Architecture of a consent management suite and integration into IHE-based regional health information networks

<p>Abstract</p> <p>Background</p> <p>The University Hospital Heidelberg is implementing a Regional Health Information Network (RHIN) in the Rhine-Neckar-Region in order to establish a shared-care environment, which is based on established Health IT standards and in particular Integrating the Healthcare Enterprise (IHE). Similar to all other Electronic Health Record (EHR) and Personal Health Record (PHR) approaches the chosen Personal Electronic Health Record (PEHR) architecture relies on the patient's consent in order to share documents and medical data with other care delivery organizations, with the additional requirement that the German legislation explicitly demands a patients' opt-in and does not allow opt-out solutions. This creates two issues: firstly the current IHE consent profile does not address this approach properly and secondly none of the employed intra- and inter-institutional information systems, like almost all systems on the market, offers consent management solutions at all. Hence, the objective of our work is to develop and introduce an extensible architecture for creating, managing and querying patient consents in an IHE-based environment.</p> <p>Methods</p> <p>Based on the features offered by the IHE profile Basic Patient Privacy Consent (BPPC) and literature, the functionalities and components to meet the requirements of a centralized opt-in consent management solution compliant with German legislation have been analyzed. Two services have been developed and integrated into the Heidelberg PEHR.</p> <p>Results</p> <p>The standard-based Consent Management Suite consists of two services. The Consent Management Service is able to receive and store consent documents. It can receive queries concerning a dedicated patient consent, process it and return an answer. It represents a centralized policy enforcement point. The Consent Creator Service allows patients to create their consents electronically. Interfaces to a Master Patient Index (MPI) and a provider index allow to dynamically generate XACML-based policies which are stored in a CDA document to be transferred to the first service. Three workflows have to be considered to integrate the suite into the PEHR: recording the consent, publishing documents and viewing documents.</p> <p>Conclusions</p> <p>Our approach solves the consent issue when using IHE profiles for regional health information networks. It is highly interoperable due to the use of international standards and can hence be used in any other region to leverage consent issues and substantially promote the use of IHE for regional health information networks in general.</p

Structural basis for 5'-ETS recognition by Utp4 at the early stages of ribosome biogenesis

Eukaryotic ribosome biogenesis begins with the co-transcriptional assembly of the 90S pre-ribosome. The ‘U three protein’ (UTP) complexes and snoRNP particles arrange around the nascent pre-ribosomal RNA chaperoning its folding and further maturation. The earliest event in this hierarchical process is the binding of the UTP-A complex to the 5'-end of the pre-ribosomal RNA (5'-ETS). This oligomeric complex predominantly consists of β-propeller and α-solenoidal proteins. Here we present the structure of the Utp4 subunit from the thermophilic fungus Chaetomium thermophilum at 2.15 Å resolution and analyze its function by UV RNA-crosslinking (CRAC) and in context of a recent cryo-EM structure of the 90S pre-ribosome. Utp4 consists of two orthogonal and highly basic β-propellers that perfectly fit the EM-data. The Utp4 structure highlights an unusual Velcro-closure of its C-terminal β-propeller as relevant for protein integrity and potentially Utp8 recognition in the context of the pre-ribosome. We provide a first model of the 5'-ETS RNA from the internally hidden 5'-end up to the region that hybridizes to the 3'-hinge sequence of U3 snoRNA and validate a specific Utp4/5'-ETS interaction by CRAC analysis.This work was supported by Deutsche Forschungsgemeinschaft (DFG) (SFB638, Z4 to I. S. and HU363/15-1 to E.H. and the Leibniz programme to I.S.); Cluster of Excellence CellNetworks (EcTOP1 to I.S. and E.H.); Funding for open access charge: DFG [Leibniz Programme]. M.K. was funded by a Kekule Fellowship (VCI)

Effects of Short Term Adiponectin Receptor Agonism on Cardiac Function and Energetics in Diabetic db/db Mice.

Objective Impaired cardiac efficiency is a hallmark of diabetic cardiomyopathy in models of type 2 diabetes. Adiponectin receptor 1 (AdipoR1) deficiency impairs cardiac efficiency in non-diabetic mice, suggesting that hypoadiponectinemia in type 2 diabetes may contribute to impaired cardiac efficiency due to compromised AdipoR1 signaling. Thus, we investigated whether targeting cardiac adiponectin receptors may improve cardiac function and energetics, and attenuate diabetic cardiomyopathy in type 2 diabetic mice. Methods A non-selective adiponectin receptor agonist, AdipoRon, and vehicle were injected intraperitoneally into Eight-week-old db/db or C57BLKS/J mice for 10 days. Cardiac morphology and function were evaluated by echocardiography and working heart perfusions. Results Based on echocardiography, AdipoRon treatment did not alter ejection fraction, left ventricular diameters or left ventricular wall thickness in db/db mice compared to vehicle-treated mice. In isolated working hearts, an impairment in cardiac output and efficiency in db/db mice was not improved by AdipoRon. Mitochondrial respiratory capacity, respiration in the presence of oligomycin, and 4-hydroxynonenal levels were similar among all groups. However, AdipoRon induced a marked shift in the substrate oxidation pattern in db/db mice towards increased reliance on glucose utilization. In parallel, the diabetes-associated increase in serum triglyceride levels in vehicle-treated db/db mice was blunted by AdipoRon treatment, while an increase in myocardial triglycerides in vehicle-treated db/db mice was not altered by AdipoRon treatment. Conclusion AdipoRon treatment shifts myocardial substrate preference towards increased glucose utilization, likely by decreasing fatty acid delivery to the heart, but was not sufficient to improve cardiac output and efficiency in db/db mice

