Pasteurella multocida toxin- induced osteoclastogenesis requires mTOR activation

Background: Pasteurella multocida toxin (PMT) is a potent inducer of osteoclast formation. Pigs suffering from an infection with toxigenic Pasteurella multocida strains develop atrophic rhinitis characterised by a loss of turbinate bones and conchae. However, on the molecular level the process of bone loss remains largely uncharacterised. Results: Recently it was found that PMT activates the serine/threonine kinase mammalian target of rapamycin (mTOR) in fibroblasts. Using RAW264.7 macrophages, we investigated the role of the mTOR complex 1 (mTORC1) in PMT-mediated osteoclast formation. PMT induces the differentiation of RAW264.7 macrophages into multinucleated, tartrate resistant acid phosphatase (TRAP) positive osteoclasts that are capable to resorb bone. In the presence of the mTORC1 inhibitor rapamycin, PMT was significantly less able to induce the formation of TRAP-positive osteoclasts. Accordingly, the resulting resorption of bone was strongly reduced. A major target of mTOR is the 70 kDa ribosomal protein S6 kinase 1 (p70 S6K1). Activated p70 S6K1 decreases the expression of programmed cell death protein 4 (PDCD4), a negative transcriptional regulator of osteoclastogenesis, at the protein and gene level. Ultimately this results in the activation of c-Jun, a component of the activator protein 1 (AP-1) complex, which is a major transcription factor for the induction of osteoclast-specific genes. We now demonstrate that c-Jun and its downstream target, the osteoclast-specific bone degrading protease cathepsin K, are upregulated upon PMT treatment in an mTOR-dependent manner. Conclusions: Activation of mTOR signalling plays a central role in the formation of osteoclasts through the bacterial toxin PMT. On the molecular level, PMT-induced activation of mTOR leads to down regulation of PDCD4, a known repressor of AP-1 complex, culminating in the activation of c-Jun, an essential transcription factor for triggering osteoclastogenesis

Two-Step-Model of Photosensitivity in Cerium-doped Fibers

The photosensitivity of various cerium-doped fibers has been experimentally investigated for both excimer- and femtosecond-laser illumination. The results of single-pulse, few-pulse and multi-pulse inscription of fiber-Bragg-gratings with both laser systems and the thermal aging of those gratings demonstrated the restrictions of the conventional color center model for cerium-doped fibers. To explain the short-term stability of single-pulse gratings against long-term stability of multi-pulse gratings, an extension into a two-step-model was deduced

Fluc-EGFP reporter mice reveal differential alterations of neuronal proteostasis in aging and disease

The cellular protein quality control machinery is important for preventing protein misfolding and aggregation. Declining protein homeostasis (proteostasis) is believed to play a crucial role in age‐related neurodegenerative disorders. However, how neuronal proteostasis capacity changes in different diseases is not yet sufficiently understood, and progress in this area has been hampered by the lack of tools to monitor proteostasis in mammalian models. Here, we have developed reporter mice for in vivo analysis of neuronal proteostasis. The mice express EGFP‐fused firefly luciferase (Fluc‐EGFP), a conformationally unstable protein that requires chaperones for proper folding, and that reacts to proteotoxic stress by formation of intracellular Fluc‐EGFP foci and by reduced luciferase activity. Using these mice, we provide evidence for proteostasis decline in the aging brain. Moreover, we find a marked reaction of the Fluc‐EGFP sensor in a mouse model of tauopathy, but not in mouse models of Huntington’s disease. Mechanistic investigations in primary neuronal cultures demonstrate that different types of protein aggregates have distinct effects on the cellular protein quality control. Thus, Fluc‐EGFP reporter mice enable new insights into proteostasis alterations in different diseases

Effectiveness of multi-professional educational interventions to train Comprehensive Geriatric Assessment (CGA) – a Systematic Review

