ECoG-based short-range recurrent stimulation techniques to stabilize tissue at risk of progressive damage: Theory based on clinical observations

We introduce theoretical concepts based on chaos control to stabilize in acute stroke the tissue at risk of progressive damage by preventing adverse effects of waves of mass neuronal depolarization. Moreover, we present clinical electrocorticography (ECoG) recordings of relevant signals suggested for the feedback control. The recordings are performed in combination with novel subdural opto-electrode technology for simultaneous laser-Doppler flowmetry in patients with aneurysmal subarachnoid haemorrhage (aSAH). In aSAH patients waves of spreading depolarization (SD) have a high incidence and cause hypoxia in tissue at risk, and, importantly, the haemodynamic response is the inverse of that seen in healthy tissue. In previous clinical studies, clusters of prolonged SDs have been measured in aSAH patients in close proximity to structural brain damage as assessed by neuroimaging, and, in theoretical studies, a mechanism was presented, suggesting how a failure of internal feedback could be a putative mechanism of such SD cluster patterns in acute stroke. 

This failing internal feedback control is now suggested to be replaced by ECoG-based short-range recurrent functional stimulation that initiates the normal hyperperfusion haemodynamic response in a demand-controlled way and stabilizes the tissue at risk during the critical phase of SD passage. The suggested method has three key features: (i) it is short-range, i.e., in the order of the distance of the ECoG electrode strip, (ii) it is demand-controlled, and (iii) it uses no prior knowledge of the target state, in particular, it adapts to conditions in the healthy physiological range. On-demand type stimulation provides minimal invasive feedback as the control force is off when the target state is reached, i.e., the tissue at risk is without SD or it is back to the physiological range (out of risk). These last two features (ii-iii) are shared with classical methods of chaos control, where major progress was made in the last years with respect to extensions for spatio-temporal wave patterns. A detailed bifurcation analysis of the nonlinear model is presented, in particular, the SD cluster forming cortical state is suggested to be caused by a delay-induced saddle-node bifurcation.
&#xa

Non-contrast renal magnetic resonance imaging to assess perfusion and corticomedullary differentiation in health and chronic kidney disease

AIMS Arterial spin labelling (ASL) MRI measures perfusion without administration of contrast agent. While ASL has been validated in animals and healthy volunteers (HVs), application to chronic kidney disease (CKD) has been limited. We investigated the utility of ASL MRI in patients with CKD. METHODS We studied renal perfusion in 24 HVs and 17 patients with CKD (age 22-77 years, 40% male) using ASL MRI at 3.0T. Kidney function was determined using estimated glomerular filtration rate (eGFR). T1 relaxation time was measured using modified look-locker inversion and xFB02;ow-sensitive alternating inversion recovery true-fast imaging and steady precession was performed to measure cortical and whole kidney perfusion. RESULTS T1 was higher in CKD within cortex and whole kidney, and there was association between T1 time and eGFR. No association was seen between kidney size and volume and either T1, or ASL perfusion. Perfusion was lower in CKD in cortex (136 ± 37 vs. 279 ± 69 ml/min/100 g; p < 0.001) and whole kidney (146 ± 24 vs. 221 ± 38 ml/min/100 g; p < 0.001). There was significant, negative, association between T1 longitudinal relaxation time and ASL perfusion in both the cortex (r = -0.75, p < 0.001) and whole kidney (r = -0.50, p < 0.001). There was correlation between eGFR and both cortical (r = 0.73, p < 0.01) and whole kidney (r = 0.69, p < 0.01) perfusion. CONCLUSIONS Significant differences in renal structure and function were demonstrated using ASL MRI. T1 may be representative of structural changes associated with CKD; however, further investigation is required into the pathological correlates of reduced ASL perfusion and increased T1 time in CKD

Changes in the profile of inequality across Europe since 2005: austerity and redistribution

We present two Gini-like inequality indices that provide a more nuanced picture of how the profile of inequality has changed across European countries since 2005. We use these indices to analyse the distributional changes that can be attributed to the push for austerity. We estimate the JV-indices for 24 European countries over 9 years, and then use this panel to analyse the distributional effects of the fiscal consolidation policies Europe endured after the 2008 crisis. We find that austerity increased income inequality in eurozone countries, but reduced income inequality in countries that do not use the euro as their currency. We uncover a significant new relationship between austerity policies and the tails of the income distribution, further suggesting that in the eurozone these policies on average amount to a redistribution from the bottom to the top

Redistribution in the age of austerity : evidence from Europe 2006 - 2013

We examine the relationship between changes in a country’s public sector fiscal position on inequality at the top and bottom of the income distribution during the age of austerity from 2006 to 2013. We use a parametric Lorenz curve model and Gini-like indices of inequality as our measures to assess distributional changes. Based on Statistics of Income and Living Conditions (EU-SILC) and IMF data for 12 European countries, we find that more severe adjustments to the cyclically adjusted primary balance (i.e., more austerity) are associated with a more unequal distribution of income driven by rising inequality at the top. The data also weakly suggests a decrease in inequality at the bottom. The distributional impact of austerity measures reflects the reliance on regressive policies and likely produces increased incentives for rent-seeking while reducing incentives for workers to increase productivity

