Cerebrovascular accidents complicating transcatheter aortic valve implantation: frequency, timing and impact on outcomes

Cerebrovascular accidents (CVA) are considered among the most serious adverse events after transcatheter aortic valve implantation (TAVI). The objective of the present study was to evaluate the frequency and timing of CVA after TAVI and to investigate the impact on clinical outcomes within 30 days of the procedure.

Long-term propensity score-matched comparison of percutaneous closure of patent foramen ovale with medical treatment after paradoxical embolism

Patients with ischemic stroke or transient ischemic attack presumably related to patent foramen ovale (PFO) are at risk for recurrent cerebrovascular events. Differences in long-term clinical outcome were investigated among patients with percutaneous PFO closure and those who received medical treatment.

Fingerprints of changes in the terrestrial carbon cycle in response to large reorganizations in ocean circulation

CO2 and carbon cycle changes in the land, ocean and atmosphere are investigated using the comprehensive carbon cycle-climate model NCAR CSM1.4-carbon. Ensemble simulations are forced with freshwater perturbations applied at the North Atlantic and Southern Ocean deep water formation sites under pre-industrial climate conditions. As a result, the Atlantic Meridional Overturning Circulation reduces in each experiment to varying degrees. The physical climate fields show changes qualitatively in agreement with results documented in the literature, but there is a clear distinction between northern and southern perturbations. Changes in the physical variables, in turn, affect the land and ocean biogeochemical cycles and cause a reduction, or an increase, in the atmospheric CO2 concentration by up to 20 ppmv, depending on the location of the perturbation. In the case of a North Atlantic perturbation, the land biosphere reacts with a strong reduction in carbon stocks in some tropical locations and in high northern latitudes. In contrast, land carbon stocks tend to increase in response to a southern perturbation. The ocean is generally a sink of carbon although large reorganizations occur throughout various basins. The response of the land biosphere is strongest in the tropical regions due to a shift of the Intertropical Convergence Zone. The carbon fingerprints of this shift, either to the south or to the north depending on where the freshwater is applied, can be found most clearly in South America. For this reason, a compilation of various paleoclimate proxy records of Younger Dryas precipitation changes are compared with our model results. The proxy records, in general, show good agreement with the model's response to a North Atlantic freshwater perturbation.

Variations of the Atlantic meridional overturning circulation in control and transient simulations of the last millennium

The variability of the Atlantic meridional overturing circulation (AMOC) strength is investigated in control experiments and in transient simulations of up to the last millennium using the low-resolution Community Climate System Model version 3. In the transient simulations the AMOC exhibits enhanced low-frequency variability that is mainly caused by infrequent transitions between two semi-stable circulation states which amount to a 10 percent change of the maximum overturning. One transition is also found in a control experiment, but the time-varying external forcing significantly increases the probability of the occurrence of such events though not having a direct, linear impact on the AMOC. The transition from a high to a low AMOC state starts with a reduction of the convection in the Labrador and Irminger Seas and goes along with a changed barotropic circulation of both gyres in the North Atlantic and a gradual strengthening of the convection in the Greenland-Iceland-Norwegian (GIN) Seas. In contrast, the transition from a weak to a strong overturning is induced by decreased mixing in the GIN Seas. As a consequence of the transition, regional sea surface temperature (SST) anomalies are found in the midlatitude North Atlantic and in the convection regions with an amplitude of up to 3 K. The atmospheric response to the SST forcing associated with the transition indicates a significant impact on the Scandinavian surface air temperature (SAT) in the order of 1 K. Thus, the changes of the ocean circulation make a major contribution to the Scandinavian SAT variability in the last millennium.

HIV-1 Nef interferes with T-lymphocyte circulation through confined environments in vivo

HIV-1 negative factor (Nef) elevates virus replication and contributes to immune evasion in vivo. As one of its established in vitro activities, Nef interferes with T-lymphocyte chemotaxis by reducing host cell actin dynamics. To explore Nef's influence on in vivo recirculation of T lymphocytes, we assessed lymph-node homing of Nef-expressing primary murine lymphocytes and found a drastic impairment in homing to peripheral lymph nodes. Intravital imaging and 3D immunofluorescence reconstruction of lymph nodes revealed that Nef potently impaired T-lymphocyte extravasation through high endothelial venules and reduced subsequent parenchymal motility. Ex vivo analyses of transendothelial migration revealed that Nef disrupted T-lymphocyte polarization and interfered with diapedesis and migration in the narrow subendothelial space. Consistently, Nef specifically affected T-lymphocyte motility modes used in dense environments that pose high physical barriers to migration. Mechanistically, inhibition of lymph node homing, subendothelial migration and cell polarization, but not diapedesis, depended on Nef's ability to inhibit host cell actin remodeling. Nef-mediated interference with in vivo recirculation of T lymphocytes may compromise T-cell help and thus represents an important mechanism for its function as a HIV pathogenicity factor.