Adrenoceptor-stimulated inflammatory response in stress-induced serum amyloid A synthesis

Rationale Stressful life events are suggested to contribute to the development of various pathologies, such as cardiovascular disorders, whose etiopathogenesis is highly associated with elevated levels of serum amyloid A (SAA) proteins. SAA synthesis inthe liver isregulated bya complex network ofcytokines actingindependently orinconcert withvarious hormones/stimulants including the stress-activated sympathetic nervous system. Objective This study aims to investigate the underlying mechanisms that regulate the stress-induced hepatic synthesis of SAA, with particular focus on adrenoceptors (AR), major components of the sympathoadrenal response to stress. Methods and results We demonstrated that repeated stress elevates IL-1β, IL-6, and TNFα serum levels in mice, accompanied by increased synthesis and secretion of hepatic SAA1/2 and SAA3, an effect that was blocked by AR antagonists. Moreover, stimulation ofα1- andβ1/2-ARsmimics thestress effectonSAA1/2 regulation, whereas α2-AR stimulation exhibitsa relatively weakimpactonSAA.InsupportoftheessentialcytokinecontributionintheAR-agonistinducedSAAproductionisthefactthat theanti-inflammatorydrug,sodiumsalicylate,preventedtheAR-stimulatedhepaticSAA1/2synthesisbyreducingIL-1βlevels, whereasIL-1βinhibitionwithAnakinramimicsthissodiumsalicylatepreventiveeffect,thusindicatingacrucial rolefor IL-1β. Interestingly, the AR-driven SAA3 synthesis was elevated by sodium salicylate in a TNFα-dependent way, supporting diverse and complex regulatory roles of cytokines in SAA production. In contrast to α1/α2-AR, the β1/2-AR-mediated SAA1/2 and SAA3 upregulation cannot be reversed by fenofibrate, a hypolipidemic drug with anti-inflammatory properties. Conclusion Taken together, these findings strongly support a critical role of the AR-stimulated inflammatory response in the hepatic SAA production under stressful conditions, highlighting distinct AR type-specific mechanisms that regulate the hepatic synthesis of SAA1/2 and SAA3.This research was supported by the European Union (European Regional Development Fund-ERDF) and the Greek national funds through the Operational Program "THESSALY-MAINLAND GREECE AND EPIRUS-2007-2013" of the National Strategic Reference Framework (NSRF 2007-2013, Grant 346985/80753) and the National Cancer Institute Intramural Research Program.info:eu-repo/semantics/publishedVersio

Adrenoceptor‐related decrease in serum triglycerides is independent of PPARα activation

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151956/1/febs14966.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151956/2/febs14966_am.pd

Greco-Roman mineral (litho)therapeutics and their relationship to their microbiome : the case of the red pigment miltos

This paper introduces a holistic approach to the study of Greco-Roman (G-R) lithotherapeutics. These are the minerals or mineral combinations that appear in the medical and scientific literature of the G-R world. It argues that they can best be described not simply in terms of their bulk chemistry/mineralogy but also their ecological microbiology and nanofraction component. It suggests that each individual attribute may have underpinned the bioactivity of the lithotherapeutic as an antibacterial, antifungal or other. We focus on miltos, the highly prized, naturally fine, red iron oxide-based mineral used as a pigment, in boat maintenance, agriculture and medicine. Five samples (four geological (from Kea, N. Cyclades) and one archaeological (from Lemnos, NE Aegean)) of miltos were analyzed with physical and biological science techniques. We show that: a. Kean miltos and Lemnian earth/miltos must have been chemically and mineralogically different; b. Lemnian miltos must have been more effective as an antibacterial against specific pathogens (Gram + and Gram − bacteria) than its Kean counterpart; c. two samples of Kean miltos, although similar, chemically, mineralogically and eco-microbiologically (phylum/class level), nevertheless, displayed different antibacterial action. We suggest that this may constituteproof of microbial ecology playing an important role in effecting bioactivity and, interestingly, at the more specific genus/species level. From the perspective of the historian of G-R science, we suggest that it may have been on account of its bioactivity, rather than simply its 'red-staining' effect, that miltos gained prominent entry into the scientific and medical literature of the G-R world

