Illustration by Jan BuchczikDecember 19, 2024 ShareSave Want to stay current with Arthur’s writing? Sign up to get an email every time a new column comes out spent most of his life on the same working-class street in Barcelona’s El Clot neighborhood he saw Spain’s bloody civil war taking place literally in front of his house Some died; others spent years in jail or were forced into exile an experience that affected him for the rest of his life Every time he wanted to make a point about society or culture he read in his local paper an article of mine about unhappiness “You have a lot of complicated theories,” he told me “but the real reason people are unhappy is very simple.” I asked him to elaborate “They don’t enjoy their dinner,” he responded “But one day a year—Christmas—we got to eat whatever we wanted That is a somewhat reductive hypothesis about global unhappiness But he was not wrong in his main contention: Happiness rises well-being requires that you discipline your will and defer your gratifications Understanding this and taking action to change your habits can make you a much happier person Read: The politics of a long-dead dictator still haunt Spain In the behavioral sciences, the most famous study of deferred gratification is the so-called marshmallow experiment undertaken in 1970 by the psychologists Walter Mischel and Ebbe B. Ebbesen. This research project brought 32 young children into a laboratory where they were offered either animal crackers or pretzel sticks (the marshmallow was an option that came only in later experiments) the researchers offered an upgrade: If the children could wait by themselves for 15 minutes without eating the snack and the researchers left the room and observed each child through a one-way mirror Ten subjects succeeded in waiting and got the additional snack; 22 of them gave in to their desire and gobbled up the treat before the 15 minutes had elapsed The researchers’ conclusion was clear: Being able to defer gratification leads to a more successful—and ultimately more satisfying—life they typically use it immediately to acquire things—because they identify having possessions as a source of happiness The researchers found that these people were less happy than people who didn’t behave this way more regulated dopamine release than mice without this skill Read: Why rich kids are so good at the marshmallow test 1. Think about the future. A research-proven approach to improving your capacity for deferred gratification is to imagine yourself in the future. In 2011, a team of researchers interested in how to elicit saving behavior employed digital aging techniques and virtual reality to enable people to interact with elderly versions of themselves. They found that after doing so the participants were more willing than other people to accept awards of money at a future date rather than immediately if you are hankering for a portion of junk-calorie carbohydrates at 4 p.m. version of yourself who forwent the snack and is hungry for a good healthy dinner Or say you are in college and have a big exam tomorrow but have just gotten invited to a party: Have a chat with the unhappy future you who took the exam after partying instead of studying Half of the group were then given an exercise in mindfulness breathing while the other half (the control group) watched a music video the mindfulness practitioners were significantly more likely than before to defer rewards (whereas the music-video watchers showed no change) this second result is not at odds with the first finding: Its conclusion is that being more conscious when you make decisions will lead you to optimize your choices So you can bring the two injunctions together and combine them to best effect: Think clearly about what you’re doing right now and then think clearly about how you will reflect on your action later think about how you are feeling at this moment or are you just self-soothing with a bit of retail therapy imagine yourself looking at the sweater in two months’ time Does it give you delight or remind you that you have to make a credit-card payment Arthur C. Brooks: Four rules for identifying your life’s work My father-in-law was right that deferring gratification leads to greater happiness The good news is that you don’t need to be in the middle of a civil war to make this skill worth cultivating But I always wondered whether he was right in his specific example: Does snacking lower well-being by ruining your enjoyment of proper meals I have been unable to find any studies of this precise curiosity so I had to triangulate some related research findings to come to a convincing answer Researchers who were studying the eating behavior of children reported in 2017 in the Journal of Nutrition Education and Behavior that kids enjoyed food more when they followed structured meal settings—such as eating at the same times each day and dining in a family setting They also tended to be less fussy about what they were eating This is broadly supportive of my father-in-law’s theory was his complete unwillingness to save money and a reckless openhandedness about spending it And this negative example supported his theory even more—though in a sad way as he constantly ducked creditors and struggled to meet his basic needs in old age Perhaps the inability to save was also an effect of the privations of his 1930s childhood: If you never know whether you’ve got enough to get through the month Even though he suffered as a result of his spendthrift ways I took a valuable lesson from his example in this too So my seasonal advice: Go to your holiday dinner good and hungry But don’t buy your holiday feast on credit is an apartment block in Valencia's historic El Cabanyal neighborhood which has been under threat of demolition for 20 years Gypsy families have occupied and restored some of the empty apartments in El Clot where they live in poverty and under threat from law enforcement El Clot neighborhood has virtually disappeared with the only remains left standing on the dockworkers' block mostly gypsy families who have occupied the abandoned apartments in the building Gypsies belong to Spain's largest ethnic minority a minority that is very heavily socially stereotyped and according to various surveys also the group most harshly rejected by mainstream society a way to explore the world and understand it trying to understand them and developing relationships with my subjects over time I seek an unbreakable but intimate portrait objectively powerful but full of personal emotion the product of commitment to people and their environment trying to represent both their strength and vulnerability Although El Clot is a slum I have not encountered either rejection or pain trying to turn this work into an affirmation of the dignity and humanity that is in all people and trying to capture in pictures the wild vitality and hope of this community more ambitious objectives: methodically documenting all aspects of gypsy culture Already a member? Not a member? Sign up Explore our Food Tours → you’ll encounter all the usual suspects of a typical residential Barcelona neighborhood: a small butcher Bodegas are the social and culinary epicenters of Barcelona – this is especially true for more residential where eating out at a proper restaurant is a rare event kept for special occasions like birthdays or anniversaries locals go to their neighborhood bodega for a small copa of nondescript red or white wine and a tapa of boquerones or some simple cold cuts we immediately felt like we were walking into a friend’s home – if we had a friend that spent all their money on wine mass-produced bodega wine is replaced with carefully selected boutique natural wine Brightly lit shelves packed with bottles are the first thing we noticed upon walking in broad-shouldered man with a warm smile and deep voice coming over to greet us The man behind Vins Per Tu is Brazil-born William “Willy” Rezende Willy decided to take up an offer from some friends to visit Barcelona After two weeks of beach-filled days and party-filled nights he decided not to return to Brazil leaving a banking career and a very surprised girlfriend behind Though Willy dreamt of owning his own place for many years it seemed impossible with Barcelona’s rising rent prices But the pandemic brought with it new opportunities: rent prices dropped locals are spending more time in their own neighborhoods.” During the spring of 2020 Willy realized that rather than competing with countless other bars and restaurants in the city center which are highly reliant on tourism to survive he could create a new gastronomic space in his own neighborhood and serve his fellow barrio locals Vins Per Tu is a vinoteca first and foremost – a space to enjoy a glass of wine and maybe take a couple of bottles home with you Willy will open a few different bottles every evening to choose from This means every visit begins with a personal interaction with Willy who will pick out something for each customer giving them something new to try,” he explains It was thanks to a chance encounter that the food offered to accompany the wine is as exciting and unique as it is. “My initial plan was to have classic bodega food – conservas some cold cuts – keep things simple,” says Willy an Argentinian chef who offered to revamp the menu The result is a selection of elevated bodega classics that incorporate fresh seasonal ingredients and modern presentation we started with succulent oysters which pay homage to Willy’s Brazilian origins with a cachaça sour foam followed by crispy pan con tomate made with artisanal coca de cristal bread and an umami-filled matrimonio (“marriage”) of pickled and preserved anchovies The special of the day was coca de caballa perfectly moist mackerel on a bed of slowly cooked confit tomatoes we finished with an another play on Catalonia-meets-Brazil with a dish of tender secreto ibérico –thin marbled cuts of pork – with a corn cream and pickled onions Willy is still playing around with the dishes and wines he offers and learning what his customers like the most His goal for Vins Per Tu to continue to open up the minds and palettes of his patrons I’m here to offer sensations and experiences,” he says art exhibitions and wine tastings – and to continue to challenge what a neighborhood bodega can be loading map - please wait...Map could not be loaded - please enable Javascript!→ more information READ MORELas Palmas Medical Center leads El Paso with innovative blood clot removal techniqueby Drew Pittock Texas (KFOX14/CBS4) — Las Palmas Medical Center recently became the first hospital in El Paso to remove a blood clot through a new Las Palmas Medical Center successfully removed a blood clot that was complicated by the presence of a venous stent or mesh tube inserted into weak or narrowed veins that improves blood flow Stent thrombosis is the medical term for a blood clot that forms near a venous stent and it can lead to various issues blood clots can form in people of all ages and for myriad reasons such as immobility during a long car or plane ride trauma to the extremities that cause inflammation in the veins or genetics RECOMMENDED:Menstrual cycle reshapes women's brains, El Paso expert explains Shami simply wants his patients to "keep walking." the mechanical thrombectomy device operates like a brillo pad that scrubs the stent clean before it can be sucked out with a catheter an alternative treatment option for venous stent thrombosis involved the use of blood thinners they're not an ideal treatment for all patients for a variety of reasons from socioeconomic status to physical traits The Las Palmas Medical Center limb preservation program has been working to improve overall limb health and quality Las Palmas Medical Center is now able to offer intervention to address chronic clots Sign up to receive the top interesting stories from in and around our community once daily in your inbox you are at risk for developing blood clots 1 in 5 blood clots are due to cancer and some of its treatments One important step to take is to understand your risk for dangerous blood clots because cancer and some of its treatments can increase your risk for blood clots Talk with your healthcare team about your risk for blood clots Make sure your cancer doctor and healthcare team know about your personal and family history of blood clots It is most important that you recognize the symptoms of blood clots and contact your cancer doctor if you experience any of them Work with your healthcare team and make a blood clot prevention plan specific to your medical history and treatment A plan to prevent blood clots can help protect the most important thing – your health – during cancer treatment Blood clots are a leading cause of death among people with cancer Early diagnosis and treatment can reduce complications of blood clots The risk of a dangerous blood clot is greatest in the first few months after cancer is diagnosed survival rates are lower for people who also have blood clots Click on the image to view and share an infographic about the risk for blood clots connected to cancer and its treatment Recognize the Signs and Symptoms of Blood Clots Signs and symptoms of a blood clot in a person’s leg or arm (also called a DVT) may include the following: Signs and symptoms of a blood clot in a person’s lung (also called a PE) may include the following: Chest pain that worsens with a deep breath or cough it is important to understand your risk for blood clots Click on the image below to view and download a list of risk factors that can help you and your cancer doctor determine your blood clot risk Talk to your healthcare team and make a plan to prevent blood clots and risk factors for blood clots and discuss these risks with your cancer doctor When you are at home recovering from surgery or if you are receiving treatment in an outpatient clinic stay alert for any signs or symptoms of blood clots Contact your cancer doctor right away if you experience any blood clot symptoms Work with your healthcare team to make a prevention plan The National Blood Clot Alliance and the Centers for Disease Control and Prevention are working on this important public health campaign to get the word out about blood clot risks and the signs and symptoms of blood clots You can be an important part of this education campaign by helping us View and download View and download The National Blood Clot Alliance The Centers for Disease Control and Prevention The information and materials on this site are provided for general information purposes only You should not rely on the information provided as a substitute for actual professional medical advice This site is not designed to and does not provide medical advice If you believe you have a medical emergency Spread the Word® is a public education campaign made possible by funding provided to the National Blood Clot Alliance by the Centers for Disease Control and Prevention under Cooperative Agreement number 1U27DD001153-05 The mark ‘CDC’ is owned by the US Department of Health and Human Services and is used with permission Use of this logo is not an endorsement by HHS or CDC of any particular product Privacy Policy References Metrics details Despite recent advances in the development of computational methods of modeling thrombosis relatively little effort has been made in developing methods of modeling blood clot embolization Such a model would provide substantially greater understanding of the mechanics of embolization as in-vitro and in-vivo characterization of embolization is difficult a method of computationally simulating embolization is developed Experiments are performed of blood clots formed in a polycarbonate tube where phosphate-buffered saline is run through the tube at increasing flow rates until the clot embolizes The experiments revealed embolization can be initiated by leading edge and trailing edge detachment or by non-uniform detachment Stress-relaxation experiments are also performed to establish values of constitutive parameters for subsequent simulations The embolization in the tube is reproduced in silico using a multiphase volume-of-fluid approach By varying the constitutive parameters at the wall embolization can be reproduced in-silico at varying flow rates and a range of constitutive parameters fitting the experiments is reported the leading edge embolization is simulated at flow rates consistent with the experiments demonstrating excellent agreement in this specific behavior A physics-based model informed by in vitro embolization data would allow for a much greater understanding of the mechanics of blood clot embolization including adhesive forces anchoring a clot and the internal stretching the clot undergoes and matched with in vitro embolization experiments where clots are embolized by the flow of phosphate-buffered saline (PBS) in a plain tube This computational model uses a volume-of-fluid approach solving separate constitutive equations for the clot and the PBS on the same computational grid Experiments were conducted on clots formed from freshly drawn bovine blood with approval from the Pennsylvania State University’s Institutional Animal Care and Use Committee and the appropriate procedures were in accordance with the relevant guidelines and regulations Methods are reported in accordance with ARRIVE guidelines for the reporting of animal experiments Blood was drawn from healthy adult female cattle (Bos taurus) into 450-mL bags containing 63 mL of citrate–phosphate-dextrose-adenine (CPDA-1) anticoagulant The blood was centrifuged at 400g for 15 min and the platelet-rich plasma (PRP) was separated from the red blood cells (RBCs) The RBCs were then centrifuged a second time at 1900g for 20 min and the resultant platelet-poor plasma (PPP) was removed from the RBCs The platelet concentration in the PRP was measured using a hemocytometer and the PRP was diluted with PPP to achieve a plasma platelet concentration of 214,000 per microliter Whole blood was then reconstituted to a hematocrit of 40% by mixing two parts RBCs to three parts reconstituted plasma 0.5 M CaCl2 was mixed with the blood to achieve a calcium concentration of 19 mM to counteract the effect of the anticoagulant To find constitutive parameters for the embolization model clots were formed in well plates with a diameter of 15 mm clots were allowed to form at 37 °C for 1 h The clots were then loaded into a mechanical tester (Instron—Norwood The height and radius of the clots were measured and they were subsequently loaded in compression at a rate of 10% per second for 1 s and then a 10% compressive strain was maintained for 30 s giving stress relaxation curves that are used to fit constitutive parameters in subsequent CFD simulations 160 µL of blood was placed carefully in the center of a straight polycarbonate connector (Qosina-Ronkonkoma USA) with an inner diameter (D) of 12.7 mm Blood was pipetted into the connector through the Luer lock port the ends were covered to prevent the clot from drying out and the blood was left to clot for 1 h at 37 °C Although flow conditions significantly impact clot composition whole-blood clots were used to better control their composition and mechanical properties Blood clot formed in polycarbonate tube with flow probe screen in the background A total of 32 embolization events were recorded with blood from a total of seven animals Samples from all animals were treated identically and there was no control group The 32 events were accepted as they provided sufficient data to report statistics of embolization Samples were excluded from the experiment in clots that failed to form no randomization or blinding was performed To further evaluate the shape of the formed blood clots seven clots were scanned using Micro-CT (computed tomography) imaging at Penn State’s Huck Institute for Life Sciences scanning was performed within 8 h of the clots forming This was performed to observe the shapes of the clots to ensure that an idealized shape used in the simulation was not substantially different from the real clots The micro-CT images of the clots were not used in the simulations Region 1 had a length of 12.7 cm (10D) and consisted of 469,800 finite-volume elements Computational regions 1 and 2. Region 1 provided a fully-developed pipe flow inlet boundary condition to region 2, which interpolated the velocity solution from the outlet of region 1 and every time point. Computational meshes used in regions 1 and 2 Region 1 used grid stretching to achieve a small y + near the wall while region 2 used more regularly shaped elements to improve solution stability for the viscoelastic equations Detailed information on the implemented model and details specific to the simulation are provided in Supplementary Materials 3 To capture the entire range of flow rates observed to produce embolization PBS was modeled with a kinematic viscosity of 1 × 10–6 m2/s consistent with that of PBS at 20° Celsius The flow rates corresponded to Reynolds numbers of 3175 based on the kinematic viscosity of the PBS These flow rates also corresponded to wall shear rates of 1200 Region 1 used a periodic inlet velocity boundary condition with an enforced average velocity the velocity field prescribed at the inlet at each timestep was equal to the velocity field at the outlet allowing the velocity field to develop over long time scales and become fully developed The velocity field at the inlet of region 2 was interpolated from the outlet of region 1 This allowed for a fully developed turbulent pipe flow to approach the clot while meeting the grid requirements of the two regions The outlets of both regions 1 and 2 used constant pressure boundary conditions These precursor simulations were performed with the goal of preventing non-physical startup transients from impacting the clot and giving a physically realistic initial velocity field for embolization simulations no modeling was performed of the clot; the clot region had an enforced zero velocity replicating a non-moving solid obstruction in the flow The clot region was modeled as the intersection of the computational domain with a spanwise-oriented cylinder To speed up the development of turbulent motions the initial conditions in the velocity field for the precursor simulations had structured noise which was allowed to develop in time To allow startup transients to pass and for turbulence to develop simulations were performed for 100 characteristic timescales at each flow rate (T = D/U where T is the characteristic timescale and U is the mean velocity at the inlet) Temporal averaging of the velocity and pressure fields was then performed for an additional 200 characteristic timescales a Courant number of less than 0.5 was enforced throughout the domain This process of running a precursor simulation provided a physically realistic initial condition for the embolization simulations and allowed for the characterization of the forces acting on the clot an interface Courant number of 0.01 was enforced replicating the breakage of a subgrid fiber network (a fibrin mesh or adhered platelets in the case of a blood clot) different values of ${\varepsilon }_{w}$ were simulated to find bounds for the threshold wall extensibility parameter where embolization occurs and the total force exerted by the clot onto the bottom wall was recorded by integration of the pressure plus the normal component of the traction vector at every timepoint during simulation runtime To assess the impact of grid resolution on embolization and other simulation outputs the 1.9 LPM case was simulated with a grid spacing in region 2 that was decreased by a factor of 1.5 resulting in 8,748,000 finite-volume elements Embolization was simulated using wall extensibility parameters determined by the lower-resolution grid to ensure that the true threshold value stayed within the same bounds grid resolution characterization was not repeated at higher flow rates the mean flow rate at embolization was 5.1 LPM and the standard deviation of flow rate at embolization was 1.1 LPM Embolization occurred at flow rates ranging from 2.3 to 7.5 LPM The average length of clots after formation was 14.2 mm with a standard deviation of 1.7 mm Left—an embolization event that has left the tube nearly clear of clotted material Some blood remains in the Luer lock through which the blood was deposited when forming the clots Right—one large remnant is left after the majority of the clot embolized Comparison between experimental and numerical stress-relaxation curves used to fit constitutive parameters in PTT model The top row shows a top-down view of the clots Below each top-down view is a front-on view of the same clot showing its cross section in the direction of flow Results from the precursor turbulent simulations are presented where overbars indicate a time-averaged quantity primes indicate fluctuations from the time-averaged quantity and plus superscripts indicate typical normalization by wall quantities for turbulent boundary layers Characteristics of the turbulent pipe flow in region 1; (a) mean velocity normalized by friction velocity vs Solid black line indicates typical log-law profile while dashed black line indicates typical linear viscous-sublayer profile; (b) streamwise-wall-normal component of Reynolds stress normalized by the square of the friction velocity Black line indicates linearly decreasing Reynolds stress $\rho$ = 1000 kg/m3 is the density of the PBS and A = 0.181 cm2 is the clot’s area projected in the streamwise direction Threshold wall extensibility parameter as a function of flow rate Dashed lines indicate upper and lower bounds of the threshold value and the black line indicates the geometric mean of the upper and lower bounds A full example of clot embolization is included in Supplemental Materials 2 where embolization is depicted at a flow rate of 4.2 LPM and a wall extensibility parameter of 5 Early fiber strain concentrations at a flow rate of 4.2 LPM and ${\varepsilon }_{w}=5$ during an embolization event show that fiber strain is concentrated at the leading edge of the clot. Clots at all flow rates with their lower-bound wall extensibility parameter fiber strain is still concentrated at the leading edge Consistent with the lower-resolution simulations the clot in the higher-resolution simulations embolized at a wall extensibility parameter of 15 and failed to embolize at a wall extensibility parameter of 12 The drag on the clot was found to be 2.84 mN 4.4% higher