Determinants of Neurological Functional Recovery Potential after Stroke in Young Adults

BACKGROUND/OBJECTIVES: Despite recent progress in stroke prevention and acute treatment, neurorehabilitation remains one of the main methods of treatment in the management of stroke patients. The aim of this study is to point out some important predicting factors of in-hospital neurorehabilitation outcomes. METHODS: A rehabilitation registry including all patients who had undergone a standardized program of neurorehabilitation at the neurorehabilitation unit of the Lausanne University Hospital, Lausanne, Switzerland, was created. Patients aged <65 years and having experienced a first ever nontraumatic stroke from 2005 to 2010 were admitted. Using logistical regression models, predicting factors for each patient were compared to the exit Functional Independence Measure (FIM) score. RESULTS: Age >55 years, gender, aphasia, hemilateral spatial neglect, spasticity, complications, length of stay >70 days, entry FIM >100 and relative possible FIM gain/week of >10% were considered to be significant and independent predicting factors of the neurorehabilitation outcome. DISCUSSION/CONCLUSION: Some factors of the in-hospital rehabilitation period have been identified before (spasticity, complications, length of stay, relative possible FIM gain/week) and should be considered for a better management of the neurorehabilitation therapy. In addition, a personalized rehabilitation strategy based on the patient's individual needs should be aimed at. The question of resource allocation can also be addressed with regard to the present findings

Microangiopathy of cutaneous blood and lymphatic capillaries in chronic venous insufficiency (CVI).

The severity of microangiopathy in patients with chronic venous insufficiency (CVI) determines the extent of the trophic disturbances of the skin. Resulting from valvular incompetence of deep and/or perforating veins and the accompanying venous outflow obstruction caused by deep venous thrombosis (DVT), the increased ambulatory venous pressure heads are transmitted retrograde into the microvasculature of the skin at the ankle region. In the present study, we have assessed the changes in the cutaneous microvasculature by dynamic fluorescence video microscopy, fluorescence microlymphography, and transcutaneous oxygen tension (tcPO2) measurements. In mild forms of CVI, capillary density, morphologic characteristics, and tcPO2 are still normal. Fluorescent light intensity is, however, significantly increased, indicating an increased transcapillary diffusion of sodium fluorescein (NaF) as a marker for enhanced leakage of the capillaries in the early stage of the disease. The pericapillary halo diameters are significantly enlarged, compared to controls (p < 0.01). In the severe stages of CVI and in patients with venous ulcers, capillary thromboses, probably caused by endothelium-blood cell interactions, may lead to a reduced capillary density. In order to enlarge the exchange surface area, the remaining skin capillaries become tortuous (capillary tufts). Parallel to the reduced capillary number, tcPO2 decreases and can be extremely low at the ulcer rim or at white atrophy spots. Fibrin cuffs are not a specific finding for venous ulceration and do not significantly impair oxygen diffusion. Fluorescence microlymphography permits visualization of the lymphatic capillaries of the superficial skin. In severe stages of CVI, the lymphatic capillary network at the medial ankle area is destroyed, and the remaining lymphatic capillary fragments have an increased permeability to FITC-dextran with a molecular weight of 150,000. These findings demonstrate a special lymphatic microangiopathy in CVI, suggesting an additional lymphatic component in the edema formation

European economic constitution and the transformation of democracy : on class and the state of law

In the context of contemporary analyses of the Europe Union as a post-democratic form of economic governance, this article explores the (ordo)liberal character of monetary union as a regime of imposed liberty. The argument holds that rather than forcing the member states into retreat, the economic constitution of Europe strengthens their liberal foundation, securing their utility as the organised force of a mode of social reproduction founded on free labour. It develops the character of the liberal state as the political form of a free market economy with reference to Adam Smith’s classical political economy and the German ordoliberal tradition, which calls for a rule-based system of federated forms of economic governance to secure a free labour economy in conditions of mass democratic aspirations for a freedom from want. It explores the rationale of the ordoliberal distinction between the liberal character and the democratic character of the state and, in this context, assesses the meaning of liberal democracy in a post-democratic Eurozone

Protein engineering of a ubiquitin-variant inhibitor of APC/C identifies a cryptic K48 ubiquitin chain binding site.

