Acute Thrombogenicity of a Durable Polymer Everolimus-Eluting Stent Relative to Contemporary Drug-Eluting Stents With Biodegradable Polymer Coatings Assessed Ex Vivo in a Swine Shunt Model

AbstractObjectivesThis study sought to evaluate whether the permanent fluoropolymer-coated Xience Xpedition everolimus-eluting stent (Xience-EES) exhibits lower acute thrombogenicity compared with contemporary drug-eluting stents (DES) with biodegradable polymer coatings in an acute swine shunt model.BackgroundPrevious pre-clinical and clinical experience suggests that several factors may influence the predisposition for acute thrombus formation of polymer-coated DES, including stent design and the polymer coating technology. It remains unclear whether relevant differences exist with respect to acute thrombogenicity, particularly between current commercial stent designs using permanent polymers and those using biodegradable polymers.MethodsAn ex vivo carotid to jugular arteriovenous porcine shunt model involving a test circuit of 3 in-line stents, was used to test acute thrombogenicity, where Xience-EES (n = 24) was compared with 4 CE-marked DES with biodegradable polymer coatings (BioMatrix Flex, Synergy, Nobori, and Orsiro [n = 6 each]). After 1 h of circulation, platelet aggregation in whole mount stents was evaluated by confocal microscopy with immunofluorescent staining against dual platelet markers (CD61/CD42b) along with scanning electron microscopy.ResultsXience-EES showed the least percentage of thrombus-occupied area as compared with the biodegradable polymer-coated DES, with a significant difference compared with BioMatrix Flex and Synergy (mean differences: [BioMatrix Flex: 15.54, 95% confidence interval [CI]: 11.34 to 19.75, p < 0.001; Synergy: 8.64, 95% CI: 4.43 to 12.84, p < 0.001; Nobori: 4.22, 95% CI: -0.06 to 8.49, p = 0.055; Orsiro: 2.95, 95% CI: -1.26 to 7.15, p = 0.286). The number of cell nuclei on strut surfaces was also the least in Xience-EES, with a significant difference relative to BioMatrix Flex, Nobori, and Orsiro (mean ratios: BioMatrix Flex: 4.73, 95% CI: 2.46 to 9.08, p < 0.001; Synergy: 1.44, 95% CI: 0.75 to 2.76, p = 0.51; Nobori: 5.97, 95% CI: 3.11 to 11.44, p < 0.001; Orsiro: 5.16, 95% CI: 2.69 to 9.91, p < 0.001).ConclusionsXience-EES’s overall design confers acute thromboresistance relative to contemporary DES with biodegradable coatings, with less platelet aggregation versus BioMatrix Flex and Synergy, and less inflammatory cell attachment versus BioMatrix Flex, Nobori, and Orsiro, in an ex vivo swine shunt model, which lends support to reported clinical findings of lower early stent thrombosis

Human Sapovirus Replication in Human Intestinal Enteroids

Human sapoviruses (HuSaVs), like human noroviruses (HuNoV), belong to the Caliciviridae family and cause acute gastroenteritis in humans. Since their discovery in 1976, numerous attempts to grow HuSaVs in vitro were unsuccessful until 2020, when these viruses were reported to replicate in a duodenal cancer cell-derived line. Physiological cellular models allowing viral replication are essential to investigate HuSaV biology and replication mechanisms such as genetic susceptibility, restriction factors, and immune responses to infection. In this study, we demonstrate replication of two HuSaV strains in human intestinal enteroids (HIEs) known to support the replication of HuNoV and other human enteric viruses. HuSaVs replicated in differentiated HIEs originating from jejunum, duodenum and ileum, but not from the colon, and bile acids were required. Between 2h and 3 to 6 days postinfection, viral RNA levels increased up from 0.5 to 1.8 log10-fold. Importantly, HuSaVs were able to replicate in HIEs independent of their secretor status and histo-blood group antigen expression. The HIE model supports HuSaV replication and allows a better understanding of host-pathogen mechanisms such as cellular tropism and mechanisms of viral replication. IMPORTANCE Human sapoviruses (HuSaVs) are a frequent but overlooked cause of acute gastroenteritis, especially in children. Little is known about this pathogen, whose successful in vitro cultivation was reported only recently, in a cancer cell-derived line. Here, we assessed the replication of HuSaV in human intestinal enteroids (HIEs), which are nontransformed cultures originally derived from human intestinal stem cells that can be grown in vitro and are known to allow the replication of other enteric viruses. Successful infection of HIEs with two strains belonging to different genotypes of the virus allowed discovery that the tropism of these HuSaVs is restricted to the small intestine, does not occur in the colon, and replication requires bile acid but is independent of the expression of histo-blood group antigens. Thus, HIEs represent a physiologically relevant model to further investigate HuSaV biology and a suitable platform for the future development of vaccines and antivirals

THU0374 Health Beliefs, Experiences and Educational Needs of Patients with Osteoporosis : A Qualitative Study by the Working Group Solid’os