than for the lower-resolution simulations This difference is acceptable as sufficiently small as it is under 5% The approximate scaling of the stress breakage argument remains at a constant order of magnitude across flow rates The experimental flow rates required to embolize the clots in the plain-tube experiments are interpolated onto the simulation data to obtain embolization drag forces and geometric mean threshold wall extensibility parameter data for each experimental embolization Using this approach gives a mean wall extensibility parameter of 2.92 with a standard deviation of 2.09 Interpolated threshold wall extensibility parameters ranged between 1.51 and 11.01 The embolization drag force had a mean value of 2.28 mN and a standard deviation of 0.93 mN The embolization drag force ranged between 0.42 mN and 4.89 mN there is simply no significant strain concentration at the trailing edge of the in silico clots The flow at the trailing edge of the clot is possibly not well enough resolved in the simulations which might explain the low strain in that region Validation of the fluid flow would help to clarify this discrepancy An additional possibility is that this discrepancy comes from the assumption in the simulations that the adhesion is uniform throughout the clot it is possible that the in vitro clots had spatially varying adhesion characteristics both from natural variability in in vitro experiments and due to potential drying of the clot at the clot-polycarbonate-air interface forming a ring of dried clot around the perimeter it is possible that embolization dynamics were impacted by the movement of the tube during experiments Although an ideal controlled experiment would have minimal movement of the tube this complication does highlight the possibility of vessel dynamics on embolization The “flag-waving” behavior observed experimentally is an especially interesting dynamic potentially providing a good validation metric for future refinements in embolization modeling The lifting of the trailing edge of the clot suggests that there may be chaotic recirculating flows that play a role in clot detachment The disagreement on leading-edge vs trailing-edge separation suggests that the mechanics of embolization are not being fully captured One possible explanation for this discrepancy is that there is insufficient spatial resolution in the in silico embolizations The trailing-edge separation and flag-waving behavior suggest that there may be a recirculating eddy downstream of the clot potentially due to the smoothing of the interface between the Newtonian and viscoelastic phases that is necessary to avoid numerical instability Another potential complication is the pulsatile nature of the peristaltic pump used to drive flow in the experiments leading to the possibility that the slight cyclic nature of the loading on the in vitro clots had some impact on the embolization dynamics Numerical issues were a particular challenge in developing the embolization model and precluded some attempts at a more careful analysis the requirement for low aspect ratio grid elements combined with the high computational cost of the simulations required near-wall grid elements that only coarsely resolved the viscous boundary layer Attempts at using local or automated grid refinement similarly met with numerical issues in particular when the clot interface approached the grid refinement interface maintaining the low interface Courant number became costly during the process of embolization so that the large majority of simulated clots were not allowed to fully embolize restricting the ability to more fully analyze the mechanics of embolization Future development of a more numerically stable solution algorithm would be desirable it should be expected that adhesion characteristics of blood clots will change depending on the material they are adhered to The adhesion characteristics of clots to polycarbonate does not necessarily give much information on adhesion characteristics of commonly used biomaterials though this still provides a good foundation to study other biomaterials the use of reconstituted whole blood in the current experiments guarantees that the platelet concentration in the clots is nearly physiological for circulating blood Applying the current model to an in vivo situation would require a much better understanding of the role of different flow conditions on clot formation and likely heterogenous mechanical property distribution The experiments and model described here provide a set of conditions and methods to interrogate in vivo conditions in the future A novel modeling approach is introduced for in silico analysis of clot embolization This approach includes multiphase modeling of a Newtonian fluid and a viscoelastic blood clot where the constitutive properties of the viscoelastic blood clot are fitted to an in vitro stress–relaxation curve Adhesion of the clot to the solid surface was modeled by a locally varying extensibility parameter to force the clot to break more aggressively at the wall than in its volume By varying the flow rate and wall extensibility parameter the functional dependence of threshold wall extensibility parameter leading to embolization on flow rate was found These simulations were compared to in vitro embolization experiments in a geometrically similar setup Experimental embolization occurred at a mean flow rate of 5.1 LPM By interpolating these results onto CFD outputs it was found that the drag force required to embolize the clot ranged between 0.42 and 4.89 mN and the wall extensibility parameter ranged between 1.51 and 11.01 suggesting a wide variability of adhesion characteristics in the in vitro experiments In silico embolization was found to occur exclusively by separation of the leading edge from the wall while in vitro embolization was found to more frequently occur by separation of the trailing edge suggesting some discrepancy between in silico and in vitro stress distribution and embolization behavior and the need for further model development Data will be made available by the corresponding author (K.B A mathematical model and numerical method for studying platelet adhesion and aggregation during blood clotting Computational model of device-induced thrombosis and thromboembolism Computational simulation of platelet deposition and activation: I Immersed-boundary-type models of intravascular platelet aggregation Development of a computational model for macroscopic predictions of device-induced thrombosis Refining a numerical model for device-induced thrombosis and investigating the effects of non-Newtonian blood models Toward modeling thrombosis and thromboembolism in laminar and turbulent flow regimes Evaluation of a novel Y-shaped extracardiac Fontan baffle using computational fluid dynamics Numerical modeling of the flow in intracranial aneurysms: Prediction of regions prone to thrombus formation Multi-constituent simulation of thrombosis in aortic dissection A new mathematical numerical model to evaluate the risk of thrombosis in three clinical ventricular assist devices A model for the formation and lysis of blood clots Computational simulations of thrombolysis in acute stroke: Effect of clot size and location on recanalisation Modelling combined intravenous thrombolysis and mechanical thrombectomy in acute ischaemic stroke: understanding the relationship between stent retriever configuration and clot lysis mechanisms Hydrodynamics in acute ischemic stroke catheters under static and cyclic aspiration conditions Computational investigation of platelet thrombus mechanics and stability in stenotic channels Computational aerodynamics development and outlook Subgrid-scale stress modelling based on the square of the velocity gradient tensor A new constitutive equation derived from network theory Stabilization of an open-source finite-volume solver for viscoelastic fluid flows Computational fluid dynamics simulation of the melting process in the fused filament fabrication additive manufacturing technique Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots Time-dependent hardening of blood clots quantitatively measured in vivo with shear-wave ultrasound imaging in a rabbit model of venous thrombosis The influence of blood composition and loading frequency on the behavior of embolus analogs Download references The authors would like to acknowledge Jose Monclova and Sara Mueller for performing micro-CT imaging and prepared the majority of the manuscript performed the in vitro embolization experiments performed the in vitro compression test experiments helped develop the embolization experimental protocol oversaw the project and was involved in manuscript preparation received a National Science Foundation Grant No This work used the Extreme Science and Engineering Discovery Environment (XSEDE) which is supported by National Science Foundation grant (ACI-1548562) has a financial interest in Cranial Devices a company which could potentially benefit from the results of this research The interest has been reviewed and is being managed by the University in accordance with its individual Conflict of Interest policy for the purpose of maintaining the objectivity of research at The Pennsylvania State University have no competing interests or conflicts related to this manuscript Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41598-023-41825-8 Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. Sign up for the Nature Briefing: AI and Robotics newsletter — what matters in AI and robotics research, free to your inbox weekly. Introduction: The histological composition of the clot influences its mechanical properties, affects the efficacy of endovascular treatment (EVT), and could determine the clinical outcome of patients with acute ischemic stroke (AIS). Insights into clot composition may guide therapeutic decision-making prior to EVT and facilitate revascularization therapies. Conclusions: The absence of HMCA and higher levels of CRP were markers of FPC. In patients with FPC, complete recanalization was most likely to be achieved when a SR was selected as first line of treatment. Mortality was higher in patients within this histologic group. Volume 12 - 2021 | https://doi.org/10.3389/fneur.2021.631343 Introduction: The histological composition of the clot influences its mechanical properties affects the efficacy of endovascular treatment (EVT) and could determine the clinical outcome of patients with acute ischemic stroke (AIS) Insights into clot composition may guide therapeutic decision-making prior to EVT and facilitate revascularization therapies Material and Methods: Consecutive patients with AIS recorded in a prospective single-center reperfusion registry from December 2015 to December 2019 and treated with EVT were included laboratory [including post-procedural C-reactive protein (CRP)] We aimed to study the relationship between histological composition of the clot with basal neuroimaging The secondary outcome was to analyze the correlation between clot composition and functional outcome at 3 months assessed by the modified Rankin scale (mRS) 360 AIS patients treated with EVT were included of whom 189 (53%) fulfilled the inclusion criteria One hundred (53%) cases of fibrin-predominant clot (FPC) were recorded Full recanalization in FPC cases was achieved with higher probability when stent retrievers (SR) were selected as the first-line device (68.2% Patients with FPC had higher levels of CRP (p = 0.02) lower frequency of the hyperdense middle cerebral artery (HMCA) in baseline imaging (p = 0.039) The multivariate analysis showed that the absence of HMCA (OR = 0.420; 95% CI 0.197–0.898; p = 0.025) and higher levels of CRP (OR = 1.01; 95% CI 1.003–1.019; p = 0.008) were predictors of FPC Leukocytes and platelet counts were not associated with clot histology Conclusions: The absence of HMCA and higher levels of CRP were markers of FPC complete recanalization was most likely to be achieved when a SR was selected as first line of treatment Mortality was higher in patients within this histologic group One of the main reasons for the lack of efficacy of EVT is the scant knowledge of the mechanical properties of the clot (6–8) and its histological composition. Both factors are relevant to attainment of successful reperfusion (9) and could aid in the development of endovascular thrombectomy devices Based on the predominant cell type, clots are usually divided into red clots (RPC), white or fibrin-rich clots (FPC), and mixed clots (MC) (10). In addition, the distribution of the fibrin network (6) and platelet clumps can be highly variable (11). Therefore, some FPC are more resistant to revascularization than others due to their higher friction coefficient (7, 8, 12) RPC demonstrate a lower density and are more easily removed as a result A better understanding of the histological composition of the clot could facilitate better clinical and angiographic outcomes and recanalization strategies including intravenous thrombolysis and clot retrieval devices The secondary outcome was to analyze the correlation between clot composition and functional outcome at 3 months as assessed by the modified Rankin scale (mRS) unicentric study based on a prospective registry of all consecutive AIS patients treated with reperfusion therapies in a tertiary stroke center between 15 December 2014 and 15 December 2019 All patients included were clinically managed according to our institutional protocols which are based on current international stroke guidelines The study was approved by the local Clinical Research Ethics Committee with reference number 2019/03/031 Written informed consent was obtained from all included patients or their relatives permitting entry of their information into our reperfusion registry and subsequent use of the data for scientific purposes in accordance with the Spanish Personal Data Protection law Flowchart of the patients included in the study Information regarding clinical stroke severity was assessed by the NIHSS (National Institute of Health Stroke Scale) on admission and during hospitalization and coagulation) and in-hospital laboratory tests were performed after EVT [biochemistry including thyroid hormones and the ratio of neutrophil and lymphocyte numbers was calculated onset to groin puncture and procedural times (time from groin puncture to the end of the endovascular procedure) Number of passes and degree of recanalization by TICI (Thrombolysis in Cerebral Infarction) scale were obtained; TICI ≥ 2B was considered as effective recanalization Prognosis at 3 months was evaluated by mRS considering good prognosis as mRS ≤ 2 and mortality mRS = 6 A basal cranial non-contrast CT was performed before EVT Data on early ischemia was evaluated on basal CT by ASPECTS Arterial occlusion was assessed on angio-CT scan and mismatch by CT perfusion All CT imaging was performed using a Philips Brilliance CT 64-slice (Koninklijke Philips Electronics N.V. and images were analyzed by a neuroradiologist At 24 h from the procedure or in the case of neurological deterioration, a control CT was performed to evaluate the presence of established infarct or hemorrhagic transformation. Symptomatic intracranial hemorrhage (PH-2) was defined according to Heidelberg criteria (14) as any intraparenchymal hemorrhage associated with an increase in the NIHSS scale score ≥ 4 points or death All baseline CTs were reviewed retrospectively on a blind basis by two independent neuroradiologists. The presence or absence of the hyperdense middle cerebral artery (HMCA) sign was classified by consensus based on visual inspection and according to the following criteria: (15) (1) spontaneous visibility of the MCA (2) attenuation of the MCA greater than in the surrounding parenchyma the case was discussed until a consensus was reached and the ratio of healthy to pathological radiodensities was also calculated The final value was considered as the arithmetic mean of the values obtained by each observer The endovascular procedures were performed using a single-plane angiography US) or an Azurion 7 B20/15 biplane model (Koninklijke Philips Electronics N.V. Netherlands) by one board-certified neurologist and a neuroradiologist General anesthesia was used systematically Endovascular procedures were performed adhering to the following general methods: 1) Vascular access by puncture of the right femoral artery using the Seldinger technique 2) Selective catheterization using a Terumo 0.030″ guidewire (Terumo Corporation Japan) and a Flowgate 8F balloon guide catheter (Stryker Corporation USA) and confirmed diagnosis of the affected territory Placement of a guide catheter in the cervical segment of the ICA in anterior circulation stroke Hyperselective catheterization of the occluded vessel and crossing of the clot with Traxcess 0.014″ microguide (MicroVention Inc Ireland) or Trevo Pro (Stryker Corporation In M2 occlusions immediately anterior to the opercular gyrus or M3 occlusions a Trevo XP or Catch mini (Balt The device is removed after 3–5 min of balloon occlusion and simultaneous manual aspiration was performed with a 60-cc syringe Other devices used to a lesser extent were Revive SE (Johnson & Johnson Removal of the device and simultaneous manual aspiration with a 60-cc In case the outcome was not satisfactory after two aspirations combined use of SR and local aspiration is undertaken.After each pass and aspiration syringe were inspected for the presence of thrombus fragments The device was gently washed with heparinized saline to remove thrombus fragments Aspirated material was gently flushed with saline to identify any smaller fragments 5) Control angiographic series in anteroposterior and lateral projections a subjective estimation was made of the red cell component and the fibrin and platelet component The quantity of polymorphonuclear cells contained in the clot and their status were also evaluated and PAS staining allowed the presence or not of bacteria to be determined as well as characteristics suggesting vascular recanalization Mixed clot with predominant component of fibrin (80–85% FPC component) The main outcome was to study the relationship between histological composition of the clot with basal neuroimaging The secondary outcome was to analyze the correlation between clot composition and functional outcome and mortality at 3 months assessed by the modified Rankin scale (mRS) A descriptive study of the variables was performed using central and scattering tendency measures for quantitative variables and the exact calculation and percentage for qualitative variables Normality of the sample was established using the Kolmogorov–Smirnov test The comparison of the categorical variables between two or more subgroups was performed using the Pearson's chi-squared test or The comparison between quantitative variables was performed with the Student's t-test The comparison between medians was performed using the Wilcoxon signed-rank test The independent effect of the clinical variables was calculated with multivariate binary logistic regression models considering the presence of an FPC clot (bad outcome) as a dependent variable The Hosmer–Lemeshow goodness-of-fit test was used to evaluate the global model fit The variables included in the multivariate analysis in addition to the time from onset of symptoms were those with statistical significance p < 0.1 in the bivariate models The odds ratio (OR) was calculated for each variable A ROC (receiver operating characteristic) curve was performed to analyze the cutoff point with the best discriminatory value of the quantitative variables A p < 0.05 was considered significant for all analyses All the results were analyzed with the statistical software IBM SPSS Statistics® Version 26 (SPSS In the study period, 360 mechanical thrombectomies were performed (Figure 1) One hundred eighty-nine (52.5%) fulfilled our inclusion criteria Reasons for exclusion were vertebrobasilar or multiple-territory occlusion (n = 47) absence of thrombus for histological analysis (n = 35) and incomplete clinical follow-up (n = 23) The mean overall age of the cohort was 69.5 years (range 28–91); one hundred (53%) of the patients were male The histological distribution of the clots was as follows: FPC: 100 (53%), MC: 46 (24%), and RPC: 43 (23%). Figure 3 shows examples of the histological types analyzed (A) (HE2×) and (B) (HE20×) Platelet fibrin-predominant clot (FPC) with moderate number of complete neutrophils (C) (HE2×) and (D) (HE20×) (E) (HE20×) and (F) (HE40×) Mixed clot (MC) with plenty of neutrophils FPC patients were more frequently under oral anticoagulation (p = 0.042) and had higher levels of CRP (p = 0.02). On the contrary, they received less IV thrombolysis (p = 0.047) compared with the rest of the cohort and had lower frequency of HMCA in baseline CT (p = 0.039). FPC patients had higher rates of mortality (p = 0.012) (Table 1) and radiological variables in patients with fibrin-predominant clot (FPC) vs Seventy-three (39%) of the patients received IV thrombolysis bridging EVT. Thirty-two (44%) had FPC. In a bivariate analysis (Table 2) patients with FPC treated with IV thrombolysis obtained higher rates of complete recanalization compared to the rest of the patients (p = 0.005) Bivariate analysis: patients treated with intravenous (IV) alteplase previous endovascular treatment (EVT) Distribution of first-line devices in patients with fibrin-predominant clot (FPC) In a multivariate analysis the absence of HMCA (OR = 0.420; 95% CI 0.197–0.898; p = 0.025) and higher levels of CRP after EVT (OR = 1.01; 95% CI 1.003–1.019; p = 0.008) were predictors of FPC (Table 4) Multivariate analysis: predictors of the fibrin-predominant clot (FPC) in all cohorts The ROC curve did not disclose any significant association between levels of CRP after the EVT and the histological composition of the clots (area under the curve 0.6 In bivariate analysis, higher baseline NIHSS and lower ASPECTS on admission were related to poor functional outcome. Higher levels of baseline glucose and CRP, tandem occlusion, TICI 2B recanalization, and PH-2 were also associated with mRS > 2, as shown in Table 5 Functional independence at 3 months and mortality Patients with TICI 2B recanalization, PH-2, and FPC (p = 0.021) had higher rates of mortality at 3 months (Table 5) The absolute number of neutrophils, lymphocytes, and their ratio (neutrophils/lymphocytes) were significantly associated with prognosis at 3 months, while a significant relationship was detected between the absolute number of lymphocytes and mortality (Table 5). None of the cell series analyzed were significantly related to the predominant histological composition (Table 1) Our series provided a substantial amount of histopathological data about heterogeneous clot samples which allowed us to perform several comparisons between histological subtypes of the thrombus with clinical and radiological variables and recanalization strategies Our main finding was the association between patients with FPC and absence of HMCA in their baseline CT scan. In line with our results, a systematic review grouping neuroimaging studies by histological characteristics demonstrated that patients with signs of HCMA on the baseline CT were more likely to have RPC (OR 9.0, 95% CI 2.6–31.2, p < 0.01) (17) higher neutrophil counts and relative neutrophilia on admission were associated with bad functional outcome while relative lymphocytosis corresponded with higher mortality To evaluate the effect of IV thrombolysis, we performed a subanalysis in patients with FPC and we found that these patients had higher complete recanalization rates. These data suggest a synergistic effect of the IV thrombolysis bridging EVT in patients with FPC and reinforce the indication of current guidelines giving IV thrombolysis if no contraindication exists (23) FPC patients had higher mortality rates compared to the rest of the cohort; these patients were more frequently under oral anticoagulation and received less intravenous thrombolysis as expected patients with FPC achieved full recanalization (TICI 3) with higher probability when SR were selected as first-line treatment There are limited studies that have taken into consideration thrombus composition when comparatively analyzing the efficacy of the main recanalization strategies (stent retrieval or aspiration). In particular, the higher coefficient of friction of FPC may increase their resistance to direct suction and may require a higher number of contact points for complete extraction. In line with our results, an experimental study comparing direct aspiration to SR (24) white clots were retrieved by the SR and balloon guide catheter with fewer distal emboli The study of the histopathological and mechanical properties of the clot should be part of the strategy for the development of new EVT endovascular devices. Behavior of clots is currently analyzed using experimental models in vitro (8, 25), thus trying to obtain better recanalization rates (12) the potential to establish predictors of the histological composition of the clots could optimize the selection of reperfusion strategies as well as extend the use of endovascular devices with a higher efficacy in case of resistant clots The fibrin structure present in a clot is a critical element that modifies its mechanical behavior, as it gives it properties of hardness (26), impenetrability (7), and friction, which involve greater technical difficulty (12), lower vascular recanalization rates, and treatment delay (18, 27) Despite this evidence, uncertainty persists regarding the relationship between clot composition, angiographic outcome, and stroke etiology (17) so the practical value of obtaining the histopathological characteristics of the clot in acute stroke remains unclear we have not been able to establish a direct association between HU determination and the predominant fibrin composition so the results could be affected by various biases The determination of a cutoff point of 60% to discriminate the predominance of a histologic subtype by a semiquantitative method makes it difficult to neatly identify subgroups and may alter the analysis Although we have used several observers to minimize variability in the analysis of images precision could have been greater if we had recorded the kappa coefficient CRP was measured only in 78% of the patients and once the EVT was completed so it cannot be categorized as a baseline biomarker The ultrasensitive