: In the German academic system, the prerequisites to gain a professorship differ among universities. Due to different scientific cooperation and exchange programs, research and academic activities have reached an intense international exchange level. Yet there is no international or even national standardization, quality assurance, and comparability to gain a medical professorship.

[The Humboldtian model in Plastic and Reconstructive Surgery - a student survey on teaching and venia legendi]. / Das Humboldt'sche Bildungsideal in der Plastischen Chirurgie ­ Studentenumfrage zur Lehre und Venia Legendi.

BACKGROUND: The workload of university hospitals and hospitals with university association includes clinical patient care as well as teaching and research in particular. The current development with focus on financial issues leads to a reduction of teaching and research capacities. Economic focus in university medicine changes priorities of academic surgery. METHODS: An online survey questioned medical students with regard to subjective assessment of quality of the academic body of university hospitals and current teaching quality. Students evaluated the current quality of teaching of postdoctoral lecturers in relation to their career stage and made suggestions for quality of teaching improvement. RESULTS: A total of 166 students participated in the survey. Of 123 students, about 78 % stated that the reputation of postdoctoral lecturers increases with the habilitation but about 85 % stated that professional expectations also rise. About 43 % of the students aim to achieve a postdoctoral lecture qualification. DISCUSSION: Among students academic career is still attractive, but restructuring and modernization of established working models is an essential prerequisite.

[Careers in plastic and aesthetic surgery: a review of habilitation and professorship of members of the DGPRAEC]. / Karriere in der Plastischen und Ästhetischen Chirurgie ­ Untersuchung zur Habilitation und Professur der Mitglieder der DGPRÄC.

Background Over the last few decades plastic and aesthetic surgery careers aimed at holding a chair as head of the department or clinical director. The current career trend shows a drain of academic teaching staff to peripheral hospitals with sole clinical focus. The achievement of a doctorate in German university medicine or obtaining the venia legendi appears to be the termination of academic careers. This brain drain with loss of expertise and scientific output imposes a problem to future progress in clinical and scientific plastic and reconstructive surgery. The causative role of our present work profile, workload and financial compensation will be discussed in this paper. Methods In order to understand this brain drain, the scientific and clinical developments of all habilitands, Assistant Professors and University Directors enlisted in our specialist society (DGPRAEC) were analyzed. The evaluation included the duration of the residency, the time span from being a specialist physician to habilitation, as well as gaining a leadership position after habilitation. Finally, the current activity of the members at university and non-university institutions was evaluated. Results A total of 1238 members were analyzed. Among these, 177 (14.3 %) members had completed the habilitation. In total, 114 (9.21 %) were included based on full available CVs. Of the listed members, 80 members (6,5 %) had an APL professorship/university professorship in April 2017. 88 CVs showed an average time span of 4.2 years from specialization to habilitation. 80 CVs revealed a 5 year time span to achieve an APL professorship/university professorship. After an average of 4.2 years, leadership positions were held. Of the analyzed habilitations, 60 % were active in peripheral hospitals at the time April 2017. Discussion The loss of scientific and clinical expertise should be prevented in order to preserve academic plastic surgery with focus on patient care, academic education and research. This could be achieved by creating more attractive working conditions.