Adult neurogenesis and its anatomical context in the hippocampus of three mole-rat species

African mole-rats (family Bathyergidae) are small to medium sized, long-lived, and strictly subterranean rodents that became valuable animal models as a result of their longevity and diversity in social organization. The formation and integration of new hippocampal neurons in adult mammals (adult hippocampal neurogenesis, AHN) correlates negatively with age and positively with habitat complexity. Here we present quantitative data on AHN in wild-derived mole-rats of 1 year and older, and briefly describe its anatomical context including markers of neuronal function (calbindin and parvalbumin). Solitary Cape molerats (Georychus capensis), social highveld mole-rats (Cryptomys hottentotus pretoriae), and eusocial naked mole-rats (Heterocephalus glaber) were assessed. Compared to other rodents, the hippocampal formation in mole-rats is small, but shows a distinct cytoarchitecture in the dentate gyrus and CA1. Distributions of the calcium-binding proteins differ from those seen in rodents; e.g., calbindin in CA3 of naked mole-rats distributes similar to the pattern seen in early primate development, and calbindin staining extends into the stratum lacunosum-moleculare of Cape mole-rats. Proliferating cells and young neurons are found in low numbers in the hippocampus of all three mole-rat species. Resident granule cell numbers are low as well. Proliferating cells expressed as a percentage of resident granule cells are in the range of other rodents, while the percentage of young neurons is lower than that observed in surface dwelling rodents. Between mole-rat species, we observed no difference in the percentage of proliferating cells. The percentages of young neurons are high in social highveld and naked mole-rats, and low in solitary Cape mole-rats. The findings support that proliferation is regulated independently of average life expectancy and habitat. Instead, neuronal differentiation reflects species-specific demands, which appear lower in subterranean rodents.http://www.frontiersin.org/Neuroanatomyhb201

Dementia in Latin America : paving the way towards a regional action plan

Regional challenges faced by Latin American and Caribbean countries (LACs) to fight dementia, such as heterogeneity, diversity, political instabilities, and socioeconomic disparities, can be addressed more effectively grounded in a collaborative setting based on the open exchange of knowledge. In this work, the Latin American and Caribbean Consortium on Dementia (LAC-CD) proposes an agenda for integration to deliver a Knowledge to Action Framework (KtAF). First, we summarize evidence-based strategies (epidemiology, genetics, biomarkers, clinical trials, nonpharmacological interventions, networking and translational research) and align them to current global strategies to translate regional knowledge into actions with transformative power. Then, by characterizing genetic isolates, admixture in populations, environmental factors, and barriers to effective interventions and mapping these to the above challenges, we provide the basic mosaics of knowledge that will pave the way towards a KtAF. We describe strategies supporting the knowledge creation stage that underpins the translational impact of KtAF

Pflegende Angehörige auf Distanz. Versorgungsstrukturen: Lücken, Bedarfe und Entwicklungsmöglichkeiten.