CRP systematic analysis before reperfusion treatment might contribute toward the elucidation of this We have only included patients with single anterior circulation occlusion and with high recanalization rates so the sample may have been excessively selected losing sensitivity in some of the known prognostic variables (as first-pass effect) The higher percentage of anticoagulated patients existing in the FPC group could condition the administration of IV thrombolysis The absence of HMCA on baseline CT and CRP levels appear to be a reliable marker of FPC which could allow an individualized treatment approach such as prior administration of intravenous thrombolysis and the use of specific thrombectomy devices the choice of a SR as first-line treatment in FPC cases was more effective in achieving complete recanalization than aspiration devices Histopathological study and identification of treatment-refractory clots improve patient characterization and could guide therapeutic strategies for recanalization The raw data supporting the conclusions of this article will be made available by the authors The studies involving human participants were reviewed and approved by CEIm of University Hospital of Albacete The patients/participants provided their written informed consent to participate in this study MER-A drafted the manuscript and performed the statistical analysis RB-A performed the histopathological analysis and drafted the manuscript All authors contributed to the article and approved the submitted version MER-A was funded by Instituto de Salud Carlos III The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest We want to thank our patients and their families Javaad Ahmad for the revision of the English grammar We acknowledge the work of the other members of the Neurology and Anesthesiology Services of the University Hospital of Albacete for the clinical management of these patients Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines for the early management of acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association Modified thrombolysis in cerebral infarction 2C/thrombolysis in cerebral infarction 3 reperfusion should be the aim of mechanical thrombectomy: insights from the ASTER trial (contact aspiration versus stent retriever for successful revascularization) First pass effect: a new measure for stroke thrombectomy devices True first-pass effect: first-pass complete reperfusion improves clinical outcome in thrombectomy stroke patients When to stop: detrimental effect of device passes in acute ischemic stroke secondary to large vessel occlusion Thrombus permeability in admission computed tomographic imaging indicates stroke pathogenesis based on thrombus histology Clot permeability and histopathology: is a clot's perviousness on CT imaging correlated with its histologic composition ANCD thrombectomy device: in vitro evaluation Histopathologic analysis of retrieved thrombi associated with successful reperfusion after acute stroke thrombectomy CT and MRI early vessel signs reflect clot composition in acute stroke Histopathologic composition of cerebral thrombi of acute stroke patients is correlated with stroke subtype and thrombus attenuation Per-pass analysis of thrombus composition in patients with acute ischemic stroke undergoing mechanical thrombectomy Classification of subtype of acute ischemic stroke Definitions for use in a multicenter clinical trial Trial of Org 10172 in Acute Stroke Treatment The Heidelberg Bleeding Classification: Classification of bleeding events after ischemic stroke and reperfusion therapy Prevalence and significance of hyperdense middle cerebral artery in acute stroke Orbit image analysis machine learning software can be used for the histological quantification of acute ischemic stroke blood clots Correlation of imaging and histopathology of thrombi in acute ischemic stroke with etiology and outcome: a systematic review The impact of histological clot composition in embolic stroke Thrombin induced platelet-fibrin clot strength in relation to platelet volume indices and inflammatory markers in patients with coronary artery disease Prothrombotic fibrin clot properties are associated with post-discharge venous thromboembolism in acutely ill medical patients Fibrin clot properties independently predict adverse clinical outcome following acute coronary syndrome: a PLATO substudy and reperfusion in ischemic stroke patients treated with mechanical thrombectomy European Stroke Organisation (ESO) – European Society for Minimally Invasive Neurological Therapy (ESMINT) guidelines on mechanical thrombectomy in acute ischaemic Stroke Endorsed by Stroke Alliance for Europe (SAFE) Influence of thrombus composition on thrombectomy: ADAPT vs balloon guide catheter and stent retriever in a flow model What to do about fibrin rich “tough clots” Comparing the Solitaire stent retriever with a novel geometric clot extractor in an in vitro stroke model Mechanical behavior of in vitro blood clots and the implications for acute ischemic stroke treatment The impact of thromboemboli histology on the performance of a mechanical thrombectomy device Proximal hyperdense middle cerebral artery sign predicts poor response to thrombolysis Permeable thrombi are associated with higher intravenous recombinant tissue-type plasminogen activator treatment success in patients with acute ischemic stroke Histologic analysis of retrieved clots in acute ischemic stroke: correlation with stroke etiology and gradient-echo MRI Citation: Hernández-Fernández F Julia-Molla E and Segura T (2021) Fibrin-Platelet Clots in Acute Ischemic Stroke Predictors and Clinical Significance in a Mechanical Thrombectomy Series Received: 19 November 2020; Accepted: 09 March 2021; Published: 20 April 2021 Copyright © 2021 Hernández-Fernández, Ramos-Araque, Barbella-Aponte, Molina-Nuevo, García-García, Ayo-Martin, Pedrosa-Jiménez, López-Martinez, Serrano-Heras, Julia-Molla and Segura. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) distribution or reproduction in other forums is permitted provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited in accordance with accepted academic practice distribution or reproduction is permitted which does not comply with these terms *Correspondence: María E. Ramos-Araque, cmFtb3NtYXJ5ZXN0aGVyQGdtYWlsLmNvbQ== †These authors have contributed equally to this work Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher 94% of researchers rate our articles as excellent or goodLearn more about the work of our research integrity team to safeguard the quality of each article we publish Jorge López Muñoz is a Spanish photographer based in Valencia. In 2016 he was shortlisted in the first ever ZEISS Photography Award 'Seeing Beyond' with his series 'El Clot' He has made solo exhibitions in CENTRO CULTURAL DE NOAIN (Navarra NANO Festival de Fotografía (FOLA Fototeca Latinoamericana Poland) and BARBASTRO FOTO Festival (Sala El Moliné He has also made a Public Art Exhibition with JR's Insideoutproject in Valencia PDN and Emerging Photographer Magazine (USA) PRISM Contemporary Photography Journal (Ireland) Magazine de La Vanguardia and RobbReport (Spain) We caught up with him a year on from his ZEISS success: This is an artistic documentary and portrait photography project 'El Clot' neighbourhood is located in El Cabanyal For the last 20 years the building and nearby homes have been threatened by demolition in order to extend an avenue to the seafront 'El Clot' inhabitants are mostly gypsy families who have occupied the abandoned apartments in the block a minority that is very heavily socially stereotyped and Although 'El Clot' is a slum I have not encountered either rejection or pain When and why did you first come to photography I decided to study photography and became professional in 2012 I earned my photography degree at the Art and Design College of Valencia (EASD) in 2015 Then I won a full-ride grant at LENS School of Visual Arts of Madrid When I started with the project I didn't know anything about the gypsies or 'El Clot' neighbourhood You've won many awards; how important have competitions been to your career I realized that most people to whom I showed the project liked it and indeed encouraged me to apply for competitions But the reason why they have been important to me is because they allowed me to exhibit my photographs around the world: they afford me a platform to make my work known internationally And – increasingly – I have received professional commissions because of that Being able to show 'El Clot' at Somerset House in London thanks to the Zeiss Competition was a blast My work is my way to explore the world and understand it I am interested in the individual and their architectural environment with real people and their real situations as a photographic object I wanted to try to understand their way of life and to capture in pictures the wild vitality and hope of this community intimate portrait - direct but sensitive - of these people in their habitat and in doing so show their vulnerability and strength Everything starts with the fascination for the other This project shows my attraction towards them First from a place of curiosity and them from obsession It is a subject that I became passionate about since second one Mine with this project was to methodically document all aspects of gypsy culture its people and its territory; having the project become a broad work about their identity I do not pretend that my images are direct mirrors of reality Because the world as such does not exist: it is created at every moment by the unique subjective vision of an artist Where in the world are you and what's next for you I am working in a new long-term personal project now But I still visit them in 'El Clot' and take pictures every now and then There are more exhibitions of it coming in several countries I do want to keep working with the gypsy community for future projects I have recently given a workshop for the first time It does not cease to amaze me the multiple readings that a project like this has according to the viewer and I find it very enriching to get to know them first hand professional commissions are arriving for coverage jorgelopezmunoz.com Look out for your first newsletter in your inbox soon We help you navigate a myriad of possibilities Sign up for our newsletter for the best of the city By entering your email address you agree to our Terms of Use and Privacy Policy and consent to receive emails from Time Out about news Sign up for our email to enjoy your city without spending a thing (as well as some options when you’re feeling flush) Our newsletter hand-delivers the best bits to your inbox Sign up to unlock our digital magazines and also receive the latest news By entering your email address you agree to our Terms of Use and Privacy Policy and consent to receive emails from Time Out about news, events, offers and partner promotions. Barcelona the first thing you'll see at Bodega Carol are the cheese wheels under glass next to the bar Carol has a top-notch cheese shop – there's particulary whiffy variety from Huelva so be advised (you could take that as a tip or a warning depending on your penchant for smelly cheese) Turn your head and have a look at the blackboard for highlights of their gastronomic offering: meatballs and pretty much anything you can imagine made from pork Their cold cuts and cured meats are made from prime Iberian raw materials Don't be fooled but what you might describe as a shabby appearance – one of its charms – this bodega has got more spirit and better food than all the posh And that's not even saying enough.Those behind Bodega Carol are quite clever They picked up an old tavern with loads of character instead of going crazy making into something it wasn't they decided to keep its working-class charm Just a couple of minutes' walk from the Encants metro station brick and wood.Wine barrels are converted into tables and there is a good variety of low-priced wines Bottles of Estrella Damm beer sell like hotcakes and fill the bar while the tables on the terrace are full of empties It attracts a neighbourhood clientele with an age range from 25 to 60 it's a living example of a classic home-grown Barcelona tavern and it's full of something that's increasingly rare in the city these days: a sense of humour Count the thousands of keyrings hanging on the walls Thanks for subscribing! Look out for your first newsletter in your inbox soon! facebook twitter spotify tiktok About us Contact us Time Out Worldwide LOS ANGELES (AP) — Los Angeles Lakers forward Brandon Ingram will miss the rest of the season after being diagnosed with a deep venous thrombosis in his right arm The Lakers announced their decision on the former No Ingram has missed the Lakers’ past two games after he reported shoulder pain following a morning shootaround last Monday Lakers coach Luke Walton said earlier this week that Ingram had pain whenever he attempted to lift his arm A deep venous thrombosis is a condition caused by a blood clot frequently accompanied by swelling and pain in a limb Blood clots have affected several prominent athletes including Chris Bosh and Serena Williams in recent years Bosh eventually retired due to blood clotting issues but many other athletes have continued to play Ingram is averaging a career-best 18.3 points and 5.1 rebounds per game along with 3.0 assists The lanky swingman’s chemistry with LeBron James has improved markedly over the course of the season despite several weeks of trade rumors linking Ingram and the rest of the Lakers’ top young players to a deal for New Orleans superstar Anthony Davis Ingram particularly excelled after the All-Star break and the trade deadline averaging 27.8 points in his six most recent games But injuries have played a major role in preventing the Lakers from developing any consistency during James’ first season alongside their young core Los Angeles might be without Lonzo Ball for the rest of the season due to a sprained ankle and Walton said Friday that the point guard is “not close” to returning despite an initial diagnosis of his injury suggesting he would be back by now the Lakers’ second-leading scorer with 18.8 points per game also is out this week with a sprained ankle The Lakers (30-35) are in 10th place in the Western Conference heading into their rivalry meeting with Boston on Saturday night They trail San Antonio by 6-plus games for the final playoff spot meaning James likely will miss the postseason for the first time since 2005 Medical experts weigh in on the condition and explore past cases of professional athletes who have suffered from it Milwaukee's star guard is on blood-thinning medication Aaron Gordon comes up clutch again for the Nuggets while the Thunder face the 1st big test of their 2025 playoff run Boston's reliance on the 3-ball backfires while New York's defenders come through in the clutch to pull off massive comeback for series-opening win Celtics announce Porzingis was questionable to return with an illness that they specified was non-Covid Breanna Stewart and Jonquel Jones glamour up alongside Angel Reese for the annual fashion event Kenny Atkinson experienced a setback on his coaching journey it fueled the 2024-25 NBA Coach of the Year Follow the NBA Playoffs with our Nightly Pulse blog featuring all the latest news scores and highlights from around the league The rustic family favorite Can Pineda has been holding down this corner of Barcelona’s El Clot neighborhood since 1904 where plenty of life could be found amongst the wooden barrels that now slumber peacefully on their perch up above the dining room the place was frequented by local factory workers who would come for a glass of wine to go with a simple meal or to drink while warming up their lunch boxes The then-owners would put a pine branch on the door to signal the arrival of the vi novell which translates roughly to “The Pine House.” El Clot is part of the new high-tech 22@ district which is focused on innovation and research but maintains in its oldest streets the spirit of the village (Sant Martí de Provençals) that once flourished here with its own market (dating back to 1889) and walls that remain from Barcelona’s first Industrial Age a small but welcoming eatery with just 30 seats decorated with the characteristic blue azulejos tiles those wooden barrels and a few excellent hams hanging behind the bar Partners and brothers-in-law Paco Cuenca (front of the house) and Jaume Jovells (head chef) have run Can Pineda since the 1970s they have gone from a simple bar to a more ambitious restaurant turning excellent seasonal and local ingredients into interesting dishes with a Catalan foundation and Spanish Instead of wine poured straight from those barrels Can Pineda now offers a selection of 200 to 300 Spanish and international wines and diners can call on the expertise of the restaurant’s sommelier There are bottles from some of the most renowned Spanish and Catalan wineries L’Ermita (Priorat) and Venus L’Universal (Mont Sant) Locals and visitors from abroad marvel over carefully prepared dishes made with ingredients such as Catalan mushrooms and fresh fish and seafood from the Mediterranean and Atlantic The sardine coca (a traditional flatbread) highlights the deeply savory qualities of the fish with caramelized onion and the crispy coca offers a delightful contrast to the fleshy fish We also like the homey meatballs (pork and beef) in a satisfyingly earthy Catalan rendition of surf and turf Another winter dish combining flavors from land and sea was the stew of artichokes and mongetas del ganxet (Catalan white beans) with a few big The white truffles that Can Pineda gets from a direct supplier in Italy’s Piedmont region bring their beguiling perfume to a few of the restaurant’s Italo-French dishes delicate fresh pasta or the pochè eggs with foie which imbue the dish with a subtle yet thoroughly enticing aroma We always make sure to save room for dessert – perhaps the praline biscuit with broiled yolk or the Roquefort cheese with pear and pepper we’ll ask for the house specialty: bombetas small bites of crispy phyllo that gush forth warm cream or chocolate when bitten into Can Pineda’s owners have been honing their craft for a long time while Jovells began working there at the tender age of 11 transforming a simple bar into one of Barcelona’s culinary institutions This article was originally published on December 9 Can Pineda, Carrer de Sant Joan de Malta 55 The method of mechanical thrombectomy (MT) is related to vascular anatomy and stroke etiology. Meniscus sign and thrombus permeability as imaging markers may be instructive for the selection of MT. This study aims to clarify the relationship among meniscus sign, thrombus permeability, and choice of MT in patients with acute middle cerebral artery occlusion. A total of 111 patients with acute middle cerebral artery occlusion (MCAO) who underwent MT were retrospectively analyzed. Clot meniscus sign was defined as the appearance of meniscoid/edge-like or single- or double-wall contrast channels besides or around insular blood clots. The radiographic, clinical, and surgical data of patients with MCAO with or without meniscus sign were compared. Patients with MCAO with positive meniscus sign have higher thrombus permeability and are more suitable for CA to acquire better clinical outcomes. Volume 13 - 2022 | https://doi.org/10.3389/fneur.2022.850429 Background and Purpose: The method of mechanical thrombectomy (MT) is related to vascular anatomy and stroke etiology Meniscus sign and thrombus permeability as imaging markers may be instructive for the selection of MT This study aims to clarify the relationship among meniscus sign and choice of MT in patients with acute middle cerebral artery occlusion Materials and Methods: A total of 111 patients with acute middle cerebral artery occlusion (MCAO) who underwent MT were retrospectively analyzed Clot meniscus sign was defined as the appearance of meniscoid/edge-like or single- or double-wall contrast channels besides or around insular blood clots and surgical data of patients with MCAO with or without meniscus sign were compared Results: The meniscus sign positive group (n = 26) has higher thrombus permeability (HUs) (26.92 ± 9.69 vs Shorter puncture-to-recanalization (P2R) time (65.5 vs higher complete recanalization rate (85.71 vs and better clinical outcome (p < 0.01) were obtained by selecting contact aspiration (CA) over stent retriever (SR) in patients with positive meniscus sign there was no significant difference in clinical outcome after receiving CA or SR Conclusion: Patients with MCAO with positive meniscus sign have higher thrombus permeability and are more suitable for CA to acquire better clinical outcomes we aimed to compare the thrombus permeability CA in patients with acute middle cerebral artery occlusion suggested by the presence of meniscus sign Ethics approval of this study was obtained from the Medical Ethics Committee of Zhongnan Hospital of Wuhan University Occlusive clot sign was defined as the angiographic appearance of the occluded site before recanalization, and the meniscus sign is a special type. Clot meniscus sign was defined as an appearance of meniscoid/edge-like or single- or double-wall contrast channels besides or around insular blood clots at the proximal end of the occluded vessel in DSA (7, 8) (Figure 2) (A,B) Images of a middle cerebral artery occlusion in patients with positive meniscus sign Measurement of thrombus permeability on non-contrast CT (nCT Three regions of interest (red circles) are placed in the proximal and distal parts of the thrombus (red arrow) to calculate the mean Hounsfield unit (HU) density value of the occlusion site All the patients underwent MT and were divided into different groups according to the first treatment with SR or CA All endovascular treatments were completed by 2 interventional neuroradiologists with more than 5 years of interventional experience (BM The first-line thrombectomy method was selected by the interventional neuroradiologists during the operation The retrievers used in the study included Solitaire FR (Medtronic A large-bore aspiration catheter (Penumbra System Reperfusion Catheter ACE™ 60; Penumbra United States) or an intermediate catheter was used in CA If the first-line method initially selected failed to achieve effective recanalization another method would be used for rescue treatment All the patients had completed CT and CTA examinations and signed informed consent before surgery the quantitative variable was expressed as mean ± standard deviation or median with interquartile range and the qualitative variable was expressed as counts and frequencies Pearson χ2 tests or Fisher exact tests were performed for categorical variables and continuous variables were compared by t-tests or the Mann–Whitney U test Multivariate logistic regression was used to evaluate the independent variables of complete recanalization in patients with positive meniscus sign P < 0.05 was considered statistically significant Statistical analyses were performed using SPSS for Windows (Version 23.0; IBM) Comparison of data between patients with and without meniscus sign Boxplots of change in thrombus permeability for different etiological groups in patients (A) with or (B) without meniscus sign Comparison of surgical data and clinical outcome among patients with meniscus sign in different MT methods Distribution of mRS score at 90 days among different groups Comparison of surgical data and clinical outcome among patients without meniscus sign in different MT methods Multivariate regression analysis for complete recanalization in patients with meniscus sign This study showed that the presence of meniscus sign was associated with AF and better prognosis could be obtained performing CA the relationship with thrombus occlusion morphology has not been further explored our research further analyzed the relationship between meniscus sign and thrombus permeability and confirmed a significant correlation between the two and this may be helpful in determining the subtype of stroke and making decisions on MT methods but the preoperative mRS score of the CA group was higher There are several limitations in this study the choice of first-line MT is completely determined by the surgeon based on clinical experience this study lacks histopathological data on thrombus and ignores the influence of different types of contrast agents when measuring thrombus permeability this study is a single-center one with small sample size and a multi-center and large-sample prospective study should be carried out in the future those with positive meniscus sign have higher thrombus permeability and are more suitable for CA as the first-line MT method to obtain higher complete recanalization rate and better functional outcomes The original contributions presented in the study are included in the article/supplementary material further inquiries can be directed to the corresponding author The studies involving human participants were reviewed and approved by the Medical Ethics Committee of Zhongnan Hospital of Wuhan University (approval number: 2020198) Written informed consent was not required for the current study in accordance with the local legislation and institutional requirements CN and ZK collected the data of the patients CN analyzed the data and drafted the manuscript This work was supported by the Translational Medicine and Interdisciplinary Research Joint Fund of Zhongnan Hospital of Wuhan University (No All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher Endovascular thrombectomy for acute ischemic stroke: a meta-analysis Thrombectomy 6 to 24 hours after stroke with a mismatch between deficit and infarct Thrombectomy for stroke at 6 to 16 hours with selection by perfusion imaging Mechanical thrombectomy of acute middle cerebral artery occlusion using trans-anterior communicating artery approach Clot perviousness is associated with first pass success of aspiration thrombectomy in the COMPASS trial Significance of angiographic clot meniscus sign in mechanical thrombectomy of basilar artery stroke Initial angiographic appearance of intracranial vascular occlusions in acute stroke as a predictor of outcome of thrombolysis: initial experience Baseline occlusion angiographic appearance on mechanical thrombectomy suggests underlying etiology and outcome Refining angiographic biomarkers of revascularization: improving outcome prediction after intra-arterial therapy Trial of Org 10172 in acute stroke treatment permeable thrombi are associated with higher intravenous recombinant tissue-type plasminogen activator treatment success in patients with acute ischemic stroke Angiographic demarcation of an occlusive lesion may predict recanalization after intra-arterial thrombolysis in patients with acute middle cerebral artery occlusion The claw sign: an angiographic predictor of recanalization after mechanical thrombectomy for cerebral large vessel occlusion doi: 10.1016/j.jstrokecerebrovasdis.2019.03.007 Ischemic stroke: what does the histological composition tell us about the origin of the thrombus Thrombus histology suggests cardioembolic cause in cryptogenic stroke Thrombus composition in acute ischemic stroke: a histopathological study of thrombus extracted by endovascular retrieval Effect of endovascular contact aspiration vs stent retriever on revascularization in patients with acute ischemic stroke and large vessel occlusion: the ASTER randomized clinical trial 'Real-world' comparison of first-line direct aspiration and stent retriever mechanical thrombectomy for the treatment of acute ischemic stroke in the anterior circulation: a multicenter international retrospective study A comparison of direct aspiration versus stent retriever as a first approach ('COMPASS'): protocol Thrombectomy for M1-middle cerebral artery occlusion: angiographic aspect of the arterial occlusion and recanalization: a preliminary observation Clot Meniscus sign: an angiographic clue for choosing between stent retriever and contact aspiration in acute basilar artery occlusion Frontline contact aspiration treatment for emergent large vessel occlusion: a review focused on practical techniques Risk of distal embolization with stent retriever thrombectomy and ADAPT Comparison of aspiration versus stent retriever thrombectomy as the preferred strategy for patients with acute terminal internal carotid artery occlusion: a propensity score matching analysis Balloon guide catheter improves revascularization and clinical outcomes with the Solitaire device: analysis of the North American Solitaire Acute Stroke Registry Sun D and Mei B (2022) Clot Meniscus Sign Is Associated With Thrombus Permeability and Choice of Mechanical Thrombectomy Technique in Acute Middle Cerebral Artery Occlusion Received: 07 January 2022; Accepted: 24 January 2022; Published: 24 February 2022 Copyright © 2022 Nie, Kang, Tu, Wu, Sun and Mei. