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Renee Davis,1 Alex Taylor,1 Regan Nally,1 Kathleen F Benson,2 Paul Stamets,1 Gitte S Jensen2 1Fungi Perfecti, Olympia, WA 98507, USA; 2NIS Labs, Klamath Falls, OR 97601, USACorrespondence: Gitte S JensenNIS Labs, 1437 Esplanade, Klamath Falls, OR 97601, USATel +1 541 884-0112Fax +1403 441-5236Email gitte@nislabs.comPurpose: To compare three fractions of a medicinal mushroom blend (MMB), MyCommunity, on immune-activation, inflammation-regulation, and induction of biomarkers involved in regenerative functions.Methods: A seventeen-species MMB was sequentially extracted: first, saline solution at ambient temperature, followed by re-extraction of the solids in ethanol, and finally resuspension of the homogenized ethanol-insoluble solids in cell-culture media. Fractions were tested on peripheral blood mononuclear cells from three healthy donors. Immunostaining, flow-cytometry, and Luminex protein-arrays measured immune-cell activation and cytokine response. Dose-responses for induction of the CD69 early activation marker and individual cytokine and growth-factor responses for each donor were evaluated. The CD69 and the combined cytokine and growth-factor results were subjected to Non-metric Multidimensional Scaling (NMDS) and multivariate ordination to aid interpretation of the aggregate immune response and pairwise permutational MANOVA on a distance-matrix to evaluate statistical differences between treatments on pooled data from all donors.Results: Differential effects were induced by water-soluble, ethanol-soluble, and insoluble immunomodulatory compounds of the MMB. The aqueous and ethanol fractions upregulated expression of CD69 on all tested cell types. Monocyte-activation was correlated with the ethanol fraction, while NKT and non-NK non-T cell-activation was more closely correlated with the aqueous fraction. The solid fraction was the most potent inducer of Tumor Necrosis Factor-α, as well as the anti-viral cytokines interferon-γ, MCP-1 (CCL-2), MIP-1α (CCL-3), and MIP-1β (CCL-4), and induced G-CSF and b-FGF—growth-factors involved in regenerative functions—and the anti-inflammatory cytokine IL-1ra.Conclusion: The aqueous, ethanol, and insoluble compounds within MMB induced differential immune-activating, anti-inflammatory, and regenerative effects. This in vitro data suggests that, upon consumption, MMB may induce a concerted series of immunomodulatory events based on the differential solubility and bioavailability of the active constituents. These differential responses support both immune-activation and resolution of the host defense-induced inflammatory reactions, thus assisting a post-response return to homeostasis.Keywords: CD69, cytokines, growth factors, anti-viral peptides, medicinal mushrooms, mycelium, immune support, redundancy analysis, rda, multivariate ordination

BackgroundThe medicinal mushroomTrametes versicolor(Tv, Turkey Tail) is often prepared for consumption as a powder from the fungal mycelium and the fermented substrate on which it grew. The goal for this study was to evaluate the immune-modulating properties of the mycelium versus the fermented substrate, to document whether an important part of the immune-activating effects resides in the metabolically fermented substrate.MethodsTv mycelium was cultured on rice flour. The mycelium and the fermented substrate were mechanically separated, dried, and milled. The initial substrate served as a control. Aqueous fractions were extracted and passed through 0.22-μm filters. The remaining solids were passed through homogenization spin columns without filtration. The aqueous and solid fractions of the initial substrate (IS), the fermented substrate (FS), and theTrametes versicolormycelium (TvM) were tested for immune-activating and modulating activities on human peripheral blood mononuclear cell cultures, to examine expression of the CD69 activation marker on lymphocytes versus monocytes, and on the T, NKT, and NK lymphocyte subsets. Culture supernatants were tested for cytokines using Luminex arrays.ResultsBoth aqueous and solid fractions of TvM triggered robust induction of CD69 on lymphocytes and monocytes, whereas FS only triggered minor induction of CD69, and IS had no activating effect. The aqueous extract of TvM had stronger activating effects than the solid fraction. In contrast, the solid fraction of IS triggered a reduction in CD69, below levels on untreated cells.Both aqueous and solid fractions of FS triggered large and dose-dependent increases in immune-activating pro-inflammatory cytokines (IL-2, IL-6), anti-inflammatory cytokines Interleukin-1 receptor antagonist (IL-1ra) and Interleukin-10 (IL-10), anti-viral cytokines interferon-gamma (IFN-γ) and Macrophage Inflammatory Protein-alpha (MIP-1α), as well as Granulocyte-Colony Stimulating Factor (G-CSF) and Interleukin-8 (IL-8). TvM triggered more modest cytokine increases. The aqueous extract of IS showed no effects, whereas the solid fraction showed modest effects on induction of cytokines and growth factors.ConclusionThe results demonstrated that the immune-activating bioactivity of a mycelial-based medicinal mushroom preparation is a combination of the mycelium itself (including insoluble beta-glucans, and also water-soluble components), and the highly bioactive, metabolically fermented substrate, not present in the initial substrate.

