Knock-Out of IKKepsilon Ameliorates Atherosclerosis and Fatty Liver Disease by Alterations of Lipid Metabolism in the PCSK9 Model in Mice.

The inhibitor-kappaB kinase epsilon (IKKε) represents a non-canonical IκB kinase that modulates NF-κB activity and interferon I responses. Inhibition of this pathway has been linked with atherosclerosis and metabolic dysfunction-associated steatotic liver disease (MASLD), yet the results are contradictory. In this study, we employed a combined model of hepatic PCSK9 overexpression and a high-fat diet for 16 weeks to induce atherosclerosis and liver steatosis.

Image scanning lensless fiber-bundle endomicroscopy.

Fiber-based confocal endomicroscopy has shown great promise for minimally-invasive deep-tissue imaging. Despite its advantages, confocal fiber-bundle endoscopy inherently suffers from undersampling due to the spacing between fiber cores, and low collection efficiency when the target is not in proximity to the distal fiber facet. Here, we demonstrate an adaptation of image-scanning microscopy (ISM) to lensless fiber bundle endoscopy, doubling the spatial sampling frequency and significantly improving collection efficiency.

[Bicycle accidents in the course of time in Münster, Germany : Analysis of changes in bicycle accidents over the past 10 years].

Background: Bicycles have been a popular means of transport for many years. Especially in times of increased climate discussion, the bicycle has moved further into focus as an environmentally friendly and cost-effective means of transport. Bike lanes and roads are becoming more crowded and new means of transport such as pedelecs or e‑scooters are emerging.

The Role of AlphαSynuclein in Mouse Models of Acute, Inflammatory and Neuropathic Pain.

(1) AlphαSynuclein (αSyn) is a synaptic protein which is expressed in the nervous system and has been linked to neurodegenerative diseases, in particular Parkinson's disease (PD). Symptoms of PD are mainly due to overexpression and aggregation of αSyn and include pain. However, the interconnection of αSyn and pain has not been clarified so far.

N-methyl-d-aspartate Receptor-mediated Preconditioning Mitigates Excitotoxicity in Human Induced Pluripotent Stem Cell-derived Brain Organoids.

Studies in rodent models of acute and chronic neurodegenerative disorders have uncovered that glutamate-induced excitotoxic cell death is mediated primarily by extrasynaptic N-methyl-d-aspartate receptors (NMDARs). Rodent neurons can also build up in an activity-dependent manner a protective shield against excitotoxicity. This form of acquired neuroprotection is induced by preconditioning with low doses of NMDA or by activation of synaptic NMDARs triggered by bursts of action potentials.

Evaluation of the Behavior of Carbon Short Fiber Reinforced Concrete (CSFRC) Based on a Multi-Sensory Experimental Investigation and a Numerical Multiscale Approach.

Carbon fiber reinforcement used in concrete has become a remarkable alternative to steel fibers. Admixing short fibers to fresh concrete and processing the material with a 3D printer leads to an orientation of fibers and a material with high uniaxial strength properties, which offers an economic use of fibers. To investigate its mechanical behavior, the material is subjected to flexural and tensional tests, combining several measuring techniques.

Inhibition of HDAC Enzymes Contributes to Differential Expression of Pro-Inflammatory Proteins in the TLR-4 Signaling Cascade.

Class I and II histone deacetylases (HDAC) are considered important regulators of immunity and inflammation. Modulation of HDAC expression and activity is associated with altered inflammatory responses but reports are controversial and the specific impact of single HDACs is not clear. We examined class I and II HDACs in TLR-4 signaling pathways in murine macrophages with a focus on IκB kinase epsilon (IKKε) which has not been investigated in this context before.

The Specific IKKε/TBK1 Inhibitor Amlexanox Suppresses Human Melanoma by the Inhibition of Autophagy, NF-κB and MAP Kinase Pathways.

Inhibitor-kappaB kinase epsilon (IKKε) and TANK-binding kinase 1 (TBK1) are non-canonical IκB kinases, both described as contributors to tumor growth and metastasis in different cancer types. Several hints indicate that they are also involved in the pathogenesis of melanoma; however, the impact of their inhibition as a potential therapeutic measure in this "difficult-to-treat" cancer type has not been investigated so far. We assessed IKKε and TBK1 expression in human malignant melanoma cells, primary tumors and the metastasis of melanoma patients.

Nasally delivered VEGFD mimetics mitigate stroke-induced dendrite loss and brain damage.