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: Bin Mei, bmV1cm9tZWkyMEAxNjMuY29t Metrics details Neutrophils and neutrophil extracellular traps (NETs) have been shown to be involved in coagulation the interactions between neutrophils or NETs and fibrin(ogen) in clots and the mechanisms behind these interactions are not yet fully understood the role of neutrophils or NETs on clot structure formation and dissolution was studied with a combination of confocal microscopy FXI and FVII-deficient plasmas were used to investigate which factors may be involved in the procoagulant effects We found both neutrophils and NETs promote clotting in plasma without the addition of other coagulation triggers indicating that other factors mediate the interaction The procoagulant effects of neutrophils and NETs were also observed in FXII- and FVII-deficient plasma only the procoagulant effects of NETs were observed while neutrophils-induced clots were less stable and more porous NETs accelerate clotting and contribute to the formation of a denser may induce clotting in a different manner to NETs questions remain whether neutrophils contribute to coagulation independently or via NETs whether both neutrophils and NETs promote clotting via the intrinsic pathway and how procoagulant factors interact with neutrophils or NETs This in vitro study aims to investigate the role of neutrophils and NETs in blood coagulation to decipher how neutrophils or NETs interact with the fibrin network The role of neutrophils or NETs on clot formation and clot dissolution was analysed by turbidity and lysis assays clot structure was determined by confocal microscopy and clot stability and pore size were investigated using permeation studies We found that both partially activated neutrophils and NETs promote clotting in plasma independently of additional triggers We also found that the procoagulant effects of NETs are independent of FXI the procoagulant effects of neutrophils are mediated via FXI Expression of neutrophil-surface antigens on isolated human neutrophils and differentiated PLB-985 cells and the capacity of NETosis of these cells The expression of antigens on cells was detected in living cells via flow cytometry (a) Expression levels of CD16 and CD66b on human neutrophils were used as the positive control Expression levels of (b) CD16 and (c) CD66b on differentiated PLB-985 cells were detected on the day 6 of treatment with 1.25% DMSO untreated cells were used as the negative control (d) Expression level of CD11b on differentiated PLB-985 cells was detected on the day 3 and day 6 of treatment with 1.25% DMSO untreated PLB-985 cells were used as a negative control and human neutrophils were used as a positive control Error bars represent SD of three technical replicates (e) Unstimulated human neutrophils using fluorescence microscopy (f) NETs generated from isolated human neutrophils stimluated with PMA (g) NETs generated from differentiated PLB-985 cells stimulated with PMA Green (cyan in overlay with blue): Alexa Fluor 488 labelled Histone H3 (citrulline R2 + R8 + R17) Effects of neutrophils and NETs on coagulation Turbidity measurements were carried out in (a) a purified fibrinogen system or in (b) NPP Differentiated PLB-985 cells or human neutrophils (200,000 cells/100 µl) or NETs (generated from 200,000 cells/100 µl) were added to purified fibrinogen or plasma Normalized percentage of MaxOD (compared to thrombin only controls) was quantified plasma (diluted 1:6) and CaCl2 (1.5 mM in purified fibrinogen or 3.33 mM in plasma) Error bars represent SD of three technical replicates in triplicates Effects of human neutrophil supernatant on clot formation showing the effects of human neutrophils (200,000 cells/100 µl) and their supernatant on clot formation when added to NPP (c) MaxOD and (d) maximum rate of clot formation (turbidity Vmax) were quantified Other concentrations: plasma (diluted 1:6) and CaCl2 (3.33 mM) Lysis analysis of the effect of human neutrophils or human NETs on clot dissolution Neutrophils (200,000 cells/100 µl) or NETs (generated from 200,000 cells/100 µl) were added to plasma (a) Average rate of lysis and (b) time from MaxOD to 50% lysis were quantified Other concentrations: plasma (diluted 1:6) Error bars represent ± SD of three technical replicates in triplicates To investigate through which pathway neutrophils/NETs promote clotting, tissue factor (TF) and FXII Inhibitors (TF antibody and Corn trypsin inhibitor (CTI)) were used to block TF and FXII in turbidity. Nevertheless, we saw no effect of these inhibitors in plasma-based experiments (Supplementary Fig. S4 online) FXI- and FVII-deficient plasmas were used in turbidity to investigate the procoagulant effects of human neutrophils and NETs Turbidity analysis of the effect of human neutrophils and human NETs on FXII (a) Human neutrophils (200,000 cells/100 µl) or (b) human NETs (generated from 200,000 cells/100 µl) were added into FXII (c) Normalized percentage of MaxOD and (d) normalized percentage of time to MaxOD were quantified Other concentrations: plasmas (diluted 1:6) and CaCl2 (3.33 mM) deficient plasma data represents 4–6 replicates Clot density and the permeability of clots with human neutrophils or human NETs (a) The overall structure of NPP clots triggered with only thrombin (b) thrombin and neutrophils (200,000 cells/100 µl) (d and e) thrombin and NETs (generated from 200,000 cells/100 µl) and (f and g) NETs only were visualized by an confocal microscopy with a 40× oil immersion objective lens (1.4 NA) f and g are images of two positions from the same slide yellow arrows indicate NETs and white arrows indicate large pores (h) The permeation coefficient (Darcy constant [Ks]) of clots were quantified Other concentrations: plasma was diluted 1:6 for confocal (except in figure e was 1:3) and 1:3 for permeation Error bars represent SEM of three technical replicates in triplicates our data indicate that highly pure neutrophils were harvested after isolation from human blood Our immunofluorescence results using a green dye marker for histone H3 show that both human neutrophils and differentiated PLB-985 cells successfully formed NETs which are positive for H3Cit These findings suggest that even though DMSO-differentiated PLB-985 cells did not possess the same granules as human neutrophils the “NETosis” capabilities of these differentiated cells are similar to that of human neutrophils Our data altogether show that PLB-985 cells are different from neutrophils and their extracellular traps may therefore not be fully identical to NETs experiments using this cell line were conducted prior to using human neutrophils in order to set up methods as well as prevent unnecessary blood draw since this cell line cannot fully differentiate into primary neutrophils it could not be a substitute for mature neutrophils and human neutrophils were always needed to confirm experimental results Although cDNA was also observed in the supernatant these findings suggest that neutrophils were potentially activated to release proteins/enzymes and DNA We also found that neutrophil-induced clotting had a significantly shorter lag time than both supernatant-induced and NETs-induced clotting but with fluctuating turbidity curves for both neutrophil-induced and supernatant-induced clots neutrophils were still undergoing further activation during the pre-coagulation period The procoagulant effects we observed in neutrophil experiments may be due to mediators released from activated neutrophils Confocal images show that NETs increased the local clot density while neutrophils-induced clots were less stable our results show that neutrophils and NETs have different effects on clot formation despite the NETs being generated from neutrophils was observed in the neutrophils’ supernatant it has no apparent inhibitory effect on coagulation in plasmas containing FXII we confirmed that both partially activated neutrophils and NETs delayed clot lysis to varying degrees our permeation data show that there were no significant differences in permeability between NET-induced clots and thrombin-induced clots suggesting their average pore sizes are similar This may be due to the fact that NETs only increased the density of fibrin fibers in areas directly surrounding them indicating that the overall permeability of clots was not altered this finding indicates that the procoagulant effects of NETs could be concentration dependent since we observed a denser clot structure in areas with more NETs our data show that partially activated neutrophils and NETs independently promote clotting in plasma via novel mechanisms in vitro and that FXI and to a lesser degree FXII play a role in the procoagulant effects of neutrophils but not NETs We also find that partially activated neutrophils and NETs delay clot lysis and that clot density is visually increased in the immediate areas surrounding NETs We propose that the procoagulant effects of neutrophils could be induced by neutrophil-secreted proteins These findings provide unique mechanistic insights into the cross-talk between neutrophils with important implications for diseases of thrombosis such as stroke Targeting mechanisms involved in this cross-talk provide tempting new prospects for future therapeutics All reagents that could be filtered were filtered with a 0.2 μm filter prior to use 5 ml of whole blood was carefully layered on the top of 5 ml Lympholyte-poly (Cedarlane) and the layer of neutrophils and all of the isolation media below this layer were carefully transferred into a new Falcon tubes Cells were then washed once with Hanks' Balanced Salt solution (HBSS) (without Ca2+/Mg2+) and centrifuged at 350 RCF for 10 min then 2 ml of Red Blood Cell (RBC) Lysis Buffer (Roche) was added to the tube to lyse the residual RBC and the cell pellet was gently resuspended Cells were then washed once with 10 ml HBSS (without Ca2+/Mg2+) and centrifuged at 250 RCF for 5 min the supernatant was discarded and the pellet was resuspended in 4 ml of HBSS (with Ca2+/Mg2+) or HEPES-buffered saline (HBS) ((If required for subsequent experiments these buffers could be supplemented with 2% w/v human serum albumin (HSA) or 2% v/v fetal bovine serum (FBS)) All Blood donors provided informed written consent according to the declaration of Helsinki and this study was approved by the University of Leeds Medicine and Health Faculty Research Ethics Committee cells were cultured in RPMI 1640 medium (R8758 Sigma-Aldrich) supplemented with 10% heat-inactivated FBS at 37 °C in a 5% CO2 with air humidified incubator cells were treated in RPMI 1640 medium supplemented with 1.25% Dimethyl Sulfoxide (DMSO Sigma-Aldrich) and heat-inactivated FBS at 37 °C in 5% CO2 for 5 days This treatment medium was renewed on day 3 The treated cells were used in experiments on day 6 round cover-slips that were pre-coated with poly-l-lysine (0.01% solution Sigma-Aldrich) were placed in wells of a 24-well cell culture plate then isolated neutrophils or PLB-985 cells were seeded (~ 200,000 cells) in 500 μl RPMI 1640 medium (supplemented with 2% FBS) per well and incubated at 37 °C in a 5% CO2 Cells were incubated at 37 °C in a 5% CO2 incubator overnight (minimally 2 h) cells were treated with 20 nM PMA in a T25 flask incubated at 37 °C in 5% CO2 for 4 h prior to experiments samples were centrifuged at 500 RCF for 5 min to precipitate residual cells or debris then the supernatant was centrifuged at 17,000 RCF for 15 min at 4 °C to harvest NETs NETs were washed once with HBS by centrifugation at 17,000 RCF for 15 min at 4 °C Before resuspended NETs were used in experiments double-stranded DNA (dsDNA) was quantified using LabTech-Nanodrop ND100 spectrophotometer at a wavelength of 260 nm to confirm that the NET concentration was consistent in every experiment Final concentrations were as follows: Fibrinogen System: 2 mg/ml Human Fibrinogen (von Willebrand factor and plasminogen depleted 1.5 mM CaCl2 and 200,000 cells or NETs (pre-generated from 200,000 cells) were diluted in HBS and premixed in a 96-well plate 0.1U/ml thrombin (Merck) was added to initiate clotting every 12 s for 4 h at 37 °C by Multiskan FC Microplate Photometer (Thermo Fisher Scientific) or a PowerWave HT Microplate Spectrophotometer (BioTek) tPA (0.03 mg/μl) was added while other conditions remained unchanged All experiments were performed in triplicate 3.33 mM Ca2+ and 200,000 cells or NETs (pre-generated from 200,000 cells) were diluted in HBS and premixed in a 96-well plate 0.1 U/ml thrombin was added to initiate clotting every 12 s for 4 h at 37 °C by Multiskan FC Microplate Photometer tPA (0.03 mg/μl) was added and all other conditions remained unchanged FXI- and FVII-deficient plasmas were purchased from George King Bio-Medical Immunofluorescence was carried out to visualize NETs which were generated on round coverslips as described above Anti-Histone H3 (citrulline R2 + R8 + R17) antibody (ab5103) and Goat anti-Rabbit IgG H&L (Alexa Fluor 488) (ab150077) were obtained from Abcam Samples on 24-well plates were fixed with paraformaldehyde (PFA Sigma-Aldrich) for 30 min inside a fume hood at room temperature followed by washing 3× with 1 ml PBS per well samples were incubated in 0.5% Triton X-100 (diluted in PBS) for 1 min at room temperature samples were incubated in blocking buffer (1% w/v bovine serum albumin (BSA) 22.52 mg/ml glycine in PBST (PBS with 0.1% v/v Tween 20)) for 30 min at room temperature to block non-specific binding of the antibodies Following one washing step with 1% BSA in PBST samples were incubated in 500 μl primary antibody (anti-Histone H3 1:250 diluted in 1% BSA) per well overnight at 4 °C then incubated with secondary antibody (Goat Anti-Rabbit IgG H&L (Alexa Fluor 488) 1:500 diluted in 1% BSA) for 1 h at room temperature in the dark followed by incubating with 300 nM 4′,6-Diamidino-2-Phenylindole coverslips were mounted upside down onto glass slides with antifade mounting medium (Vector Laboratories) Slides were allowed to dry for at least 1 h at room temperature in the dark Slides were imaged via 20x (0.8 NA) or 40x (1.0 NA) lenses with Diode 405 nm laser and Argon 488 nm laser filter by using an Airyscan Upright Confocal Microscope (Zeiss LSM880) or Fluorescence Microscope (Zeiss AX10—Zen software) Fluorescent Labeling was carried out to visualize clots FITC labeled fibrinogen (25 μg/ml) was added into plasma The reaction mixture was prepared by diluting plasmas (diluted 1:6 or 1:3) CaCl2 (3.33 mM) and 200,000 cells (with 100 nM PMA) or NETs (pre-generated from 200,000 cells) in HBS Thrombin (0.1U/ml) was added to initiate clotting Then 30 μl of the mixture was immediately transferred into a well of an uncoated 8-well Ibidi slide (Ibidi GmbH) The slide was placed into a dark humidity chamber for 2 h at room temperature Slides were imaged via 40× oil immersion objective lens (1.4 NA) with Diode 405 nm laser and Argon 488 nm laser filter by using an Airyscan Inverted Confocal Microscope (Zeiss LSM880) 21–23 slices) were combined to form 3D images via Fiji-ImageJ All statistical analyses were performed using GraphPad Prism 7 A normal distribution of the data used in two-tailed unpaired t-test was checked by Shapiro–Wilk (W) test (P > 0.05) Differences in the expression levels of CD16 (W = 0.9306) and CD66b (W = 0.9355) on differentiated PLB-985 cells were determined by two-tailed unpaired t-test maximum optical density (MaxOD) (W = 0.9713) and turbidity Vmax (W = 0.9130) of human neutrophil supernatant were determined by two-tailed unpaired t test Other turbidity and lysis data were determined by one-way ANOVA analysis with Tukey's multiple comparisons test (Alpha = 0.05) Differences in Ks were determined by one-way ANOVA with Tukey's multiple comparisons test (Alpha = 0.05) Contrast of confocal and fluorescence images were adjusted by Fiji-Image J P values < 0.05 were considered to indicate statistical significance All methods and analyses were performed in accordance with the relevant guidelines and regulations The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request Edwards, S. 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Haemost. https://doi.org/10.1111/jth.14402 (2019) Factor XIII A-subunit V34L variant affects thrombus cross-linking in a murine model of thrombosis An international study on the standardization of fibrin clot permeability measurement: Methodological considerations and implications for healthy control values Download references This work was supported by a British Heart Foundation (BHF) Programme Grant (RG/18/11/34036) and Wellcome Investigator Award (204951/B/16/Z) to RASA George (Biomolecular Mass Spectrometry Facility University of Leeds) for protein identification by mass spectrometry Hardy for assistance with turbidity and lysis measurements Discovery and Translational Science Department Institute of Cardiovascular and Metabolic Medicine The Astbury Centre for Structural Molecular Biology assisted with the experiments and the analysis of the data The authors declare no competing interests Download citation DOI: https://doi.org/10.1038/s41598-021-81268-7 a shareable link is not currently available for this article Sign up for the Nature Briefing newsletter — what matters in science Metrics details To demonstrate the long-term effect of cystotomy with or without fibrinogen clot removal for treatment-resistant cystoid macular edema (CME) secondary to branch retinal vein occlusion (BRVO) We retrospectively analyzed medical records of 22 eyes of 22 patients with treatment-resistant CME secondary to BRVO with 12 months observation after cystotomy with or without fibrinogen clot removal LogMAR-converted best corrected visual acuity (BCVA) was statistically better at 12 months after surgery (0.30 ± 0.30) than preoperative BCVA (0.39 ± 0.27) (p = 0.01) The central sensitivity of microperimetry (dB) was maintained during follow-up (preoperative sensitivity: 25.4 ± 4.1 postoperative sensitivity at 12 months after the surgery: 25.9 ± 4.2 there was a significant improvement in the central retinal thickness (CRT) on optical coherence tomography (OCT) (303.7 ± 80.1) (μm) compared with the preoperative CRT (524.2 ± 114.8) (p < 0.01) The preoperative reflectivity in cystoid cavity on OCT was significantly higher in patients with fibrinogen clot removal (n = 5) than in patients without fibrinogen clot removal (n = 17) (p < 0.01) For treatment-resistant CME secondary to BRVO Cystotomy with or without fibrinogen clot removal may be one of the treatment options treatment-resistant refractory foveal cystoid macular edema (rfCME) still exists standard therapy alone cannot achieve complete remission of macular edema in all cases and the pathology involved in resistance to therapy remains unknown a novel decisive therapy is yet to be developed for this unmet need These outcomes suggest the effectiveness of cystotomy and fibrinogen clot removal for rfCME secondary to BRVO but the details have not been investigated This study thus aimed perform a functional and anatomical assessment of cystotomy for rfCME secondary to treatment-resistant BRVO The change in perioperative external limiting membrane (ELM) status and discontinuity was not statistically different between preoperative (9/5/8) and 12 months postoperative (11/5/6) (p = 0.90) An 86-year -old woman was referred to us for the treatment of prolonged resistant cystoid macular edema (CME) secondary to branch retinal vein occlusion in the right eye best corrected decimal visual acuity (BCVA) was 0.6 A fundus examination revealed a CME and postlaser chorioretinal scars (A) The foveal cystoid cavity showed higher reflectivity compared to the vitreous on optical coherence tomography finding (B) Cystotomy and fibrinogen clot removal were performed for the treatment of CME CME subsided immediately after surgery with no recurrence during the follow-up period of 12 months (C 1 month E 12 months after the surgery).The patient had BCVA of 1.0 at the last medical examination The results of the preoperative blood examination were not different between the two groups (Table 2) This result may suggest that cystotomy is not only effective for rfCME following DR but also for CME caused by any microvascular retinal disorder further investigations for other diseases are warranted we speculate that in vivo overproduction of fibrinogen may be associated with the onset or progression of various microvascular retinal disorders including RVO fibrinogen clots formed in CME are similar to those which develop in two distinct diseases of different etiologies—i.e. DM and RVO—and future investigations are needed to study the role of the presence of fibrinogen in the onset or progression of CME The limitations of this study are as follows non-controlled pilot study conducted with a small sample size and warrants a prospective controlled trial with a larger cohort for further investigation the number of cases in which the fibrinogen clot was removed was very small and there was a large difference between the number of total cases in the removed and non-removed groups it is difficult to conclusively evaluate the difference in therapeutic effect between the two groups and the comparison between the groups made in this study should be considered only as reference data this study reported that cystostomy could resolve CME resistant to other therapies our findings support the efficacy of cystotomy for rfCME secondary to BRVO Anti-VEGF is the first-line therapy for CME secondary to BRVO; however cystotomy may be an effective option for rfCME resistant to conventional treatments it will be important to conduct a controlled trial of patients who undergo vitrectomy for CME resistant to various conservative therapies and subsequently undergo cystotomy and compare the outcomes with those who do not undergo further surgery cystotomy with or without fibrinogen clot removal was found to be effective for the long-term anatomical and functional improvement of refractory CME secondary to BRVO Our study was performed after obtaining the approval of the Ethics Committee of Kobe University Graduate School of Medicine (approval number: 170083) The procedure conformed to the tenets of the Declaration of Helsinki Patient inclusion criteria included surgeries performed at Kobe University Hospital from September 2014 through January 2019 informed consent was not obtained from each patient because of the retrospective Although the need for informed consent was waived by the Ethics Committee of Kobe University Graduate School of Medicine patients were able to withdraw consent any-time for providing information about this study which could be accessed on the hospital homepage as an opt-out choice Surgery was introduced when CME secondary to BRVO was resistant to all existing conventional treatments such as an intravitreal anti-VEGF injection a sub-tenon triamcinolone acetonide injection (STA) direct photocoagulations for microaneurysms and PPV with internal limiting membrane peeling Intravitreal anti-VEGF administration was given at least 3 times to all patients prior to this study The average number of doses of anti-VEGF drug is 5.9 ± 5.1 STA was performed at the discretion of the attending physician and at the patient's request When it was judged that the causative microaneurysm could be identified from the observation of the fundus and the findings of optical coherence tomography direct photocoagulation of the microaneurysm was performed Due to poor response to conventional therapies such as anti-VEGF therapy and retinal photocoagulation described above all 22 patients underwent PPV with internal limiting membrane peeling prior to this study The Patients who had been followed-up at least for 12 months after surgery were enrolled The following clinical variables were analyzed: sex best corrected decimal visual acuity (BCVA) central sensitivity (CS) on microperimetry (MP-3; NIDEK CO. presence or absence of fibrinogen clot removal during surgery and the parameters