Die Spontanheilungsversuche des vorderen Kreuzbands : eine experimentelle Untersuchung

Fragestellung Spontanheilungen von Rupturen des vorderen Kreuzbandes (VKB) wurden wiederholt mittels MRT beschrieben. In grundlegenden tierexperimentellen Untersuchungen wird geschlussfolgert, dass es keine Regeneration gäbe. Die Morphologie der Spontanheilung des VKB wurde im Tiermodell des Kaninchens untersucht. Methoden 32 männliche Kaninchen wurden medial arthrotomiert und das VKB durchtrennt. Die Durchtrennung erfolgte unter Sicht mittels Nr. 15 Skalpell, zusätzlich wurde die vollständige Trennung der Stümpfe durch mehrfache Instrumentenpassage kontrolliert. Eine Resektion von Fasern erfolgte nicht. Je 8 Tiere wurden 2, 4, 8 und 12 Wochen nach dem Eingriff getötet. Die Morphologie der Heilungsverläufe wurde nach Lo et al. [1] klassifiziert, neue Typen der Klassifikation hinzugefügt. Typ B (intrasynoviale Ruptur) und Typ C (knöcherner Ausriss) waren studienbedingt nicht möglich. Die Studie war vom Regierungspräsidium genehmigt. Ergebnisse Die untersuchten Tiere hatten einen unauffälligen postoperativen Verlauf. Bei unterschiedlicher Ausprägung hatten alle Tiere makroskopisch eine Knorpelschädigung. Nach chirurgischer Durchtrennung waren die VKBenden durchschnitten (mop ended Typ A). Dieser Typ wurde bei der Dissektion nicht mehr vorgefunden. Die VKBstümpfe waren bei Dissektion: retrahiert (Typ D), mit dem hinteren Kreuzband verwachsen (E), resorbiert (F), miteinander verbunden = narbengeheilt (G), oder es lag eine Kombination (H) verschiedener Typen vor. Als neue Typen wurden Verwachsungen mit dem Meniskus (I) oder mit der Gelenkkapsel bzw. dem Fettkörper (K) beschrieben. Die VKBstümpfe waren gering (G 1 = 7), deutlich (G2 = 3 bzw. 4 insges. bei zusätzlicher Verwachsung mit dem Innenmeniskus) oder hypertroph (G 3 = 3) miteinander verwachsen. [Tab. 1] Schlussfolgerungen Der VKBriss führt häufig zur Kniegelenksinstabilität und Osteoarthrose. Nach Durchtrennung des VKB wird in Studien der Osteoarthroseforschung im Kaninchenmodell der Befund nie detailliert. In einem systematischen Vergleich der Regenerationsfähigkeit von partiell und komplett durchtrennten VKBs fanden Hefti et al. [2] weder bei skeletall unreifen noch bei jungen erwachsenen Kaninchen eine Regeneration nach kompletter Durchtrennung. Sie berichteten als Regelfall die Resorption nach 3 Monaten, in 2 Fällen Verwachsungen mit dem hinteren Kreuzband. Die hier berichteten Daten sind im Gegensatz zu Hefti's Untersuchungen. Sie stimmen aber gut mit humanen MRT-Untersuchungen und Arthroskopien nach Kreuzbandverletzungen überein. Das VKB versucht durch Verwachsung eine Heilung der VKBstümpfe zu erzielen oder Anschluss an andere Kniegelenksstrukturen zu gewinnen. Somit besteht auch im Tiermodell des Kaninchens eine gewisse Spontanheilungsaktivität des VKB, deren biomechanische Stabilität allerdings oft unzureichend erschien. Eine Kniegelenksarthrose entwickelte sich in den untersuchten Gelenken