Introduction: As the world population ages, health and social care professionals are increasingly confronted with patients with chronic long-term conditions and multimorbidity, requiring an extensive assessment and integrated care management strategy. The aim of this paper was to systematically collect and assess evidence of interprofessional education and training strategies for Comprehensive Geriatric Assessment (CGA) to build a competent health workforce. Methods: A systematic review was conducted according to PRISMA guidelines and the databases Medline, CINAHL, Cochrane and Embase were searched for studies illustrating effectiveness of educational interventions for teaching and training CGA in an interprofessional context. Results: Based on 21 identified studies, a great variability and heterogeneity in duration, setting and design of the interventions was identified. Promising results were found in the domains analysed, ranging from knowledge and skills; practices and behaviour; patient health outcomes; attitudes and perceptions to collaboration and quality of care. Discussion: Education and training of transversal skills within a continuous learning approach is key to equip the health care workforce for successful CGA performance in an interprofessional environment. Conclusion: Further research in this field is recommended to strengthen the evidence-base towards development of a resilient and integrated health care workforce for an ageing population. Kurzfassung Hintergrund: Aufgrund der zunehmenden Alterung der Weltbevölkerung sehen sich Fachkräfte des Gesundheits- und Sozialwesens immer häufiger mit Patient*innen mit chronischen Erkrankungen (bzw. Langzeiterkrankungen) und Multimorbidität, welche eine umfassende Beurteilung und eine integrierte Versorgungsmanagementstrategie erfordern, konfrontiert. Ziel der vorliegenden Arbeit war es, systematisch Evidenz für interprofessionelle Aus- und Weiterbildungsstrategien für ein Comprehensive Geriatric Assessment (CGA) zu sammeln und zu bewerten, um Kompetenz im Gesundheits- und Sozialwesen zu generieren. Methodik: Es wurde eine systematische Übersichtsarbeit gemäß den PRISMA-Richtlinien durchgeführt und die Datenbanken Medline, CINAHL, Cochrane und Embase im Zuge dessen nach Studien durchsucht, welche die Wirksamkeit von Bildungsmaßnahmen zur Vermittlung und Ausbildung von CGA in einem interprofessionellen Kontext belegen. Ergebnisse: Basierend auf 21 identifizierten Studien wurde eine große Variabilität und Heterogenität in Bezug auf Dauer, Setting und Design der Interventionen festgestellt. Vielversprechende Ergebnisse wurden in den analysierten Bereichen gefunden, welche von Wissen und Fähigkeiten, Praktiken und Verhalten, gesundheitlichen Ergebnissen für Patient*innen, Einstellungen und Wahrnehmungen bis hin zu Zusammenarbeit und Qualität der Versorgung reichen. Diskussion: Die Aus- und Weiterbildung von transversalen Fähigkeiten im Rahmen eines kontinuierlichen Lernansatzes ist der Schlüssel dazu, Angehörige der Gesundheits- und Sozialprofessionen mit entsprechendem Werkzeug auszustatten, um geriatrische Assessments (CGA) erfolgreich im interprofessionellen Umfeld durchführen zu können. Schlussfolgerung: Es besteht der Bedarf für weitere Forschungsvorhaben in diesem Bereich, um die Evidenzbasis für die Entwicklung eines zuverlässigen, integrierten Gesundheitspersonals für eine alternde Bevölkerung zu stärken. Schlüsselwörter: Integrierte Versorgung; Comprehensive Geriatric Assessment; Ausund Weiterbildung; interprofessionelle Bildung; Alterun

Maternal neurofascin-specific autoantibodies bind to structures of the fetal nervous system during pregnancy, but have no long term effect on development in the rat

Neurofascin was recently reported as a target for axopathic autoantibodies in patients with multiple sclerosis (MS), a response that will exacerbate axonal pathology and disease severity in an animal model of multiple sclerosis. As transplacental transfer of maternal autoantibodies can permanently damage the developing nervous system we investigated whether intrauterine exposure to this neurofascin-specific response had any detrimental effect on white matter tract development. To address this question we intravenously injected pregnant rats with either a pathogenic anti-neurofascin monoclonal antibody or an appropriate isotype control on days 15 and 18 of pregnancy, respectively, to mimic the physiological concentration of maternal antibodies in the circulation of the fetus towards the end of pregnancy. Pups were monitored daily with respect to litter size, birth weight, growth and motor development. Histological studies were performed on E20 embryos and pups sacrificed on days 2, 10, 21, 32 and 45 days post partum. Results: Immunohistochemistry for light and confocal microscopy confirmed passively transferred anti-neurofascin antibody had crossed the placenta to bind to distinct structures in the developing cortex and cerebellum. However, this did not result in any significant differences in litter size, birth weight, or general physical development between litters from control mothers or those treated with the neurofascin-specific antibody. Histological analysis also failed to identify any neuronal or white matter tract abnormalities induced by the neurofascin-specific antibody. Conclusions: We show that transplacental transfer of circulating anti-neurofascin antibodies can occur and targets specific structures in the CNS of the developing fetus. However, this did not result in any pre- or post-natal abnormalities in the offspring of the treated mothers. These results assure that even if anti-neurofascin responses are detected in pregnant women with multiple sclerosis these are unlikely to have a negative effect on their children

Chefs in Future Integrated Healthcare - Current State and Innovation Needs: A First Overview of the NECTAR Project (aN Eu Curriculum for Chef gasTro-Engineering in Primary Food Care)

: People in need of care, chronic or acute, often present problematic food intake and special nutritional needs. Integrated, person-centred and pro-active food and nutritional care delivery has been proven effective for people in health care. However, skills mismatches have been reported in different professions involved, which also applies to the role of chefs in healthcare. The EU funded project NECTAR aims at closing this gap by creating a new job profile, called Chef Gastro-Engineering (CGE). The current publication summarizes the status quo in hospitals and gives a perspective on the future role of chefs in integrated healthcare delivery

Can Integrated Care Help in Meeting the Challenges Posed on Our Health Care Systems by COVID-19? Some Preliminary Lessons Learned from the European VIGOUR Project

The COVID-19 pandemic puts health and care systems under pressure globally. This current paper highlights challenges arising in the care for older and vulnerable populations in this context and reflects upon possible perspectives for different systems making use of nested integrated care approaches adapted during the work of the EU-funded project VIGOU