determined by optical coherence tomography (OCT) including central retinal thickness (CRT) (µm) and continuity of the external limiting membrane (ELM) Microperimetry was performed on all patients with MP-3 in a dark room with pupillary dilation We used the macula 12S2 program for this study A white stimulus with Goldmann III in size and duration of 200 ms was projected onto a white background at 31.4 asb The stimulus dynamic range for the MP-3 was 34 dB and the light threshold was determined by a 4–2 staircase strategy The mean retinal sensitivity of the central 9 points was defined as CS-MP3 and used for the statistical analysis and continuity of subfoveal ELM were assessed using spectral domain OCT (Spectralis HRA + OCT; Heidelberg Engineering For the evaluation of cystoid cavity reflectivity six-line radial scans (30 degrees) centered on the presumed fovea were obtained and the inverted grayscale vertical images were used for further investigation The cystoid cavities in OCT images were circumscribed manually followed by measurement of the average reflectivity in this area using the Image J software (version 1.48 We used the reflectivity levels of the vitreous cavity as the standard in each image The reflectivity value of the cystoid cavity relative to the vitreous cavity was calculated as an arbitrary unit (AU) The results of preoperative blood examination were also assessed The inspection items were as follows: blood glucose (BS) (mg/dL) prothrombin time-international normalized ratio (PT-INR) activated partial thromboplastin time (APTT) (s) The unpaired t-test for continuous variables and the chi-square test and Fisher’s exact probability test for dichotomous variables were used to compare the parameters listed above followed by post hoc analysis using Wilcoxon t-test with Bonferroni correction was used to evaluate the time course changes in BCVA The Landolt-decimal BCVA was converted to the logarithm of the minimal angle of resolution (logMAR) for statistical analysis Statistical analyses were performed using statistical software (SPSS Statistical significance was inferred for p < 0.05 All surgeries were performed as previously reported7 standard 27-gauge PPV with a non-contact wide-angle viewing system (Resight; Carl Zeiss Meditec AG Germany) was performed by one experienced surgeon (HI) in the same operating room The Constellation Vision System (Alcon Laboratories phacoemulsification and intraocular lens implantation with 2.4 mm bent transconjunctival single-plane sclera-corneal or clear corneal incision were performed using the same machine for all phakic eyes by using 27-gauge microforceps or microscissors the outer wall of subfoveal cystoid space was torn or incised if the surgeon could visually confirm the presence of an exposed fibrinogen clot in the cyst space it was directly grasped and excised using 27-gauge microforceps STA and/or intravitreal triamcinolone acetonide injection immediately at the end of the surgery were not performed on any case in this study If the surgeon was unable to identify the presence of a fibrinogen clot visually no manipulation was done in the cystoid cavity The datasets generated during and/or analyzed during the current study are available from H the corresponding author on reasonable request The Branch Vein Occlusion Study Group Argon laser photocoagulation for macular edema in branch vein occlusion Prognostic factors for retinal vein occlusion: Prospective study of 175 cases The prevalence of retinal vein occlusion: pooled data from population studies from the United States Functional outcome of macular edema in different retinal disorders Ang, J. L. et al. A systematic review of real-world evidence of the management of macular oedema secondary to branch retinal vein occlusion. Eye 1, 1. https://doi.org/10.1038/s41433-020-0861-9 (2020) Cystotomy for diabetic cystoid macular edema Effectiveness of en bloc removal of fibrinogen-rich component of cystoid lesion for the treatment of cystoid macular edema Maki, H. et al. The long-term effect of cystotomy with fibrinogen clot removal for a cystoid macular edema secondary to idiopathic macular telangiectasia type 1: a case report. Retin. Cases Brief. Rep. 1, 1. https://doi.org/10.1097/ICB.0000000000001117 (2020) The long-term effect of cystotomy with or without the fibrinogen clot removal for the refractory cystoid macular edema secondary to diabetic retinopathy Nonproliferative Diabetic Retinopathy And Diabetic Macular Edema Experimental Retinal Vein Occlusion in the Rhesus Monkey Radioactive Microsphere and Radioautographic Studies [Proceedings] and lipid parameters in Indian type 2 diabetic males Elevation of fibrinogen and thrombin-antithrombin III complex levels of type 2 diabetes mellitus patients with retinopathy and nephropathy Concentration of acute phase factors in vitreous fluid in diabetic macular edema Vitreous fibronectin and fibrinogen expression increased in eyes with proliferative diabetic retinopathy after intravitreal anti-VEGF therapy Characterization of the vitreous proteome in diabetes without diabetic retinopathy and diabetes with proliferative diabetic retinopathy Immunohistochemical detection of extravasated fibrinogen (fibrin) in human diabetic retina Risk factors for hemiretinal vein occlusion: comparison with risk factors for central and branch retinal vein occlusion: The eye disease case-control study Hypercoagulable states in patients with retinal venous occlusion Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies Predictive value of the vitamin K epoxide reductase complex subunit 1 G-1639A and C1173T single nucleotide polymorphisms in retinal vein occlusion Proteins involved in focal adhesion signaling pathways are differentially regulated in experimental branch retinal vein occlusion Abnormal blood viscosity and haemostasis in long-standing retinal vein occlusion Abnormal blood rheology in retinal vein occlusion: A preliminary report Download references Kobe University Graduate School of Medicine performed the critical review and revision of the manuscript Download citation DOI: https://doi.org/10.1038/s41598-021-88149-z Explore our Food Tours → we’ve grown accustomed to the barrage of lists telling us where to travel during the next 12 months Oftentimes these places are a country or even a whole region – you could spend an entire year exploring just one of the locations listed and still barely make a dent for us the neighborhood is the ideal unit of exploration Celebrating neighborhood life and businesses is essential to what we do as Culinary Backstreets we’ve been dedicated to publishing the stories of unsung local culinary heroes and visiting them on our food walks particularly in neighborhoods that are off the beaten path Last January, we declared 2018 as “The Year of the Neighborhood,” and what a fruitful year it was We had our fair share of fresh experiences and were also able to contribute to the economies of neighborhoods otherwise neglected by the tourism industry Tourism is an important economic force in many cities one that’s based on the sound health of all of a city’s neighborhoods we are happy to again focus on neighborhoods off the main tourist trail in 2019 as well as the people and places that keep them going Below is a compilation of the less-visited areas that our correspondents are planning to explore this year: Barcelona: El Clot and Poblenou Northeast of Barcelona’s polished Modernist center and rebuilt Gòtic alleys the Sant Martí district straddles the line between past and future It represents a fascinating spectrum of Barcelona a place charged with tons of real power: some of the most exciting projects in the city like 22@ district sit alongside traditional markets and long-standing modest homes Yet this range is best experienced in two adjacent neighborhoods which has sold bulk wine for over a century a contemporary restaurant specializing in an ambitious menu of small plates intended for sharing Perhaps no place better bridges the past and present in this area than L’Artesana The restaurant’s name pays tribute to an old workers’ cooperative while their contemporary takes on traditional recipes appeal to the 21st-century workers looking for a satisfying and affordable lunch – in some ways Click here to read the full neighborhood guide COLORADO SPRINGS, Colo. — The Air Force Academy cadet who died on his way to class last month suffered a blood clot stemming from a rare foot injury he suffered weeks earlier according to an El Paso County coroner’s report a 21-year-old offensive lineman on the Air Force football team died following a “medical emergency” he suffered while leaving his dorm on Jan The coroner’s report says Brown died of “pulmonary thromboembolism due to deep vein thrombosis resulting from Lisfranc injury of the left lower extremity.” Brown suffered a ligament injury in his Lisfranc joint – the area where bones in the foot connect near the midfoot The Lisfranc injury caused blood clotting in the veins of his lower leg The Mayo Clinic describes the potential complications from deep vein thrombosis like this: Lisfranc injuries are relatively uncommon, happening to one in 55,000 Americans and accounting for just 0.2% of broken bone injuries, according to the Cleveland Clinic. Officials at the time of Brown’s death said life-saving measures were attempted Brown, a Cadet 3rd Class – the Air Force classification for sophomores – played center for the academy’s football team He played high school football in Lake Charles staff and entire Academy have been so blessed and fortunate to have Hunter as a part of our lives He was a pure joy to coach and have as a teammate," said Troy Calhoun and no one unselfishly pulled harder for others than Hunter." Brown graduated from the Air Force Academy Preparatory School in May 2021 and was pursuing a major in management Update: Casa Lucio is sadly no longer open Editor’s note: The year is coming to an end which means it’s time for us to look back on all the great eating experiences we had in 2014 and name our favorites among them make magic using excellent ingredients and regional Spanish traditions with a little help from such wonderful additions as Italian white truffles and French foie gras Jovells excels at bringing out the best in what’s seasonal such as a surf and turf of mushrooms and squid Menu mainstays like the oxtail are also brilliantly executed the cellar holds a selection of more than 200 wines Morro Fi was originally a bare-bones place on the corner where locals from this part of L’Eixample would meet to have a glass of wine Marc Monzó and Guillermo Pfaff took it over and gave it new life for example) and international craft beers there are more than 200 different bottled beers The El Paso-born Lucha Libre star Cassandro el Exótico was rushed to the hospital where doctors found a blood clot in his brain better known as Cassandro el Exótico is a luchador who was born right here in El Paso Cassandro is known as the Liberace of Lucha Libre an extravagant wrestler with high-flying skills and a big personality inside and outside the ring His name and life have become so well-known Hollywood is going to tell his life story in a movie Cassandro el Exótico is a popular wrestler and fans were given a scare this week when he didn't show up for a match Cassandro had a match scheduled for Monday and he wasn't feeling well It was then that doctors discovered the clot A video was posted on Facebook of the wrestling event shows the hosts making the announcement that they would be holding a prayer circle for Cassandro who had been taken to the hospital for a medical emergency: Later, an official statement was released regarding Cassandro el Exótico's condition and posted on the Solo Lucha Facebook page: El luchador exótico fue intervenido quirúrgicamente para extraerle un coágulo del.. Posted by Sólo Lucha on Monday, May 10, 2021 We're wishing Cassandro el Exótico a speedy recovery and return to the ring Lucha libre just isn't the same without this legendary character The El Paso-born Lucha Libre star Cassandro el Exótico was rushed to the hospital where doctors found a blood clot in his brain.\nRead More A video was posted on Facebook of the wrestling event shows the hosts making the announcement that they would be holding a prayer circle for Cassandro Later, an official statement was released regarding Cassandro el Exótico's condition and posted on the Solo Lucha Facebook page: Posted by Sólo Lucha on Monday, May 10, 2021 NEW YORK (AP) — Al Roker is recovering after he was hospitalized last week for blood clots the NBC "Today" show weather anchor said Friday "So many of you have been thoughtfully asking where I've been Last week I was admitted to the hospital with a blood clot in my leg which sent some clots into my lungs," Roker I am so fortunate to be getting terrific medical care and on the way to recovery," he wrote "Thanks for all the well wishes and prayers and hope to see you soon His co-anchors wished him well online and on the show counting the days xoxoxo," Hoda Kotb said in a comment on Roker's post we've all talked to him," Savannah Guthrie said on Friday's show It wasn't immediately announced whether Roker would be able to co-host NBC's coverage of the Macy's Thanksgiving Day Parade Roker also was off the air in 2020 for two weeks after he underwent successful surgery for prostate cancer Roker said he went public with his diagnosis to highlight the risk of prostate cancer The preservation and protection of heritage and the promotion of protected housing in the neighbourhoods of El Clot and El Camp de l’Arpa will be assured with the initial approval of an amendment to the General Metropolitan Plan by the Commission for Ecology The previous heritage protection for both neighbourhoods was set out in the Protection Plan for the Architectural Historical and Artistic Heritage of Sant Martí an update was needed to the heritage protection regulations for the character of the two neighbourhoods The update was also needed for defining measures to foster new protected housing a suspension was introduced on permits for new buildings and major renovations so that the new urban planning could be drafed The document now presented updates the regulations to ensure that both neighbourhoods conserve their identity the amendment to the plan proposes 13 new heritage sets and 12 new individual elements 149 new plots are being proposed for heritage protection bringing the overall number to 204 protected plots The amendment to the plan also introduces rules that determine the urban protection of various corridors settings and traditional façades with heritage value The proposal includes 589 plots where any work or change would have to take into account the aesthetic and compositional criteria of buildings to integrate the architectural project into the landscape and identity of their façades Of the 2,664 plots in the areas covered by the MPGM the proposal includes protection for 793 of them meaning that practically a third would get some sort of protection One of cornerstones of the new urban planning is to favour public housing It combines measures such as expropriation quotas reserved for protected housing on unconsolidated urban land and the general classification of protected housing The plan is for a potential volume of between 1,000 and 1,500 new protected homes 436 of them on the initiative of the City Council to guarantee that local people continue living in these neighbourhoods Revision of effects for current urban planning The document revises the effects for current urban planning and sets out a series of criteria for addressing these The criteria refer to the relationship between the element and the façade the heritage interest and consolidation of the element and the presence of party walls in relation to the façade Plots given over to green space will gain another 3,000 square metres while there are another 11,000 square metres for facilities The project also promotes sustainable mobility and commerce and applies environmental criteria to increase greenery and biodiversity in urban interventions An extensive participatory process was involved to create the document for initial approval along with the main organisations in the neighbourhoods Four sessions were held with members of the public along with five sectoral meetings to work on areas such as facilities There were also two feedback sessions and two exploratory walks A monitoring commission has also been set up with the presence of the local residents’ association for the two neighbourhoods the Federació d’Entitats and the Taller d’Història del Clot – Camp de l’Arpa Please enable JS and disable any ad blocker It's time for a new edition of La Puça in the Clot neighbourhood You'll find stalls of second-hand treasures artisan crafts and vintage delights in a lovely area of the city Do some shopping and get to know a lesser-explored part of Barcelona while you're at it Volume 12 - 2021 | https://doi.org/10.3389/fmicb.2021.649534 Bacterial infection and thrombosis are highly correlated especially in patients with indwelling medical devices are a common cause of medical device infections owing to their biofilm forming capacity which provides protection from antibiotics and host immune response Attention has been drawn to the interaction between S little is known regarding the impact of the transition from planktonic to biofilm forming phenotype on this interaction Here we investigate the growth phase dependence of bacteria-fibrinogen interaction and the resulting effect on fibrin clot formation Flow cytometry demonstrated growth phase dependent affinity for fibrinogen epidermidis to a fibrinogen coated surface under continuous flow conditions in vitro The bacterial deposition rate onto fibrinogen was significantly greater for stationary (5,360 ± 1,776 cells/cm2s) versus exponential phase (2,212 ± 264 the expression of sdrG–a cell surface adhesion protein with specificity for fibrinogen–was upregulated ∼twofold in the stationary versus the exponential phase Rheometry and confocal microscopy demonstrated that stationary phase S epidermidis slows clot formation and generates a more heterogeneous fibrin network structure with greater elasticity (G′ = 5.7 ± 1.0 Pa) compared to sterile fibrinogen (G′ = l.5 ± 0.2 Pa) while exponential phase cells had little effect This work contributes to the current understanding of the growth phase dependent regulation of bacterial virulence factors and the correlation between bacterial infection and thrombosis SdrG is considered a critical mediator of the interaction between S Once the biofilm becomes densely populated and encased in EPS some of the bacteria detach as planktonic (i.e. flocs) of bacteria that can attach to a new substrate elsewhere and develop another biofilm Each phase of the life cycle requires specific protein machinery to be most effective and the bacteria display phenotypic changes as they progress from planktonic to biofilm phenotype While the change in phenotype is key in biofilm formation little is known about the impact of growth phase on bacteria-host protein interaction epidermidis binding to fibrinogen focuses specifically on cells in the stationary phase of growth The goal of this work is to explore the phenotypic differences between stationary and exponential phase S epidermidis in the scope of their interactions with fibrinogen and their impact on fibrin network formation We first applied flow cytometry to characterize the growth-phase dependent bacterial affinity for fibrinogen Understanding that force/shear loading affect fibrinogen binding epidermidis surface deposition onto fibrinogen in a continuously flowing model mimicking seeding of an intravascular device we compared phase differences in gene expression of S epidermidis cell surface proteins with potential impact on adhesion and interaction with host coagulation proteins we performed rheology and confocal microscopy to evaluate the structure and mechanics of exponential versus stationary phase S A 30 mL sample of the culture at this phase was removed and left undisturbed for 30–60 min at room temperature to allow for settling of flocculated cells prior to use in subsequent studies the remaining culture was returned to the incubator at 37°C to continue growth under agitation until an optical density of 1.4 ± 0.05 was obtained Since rheometry experiments required significantly larger volumes separate cultures were grown to exponential and stationary phases as defined above Staphylococcus epidermidis were cultured to exponential and stationary phase as described above Cell density was quantified in each sample with a Incyto Hemacytometer (Thermo Fisher Scientific United States) and cells were centrifuged into a pellet at 5,000 rpm for 3 min and pelleted cells were diluted to concentration of 2.0 × 109 cells/mL Two conditions were prepared in triplicate for each growth phase–unlabeled control and labeled fibrinogen Control and labeled fibrinogen pellets were resuspended in 1X Hank’s Buffered Salt Solution (with Calcium Fluorescently labeled fibrinogen (Alexafluor 647 Fibrinogen United States) was added to a final concentration of 0.5 mg/mL and incubated for 15 min Cells were then analyzed by flow cytometry (Cytoflex Histograms of area fluorescence (excitation 650 nm/emission 668 nm) from 105 events per sample were obtained Mean fluorescence intensity (MFI) was determined as a surrogate for total fibrinogen concentration on the cell surface using FCS Express (v.7 Nine experiments were completed in triplicate with the median and interquartile range (IQR) reported Statistical analyses were performed with Wilcoxon paired signed rank test with significance defined as p < 0.05 The stationary phase sample was diluted with normal saline to match optical density of the exponential phase culture then left undisturbed at 20°C for 1 h to remove large flocculates Exponential and stationary phase cells were fluorescently labeled with Syto 9 (Thermo Fisher Scientific Cells were loaded into a 10 mL syringe on a standard syringe pump (Harvard Apparatus) Fibrinogen coated glass coverslips were assembled into a parallel-plate flow chamber (Warner instruments RC-31 with 250 μm thick Cell suspensions were infused at a rate of 125 μL/min (Reynolds number = 1.2 wall shear stress = 0.067 Pa) through the parallel-plate flow chamber mounted on a epifluorescent microscope (Nikon Eclipse 80i) A total of 10 experiments were completed in duplicate and the mean for each experiment was used Custom image analysis was performed using MATLAB (v.R2018b a new adhesion event was defined as the new appearance of a bacterium which persisted for two or more consecutive images in a single location The deposition rate was calculated as the slope of adhesion events versus time for each experimental replicate Residence time was defined as the total time a single bacterium persisted at a single location Student’s paired t-test was used for hypothesis testing comparing deposition rate versus growth phase with p < 0.05 defined as significant a χ2 test was used to compare the population of bacteria persisting for greater than 500 s for each growth phase with significance defined as p < 0.01 epidermidis grown to either exponential or stationary phase One mL of bacterial cultures was centrifuged at 8,000 rpm for 1 min to pellet the cells Cell lysis was achieved with 5 μL lysostaphin (2 μg/μL) incubation at 37°C for 45 min followed by addition of 75 μL of TRIzol and vigorous pipetting Samples were vortexed and then centrifuged at 12,000 rpm for 10 min at 4°C Supernatant was removed and incubated at room temperature for 5 min Chloroform (15 μL) was added to the sample and incubated at room temperature for 3 min samples were centrifuged at 12,000 rpm for 15 min at 4°C The aqueous phase was isolated and transferred to RNeasy Mini Kit spin columns (Qiagen) and RNA was purified per the manufacturer’s instructions High quality RNA yield was confirmed by UV spectrophotometry (NanoDrop 2000 Thermo Scientific) and RNA integrity was confirm using a Bioanalyzer (Agilent 2100) Samples were stored at –80°C prior to RT-PCR exponential phase) was determined using the ΔΔCT method with the 16s ribosomal subunit as an endogenous control Student’s t-test was used for hypothesis testing of significance (p < 0.05) of the fold change in gene expression p-values were corrected for multiple comparisons using Benjamin-Hochberg control of false-discovery rate Statistical comparisons were made via ANOVA with post-hoc pair-wise Tukey test with significance level of p < 0.05 Figure 1A shows an example of a single flow cytometry experiment to quantify fibrinogen affinity. The mean fluorescence of the stationary phase population is greater than that of the exponential phase with a similar distribution. Composite mean fluorescence index of all experiments (N = 9 with triplicate measures) is shown in Figure 1B epidermidis incubated with fluorescently labeled fibrinogen was significantly higher as compared to exponential phase under the same condition (3,642 ± 349 vs Flow cytometry of Staphylococcus epidermidis incubated with fluorescently labeled fibrinogen (A) Example density plot of fibrinogen fluorescence for a single flow cytometry experiment (B) Standard box (IQR) and whiskers (1.5*IQR) plot of mean fluorescence of S epidermidis in exponential versus stationary phase Bacterial cell concentration was 4 × 109 cells/mL and fibrinogen concentration was 0.5 mg/mL N = 9 paired experiments with triplicate measurements Most notably there was a population of stationary phase cells that had a residence time of greater than 500 s skewing the distribution to the right as compared to the exponential phase only 2.7% of exponential cells had a residence time of greater than 500 s while 13.1% of the stationary phase cell had a residence time greater than 500 s (p = 0.004) epidermidis to a fibrinogen coated surface under continuous flow (A–E) Representative sequential images of fluorescently labeled S epidermidis (green) captured every 3 s with absence of a cell in white frame in panel (A) adhesion event demonstrated in frames (B–D) and subsequent absence in panel (E) representing a release event Time between frames (B–E) represents the residence time of that single cell (F) Graphical representation of a single experiment of adhesion events over time for exponential (green) versus stationary phase (red) (G) Deposition rate of exponential versus stationary phase S epidermidis