Ubiquitin (Ub)-mediated proteolysis is a fundamental mechanism used by eukaryotic cells to maintain homeostasis and protein quality, and to control timing in biological processes. Two essential aspects of Ub regulation are conjugation through E1-E2-E3 enzymatic cascades and recognition by Ub-binding domains. An emerging theme in the Ub field is that these 2 properties are often amalgamated in conjugation enzymes. In addition to covalent thioester linkage to Ub's C terminus for Ub transfer reactions, conjugation enzymes often bind noncovalently and weakly to Ub at "exosites." However, identification of such sites is typically empirical and particularly challenging in large molecular machines. Here, studying the 1.2-MDa E3 ligase anaphase-promoting complex/cyclosome (APC/C), which controls cell division and many aspects of neurobiology, we discover a method for identifying unexpected Ub-binding sites. Using a panel of Ub variants (UbVs), we identify a protein-based inhibitor that blocks Ub ligation to APC/C substrates in vitro and ex vivo. Biochemistry, NMR, and cryo-electron microscopy (cryo-EM) structurally define the UbV interaction, explain its inhibitory activity through binding the surface on the APC2 subunit that recruits the E2 enzyme UBE2C, and ultimately reveal that this APC2 surface is also a Ub-binding exosite with preference for K48-linked chains. The results provide a tool for probing APC/C activity, have implications for the coordination of K48-linked Ub chain binding by APC/C with the multistep process of substrate polyubiquitylation, and demonstrate the power of UbV technology for identifying cryptic Ub-binding sites within large multiprotein complexes

Ross procedure: is the root replacement technique superior to the sub-coronary implantation technique? Long-term results.

There is controversy over the use of the Ross procedure with regard to the sub-coronary and root replacement technique and its long-term durability. A systematic review of the literature may provide insight into the outcomes of these two surgical subvariants. A systematic review of reports between 1967 and February 2013 on sub-coronary and root replacement Ross procedures was undertaken. Twenty-four articles were included and divided into (i) sub-coronary technique and (ii) root replacement technique. The 10-year survival rate for a mixed-patient population in the sub-coronary procedure was 87.3% with a 95% confidence interval (CI) of 79.7-93.4 and 89.1% (95% CI, 85.3-92.1) in the root replacement technique category. For adults, it was 94 vs 95.3% (CI, 88.9-98.1) and in the paediatric series it was 90 vs 92.7% (CI, 86.9-96.0), respectively. Freedom from reoperation at 10 years was, in the mixed population, 83.3% (95% CI, 69.9-93.4) and 93.3% (95% CI, 89.4-95.9) for sub-coronary versus root replacement technique, respectively. In adults, it was 98 vs 91.2% (95% CI, 82.4-295.8), and in the paediatric series 93.3 vs 92.0% (95% CI, 86.1-96.5) for sub-coronary versus root replacement technique, respectively. The Ross procedure arguably has satisfactory results over 5 and 10 years for both adults and children. The results do not support the advantages of the sub-coronary technique over the root replacement technique. Root replacement was of benefit to patients undergoing reoperations on neoaorta and for long-term survival in mixed series

Time-resolved cryo-EM (TR-EM) analysis of substrate polyubiquitination by the RING E3 anaphase-promoting complex/cyclosome (APC/C)