Over-the-scope clip (OTSC (R)) closure of a recto-acetabular fistula

A 25-year-old male Syrian refugee presented in our hospital with recurrent hip infections after having undergone hip arthroplasty abroad following destruction of his right hip joint by shell splinters in the Syrian civil war. The patient underwent hip arthroplasty revision with implantation of a cement spacer. CT-scan with rectal contrast media filling revealed a rectoacetabular fistula. Consecutively, the patient underwent ileostomy formation. The fistula was then successfully closed by endoscopic over-the-scope clipping (OTSC (R)). Fistulas between intestines and joints rarely develop and in the few cases published mostly extensive abdominal rescue surgery has been performed. Here, we present a case of a traumatic rectoacetabular fistula that was successfully closed by OTSC. This innovative method could represent a safe and suitable option to effectively close fistulas between joints and intestines thereby avoiding extensive rescue surgery with bowel resection or permanent ostomy

Predicting erythropoietin resistance in hemodialysis patients with type 2 diabetes

<p>Background: Resistance to ESAs (erythropoietin stimulating agents) is highly prevalent in hemodialysis patients with diabetes and associated with an increased mortality. The aim of this study was to identify predictors for ESA resistance and to develop a prediction model for the risk stratification in these patients.</p> <p>Methods: A post-hoc analysis was conducted of the 4D study, including 1015 patients with type 2 diabetes undergoing hemodialysis. Determinants of ESA resistance were identified by univariate logistic regression analyses. Subsequently, multivariate models were performed with stepwise inclusion of significant predictors from clinical parameters, routine laboratory and specific biomarkers.</p> <p>Results: In the model restricted to clinical parameters, male sex, shorter dialysis vintage, lower BMI, history of CHF, use of ACE-inhibitors and a higher heart rate were identified as independent predictors of ESA resistance. In regard to routine laboratory markers, lower albumin, lower iron saturation, higher creatinine and higher potassium levels were independently associated with ESA resistance. With respect to specific biomarkers, higher ADMA and CRP levels as well as lower Osteocalcin levels were predictors of ESA resistance.</p> <p>Conclusions: Easily obtainable clinical parameters and routine laboratory parameters can predict ESA resistance in diabetic hemodialysis patients with good discrimination. Specific biomarkers did not meaningfully further improve the risk prediction of ESA resistance. Routinely assessed data can be used in clinical practice to stratify patients according to the risk of ESA resistance, which may help to assign appropriate treatment strategies.</p&gt

The potential role of T-cells and their interaction with antigen-presenting cells in mediating immunosuppression following trauma-hemorrhage

Objective: Trauma-hemorrhage results in depressed immune responses of antigen-presenting cells (APCs) and T-cells. Recent studies suggest a key role of depressed T-cell derived interferon (IFN)-g in this complex immune cell interaction. The aim of this study was to elucidate further the underlying mechanisms responsible for dysfunctional T-cells and their interaction with APCs following trauma-hemorrhage. Design: Adult C3H/HeN male mice were subjected to trauma-hemorrhage (3-cm midline laparotomy) followed by hemorrhage (blood pressure of 35�5mmHg for 90 min and resuscitation) or sham operation. At 24 h thereafter, spleens were harvested and T-cells (by Microbeads) and APCs (via adherence) were Isolated. Co-cultures of T-cells and APCs were established for 48 h and stimulated with concanavalin A and lipopolysaccharide. T-Cell specific cytokines known to affect APC function (i.e. interleukin(IL)-2, IL-4 and granulocyte-macrophage colony-stimulating factor (GM-CSF)) were measured in culture supernatants by Multiplex assay. The expression of MHC class II as well as co-stimulatory surface molecules on T-cells and APCs was determined by flow cytometry. Results: The release of IL-4 and GM-CSF by T-cells was suppressed following trauma-hemorrhage, irrespective of whether sham or trauma-hemorrhage APCs were present. Antigen-presenting cells from animals subjected to trauma-hemorrhage did not affect T-cell derived cytokine release by sham T-cells. In contrast, T-cells from traumahemorrhage animals depressed MHC class II expression of CD11c(þ) cells, irrespective of whether APCs underwent sham or trauma-hemorrhage procedure. Surprisingly, co-stimulatory molecules on APCs (CD80, CD86) were not affected by trauma-hemorrhage. Conclusions: These results suggest that beside IFN-g other T-cell derived cytokines contribute to immunosuppression following trauma-hemorrhage causing diminished MHC II expression on APCs. Thus, T-cells appear to play an important role in this interaction at the time-point examined. Therapeutic approaches should aim at maintenance of T-cell function and their interaction with APCs to prevent extended immunosuppression following trauma-hemorrhage