for N = 10 paired experiments with duplicate measures (H) Residence time probability distribution of exponential versus stationary phase S epidermidis for all 10 paired experiments with duplicate measures There was a 3.5-fold increase in sspA expression in the stationary versus exponential phase icaR showed a decrease in expression in the transition from exponential to stationary phase Fold change in gene expression for stationary (Sp) versus exponential phase (Ep) The first step represents a transient plateau at a lower elastic modulus than the pure fibrin clot This plateau is followed by a second rapid increase in G′ to a final steady-state value of 5.7 ± 1.0 Pa This two-step kinetic profile of clot formation is completely absent for exponential phase S epidermidis of the same cell concentration the steady state for this condition is not reached within 100 min The growth of the elastic modulus of the exponential phase is significantly retarded relative to the stationary phase Its kinetics are also somewhat slower than pure fibrin The final (t = 100 min) modulus of the exponential phase is not significantly lower than that of pure fibrin (1.3 ± 0.4 Pa) Staphylococcus epidermidis alters fibrin elasticity and structure in a growth phase dependent manner of pure fibrin clot (0.5 mg/mL) (black) and fibrin clots infected by stationary and (red) Error bars denote standard deviation with N = 3 (B) Mesh size characterization of steady-state pure fibrin clot and fibrin clots infected with stationary and exponential phase S Error bars denote standard deviations with N = 5 Note that the stack bars (gray and red) in the stationary phase condition indicate two characteristic mesh sizes (C) Axial projections of a pure fibrin clot a fibrin clot infected with (D) exponential and (E) stationary phase S cell concentrations are all 4 × 109 cells/mL and fibrin concentration is 0.5 mg/mL but rather some other difference in the bacteria related to its growth phase There are likely many other phenotypic differences associated with growth phase that aid in survival and virulence This study demonstrates the growth phase dependent interactions between S We further elucidated the resulting growth phase dependent effect of S epidermidis in its stationary phase–versus exponential phase–expresses more sdrG and adheres more frequently and for a longer duration to a fibrinogen coated surface epidermidis during thrombin-catalyzed polymerization of fibrinogen generates a heterogeneous fibrin network structure that is four times stiffer than pure fibrin in its absence This effect is not observed if exponential phase S Here we consider the possible explanations for the correlation between adhesion to fibrinogen and the resulting influence on fibrin clot formation and increased risk of embolism as a potential virulence factor for biofilm infected indwelling medical devices The resulting disorganized fibrin network microstructure leads to instability and ultimately rupture a serine protease which cleaves fibrinogen may offer an additional means of dispersion via thromboembolism and further disseminate infection the exact contribution of this protease to clot rupture was not specifically evaluated in this study and is the subject of future work Figure 4. Hypothesized mechanism for the observed phenomenon in Figure 3 epidermidis cells (blue circles) have sufficient affinity for fibrinogen (red lines) the attraction between cells and fibrinogen generate a heterogeneous fibrinogen distribution that results in a heterogeneous fibrin network structure This has profound implications on fibrin network elasticity and ultimately potential for embolization the potential for adhesion to a new surface location is facilitated and the process starts anew this study demonstrates the growth phase dependent interaction between S epidermidis and fibrinogen and the resulting effect of S It contributes to the current understanding of growth phase dependent regulation of S epidermidis virulence factors and the association between bacterial infection and thrombosis It also provides fodder for investigation of the mechanisms of and pharmaceutical solutions to infection-induced thromboembolism and EM-N performed the experiments and generated the data This 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This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) *Correspondence: J. Scott VanEpps, anZhbmVAbWVkLnVtaWNoLmVkdQ==; Michael J. Solomon, bWpzb2xvQHVtaWNoLmVkdQ== †These authors have contributed equally to this work Metrics details A prothrombotic state is a typical feature of type 2 diabetes mellitus (T2DM) A variety of poorly elucidated mechanisms behind impaired fibrinolysis in this disease have been reported indicating complex associations between platelet activation elevated plasminogen antigen inhibitor-1 levels which are closely associated with obesity Abnormal fibrin clot structure is of paramount importance for relative resistance to plasmin-mediated lysis in T2DM increased release of neutrophil extracellular traps along with posttranslational modifications of fibrinogen and plasminogen have been regarded to contribute to altered clot structure and impaired fibrinolysis in T2DM Antidiabetic agents such as metformin and insulin have been reported to improve fibrin properties and accelerate fibrinolysis in T2DM recent evidence shows that hypofibrinolysis has a predictive value in terms of cardiovascular events and cardiovascular mortality in T2DM patients This review presents the current data on the mechanisms underlying arterial and venous thrombotic complications in T2DM patients with an emphasis on hypofibrinolysis and its impact on clinical outcomes We also discuss potential modulators of fibrinolysis in the search for optimal therapy in diabetic patients the current evidence indicates that T2DM substantially elevates arterial thromboembolic risk while its impact on VTE risk and complications is largely associated with increased BMI The most relevant research on hypofibrinolysis and its clinical implications in T2DM was reviewed We included papers regarding the cellular components including platelet hyperactivity and pathological structure and function of erythrocytes They have been followed by papers describing the endothelial dysfunction enhanced thrombin generation (TG) and inflammatory state including neutrophil cellular traps (NETs) Then we proceeded to the review of literature in the topic of qualitative and quantitative changes of fibrinogen with a special emphasis on the posttranslational modifications of fibrinogen This has been followed by the analogical modifications of proteins involved in fibrinolysis In the part devoted to the pharmacological interventions Results of basic research and clinical trials were selected from PubMed and Web of Science from January 2000 to May 2021 supported by a few seminal papers from previous years Mechanisms involved in hypofibrinolysis in type 2 diabetes mellitus (T2DM) patients The main contributors to hypofibrinolysis in T2DM are platelet activation increased fibrinogen level along with its modifications Obesity represented by high body mass index (BMI) Glc) all lead to platelet activation reflected by increased release of thromboxane A2 (TXA2) Another contributor to platelet activation is oxidative stress which is reflected by increased synthesis of F2-isoprostane 8-iso-prostaglandin F2α (8-iso-PGF2α) a product of low-density-lipoprotein (LDL) cholesterol peroxidation Down-regulation of the insulin receptor substrate 1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) pathways with enhancement of mitogen-activated protein kinase (MAPK) result in decreased nitric oxide (NO) synthesis and increased PAI-1 release Advanced glycation end-products (AGE) stimulate overactive NADPH oxidases (NOX) reactive oxygen species (ROS)-producing enzyme complexes which in turn generates tissue factor (TF) in ECs AGE stimulate monocytes (Mo)/macrophages (Ma) to produce increased amounts of TF Another source of TF are the vascular smooth muscle cells (VSMCs) Increased TF initiates the extrinsic pathway of coagulation and together with factor VII (VIIa activated factor VII) lead to enhanced thrombin generation Weibel-Palade bodies release increased amounts of von Willebrand factor (vWF) which along with increased factor VIII (VIIIa form the intrinsic pathway of thrombin generation Increase in both components of the prothrombinase complex Other factors underlying enhanced thrombin generation are central obesity represented by increased waist-hip circumference (WHC) ratio and time since T2DM diagnosis exceeding 5 years increased interleukins 6 and 8 (IL-6 and IL-8) along with ROS stimulate neutrophils to form the neutrophil extracellular traps (NETs) with an important stage of chromatin decondensation mediated by peptidylarginine deiminase 4 (PAD4) followed by a release of nuclear components depicted in light blue and granular components depicted in dark blue myeloperoxidase (MPO) and neutrophil elastase (NE) Obesity represented by increased BMI elevates both CRP and complement C3 (C3) levels IL-6 and insulin resistance contribute to elevated fibrinogen concentration while hyperglycemia and ROS result in posttranslational modifications such as fibrinogen glycation (–Glc) and oxidation (–ROS) The fibrin network formed from modified fibrinogen with increased amounts of incorporated α2-antiplasmin (a2AP) characterized by enhanced crosslinking by factor XIII (FXIII) being composed of thinner and highly branched fibrin fibers increased amount of polyhedrocytes are found in the contracted thrombi of diabetic patients diminished binding of plasminogen and tissue plasminogen activator (tPA) to fibrin originating from adipocytes and hepatocytes are also involved in hypofibrinolysis observed in T2DM Glycation of plasminogen was reported in type 1 diabetes mellitus patients and therefore is marked with asterisks α2-antiplasmin is another protein implicated in fibrinolysis and found to be glycated in T2DM and this can be most likely extrapolated to diabetic patients enhanced TX-dependent platelet activation is a typical phenomenon in T2DM patients and is associated with oxidative stress at least in part through enhanced release of PAI-1 and PMP changes in ultrastructure of the erythrocyte membrane result in its altered mechanical properties the current evidence convincingly shows that endothelial dysfunction in T2DM driven by disturbed signaling in the arterial wall along with overactive NOX is related to hypofibrinolysis through increased expression of PAI-1 current evidence supports the role of enhanced TG in the development of cardiovascular complications in T2DM patients with some of these complications likely being related to hypofibrinolysis many recent investigations have revealed that NETs and complement C3 are novel contributors to hypofibrinolysis in T2DM Their prognostic value regarding cardiovascular mortality in T2DM remains to be established hyperfibrinogenemia might contribute to decreased fibrin clot lysability and subsequent thromboembolism in T2DM patients; however its impact does not appear to be independent of other cardiovascular risk factors although some of the oxidized sites were near these crucial sites current evidence shows that the diabetic milieu promotes fibrinogen modifications which are of paramount importance in the formation of abnormal fibrin clot structure this could be due to different glycation patterns; however this should be investigated in future studies modifications of both fibrinogen and plasminogen are implicated in hypofibrinolysis in T2DM with possible links to compromised fibrinolysis Whether this would serve some pathway how empagliflozin could decrease prothrombotic tendency in T2DM current data suggest that iron may be involved in hypofibrinolysis in T2DM there have been no reports on the effect of the new antidiabetic drugs on clot lysis time in patients with T2DM The current evidence indicates that impaired fibrinolysis characterizes patients with T2DM the optimal test to assess the efficiency of fibrinolysis in this disease remains to be established given several assays used in clinical studies in recent years and their limitations Recent studies have identified novel mechanisms involved in hypofibrinolysis in T2DM including NETs and posttranslational modifications of proteins involved in fibrin formation and lysis including the fact that prolonged T2DM duration and decreased glycemic levels are factors contributing to altered fibrin structure and impaired lysis The beneficial effects of antidiabetic drugs could be at least in part associated with fibrinolysis Novel antidiabetic drugs are undoubtedly an integral part of T2DM treatment it is required that further studies regarding their impact on fibrinolysis be conducted Due to the major involvement of protein glycation it might be speculated that all hypoglycemic agents may improve fibrinolysis treatment with low-dose FXa inhibitors and aspirin in diabetic patients at high risk for cardiovascular mortality could also be beneficial in terms of fibrinolysis multiple interventions are needed to improve fibrinolysis in T2DM Further studies are needed to evaluate the actual role of enhanced fibrinolysis in the prevention of morbidity and mortality in a rapidly growing population of patients with T2DM 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Diabetes Obes Metab. 2021. https://doi.org/10.1111/dom.14517 Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34) Decreased mortality associated with the use of metformin compared with sulfonylurea monotherapy in type 2 diabetes Beneficial effects of metformin on haemostasis and vascular function in man Effect of metformin on methylglyoxal metabolism in patients with type 2 diabetes Metformin uniquely prevents thrombosis by inhibiting platelet activation and mtDNA release The antidiabetic drug metformin blunts NETosis in vitro and reduces circulating NETosis biomarkers in vivo Effects of short-term treatment with metformin on markers of endothelial function and inflammatory activity in type 2 diabetes mellitus: a randomized Metformin is associated with reduced tissue factor procoagulant activity in patients with poorly controlled diabetes The effect of dimethylbiguanide on thrombin activity Advanced glycation end products evoke endothelial cell damage by stimulating soluble dipeptidyl peptidase-4 production and its interaction with mannose 6-phosphate/insulin-like growth factor II receptor Effect of dipeptidyl peptidase-4 inhibitor vildagliptin on plasminogen activator inhibitor-1 in patients with diabetes mellitus Effect of linagliptin compared with glimepiride on postprandial glucose metabolism islet cell function and vascular function parameters in patients with type 2 diabetes mellitus receiving ongoing metformin treatment Glucagon-like peptide-1 receptor Agonists (GLP-1RAs) improve biomarkers of inflammation and oxidative stress: a systematic review and meta-analysis of randomised controlled trials Empagliflozin decreases the plasma concentration of plasminogen activator inhibitor-1 (PAI-1) in patients with type 2 diabetes: Association with improvement of fibrinolysis The recovery of platelet cyclooxygenase activity explains interindividual variability in responsiveness to low-dose aspirin in patients with and without diabetes Aspirin in the primary prevention of cardiovascular disease in diabetes mellitus: a new perspective Aspirin for primary prevention of cardiovascular outcomes in diabetes mellitus: an updated systematic review and meta-analysis Aspirin for primary cardiovascular prevention: why the wonder drug should not be precipitously dismissed Aspirin acetylates fibrinogen and enhances fibrinolysis Fibrinolytic effect is independent of changes in plasminogen activator levels Why does aspirin decrease the risk of venous thromboembolism On old and novel antithrombotic effects of acetyl salicylic acid Effects of aspirin on clot structure and fibrinolysis using a novel in vitro cellular system Early glycemic control and magnitude of HbA1c reduction predict cardiovascular events and mortality: population-based cohort study of 24,752 metformin initiators Role of combination antiplatelet and anticoagulation therapy in diabetes mellitus and cardiovascular disease: insights from the COMPASS trial Rivaroxaban in patients with a recent acute coronary syndrome Assessment of patients with coronary artery disease who may benefit from the use of rivaroxaban in the real world: implementation of the COMPASS trial criteria in the TERCET registry population Plasma fibrin clot properties in the G20210A prothrombin mutation carriers following venous thromboembolism: the effect of rivaroxaban Apixaban enhances endogenous fibrinolysis in patients with atrial fibrillation Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men The effects of high- and medium-dose metfformin therapy on cardiovascular risk factors in patients with type II diabetes Download references This work was supported by the Jagiellonian University Medical College (K/ZDS/005802 to A.U.) AHB-W contributed to the work by reviewing literature AU conceived the topic and revised the manuscript Both authors read and approved the final manuscript The authors declare that they have no competing interests unless otherwise stated in a credit line to the data Download citation DOI: https://doi.org/10.1186/s12933-021-01372-w WASHINGTON - Doctors treating Secretary of State Hillary Rodham Clinton for a blood clot in her head said blood thinners are being used to dissolve the clot and they are confident she will make a full recovery Clinton didn't suffer a stroke or neurological damage from the clot that formed after she suffered a concussion during a fainting spell at her home in early December was admitted to New York-Presbyterian Hospital on Sunday when the clot turned up on a follow-up exam on the concussion The clot is located in the vein in the space between the brain and the skull behind the right ear She will be released once the medication dose for the blood thinners has been established Lisa Bardack of the Mount Kisco Medical Group and Dr Gigi El-Bayoumi of George Washington University said Clinton was making excellent progress and was in good spirits Clinton's complication "certainly isn't the most common thing to happen after a concussion" and is one of the few types of blood clots in the skull or head that are treated with blood thinners a neurologist who is director of Duke University's stroke center The area where Clinton's clot developed is "a drainage channel the equivalent of a big vein inside the skull It's how the blood gets back to the heart," Goldstein said Blood thinners usually are enough to treat the clot and it should have no long-term consequences if her doctors are saying she has suffered no neurological damage from it then fell ill with a stomach virus in early December that left her severely dehydrated and forced her to cancel a trip to North Africa and the Middle East she had canceled only two scheduled overseas trips one to Europe after breaking her elbow in June 2009 and one to Asia after the February 2010 earthquake in Haiti fell and suffered a concussion while at home alone in mid-December as she recovered from the virus This isn't the first time Clinton has suffered a blood clot midway through her husband's second term as president Clinton was in New York fundraising for the midterm elections when a swollen right foot led her doctor to diagnose a clot in her knee requiring immediate treatment Clinton had planned to step down as secretary of state at the beginning of President Barack Obama's second term Whether she will return to work before she resigns remained a question Democrats are privately if not publicly speculating: How might her illness affect a decision about running for president in 2016 Clinton says she plans to spend the next year resting She has long insisted she had no intention of mounting a second campaign for the White House four years from now and she would almost certainly emerge as the Democrat to beat if she decided to give in to calls by Democratic fans and run again Her age - and thereby health - would probably be a factor under consideration given that Clinton would be 69 when sworn in That might become even more of an issue in the early jockeying for 2016 if what started as a bad stomach bug becomes a prolonged Not that Democrats are willing to talk openly about the political implications of a long illness choosing to keep any discussions about her condition behind closed doors Democrats reject the notion that a blood clot could hinder her political prospects "Some of those concerns could be borderline sexist," said Basil Smikle a Democratic strategist who worked for Clinton when she was a senator "Dick Cheney had significant heart problems when he was vice president It isn't uncommon for presidential candidates' health - and age - to be an issue had to rebut concerns he was too old to be commander in chief or that his skin cancer could resurface Two decades after Clinton became the first lady signs of her popularity - and her political strength - are ubiquitous Obama had barely declared victory in November when Democrats started zealously plugging Clinton as their strongest White House contender four years from now "Wouldn't that be exciting?" House Democratic leader Nancy Pelosi declared in December Even Republicans concede that were she to run Clinton would be a force to be reckoned with "Trying to win that will be truly the Super Bowl," Newt Gingrich the former House Speaker and 2012 GOP presidential candidate "The Republican Party today is incapable of competing at that level." Americans admire Clinton more than any other woman in the world according to a Gallup poll released Monday - the 17th time in 20 years that Clinton has claimed that title And a recent ABC News/Washington Post poll found that 57 percent of Americans would support Clinton as a candidate for president in 2016 Websites have already cropped up hawking "Clinton 2016" mugs and tote bags Clinton's three-week absence from the State Department has raised eyebrows among some conservative commentators who questioned the seriousness of her ailment after she canceled planned Dec 20 testimony before Congress on the deadly attack on the U.S Clinton had been due to discuss with lawmakers a scathing report she had commissioned on the attack It found serious failures of leadership and management in two State Department bureaus were to blame for insufficient security at the facility Clinton took responsibility for the incident before the report was released Four officials cited in the report have either resigned or been reassigned Barcelona is the largest city in Catalonia, an autonomous Spanish region known for football, art, architecture and a commitment to the Catalan language. Named the best non-capital city in the world for tech by the Savills Index, the area is also the fifth most digitized in Europe placing it ahead of countries like Germany and the United Kingdom TravelPerk is a global SaaS company that provides an all-in-one platform for managing corporate travel Founded in 2015 and headquartered in Barcelona it offers solutions for booking flights and accommodations streamlining approval workflows and managing travel expenses With 24/7 customer support and tools for sustainability and policy management TravelPerk serves businesses around the world through its team of over 1,200 employees who work across offices in Europe and the United States Dynatrace provides B2B companies with software for observability and continuous runtime application security Its platform maintains digital borders and responds to IT issues which enables users to automate cloud operations The company’s Barcelona office is a short walk from Parque del Clot. Mirakl was founded in 2012 and has an office in the Sant Gervasi-Galvany area The company provides B2B and retail brands with digital products Its solutions include Mirakl Platform for setting up online marketplaces which allows sellers to receive secure payments which makes personalized product recommendations based on artificial intelligence. Personio serves small and medium-sized businesses as an all-in-one HR solution to streamline the people management cycle it enables brands to manage their employees and scale up their business The company has its office on the banks of Jardines de Salvador Espriu. CrowdStrike provides cybersecurity services such as threat intelligence It uses artificial intelligence to provide endpoint threat protection The company’s solutions are used in areas that include retail Mixpanel has an office in El Parc i la Llacuna del Poblenou The company’s event analytics platform enables users to glean revenue and customer data insights Its platform creates real-time charts to show how people interact with a user’s brand and products with data like retention and conversion rates The AirDNA platform offers short-term rental intelligence based on a database that encompasses 10 million rental properties across thousands of global markets The company’s solutions serve more than 1.3 million users Rose Velazquez contributed reporting to this story growing up gay in Ireland and writing his first poetry collection at the age of 66 In bed he amuses himself by identifying the difference between blood clots (a new emergency) and cancer: “Boris Johnson would be a blood clot … Angela Merkel the cancer.” He is surely Ireland’s most prolific and prestigious living writer Broodingly striking in appearance – in a movie he would be the gangster with a kind heart – he is animated gracious and gossipy in conversation: we are on a video call from Los Angeles where he spends part of the year with his boyfriend He is very much alive (he played tennis yesterday) Meeting Tóibín in person (in more normal times) is to be struck by the disconnect between this ebullient mournful fictional worlds for which he is famous are as steeped in gentle misery as his native Wexford is in rain “I’d love to have an integrated personality,” he once told a psychiatrist friend (he has a way of telling stories that sound like the beginning of a joke) Tóibín said: “The books are so filled with melancholy and I wander about like some sort of party animal.” “Well which would you like to be?” his friend asked To which he replied “I don’t know.” “Oh go away!” the psychiatrist said “I have serious patients with serious problems.” For a man who