Dyshidrosiform bullous pemphigoid is a variant of bullous pemphigoid. At least 84 patients with dyshidrosiform bullous pemphigoid have been described. Dyshidrosiform bullous pemphigoid usually ...presents with pruritic blisters in elderly individuals; the hemorrhagic or purpuric lesions on the palms and soles can be the only manifestation of the disease. However, bullae may concurrently or subsequently appear on other areas of the patient's body. Patients typically improve after the diagnosis is established and treatment is initiated. The mainstay of therapy is systemic corticosteroids, with or without topical corticosteroids, and systemic dapsone or immunosuppressants. Drug-related or nickel-induced dyshidrosiform bullous pemphigoid improves after stopping the associated agent; however, systemic therapy has also been required to achieve resolution of the blisters. Similar to classic bullous pemphigoid, neurologic conditions and psychiatric disorders have been observed in dyshidrosiform bullous pemphigoid patients. The new onset of recurrent or persistent blisters on the palms, soles, or both of an elderly individual should prompt the clinician to consider the diagnosis of dyshidrosiform bullous pemphigoid.
Sjögren's Syndrome (SjS) is a chronic, systemic autoimmune disease causing xerostomia, xerophthalmia, and systemic symptoms. The principal pathological finding in SjS is the accumulation of ...lymphocytes in exocrine glandular tissue and elsewhere, leading to secretory dysfunction and other abnormalities. A rational therapeutic approach might be to interfere with lymphocyte migration to the periphery from central lymphoid tissues. We thus examined in an animal model of SjS the effects of Fingolimod (FTY720, Gilenya™), which interferes with migration of lymphocytes to peripheral sites. Fingolimod induces sequestration of lymphocytes in lymphoid organs by altering lymphocyte expression of sphingosine-1-phosphate receptors. In the C57Bl/6. NOD.Aec1Aec2 (AEC) model of SjS, Fingolimod reduced circulating T and B cell numbers. Treatment of AEC mice with Fingolimod increased salivary output and decreased the size of salivary gland infiltrates. Oral Fingolimod thus merits further consideration in the management of SjS in humans.
•Fingolimod (FTY720), a sphingosine-1-P antagonist, blocks lymphocyte traffic.•Sjogren's syndrome is characterized by lymphocytes infiltrating exocrine glands.•Fingolimod treatment of a Sjogren's syndrome mouse model (AEC1/AEC2) reduced salivary gland infiltrates.•Concomitantly, fingolimod treated mice showed improvement of stimulated saliva production.•Fingolimod (a licensed drug) may improve salivary function in human Sjogren's syndrome.
Most previous research on gender inequality and management has been concerned with the question of access to managerial jobs and the "glass ceiling." We offer the first large-scale analysis that ...turns this question around, asking whether the gender characteristics of managers-specifically, the gender composition and relative status of female managers-affect inequality for the nonmanagerial workers beneath them. Results from three-level hierarchical linear models, estimated on a unique nested data set drawn from the 2000 Census, suggest that greater representation of women in management does narrow the gender wage gap. Model predictions show, however, that the presence of high-status female managers has a much larger impact on gender wage inequality. We conclude that the promotion of women into management positions may benefit all women, but only if female managers reach relatively high-status positions.
The nuclear receptors PPAR-γ and LXRs regulate macrophage lipid metabolism and macrophage mediated inflammation. We examined the influence of these molecules on macrophage alternative activation, ...with particular focus on differentiation of "M2c" anti-inflammatory cells.
We cultured human monocytes in M0, M1, M2a or M2c macrophage differentiating conditions, in the presence or absence of PPAR-γ and LXR ligands. Flow cytometry was used to analyze membrane expression of phenotypic markers. Basal and LPS-stimulated production of soluble mediators was measured by ELISA. Efferocytosis assays were performed by coincubating monocytes/macrophages with apoptotic neutrophils.
We found that PPAR-γ inhibition, using the PPAR-γ antagonist GW9662, elicits differentiation of M2c-like (CD206(+) CD163(+) CD16(+)) cells and upregulation of the MerTK/Gas6 axis. Exposure of differentiating macrophages to IFN-γ, GM-CSF or LPS (M1 conditions), however, hampers GW9662 induction of MerTK and Gas6. When macrophages are differentiated with IL-4 (M2a conditions), addition of GW9662 results into an M2a (CD206(+) CD209(+) CD163(-) MerTK(-)) to M2c (CD206(high) CD209(-) CD163(+) MerTK(+)) polarization shift. Conversely, in the presence of dexamethasone (M2c conditions), the PPAR-γ agonist rosiglitazone attenuates CD163 and MerTK upregulation. The LXR agonist T0901317 induces MerTK independently of M2c polarization; indeed, CD206, CD163 and CD16 are downregulated. GW9662-differentiated M2c-like cells secrete high levels of Gas6 and low amounts of TNF-α and IL-10, mimicking dexamethasone effects in vitro. However, unlike conventional M2c cells, GW9662-differentiated cells do not show enhanced efferocytic ability.
Our results provide new insights into the role of PPAR-γ and LXR receptors in human macrophage activation and reveal the existence of different patterns regulating MerTK expression. Unexpectedly, PPAR-γ appears to negatively control the expansion of a discrete subset of M2c-like anti-inflammatory macrophages.
Many argue that swift and fundamental interventions in the system of scholarly communication are needed. However, there are substantial disagreements over the short- and long-term benefits of most ...proposed approaches to changing the practice of science communication, and the lack of systematic, empirically based research in this area makes these controversies difficult to resolve. We argue that experience within public health can be usefully applied to scholarly communication.
Starting with the history of DDT (Dichlorodiphenyltrichloroethane) application, we illustrate four ways complex human systems threaten reliable predictions and blunt ad-hoc interventions. We then show how these apply to interventions in scholarly publication – open access based on the article processing charge (APC), and preprints – to yield surprising results. Finally, we offer approaches to help guide the design of future interventions: identifying measures and outcomes, developing infrastructure, incorporating assessment, and contributing to theories of systemic change.
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