Losartan Treatment Attenuates Tumor-induced Myocardial Dysfunction

Fatigue and muscle wasting are common symptoms experienced by cancer patients. Data from animal models demonstrate that angiotensin is involved in tumor-induced muscle wasting, and that tumor growth can independently affect myocardial function, which could contribute to fatigue in cancer patients. In clinical studies, inhibitors of angiotensin converting enzyme (ACE) can prevent the development of chemotherapy-induced cardiovascular dysfunction, suggesting a mechanistic role for the renin–angiotensin–aldosterone system (RAAS). In the present study, we investigated whether an angiotensin (AT) 1-receptor antagonist could prevent the development of tumor-associated myocardial dysfunction. Methods and results: Colon26 adenocarcinoma (c26) cells were implanted into female CD2F1 mice at 8 weeks of age. Simultaneously, mice were administered Losartan (10 mg/kg) daily via their drinking water. In vivo echocardiography, blood pressure, in vitro cardiomyocyte function, cell proliferation assays, and measures of systemic inflammation and myocardial protein degradation were performed 19 days following tumor cell injection. Losartan treatment prevented tumor-induced loss of muscle mass and in vitro c26 cell proliferation, decreased tumor weight, and attenuated myocardial expression of interleukin-6. Furthermore, Losartan treatment mitigated tumor-associated alterations in calcium signaling in cardiomyocytes, which was associated with improved myocyte contraction velocity, systolic function, and blood pressures in the hearts of tumor-bearing mice. Conclusions: These data suggest that Losartan may mitigate tumor-induced myocardial dysfunction and inflammation

Non-contrast renal magnetic resonance imaging to assess perfusion and corticomedullary differentiation in health and chronic kidney disease

AIMS Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. METHODS We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and xFB02;ow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. RESULTS T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. CONCLUSIONS Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD

Lesetest für Berufsschüler/innen LTB-3. Handbuch

Klassenarbeiten, Klausuren und Fachprüfungen dauern oft mehrere Stunden,sowohl in ihrer Dauer wie in ihrer Auswertung. Die Dauer der Prüfungen ist in Prüfungsordnungen vorgegeben. Der vorliegende Test ermöglicht es, auf ökonomische und objektive Weise die Lesekompetenz von Schülerinnen und Schülern zu erfassen. Er ist einfach handzuhaben, Testdurchführung und -auswertung nehmen nur wenig Zeit in Anspruch und ermöglichen eine problemlose Integration in den Schulalltag. Ein Test kann nicht von einer Person entwickelt werden und so stehen als Autoren und Berater mehrere Personen auf der Titelseite. Neben den genannten Mitwirkenden waren noch unzählige Personen beteiligt, die hier und da konstruktiv an einer Frage „herumkritisierten“

Additive Manufacturing: Opportunities and Challenges for Functional Magnetic Materials

Additive manufacturing (AM), also known as 3D printing, is transforming manufacturing due to a highly digital approach, the ability to near-net shape manufacture highly complex internal and external shapes of nearly any material, and targeted pore and grain microstructure (thus, properties)

Resilience, Hardship and Social Conditions

This document is the Accepted Manuscript version of the following article: Hulya Dagdeviren, Matthew Donoghue, and Markus Promberger, ‘Resilience, Hardship and Social Conditions’, Journal of Social Policy, Vol. 45 (1), pp. 1-20, first published online 21 July 2015. The final, published version is available online at DOI: https://doi.org/10.1017/S004727941500032X © 2015 Cambridge University Press.This paper provides a critical assessment of the term ‘resilience’ – and its highly agent-centric conceptualisation – when applied to how individuals and households respond to hardship. We provide an argument for social conditions to be embedded into the framework of resilience analysis. Drawing on two different perspectives in social theory, namely the structure-agent nexus and path dependency, we aim to demonstrate that the concept of resilience, if understood in isolation from the social conditions within which it may or may not arise, can result in a number of problems. This includes misidentification of resilience, ideological exploitation of the term and inability to explain intermittence in resilience.Peer reviewedFinal Accepted Versio

Next-generation sequencing diagnostics of bacteremia in septic patients

Background: Bloodstream infections remain one of the major challenges in intensive care units, leading to sepsis or even septic shock in many cases. Due to the lack of timely diagnostic approaches with sufficient sensitivity, mortality rates of sepsis are still unacceptably high. However a prompt diagnosis of the causative microorganism is critical to significantly improve outcome of bloodstream infections. Although various targeted molecular tests for blood samples are available, time-consuming blood culture-based approaches still represent the standard of care for the identification of bacteria. Methods: Here we describe the establishment of a complete diagnostic workflow for the identification of infectious microorganisms from seven septic patients based on unbiased sequence analyses of free circulating DNA from plasma by next-generation sequencing. Results: We found significant levels of DNA fragments derived from pathogenic bacteria in samples from septic patients. Quantitative evaluation of normalized read counts and introduction of a sepsis indicating quantifier (SIQ) score allowed for an unambiguous identification of Gram-positive as well as Gram-negative bacteria that exactly matched with blood cultures from corresponding patient samples. In addition, we also identified species from samples where blood cultures were negative. Reads of non-human origin also comprised fragments derived from antimicrobial resistance genes, showing that, in principle, prediction of specific types of resistance might be possible. Conclusions: The complete workflow from sample preparation to species identification report could be accomplished in roughly 30 h, thus making this approach a promising diagnostic platform for critically ill patients suffering from bloodstream infections

