Angiopoietin-2 predicts morbidity in adults with Fontan physiology.

Morbidity in patients with single-ventricle Fontan circulation is common and includes arrhythmias, edema, and pulmonary arteriovenous malformations (PAVM) among others. We sought to identify biomarkers that may predict such complications. Twenty-five patients with Fontan physiology and 12 control patients with atrial septal defects (ASD) that underwent cardiac catheterization were included. Plasma was collected from the hepatic vein and superior vena cava and underwent protein profiling for a panel of 20 analytes involved in angiogenesis and endothelial dysfunction. Ten (40%) of Fontan patients had evidence of PAVM, eighteen (72%) had a history of arrhythmia, and five (20%) were actively in arrhythmia or had a recent arrhythmia. Angiopoietin-2 (Ang-2) was higher in Fontan patients (8,875.4 ± 3,336.9 pg/mL) versus the ASD group (1,663.6 ± 587.3 pg/mL, p < 0.0001). Ang-2 was higher in Fontan patients with active or recent arrhythmia (11,396.0 ± 3,457.7 vs 8,118.2 ± 2,795.1 pg/mL, p < 0.05). A threshold of 8,500 pg/mL gives Ang-2 a negative predictive value of 100% and positive predictive value of 42% in diagnosing recent arrhythmia. Ang-2 is elevated among adults with Fontan physiology. Ang-2 level is associated with active or recent arrhythmia, but was not found to be associated with PAVM

Mentale Gehalte und erweiterter Geist: Warum das Argument der Nichtabgeleitetheit scheitert

Hundertmark F. Mentale Gehalte und erweiterter Geist: Warum das Argument der Nichtabgeleitetheit scheitert. In: Michel JG, Boström KJ, Pohl M, eds. Ist der Geist im Kopf?: Beiträge zur These des erweiterten Geistes. Münster: mentis; 2016: 133-160.Der These des erweiterten Geistes zufolge befinden sich manche mentalen Repräsentationen außerhalb der körperlichen Grenzen der Wesen, zu denen sie gehören. Einer der stärksten Einwände gegen diese These stellt das Argument der Nichtabgeleitetheit von Frederick Adams, Ken Aizawa und Jerry Fodor dar. Dieses Argument setzt voraus, dass genuine mentale Repräsentationen nichtabgeleitete Gehalte haben – ihre semantischen Eigenschaften sind also nicht durch Absichten, Wünsche oder Konventionen konstituiert. Repräsentationen mit nichtabgeleitetem Gehalt finden sich jedoch, so das Argument weiter, nur innerhalb der körperlichen Grenzen mentaler Wesen. Ich werde dafür argumentieren, dass das Argument der Nichtabgeleitetheit scheitert, da es insbesondere bei Tieren externe Repräsentationen gibt, deren Gehalt nichtabgeleitet ist. Dies folgt jedenfalls aus der aussichtsreichsten Theorie nichtabgeleiteter Repräsentationen, der Teleosemantik, und es gibt gute Gründe anzunehmen, dass auch andere naturalistische Gehaltstheorien dieselbe Implikation haben

Monosynaptic Stretch Reflex Fails to Explain the Initial Postural Response to Sudden Lateral Perturbations

Postural reflexes are essential for locomotion and postural stability, and may play an important role in the etiology of chronic back pain. It has recently been theoretically predicted, and with the help of unilateral perturbations of the trunk experimentally confirmed that the sensorimotor control must lower the reflex amplitude for increasing reflex delays to maintain spinal stability. The underlying neuromuscular mechanism for the compensation of postural perturbations, however, is not yet fully understood. In this study, we applied unilateral and bilateral sudden external perturbations to the trunk of healthy subjects and measured the muscular activity and the movement onset of the trunk. We found that the onset of the trunk muscle activity is prior to, or coincident with, the onset of the trunk movement. Additionally, the results of our experiments imply that the muscular response mechanism integrates distant sensory information from both sides of the body. These findings rule out a simple monosynaptic stretch reflex in favor of a more complex polysynaptic postural reflex mechanism to compensate postural perturbations. Moreover, the previously predicted negative correlation between reflex delay and reflex gain was also confirmed for bilateral perturbations

A pilot study of a phenomenological model of adipogenesis in maturing adipocytes using Cahn–Hilliard theory

We consider the accumulation and formation of lipid droplets in an adipocyte cell. The process incorporates adipose nucleation (adipogenesis) and growth. At later stages, there will be merging of droplets and growth of larger droplets at the expense of the smaller droplets, which will essentially undergo lipolysis. The process is modeled by the use of the Cahn–Hilliard equation, which is mass-conserving and allows the formation of secondary phases in the context of spinodal decomposition. The volume of fluid (VOF) method is used to determine the total area that is occupied by the lipids in a given cross section. Further, we present an algorithm, applicable to all kinds of grids (structured or unstructured) in two spatial dimensions, to count the number of lipid droplets and the portion of the domain of computation that is occupied by the lipid droplets as a function of time during the process. The results are preliminary and are validated from a qualitative point using experiments carried out on cell cultures. It turns out that the Cahn–Hilliard theory can model many of the features during adipogenesis qualitatively

Integrins are enriched on aberrantly fucosylated tumour‐derived urinary extracellular vesicles

Urinary extracellular vesicles (uEVs) are enriched with glycosylated proteins which have been extensively studied as putative biomarkers of urological cancers. Here, we characterized the glycosylation and integrin profile of EVs derived from urological cancer cell lines. We used fluorescent europium-doped nanoparticles coated with lectins and antibodies to identify a biomarker combination consisting of integrin subunit alpha 3 (ITGA3) and fucose. In addition, we used the same cancer cell line-derived EVs as analytical standards to assess the sensitivity of the ITGA3-UEA assay. The clinical performance of the ITGA3-UEA assay was analysed using urine samples of various urological pathologies including diagnostically challenging benign prostatic hyperplasia (BPH), prostate cancer (PCa) and bladder cancer (BlCa). The assay can significantly discriminate BlCa from all other patient groups: PCa (9.2-fold; p = 0.00038), BPH (5.5-fold; p = 0.004) and healthy individuals (and 23-fold; p = 0.0001). Our results demonstrate that aberrantly fucosylated uEVs and integrin ITGA3 can be detected with fucose-specific lectin UEA in a simple bioaffinity assay for the detection of BlCa directly from unprocessed urine.</p

Acknowledgement to reviewers of JSAN in 2016

The editors of JSAN would like to express their sincere gratitude to the following reviewers for assessing manuscripts in 2016.[...

Mesenchymal cell survival in airway and interstitial pulmonary fibrosis

Fibrotic reactions in the airways of the lung or the pulmonary interstitium are a common pathologic outcome after exposure to a wide variety of toxic agents, including metals, particles or fibers. The survival of mesenchymal cells (fibroblasts and myofibroblasts) is a key factor in determining whether a fibroproliferative response that occurs after toxic injury to the lung will ultimately resolve or progress to a pathologic state. Several polypeptide growth factors, including members of the platelet-derived growth factor (PDGF) family and the epidermal growth factor (EGF) family, are prosurvival factors that stimulate a replicative and migratory mesenchymal cell phenotype during the early stages of lung fibrogenesis. This replicative phenotype can progress to a matrix synthetic phenotype in the presence of transforming growth factor-β1 (TGF-β1). The resolution of a fibrotic response requires growth arrest and apoptosis of mesenchymal cells, whereas progressive chronic fibrosis has been associated with mesenchymal cell resistance to apoptosis. Mesenchymal cell survival or apoptosis is further influenced by cytokines secreted during Th1 inflammation (e.g., IFN-γ) or Th2 inflammation (e.g., IL-13) that modulate the expression of growth factor activity through the STAT family of transcription factors. Understanding the mechanisms that regulate the survival or death of mesenchymal cells is central to ultimately developing therapeutic strategies for lung fibrosis