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Introduction: The German PID-NET registry was founded in 2009, serving as the first national registry of patients with primary immunodeficiencies (PID) in Germany. It is part of the European Society for Immunodeficiencies (ESID) registry. The primary purpose of the registry is to gather data on the epidemiology, diagnostic delay, diagnosis, and treatment of PIDs.
Methods: Clinical and laboratory data was collected from 2,453 patients from 36 German PID centres in an online registry. Data was analysed with the software Stata® and Excel.
Results: The minimum prevalence of PID in Germany is 2.72 per 100,000 inhabitants. Among patients aged 1–25, there was a clear predominance of males. The median age of living patients ranged between 7 and 40 years, depending on the respective PID. Predominantly antibody disorders were the most prevalent group with 57% of all 2,453 PID patients (including 728 CVID patients). A gene defect was identified in 36% of patients. Familial cases were observed in 21% of patients. The age of onset for presenting symptoms ranged from birth to late adulthood (range 0–88 years). Presenting symptoms comprised infections (74%) and immune dysregulation (22%). Ninety-three patients were diagnosed without prior clinical symptoms. Regarding the general and clinical diagnostic delay, no PID had undergone a slight decrease within the last decade. However, both, SCID and hyper IgE- syndrome showed a substantial improvement in shortening the time between onset of symptoms and genetic diagnosis. Regarding treatment, 49% of all patients received immunoglobulin G (IgG) substitution (70%—subcutaneous; 29%—intravenous; 1%—unknown). Three-hundred patients underwent at least one hematopoietic stem cell transplantation (HSCT). Five patients had gene therapy.
Conclusion: The German PID-NET registry is a precious tool for physicians, researchers, the pharmaceutical industry, politicians, and ultimately the patients, for whom the outcomes will eventually lead to a more timely diagnosis and better treatment.
Patients with ataxia-telangiectasia (A-T) suffer from progressive cerebellar ataxia, immunodeficiency, respiratory failure, and cancer susceptibility. From a clinical point of view, A-T patients with IgA deficiency show more symptoms and may have a poorer prognosis. In this study, we analyzed mortality and immunity data of 659 A-T patients with regard to IgA deficiency collected from the European Society for Immunodeficiencies (ESID) registry and from 66 patients with classical A-T who attended at the Frankfurt Goethe-University between 2012 and 2018. We studied peripheral B- and T-cell subsets and T-cell repertoire of the Frankfurt cohort and survival rates of all A-T patients in the ESID registry. Patients with A-T have significant alterations in their lymphocyte phenotypes. All subsets (CD3, CD4, CD8, CD19, CD4/CD45RA, and CD8/CD45RA) were significantly diminished compared to standard values. Patients with IgA deficiency (n = 35) had significantly lower lymphocyte counts compared to A-T patients without IgA deficiency (n = 31) due to a further decrease of naïve CD4 T-cells, central memory CD4 cells, and regulatory T-cells. Although both patient groups showed affected TCR-ß repertoires compared to controls, no differences could be detected between patients with and without IgA deficiency. Overall survival of patients with IgA deficiency was significantly diminished. For the first time, our data show that patients with IgA deficiency have significantly lower lymphocyte counts and subsets, which are accompanied with reduced survival, compared to A-T patients without IgA deficiency. IgA, a simple surrogate marker, is indicating the poorest prognosis for classical A-T patients. Both non-interventional clinical trials were registered at clinicaltrials.gov 2012 (Susceptibility to infections in ataxia-telangiectasia; NCT02345135) and 2017 (Susceptibility to Infections, tumor risk and liver disease in patients with ataxia-telangiectasia; NCT03357978)
This case series assessed a commercial airline flight from Tel Aviv, Israel, to Frankfurt, Germany, that occurred on March 9th, 2020. Among 102 passengers on a Boeing 737-900 aircraft were 24 members of a tourist group. Starting 7 days earlier, the group had contact with a hotel manager who later received a diagnosis of coronavirus disease 2019 (COVID-19). No member of the group had received a diagnosis of COVID-19 before the flight, and no measures to prevent transmission (eg, wearing of masks) had been applied. The flight duration was 4 hours 40 minutes.