Culture and personality revisited: Behavioral profiles and within‐person stability in interdependent (vs. independent) social orientation and holistic (vs. analytic) cognitive style

ObjectiveWe test the proposition that both social orientation and cognitive style are constructs consisting of loosely related attributes. Thus, measures of each construct should weakly correlate among themselves, forming intraindividually stable profiles across measures over time.MethodStudy 1 tested diverse samples of Americans (N = 233) and Japanese (N = 433) with a wide range of measures of social orientation and cognitive style to explore correlations among these measures in a cross‐cultural context, using demographically heterogeneous samples. Study 2 recruited a new sample of 485 Americans and Canadians and examined their profiles on measures of social orientation and cognitive style twice, one month apart, to assess the stability of individual profiles using these variables.ResultsDespite finding typical cross‐cultural differences, Study 1 demonstrated negligible correlations both among measures of social orientation and among measures of cognitive style. Study 2 demonstrated stable intraindividual behavioral profiles across measures capturing idiosyncratic patters of social orientation and cognitive style, despite negligible correlations among the same measures.ConclusionThe results provide support for the behavioral profile approach to conceptualizing social orientation and cognitive style, highlighting the need to assess intraindividual stability of psychological constructs in cross‐cultural research.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162694/2/jopy12536_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162694/1/jopy12536.pd

MyEcoCost - forming the nucleus of a novel environmental accounting system: vision, prototype and way forward

The innovative software system "myEcoCost" enables to gather and communicate resource and environmental data for products and services in global value chains. The system has been developed in the consortium of the European research project myEcoCost and forms a basis of a new, highly automated environmental accounting system für companies and consumers. The prototype of the system, linked to financial accounting of companies, was developed and tested in close collaboration with large and small companies. This brochure gives a brief introduction to the vision linked to myEcoCost: a network formed by collaborative environmental accounting nodes collecting environmental data at each step in a product's value chains. It shows why better life cycle data are needed and how myEcoCost addresses and solves this problem. Furthermore, it presents options for a future upscaling of highly automated environmenal accounting for prodcuts and services

A mouse model for the human pathogen Salmonella typhi

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a life-threatening human disease. The lack of animal models due to S. Typhi's strict human host specificity has hindered its study and vaccine development. We find that immunodeficient Rag2(-/-) γc(-/-) mice engrafted with human fetal liver hematopoietic stem and progenitor cells are able to support S. Typhi replication and persistent infection. A S. Typhi mutant in a gene required for virulence in humans was unable to replicate in these mice. Another mutant unable to produce typhoid toxin exhibited increased replication, suggesting a role for this toxin in the establishment of persistent infection. Furthermore, infected animals mounted human innate and adaptive immune responses to S. Typhi, resulting in the production of cytokines and pathogen-specific antibodies. We expect that this mouse model will be a useful resource for understanding S. Typhi pathogenesis and for evaluating potential vaccine candidates against typhoid fever

Controlled antibody release from gelatin for on-chip sample preparation

A practical way to realize on-chip sample preparation for point-of-care diagnostics is to store the required reagents on a microfluidic device and release them in a controlled manner upon contact with the sample. For the development of such diagnostic devices, a fundamental understanding of the release kinetics of reagents from suitable materials in microfluidic chips is therefore essential. Here, we study the release kinetics of fluorophore-conjugated antibodies from (sub-) µm thick gelatin layers and several ways to control the release time. The observed antibody release is well-described by a diffusion model. Release times ranging from ~20 s to ~650 s were determined for layers with thicknesses (in the dry state) between 0.25 µm and 1.5 µm, corresponding to a diffusivity of 0.65 µm2/s (in the swollen state) for our standard layer preparation conditions. By modifying the preparation conditions, we can influence the properties of gelatin to realize faster or slower release. Faster drying at increased temperatures leads to shorter release times, whereas slower drying at increased humidity yields slower release. As expected in a diffusive process, the release time increases with the size of the antibody. Moreover, the ionic strength of the release medium has a significant impact on the release kinetics. Applying these findings to cell counting chambers with on-chip sample preparation, we can tune the release to control the antibody distribution after inflow of blood in order to achieve homogeneous cell staining