Long-term cost-effectiveness of matrix-associated chondrocyte implantation in the German health care system: a discrete event simulation.

Introduction: Cartilage defects in the knee can be caused by injury, various types of arthritis, or degeneration. As a long-term consequence of cartilage defects, osteoarthritis can develop over time, often leading to the need for a total knee replacement (TKR). The treatment alternatives of chondral defects include, among others, microfracture, and matrix-associated autologous chondrocyte implantation (M-ACI).

Treatment Costs of Matrix-Associated Autologous Chondrocyte Implantation Compared With Microfracture: Results of a Matched-Pair Claims Data Analysis on the Treatment of Cartilage Knee Defects in Germany.

Background: Articular cartilage damage is caused by traumatic sport accidents or age-related degeneration and might lead to osteoarthritis, which represents a socioeconomic burden to society. Cartilage damage in the knee is commonly treated surgically with microfracture (MFX) or matrix-associated autologous chondrocyte implantation (MACI).

Purpose: To quantify the initial and follow-up costs associated with MFX and MACI treatments from the viewpoint of statutory health insurance in Germany.

Matrix-Associated Chondrocyte Implantation Is Associated With Fewer Reoperations Than Microfracture: Results of a Population-Representative, Matched-Pair Claims Data Analysis for Cartilage Defects of the Knee.

Background: Symptomatic cartilage defects of the knee are commonly surgically treated by microfracture (MFX) or matrix-associated chondrocyte implantation (M-ACI). Several randomized controlled trials have compared MFX and M-ACI, showing a tendency to lower reoperation rates for M-ACI, but results vary widely between studies.

Purpose: To compare reoperation rates after MFX and M-ACI in cartilage defects of the knee outside clinical trials in a representative sample of the population.

The prevalence of diagnosed α1-antitrypsin deficiency and its comorbidities: results from a large population-based database.

α-Antitrypsin deficiency (AATD) is a genetically determined disorder that is associated with different clinical manifestations. We aimed to assess the prevalence of diagnosed AATD and its comorbidities using a large healthcare database.In this retrospective longitudinal observational study, we analysed data from 4 million insurants.

Dynamic of ligand binding to Drosophila melanogaster ecdysteroid receptor.

Ligand binding to ecdysone receptor (EcR) is an autonomous function of the ligand binding domain (LBD) and is not modified by other receptor domains or tags fused to the LBD. Association and dissociation velocity of hormone to EcR was studied in the absence and presence of its main dimerization partner Ultraspiracle (USP). Mutational analysis of the EcR(LBD) revealed that ligand entry and exit is affected differently by the same point mutation, indicating that different pathways are used for association and dissociation of the ligand.

Functional studies on the ligand-binding domain of Ultraspiracle from Drosophila melanogaster.

The functional insect ecdysteroid receptor is comprised of the ecdysone receptor (EcR) and Ultraspiracle (USP). The ligand-binding domain (LBD) of USP was fused to the GAL4 DNA-binding domain (GAL4-DBD) and characterized by analyzing the effect of site-directed mutations in the LBD. Normal and mutant proteins were tested for ligand and DNA binding, dimerization, and their ability to induce gene expression.

Characterization of the ligand-binding domain of the ecdysteroid receptor from Drosophila melanogaster.

Mutants created by site-directed mutagenesis were used to elucidate the function of amino acids involved in ligand binding to ecdysteroid receptor (EcR) and heterodimer formation with ultraspiracle (USP). The results demonstrate the importance of the C-terminal part of the D-domain and helix 12 of EcR for hormone binding. Some amino acids are involved either in ligand binding to EcR (E476, M504, D572, I617, N626) or ligand-dependent heterodimerization as determined by gel mobility shift assays (A612, L615, T619), while others are involved in both functions (K497, E648).

Ligand-induced heterodimerization between the ligand binding domains of the Drosophila ecdysteroid receptor and ultraspiracle.

The insect ecdysteroid receptor consists of a heterodimer between EcR and the RXR-orthologue, USP. We addressed the question of whether this heterodimer, like all other RXR heterodimers, may be formed in the absence of ligand and whether ligand promotes dimerization. We found that C-terminal protein fragments that comprised the ligand binding, but not the DNA binding domain of EcR and USP and which were equipped with the activation or DNA binding region of GAL4, respectively, exhibit a weak ability to interact spontaneously with each other.

Expression of ecdysteroid receptor and ultraspiracle from Chironomus tentans (Insecta, Diptera) in E. coli and purification in a functional state.

Full length clones of ecdysteroid receptor (EcR) and Ultraspiracle (USP) from Chironomus tentans were expressed as GST fusion proteins in E. coli and purified by affinity chromatography. The absence of detergents during the purification procedure is essential for retaining receptor function, especially ligand binding.