The digital transformation of healthcare - An interview with Werner Dorfmeister.

In this interview, Werner Dorfmeister, a Vice President at DasLab and a former Global Sales Director at Karl Storz, reports on the current developments of digital technologies in the field of medical instruments and services. It is a sector where digitalization affects all processes within hospitals as well as pre- and post-surgical activities. Due to the many actors involved, who use different information systems, and the strong regulation of the entire healthcare sector, crafting digital solutions is complex, but nevertheless promising and necessary. Among the key areas mentioned in the interview are telemedicine, hospital and patient management and a sector-wide digital infrastructure. Digital platforms are described as important enablers to address current inefficiencies and to leverage future potentials towards patient-orientation, such as digital patient pathways.

Werner Dorfmeister was Global Sales Director at Karl Storz SE & Co. KG, a global producer of medical devices headquartered in Tuttlingen, Germany. The company was founded in 1945 and employs about 6'000 people today with annual revenues of approximately two billion Euros. Starting with the invention of the endoscope, Karl Storz has a long tradition in pioneering innovations in the fields of classical, heart and neuro surgery as well as gynecology and otolaryngology. The company is one of the largest producers of surgery instruments and has constantly enhanced its product portfolio with electronic devices and conceptualizing entirely integrated operating rooms. In March 2021, Werner joined DasLab GmbH, a German start-up company that focuses on the digitalization in the field of laboratory medicine. As Vice President Business and Partnerships, he is not only involved in the diagnostics of the Corona pandemic, but also investigates perspectives related to the "digital path" among laboratories, patients and healthcare organizations such as hospitals, physicians and insurance companies. Before joining Karl Storz, he was responsible for global solutions and commercial functions at the B2B services firm DXC.technology, which is a spin-off from Hewlett Packard Enterprises where Werner has worked in various positions since 2008. Prior to this position, he was sales manager at VMware and Microsoft. Werner has a degree in management with an emphasis in business informatics from the Donau University Krems and an MBA in media management from St. Pölten University of Applied Sciences in Austria. Since 1998, he is also a visiting professor at Donau University Krems and since 2014 he is a member of Electronic Markets' advisory board. The pictures show him on the left followed by the interviewers Rainer Alt and Hans-Dieter Zimmermann.

Capillary electrophoresis-mass spectrometry for the direct analysis of glyphosate: method development and application to beer beverages and environmental studies.

In this study, we developed and validated a CE-TOF-MS method for the quantification of glyphosate (N-(phosphonomethyl)glycine) and its major degradation product aminomethylphosphonic acid (AMPA) in different samples including beer, media from toxicological analysis with Daphnia magna, and sorption experiments. Using a background electrolyte (BGE) of very low pH, where glyphosate is still negatively charged but many matrix components become neutral or protonated, a very high separation selectivity was reached. The presence of inorganic salts in the sample was advantageous with regard to preconcentration via transient isotachophoresis. The advantages of our new method are the following: no derivatization is needed, high separation selectivity and thus matrix tolerance, speed of analysis, limits of detection suitable for many applications in food and environmental science, negligible disturbance by metal chelation. LODs for glyphosate were < 5 µg/L for both aqueous and beer samples, the linear range in aqueous samples was 5-3000 µg/L, for beer samples 10-3000 µg/L. For AMPA, LODs were 3.3 and 30.6 µg/L, and the linear range 10-3000 µg/L and 50-3000 µg/L, for aqueous and beer samples, respectively. Recoveries in beer samples for glyphosate were 94.3-110.7% and for AMPA 80.2-100.4%. We analyzed 12 German and 2 Danish beer samples. Quantification of glyphosate and AMPA was possible using isotopically labeled standards without enrichment, purification, or dilution, only degassing and filtration were required for sample preparation. Finally, we demonstrate the applicability of the method for other strong acids, relevant in food and environmental sciences such as N-acetyl glyphosate, N-acetyl AMPA (present in some glyphosate resistant crop), trifluoroacetic acid, 2-methyl-4-chlorophenoxyacetic acid, glufosinate and its degradation product 3-(methylphosphinico)propionic acid, oxamic acid, and others.

3D-electron microscopic characterization of interstitial cells in the human bladder upper lamina propria.