Patient and family engagement (PFE) is vital to the spirit of the medical home. This article reflects the efforts of an expert consensus panel, the Patient and Family Engagement Workgroup, as part of the Society of General Internal Medicine's 2013 Research Conference.To review extant literature on PFE in pediatric and adult medicine and quality improvement, highlight emerging best practices and models, suggest questions for future research, and provide references to tools and resources to facilitate implementation of PFE strategies.We conducted a narrative review of relevant articles published from 2000 to 2015. Additional information was retrieved from personal contact with experts and recommended sources from workgroup members.Despite the theoretical importance of PFE and policy recommendations that PFE occurs at all levels across the health care system, evidence of effectiveness is limited, particularly for quality improvement. There is some evidence that PFE is effective, mostly related to engagement in the care of individual patients, but the evidence is mixed and few studies have assessed the effect of PFE on health outcomes. Measurement issues and the lack of a single comprehensive conceptual model pose challenges to progress in this field. Recommendations for future research and a list of practical tools and resources to facilitate PFE are provided.Although PFE appeals to patients, families, providers, and policy-makers, research is needed to assess outcomes beyond satisfaction, address implementation barriers, and support engagement in practice redesign and quality improvement. Partnering with patients and families has great potential to support high-quality health care and optimize outcomes.

En 1852, le gouvernement francais etablit une colonie penitentiaire pour ses prisonniers politiques en Algerie dans l'esprit du systeme Australien. Face aux politiques coloniales contradictoires et a l'opposition des prisonniers eux-memes, cette tentative de colonisation forcee prit fin en 1858. Tandis que l'administration francaise en Algerie avait pour directive de traiter les transportes comme des colons libres potentiels, Paris continuait d'insister sur une politique dure d'isolation des prisonniers, ce qui coutait cher a la colonie. Simultanement, Napoleon III commencait a grâcier les transportes comme preuve de sa generosite, mettant ainsi sa popularite avant les necessites de la politique coloniale et les considerations de securite nationale. Une telle confusion ne fit que renforcer le desire des prisonniers de quitter l'Afrique.

This report summarizes accomplishments made by the McKenzie River Focus Watershed Council in the areas of coordination and administration during Fiscal Year 1998. Coordination and administration consists of tasks associated with Focus Watershed Council staffing, project management, and public outreach.

We conducted a field study to test the hypothesis that gray-tailed voles Microtus canicaudus would move from preferred tall-grass habitat into open, short-grass habitat after exposure to the odours of a mustelid predator in their preferred tall-grass habitat. We also tested the hypothesis that if voles did not avoid the odours of a mustelid predator, they would exhibit suppressed reproduction, delayed sexual maturation, and decreased activity. The experiment was conducted from May to August 1996 in 0.2-ha enclosures in which one-half of each enclosure contained tall grass and in the other one-half the grass was mowed to a height of 5-20 cm. The proportion of voles living in the preferred tall-grass habitat averaged > 0.9 and did not differ significantly before, during, or after voles were exposed to faeces and urine of mink Mustela vison (a mustelid predator), or rabbit Oryctolagus cumiculus (a nonpredator, control). We observed no significant differences between treatments in reproductive rates, time to sexual maturation, juvenile recruitment, or activity. We conclude that in a field situation, gray-tailed voles do not exhibit a behavioural or demographic response to simulated predation risk by a mustelid predator (odours of faeces and urine). The disagreement between our results and those obtained from laboratory studies is discussed.

