Biodegradable Paclitaxel-loaded Nanoparticles and Stent Coatings as Local Delivery Systems for the Prevention of Restenosis

Despite improved technologies restenosis remains the main problem of catheter-based interventions after a percutaneous transluminal angioplasty in artery disease. Local and sustained application of antiproliferative agents is a promising approach to solve the problem of intimal hyperplasia. In recent years, two different concepts for local drug delivery have attained increased importance: On the one hand, colloidal drug carriers, which can be infused directly into the vessel wall during the angioplasty procedure using special delivery catheters and on the other hand, the development of drug eluting stents. Biocompatible, biodegradable polymers are one of the most important instruments used to control the release of pharmacological active substances. A new type of branched, biodegradable polyesters, poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) (PVA-g-PLGA), possesses very interesting features for the local and sustained release of paclitaxel. Therefore, the objective of this work was to investigate these polymers with regard to the preparation of paclitaxel loaded nanoparticles and stent coatings, and to evaluate their applicability as drug carriers to prevent intimal hyperplasia

Biodegradable Paclitaxel-loaded Nanoparticles and Stent Coatings as Local Delivery Systems for the Prevention of Restenosis

Despite improved technologies restenosis remains the main problem of catheter-based interventions after a percutaneous transluminal angioplasty in artery disease. Local and sustained application of antiproliferative agents is a promising approach to solve the problem of intimal hyperplasia. In recent years, two different concepts for local drug delivery have attained increased importance: On the one hand, colloidal drug carriers, which can be infused directly into the vessel wall during the angioplasty procedure using special delivery catheters and on the other hand, the development of drug eluting stents. Biocompatible, biodegradable polymers are one of the most important instruments used to control the release of pharmacological active substances. A new type of branched, biodegradable polyesters, poly(vinyl alcohol)-graft-poly(lactide-co-glycolide) (PVA-g-PLGA), possesses very interesting features for the local and sustained release of paclitaxel. Therefore, the objective of this work was to investigate these polymers with regard to the preparation of paclitaxel loaded nanoparticles and stent coatings, and to evaluate their applicability as drug carriers to prevent intimal hyperplasia

Use of Formative Assessment to Structure Flexible Differentiated Learning Groups: A Pathway to Equity

The action research contained in this study seeks to identify the impact of formative assessment in the structuring of flexible differentiation in order to provided equity within the self-contained classroom for all intersectionalities amongst elementary students. Grounded in community of practice theory, the research explores structures within flexible differentiation and small group learning that provide students of varied and overlapping identities with access and equity within the four walls of the self-contained classroom. Additionally, the influence of flexible differentiation on the affective nature of students was explored. The teacher-researcher utilized a mixed-methods approach in order to provide a holistic picture. Data analysis in this research study revealed that the impact of differentiation on student achievement appeared to be situational and that key elements of differentiation, such as teacher proximity and intentionality in instruction, contributed to student\u27s academic growth

\u3ci\u3ePseudomonas\u3c/i\u3e HopU1 modulates plant immune receptor levels by blocking the interaction of their mRNAs with GRP7

Pathogens target important components of host immunity to cause disease. The Pseudomonas syringae type III-secreted effector HopU1 is a mono-ADP-ribosyltransferase required for full virulence on Arabidopsis thaliana. HopU1 targets several RNA-binding proteins including GRP7, whose role in immunity is still unclear. Here, we show that GRP7 associates with translational components, as well as with the pattern recognition receptors FLS2 and EFR. Moreover, GRP7 binds specifically FLS2 and EFR transcripts in vivo through its RNA recognition motif. HopU1 does not affect the protein–protein associations between GRP7, FLS2 and translational components. Instead, HopU1 blocks the interaction between GRP7 and FLS2 and EFR transcripts in vivo. This inhibition correlates with reduced FLS2 protein levels upon Pseudomonas infection in a HopU1- dependent manner. Our results reveal a novel virulence strategy used by a microbial effector to interfere with host immunity

\u3ci\u3ePseudomonas\u3c/i\u3e HopU1 modulates plant immune receptor levels by blocking the interaction of their mRNAs with GRP7

Pathogens target important components of host immunity to cause disease. The Pseudomonas syringae type III-secreted effector HopU1 is a mono-ADP-ribosyltransferase required for full virulence on Arabidopsis thaliana. HopU1 targets several RNA-binding proteins including GRP7, whose role in immunity is still unclear. Here, we show that GRP7 associates with translational components, as well as with the pattern recognition receptors FLS2 and EFR. Moreover, GRP7 binds specifically FLS2 and EFR transcripts in vivo through its RNA recognition motif. HopU1 does not affect the protein–protein associations between GRP7, FLS2 and translational components. Instead, HopU1 blocks the interaction between GRP7 and FLS2 and EFR transcripts in vivo. This inhibition correlates with reduced FLS2 protein levels upon Pseudomonas infection in a HopU1- dependent manner. Our results reveal a novel virulence strategy used by a microbial effector to interfere with host immunity

Functionalized Synthetic Biodegradable Polymer Scaffolds for Tissue Engineering

Scaffolds (artificial ECMs) play a pivotal role in the process of regenerating tissues in 3D. Biodegradable synthetic polymers are the most widely used scaffolding materials. However, synthetic polymers usually lack the biological cues found in the natural extracellular matrix. Significant efforts have been made to synthesize biodegradable polymers with functional groups that are used to couple bioactive agents. Presenting bioactive agents on scaffolding surfaces is the most efficient way to elicit desired cell/material interactions. This paper reviews recent advancements in the development of functionalized biodegradable polymer scaffolds for tissue engineering, emphasizing the syntheses of functional biodegradable polymers, and surface modification of polymeric scaffolds. Significant efforts have been made to develop functional biodegradable scaffolds for tissue regeneration that can enhance cell function and guide new tissue formation. This paper discusses the recent advancements of functionalizing synthetic biodegradable polymer scaffolds, focusing on polymer synthesis, surface modification, and cellular response on these functionalized scaffolds.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/92034/1/911_ftp.pd

Sick leave and work disability in patients with early arthritis

We studied the occurrence of sick leave and work disability, the presence of workplace adaptations and the usage of professional guidance related to working problems in patients with early arthritis. Inclusion criteria were arthritis symptoms of less than 2 years duration and a paid job at the time of diagnosis. Assessments were done in connection with an early arthritis clinic (EAC) at entry into the cohort and 12 months thereafter by means of a questionnaire comprising questions on sick leave (absenteeism from work reported to the employer), work disability (receiving a full or partial work disability pension), unemployment, work adaptations and professional guidance related to working problems. Fifty-seven of the 69 participants (83%) had an arthritis symptom duration of <6 months. The number of patients with sick leave due to arthritis in the past 12 months decreased from 28 (41%) at study entry to 18 (26%) after 12 months of follow-up. The number of patients receiving a work disability pension increased from 5 (7%) at study entry to 13 (19%) after 12 months of follow-up (10 partial and 3 full). Sick leave in the 12 months before study entry appeared to be the most important predictor of the institution or increase in a work disability pension (odds ratio, 16.1; 95%CI, 1.8–142.8). Between study entry and follow-up, the number of patients with workplace adaptations increased from 20 (29%) to 28 (42%), whereas the number of patients receiving vocational guidance decreased from 48 (70%) to 36 (52%). In patients with early arthritis and a paid job, arthritis-related sick leave was common and occurred in part before patients entered the EAC and a diagnosis was made. About 20% of the patients became permanently work disabled, with partial work disability being more common than full work disability. Considerable proportions of patients received workplace adaptations and professional guidance with working problems

Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies