Chronic limb-threatening ischemia: when is enough enough?

Vascular Surger

Successful Reduction of Creatine Kinase and Myoglobin Levels in Severe Rhabdomyolysis Using Extracorporeal Blood Purification (CytoSorb®)

Rhabdomyolysis, if severe, can lead to acute kidney injury (AKI). Myoglobin is an iron and oxygen-binding protein that is freely filtered by the glomerulus. Precipitation of myoglobin in the nephrons' distal parts is responsible for tubular damage with AKI as a consequence. Extracorporeal clearance of myoglobin is conventionally attempted by the use of continuous renal replacement therapy (CRRT) with high cut-off dialysis membranes to limit the extent of the damage. We describe a case of a 56-year-old man with traumatic crush injury and a persistent source of muscle ischaemia unresponsive to high dose CRRT with EMiC-2 filter. Due to therapy failure, he was subsequently treated with the addition of a haemoadsorber (CytoSorb®) to the circuit. This reduced myoglobin and creatine kinase

Direct simulation of ion beam induced stressing and amorphization of silicon

Using molecular dynamics (MD) simulation, we investigate the mechanical response of silicon to high dose ion-irradiation. We employ a realistic and efficient model to directly simulate ion beam induced amorphization. Structural properties of the amorphized sample are compared with experimental data and results of other simulation studies. We find the behavior of the irradiated material is related to the rate at which it can relax. Depending upon the ability to deform, we observe either the generation of a high compressive stress and subsequent expansion of the material, or generation of tensile stress and densification. We note that statistical material properties, such as radial distribution functions are not sufficient to differentiate between different densities of amorphous samples. For any reasonable deformation rate, we observe an expansion of the target upon amorphization in agreement with experimental observations. This is in contrast to simulations of quenching which usually result in denser structures relative to crystalline Si. We conclude that although there is substantial agreement between experimental measurements and most simulation results, the amorphous structures being investigated may have fundamental differences; the difference in density can be attributed to local defects within the amorphous network. Finally we show that annealing simulations of our amorphized samples can lead to a reduction of high energy local defects without a large scale rearrangement of the amorphous network. This supports the proposal that defects in amorphous silicon are analogous to those in crystalline silicon.Comment: 13 pages, 12 figure

The tumor suppressor MIR139 is silenced by POLR2M to promote AML oncogenesis

MIR139 is a tumor suppressor and is commonly silenced in acute myeloid leukemia (AML). However, the tumor-suppressing activities of miR-139 and molecular mechanisms of MIR139-silencing remain largely unknown. Here, we studied the poorly prognostic MLL-AF9 fusion protein-expressing AML. We show that MLL-AF9 expression in hematopoietic precursors caused epigenetic silencing of MIR139, whereas overexpression of MIR139 inhibited in vitro and in vivo AML outgrowth. We identified novel miR-139 targets that mediate the tumor-suppressing activities of miR-139 in MLL-AF9 AML. We revealed that two enhancer regions control MIR139 expression and found that the polycomb repressive complex 2 (PRC2) downstream of MLL-AF9 epigenetically silenced MIR139 in AML. Finally, a genome-wide CRISPR-Cas9 knockout screen revealed RNA Polymerase 2 Subunit M (POLR2M) as a novel MIR139-regulatory factor. Our findings elucidate the molecular control of tumor suppressor MIR139 and reveal a role for POLR2M in the MIR139-silencing mechanism, downstream of MLL-AF9 and PRC2 in AML. In addition, we confirmed these findings in human AML cell lines with different oncogenic aberrations, suggesting that this is a more common oncogenic mechanism in AML. Our results may pave the way for new targeted therapy in AML.Proteomic

Probing Tectonic Topography in the Aftermath of Continental Convergence in Central Europe

Continental topography is at the interface of processes taking place at depth in the Earth,at its surface,and above it.Topography influences society, not only in terms of slow processes of landscape change and earthquakes,but also in terms of how it affects climate.The Pannonian Basin–Carpathian Orogen System in Central and Eastern Europe represents a key natural laboratory for the development of a new generation of models for ongoing orogeny and its effect on continental topography development (Figure 1).This system comprises some of the best documented sedimentary basins in the world,located within the Alpine orogenic belt, at the transition between the western European lithosphere and the East European Craton. It includes one of the most active seismic zones in Europe,with intermediate depth (50–220 km) mantle earthquakes of significant magnitude occurring in a geographically restricted area in the Vrancea zone of southeastern Romania

Mouse models of frontotemporal dementia: a comparison of phenotypes with clinical symptomatology

Frontotemporal dementia (FTD) is the second most common cause of young onset dementia. It is increasingly recognized that there is a clinical continuum between FTD and amyotrophic lateral sclerosis (ALS). At a clinical, pathological and genetic level there is much heterogeneity in FTD, meaning that our understanding of this condition, pathophysiology and development of treatments has been limited. A number of mouse models focusing predominantly on recapitulating neuropathological and molecular changes of disease have been developed, with most transgenic lines expressing a single specific protein or genetic mutation. Together with the species-typical presentation of functional deficits, this makes the direct translation of results from these models to humans difficult. However, understanding the phenotypical presentations in mice and how they relate to clinical symptomology in humans is essential for advancing translation. Here we review current mouse models in FTD and compare their phenotype to the clinical presentation in patients

The role of reactive oxygen species in apoptosis of the diabetic kidney

Increased levels of reactive oxygen species (ROS) by hyperglycemia can induce apoptosis of renal cells and diabetic nephropathy. The redox balance in the renal cell seems, therefore, of the utmost importance. ROS-mediated apoptosis may be further aggravated by an inadequate cytoprotective response against ROS. When there are insufficient cytoprotective and ROS scavenging molecules, ROS lead to considerable cellular damage and to a point of no return in apoptosis. Induction of cytoprotective proteins may prevent or attenuate apoptosis, renal cell injury, and finally diabetic nephropathy. Here, we discuss some mechanisms of apoptosis and several strategies that have been probed to ameliorate, or to prevent apoptosis in the diabetic kidney

Suicide prevention for youth - a mental health awareness program: lessons learned from the Saving and Empowering Young Lives in Europe (SEYLE) intervention study

Background: The Awareness program was designed as a part of the EU-funded Saving and Empowering Young Lives in Europe (SEYLE) intervention study to promote mental health of adolescents in 11 European countries by helping them to develop problem-solving skills and encouraging them to self-recognize the need for help as well as how to help peers in need. Methods: For this descriptive study all coordinators of the SEYLE Awareness program answered an open-ended evaluation questionnaire at the end of the project implementation. Their answers were synthesized and analyzed and are presented here. Results: The results show that the program cultivated peer understanding and support. Adolescents not only learned about mental health by participating in the Awareness program, but the majority of them also greatly enjoyed the experience. Conclusions: Recommendations for enhancing the successes of mental health awareness programs are presented. Help and cooperation from schools, teachers, local politicians and other stakeholders will lead to more efficacious future programs