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lities that change the anatomy and physiology of individual patients, with new targets such as the abnormal metabolic signal.A future-oriented approach is the application of Digital Twins for process development, optimization and finally during manufacturing. Digital Twins are detailed virtual representations of bioprocesses with predictive capabilities. In biotechnology, Digital Twins can be used to monitor processes and to provide data for process control and optimization. Central and crucial components of Digital Twins are mathematical process models, which are capable to describe and predict cultivations with high fidelity. Detailed mechanistic models in particular are suitable for both use in Digital Twins and for the development of process control strategies.In this chapter the requirements that process models must fulfil in order to be used for process optimization and finally in Digital Twins will be described. Different types of models, including mechanistic as well as compartmentalized models, are outlined and their application in Digital Twins and for process optimization is explained. Finally, a structured, compartmentalized process model, which was specifically designed for process optimization and has already been used in Digital Twins, is highlighted.Glycosylation is a key factor determining the pharmacological properties of biotherapeutics, including their stability, solubility, bioavailability, pharmacokinetics, and immunogenicity. As such, comprehensive information about glycosylation of biotherapeutics is critical to demonstrate similarity. Regulatory agencies also require extensive documentation of the comprehensive analyses of glycosylation-related critical quality attributes (CQAs) during the development, manufacturing, and release of biosimilars. Mass spectrometry has catalysed tremendous advancements in the characterisation of glycosylation CQAs of biotherapeutics. Here we provide a perspective overview on the MS-based technologies relevant for biotherapeutic product characterisation with an emphasis on the recent developments that allow determination of glycosylation features such as site of glycosylation, sialic acid linkage, glycan structure, and content.

The optimal timing for surgery of congenital nasolacrimal duct obstruction (CNLDO) is controversially discussed. An aspect that has not yet been studied in this context is the path from first symptoms to the initial diagnosis and surgical treatment with respect to social factors and burden of suffering. The aim of this study was areal-life analysis of the entire course of the disease.

Monocentric, retrospective study evaluating children with CNLDO (n = 147) who underwent surgery. The minimum follow-up was 3months (26 ± 14months). The patient information was collected by telephone using aquestionnaire especially created for this purpose. The famelial suffering was measured on ascale of 1-5.

Data were collected from 118 parents with amean follow-up of 26months. First symptoms occurred at a median age of 1month. The diagnosis was confirmed through apediatrician/ophthalmologist after amedian of 6months. An assignment to areferral center for surgical treatment was performed amedian of 18months after the firsnt, an early consultation at a surgical department is recommended.Acquired tumors of lymphatic vessels are rare. Clinically, progressive lymphangioma usually appears as circumscribed plaques of small to medium size. In contrast, our case of a 13-year-old boy demonstrates a case of progressive lymphangioma with a solitary large indurated plaque. No extracutaneous manifestation was found. Systemic therapy with corticosteroids and methotrexate resulted in an improvement of the patient’s condition. Dependent on clinical course and appearance of the disease, therapy with mTOR inhibitors may be considered as a therapeutic option.A 64-year old man developed alopecia universalis after one month of treatment with metformin and sitagliptin, a dipeptidyl peptidase‑4 (DPP-4) inhibitor. Diabetes treatment was changed to another genericum of sitagliptin and dapagliflozin. Following our recommendation, sitagliptin was interrupted and monotherapy with dapagliflozin was continued. After 6 weeks, sitagliptin was reassumed due to unsatisfactory diabetes control. Alopecia did not improve. We suspect a connection between DPP‑4 inhibition and development of alopecia due to its immunological potential. We assume that the treatment interruption might have been too short to induce regrowth of hair. Eliglustat DPP‑4 may result in both inhibition and activation of the immune system.Transient receptor potential melastatin 4 (TRPM4) cation channels act in cardiomyocytes as a negative modulator of the L-type Ca2+ current. Ubiquitous Trpm4 deletion in mice leads to an increased β-adrenergic inotropy in healthy mice as well as after myocardial infarction. In this study, we set out to investigate cardiac inotropy in mice with cardiomyocyte-specific Trpm4 deletion. The results guided us to investigate the relevance of TRPM4 for catecholamine-evoked Ca2+ signaling in cardiomyocytes and inotropy in vivo in TRPM4-deficient mouse models of different genetic background. Cardiac hemodynamics were investigated using pressure-volume analysis. Surprisingly, an increased β-adrenergic inotropy was observed in global TRPM4-deficient mice on a 129SvJ genetic background, but the inotropic response was unaltered in mice with global and cardiomyocyte-specific TRPM4 deletion on the C57Bl/6N background. We found that the expression of TRPM4 proteins is about 78 ± 10% higher in wild-type mice on the 129SvJ versus C57Bl/6N background. In accordance with contractility measurements, our analysis of the intracellular Ca2+ transients revealed an increase in ISO-evoked Ca2+ rise in Trpm4-deficient cardiomyocytes of the 129SvJ strain, but not of the C57Bl/6N strain. No significant differences were observed between the two mouse strains in the expression of other regulators of cardiomyocyte Ca2+ homeostasis. We conclude that the relevance of TRPM4 for cardiac contractility depends on homeostatic TRPM4 expression levels or the genetic endowment in different mouse strains as well as on the health/disease status. Therefore, the concept of inhibiting TRPM4 channels to improve cardiac contractility needs to be carefully explored in specific strains and species and prospectively in different genetically diverse populations of patients.