Data on the long-term behavior of computer-aided designed/computer-aided manufactured (CAD-CAM) resin-based composites are sparse. To achieve higher predictability on the mechanical behavior of these materials, the aim of the study was to establish a mathematical relationship between the material thickness of resin-based materials and their fracture load. The tested materials were Lava Ultimate (LU), Cerasmart (GC), Enamic (EN), and Telio CAD (TC). For this purpose, 60 specimens were prepared, each with five different material thicknesses between 0.4 mm and 1.6 mm (N = 60, n = 12). The fracture load of all specimens was determined using the biaxial flexural strength test (DIN EN ISO 6872). Regression curves were fitted to the results and their coefficient of determination (R2) was computed. Cubic regression curves showed the best R2 approximation (LU R2 = 0.947, GC R2 = 0.971, VE R2 = 0.981, TC R2 = 0.971) to the fracture load values. These findings imply that the fracture load of all tested resin-based materials has a cubic relationship to material thickness. By means of a cubic equation and material-specific fracture load coefficients, the fracture load can be calculated when material thickness is given. The approach enables a better predictability for resin-based restorations for the individual patient. Hence, the methodology might be reasonably applied to other restorative materials.
Für das Verständnis der Proteinfaltung ist es von Interesse, die phi,psi-Torsionswinkelverteilung und deren Abhängigkeiten innerhalb einer Polypeptidkette zu kennen. Mit der in dieser Arbeit verwendeten Kombination aus MD-Simulation und NMR-Spektroskopie wird die Abhängigkeit der Konformationsverteilung kurzer alaninbasierter Modellpeptide mit einer Genauigkeit von 5 % bestimmt. Die Berechnung der thermischen Populationen der einzelnen Konformationen beruht auf einer Minimierung der Differenz aus experimentellen und berechneten skalaren Kopplungskonstanten. Trialanin populiert überwiegend den Bereich der Polyprolin Typ II Helix (~ 90 %) und daneben den beta-Faltblattbereich mit ca. 10%, jedoch nicht den alphaR-helicalen Bereich. Diese Konformationsverteilung ändert sich nicht signifikant mit zunehmender Kettenlänge in der Peptidreihe Ala3 bis Ala7. Das in der Seitenkette verzweigte Trivalin populiert dagegen alle drei Konformationsbereiche signifikant. Aufgrund der Periodizität der Torsionswinkel populiert Triglycin einen zusammenhängenden Bereich, der sich an den vier Ecken des Ramachandran-Diagramms befindet. Zudem befindet es sich in einem langsamen konformationellen Gleichgewicht zwischen der cis- und trans-Konformation der Peptidbindung. Die Temperaturabhängigkeit der Konformationsverteilung wird am Beispiel von Trialanin untersucht. Die 3J(HN,Ha) Kopplungskonstanten nehmen linear mit der Temperatur zu. Dies ist auf eine Zunahme des beta-Faltblattanteils zurückzuführen und kann theoretisch beschrieben werden. Die Konformationsverteilung der Trialaninsequenz innerhalb einer heteropolymeren Aminosäuresequenz ist von der Kettenlänge der an dem N- und C-Terminus angefügten heteropolymeren Aminosäuresequenz abhängig. Dies wird an zwei Peptiden, abgeleitet von der Sequenz des Proteins Lysozym aus Hühnereiweiß, gezeigt. Das kürzere Peptid hat an beiden Enden jeweils drei Aminosäurereste angefügt, das längere jeweils acht Aminosäurereste. Die Konformationsverteilung der Trialanisequenz des kürzeren Peptids entspricht nahezu der in der Peptidreihe Ala3 bis Ala7. Die Verteilung des längeren Peptids ist dagegen deutlich verschieden (~ 35% alphaR-helicaler Anteil). Die 1HN und 15N chemischen Verschiebungen der Trialaninsequenz des längeren Peptids sind mit denen des entfalteten Lysozym-Proteins identisch und demzufolge aller wahrscheinlichkeit nach auch die Konformationsverteilung. Kurze homopolymere Peptide eignen sich deshalb nicht als Modell für Aminosäuresequenzen in längeren heteropolymeren Peptiden.