AIMS: To explore the ultrastructure of interstitial cells in the upper lamina propria of the human bladder, to describe the spatial relationships and to investigate cell-cell contacts. METHODS: Focused ion beam scanning electron microscopy (FIB-SEM), 3-View SEM and confocal laser scanning microscopy were used to analyze the 3D ultrastructure of the upper lamina propria in male and female human bladders. RESULTS: 3View-SEM image stacks as large as 59 × 59 × 17 µm3 (xyz) at a resolution of 16 × 16 × 50 nm3 and high resolution (5 × 5 × 10 nm3 ) FIB-SEM stacks could be analyzed. Interstitial cells with myoid differentiation (mIC) and fibroblast like interstitial cells (fIC) were the major cell types in the upper lamina propria. The flat, sheet-like ICs were oriented strictly parallel to the urothelium. No spindle shaped cells were present. We furthermore identified one branched cell (bIC) with several processes contacting urothelial cells by penetrating the basal membrane. This cell did not make any contacts to other ICs within the upper lamina propria. We found no evidence for the occurrence of telocytes in the upper lamina propria. CONCLUSIONS: Comprehensive 3D-ultrastructural analysis of the human bladder confirmed distinct subtypes of interstitial cells. We provide evidence for a foremost unknown direct connection between a branched interstitial cell and urothelial cells of which the functional role has still to be elucidated. 3D-ultrastructure analyses at high resolution are needed to further define the subpopulations of lamina propria cells and cell-cell interactions.

Autophagy initiation by ULK complex assembly on ER tubulovesicular regions marked by ATG9 vesicles.

Autophagosome formation requires sequential translocation of autophagy-specific proteins to membranes enriched in PI3P and connected to the ER. Preceding this, the earliest autophagy-specific structure forming de novo is a small punctum of the ULK1 complex. The provenance of this structure and its mode of formation are unknown. We show that the ULK1 structure emerges from regions, where ATG9 vesicles align with the ER and its formation requires ER exit and coatomer function. Super-resolution microscopy reveals that the ULK1 compartment consists of regularly assembled punctate elements that cluster in progressively larger spherical structures and associates uniquely with the early autophagy machinery. Correlative electron microscopy after live imaging shows tubulovesicular membranes present at the locus of this structure. We propose that the nucleation of autophagosomes occurs in regions, where the ULK1 complex coalesces with ER and the ATG9 compartment.

FIB-SEM tomography of human skin telocytes and their extracellular vesicles.

We have shown in 2012 the existence of telocytes (TCs) in human dermis. TCs were described by transmission electron microscopy (TEM) as interstitial cells located in non-epithelial spaces (stroma) of many organs (see www.telocytes.com). TCs have very long prolongations (tens to hundreds micrometers) named Telopodes (Tps). These Tps have a special conformation with dilated portions named podoms (containing mitochondria, endoplasmic reticulum and caveolae) and very thin segments (below resolving power of light microscopy), called podomers. To show the real 3D architecture of TC network, we used the most advanced available electron microscope technology: focused ion beam scanning electron microscopy (FIB-SEM) tomography. Generally, 3D reconstruction of dermal TCs by FIB-SEM tomography revealed the existence of Tps with various conformations: (i) long, flattened irregular veils (ribbon-like segments) with knobs, corresponding to podoms, and (ii) tubular structures (podomers) with uneven calibre because of irregular dilations (knobs) - the podoms. FIB-SEM tomography also showed numerous extracellular vesicles (diameter 438.6 ± 149.1 nm, n = 30) released by a human dermal TC. Our data might be useful for understanding the role(s) of TCs in intercellular signalling and communication, as well as for comprehension of pathologies like scleroderma, multiple sclerosis, psoriasis, etc.

Content delivery to newly forming Weibel-Palade bodies is facilitated by multiple connections with the Golgi apparatus.

Weibel-Palade bodies (WPBs) comprise an on-demand storage organelle within vascular endothelial cells. It's major component, the hemostatic protein von Willebrand factor (VWF), is known to assemble into long helical tubules and is hypothesized to drive WPB biogenesis. However, electron micrographs of WPBs at the Golgi apparatus show that these forming WPBs contain very little tubular VWF compared with mature peripheral WPBs, which raises questions on the mechanisms that increase the VWF content and facilitate vesicle growth. Using correlative light and electron microscopy and electron tomography, we investigated WPB biogenesis in time. We reveal that forming WPBs maintain multiple connections to the Golgi apparatus throughout their biogenesis. Also by volume scanning electron microscopy, we confirmed the presence of these connections linking WPBs and the Golgi apparatus. From electron tomograms, we provided evidence that nontubular VWF is added to WPBs, which suggested that tubule formation occurs in the WPB lumen. During this process, the Golgi membrane and clathrin seem to provide a scaffold to align forming VWF tubules. Overall, our data show that multiple connections with the Golgi facilitate content delivery and indicate that the Golgi appears to provide a framework to determine the overall size and dimensions of newly forming WPBs.