Hintergrund: Das Promotionsvorhaben „Pflegende Angehörige auf Distanz – Versorgungsstrukturen: Lücken, Bedarfe und Entwicklungsmöglichkeiten“ verortet sich im Forschungsgebiet Häusliche/Ambulante Pflege und richtet dabei den Blick auf eine deutlich wachsende und doch in Deutschland bislang in der Versorgungsforschung kaum wahrgenommene Zielgruppe: Pflegende Angehörige, die bei räumlicher Entfernung für ihre hilfe- und pflegebedürftigen Angehörigen Sorge tragen. Dabei steht die Frage im Vordergrund, wie im Sinne einer „Collaborative Care“ die Versorgungssituation von auf Distanz pflegenden Familien optimiert werden kann. Methodik: Ein qualitativ-explorativer Forschungsansatz in Form von leitfadengestützten Interviews ermöglicht es zunächst, ausgehend von der spezifischen Nutzer- und Patientenperspektive „pflegender Angehöriger auf Distanz“, zu untersuchen, welche besonderen Herausforderungen und Bedarfe vorliegen und welche Versorgungslücken offensichtlich werden (n = 17). In einer Methodenkombination erfolgt die Auswertung zunächst inhaltsanalytisch-strukturierend (Mayring), in einem zweiten Schritt auch rekonstruktiv (Bohnsack). Trianguliert werden diese Ergebnisse mit der Perspektive von Expert*innen im Versorgungssystem (n = 22). Ergebnisse: Räumliche Entfernung zeigt Auswirkungen auf die Entscheidung zur Pflege, entfaltet Konsequenzen über den gesamten Pflegeprozess und bringt spezifische Belastungen mit sich. Erkennbar wird eine diverse Zielgruppe mit einem breiten Aufgabenspektrum und vielfältigen Herausforderungen, vor allem im emotionalen Bereich. Die rekonstruktive Auswertung generiert fünf typische Orientierungen (pragmatisch, netzwerkend, resignativ, integrierend, fürsprechend), aus denen sich jeweils unterschiedliche Bedarfe und Interventionsoptionen ableiten lassen. Die Expert*innen-interviews verweisen auf Lücken und Chancen des Versorgungssystems. Hürden werden vor allem in der Koordination sowie in geregelten Kommunikationsstrukturen gesehen. Handlungsleitende Empfehlungen weisen auf neue Beratungs- und Begleitungsaufgaben hin, lassen neue Engagementprofile (auch im Kontext von Techniknutzung) erkennen und betonen die Notwendigkeit, entfernt lebende Angehörige wertschätzend wahrzunehmen, anzusprechen und zu beteiligen. Schlussfolgerung: Im Kontext des demografischen Wandels steigt die Zahl älterer und pflegebedürftiger Menschen. Ihre Versorgung wird ohne die Stabilisierung der zentralen Stütze „pflegender Angehöriger“ nicht zu gewährleisten sein, wobei sich mit zunehmender räumlicher Entfernung neue, bislang unbeantwortete, Herausforderungen ergeben

Inhibiting the immunoproteasome exacerbates the pathogenesis of systemic Candida albicans infection in mice

Apart from its role in MHC class I antigen processing, the immunoproteasome has recently been implicated in the modulation of T helper cell differentiation under polarizing conditions in vitro and in the pathogenesis of autoimmune diseases in vivo. In this study, we investigated the influence of LMP7 on T helper cell differentiation in response to the fungus Candida albicans. We observed a strong effect of ONX 0914, an LMP7-selective inhibitor of the immunoproteasome, on IFN-γ and IL-17A production by murine splenocytes and human peripheral blood mononuclear cells (PBMCs) stimulated with C. albicans in vitro. Using a murine model of systemic candidiasis, we could confirm reduced generation of IFN-γ- and IL-17A-producing cells in ONX 0914 treated mice in vivo. Interestingly, ONX 0914 treatment resulted in increased susceptibility to systemic candidiasis, which manifested at very early stages of infection. Mice treated with ONX 0914 showed markedly increased kidney and brain fungal burden which resulted in enhanced neutrophil recruitment and immunopathology. Together, these results strongly suggest a role of the immunoproteasome in promoting proinflammatory T helper cells in response to C. albicans but also in affecting the innate antifungal immunity in a T helper cell-independent manner.publishe

Optimizing multiplexed imaging experimental design through tissue spatial segregation estimation

Recent advances in multiplexed imaging methods allow simultaneous detection of dozens of proteins and hundreds of RNAs, enabling deep spatial characterization of both healthy and diseased tissues. Parameters for the design of optimal multiplex imaging studies, especially those estimating how much area has to be imaged to capture all cell phenotype clusters, are lacking. Here, using a spatial transcriptomic atlas of healthy and tumor human tissues, we developed a statistical framework that determines the number and area of fields of view necessary to accurately identify all cell phenotypes that are part of a tissue. Using this strategy on imaging mass cytometry data, we identified a measurement of tissue spatial segregation that enables optimal experimental design. This strategy will enable an improved design of multiplexed imaging studies.ISSN:1548-7105ISSN:1548-709