Effects of radial motion on interchange injections at Saturn

Charged particle injections are regularly observed in Saturn's inner magnetosphere by Cassini. They are attributed to an ongoing process of flux-tube interchange driven by the strong centrifugal force associated with Saturn's rapid rotation. Numerical simulations suggest that these interchange injections can be associated with inward flow channels, in which plasma confined to a narrow range of longitudes moves radially toward the planet, gaining energy, while ambient plasma in the adjacent regions moves more slowly outward. Most previous analyses of these events have neglected this radial motion and inferred properties of the events under the assumption that they appear instantaneously at the spacecraft's L-shell and thereafter drift azimuthally. This paper describes features of injections that can be related to their radial motion prior to observation. We use a combination of phase space density profiles and an updated version of a test-particle model to quantify properties of the injection. We are able to infer the longitudinal width of the injection, the radial travel time from its point of origin, and the starting L shell of the injection. We can also predict which energies can remain inside the channel during the radial transport. To highlight the effects of radial propagation at a finite speed, we focus on those interchange injections without extensive features of azimuthal dispersion. Injections that have traveled radially for one or more hours prior to observation would have been initiated at a different local time than that of the observation. Finally, we describe an injection where particles have drifted azimuthally into a flow channel prior to observation by Cassini. (C) 2015 Elsevier Inc. All rights reserved

Ion composition in interchange injection events in Saturn\u27s magnetosphere

Interchange injection events are commonly observed by the Cassini spacecraft in the region between about 6 and 12 Rs (1 Rs = 60,268 km) and even frequently beyond. In this study, 13 examples of interchange injection events are identified in Cassini-Cassini Plasma Spectrometer data under special conditions such that time-of-flight (TOF) mass spectra could be obtained from entirely within the events. Using the TOF data to separate the main ion species H+, H2+, and W+, approximate densities of each species are calculated under the assumption that all distributions were isotropic. The light-ion density ratios, H2+/H+, in the injection events are not discernibly different from those ratios in control intervals from the ambient plasma. However, the water-group ration, W+/H+, is significantly lower than ambient. The comparison of the measured density ratios with the range of values observed throughout Saturn\u27s magnetosphere indicates that the values of W+/H+ that are as low as those observed within the injection events are found primarily beyond L~14 (where L is the equatorial crossing distance, in Saturn radius, of a dipole field line), indicating that the injection events are delivering plasma from the outer magnetosphere at times traveling at least 6 Rs

Derivation of relativistic SEP properties through neutron monitor data modeling

The Ground Level Enhancement (GLE) data recorded by the worldwide Neutron Monitor (NM) network are useful resources for space weather modeling during solar extreme events. The derivation of Solar Energetic Particles (SEPs) properties through NM-data modeling is essential for the study of solar-terrestrial physics, providing information that cannot be obtained through the exclusive use of space techniques; an example is the derivation of the higher-energy part of the SEP spectrum. We briefly review how the application of the Neutron Monitor Based Anisotropic GLE Pure Power Law (NMBANGLE PPOLA) model (Plainaki et al. 2010), can provide the characteristics of the relativistic SEP flux, at a selected altitude in the Earth's atmosphere, during a GLE. Technically, the model treats the NM network as an integrated omnidirectional spectrometer and solves the inverse problem of the SEP-GLE coupling. As test cases, we present the results obtained for two different GLEs, namely GLE 60 and GLE 71, occurring at a temporal distance of ~ 11 years

Toward shared decision-making in degenerative cervical myelopathy: Protocol for a mixed methods study

Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this. The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes. Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders. Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway. This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community. DERR1-10.2196/46809. [Abstract copyright: ©Irina Sangeorzan, Grazia Antonacci, Anne Martin, Ben Grodzinski, Carl M Zipser, Rory K J Murphy, Panoraia Andriopoulou, Chad E Cook, David B Anderson, James Guest, Julio C Furlan, Mark R N Kotter, Timothy F Boerger, Iwan Sadler, Elizabeth A Roberts, Helen Wood, Christine Fraser, Michael G Fehlings, Vishal Kumar, Josephine Jung, James Milligan, Aria Nouri, Allan R Martin, Tammy Blizzard, Luiz Roberto Vialle, Lindsay Tetreault, Sukhvinder Kalsi-Ryan, Anna MacDowall, Esther Martin-Moore, Martin Burwood, Lianne Wood, Abdul Lalkhen, Manabu Ito, Nicky Wilson, Caroline Treanor, Sheila Dugan, Benjamin M Davies. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 09.10.2023.

