Iron chelators inhibit amyloid-beta-induced production of lipocalin 2 in cultured astrocytes

Lipocalin 2 (Lcn2) has been implicated to play a role in various neurodegenerative diseases, and normalizing its overexpression may be of therapeutic potential. Iron chelators were found to reduce Lcn2 levels in certain animal models of CNS injury. Focusing on Alzheimer's disease (AD), we found that the iron chelators deferoxamine and deferiprone inhibited amyloid-β (Aβ)-induced Lcn2 production in cultured primary astrocytes. Accordingly, Aβ-exposure increased astrocytic ferritin production, indicating the possibility that Aβ induces iron accumulation in astrocytes. This effect was not significantly modulated by Lcn2. Known neuroprotective effects of iron chelators may rely in part on normalization of Lcn2 levels

Living in the past, present, and future: measuring temporal orientation with language

OBJECTIVE: Temporal orientation refers to individual differences in the relative emphasis one places on the past, present, or future, and is related to academic, financial, and health outcomes. We propose and evaluate a method for automatically measuring temporal orientation through language expressed on social media. METHOD: Judges rated the temporal orientation of 4,302 social media messages. We trained a classifier based on these ratings, which could accurately predict the temporal orientation of new messages in a separate validation set (accuracy/mean sensitivity = .72; mean specificity = .77). We used the classifier to automatically classify 1.3 million messages written by 5,372 participants (50% female, aged 13-48). Finally, we tested whether individual differences in past, present, and future orientation differentially related to gender, age, Big Five personality, satisfaction with life, and depressive symptoms. RESULTS: Temporal orientations exhibit several expected correlations with age, gender, and Big Five personality. More future-oriented people were older, more likely to be female, more conscientious, less impulsive, less depressed, and more satisfied with life; present orientation showed the opposite pattern. CONCLUSION: Language-based assessments can complement and extend existing measures of temporal orientation, providing an alternative approach and additional insights into language and personality relationships. This article is protected by copyright. All rights reserved.Support for this article was provided by grant #63597 from the Robert Wood Johnson Foundation (M. E. P. Seligman, PI) and by a grant from the Templeton Religion Trust (M.E.P. Seligman, H. A. Schwartz, L. H. Ungar, co-PIs)

Denktank Overlijdensschade: nieuwe richting benadering en berekening overlijdensschade

De denktank overlijdensschade is ontstaan, omdat de rekenmethodiek voor overlijdensschade niet uit te leggen is aan nabestaanden en geen recht doet aan de maatschappelijke ontwikkelingen. Diverse professionals besloten niet langer slechts te ageren tegen de bestaande situatie, maar er werkelijk wat aan te doen. Dit heeft geresulteerd in een conceptnotitie ‘Nieuwe richting benadering en berekening overlijdensschade’. In dit artikel wordt deze notitie kort besproken

Notitie Denktank Overlijdensschade. Nieuwe richting benadering en berekening overlijdensschade

In 2009 is een werkgroep onder de naam Denktank Overlijdensschade gestart met het bestuderen van een ander, aan de huidige tijd aangepast model voor de berekening van overlijdensschade. Doelstelling was te komen tot een, ook voor nabestaanden, transparantie systematiek welke recht doet aan de vorderingsgerechtigdheid van de nabestaanden. In 2014 heeft de Denktank Overlijdensschade haar werkzaamheden voltooid met het opleveren van een nieuwe rekenmethodiek. In deze Notitie wordt beschreven hoe de Denktank tot deze nieuwe benadering van het berekenen van overlijdensschade is gekomen, welke onderzoeken daaraan ten grondslag liggen en wat de uiteindelijke rekenregel is, die nu voorgesteld wordt. Kern van de nieuwe methodiek is het uitgangspunt dat het gezin als economische eenheid wordt beschouwd, voor én na het overlijden

NKp46+ natural killer cells develop an activated/memory-like phenotype and contribute to innate immunity against experimental filarial infection

