20 research outputs found
In Vitro Ceramic Scaffold Mineralization: Comparison Between Histological and Micro-Computed Tomographical Analysis
The porous structure of beta-tricalcium phosphate (β-TCP) scaffolds was assessed by conventional histomorphometry and micro-computed tomography (micro-CT) to evaluate the substitutability of time-consuming histomorphometry by rapid micro-CT. Extracellular matrix mineralization on human mesenchymal stem cell seeded β-TCP scaffolds was scanned by means of micro-CT after 6weeks in cultivation and evaluated morphometrically. For the histomorphometric analysis, undecalcified sections were prepared in the mediosagittal plane of the cylindrical tissue-engineered constructs. The sections were scanned at a nominal resolution of 8μm and stained with von Kossa and Toluidine Blue. Pores were analyzed with both methods for morphometrical parameters such as horizontal/vertical diameter and pore/mineralized tissue area. Results showed highly significant correlations between histomorphometry and micro-CT for pore horizontal length (r=0.95), pore vertical length (r=0.96), pore area (r=0.97), and mineralized tissue area (r=0.82). Mean percentage differences between histomorphometry and micro-CT measurements ranged from 1.4% (pore vertical diameter) to 14.0% (area of mineralized tissue). With its high image precision, micro-CT qualifies as an additional tool for endpoint evaluation measurements of mineralized tissue development within tissue-engineered constructs also in ceramic scaffold
»Twist«: Das Kippbild als Metapher der Literatur. Das Beispiel der Stoffe Friedrich Dürrenmatts
Comparing Methods of Characterizing Energetic Disorder in Organic Solar Cells
The energetic disorder has been known for decades to limit the performance of structurally disordered semiconductors such as amorphous silicon and organic semiconductors. However, in the past years, high-performance organic solar cells have emerged showing a continuously reduced amount of energetic disorder. While searching for future high-efficiency material systems, it is therefore important to correctly characterize this energetic disorder. While there are several techniques in the literature, the most common approaches to probe the density of defect states are using optical excitation as in external quantum efficiency measurements, or sequential filling of the tail states by applying an external voltage as in admittance spectroscopy. A metanalysis of available literature, as well as the experiments using four characterization techniques on two material systems, reveal that electrical, voltage-dependent measurements frequently yield higher values of energetic disorder than optical measurements. With drift-diffusion simulations, it is demonstrated that the approaches probe different energy ranges of the subband-gap density of states. The limitations of the techniques are further explored and it is found that extraction of information from a capacitance-voltage curve can be inhibited by internal series resistance. Thereby, the discrepancies between measurement techniques with sensitivity to different energy ranges and electronic parameters are explained
In Vitro Ceramic Scaffold Mineralization: Comparison Between Histological and Micro-Computed Tomographical Analysis
ISSN:1573-9686ISSN:0191-5649ISSN:0090-696
Total Plasma Exchange in Neuromuscular Junction Disorders—A Single-Center, Retrospective Analysis of the Efficacy, Safety and Potential Diagnostic Properties in Doubtful Diagnosis
Neuromuscular junction disorders (NJDs) are a heterogeneous group of diseases including myasthenia gravis (MG). In some cases, patients are present with myasthenic symptoms without evidence of autoimmune antibodies, making diagnosis challenging. Total plasma exchange (TPE) has proven efficacy in NJDs. The objective is to describe the safety and efficacy of TPE in NJD patients with questionable disease activity or uncertain diagnosis in order to assess the diagnostic potential of TPE. We report an observational, retrospective cohort study of clinical routine data. All the data were derived from the electronic medical records of the Department of Neurology at University Hospital Essen. We searched for patients with NJDs between 1 July 2018 and 30 June 2021. Of the 303 patients who presented to the department with NJDs, 20 were treated with TPE; 9 patients did not show a measurable benefit from TPE (45%), 6 of whom were diagnosed with seronegative MG. Of these, 3 (50%) had long-standing ocular symptoms. There were decreases in the mean arterial pressure, hemoglobin, hematocrit and fibrinogen during treatment, which were not considered clinically relevant. In (seronegative) myasthenic patients, TPE may help to verify an uncertain diagnosis or to reveal possible muscle damage, allowing unnecessary therapy to be avoided