Toward Shared Decision-Making in Degenerative Cervical Myelopathy: Protocol for a Mixed Methods Study

BACKGROUND Health care decisions are a critical determinant in the evolution of chronic illness. In shared decision-making (SDM), patients and clinicians work collaboratively to reach evidence-based health decisions that align with individual circumstances, values, and preferences. This personalized approach to clinical care likely has substantial benefits in the oversight of degenerative cervical myelopathy (DCM), a type of nontraumatic spinal cord injury. Its chronicity, heterogeneous clinical presentation, complex management, and variable disease course engenders an imperative for a patient-centric approach that accounts for each patient's unique needs and priorities. Inadequate patient knowledge about the condition and an incomplete understanding of the critical decision points that arise during the course of care currently hinder the fruitful participation of health care providers and patients in SDM. This study protocol presents the rationale for deploying SDM for DCM and delineates the groundwork required to achieve this. OBJECTIVE The study's primary outcome is the development of a comprehensive checklist to be implemented upon diagnosis that provides patients with essential information necessary to support their informed decision-making. This is known as a core information set (CIS). The secondary outcome is the creation of a detailed process map that provides a diagrammatic representation of the global care workflows and cognitive processes involved in DCM care. Characterizing the critical decision points along a patient's journey will allow for an effective exploration of SDM tools for routine clinical practice to enhance patient-centered care and improve clinical outcomes. METHODS Both CISs and process maps are coproduced iteratively through a collaborative process involving the input and consensus of key stakeholders. This will be facilitated by Myelopathy.org, a global DCM charity, through its Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy community. To develop the CIS, a 3-round, web-based Delphi process will be used, starting with a baseline list of information items derived from a recent scoping review of educational materials in DCM, patient interviews, and a qualitative survey of professionals. A priori criteria for achieving consensus are specified. The process map will be developed iteratively using semistructured interviews with patients and professionals and validated by key stakeholders. RESULTS Recruitment for the Delphi consensus study began in April 2023. The pilot-testing of process map interview participants started simultaneously, with the formulation of an initial baseline map underway. CONCLUSIONS This protocol marks the first attempt to provide a starting point for investigating SDM in DCM. The primary work centers on developing an educational tool for use in diagnosis to enable enhanced onward decision-making. The wider objective is to aid stakeholders in developing SDM tools by identifying critical decision junctures in DCM care. Through these approaches, we aim to provide an exhaustive launchpad for formulating SDM tools in the wider DCM community. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID) DERR1-10.2196/46809

Perceived economic self‑sufficiency: a countryand generation‑comparative approach

We thank Michael Camasso and Radha Jagannathan as well as Asimina Christoforou, Gerbert Kraaykamp, Fay Makantasi, Tiziana Nazio, Kyriakos Pierrakakis, Jacqueline O’Reilly and Jan van Deth for their contribution to the CUPESSE project (Seventh Framework Programme; Grant Agreement No. 61325). CUPESSE received additional funding from the Mannheim Centre for European Social Research (MZES) and the Field of Focus 4 “Self-Regulation and Regulation: Individuals and Organisations” at Heidelberg University. We further acknowledge helpful comments on this article by two anonymous reviewers. Julian Rossello provided valuable research assistance.Electronic supplementary material The online version of this article (https ://doi.org/10.1057/ s4130 4-018-0186-3) contains supplementary material, which is available to authorized users.Existing datasets provided by statistical agencies (e.g. Eurostat) show that the economic and financial crisis that unfolded in 2008 significantly impacted the lives and livelihoods of young people across Europe. Taking these official statistics as a starting point, the collaborative research project “Cultural Pathways to Economic Self-Sufficiency and Entrepreneurship in Europe” (CUPESSE) generated new survey data on the economic and social situation of young Europeans (18–35 years). The CUPESSE dataset allows for country-comparative assessments of young people’s perceptions about their socio-economic situation. Furthermore, the dataset includes a variety of indicators examining the socio-economic situation of both young adults and their parents. In this data article, we introduce the CUPESSE dataset to political and social scientists in an attempt to spark a debate on the measurements, patterns and mechanisms of intergenerational transmission of economic self-sufficiency as well as its political implications.CUPESSE project (Seventh Framework Programme; Grant Agreement No. 61325