International audienceBackground Real life experience and health beliefs impact quality of life and adherence to medication. Educational management programs have proved beneficial for patients with osteoporosis (OP).Objectives To understand perceptions and educational needs of patients with different types of osteoporosis. The aim was to target patients perceptive to help the construction of educational programs.Methods Focus group were conducted with a semi directive interview guide developed by the multidisciplinary working group SOLID’OS including rheumatologists, health care professionals, members of a patient association and experts in qualitative research. Interviews involved 18 post-menopausal women with osteoporotic fractures (2 groups), 10 post-menopausal women without osteoporotic fractures (2 groups), 14 men with osteoporosis (2 groups) and 10 patients with corticosteroid (CS) -induced osteoporosis (2 groups). Each group included 4 to 10 patients in 7 different cities. Thematic analysis was performed.Results A wide range of health beliefs about OP was found : OP is considered as a natural consequence of aging or on the contrary leads to dramatic feelings and self-depreciation. Patients regret the delay to diagnosis before fractures occur. Patients are in fear of new fractures and consequently limit their daily life activities. Patients with CS-induced osteoporosis take better care of the causal disease than of OP. Men have negative perceptions, considering that OP principally affects women. Men have difficulties to cope with the loss of their functional abilities.Patients have a rather good knowledge of treatment except for CS treated patients whose knowledge is lower. Some patients are confident in health care providers and medication efficacy whereas others focus on adverse effects and doubt of the benefit of treatments. All patients need support and look for evidence of treatments efficacy. Patients show a great interest for non-pharmacologic management such as calcium intake and physical activity. Errors are frequent about adverse effects of calcium and milk, which for instance is believed to cause arthritis.Patients feel that group follow up by health professionals will enhance their motivation especially for exercises. They show preferences for group education close to their place of residence. Men often go on the Internet for brief information and like booklets.Education should include physical activity, fall prevention and dietetics. The benefit of including partners remains doubtful for almost all patients.Conclusions This qualitative study showed that patients’ perspective differ according to the type of osteoporosis. A personalized assessment of patients’ needs and objectives should then be performed before inclusion in educational programs. Patients have a major interest for non-pharmacological treatments and prefer group education

Multifunctionality of floodplain landscapes : Relating management options to ecosystem services

The concept of green infrastructure has been recently taken up by the European Commission for ensuring the provision of ecosystem services (ESS). It aims at the supply of multiple ESS in a given landscape, however, the effects of a full suite of management options on multiple ESS and landscape multifunctionality have rarely been assessed. In this paper we use European floodplain landscapes as example to develop an expert based qualitative conceptual model for the assessment of impacts of landscape scale interventions on multifunctionality. European floodplain landscapes are particularly useful for such approach as they originally provided a high variety and quantity of ESS that has declined due to the strong human impact these landscapes have experienced. We provide an overview of the effects of floodplain management options on landscape multifunctionality by assessing the effects of 38 floodplain management interventions on 21 relevant ESS, as well as on overall ESS supply. We found that restoration and rehabilitation consistently increased the multifunctionality of the landscape by enhancing supply of provisioning, regulation/maintenance, and cultural services. In contrast, conventional technical regulation measures and interventions related to extraction, infrastructure and intensive land use cause decrease in multifunctionality and negative effects for the supply of all three aspects of ESS. The overview of the effects of interventions shall provide guidance for decision makers at multiple governance levels. The presented conceptual model could be effectively applied for other landscapes that have potential for a supply of a high diversity of ESS. © 2014 Springer Science+Business Media Dordrecht

Multivariate optimization and validation of a CZE method for the analysis of pridinol mesylate and meloxicam in tablets

A capillary zone electrophoresis method for the simultaneous determination of pridinol mesylate (PRI) and meloxicam (MEL) employing epinastine hydrochloride and piroxicam as internal standards, was developed and optimized employing experimental design and response surface methodologies. The separation was optimally achieved in less than 2 min at 30 kV in an uncoated fused-silica capillary (41.4 cm × 75 μm I.D.), employing an 18 mmol L-1 sodium phosphate buffer solution (pH 5.90) at 25 °C. Samples were injected in hydrodynamic mode (50 mbar, 5 s) and the analytes were spectrophotometrically detected at 200 nm. Method robustness was demonstrated by ANOVA of determinations performed under conditions slightly different from the optimum. The method was validated regarding separation selectivity (peak purity factors > 0.99), linearity and range (PRI = 17.6-31.4 mg L-1; MEL = 66.5-122.5 mg L-1), accuracy (PRI = 100.2-101.9%; MEL = 98.9-100.7%) and precision. The RSD values obtained were ≥1.3% for injection repeatability and ≥1.9% for intra-day precision. The limits of detection (1.0 and 0.9 mg L-1) and quantification (3.3 and 16.5 mg L-1) of PRI and MEL, respectively, were also determined. The method was successfully applied to the determination of both drugs in three brands of tablet formulations. No statistically significant differences were observed when these results were compared with those of a RP-HPLC method.Fil: Vignaduzzo, Silvana Edit. Universidad Nacional de Rosario; ArgentinaFil: Vera Candioti, Luciana. National University Of The Litoral; ArgentinaFil: Castellano, Patricia Margarita. Universidad Nacional de Rosario; ArgentinaFil: Goicoechea, Hector Casimiro. Universidad Nacional del Litoral; ArgentinaFil: Kaufman, Teodoro Saul. Universidad Nacional de Rosario; Argentin