Biochemisches Monitoring nach Meniskektomie

Fragestellung Die Schädigung des Kollagennetzwerks ist ein frühes Ereignis der Arthrose (OA). Wir untersuchten ein Kollagen Typ II -Neoepitop (CTX) in der Synovialflüssigkeit (SF) nach kompletter medialer Meniskektomie (ME). Methoden 32 NZW-Kaninchen hatten eine ME des rechten Kniegelenks. Kontrolle: 11 shamoperierte, 8 unoperierte Kaninchen. Die ME-Kaninchen wurden nach 2 (n = 8), 4 (n = 8) , 8 (n = 8) und 12 (n = 8) Wochen getötet, SF-lavagen beider Kniegelenke durchgeführt. Der ELISA misst ein Kollagen Typ II - Neoepitop, das nach Spaltung der C-telopeptide cross-linking Domaine entsteht. Makroskopisch: Grading beider Kniegelenke mit einem 9 Felder-Schema: Einzelflächen und Gesamtsummen von Tibia, Femur (jeweils medial und lateral) und Patella Histologisch: Grading mit H&E und Safranin O Schnitten (u.a. Proteoglykangehalt, Matrixstruktur, Zellularität, Tidemark und Osteophyten) Statistik: Wilcoxon - und Mann - Whitney U Test. Ergebnisse Makroskopisch: signifikante Veränderungen von medialer Tibia und Femur ab 2 Wochen nach ME, im Vergleich mit Gegenseite und mit nichtoperierten Kaninchen. Histologisch: beginnende OA zu allen Zeitpunkten. ME Knie: CTX Werte in der SF deutlich erhöht, zum kontralateralen Knie für 2, 4, 8 und 12 Wochen signifikant. Nichtoperierte Tiere: keine Unterschiede linkes vs. rechtes Knie, im Vergleich zur ME zu allen Zeitpunkten signifikant niedriger. Schlussfolgerungen Knorpelmarker sind Parameter der OA. Die Metalloproteinasen 1, 8 und 13 erzeugen ein Kollagen Typ II - Neoepitop, das zum Monitoring der arthrotischen Veränderungen geeignet erscheint

Anti-Mullerian-Hormone during pregnancy and peripartum using the new Beckman Coulter AMH Gen II Assay

Background: AMH levels determined by the conventional AMH assay declined during pregnancy and postpartum. A new Beckman Coulter AMH Gen II assay removes the potentially assay-interfering complement which is activated in pregnancy. The aim of this study was to evaluate if the decline of AMH levels in the serum of pregnant women during the course of pregnancy and peripartum was assay-dependent and thus artificial. Methods: In this cross-sectional study prepartal blood samples were collected from 62 patients (median age 30.6 years [interquartile range: 25.6 - 34.5]) in the third trimester of pregnancy and again 1–4 days after delivery between 2011 and 2012. In another cohort of 11 patients (median age 34.1 years [interquartile range: 32.6 - 37.8]) blood samples were taken in different trimesters of pregnancy between 1995 and 2001. The conventional and the modified AMH assay were performed in the same patient serum samples. We used the conventional and the modified AMH-Gen-II ELISA (Beckman Coulter, Immunotech, Webster, USA) for the assessment of AMH levels. The Wilcoxon signed rank test was used for determining differences between AMH levels pre- and postpartum. The method of Bland and Altman was applied for analyzing the agreement of both methods for determining AMH levels. Results: AMH values peripartum were lower than those expected in fertile non-pregnant women of comparable age. An overall mean difference of 0.44 ng/ml was observed between the conventional and the modified assay. Measurements with the modified assay showed a significant decline of postpartal levels compared with prepartal levels which is consistent with values obtained using the conventional assay (both p < 0.00001). Compared to the longitudinal measurements of AMH levels determined using the conventional assay, AMH levels obtained using the modified assay suggest a steeper decline of values during the course of pregnancy. Conclusion: By comparing the conventional assay for AMH determination with the modified assay the present study confirmed that AMH levels decline during the course of pregnancy and early after delivery

Probabilistic (logic) programming concepts

A multitude of different probabilistic programming languages exists today, all extending a traditional programming language with primitives to support modeling of complex, structured probability distributions. Each of these languages employs its own probabilistic primitives, and comes with a particular syntax, semantics and inference procedure. This makes it hard to understand the underlying programming concepts and appreciate the differences between the different languages. To obtain a better understanding of probabilistic programming, we identify a number of core programming concepts underlying the primitives used by various probabilistic languages, discuss the execution mechanisms that they require and use these to position and survey state-of-the-art probabilistic languages and their implementation. While doing so, we focus on probabilistic extensions of logic programming languages such as Prolog, which have been considered for over 20 years

Lifted graphical models: a survey

Lifted graphical models provide a language for expressing dependencies between different types of entities, their attributes, and their diverse relations, as well as techniques for probabilistic reasoning in such multi-relational domains. In this survey, we review a general form for a lifted graphical model, a par-factor graph, and show how a number of existing statistical relational representations map to this formalism. We discuss inference algorithms, including lifted inference algorithms, that efficiently compute the answers to probabilistic queries over such models. We also review work in learning lifted graphical models from data. There is a growing need for statistical relational models (whether they go by that name or another), as we are inundated with data which is a mix of structured and unstructured, with entities and relations extracted in a noisy manner from text, and with the need to reason effectively with this data. We hope that this synthesis of ideas from many different research groups will provide an accessible starting point for new researchers in this expanding field