Substrate polyubiquitination drives a myriad of cellular processes, including the cell cycle, apoptosis and immune responses. Polyubiquitination is highly dynamic, and obtaining mechanistic insight has thus far required artificially trapped structures to stabilize specific steps along the enzymatic process. So far, how any ubiquitin ligase builds a proteasomal degradation signal, which is canonically regarded as four or more ubiquitins, remains unclear. Here we present time-resolved cryogenic electron microscopy studies of the 1.2MDa E3 ubiquitin ligase, known as the anaphase-promoting complex/cyclosome (APC/C), and its E2 co-enzymes (UBE2C/UBCH10 and UBE2S) during substrate polyubiquitination. Using cryoDRGN (Deep Reconstructing Generative Networks), a neural network-based approach, we reconstruct the conformational changes undergone by the human APC/C during polyubiquitination, directly visualize an active E3-E2 pair modifying its substrate, and identify unexpected interactions between multiple ubiquitins with parts of the APC/C machinery, including its coactivator CDH1. Together, we demonstrate how modification of substrates with nascent ubiquitin chains helps to potentiate processive substrate polyubiquitination, allowing us to model how a ubiquitin ligase builds a proteasomal degradation signal

Evolution von Staatlichkeit—mit einem Exkurs zu N. Elias’„Soziogenese des Staates“

"Wenn man 'Staat' nicht normativ als wohldefiniertes Gefüge aufeinander verweisender Institutionen legitimer Ordnung, sondern als gewachsene soziale Institution betrachtet, wenn man also die Evolution staatlich legitimierter und sanktionierter Interventionen in die Gesellschaft aus politisch-soziologischer Perspektive funktional untersucht, dann tauchen neue Muster 'staatlicher' Funktionalität im zunehmend global interdependenten sozio-ökonomischen Geschehen auf. Der Beitrag behandelt in diesem Zusammenhang die folgenden Fragen: Wie versuchen neuere Staatstheorien den funktionalen Wandel staatlicher Instanzen im gesellschaftlichen Gefüge zu erfassen und zu erklären? Was leisten Norbert Elias' Zivilisations- und Staatsbildungstheorie sowie Figurationstheorie für eine empirische Analyse der Evolution und Funktionsbestimmung (nach-)moderner Staatlichkeit? Liefert der Blick auf Staatlichkeit in evolutionärer Perspektive Ansatzpunkte für eine 'aufgeklarte Staatstheorie'? Welche Aufgabenfolgen daraus für die theoretische und empirische Erforschung gegenwärtiger und möglicher künftiger Funktionen von Staatlichkeit?

Ludwig von Mises and the 'Ordo-Interventionists' More than Just Aggression and Contempt?

This paper explores the four decades of intellectual relationship between the Austrian School economist Ludwig von Mises (1881-1973) and two major representatives of German ordoliberalism, Walter Eucken (1891-1950) and Wilhelm Röpke (1899-1966). The timespan covered starts in the early 1920s and terminates with Röpke's passing in 1966, a period featuring numerous encounters in person and several debates in published works, accompanied by exchange in correspondence. The central goal of the paper is to provide a more nuanced understanding of the reasons for the hostile climate and the confrontation patterns than earlier narratives in secondary literature. A key tool is the technique of embedding the scholarly component of the interactions into a complex network of interpersonal relationships. The four decades are separated into five distinct phases with differently nuanced communication patterns: 1) early socialization echoing the animosities between the Austrian School and the Historical School; 2) initial debates in the 1920s and early 1930s on business cycle theory and policy where seniority and maturity play an important role; 3) clashes on political economy and social philosophy at the Colloque Walter Lippmann in 1938 and during the two initial decades of the Mont Pèlerin Society after 1947; 4) coexistence during the German "economic miracle"; 5) exchanges in the 1960s, including a discussion of archival materials never published before about Mises' only honorary doctorate in economics, awarded to him by the University of Freiburg in 1964. Based on this historical account at the heart of the paper, conjectures are formulated as to why - despite the common ground in the inquiries pursued - the protagonists continuously fail to engage in more fruitful scholarly debates, and hypotheses are formulated about the substantive core at stake. In addition, a critical overview of selected strands within the extensive historiographic literature exploring the Austrian School and ordoliberalism in recent decades is provided, including a specific reading of the concept of neoliberalism