can plough through a weighty biography in a day (preferably in a hammock in the California garden he shows off when he angles the computer) or turn out more than 20,000 words one of the hardest things about his illness was that he was unable to read or write This is something known only to “the chemo club” “How could it be that you couldn’t even turn on Bach Anywhere I’ve ever been there’s a poemThe steroids during which “grinding time” he was able to write a couple of poems He hadn’t seriously written poetry since his teens a line would come to him out of the blue “like a melody” The rest of the poem would materialise quite quickly and in the mornings he would get up and cut some lines but the collection is not all about the motherland which coincidentally was built on the site of the fictional house of Joyce’s Blooms “How very strange to be in this space where Leopold and Molly once were,” he would muse in bed He will be doing Ulysses when he returns to Columbia University To finish The Magician he switched from his customary longhand to a computer I needed to get the book done before a recurrence,” he says Like The Master, Tóibín’s acclaimed 2004 novel about Henry James, The Magician is another portrait of a sexually repressed artist “I don’t have a third,” he says of this trick of inhabiting the inner-worlds of great writers to explore his theme of creativity driven by thwarted desire Both writers were hugely important to him during his late teens and early 20s left him “fascinated by figures who had lived in the shadows erotically” to the sense of James and Mann as being “like ghosts in certain rooms” a distance created by their “uneasy homosexuality” James’s work is filled with sexual secrets.” Saoirse Ronan and Emory Cohen in the 2015 film adaptation of Tóibín’s novel Brooklyn Photograph: Lionsgate/AllstarTóibín’s life has parallels with both authors (he shares James’s unapologetic sociability) who ends up in exile in LA; he even taught at Princeton “You end up exploring the things that interest you,” Tóibín says “Obviously there were things I had to imagine: the money and the power the rise of Hitler.” Mann doesn’t emerge as an heroic figure either privately (he didn’t attend his son Klaus’ funeral because he was on a book tour) or as the most influential writer in Germany during the interwar years: a willingness to write morally ambiguous complex or unlikeable characters is “essential” in fiction From his first novel The South he has returned repeatedly to the stretch of Wexford coast of his childhood He would never have believed that this “very mild place where in summer there is more drizzle than rain more cloud than sun” could have provided him with “enough expression or felt life or drama” as the backdrop for so many novels “Going back to it over and over has been rich and surprising.” But, like so many of his Irish literary forebears, he also needs to escape; each novel he says, is a reaction against its predecessor. After his fourth, the Booker shortlisted The Blackwater Lightship in which three generations of women and three gay men are stuck in a crumbling house on the coast for seven days – “there’s a lot of rain and a lot of making of tea and a lot of recriminations” – it was a relief to absorb himself in the sophisticated milieu of Henry James more elaborate dialogue and to have a lot of duchesses” because you want the reading process to be immersive in the same wayBut then he was done with duchesses and wanted to go back home which returns to Enniscorthy and the lives of small-town Irish people a book of yours we can finally read,” someone told him an austerely moving fictionalisation of the aftermath of his father’s death he felt “I never ever want to go back to that house again I never want to go back into that sort of slow-burning grief.” And so it was a pleasure to turn to the cosmopolitan “after writing another Irish novel in which no one has a penny.” While he might be in sunny California right now Another constant in his fiction is the longing for an absent mother (when his father was taken ill suddenly he didn’t see his mother for three months) when the young Thomas is left alone for a year in Lubeck “It won’t go away!” Tóibín whispers theatrically complicated female characters – Eilis Lacey in Brooklyn Nora Webster – to a childhood spent in a houseful of women Also his fascination with the gaps between what is said and what is felt On a good day, he will do nothing but write. “You need to immerse yourself in it, because you want the reading process to be immersive in the same way,” he says. “It is a question of being in your mental pyjamas all day.” He is back to writing by hand – holding a neatly written notebook with early pages of the new Brooklyn to the screen – making corrections and additions when he types it up. Read more“What will happen if you get writer’s block?” a bank clerk once asked ‘Will you stop that nonsense!’ Writer’s block for God’s sake It is one of those things that other people think writers have.” Despite his prodigious output and boundless curiosity that there are other people who are out there working really hard and that I’m not one of those people writing is a form of self-erasure: “the page is not a mirror “to hand over the feelings to the character and to make sure they are not yours You are not here,” he says covering his face with his hands except what’s blank and you have to fill it.” This article was amended on 15 December 2021 not Princeton as stated in an earlier version The Magician by Colm Tóibín is published by Viking (£18.99). To support the Guardian and Observer order your copy at guardianbookshop.com surgical specialist who flew in from New Orleans Thursday afternoon said the operation was a “complete success” and predicted a complete recovery for the diminutive golf champion “He should recover from the effects of surgery within a week and be up and around in a few months,” the surgeon said Hogan had been reported in serious condition most of the day Thursday The doctor said he had made an incision in the golfer’s abdomen and tied off the vein through which the clots had appeared The two clots which had endangered the golf star’s life had been absorbed by his system Hogan was in the operating room about two hours Royal Hogan would make no predictions concerning his brother’s release form the hospital Hogan was given “a large transfusion” before submitting to surgery Hogan was only slightly injured in the crash Anxious friends of the golfing star kept Mrs Hogan and Royal Hogan busy on the telephone much of the time Thursday The callers included Golf Stars Jimmy Thompson Here is a link to more Ben Hogan photos This menu requires arrow keys to be able to use it. The menu has up to three levels: Work is under way to draft a document for the protection of the traditional fabric and architectural heritage of these two parts of the city, the goal being to protect their unique character and identifying values. The protection of heritage in these two neighbourhoods has so far been provided for in the plan for the protection of architectural, historical and artistic heritage in Sant Martí, approved in the year 2000, along with the plans for the rest of the city, and renewing the catalogue from 1979. The aim of the new document will be to preserve the value and identity of these two spaces, bringing up to date the existing regulation which protects properties and buildings but which is mainly based on monumental criteria. The regulation will now include aspects relating to the character of the neighbourhoods, elements from their history, the urban landscape, historical memory and the environment. Both neighbourhoods retain a clear coherence which has been affected by some actions and urban planning decisions. The drafting of this new plan will enable the two neighbourhoods to remain recognisable in the future. The drafting of the document means that the issue of new building permits and major renovation permits in this area will be suspended for up to a year at most, to avoid any substantial changes in the two neighbourhoods. but he remembers the Spanish Civil War vividly A lifetime resident of Barcelona's El Clot neighborhood he was only 3 when the conflict started and 5 when the Catalan capital became one of the first major cities in the world to suffer sustained 'carpet bombings' with the main purpose of instilling terror among civilians. Bachs still resides in the very same apartment complex on Carrer Mallorca street that he lived in as a child with his family. "My father was drafted in 1938 and sent to the Ebre," he told Catalan News in a recent interview from his building's lobby explaining that while he fought in the bloody southern Catalonia battle and brother waited out the war in Barcelona. "The buildings in front of ours didn't exist back then and you could see Carmel where the antiaircraft defense was," he said of what today is known as the Carmel Bunkers on Turó de la Rovira hill a popular viewpoint frequented by tourists and day drinkers "From our window we could see them firing tracer bullets toward the sea." But once the air raid sirens began ringing out the closest bomb shelter was located right beneath them "We'd play in the shelter's tunnels," he said while adults "would talk about who had gotten a letter" from the front boom' but when it was over you'd leave and that was it." 85 years after Barcelona's notorious 'carpet bombings' but Bachs no longer goes down there - the stairs are far too hard on his 90-year-old frame. "These shelters speak to the way Barcelona residents fought for survival and their values," Domènech said; most were built shortly after the war broke out in 1936, with a higher concentration of them in areas with strong neighborhood associations and community ties. Tucked away from sight beneath the intersection of Barcelona's Mallorca, Biscaia, and Clot streets lies an underground maze of tunnels, some more spacious and well lit than others. Despite the passage of time, it remains in remarkable condition, closed off to the public who for the most part have no idea of its existence. "Unfortunately, there are no longer many shelter children left," Ana Sánchez says. "Manel Bachs is a unique witness." Get the day's biggest stories right to your phone Mar 29, 2024Al Roker is back at work and doing well over a year after his medical absence in 2022 The beloved weatherman returned to TV on Friday after an extended absence for medical reasons beginning in fall 2022 Related: Get to Know Al Roker's Other Half Deborah Roberts While Roker told his co-workers on the TODAY show that he's "got a number of issues," he shared and every day I feel a little bit better." Here is everything we know about Al Roker's health that he had recently been admitted to the hospital "with a blood clot in my leg which sent some clots into my lungs." In a post on Instagram he wrote, "After some medical whack-a-mole, I am so fortunate to be getting terrific medical care and on the way to recovery. Thanks for all the well wishes and prayers and hope to see you soon Roker has shared just how many complicating factors were at play. I had blood clots that they think came up after I had COVID in September and then I had this internal bleeding going on," he shared They were trying to figure out where it was Related: Al Roker's Best Grilling Tips Roker was hospitalized for blood clots in November 2022 Roker was taken back to the hospital via ambulance the day after he was first released on Thanksgiving. One witness told the outlet “Al was taken from his home in a stretcher back to the hospital on Friday Roker had a clean bill of health and was back on TV but he took another leave in May 2023 for a knee replacement "Thank you all so much for being so concerned about him and so interested in his well-being" Rokers' wife Roberts said in a Sunday "As many of you know he had a knee re-replacement so a knee that had been replaced many many years ago had problems and had to be re-replaced. It makes it slow-going so it's a little bit harder to snap back from but he's doing pretty well Does Al Roker have blood clots?Roker was first admitted to the hospital in November 2022 with a blood clot in his leg which he revealed sent "some clots" into his lungs Related: TODAY Staff Surprises Al Roker As He Recovers at Home Where is Al Roker on TODAY?Roker was absent from the NBC program due to his health scare in late 2022 and early January 2023 Speaking to his TODAY colleagues about why he hasn't come back to the show just yet he said: "You lose a certain amount of muscle mass for every week you’re in the hospital and I was in the hospital for four weeks." "It’s just a certain amount of weakness I’m doing physical therapy every day I've got to just get my strength back." but was absent for much of May following a knee replacement "Al is chomping at the bit to try to get back to work, but the doctor just wants him to take it slowly so that he can continue to heal well," Roberts said on May 21, 2023. "So on Al's behalf and our family's behalf thank you so much and I'm sure he'll be popping up soon .. He's trying to obey the doctor's orders so that he can get back to work and to play as soon as possible so just wanted to give you a little update on him." Where has Al Roker been?Roker was recovering at home from a knee replacement that he underwent in early May 2023 Roker told his colleagues, "This [knee replacement] is a little more complicated because it's what they call a revision—it was a replacement of a replacement So we've just been kind of hanging out From November 2022 to January 2023, Roker was recovering from blood clots at home. On Dec. 8, 2022, the weatherman announced that he was back at home following his second hospital stint. @todayshow family and all your thoughts and prayers," he wrote on Instagram. Is Al Roker sick?Roker is fully recovered after being hospitalized for blood clots in November 2022 he underwent a successful knee replacement surgery In 2020, Roker revealed that he was battling prostate cancer and underwent surgery to have his prostate removed that Roker's knee replacement surgery recovery went well explaining that he was icing and elevating his knee and taking it easy then would undergo several months of physical therapy What type of knee replacement did Al Roker have?In May 2023 Roker underwent surgery to replace "a replacement" left knee This is called a "knee revision" surgery Because most knee replacements last 20 years having had his first knee replacement in his 40s Who operated on Al Roker's knee? David J. Mayman, MD, hip and knee surgeon at the Hospital for Special Surgery in New York City, performed Roker's knee revision surgery in 2023 a left knee replacement and a revision knee surgery for his left knee Next, Find Out Which TODAY Host Was the Only One Who Went to Their High School Prom GRAB AND GO  A new medical device uses a catheter to deliver a wire mesh stent to snag and remove stroke-causing blood clots from inside brain arteries GRAB AND GO A new medical device uses a catheter to deliver a wire mesh stent to snag and remove stroke-causing blood clots from inside brain arteries By Nathan Seppa doctors have begun treating strokes caused by blood clots in the brain by the most direct route imaginable — approaching the blockage from inside the artery The concept is well-tested. Obstructed heart vessels are routinely opened with balloon-tipped catheters threaded up to the blockage. Attempts to clear obstructions in the brain have proved devilishly difficult, though (SN: 10/8/11, p. 14) We summarize the week's scientific breakthroughs every Thursday By subscribing, you agree to our Terms & Privacy Policy. You must be 13 or older to sign up For full digital access, consider a $2.99 per month subscription a string of successes using a new device made just for the brain has rendered clot extraction a reality Five studies all show that people in the throes of a major clot-based stroke are better off getting the clot removed by a stent-tipped catheter plus standard care than by getting standard care alone Four trials were stopped early because the device’s benefit was indisputable “This is a once-in-a-generation change in acute stroke care,” says neurologist Jeffrey Saver director of the UCLA Stroke Center in Los Angeles “It’s been about 20 years since the last stroke therapy — tPA — came along,” he says It’s a clot-dissolving drug given intravenously to some stroke patients But while dissolving a clot with tPA is less invasive than extracting it with a mechanical device tPA clears obstructions from only about one-third of jammed cerebral arteries “A retrievable stent can open up 80 to 90 percent of them,” says Saver who coauthored one of the clot extraction trials Clots in major arteries of the brain can cause disabling strokes This illustration depicts how an obstruction can starve a part of the brain (shaded area) by shutting off its blood flow will expand the number of stroke patients who are treatable a neurologist and emergency medicine doctor at the University of Calgary in Canada the clot retriever might extend the crucial time window after stroke onset in which treatment can be performed in some patients without risk of doing more harm than good all published in the New England Journal of Medicine this year included patients who had a large blood clot in a major cerebral artery roughly 800,000 people in the United States have a stroke a neurologist and acting director of the National Institute of Neurological Disorders and Stroke in Bethesda This is what fills up nursing homes and care centers,” he says “These strokes rob people of their personality and ability to function.” Antibodies that bind to a protein called platelet factor 4 may be behind rare blood clots (one illustrated) that develop in some people vaccinated with AstraZeneca’s or Johnson & Johnson’s COVID-19 vaccines A new survey describes a range of neurological and psychiatric symptoms in patients hospitalized with COVID-19 (general brain MRI images shown) health officials stopped administering the Johnson & Johnson COVID-19 vaccine at federal vaccination sites after reports that six out of 6.8 million people developed deadly blood clots Patients in these trials were randomly assigned to get the clot extracted or to get tPA or a doctor inserts a catheter into a large artery in the groin then threads it up to the brain a wire inside of it tunnels through the obstruction The doctor withdraws the wire and replaces it with the stent-retriever device restoring blood flow that rescues the starving brain cells downstream that have not yet died 60 percent of patients getting the extraction procedure were functionally independent compared with 35 percent getting just tPA “I think this is the biggest thing to ever happen because you can really take somebody who’s going to have a horrible outcome and save them.” The clock starts ticking the moment a blood clot lodges in a major brain artery about 2 million neurons die on average each minute until blood flow is restored “The biological imperative is speed.” Stroke patients routinely undergo a quick CT scan at a hospital or stroke center to discern whether they have a bleeding or clot-based stroke Patients with clots who qualify are given tPA with high blood pressure or certain other conditions can’t receive it the drug fails to dissolve big clots most of the time The shortcomings of tPA spurred research into mechanical extraction devices (SN: 2/17/07, p. 99) But brain arteries are curvy and fragile compared with heart vessels and merely inserting a device into the brain risks collateral damage patients treated with older-generation brain-clot retrievers and tPA fared no better than those just getting tPA Stroke patients randomly assigned to get a clot removal procedure in addition to a standard clot-dissolving drug (tPA) did better three months later than those treated with the drug alone But testing was already under way for the new stent-retriever device a pharmaceutical company acquired this year by Minneapolis-based Medtronic The results now show that the device safely removes brain clots Not all patients in the recent studies recovered fully after clot extraction probably because the brain had sustained too much damage before blood flow was restored the high-tech advance arrives at a good time and emergency departments and stroke centers have become more efficient in promptly moving patients from scanning rooms to an angiography lab for catheter insertion the time window for treating strokes with tPA has been up to 3 to 4½ hours With more accurate brain imaging and the availability of clot retraction the window could now widen in people who have a slow rate of tissue loss “Our study showed a benefit through six hours” with retraction Bits of clot drifting downstream can block smaller arteries are likely to come out soon governing stent retrieval The new results will probably require some regional hospitals in rural areas to add doctors or other staff trained in the new technology One curious finding that begs for more research also emerged from these studies Patients might do well to be conscious during clot retrieval a neurologist at the University of Pittsburgh who coauthored three of the five stroke papers “but the outcomes were dramatically better with the patient awake.” COME AND GET IT The clot-retrieving device called Solitaire can extract clots from delicate a tubelike catheter and wire are inserted into a large artery in the groin and threaded up to the brain The wire pokes through the obstructing blood clot as a guide for the catheter Then the wire is retracted and replaced by the clot-removing device allowing the spring-loaded device to pop open and snatch the clot The retriever and clot then get reeled back to the catheter Questions or comments on this article? E-mail us at feedback@sciencenews.org | Reprints FAQ A version of this article appears in the June 13, 2015 issue of Science News T.G. Jovin et al. Thrombectomy within 8 hours after symptom onset in ischemic stroke J.L. Saver et al. Stent-retriever thrombectomy after intravenous t-PA vs. t-PA alone in stroke To build immunity to bites from venomous snakes like this water cobra Tim Friede injected himself with doses of venom over time The diabetes and weight loss drug semaglutide may also help people with a severe form of fatty liver disease called MASH In cities that have stopped adding fluoride to drinking water Vials of milk await testing for avian influenza at Cornell University in Ithaca Infecting dairy cattle hasn’t yet given H5N1 bird flu an evolutionary boost toward easy person-to-person spread More children than ever before were diagnosed with autism in 2022 Experts say most of the rise is because of better detection and increased awareness of the developmental condition NIH suspended funding for two clinical trials investigating how to better protect organ transplant recipients from COVID-19 The money is needed to complete the data analyses Researchers are investigating whether a drug used for heavy metal poisoning might prevent harm to people from the venom of the puff adder The snakes’ venom contains proteins that need zinc to do their damaging work Science News was founded in 1921 as an independent nonprofit source of accurate information on the latest news of science our mission remains the same: to empower people to evaluate the news and the world around them It is published by the Society for Science a nonprofit 501(c)(3) membership organization dedicated to public engagement in scientific research and education (EIN 53-0196483) enter your e-mail address for full access to the Science News archives and digital editions tree-lined boulevard that runs through the neighborhood of the same name groups of friends and chummy neighbors who have been seduced by the peaceful village atmosphere and the proximity of the beach recently opened on the ground floor of an old house – formerly a traditional bodega that sold bulk wine and now one of the most delightful tapas bars in the area met while working together at Hotel Diagonal 00 in Barcelona the former as lodging director and the latter as the executive chef When Misan was looking to start his own personal project with all his professional cooking experience (such as at Dos with the Torres twins the perfect partner to join him on this adventure Misan has lived in El Clot and Poblenou for 16 years and knew it was the right location for the kind of place he wanted to open: a casual spot with excellent uncomplicated food served in a warm atmosphere and at gentle prices (the menu del día is just €10) Misan has decorated El 58 with comics and art The sock-monkey-like stuffed red dolls – all named Quim – hanging from the walls and flying through the space were made by architect and artist Aleix Antillach The usual scene here includes kids playing and friends holding forth while clutching refreshing gin and tonics in the backyard (a glorious setting on fine spring days) Drinkers can refresh their vermuts with the old-school soda siphons that can be found throughout the bar Martínez has created a mix of traditional and contemporary tapas and platillos (little dishes to share not strictly tapas) with some international touches (French and Asian There are more than 30 different tapas listed on the blackboard it’s clear that Martínez knows how to combine ingredients in ways that are not only felicitous but also surprising (in a good way of course) and that he knows how to highlight the best qualities of each ingredient he uses The menu changes according to season – and sometimes the weather the traditional winter stews of butifarra and chickpeas have made way for lighter fare Popular tapas include the salmon mini burgers marinated fried chicken with wasabi-honey mayonnaise and the terrific patatas bravas inspired by those of renowned restaurant Bohemic made with a caramelized-garlic mayonnaise and another sauce of dried tomato We also love the Andalusian-style eggplant fried and perfumed with honey and rosemary – it’s a dish that transports us straight to the Mediterranean Fish and seafood hold a prominent place on the menu as should be the case in a restaurant so close to the beach Martínez serves Japanese-inspired sashimi – silken slices of tuna salmon and scallop – as well as salmon tataki and a delicate cod carpaccio pointed up by olives which he marinates and fries to just the right tenderness and spices with cumin a touch of smoked