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With the increasing prevalence of atrial fibrillation (AF), it entails expanding oral anticoagulants (OACs) use, carrying a higher risk of associated hemorrhagic events, including intracranial hemorrhage (ICH). Despite advances in OACs development with a better safety profile and reversal agent for these anticoagulants, there is still no consensus on the optimal management of patients with OACs-associated ICH. In this review, the authors have carried out an exhaustive search on the advances in recent years. The authors provide an update on the management of ICH in anticoagulated patients, as well as an update on the latest evidence on anticoagulation resumption, recent therapeutic strategies, and investigational drugs that could play a role in the future. Following an ICH event in an anticoagulated patient, a comprehensive clinical evaluation is imperative. Anticoagulation should be promptly withdrawn and reversed. Once the patient is stabilized, a reintroduction of anticoagulation should be considered, typically within a timeframe of 4–8 weeks, if feasible. If re-anticoagulation is not possible, alternative options such as Left Atrial Appendage Occlusion are available. [ABSTRACT FROM AUTHOR]

Medicane Ianos in September 2020 was one of the strongest medicanes observed in the last 25 years. It was, like other medicanes, a very intense cyclone evolving from a baroclinic mid-latitude low into a tropical-like cyclone. The dynamical elements necessary to improve the predictability of Ianos are explored with the use of simulations with the Met Office Unified Model (MetUM) at 2.2 km grid spacing for five different initialisation times, from four to two days before Ianos's landfall. Simulations are also performed with the Sea Surface Temperature (SST) uniformly increased and decreased by 2 K from analysis to explore the impact of enhanced and reduced sea-surface surface fluxes on Ianos's evolution. All the simulations with +2 K SST are able to simulate medicane Ianos, albeit too intensely. The simulations with control SST initialised at the two earliest times fail to capture intense preceding precipitation events at the right locations, and the subsequent development of Ianos. Amongst the simulations with -2 K SST, only the one initialised at the latest time develops the medicane. Links between sea-surface fluxes and upper-level baroclinic processes are investigated. We find (i) a bubble of low-valued potential vorticity (PV) formed within a trough above where Ianos developed, diabatic processes associated with a preceding precipitation event triggered a balanced divergent flow in the upper-levels which contributed to the creation and maintenance this low-PV bubble, as shown by results from a semi-geostrophic inversion tool, (ii) Upper-level geostrophic vorticity advection associated with the low-PV bubble forced quasi-geostrophic ascent during Ianos's cyclogenesis, and (iii) diabatic processes dominated by deep convection formed a vertical PV tower in Ianos and continued to produce diabatically-induced divergent outflow aloft, thus sustaining Ianos's development. Simulations missing any of these three elements do not develop medicane Ianos. Our results imply that preceding convection was essential for the subsequent development of Ianos, highlighting the importance of the interactions between near-surface small-scale diabatic processes and the upper-level quasi-geostrophic flow. A warmer SST strengthens the processes and thus enables Ianos to be predicted in simulations initiated at the earlier times that failed to generate the medicane with control SSTs. [ABSTRACT FROM AUTHOR]

A multi-season convection permitting regional climate simulation of the Maritime Continent using the Met Office Unified Model with 2.2-km grid spacing is presented and evaluated. The simulations pioneer the use of atmosphere-ocean coupling with the multi-column K profile parametrisation (KPP) mixed layer ocean model in atmospheric convection permitting climate simulations. Comparisons are made against a convection parametrised simulation in which it is nested, and which in turn derives boundary conditions from ERA5 reanalysis. This paper describes the configuration, performance of the mean state and variability of the two simulations compared against observational datasets. The models both have minor sea surface temperature (SST) and wet precipitation biases. The diurnal cycle, representation of equatorial waves and relationship between SST and precipitation are all improved in the convection permitting model compared to the convection parametrised model. The MJO is present in both models with a faster than observed propagation speed. However, it is unclear whether fidelity of the MJO simulation is inherent to the model or whether it predominantly arises from the forcing at the boundaries. [ABSTRACT FROM AUTHOR]

On 18 September 2020, medicane Ianos hit the western coast of Greece resulting in flooding and severe damage at several coastal locations. In this work, we aim at evaluating its impact on sea conditions and the associated uncertainty through the use of an ensemble of numerical simulations. We applied a coupled wave-current model to an unstructured mesh representing the whole Mediterranean Sea, with a grid resolution increasing in the Ionian Sea along the cyclone path and the landfall area. To investigate the uncertainty of modelling sea levels and waves for such an intense event, we performed a multimodel ensemble of ocean simulations using several coarse (10 km) and high-resolution (2 km) meteorological forcings from different mesoscale models. The performance of the ocean and wave models was evaluated against observations retrieved from fixed monitoring stations and satellites. All model runs emphasized the occurrence of severe sea conditions along the cyclone path and at the coast. Due to the rugged and complex coastline, extreme sea levels are localised at specific coastal sites. However, numerical results show a large spread of the simulated sea conditions for both the sea level and waves highlighting the large uncertainty in simulating this kind of extreme event. The multi-model / multi-physics approach allows us to assess how the uncertainty propagates from meteorological to ocean variables and the subsequent coastal impact. The ensemble mean and standard deviation were combined to prove the hazard scenarios of the potential impact of such an extreme event to be used in a flood risk management plan. [ABSTRACT FROM AUTHOR]

Gossypol is a natural disesquiter-pene that blocks the activity of the mammalian facilitative hexose transporter GLUT1. In human HL-60 cells, which express GLUT1, Chinese hamster ovary ceils overexpressing GLUT1, and human erythrocytes, gossypol inhibited hexose transport in a concentration-dependent fashion, indicating that blocking of GLUT1 activity is independent of cellular context. With the exception of red blood cells, the inhibition of cellular transport was instantaneous. Gossypol effect was specific for the GLUT1 transporter since it did not alter the uptake of nicotinamide by human erythrocytes. Gossypol affects the glucose-displaceable binding of cytochalasin B to GLUT1 in human erythrocyte ghost in a mixed noncompetitive way, with a [K.sub.i] value of 20 [micro]M. Likewise, GLUT1 fluorescence was quenched ~80% by gossypol, while Stern-Volmer plots for quenching by iodide displayed increased slopes by gossypol addition. These effects on protein fluorescence were saturable and unaffected by the presence of D-glucose. Gossypol did not alter the affinity of D-glucose for the external substrate site on GLUT1. Kinetic analysis of transport revealed that gossypol behaves as a noncompetitive inhibitor of zero-trans (substrate outside but not inside) transport, but it acts as a competitive inhibitor of equilibrium-exchange (substrate inside and outside) transport, which is consistent with interaction at the endofacial surface, but not at the exofacial surface of the transporter. Thus, gossypol behaves as a quasi-competitive inhibitor of GLUT1 transport activity by binding to a site accessible through the internal face of the transporter, but it does not, in fact, compete with cytochalasin B binding. Our observations suggest that some effects of gossypol on cellular physiology may be related to its ability to disrupt the normal hexose flux through GLUT1, a transporter expressed in almost every kind of mammalian cell and responsible for the basal uptake of glucose. glucose transport; GLUT1 transporter; transporter inhibition