Neurofilament Heavy Chain and Tau Protein Are Not Elevated in Cerebrospinal Fluid of Adult Patients with Spinal Muscular Atrophy during Loading with Nusinersen
Nusinersen is the first approved drug for the treatment of spinal muscular atrophy (SMA). Treatment of SMA with nusinersen is based on a fixed dosing regimen. For other motoneuron diseases, such as amyotrophic lateral sclerosis (ALS), biomarkers are available for clinical diagnostics; however, no such biomarkers have yet been found for SMA. Serum and cerebrospinal fluid (CSF) samples of 11 patients with adult SMA type 3 were prospectively collected and analyzed during loading with nusinersen. Neurofilament heavy chain, tau protein, S100B protein, and neuron-specific enolase were investigated as potential biomarkers of motor neuron destruction. No significant pathological alterations in levels of neurofilament heavy chain, tau protein, or S100B protein were detected in the CSF or blood samples under baseline conditions or during loading with nusinersen. Neuron-specific enolase was marginally elevated in CSF and blood samples without significant alteration during treatment. In a mixed cohort of adult patients with SMA type 3, neurofilament heavy chain, tau protein, S100B protein, and neuron-specific enolase do not serve as potential biomarkers during the loading phase of nusinersen. The slow progression rate of SMA type 3 may not lead to detectable elevation of levels of these common markers of axonal degradation
Assessment of Bulbar Function in Adult Patients with 5q-SMA Type 2 and 3 under Treatment with Nusinersen
The antisense oligonucleotide nusinersen has been shown to improve trunk and limb motor function in patients with spinal muscular atrophy (SMA). Bulbar dysfunction, which is regularly present in SMA, is not captured by standard motor scores, and validated measurement instruments to assess it have not yet been established. Data on whether and how bulbar function changes under gene-based therapies in adult SMA patients are also unavailable. Here, we present data on the course of bulbar dysfunction assessed prospectively before nusinersen treatment initiation and 6 and 14 months later in 23 adult SMA patients using the Sydney Swallow Questionnaire (SSQ) and the bulbar subscore of the Amyotrophic Lateral Sclerosis Functional Rating Scale Revised (ALSFRS-R). While no improvement in bulbar scores was observed under treatment with nusinersen, the absence of a decline still implies a therapeutic effect of nusinersen on bulbar dysfunction. The results of this study aim to contribute to a standardized assessment of bulbar function in adult SMA patients, which may show therapeutic effects of gene-based therapies that are not evident from standard motor scores
Neurofilament Heavy Chain and Tau Protein Are Not Elevated in Cerebrospinal Fluid of Adult Patients with Spinal Muscular Atrophy during Loading with Nusinersen
Nusinersen treatment in adult patients with spinal muscular atrophy: a safety analysis of laboratory parameters
Background!#!Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) that improves motor function in patients with spinal muscular atrophy (SMA). In addition to efficacy, the safety of a therapy is the decisive factor for the success of the treatment. For some ASOs, various organ toxicities have been described, such as thrombocytopenia, renal and liver impairment, or coagulation abnormalities. However, systematic data on laboratory parameters under treatment with nusinersen are mainly available from studies in infants and children. Therefore, our aim was to assess the safety of nusinersen therapy in adult SMA patients.!##!Methods!#!Laboratory data from 404 nusinersen injections performed in 50 adult patients with SMA type 2 and type 3 were retrospectively analyzed.!##!Results!#!The total observation period was 76.9 patient-years, and patients received up to 12 injections. Our data provides no new safety concerns. In cerebrospinal fluid (CSF), the mean white blood cell count and lactate remained stable over time. Total CSF protein increased by 2.9 mg/dL. No change in mean platelet count was observed under therapy. Only one patient showed sporadic mild thrombocytopenia. Coagulation parameters and inflammatory markers were stable. The mean creatinine level decreased by 0.09 mg/dL. Analysis of mean liver enzyme levels revealed no relevant changes during treatment.!##!Conclusion!#!Our data demonstrate a favorable safety profile of nusinersen therapy in adult SMA patients under longer-term 'real-world' conditions. In particular, we found no evidence of clinically relevant platelet declines, coagulopathies, or renal or hepatic organ toxicities, which are common concerns with the use of ASOs