50 research outputs found

    33356 A multinational chart review to examine gastrointestinal symptoms and their management in patients treated with apremilast for plaque psoriasis

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    Background: Diarrhea and nausea are the most common adverse events observed in phase 3 clinical trials and real-world studies of apremilast, an oral phosphodiesterase-4 inhibitor indicated for moderate-to-severe plaque psoriasis. Methods: A retrospective chart review was conducted between June and November 2020 in the United States (US) and France among patients with moderate psoriasis experiencing gastrointestinal (GI) symptoms within 3 months of initiating apremilast. Results: Dermatologists in US (200) and in France (52) abstracted patient charts (US: 494, France: 128). The following GI symptoms were reported: ‒diarrhea (US: 67% [331/494]; France: 76% [97/128]) with median time from onset to resolution/improvement of 26 days (US) and 21 days (France) ‒nausea (US: 52% [255/494]; France: 34% [44/128]) with median time from onset to resolution/improvement of 21 days (US) and 24 days (France). Management strategies for diarrhea included pharmacologic (loperamide/bismuth subsalicylate/racecadotril) with or without nonpharmacologic (dietary modifications, taking with food)/fiber (US: 30% [99/331], France: 41% [40/97]) and nonpharmacologic only (US: 32% [105/331], France: 27% [26/97]). Management strategies for nausea included pharmacologic (diphenhydramine/metoclopramide/metopimazine) with or without nonpharmacologic (dietary modifications, taking with food, avoidance of vigorous activity) (US: 5% [14/255], France: 30% [13/44]) and nonpharmacologic only (US: 58% [147/255], France: 36% [16/44]). Resolution/improvement of GI symptoms was observed in patients who used pharmacologic strategies and nonpharmacologic strategies. Conclusions: Recommendations to manage diarrhea and nausea after apremilast initiation with pharmacologic or non-pharmacologic strategies were effective and symptoms usually resolved within 3-4 weeks of onset

    Evidence for the Role of Horizontal Transfer in Generating pVT1, a Large Mosaic Conjugative Plasmid from the Clam Pathogen, Vibrio tapetis

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    The marine bacterium Vibrio tapetis is the causative agent of the brown ring disease, which affects the clam Ruditapes philippinarum and causes heavy economic losses in North of Europe and in Eastern Asia. Further characterization of V. tapetis isolates showed that all the investigated strains harbored at least one large plasmid. We determined the sequence of the 82,266 bp plasmid pVT1 from the CECT4600T reference strain and analyzed its genetic content. pVT1 is a mosaic plasmid closely related to several conjugative plasmids isolated from Vibrio vulnificus strains and was shown to be itself conjugative in Vibrios. In addition, it contains DNA regions that have similarity with several other plasmids from marine bacteria (Vibrio sp., Shewanella sp., Listonella anguillarum and Photobacterium profundum). pVT1 contains a number of mobile elements, including twelve Insertion Sequences or inactivated IS genes and an RS1 phage element related to the CTXphi phage of V. cholerae. The genetic organization of pVT1 underscores an important role of horizontal gene transfer through conjugative plasmid shuffling and transposition events in the acquisition of new genetic resources and in generating the pVT1 modular organization. In addition, pVT1 presents a copy number of 9, relatively high for a conjugative plasmid, and appears to belong to a new type of replicon, which may be specific to Vibrionaceae and Shewanelleacae

    The Staphylococcus aureus RNome and Its Commitment to Virulence

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    Staphylococcus aureus is a major human pathogen causing a wide spectrum of nosocomial and community-associated infections with high morbidity and mortality. S. aureus generates a large number of virulence factors whose timing and expression levels are precisely tuned by regulatory proteins and RNAs. The aptitude of bacteria to use RNAs to rapidly modify gene expression, including virulence factors in response to stress or environmental changes, and to survive in a host is an evolving concept. Here, we focus on the recently inventoried S. aureus regulatory RNAs, with emphasis on those with identified functions, two of which are directly involved in pathogenicity

    MMP19 Is Essential for T Cell Development and T Cell-Mediated Cutaneous Immune Responses

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    Matrix metalloproteinase-19 (MMP19) affects cell proliferation, adhesion, and migration in vitro but its physiological role in vivo is poorly understood. To determine the function of MMP19, we generated mice deficient for MMP19 by disrupting the catalytic domain of mmp19 gene. Although MMP19-deficient mice do not show overt developmental and morphological abnormalities they display a distinct physiological phenotype. In a model of contact hypersensitivity (CHS) MMP19-deficient mice showed impaired T cell-mediated immune reaction that was characterized by limited influx of inflammatory cells, low proliferation of keratinocytes, and reduced number of activated CD8+ T cells in draining lymph nodes. In the inflamed tissue, the low number of CD8+ T cells in MMP19-deficient mice correlated with low amounts of proinflammatory cytokines, especially lymphotactin and interferon-inducible T cell α chemoattractant (I-TAC). Further analyses showed that T cell populations in the blood of immature, unsensitized mice were diminished and that this alteration originated from an altered maturation of thymocytes. In the thymus, thymocytes exhibited low proliferation rates and the number of CD4+CD8+ double-positive cells was remarkably augmented. Based on the phenotype of MMP19-deficient mice we propose that MMP19 is an important factor in cutaneous immune responses and influences the development of T cells

    Variability of heat stability of goat milk

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    Session 09 *INRA Station Génétique des Animaux 31326 Castanet-Tolosan (FRA) Diffusion du document : INRA Station Génétique des Animaux 31326 Castanet-Tolosan (FRA) "Chantier qualité spécifique "Auteurs Externes" département de Génétique animale : uniquement liaison auteur au référentiel HR-Access "International audienc
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