The functional dynamics and cellular sources of oxidative stress are central to understanding MS pathogenesis but remain elusive, due to the lack of appropriate detection methods. Here we employ NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX enzymes) in vivo to identify inflammatory monocytes, activated microglia, and astrocytes expressing NOX1 as major cellular sources of oxidative stress in the central nervous system of mice affected by experimental autoimmune encephalomyelitis (EAE). This directly affects neuronal function in vivo, indicated by sustained elevated neuronal calcium. The systemic involvement of oxidative stress is mirrored by overactivation of NOX enzymes in peripheral CD11b+ cells in later phases of both MS and EAE. This effect is antagonized by systemic intake of the NOX inhibitor and anti-oxidant epigallocatechin-3-gallate. Together, this persistent hyper-activation of oxidative enzymes suggests an “oxidative stress memory” both in the periphery and CNS compartments, in chronic neuroinflammation.Electronic supplementary materialThe online version of this article (doi:10.1007/s00401-015-1497-x) contains supplementary material, which is available to authorized users.

Most multiple sclerosis (MS) patients develop over time a secondary progressive disease course, characterized histologically by axonal loss and atrophy. In early phases of the disease, focal inflammatory demyelination leads to functional impairment, but the mechanism of chronic progression in MS is still under debate. Reactive oxygen species generated by invading and resident central nervous system (CNS) macrophages have been implicated in mediating demyelination and axonal damage, but demyelination and neurodegeneration proceed even in the absence of obvious immune cell infiltration, during clinical recovery in chronic MS. Here, we employ intravital NAD(P)H fluorescence lifetime imaging to detect functional NADPH oxidases (NOX1–4, DUOX1, 2) and, thus, to identify the cellular source of oxidative stress in the CNS of mice affected by experimental autoimmune encephalomyelitis (EAE) in the remission phase of the disease. This directly affects neuronal function in vivo, as monitored by cellular calcium levels using intravital FRET–FLIM, providing a possible mechanism of disease progression in MS.

Background Organizational health literacy (OHL) aims to respond to the health literacy needs of patients by improving health information and services and making them easier to understand, access, and apply. This scoping review primarily maps criteria characterizing health literate health care organizations. Secondary outcomes are the concepts and terminologies underlying these criteria as well as instruments to measure them. Methods The review was carried out following the JBI Manual on scoping reviews. The databases CINAHL, Cochrane Library, JSTOR, PsycINFO, PubMed, Web of Science Core Collection, and Wiley Online Library were searched in July 2020. Three researchers screened the records and extracted the data. The results were synthesized systematically and descriptively. Results The literature search resulted in 639 records. After removing duplicates, screening by title and abstract, and assessing full-texts for eligibility, the scoping review included 60 publications. Criteria for OHL were extracted and assigned to six main categories (with 25 subcategories). The most prevalent topic of organizational health literacy refers to communication with service users. Exemplary criteria regarding this main category are the education and information of service users, work on easy-to-understand written materials as well as oral exchange, and verifying understanding. The six main categories were defined as 1) communication with service users; 2) easy access & navigation; 3) integration & prioritization of OHL; 4) assessments & organizational development; 5) engagement & support of service users, and 6) information & qualification of staff. The criteria were based on various concepts and terminologies. Terminologies were categorized into four conceptual clusters: 1) health literacy in various social contexts; 2) health literate health care organization; 3) organizational behavior, and 4) communication in health care. 17 different assessment tools and instruments were identified. Only some of the toolkits and instruments were validated or tested in feasibility studies. Conclusions Organizational health literacy includes a significant number of distinct organizational criteria. The terminologies used in the OHL literature are heterogeneous based on a variety of concepts. A comprehensive, consensus-based conceptual framework on OHL is missing.

The development of intravital Förster Resonance Energy Transfer (FRET) is required to probe cellular and tissue function in the natural context: the living organism. Only in this way can biomedicine truly comprehend pathogenesis and develop effective therapeutic strategies. Here we demonstrate and discuss the advantages and pitfalls of two strategies to quantify FRET in vivo—ratiometrically and time-resolved by fluorescence lifetime imaging—and show their concrete application in the context of neuroinflammation in adult mice.