Confocal laser endomicroscopy in head and neck cancer: steps forward?

Purpose of review Confocal laser endomicroscopy (CLE) is a novel, noninvasive technique used to obtain microanatomical images of the inner lining of hollow organs. It has been used in a variety of clinical specialties to aid in the diagnosis and treatment planning of inflammatory and neoplastic processes. Our intent is to provide an up-to-date review of the literature in the setting of head and neck diseases as well as describing our own initial results and areas of future research. Recent findings With increasing experience using CLE in the upper aerodigestive tract (UADT), evidence is mounting that this method can be a useful adjunct to standard endoscopy and other diagnostic techniques. Recent publications have shown that by using CLE, microanatomical structures of healthy and diseased mucosa can easily be identified, allowing for a differentiation of dysplastic/neoplastic and benign mucosal lesions. Standardized diagnostic protocols as well as clinically relevant classification systems for the UADT have not yet been described. Summary CLE is an imaging modality that allows real-time visualization of mucosal cellular architecture and other histologic characteristics. First reports on its use in the UADT have yielded promising results, but the true value of this method is yet to be determined

On the Aggregation of Rules for Knowledge Graph Completion

Rule learning approaches for knowledge graph completion are efficient, interpretable and competitive to purely neural models. The rule aggregation problem is concerned with finding one plausibility score for a candidate fact which was simultaneously predicted by multiple rules. Although the problem is ubiquitous, as data-driven rule learning can result in noisy and large rulesets, it is underrepresented in the literature and its theoretical foundations have not been studied before in this context. In this work, we demonstrate that existing aggregation approaches can be expressed as marginal inference operations over the predicting rules. In particular, we show that the common Max-aggregation strategy, which scores candidates based on the rule with the highest confidence, has a probabilistic interpretation. Finally, we propose an efficient and overlooked baseline which combines the previous strategies and is competitive to computationally more expensive approaches.Comment: KLR Workshop@ICML202

The impact of superficial femoral artery (SFA) occlusion on the outcome of proximal sartorius muscle transposition flaps in vascular surgery patients

ObjectivesTo demonstrate the feasibility and safety of proximal sartorius muscle rotational flaps in patients with peripheral occlusive artery disease.MethodsRetrospective analysis of 53 patients with 56 proximal sartorius muscle flaps. Indication for a flap procedure was postoperative calcitrant lymphorrhea in nine, graft at risk in 13, and graft infection in 34 procedures. Pre- and postoperative patencies of the superficial femoral artery (SFA) and profundal femoral artery (PFA) were documented. Flap viability, wound healing, and limb salvage were examined at follow-up.ResultsIn 59% of the procedures in this series, the SFA was occluded. The PFA was patent in all patients. Flap viability (100% vs 94%), rate of new (4% vs 6%), and recurrent infections (9% vs 6%), loss of vascular reconstruction rate (9% vs 9%), and limb salvage rate (100% vs 88%) did not differ significantly between the SFA patent and the SFA occluded group. There were four new infections (7%) and three recurrent infections (5.5%) during follow-up, five of which led to a loss of reconstruction. In four of those five patients, the sartorius flap was viable. Two patients died during the immediate postoperative period from septic multi-organ failure (3%). At a median follow-up of 6.4 months, 54 flaps were viable and wound closure was achieved in all surviving 51 patients. Limb salvage rate was 93%.ConclusionsBiologic protection procedures as local muscle flaps are vital adjuncts to vascular surgery techniques in the treatment of complicated wounds in the groin. Occlusion of the SFA in the presence of a patent PFA is not associated with an increased risk of flap loss in proximal sartorius muscle rotational flaps

Potentiation of Glycine-Gated NR1/NR3A NMDA Receptors Relieves Ca2+-Dependent Outward Rectification