The Atlantic meridional overturning circulation (AMOC) is a system of ocean currents that has an essential role in Earth’s climate, redistributing heat and influencing the carbon cycle1, 2. The AMOC has been shown to be weakening in recent years1; this decline may reflect decadal-scale variability in convection in the Labrador Sea, but short observational datasets preclude a longer-term perspective on the modern state and variability of Labrador Sea convection and the AMOC1, 3,4,5. Here we provide several lines of palaeo-oceanographic evidence that Labrador Sea deep convection and the AMOC have been anomalously weak over the past 150 years or so (since the end of the Little Ice Age, LIA, approximately ad 1850) compared with the preceding 1,500 years. Our palaeoclimate reconstructions indicate that the transition occurred either as a predominantly abrupt shift towards the end of the LIA, or as a more gradual, continued decline over the past 150 years; this ambiguity probably arises from non-AMOC influences on the various proxies or from the different sensitivities of these proxies to individual components of the AMOC. We suggest that enhanced freshwater fluxes from the Arctic and Nordic seas towards the end of the LIA—sourced from melting glaciers and thickened sea ice that developed earlier in the LIA—weakened Labrador Sea convection and the AMOC. The lack of a subsequent recovery may have resulted from hysteresis or from twentieth-century melting of the Greenland Ice Sheet6. Our results suggest that recent decadal variability in Labrador Sea convection and the AMOC has occurred during an atypical, weak background state. Future work should aim to constrain the roles of internal climate variability and early anthropogenic forcing in the AMOC weakening described here.

Research framework: In 1881 the French Third Republic allocated yearly pensions to nearly 25,000 elderly citizens as reparations for political oppression suffered thirty years earlier during the previous regime. To receive a pension, each former political prisoner ( proscrit ), their widows or children, wrote letters describing their punishment and the wider multi-generational impact of that oppression.Objectives: This article uncovers understandings shared by Republican administrators and a particular group of their staunch working-class supporters - artisans, rural laborers, and small-town shopkeepers - of the definitions of old age, expectations for life trajectories, and how gender affected both expectations and experiences.Methodology: Historical, qualitative analysis of archival documents at the French National Archives and departments of the Ain, Allier, Drôme, Hérault, Rhône, Saône-et-Loire, Vaucluse and Yonne, France.Results: Analysis demonstrates pension applicants drew upon common understandings of gender and age-based roles to strengthen their claims to pensions both as erstwhile heroes of the newly democratic regime and as members of an indigent, elderly poor worthy of government aid.Conclusions: Former proscrits , their families and Republican administrators shared assumptions about the definition of the onset of old age as linked to gender; about expectations that elderly men would work indefinitely in old age until physically unable to do so but that the specter of elderly working women was shameful and a blot on Republican values; and about an understanding that pensions allowed a dignified old-age for both male and female applicants by undoing dangerous shifts in gender roles perceived as triggered by the political oppression decades earlier.Contribution: The article contributes to scholarship on changing European understandings of the gendered dimensions of old age in the late 19th century, just before decades of social welfare legislation., Cadre de la recherche : En 1881, la Troisième République française allouait des pensions viagères à presque 25 000 vieux citoyens, comme réparation de l’oppression politique qu’ils avaient subie trente ans auparavant sous le régime précédent. Afin de recevoir une pension, chaque ancien proscrit, sa veuve ou ses enfants, devait décrire sa peine et les répercussions multigénérationnelles de ce châtiment dans une pétition.Objectifs : Cet article décrit le consensus de l’administration républicaine et d’une partie de ses fidèles partisans (artisans, paysans ouvriers et commerçants des petites villes) sur la définition de la vieillesse, sur ce qu’on espérait du bon déroulement des dernières années de la vie, et sur la façon dont le genre affectait à la fois l’anticipation et l’expérience de la vieillesse.Méthodologie : L’analyse historique et qualitative des fonds aux Archives nationales de France et aux Archives départementales de l’Ain, de l’Allier, de la Drôme, de l’Hérault, du Rhône, de la Saône-et-Loire, du Vaucluse, et de l’Yonne. Résultats : L’analyse montre que les demandeurs de pension orientaient leur pétition sur une idée précise des rôles de genre et d’âge pour renforcer leur droit à une pension basée sur leur double statut de héros républicain et vieillard indigent digne de l’aide gouvernementale.Conclusions : L’analyse montre que les demandeurs de pension s’appuyaient sur une vision commune de la vieillesse, dont le point de départ était lié au sexe de l’individu. Cette conception de la vieillesse comprenait l’attente que les vieillards devaient travailler sans relâche, jusqu’à épuisement physique total, alors que l’idée de vieilles femmes au travail était gênante et entachait les valeurs républicaines. Les demandeurs de pension estimaient que les pensions procureraient une vieillesse digne aux proscrits autant qu’à leur veuve, en annulant l’instabilité des rôles de genre enclenchée par l’oppression politique trente ans auparavant.Contribution : Cet article contribue à l’avancement des recherches sur la perception de la vieillesse et des rôles de genre à la fin de la vie en France à l’orée de législations sociales sur le continent européen.