Two pore domain potassium channels in cerebral ischemia: a focus on K2P9.1 (TASK3, KCNK9)

BACKGROUND: Recently, members of the two-pore domain potassium channel family (K2P channels) could be shown to be involved in mechanisms contributing to neuronal damage after cerebral ischemia. K2P3.1-/- animals showed larger infarct volumes and a worse functional outcome following experimentally induced ischemic stroke. Here, we question the role of the closely related K2P channel K2P9.1. METHODS: We combine electrophysiological recordings in brain-slice preparations of wildtype and K2P9.1-/- mice with an in vivo model of cerebral ischemia (transient middle cerebral artery occlusion (tMCAO)) to depict a functional impact of K2P9.1 in stroke formation. RESULTS: Patch-clamp recordings reveal that currents mediated through K2P9.1 can be obtained in slice preparations of the dorsal lateral geniculate nucleus (dLGN) as a model of central nervous relay neurons. Current characteristics are indicative of K2P9.1 as they display an increase upon removal of extracellular divalent cations, an outward rectification and a reversal potential close to the potassium equilibrium potential. Lowering extracellular pH values from 7.35 to 6.0 showed comparable current reductions in neurons from wildtype and K2P9.1-/- mice (68.31 +/- 9.80% and 69.92 +/- 11.65%, respectively). These results could be translated in an in vivo model of cerebral ischemia where infarct volumes and functional outcomes showed a none significant tendency towards smaller infarct volumes in K2P9.1-/- animals compared to wildtype mice 24 hours after 60 min of tMCAO induction (60.50 +/- 17.31 mm3 and 47.10 +/- 19.26 mm3, respectively). CONCLUSIONS: Together with findings from earlier studies on K2P2.1-/- and K2P3.1-/- mice, the results of the present study on K2P9.1-/- mice indicate a differential contribution of K2P channel subtypes to the diverse and complex in vivo effects in rodent models of cerebral ischemia

Clinical results of the Metha short hip stem: a perspective for younger patients?

In recent years, various uncemented proximal metaphyseal hip stems were introduced for younger patients as a bone preserving strategy. Initial osteodensitometric analyses of the surrounding bone of short stems indicate an increase of bone mass with secondary bone ingrowth fixation as a predictor of long-term survival of these types of implants. We report the outcome of 151 modular Metha short hip stem implants in 148 patients between March 2005 and October 2007. The mean follow-up was 5.8±0.7 years and the mean age of the patients was 55.7±9.8 years. Along with demographic data and co-morbidities, the Harris Hip Score (HHS), the Hip dysfunction and Osteoarthritis Outcome Score (HOOS), and also the results of a patient-administered questionnaire were recorded pre-operatively and at follow-up. The mean HHS increased from 46±17 pre-operatively to 90±5 the HOOS improved from 55±16 pre-operatively to 89±10 at the final follow-up. A total of three patients have been revised, two for subsidence with femoral revision and one for infection without femoral revision (Kaplan Meier survival estimate 98%). The radiological findings showed no radiolucent lines in any of the patients. The modular Metha short hip stem was implanted in younger patients, who reported an overall high level of satisfaction. The clinical and radiographic results give support to the principle of using short stems with metaphyseal anchorage. However, long-term results are necessary to confirm the success of this concept in the years to come

SmartAQnet: remote and in-situ sensing of urban air quality

our time. However, it is very difficult for many cities to take measures to accommodate today’s needs concerning e.g. mobility, housing and work, because a consistent fine-granular data and information on causal chains is largely missing. This has the potential to change, as today, both large-scale basic data as well as new promising measuring approaches are becoming available. The project “SmartAQnet”, funded by the German Federal Ministry of Transport and Digital Infrastructure (BMVI), is based on a pragmatic, data driven approach, which for the first time combines existing data sets with a networked mobile measurement strategy in the urban space. By connecting open data, such as weather data or development plans, remote sensing of influencing factors, and new mobile measurement approaches, such as participatory sensing with low-cost sensor technology, “scientific scouts” (autonomous, mobile smart dust measurement device that is auto-calibrated to a high-quality reference instrument within an intelligent monitoring network) and demand-oriented measurements by light-weight UAVs, a novel measuring and analysis concept is created within the model region of Augsburg, Germany. In addition to novel analytics, a prototypical technology stack is planned which, through modern analytics methods and Big Data and IoT technologies, enables application in a scalable way

Activity Modes in Thalamocortical Relay Neurons are Modulated by Gq/G11 Family G-proteins – Serotonergic and Glutamatergic Signaling