Glycine has diverse functions within the mammalian central nervous system. It inhibits postsynaptic neurons via strychnine-sensitive glycine receptors (GlyRs) and enhances neuronal excitation through co-activation of N-methyl-D-aspartate (NMDA) receptors. Classical Ca2+-permeable NMDA receptors are composed of glycine-binding NR1 and glutamate-binding NR2 subunits, and hence require both glutamate and glycine for efficient activation. In contrast, recombinant receptors composed of NR1 and the glycine binding NR3A and/or NR3B subunits lack glutamate binding sites and can be activated by glycine alone. Therefore these receptors are also named “excitatory glycine receptors”. Co-application of antagonists of the NR1 glycine-binding site or of the divalent cation Zn2+ markedly enhances the glycine responses of these receptors. To gain further insight into the properties of these glycine-gated NMDA receptors, we investigated their current-voltage (I–V) dependence. Whole-cell current-voltage relations of glycine currents recorded from NR1/NR3B and NR1/NR3A/NR3B expressing oocytes were found to be linear under our recording conditions. In contrast, NR1/NR3A receptors displayed a strong outwardly rectifying I–V relation. Interestingly, the voltage-dependent inward current block was abolished in the presence of NR1 antagonists, Zn2+ or a combination of both. Further analysis revealed that Ca2+ (1.8 mM) present in our recording solutions was responsible for the voltage-dependent inhibition of ion flux through NR1/NR3A receptors. Since physiological concentrations of the divalent cation Mg2+ did not affect the I–V dependence, our data suggest that relief of the voltage-dependent Ca2+ block of NR1/NR3A receptors by Zn2+ may be important for the regulation of excitatory glycinergic transmission, according to the Mg2+-block of conventional NR1/NR2 NMDA receptors

Bypass of lethality with mosaic mice generated by Cre–loxP-mediated recombination

AbstractBackground The analysis of gene function based on the generation of mutant mice by homologous recombination in embryonic stem cells is limited if gene disruption results in embryonic lethality. Mosaic mice, which contain a certain proportion of mutant cells in all organs, allow lethality to be circumvented and the potential of mutant cells to contribute to different cell lineages to be analyzed. To generate mosaic animals, we used the bacteriophage P1-derived Cre–loxP recombination system, which allows gene alteration by Cre-mediated deletion of loxP-flanked gene segments.Results We generated nestin–cre transgenic mouse lines, which expressed the Cre recombinase under the control of the rat nestin promoter and its second intron enhancer. In crosses to animals carrying a loxP-flanked target gene, partial deletion of the loxP-flanked allele occurred before day 10.5 post coitum and was detectable in all adult organs examined, including germ-line cells. Using this approach, we generated mosaic mice containing cells deficient in the γ-chain of the interleukin-2 receptor (IL-2Rγ); in these animals, the IL-2Rγ-deficient cells were underrepresented in the thymus and spleen. Because mice deficient in DNA polymerase β die perinatally, we studied the effects of DNA polymerase β deficiency in mosaic animals. We found that some of the mosaic polymerase β-deficient animals were viable, but were often reduced in size and weight. The fraction of DNA polymerase β-deficient cells in mosaic embryos decreased during embryonic development, presumably because wild-type cells had a competitive advantage.Conclusions The nestin–cre transgenic mice can be used to generate mosaic animals in which target genes are mutated by Cre-mediated recombination of loxP-flanked target genes. By using mosaic animals, embryonic lethality can be bypassed and cell lineages for whose development a given target gene is critical can be identified. In the case of DNA polymerase β, deficient cells are already selected against during embryonic development, demonstrating the general importance of this protein in multiple cell types

Determination of Bulk Magnetic Volume Properties by Neutron Dark-Field Imaging

For the production of high-class electrical steel grades a deeper understanding of the magnetic domain interaction with induced mechanical stresses is strongly required. This holds for non-oriented (NO) as well as grain-oriented (GO) steels. In the case of non-oriented steels the magnetic property degeneration after punching or laser cutting is essential for selecting correct obstructing material grades and designing efficient electrical machines. Until now these effects stay undiscovered due to the lack of adequate investigation methods that reveal local bulk information on processed laminations. Here we show how the use of a non-destructive testing method based on a neutron grating interferometry providing the dark-field image contrast delivers spatially-resolved transmission information about the local bulk domain arrangement and domain wall density. With the help of this technique it is possible to visualize magnetization processes within the NO laminations. Different representative manufacturing techniques are compared in terms of magnetic flux density deterioration such as punching, mechanically cutting by guillotine as well as laser fusion cutting using industrial high power laser beam sources. For GO steel laminations the method is applicable on the one hand to visualize the internal domain structure without being hindered by the coating layer. On the other hand, we can show the influence of the coating layer onto the underlying domain structure