Are there differences between stemless and conventional stemmed shoulder prostheses in the treatment of glenohumeral osteoarthritis?

Background: Conventional stemmed anatomical shoulder prostheses are widely used in the treatment of glenohumeral osteoarthritis. The stemless shoulder prosthesis, in contrast, is a new concept, and fewer outcome studies are available. Therefore, the purpose of the study was to investigate the early functional outcome and postoperative proprioception of a stemless prosthesis in comparison with a standard stemmed anatomic shoulder prosthesis. Methods: Twelve patients (mean age 68.3 years [SD ± 5.4]; 5 female, 7 male) with primary glenohumeral osteoarthritis of the shoulder were enrolled, who underwent total shoulder arthroplasty (TSA) with a stemless total shoulder prosthesis, Total Evolution Shoulder System (TESS®; Biomed, France). The control group consisted of twelve (age and gender matched) patients (mean age 67.8 years; [SD ± 7.1]; 9 female, 3 male), getting a TSA with a standard anatomic stemmed prosthesis, Aequalis® Shoulder (Tournier, Lyon, France). Patients were examined the day before and six months after surgery. The pre- and postoperative Constant Score (CS) was evaluated and proprioception was measured in a 3D video motion analysis study using an active angle-reproduction (AAR) test. Results: Comparing the postoperative CS, there was no significant difference between the groups treated with the TESS® prosthesis (48.0 ± 13.8 points) and the Aequalis® prosthesis (49.3 ± 8.6 points; p = 0.792). There was no significant difference in postoperative proprioception between the TESS® group (7.2° [SD ± 2.8]) and the Aequalis® group(8.7° [SD ± 2.7]; p = 0.196), either. Comparison of in the results of CS and AAR test pre- and postoperatively showed no significant differences between the groups. Discussion: In patients with glenohumeral osteoarthritis, treated with TSA, the functional and the proprioceptive outcome is comparable between a stemless and a standard stemmed anatomic shoulder prosthesis at early followup. Conclusion: Further follow-up is necessary regarding the long-term performance of this prosthesis. Trial registration: Current Controlled Trials DRKS 00007528. Registered 17 November 201

Maml1 acts cooperatively with Gli proteins to regulate Sonic hedgheog signaling pathway

Sonic hedgehog (Shh) signaling is essential for proliferation of cerebellar granule cell progenitors (GCPs) and its misregulation is linked to various disorders, including cerebellar cancer medulloblastoma. The effects of Shh pathway are mediated by the Gli family of transcription factors, which controls the expression of a number of target genes, including Gli1. Here, we identify Mastermind-like 1 (Maml1) as a novel regulator of the Shh signaling since it interacts with Gli proteins, working as a potent transcriptional coactivator. Notably, Maml1 silencing results in a significant reduction of Gli target genes expression, with a negative impact on cell growth of NIH3T3 and Patched1−/− mouse embryonic fibroblasts (MEFs), bearing a constitutively active Shh signaling. Remarkably, Shh pathway activity results severely compromised both in MEFs and GCPs deriving from Maml1−/− mice with an impairment of GCPs proliferation and cerebellum development. Therefore Maml1−/− phenotype mimics aspects of Shh pathway deficiency, suggesting an intrinsic requirement for Maml1 in cerebellum development. The present study shows a new role for Maml1 as a component of Shh signaling, which plays a crucial role in both development and tumorigenesis

cryoWriter: a blotting free cryo-EM preparation system with a climate jet and cover-slip injector

Electron microscopy (EM) introduced a fast and lasting change to structural and cellular biology. However, the sample preparation is still the bottleneck in the cryogenic electron microscopy (cryo-EM) workflow. Classical specimen preparation methods employ a harsh paper-blotting step, and the protein particles are exposed to a damaging air-water interface. Therefore, improved preparation strategies are urgently needed. Here, we present an amended microfluidic sample preparation method, which entirely avoids paper blotting and allows the passivation of the air-water interface during the preparation process. First, a climate jet excludes oxygen from the sample environment and controls the preparation temperature by varying the relative humidity of the grid environment. Second, the integrated "coverslip injector" allows the modulation of the air-water interface of the thin sample layer with effector molecules. We will briefly discuss the climate jet's effect on the stability and dynamics of the sample thin films. Furthermore, we will address the coverslip injector and demonstrate significant improvement in the sample quality

Atomic Force Microscopy-Based Screening of Drug-Excipient Miscibility and Stability of Solid Dispersions

ABSTRACT: Purpose: Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method. Methods: Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature. Results: Combinations that have the potential to form a molecular disperse mixture are identified. Their potential to phase separate is determined through imaging at molecular length scales, which results in short observation time. De-mixing is quantified by phase separation analysis, and the drug/polymer combinations are ranked to identify the most stable combinations. Conclusions: The presented results demonstrate that drug/polymer miscibility and stability of solid dispersions, with many mechanistic details, can be analyzed with Atomic Force Microscopy. The assay allows to identify well-miscible and stable combinations within hours or a few day

Atomic Force Microscopy-Based Screening of Drug-Excipient Miscibility and Stability of Solid Dispersions

PURPOSE: Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method. METHODS: Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature. RESULTS: Combinations that have the potential to form a molecular disperse mixture are identified. Their potential to phase separate is determined through imaging at molecular length scales, which results in short observation time. De-mixing is quantified by phase separation analysis, and the drug/polymer combinations are ranked to identify the most stable combinations. CONCLUSIONS: The presented results demonstrate that drug/polymer miscibility and stability of solid dispersions, with many mechanistic details, can be analyzed with Atomic Force Microscopy. The assay allows to identify well-miscible and stable combinations within hours or a few days

First Study of Combined Blazar Light Curves with FACT and HAWC

For studying variable sources like blazars, it is crucial to achieve unbiased monitoring, either with dedicated telescopes in pointing mode or survey instruments. At TeV energies, the High Altitude Water Cherenkov (HAWC) observatory monitors approximately two thirds of the sky every day. It uses the water Cherenkov technique, which provides an excellent duty cycle independent of weather and season. The First G-APD Cherenkov Telescope (FACT) monitors a small sample of sources with better sensitivity, using the imaging air Cherenkov technique. Thanks to its camera with silicon-based photosensors, FACT features an excellent detector performance and stability and extends its observations to times with strong moonlight, increasing the duty cycle compared to other imaging air Cherenkov telescopes. As FACT and HAWC have overlapping energy ranges, a joint study can exploit the longer daily coverage given that the observatories' locations are offset by 5.3 hours. Furthermore, the better sensitivity of FACT adds a finer resolution of features on hour-long time scales, while the continuous duty cycle of HAWC ensures evenly sampled long-term coverage. Thus, the two instruments complement each other to provide a more complete picture of blazar variability. In this presentation, the first joint study of light curves from the two instruments will be shown, correlating long-term measurements with daily sampling between air and water Cherenkov telescopes. The presented results focus on the study of the variability of the bright blazars Mrk 421 and Mrk 501 during the last two years featuring various flaring activities.Comment: 6 pages, 2 figures. Contribution to the 6th International Symposium on High Energy Gamma-Ray Astronomy (Gamma2016), Heidelberg, Germany. To be published in the AIP Conference Proceeding