Paracrine interleukin 6 induces cerebral remodeling at early stages after unilateral common carotid artery occlusion in mice

AIMS: Carotid artery disease is frequent and can result in chronic modest hypoperfusion of the brain. If no transient ischemic attack or stroke occur, it is classified asymptomatic. In the long-term, though, it can lead to cognitive impairment. Fostering cerebral remodeling after carotid artery occlusion might be a new concept of treatment. Paracrine Interleukin 6 (IL-6) can induce such remodeling processes at early stages. However, it has neurodegenerative long-term effects. With this exploratory study, we investigated the effect of paracrine IL-6 on cerebral remodeling in early stages after asymptomatic carotid artery occlusion to identify new treatment targets. METHODS AND RESULTS: To mimic a human asymptomatic carotid artery disease, we used a mouse model of unilateral common carotid artery (CCA) occlusion. We developed a mouse model for inducible paracrine cerebral IL-6 expression (Cx30-Cre-ERT2;FLEX-IL6) and induced IL-6 2 days after CCA occlusion. We studied the effects of paracrine IL-6 after CCA occlusion on neuronal connectivity using diffusion tensor imaging and on local proteome regulations of the hypo-perfused striatum and contralateral motor cortex using mass spectrometry of laser capture micro-dissected tissues. Paracrine IL-6 induced cerebral remodeling leading to increased inter-hemispheric connectivity and changes in motor system connectivity. We identified changes in local protein abundance which might have adverse effects on functional outcome such as upregulation of Synuclein gamma (Sncg) or downregulation of Proline Dehydrogenase 1 (Prodh). However, we also identified changes in local protein abundance having potentially beneficial effects such as upregulation of Caprin1 or downregulation of GABA transporter 1 (Gat1). CONCLUSIONS: Paracrine cerebral IL-6 at early stages induces changes in motor system connectivity and the proteome after asymptomatic CCA occlusion. Our results may help to distinguish unfavorable from beneficial IL-6 dependent protein regulations. Focusing on these targets might generate new treatments to improve long-term outcome in patients with carotid artery disease

Finite-Temperature Transport in Finite-Size Hubbard Rings in the Strong-Coupling Limit

We study the current, the curvature of levels, and the finite temperature charge stiffness, D(T,L), in the strongly correlated limit, U>>t, for Hubbard rings of L sites, with U the on-site Coulomb repulsion and t the hopping integral. Our study is done for finite-size systems and any band filling. Up to order t we derive our results following two independent approaches, namely, using the solution provided by the Bethe ansatz and the solution provided by an algebraic method, where the electronic operators are represented in a slave-fermion picture. We find that, in the U=\infty case, the finite-temperature charge stiffness is finite for electronic densities, n, smaller than one. These results are essencially those of spinless fermions in a lattice of size L, apart from small corrections coming from a statistical flux, due to the spin degrees of freedom. Up to order t, the Mott-Hubbard gap is \Delta_{MH}=U-4t, and we find that D(T) is finite for n<1, but is zero at half-filling. This result comes from the effective flux felt by the holon excitations, which, due to the presence of doubly occupied sites, is renormalized to \Phi^{eff}=\phi(N_h-N_d)/(N_d+N_h), and which is zero at half-filling, with N_d and N_h being the number of doubly occupied and empty lattice sites, respectively. Further, for half-filling, the current transported by any eigenstate of the system is zero and, therefore, D(T) is also zero.Comment: 15 pages and 6 figures; accepted for PR

Motivation and Knowledge Sharing through Social Media within Danish Organizations

Part 3: Creating Value through ApplicationsInternational audienceBased on an empirical quantitative study, this article investigates employee motivation in Danish companies and aims at determining which factors affect employees’ knowledge sharing through social media in a working environment. Our findings pinpoint towards the potential social media have for enhancing internal communication, knowledge sharing and collaboration in organizations, but the adoption is low, at this point, due to mainly organizational and individual factors. Technological factors do not seem to affect employees’ motivation for knowledge sharing as much as previous research has found, but it is the influence from the combination of individual and organizational factors, which affect the adoption of the platforms. A key finding in the study is that knowledge sharing is not a ‘social dilemma’ as previous studies have found. The study shows a positive development in employees’ willingness to share knowledge, because knowledge sharing is considered more beneficial than to hoard it

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

Preoperative medical treatment in Cushing&apos;s syndrome : frequency of use and its impact on postoperative assessment : data from ERCUSYN

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). Patients and methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results