In the adult brain, vascular endothelial growth factor D (VEGFD) is required for structural integrity of dendrites and cognitive abilities. Alterations of dendritic architectures are hallmarks of many neurologic disorders, including stroke-induced damage caused by toxic extrasynaptic NMDA receptor (eNMDAR) signaling. Here we show that stimulation of eNMDARs causes a rapid shutoff of expression, leading to a dramatic loss of dendritic structures.

5-Amino-1-β-D-Ribofuranosyl-Imidazole-4-Carboxamide (AICAR) Reduces Peripheral Inflammation by Macrophage Phenotype Shift.

The stimulation of the AMP-activated kinase (AMPK) by 5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide (AICAR) has been associated with antihyperalgesia and the inhibition of nociceptive signaling in the spinal cord in models of paw inflammation. The attenuated nociception comes along with a strongly reduced paw edema, indicating that peripheral antiinflammatory mechanisms contribute to antinociception. In this study, we investigated the impact of AICAR on the immune cell composition in inflamed paws, as well as the regulation of inflammatory and resolving markers in macrophages.

Two-photon lensless micro-endoscopy with in-situ wavefront correction.

Multi-core fiber-bundle endoscopes provide a minimally-invasive solution for deep tissue imaging and opto-genetic stimulation, at depths beyond the reach of conventional microscopes. Recently, wavefront-shaping has enabled lensless bundle-based micro-endoscopy by correcting the wavefront distortions induced by core-to-core inhomogeneities. However, current wavefront-shaping solutions require access to the fiber distal end for determining the bend-sensitive wavefront-correction.

Post-injury Nose-to-Brain Delivery of Activin A and SerpinB2 Reduces Brain Damage in a Mouse Stroke Model.

Synaptic NMDA receptors activating nuclear calcium-driven adaptogenomics control a potent body-own neuroprotective mechanism, referred to as acquired neuroprotection. Viral vector-mediated gene transfer in conjunction with stereotactic surgery has previously demonstrated the proficiency of several nuclear calcium-regulated genes to protect in vivo against brain damage caused by toxic extrasynaptic NMDA receptor signaling following seizures or stroke. Here we used noninvasive nose-to-brain administration of Activin A and SerpinB2, two secreted nuclear calcium-regulated neuroprotectants, for post-injury treatment of brain damage following middle cerebral artery occlusion (MCAO) in C57BL/6N mice.

[How Probable is it That Seniors Using an E-Bike Will Have an Accident? - A New Health Care Topic, Also for Consulting Doctors].

Background: In Germany there are more than 70 million bicycles. Because of technical progress, over 200,000 electro-assisted bikes were sold in Germany in 2010 alone. In 2013, the number increased to 410,000.

Isolated and concomitant minimally invasive minithoracotomy aortic valve surgery.

Objective: To evaluate whether the outcomes of minimally invasive aortic valve surgery were similar in younger versus older patient groups, as well as whether concomitant minimally invasive aortic valve replacement (AVR) surgeries added significant risks in these populations.

Methods: We performed a single-institution retrospective analysis of 1018 patients undergoing isolated AVR and 378 patients undergoing concomitant AVR procedures over a 6-year period. All surgeries were via a right minithoracotomy approach, and patients who underwent reoperation were excluded.

Energy Exchange in Driven Open Quantum Systems at Strong Coupling.

The time-dependent energy transfer in a driven quantum system strongly coupled to a heat bath is studied within an influence functional approach. Exact formal expressions for the statistics of energy dissipation into the different channels are derived. The general method is applied to the driven dissipative two-state system.

Nuclear Calcium Buffering Capacity Shapes Neuronal Architecture.

Calcium-binding proteins (CaBPs) such as parvalbumin are part of the cellular calcium buffering system that determines intracellular calcium diffusion and influences the spatiotemporal dynamics of calcium signals. In neurons, CaBPs are primarily localized to the cytosol and function, for example, in nerve terminals in short-term synaptic plasticity. However, CaBPs are also expressed in the cell nucleus, suggesting that they modulate nuclear calcium signals, which are key regulators of neuronal gene expression.

Minimally invasive aortic valve replacement in octogenarians performed via a right anterior thoracotomy approach.

Background And Aim Of The Study: A significant number of patients aged > or =80 years are denied aortic valve surgery due to the assumption of poor outcomes with surgery. The study aim was to evaluate the outcomes of minimally invasive aortic valve replacement (AVR), performed via a right anterior thoracotomy approach, in octogenarians.

Methods: A retrospective review was conducted of all minimally invasive isolated AVRs in patients aged > or =80 years performed at the authors' institution between February 2009 and April 2014.