Überlebensstrategien von Musiker*innen während der Pandemie

Die Musik-, Kunst- und Kulturszene ist vielfältig und lebt von Individualität. An der Diskussionsrunde zum Thema „Überlebensstrategien während der Pandemie“ nehmen die Musiker*innen Lindy Huppertsberg, Pat Appleton, Martin Verdonk, Tommy Baldu und Markus Birkle am 10.05.2021 teil. Die Teilnehmer*innen der Diskussionsrunde erwirtschaften ihr Einkommen primär über Konzertgagen und sind als freischaffende Musiker*innen etabliert und erfolgreich in der Musikwelt tätig. Trotz großer Übereinstimmungen werden Strategien während der Krise bemerkenswert individuell gewählt. Ebenso vielschichtig ist der Fokus bei der Karriereplanung und Auswahl der musikalischen Projekte. Zwei essenzielle Themenbereiche kristallisieren sich im Verlauf der Unterhaltung heraus: Zum einen die persönlichen singulären Strategien für ein wirtschaftliches Überleben, zum anderen die Auseinandersetzung mit dem Verlust der Möglichkeit auf Resonanz und Empathie mit Mitmusiker*innen und dem Publikum. Die Frage wird aufgeworfen, ob Kulturschaffende einer Gesellschaft eine emotionale Stimme geben

Structural basis for 5'-ETS recognition by Utp4 at the early stages of ribosome biogenesis.

Eukaryotic ribosome biogenesis begins with the co-transcriptional assembly of the 90S pre-ribosome. The 'U three protein' (UTP) complexes and snoRNP particles arrange around the nascent pre-ribosomal RNA chaperoning its folding and further maturation. The earliest event in this hierarchical process is the binding of the UTP-A complex to the 5'-end of the pre-ribosomal RNA (5'-ETS). This oligomeric complex predominantly consists of β-propeller and α-solenoidal proteins. Here we present the structure of the Utp4 subunit from the thermophilic fungus Chaetomium thermophilum at 2.15 Å resolution and analyze its function by UV RNA-crosslinking (CRAC) and in context of a recent cryo-EM structure of the 90S pre-ribosome. Utp4 consists of two orthogonal and highly basic β-propellers that perfectly fit the EM-data. The Utp4 structure highlights an unusual Velcro-closure of its C-terminal β-propeller as relevant for protein integrity and potentially Utp8 recognition in the context of the pre-ribosome. We provide a first model of the 5'-ETS RNA from the internally hidden 5'-end up to the region that hybridizes to the 3'-hinge sequence of U3 snoRNA and validate a specific Utp4/5'-ETS interaction by CRAC analysis

Model of co-transcriptional assembly of the 90S pre-ribosome.

<p>The nascent 5'-ETS (black line) recruits the early 90S modules (UTP-A, UTP-B, and U3 snoRNP) in a hierarchical fashion, with the UTP-A complex being the first one that binds to the extreme 5'-end of the pre-rRNA. This early assembly intermediate, together with the subsequently transcribed pre-18S rRNA (yellow line) and additional factors, forms the 90S pre-ribosome. Complexes are labeled accordingly. The 3'-hinge region is highlighted in pink. Figure is adapted from [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0178752#pone.0178752.ref009" target="_blank">9</a>].</p

Uncommon Velcro-closure of the C-terminal β-propeller 2.

<p><b>(A)</b> Schematic representation of the last blade 14 of Utp4. The four β-strands of the blade are represented as arrows in different colours: 14A and B (C-terminus of β-propeller 2, red), 14C (N-terminus of β-propeller 1, blue), and 14D ((His)₆-TEV-tag, grey). <b>(B)</b> Close-up of blade 14 complemented by the very N-terminus of the polypeptide chain, forming an uncommon parallel β-strand 14C (blue) and the artificial TEV site (grey) forming an antiparallel β-strand 14D. The highly conserved residues and their hydrogen-bonding network stabilizing the blade and therefore the Velcro-closure of β-propeller 2 are represented in sticks. Salt-bridges are indicated by dashed lines.</p

Structure of Utp4 from <i>Chaetomium thermophilum</i>.

<p><b>(A)</b> Domain architecture of Utp4. Domains present in the crystal structure are given by residue numbers and are highlighted in colour. The N-terminal β-propeller 1 covers residues from 38 to 381 and is shown in blue and the C-terminal β-propeller 2 (residues 393 to 890) in red. (His)₆-tag and TEV-site are represented in grey. <b>(B)</b> The overall structure of Utp4 presents two 7-bladed β-propellers in tandem. N- and C-termini are indicated and blades are numbered. Each β-blade consists of four β-strands (ABCD). <b>(C)</b> Tertiary interaction of β-propellers. A hairpin between β-strands 2A and 2B of β-propeller 1 packs against an α-helix between β-strands 10D and 11A of β-propeller 2 (view rotated by 90° in respect to <b>A</b>). <b>(D)</b> Surface charge (left panel) and conservation (right panel) of Utp4. The electrostatic surface (red: negative, blue: positive, contoured at ±5 <i>k</i>_<i>B</i>T/e) indicates extended positively charged patches in both β-propellers. Sequence conservation mapped on the molecular surface (magenta: conserved, cyan: variable) is most pronounced around a highly positive charged patch at the N-terminus (indicated with ‘N’).</p