In thalamocortical relay (TC) neurons, G-protein-coupled receptors play an important part in the control of activity modes. A conditional Gαq knockout on the background of a constitutive Gα11 knockout (Gαq/Gα11−/−) was used to determine the contribution of Gq/G11 family G-proteins to metabotropic serotonin (5-HT) and glutamate (Glu) function in the dorsal part of the lateral geniculate nucleus (dLGN). In control mice, current clamp recordings showed that α-m-5-HT induced a depolarization of Vrest which was sufficient to suppress burst firing. This depolarization was concentration-dependent (100 μM: +6 ± 1 mV, n = 10; 200 μM: +10 ± 1 mV, n = 7) and had a conditioning effect on the activation of other Gαq-mediated pathways. The depolarization was significantly reduced in Gαq/Gα11−/− (100 μM: 3 ± 1 mV, n = 11; 200 μM: 5 ± 1 mV, n = 6) and was apparently insufficient to suppress burst firing. Activating Gαq-coupled muscarinic receptors affected the magnitude of α-m-5-HT-induced effects in a reciprocal manner. Furthermore, the depolarizing effect of mGluR1 agonists was significantly reduced in Gαq/Gα11−/− mice. Immunohistochemical stainings revealed binding of 5-HT2CR- and mGluR1α-, but not of 5-HT2AR-specific antibodies in the dLGN of Gαq/Gα11−/− mice. In conclusion, these findings demonstrate that transmitters of ascending brainstem fibers and corticofugal fibers both signal via a central element in the form of Gq/G11-mediated pathways to control activity modes in the TC system

Robot-Assisted versus Laparoscopic Donor Nephrectomy: A Comparison of 250 Cases

Living kidney donation is the best treatment for end-stage renal disease, however, the best surgical approach for minimally-invasive donor nephrectomy (DN) is still a matter of debate. This bi-centric study aimed to retrospectively compare perioperative outcomes and postoperative kidney function after 257 transperitoneal DNs including 52 robot-assisted (RDN) and 205 laparoscopic DNs (LDN). As primary outcomes, the intraoperative (operating time, warm ischemia time (WIT), major complications) and postoperative (length of stay, complications) results were compared. As secondary outcomes, postoperative kidney and graft function were analyzed including delayed graft function (DGF) rates, and the impact of the surgical approach was assessed. Overall, the type of minimally-invasive donor nephrectomy (RDN vs. LDN) did not affect primary outcomes, especially not operating time and WIT; and major complication and DGF rates were low in both groups. A history of smoking and preoperative kidney function, but not the surgical approach, were predictive for postoperative serum creatinine of the donor and recipient. To conclude, RDN and LDN have equivalent perioperative results in experienced centers. For this reason, not the surgical approach, but rather the graft- (preoperative kidney function) and patient-specific (history of smoking) aspects impacted postoperative kidney function

Numerical simulation and experimental validation of the cladding material distribution of hybrid semi-finished products produced by deposition welding and cross-wedge rolling

The service life of rolling contacts is dependent on many factors. The choice of materials in particular has a major influence on when, for example, a ball bearing may fail. Within an exemplary process chain for the production of hybrid high-performance components through tailored forming, hybrid solid components made of at least two different steel alloys are investigated. The aim is to create parts that have improved properties compared to monolithic parts of the same geometry. In order to achieve this, several materials are joined prior to a forming operation. In this work, hybrid shafts created by either plasma (PTA) or laser metal deposition (LMD-W) welding are formed via cross-wedge rolling (CWR) to investigate the resulting thickness of the material deposited in the area of the bearing seat. Additionally, finite element analysis (FEA) simulations of the CWR process are compared with experimental CWR results to validate the coating thickness estimation done via simulation. This allows for more accurate predictions of the cladding material geometry after CWR, and the desired welding seam geometry can be selected by calculating the cladding thickness via CWR simulation. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Impact of daclizumab, low-dose cyclosporine, mycophenolate mofetil and steroids on renal function after kidney transplantation

Background. Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. Methods. We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. Results. Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 ± 17) than standard patients (29 ± 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). Conclusion. We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reaction

Forward and backward diffraction radiation of relativistic electrons in a dielectric targets

BACKGROUND: Early and long-term use of cyclosporine A (CsA) leads to increased risks of renal toxicity. We hypothesized that administration of daclizumab in combination with mycophenolate mofetil (MMF) allows a relevant reduction in the dose of CsA. METHODS: We carried out a 3-year, prospective, randomized, controlled clinical multi-centre trial in 156 patients. The patients were randomized to standard treatment (CsA, MMF, steroids) or to high-dose daclizumab (first dose: 2 mg/kg), in combination with low-dose CsA, MMF and steroids. We maintained the mean CsA levels of daclizumab patients at 57% of standard patients (132 versus 216 ng/ml) on Day 7 post-transplant, and 84% by 6 months. RESULTS: Primary outcome, creatinine clearance (with imputation of informative dropouts) at 12 months, was significantly better in daclizumab-treated (34 +/- 17) than standard patients (29 +/- 17; P = 0.028, two sided). Only 5 cases of BPAR were recorded in the daclizumab compared to 22 in the standard group (P = 0.0016). Daclizumab patients had 91% event-free survival after 1 year compared to 66% in standard patients (P = 0.00017). CONCLUSION: We demonstrate here that high-dose daclizumab in combination with lower CsA levels in adult renal transplant recipients is as or more effective than standard regimen (CsA, MMF, steroids) and may result in better outcomes at 12 months post-transplant with no increase in adverse reactions