Efalizumab-induced severe thrombocytopenia can be resolved

Efalizumab is a monoclonal a humanized recombinant IgG1 monoclonal antibody which targets the CD11a, the alpha-subunit of LFA-1 (lymphocyte function-associated antigen-1). It acts by blocking the T-lymphocyte pathogenetic mechanisms of psoriasis. Thrombocytopenia is an adverse event that occurs during therapy. Thrombocytopenia can be mild and can occur quite early during treatment, together with leukocytosis. Both adverse events tend to normalize with ongoing therapy, or, in cases worsening, with therapy suspension. There have been multiple reports of thrombocytopenia associated with efalizumab therapy for the treatment of psoriasis. The general recommendation is to check platelet counts monthly for the first 3 months of efalizumab therapy, then every 3 months for the duration of therapy. According to our experience on a wide range of patients, it is useful to check platelets every month for the first 6 months of therapy. We report a case of efalizumab-associated thrombocytopenia that occurred after 16 weeks of therapy together with clinical worsening of skin lesions. The peculiarity of our case is the absence of signs and symptoms linked to thrombocytopenia and the quick return to normal platelet count without corticosteroid therapy

Itch in psoriasis: epidemiology, clinical aspects and treatment options

F Prignano, F Ricceri, L Pescitelli, T LottiDepartment of Dermatological Sciences, University of Florence,Florence, ItalyBackground: Pruritus is an important symptom in psoriasis vulgaris, may be severe and seriously affect the quality of life of patients, but published data on its frequency and characteristics are limited.Objective: The study objective was to characterize the prevalence of itch in psoriatic patients and the effect of treatment modalities by using a comprehensive itch questionnaire of our own design.Methods: A structured itch questionnaire was given to 90 patients with moderate to severe chronic-plaque psoriasis selected consecutively from the patients visiting the Department of Dermatology of the University of Florence. The questionnaire concerned the areas involved in psoriasis and pruritus, the pruritus characteristics, the worsening and relieving factors and treatment modalities. Itch intensity was reflected by a 10 point visual analog scale (VAS) and the degree of symptoms discriminated between mild (1–3), moderate (4–7) and severe (8–10).Results: Almost 85% of psoriatic patients suffered from itching; the frequency of pruritus was daily and mean intensity by VAS scale was moderate. Presence and intensity of pruritus and body mass index (BMI) were correlated. 40% of patients with pruritus were overweight (BMI > 25 < 30) and 10% obese (BMI > 30). Almost all patients appeared unsatisfied with the available treatment modalities for pruritus in psoriasis. Emollients, topical steroids and calcipotriol cream could relieve pruritus but their effect was temporary. Among the antipsoriatic therapies, phototherapy with narrow band ultraviolet B (nb-UVB) was the most effective treatment in reducing pruritus. Biological therapies, mainly etanercept and efalizumab, proved useful in its control.Conclusions: The questionnaire was a useful tool to characterize itch, and the results might help us to better understand pruritus in psoriasis. The results confirmed the need for a global study of psoriasis with regard to both the cutaneous manifestations and the itch symptom.Keywords: itch, psoriasis, pruritus, epidemiology, phototherapy, etanercept, efalizuma

Coexistence of pressure-induced structural phases in bulk black phosphorus: a combined x-ray diffraction and Raman study up to 18 GPa

We report a study of the structural phase transitions induced by pressure in bulk black phosphorus by using both synchrotron x-ray diffraction for pressures up to 12.2 GPa and Raman spectroscopy up to 18.2 GPa. Very recently black phosphorus attracted large attention because of the unique properties of fewlayers samples (phosphorene), but some basic questions are still open in the case of the bulk system. As concerning the presence of a Raman spectrum above 10 GPa, which should not be observed in an elemental simple cubic system, we propose a new explanation by attributing a key role to the non-hydrostatic conditions occurring in Raman experiments. Finally, a combined analysis of Raman and XRD data allowed us to obtain quantitative information on presence and extent of coexistences between different structural phases from ~5 up to ~15 GPa. This information can have an important role in theoretical studies on pressure-induced structural and electronic phase transitions in black phosphorus

Estimate of the impact of background particles on the X-Ray Microcalorimeter Spectrometer on IXO

We present the results of a study on the impact of particles of galactic (GCR) and solar origin for the X-ray Microcalorimeter Spectrometer (XMS) aboard an astronomical satellite flying in an orbit at the second Lagrangian point (L2). The detailed configuration presented in this paper is the one adopted for the International X-Ray Observatory (IXO) study, however the derived estimates can be considered a conservative limit for ATHENA, that is the IXO redefined mission proposed to ESA. This work is aimed at the estimate of the residual background level expected on the focal plane detector during the mission lifetime, a crucial information in the development of any instrumental configuration that optimizes the XMS scientific performances. We used the Geant4 toolkit, a Monte Carlo based simulator, to investigate the rejection efficiency of the anticoincidence system and assess the residual background on the detector.Comment: 18 pages, 9 figure

Fibroblasts to keratinocytes redox signaling: The possible role of ROS in psoriatic plaque formation

Although the role of reactive oxygen species-mediated (ROS-mediated) signalling in physiologic and pathologic skin conditions has been proven, no data exist on the skin cells ROS-mediated communication. Primary fibroblasts were obtained from lesional and non-lesional skin of psoriatic patients. ROS, superoxide anion, calcium and nitric oxide levels and lipoperoxidation markers and total antioxidant content were measured in fibroblasts. NADPH oxidase activity and NOX1, 2 and 4 expressions were assayed and NOX4 silencing was performed. Fibroblasts and healthy keratinocytes co-culture was performed. MAPK pathways activation was studied in fibroblasts and in co-cultured healthy keratinocytes. Increased intracellular calcium, •NO and ROS levels as well as an enhanced NADPH oxidase 4 (NOX4)–mediated extracellular ROS release was shown in lesional psoriatic vs. control fibroblasts. Upon co-culture with lesional fibroblasts, keratinocytes showed p38 and ERK MAPKs pathways activation, ROS, Ca2+ and •NO increase and cell cycle acceleration. Notably, NOX4 knockdown significantly reduced the observed effects of lesional fibroblasts on keratinocyte cell cycle progression. Co-culture with non-lesional psoriatic and control fibroblasts induced slight cell cycle acceleration, but notable intracellular ROS accumulation and ERK MAPK activation in keratinocytes. Collectively, our data demonstrate that NOX4 expressed in dermal fibroblasts is essential for the redox paracrine regulation of epidermal keratinocytes proliferation

The Circular Economy: What, Why, How and Where

This paper was prepared as a background document for an OECD/EC high-level expert workshop on “Managing the transition to a circular economy in regions and cities” held on 5 July 2019 at the OECD Headquarters in Paris, France. It sets a basis for reflection and discussion. The background paper should not be reported as representing the official views of the European Commission, the OECD or one of its member countries. The opinions expressed and arguments employed are those of the author(s)