WNT10A variants: following the pattern of inheritance in tooth agenesis and self-reported family history of cancer

Clinical Oral Investigations - The aim of this study was the analysis of WNT10A variants in seven families of probands with various forms of tooth agenesis and self-reported family history of...     

Randomized prospective trial of fractionated stereotactic radiosurgery with chemotherapy versus chemotherapy alone for bevacizumab-resistant high-grade glioma

Journal of Neuro-Oncology - Outcomes for patients with recurrent high-grade glioma (HGG) progressing on bevacizumab (BEV) are dismal. Fractionated stereotactic radiosurgery (FSRS) has been shown to...     

The synthetic antimicrobial peptide LTX21 induces inflammatory responses in a human whole blood model and a murine peritoneum model

The global spread of antimicrobial resistance and the increasing number of immune‐compromised patients are major challenges in modern medicine. Targeting bacterial virulence or the human host immune system to increase host defence are important strategies in the search for novel antimicrobial drugs. We investigated the inflammatory response of the synthetic short antimicrobial peptide LTX21 in two model systems: a human whole blood ex vivo model and a murine in vivo peritoneum model – both reflecting early innate immune response. In the whole blood model, LTX21 increased the secretion of a range of different cytokines, decreased the level of tumour necrosis factor (TNF) and activated the complement system. In a haemolysis assay, we found 2.5% haemolysis at a LTX21 concentration of 500 mg/L. In the murine model, increased influx of white blood cells (WBCs) and polymorphonuclear neutrophils (PMNs) in the murine peritoneal cavity was observed after treatment with LTX21. In addition, LTX21 increased monocyte chemoattractant protein‐1 (MCP‐1). In conclusion, LTX21 affected the inflammatory response; the increase in cytokine secretion, complement activation and WBC influx indicates an activated inflammatory response. The present results indicate the impact of LTX21 on the host–pathogen interplay. Whether this will also affect the course of infection has to be investigated.     

Compressed sensing with signal averaging for improved sensitivity and motion artifact reduction in fluorine‐19 MRI

Fluorine‐19 (¹⁹F) MRI of injected perfluorocarbon emulsions (PFCs) allows for the non‐invasive quantification of inflammation and cell tracking, but suffers from a low signal‐to‐noise ratio and extended scan time. To address this limitation, we tested the hypotheses that a ¹⁹F MRI pulse sequence that combines a specific undersampling regime with signal averaging has both increased sensitivity and robustness against motion artifacts compared with a non‐averaged fully sampled pulse sequence, when both datasets are reconstructed with compressed sensing. As a proof of principle, numerical simulations and phantom experiments were performed on selected variable ranges to characterize the point spread function of undersampling patterns, as well as the vulnerability to noise of undersampling and reconstruction parameters with paired numbers of x signal averages and acceleration factor x (NAx ‐AFx ). The numerical simulations demonstrated that a probability density function that uses 25% of the samples to fully sample the k‐space central area allowed for an optimal balance between limited blurring and artifact incoherence. At all investigated noise levels, the Dice similarity coefficient (DSC) strongly depended on the regularization parameters and acceleration factor. In phantoms, the motion robustness of an NA8‐AF8 undersampling pattern versus NA1‐AF1 was evaluated with simulated and real motion patterns. Differences were assessed with the DSC, which was consistently higher for the NA8‐AF8 compared with the NA1‐AF1 strategy, for both simulated and real cyclic motion patterns (P < 0.001). Both strategies were validated in vivo in mice (n = 2) injected with perfluoropolyether. Here, the images displayed a sharper delineation of the liver with the NA8‐AF8 strategy than with the NA1‐AF1 strategy. In conclusion, we validated the hypotheses that in ¹⁹F MRI the combination of undersampling and averaging improves both the sensitivity and the robustness against motion artifacts.