Lymphatic filariasis and onchocerciasis are major neglected tropical diseases affecting over 90 million people worldwide with painful and profoundly disfiguring pathologies (such as lymphoedema or blindness). Type 2 inflammation is a hallmark of filarial nematode tissue infection and is implicated both in eosinophil dependent immunity and lymphatic or ocular immunopathologies. Type-2 innate lymphoid cells (ILC2) are known to play an important role in the initiation of type 2 inflammation in helminth infection. We therefore tracked comparative IL-12Rβ2+ ILC1, ST2+ ILC2 and NKp46+ natural killer (NK) innate lymphoid cell population expansions during Brugia malayi experimental peritoneal filarial infections using either immunocompetent or immunodeficient mice. In immunocompetent BALB/c animals, NKp46+ NK cells rapidly expanded representing over 90% of the ILC population in the first week of infection, whereas, surprisingly, ST2+ ILC2 failed to expand. NKp46+ NK cell expansions were confirmed in RAG2 deficient mice lacking adaptive immunity. Ablation of the NKp46+ NK cell compartment in RAG2 common gamma chain (gc) mice led to increased susceptibility to chronic adult B. malayi infection. This data was recapitulated using an Onchocerca ochengi male worm peritoneal implant model. When NKp46+ NK cells were depleted in RAG2 deficient mice using anti-NKp46 or asialo GM1 antibody injections over the first five weeks of B. malayi infection, susceptibility to adult B. malayi infection was significantly increased by 2-3 fold with concomitant impairment in eosinophil or neutrophil recruitments. Finally, we demonstrate that in RAG2 deficient mice, drug clearance of a primary adult B. malayi infection followed by challenge infection leads to resistance against early larval B. malayi establishment. This innate resistance is associated with bolstered NK and eosinophils whereby NKp46+ NK cells express markers of memory-like/enhanced activation (increased expression of interferon gamma and Ly6C). Our data promotes a novel functional role for NKp46+ NK cells in immunoprotection against experimental primary and secondary filarial infection which can proceed in the absence of adaptive immune regulation

The routinisation of management controls in software.

Author's post-print version. Final version published by Springer; available online at http://link.springer.com/Our paper aims to explore management control as complex and intertwining process over time, rather than the (mainstream) fixation on rational, optimising tools for ensuring business success. We set out to contribute towards our understanding of why and how particular management controls evolve over time as they do. We discuss how the management control routines of one organisation emerged and reproduced (through software), and moved towards a situation of becoming accepted and generally unquestioned across much of the industry. The creativity and championing of one particular person was found to be especially important in this unfolding change process. Our case study illuminates how management control (software) routines can be an important carrier of organisational knowledge, both as an engine for continuity but also potentially as a catalyst for change. We capture this process by means of exploring the ‘life-story’ of a piece of software that is adopted in the corrugated container industry

Use of generic medicines in Latvia : Awareness, opinions and experiences of the population

Funding Information: Funding was provided by EEA Financial Mechanism and Latvian state (award number 2012.EEZ/DAP/MIC/183). The project is financially supported by Iceland, Liechtenstein and Norway. Publisher Copyright: © 2019 The Author(s).Background: To stimulate use of generic medicines a combination of supply and demand side mechanisms are employed in the Latvian reimbursement system. It is reported that patients have high out-of-pocket pharmaceutical spending and that they overpay by not choosing generic medicines. Patient preferences may be an important obstacle in implementing generic policy. Objective of this study was to assess awareness, opinions and experience of the Latvian population regarding use of generic medicines. Methods: Survey of representative sample of the population of Latvia (n = 1005) aged 18-74 was conducted in March 2015. The survey was distributed in Latvian and Russian languages using Computer Assisted Web Interviews. Associations between experience with generic medicines, preference for medicines, and sociodemographic variables were tested with Pearson Chi-square statistics. Associations between the previous experience and information given by different sources versus choice between medicines were tested with Spearman's correlation test. Results: 72.3% of the population were informed about generic medicines. Men (66.9%) and respondents with primary or secondary education (58.3%; 69.3%) were less informed compared to total (72.3%). From those who recalled using generic medicines (n = 441), 94.4% evaluated their experience as positive or neutral. Despite this, only 21% of the population would opt for generic medicines. The strongest preference for brand-name medicines was in the age group > 55 (40.5%). Opinion of a physician was the most important factor when choosing between generic and brand-name medicines (88.7%). The more positive the information provided by general practitioners, physician specialists, pharmacists, family members, friends and internet is perceived, the more likely respondents are to choose generic medicines (p < 0.001). Conclusion: This study demonstrates that people in Latvia are aware of generic medicines but only a minority of the population would choose them when presented with a choice. It is therefore important that health care professionals provide objective and unbiased information about generic medicines to their patients. Interventions should aim to reach groups that are less informed and to improve providers' understanding and communication with patients about generics.publishersversionPeer reviewe