Oxymethylene Ether (OME) Fuel Catalyst Screening Using In Situ NMR Spectroscopy

Online NMR measurements are introduced in the current study as a new analytical setup for investigation of the oxymethylene dimethyl ether (OME) synthesis. For the validation of the setup, the newly established method is compared with state‐of‐the‐art gas chromatographic analysis. Afterwards, the influence of different parameters, such as temperature, catalyst concentration and catalyst type on the OME fuel formation based on trioxane and dimethoxymethane is investigated. As catalysts, Amberlyst TM 15 (A15) and trifluoromethanesulfonic acid (TfOH) are utilized. A kinetic model is applied to describe the reaction in more detail. Based on these results, the activation energy (A15: 48.0 kJ mol −1 and TfOH: 72.3 kJ mol −1 ) and the order in catalyst (A15: 1.1 and TfOH: 1.3) are calculated and discussed

3D‐Printable Shape‐Memory Polymers Based on Halogen Bond Interactions

The supramolecular halogen bonding (XB) is utilized for the first time for the preparation of shape‐memory polymers. For this purpose, an iodotriazole‐based bidentate XB donor featuring a methacrylamide is synthesized. Free radical polymerization of the XB donor monomer together with butyl methacrylate, triethylene glycole dimethacrylate, and methacrylic acid results in covalently cross‐linked polymer networks bearing both, halogen bond acceptors and donors, in their side chains. While the reversible halogen bond interactions can act as switching unit, the required stable phase of the shape‐memory polymers is formed by covalent cross‐links. The successful formation of the supramolecular cross‐links is proven via Fourier‐transform Raman spectroscopy. Furthermore, the thermal properties are investigated via differential scanning calorimetry and thermo gravimetric analysis. Thermo‐mechanical analysis reveals excellent shape‐memory abilities with fixity rates above 95% and recovery rates up to 99%. Moreover, it is possible to 3D‐print this kind of material exhibiting the ability to recover its shape within a few seconds at 130 °C

Leveraging mobility data to analyze persistent SARS-CoV-2 mutations and inform targeted genomic surveillance

Given the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6500 SARS-CoV-2 Alpha genomes (B.1.1.7) across 7 months within Thuringia while collecting patients’ isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are subclusters. Mobile service data can indicate these clusters’ spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept was successfully implemented as a proof-of-concept for a mobility-guided sampling strategy in response to the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance.Introduction Results and discussion The Alpha lineage spread rapidly through Thuringia, showing a pattern similar to its nationwide spread Monitoring of Alpha subclusters in Thuringia reveals temporally and regionally restricted distribution patterns Mobile service data indicates Alpha subcluster spread and sampling bias Proof of principle: mobile service data-guided sampling for genomic surveillance for Omicron BQ.1.1 Conclusion Methods Sampling Sample preparation and sequencing Alpha spread datasets Subcluster identification Mobile service data Research in context Declaration of generative AI and AI-assisted technologies in the writing proces

Prognostic relevance of caspase 8 -652 6N InsDel and Asp302His polymorphisms for breast cancer

BACKGROUND: The minor allele of two caspase 8 polymorphisms, namely CASP8 -652 6N InsDel (rs3834129) and CASP8 Asp302His (rs1045485), were repeatedly associated with reduced breast cancer susceptibility. Contrarily, the presence of the -652 6N Del or the CASP8 302His variant was reported to be an unfavorable prognostic factor in colorectal cancer or neuroblastoma. However, prognostic relevance of these genetic variants for breast cancer is completely unknown and is therefore adressed by the current study. METHODS: Genotyping was performed by pyrosequencing. Caspase 8 mRNA expression was quantified by comparative RT-qPCR. RESULTS: We observed an allele-dose dependent association between CASP8 -652 6N InsDel and caspase 8 mRNA expression in breast cancer tissue, with homozygous deletion carriers showing lowest relative caspase 8 expression (p = 0.0131). Intriguingly, the presence of the -652 6N Del or the 302His variant was shown to be a negative prognostic factor for breast cancer in terms of an allele-dose dependent influence on overall survival (OS, p = 0.0018, p = 0.0150, respectively). Moreover, both polymorphisms were independent predictors of OS after adjusting for co-variats (p = 0.007, p = 0.037, respectively). Prognostic relevance of both polymorphisms were confirmed to be independent from each other and combined analysis of diplotypes revealed an additive influence upon OS (p = 0.0002). CONCLUSION: This is the first report, showing negative and independent prognostic impact of the CASP8 -652 6N Del and the 302His variant for breast cancer. Our data provide rationale to further validate clinical utility of these polymorphisms for breast cancer and to extend this investigation to a broad scope of other malignancies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12885-016-2662-x) contains supplementary material, which is available to authorized users