Optimizing multiplexed imaging experimental design through tissue spatial segregation estimation

Recent advances in multiplexed imaging methods allow simultaneous detection of dozens of proteins and hundreds of RNAs enabling deep spatial characterization of both healthy and diseased tissues. Parameters for design of optimal sequencing-based experiments have been established, but such parameters, especially those estimating how much area has to be imaged to capture all cell phenotype clusters, are lacking for multiplex imaging studies. Here, using a spatial transcriptomic atlas of healthy and tumor human tissues, we developed a new statistical framework that determines the number and area of fields of view necessary to accurately identify all cell types that are part of a tissue. Using this strategy on imaging mass cytometry data, we identified a measurement of tissue spatial segregation that enables optimal experimental design. This strategy will enable significantly improved design of multiplexed imaging studies

General practitioners’ communication on complementary and integrative medicine for cancer patients: findings from an analysis of consultations with standardised patients

Objective: Our aim was to explore whether general practitioners (GPs) communicate with cancer patients on complementary and integrative medicine (CIM) in a patient-centred and case-specific manner. Methods: We designed two cases of standardised breast cancer patients and allocated 29 GPs to hold a consultation either with Case 1 or Case 2. Case 1 presented with fears of possible physical side effects of hormone treatment. Case 2 feared a loss in social functioning because of nausea and emesis as possible side effects of chemotherapy. Consultations were audiotaped and analysed using the Roter Interaction Analysis System (RIAS). We analysed whether recommended CIM treatments and GPs' focus on psychosocial or medical and therapy-related content differed according to whether they were counselling Case 1 or Case 2. Results: In consultations with Case 1, GPs rather focused on medical and therapy-related content and most often recommended mistletoe, diets and sports. In contrast, GPs focused on psychosocial content and they most often recommended methods of self-care when counselling Case 2. Conclusion: The GPs in our sample reacted case-specifically to the patients' interest in CIM. Such responsive and patient-centred communication is a valuable resource but is often time-consuming. Adequate training and reimbursement should therefore be considered for GPs

Cancer-associated fibroblast phenotypes are associated with patient outcome in non-small cell lung cancer

Despite advances in treatment, lung cancer survival rates remain low. A better understanding of the cellular heterogeneity and interplay of cancer-associated fibroblasts (CAFs) within the tumor microenvironment will support the development of personalized therapies. We report a spatially resolved single-cell imaging mass cytometry (IMC) analysis of CAFs in a non-small cell lung cancer cohort of 1,070 patients. We identify four prognostic patient groups based on 11 CAF phenotypes with distinct spatial distributions and show that CAFs are independent prognostic factors for patient survival. The presence of tumor-like CAFs is strongly correlated with poor prognosis. In contrast, inflammatory CAFs and interferon-response CAFs are associated with inflamed tumor microenvironments and higher patient survival. High density of matrix CAFs is correlated with low immune infiltration and is negatively correlated with patient survival. In summary, our data identify phenotypic and spatial features of CAFs that are associated with patient outcome in NSCLC.ISSN:1535-6108ISSN:1878-368

Compensation of Signal Spillover in Suspension and Imaging Mass Cytometry

The advent of mass cytometry increased the number of parameters measured at the single-cell level while decreasing the extent of crosstalk between channels relative to dye-based flow cytometry. Although reduced, spillover still exists in mass cytometry data, and minimizing its effect requires considerable expert knowledge and substantial experimental effort. Here, we describe a novel bead-based compensation workflow and R-based software that estimates and corrects for interference between channels. We performed an in-depth characterization of the spillover properties in mass cytometry, including limitations defined by the linear range of the mass cytometer and the reproducibility of the spillover over time and across machines. We demonstrated the utility of our method in suspension and imaging mass cytometry. To conclude, our approach greatly simplifies the development of new antibody panels, increases flexibility for antibody-metal pairing, opens the way to using less pure isotopes, and improves overall data quality, thereby reducing the risk of reporting cell phenotype artifacts.ISSN:2405-472