paprika and other spices We’ve only just scratched the surface on Martínez’s long list of tapas and we look forward to returning to see what else he has cooking – as well as to soak up some sun in the backyard Editor’s note: To celebrate the our 2019 neighborhood guide we will be republishing dispatches from the less-visited areas – like Poblenou – that our correspondents are planning to explore this year The Catalan railway operator Ferrocarrils de la Generalitat de Catalunya (FGC) is preparing to launch a new express train service connecting central Barcelona with Barcelona-El Prat Airport in 2026 The company gave a presentation at the Tomorrow Mobility World Congress and released details of the new trains which Alstom and Stadler are currently manufacturing At the Tomorrow Mobility World Congress confirmed that testing will begin in late 2025 Alstom is building the ten airport trains in its factory in Vallès Occidental sturdier and wider” than FGC’s existing models According to the press release each train will have five cars with 20 doors (10 on each side) and a capacity of 656 passengers The doors will have red and green lights indicating closure and opening to aid passengers with hearing impairments the trains will feature 20 panoramic screens displaying train information and nine panoramic screens with information about airport arrivals and departures There will also be ample storage space for luggage 12 LED screens will display information to passengers on the platforms with no steps between the platform and the train car and automatic ramps at the doors close to the areas designated for passengers with reduced mobility Each train will have two spaces reserved for people with reduced mobility and two multifunctional spaces for bicycles after renovating the existing infrastructure currently operated by Rodalies is expected to open in 2026 and will run every 15 minutes It will cover the distance between Passeig de Gràcia station and Terminal 1 in less than 20 minutes The 22.7 km line will have nine stations: Sant Andreu FGC also announced plans to operate a new service between Lleida and Manresa starting at the end of 2025 This 120 km line will see 12 daily departures in each direction between Lleida and Cervera with five of these trains continuing to Manresa Stadler is currently building four three-car electric trains for the Lleida-Manresa service They will feature similar accessibility and passenger information systems to the airport trains FGC plans to hire 70 new train drivers to staff the new services The cost of the ten airport trains is €107 million with an additional €50.9 million for 15 years of maintenance and €19.5 million for constructing a maintenance workshop The four Lleida-Manresa trains will cost €44 million with maintenance costs over 15 years totaling €21.2 million Iberian Blackout Raises Concerns Over Grid Resilience NIS2 Directive Casts a Wider Net Over Smart City Infrastructure Global Forces Put European Cities at Crossroads WeRide Cruises Barcelona with Driverless Robobus Trump’s War on DEI Affects Diversity & LGBT Rights Your Ads Privacy ChoicesIMDb Jordan Feldstein — who was also Maroon 5's manager — died at age 40 last December Metrics details Despite increased atherothrombotic risk in type 2 diabetes mellitus (T2DM) the best preventative antithrombotic strategy remains undetermined We defined the effects of three antiplatelet agents on functional readout and biomarker kinetics in platelet activation and coagulation in patients with T2DM 56 patients with T2DM were randomised to antiplatelet monotherapy with aspirin 75 mg once daily (OD) clopidogrel 75 mg OD or prasugrel 10 mg OD during three periods of a crossover study Platelet aggregation (PA) was determined by light-transmittance aggregometry and P-selectin expression by flow cytometry inflammation and coagulation were measured Plasma levels of 14 miRNA were assessed by quantitative polymerase chain reactions 24 (43%) were receiving aspirin for primary prevention of ischaemic events and 32 (57%) for secondary prevention Prasugrel was the strongest inhibitor of ADP-induced PA (mean ± SD maximum response to 20μmol/L ADP 77.6 ± 8.4% [aspirin] vs P-selectin expression (30 μmol/L ADP; 45.1 ± 21.4% vs p < 0.001) and collagen-induced PA (2 μg/mL; 62.1 ± 19.4% vs Fibrin clot dynamics and levels of coagulation and inflammatory proteins were similar miR-197 (p = 0.009) and miR-223 (p = 0.014) were demonstrated during prasugrel-therapy vs Circulating miR-197 was lower in those cardiovascular disease during therapy with aspirin (p = 0.039) or prasugrel (p = 0.0083) Prasugrel monotherapy in T2DM provided potent platelet inhibition and reduced levels of a number of platelet-associated miRNAs miR-197 is a potential marker of cardiovascular disease in this population Clinical outcome studies investigating prasugrel monotherapy are warranted in individuals with T2DM Trial registration EudraCT, 2009-011907-22. Registered 15 March 2010, https://www.clinicaltrialsregister.eu/ctr-search/trial/2009-011907-22/GB prasugrel as SAPT has not been well studied and data on patients with T2DM are scarce Prasugrel monotherapy in individuals with T2DM may offer superior anti-thrombotic properties compared with aspirin or clopidogrel The aim of this study was to comprehensively characterise and compare the effects of the three drugs on platelet function inflammation and expression of miRNAs in a cohort of T2DM patients Venous blood samples were collected by venepuncture and anticoagulated with trisodium citrate dihydrate 3.13% Platelet-rich plasma was prepared by centrifugation for 10 min at 200×g and platelet-poor plasma was prepared by further centrifugation for 10 min at 1500×g All analyses described below were undertaken by individuals blinded to the sample details and type of antiplatelet treatment Maximum (MA) and final (FA) aggregation responses at 6 min after agonist injection and repeated if a discrepancy of > 10% was observed between the readings citrated platelet-poor plasma samples were mixed with standard lysis and activation mixes to form acellular clots Serial absorbance was measured using an automated plate reader during clot formation until lysis was achieved representing the period from the addition of clot activation mix to the start of clot formation (a measure of clotting tendency) a representation of fibre thickness and clot density) and lysis time (time from full clot formation to 50% lysis Total RNA was isolated using the miRNeasy Mini kit (Qiagen 100 µL of plasma were combined with 694.75 µL of QIAzol 4 µL of diluted Caenorhabditis elegans miR-39-3p (cel-miR-39) spike-in and 1.25 µL carrier MS2 Following a brief incubation at ambient temperature 140 µL of chloroform were added and the solution was mixed vigorously Samples were then centrifuged at 13,500 relative centrifugal force (rcf) for 15 min at 4 °C The upper aqueous phase was carefully transferred to a new tube and 1.5 volumes of ethanol were added The samples were then applied directly to columns and washed according to the company’s protocol Total RNA was eluted with 35 µL of nuclease-free water A fixed volume of 3 μL of the 35μL RNA eluate was used as input for reverse transcription (RT) reactions MiRNAs were reverse-transcribed using Megaplex RT Primer Pools (Human Pool A version 2.1; Life Technologies Germany) and the TaqMan MicroRNA RT kit (Life Technologies Germany) according to the manufacturer’s instructions Templates were pre-amplified using Megaplex PreAmp Primers (Primers A version 2.1) and PreAmp Mastermix (Life Technologies) with 12 cycles of 95 °C for 15 s and 60 °C for 4 min Pre-amplification product was 72 times diluted and 2.25 μL were combined with 0.25 μL TaqMan microRNA assay (20×) (Life Technologies) and 2.5 μL TaqMan Universal PCR Master Mix No AmpErase UNG (2×) to a final volume of 5 μL RT-qPCR was performed on an Applied Biosystems Viia 7 thermocycler at 95 °C for 10 min followed by 40 cycles of 95 °C for 15 s and 60 °C for 1 min Clinical data were blinded to laboratory personnel The three treatments were compared by repeated measures ANOVA with Greenhouse–Geisser correction The primary endpoints of the study were platelet aggregation responses to ADP collagen and AA; platelet P-selectin expression and fibrin clot dynamics For variables with a significant difference (p < 0.05) between the treatments pairwise comparisons were performed using Bonferroni correction SPSS statistics v25 (IBM software) was used for these analyses and graphical representations generated using GraphPad PRISM v7 Correlation and subgroup analyses were performed using RStudio v1.1.456: adjustment for multiple comparisons was not made for these as they were exploratory and intended for hypothesis generation A total of 56 patients were needed to detect a 10% difference in platelet aggregation response to various agonists comparing the different therapies at p < 0.05 and 90% power based on the assumption that the common standard deviation of the response variable is 16% The study also had the power to detect a 7% difference in clot final turbidity based on the assumption that standard deviation for the response variable is 11% (p < 0.05 Of 310 patients who were approached, 64 were enrolled and 56 completed the study (Additional file 1: Figure S1). Baseline characteristics are shown in Table 1 a Maximum platelet aggregation responses assessed by light transmittance aggregometry AA arachidonic acid; b proportions of participants during each treatment period with high (HRPR) and low residual platelet reactivity (LRPR) defined as a maximum aggregation response to 20 μmol/L ADP of > 59% and ≤ 59% respectively Comparing platelet aggregation responses when receiving standard-of-care aspirin 75 mg OD to those at the end of the study aspirin period, there were no differences (Additional file 1: Table S1) Platelet P-selectin expression in response to stimulation with ADP at concentrations of 0.3 No significant differences in fibrinogen, circulating leukocyte count, CRP or complement C3 were observed between the treatments (all p > 0.05, Table 2) Quantification of plasma levels of miR-21, miR-24, miR-126, miR-191, miR-197 and miR-223 using the 2−ΔΔcq method, expressed relative to the mean value when receiving aspirin Correlation between platelet P-selectin expression Dark blue lines indicate those of best linear fit light blue shading indicates 95% confidence interval R and p values were produced by Pearson correlation analysis Relative quantification of circulating miR-197 in participants with and without a history of cardiovascular disease during the three treatment periods In concert with this was the fact that there was a large reduction in the proportion of patients with HRPR when receiving clopidogrel vs P-selectin expression after stimulation with ADP followed a similar pattern to the aggregation responses perhaps representing the best global assessment of effects on platelet macroaggregation was more strongly inhibited by prasugrel than aspirin and clopidogrel suggesting that prasugrel acts as the most potent antiplatelet drug of the three when used as monotherapy in patients with T2DM supports the association between plasma levels of these miRNAs and platelet function This has not been reported before in individuals with diabetes receiving antiplatelet therapy and future research is required to understand the specific role of each of the miRNAs which may help with risk stratification and/or uncover alternative therapeutic targets to control platelet activation in this population our data suggest that prasugrel monotherapy is superior to either aspirin or clopidogrel in inhibiting platelet function in diabetes From a translational perspective these findings could have the potential to be implemented in personalised treatment options for patients with T2DM and cardiovascular disease our miRNA results indicate that assessing response to antiplatelet therapy does not necessarily require fresh blood samples and tests can be conducted on miRNA measurements as biomarkers from stored acellular plasma samples miRNA measurements may provide a platform to identify patients at greater risk of ischaemic heart disease relating to their platelet function Based on these data and acknowledging that platelet activation is the central process in the development of atherothrombosis a trial assessing the effects on clinical outcomes of prasugrel monotherapy may be warranted for the primary or secondary prevention of ischaemic heart disease in patients with T2DM further analysing the role of miRNA in predicting vascular outcome in individuals with diabetes may offer a tool to measure the clinical efficacy of antiplatelet agents All data generated or analysed during this study are included in this published article and its Additional file 1 clopidogrel vs aspirin in patients at risk of ischaemic events high on-treatment residual platelet reactivity P2Y purinoceptor type 12 (platelet adenosine diphosphate receptor) reverse transcription quantitative polymerase chain reaction Global burden of thrombosis: epidemiologic aspects Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart Hypofibrinolysis in diabetes: a therapeutic target for the reduction of cardiovascular risk Diabetes and antiplatelet therapy: from bench to bedside Long-term antiplatelet therapy following myocardial infarction: implications of PEGASUS-TIMI 54 Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation Prasugrel versus clopidogrel in patients with acute coronary syndromes Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-thrombolysis in myocardial infarction 38 trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE) Amplified benefit of clopidogrel versus aspirin in patients with diabetes mellitus The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease Aspirin for primary prevention of cardiovascular events in people with diabetes: a position statement of the american diabetes association a scientific statement of the american heart association and an expert consensus document of the American College of Cardiology Foundation Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial Effects of aspirin for primary prevention in persons with diabetes mellitus Effect of CYP2C19 and ABCB1 single nucleotide polymorphisms on outcomes of treatment with ticagrelor versus clopidogrel for acute coronary syndromes: a genetic substudy of the PLATO trial Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the 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meta-analyses of randomized controlled trials Cardiovascular Disease and Risk Management: Standards of Medical Care in Diabetes-2019 2019 ACC/AHA Guideline on the Primary Prevention of Cardiovascular Disease: a Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines Antiplatelet effect of aspirin during 24 h in patients with type 2 diabetes without cardiovascular disease Evolving pattern of platelet P2Y12 inhibition in patients with acute coronary syndromes Ticagrelor improves blood viscosity-dependent microcirculatory flow in patients with lower extremity arterial disease: the Hema-kinesis clinical trial Efficacy and safety of ticagrelor in comparison to clopidogrel in elderly patients with ST-segment-elevation myocardial infarctions Safety and efficacy of low-dose prasugrel as part of triple therapy with aspirin and oral anticoagulants in patients with atrial fibrillation undergoing percutaneous coronary intervention-from the TWMU-AF PCI registry Platelet function during extended prasugrel and clopidogrel therapy for patients with ACS treated without revascularization: the TRILOGY ACS platelet function substudy A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA miRNA-197 and miRNA-223 predict cardiovascular death in a cohort of patients with symptomatic coronary artery disease Download references Parker is funded by a British Heart Foundation Clinical Training Research Fellowship (FS/18/49/33752) Schulte is the recipient of a research fellowship by the Deutsche Forschungsgemeinschaft (DFG) (SCHU 2983/1-1) Barwari is funded by a British Heart Foundation (BHF) Interdisciplinary Ph.D Mayr is a BHF Chair Holder (CH/16/3/32406) with BHF programme Grant support (RG/16/14/32397) This study was funded by Eli Lilly through an investigator-led grant Eli Lilly was not involved in the design of the study; collection analysis or interpretation of data; writing the report; or the decision to submit the report for publication Department of General and Interventional Cardiology Leeds Institute of Cardiovascular and Metabolic Medicine The study was conceived and supervised by RAA MM and TB designed and oversaw the microRNA analysis SMP and RAA recruited patients and obtained study samples collated results and produced the first draft of the manuscript All authors read and approved the final manuscript The study was approved by NHS Research Ethics Service (reference 09/H1307/110) Written consent was obtained from participants before any study activities took place M Mayr filed and licensed patent applications on miRNAs as biomarkers (EP15193448.6 Mayr filed and licensed patent applications on miRNAs as biomarkers (EP15193448.6 RF Storey reports institutional research grants/support from AstraZeneca and GlyCardial Diagnostics; consultancy fees from Amgen Portola and Thromboserin; and honoraria from AstraZeneca received honoraria and educational and research support from Abbott Diabetes Care The other authors report no relevant disclosures Download citation DOI: https://doi.org/10.1186/s12933-019-0981-3 Unofficial weather station at 2,300 meters above sea level in a mountain hollow amid Storm Filomena, which might carry heavy snowfall It is not in Siberia, the Mount Everest or the Arctic Circle. El Clot del Tuc de la Llança is a mountain hollow in the Catalan Pyrenees, and on Wednesday it registered a surreal temperature: -34.1ºC. Beyond cold, beyond freezing. An unofficial weather station owned by Baqueira Beret ski resort in the site hit the lowest value ever recorded in the Iberian Peninsula at 5.19 am local time – lower than the previous all-time low, of -32ºC in 1956 in Estany Gento, not very far in the same mountain range. The record, pending official evaluation, was registered in a station managed by Meteo Pirineu organization at 2,300 meters above sea level. Despite being unofficial, the Alt Pirineu natural park has shared the details of the record, saying that the station is "very reliable." It is an uninhabited area, so nobody had to bear this insanely freezing temperature. The temperature dropped by around 20 degrees in around four hours, a phenomenon which is called cold air pool. Sergi González, a researcher at Aemet, Spain's meteo agency, said on Twitter that "this phenomenon happened with clear sky and calm winds, which favored the cooling of the nearby air in the surface of mountain slopes." "Cold air weighs more and due to gravity it has gone down to the deepest areas. In Clot this cold air has piled up," he added. The figure came amid especially cold days across the country – this usual weather is due to a storm called Filomena, which might carry a heavy snowfall between Thursday and Saturday in large parts of Catalonia. Some snowflakes have already been noticed at sea level, and more snow near the coast might follow. The Catalan meteo service has issued an alert for snow for Thursday affecting a dozen counties in the southwest, in the Ebre, Tarragona and Lleida areas – for Friday, some more unusual snow might fall in the river Ebre area. v1.1.0. Copyright © 2025. Powered by EBANTIC. All rights reserved. Painting by Jorge Rodríguez Gerada on the Sant Martí Civic Centre.Photo: Vicente Zambrano The legacy of Barcelona’s artists, some of whom have achieved wide renown, has been enriched by contributions from high profile artists from around the world. The great boom that Barcelona experienced around the year 2000 as a centre for urban art has left a legacy of artists that started out in this scene and have now achieved widespread recognition. Maybe the grand old man of graffiti art is Xupet Negre, who has been painting on Barcelona’s walls and furniture since 1989. His emblem, a black baby’s dummy often surrounded by pacifist symbols and words, is one of the images that we can most frequently find as we walk around the city. The spirit of the mountain, by Sixe Paredes, on a wall of Lepant Street, 424.Photo: Vicente Zambrano Mural of El Pez in the street of Creu Coberta, in the district of Sants.Photo: Vicente Zambrano Another major figure is El Pez, creator of the style that he himself christened the “Barcelona Happy Style”. Clearly influenced by his origins in graffiti, his pieces are full of colour and always feature his symbol, a fish with an enormous smile. In Barcelona, some of his pieces can be seen in La Escocesa and in Sant Adrià del Besòs. If you are lucky, you might even see a lorry decorated by him driving around the city. The shark painted by Blu in Carmel, with hundred euro notes for scales, is one of the oldest murals in the city.Photo: Vicente Zambrano Tribute to Carmen Amaya by Btoy and Uriginal in Clot park.Photo: Vicente Zambrano Your email address will not be published. Required fields are marked * Save my name, email, and website in this browser for the next time I comment. The first kiosks were built in Barcelona in the mid-19th century, either to sell products or shelter musical performances. However, the first newspaper kiosk was the initiative of an evening paper born in 1888: El Noticiero Universal. From La Rambla, newspaper kiosks spread throughout the city. The last few years haven’t been kind to sellers of printed press. Over the course of a decade, 35% of kiosks in Barcelona have closed. The recession –and, above all, new ways of getting information– are causing many to shut down. Aware of the problem, the sector and the administration are taking on a necessary reconversion. There are about 50 interior gardens open to the public in the Eixample. And in each block interior we find this reduced microcosm, each with its own particularities and features. But they all have certain things in common: spaces for leisure use, their imitation of nature and their perceptual isolation, which facilitates neighbourhood socialising. Climate change and air pollution have driven the world’s great cities towards a change in paradigm. After a century of cars ruling the streets, the largest metropolises are starting to restrict their use. Officially, science was a man’s affair in Barcelona until very recently. This can be seen, for example, in the gallery of names of illustrious academics in the Paranimf of the University of Barcelona, which only includes one woman: 17th-century philosopher Juliana Morell. However, if we look under the surface, we find that women have in fact been involved in the scientific and technical life of the city in many different ways. From the 70´s, the historical establishments – neighbourhood cinemas and other, classier, first - run downtown cinemas – came up time and again against the challenge of survival. Throughout this struggle, and over and above the overpowering creeping commercialism, alternative circuits have been established that have allowed new experiences for cinema-lovers while preserving the best of the traditional ones. In Catalonia, 7% of all food purchased by families, restaurants and shops each year is wasted. Food waste is a global problem which can be fought by means of better laws and social projects, in addition to individual and household initiatives. The Model prison has since been emptied of its prisoners. Now, for the residents in this part of the city, it represents both an opportunity and a danger, as they watch to see what sort of restoration will be given to this large chunk of their neighbourhood, following four decades of calls for the prison’s closure in order to make way for amenities, green spaces and schools. "We've had brunch every day since we arrived in Barcelona," says an American tourist savoring a French toast with scrambled eggs at one of the Catalan capital's pioneering brunch spots. thousands of tourists flock daily to the Catalan capital's thriving brunch scene especially in the city's central tourist areas. Tourism is a major driver of this trend. In 2023, Barcelona welcomed nearly 16 million international visitors According to Google Maps data analyzed by Catalan News Barcelona has more than 180 places that offer brunch includes specialized brunch spots as well as general cafes bakeries and restaurants with broader menus that offer brunch options. such as those near the Sagrada Familia and the Gothic Quarter have also become hotspots for brunch lovers. The location of most brunch spots in Barcelona suggests that brunch is largely a tourist-driven phenomenon rather than a local tradition Even the expat community - often cited as another factor behind the rise of brunch spots - seems to play a secondary role compared to the overwhelming influence of tourism "Brunch is a little more unusual in the local culture so we see more international customers than locals it's mostly travelers," says Billy Thorens one of the city's most popular brunch destinations Thorens opened Billy Brunch in 2018 as one of the first dedicated brunch venues in the Eixample district the business has expanded to six locations across the city The Swiss entrepreneur attributes his decision to open the restaurant to a combination of business opportunity Barcelona's favorable weather and high quality of life "I chose Eixample for its proximity to everything The Sagrada Família brings people year-round," he explains have spurred the rise of increasingly extravagant brunch venues often adorned with pink floral decor and elaborate design elements The menu at Billy Brunch continues to focus on traditional fare with good eggs and good coffee in a pleasant atmosphere," Thorens describes "There is a demand for fanciness - it works with TikTok but our traditional brunch will last forever," he adds the charm of Billy Brunch resonates on social media as well tourists from the United States enjoying a meal there told us that social media led them to the spot the exterior was really aesthetic," they say Talking to several customers who enjoy brunch at Billy Brunch it is clear that the main draws are the healthy protein-rich food - especially the eggs - and the inviting atmosphere but they're not necessarily looking for a heavy meal with wine," Billy explains "They want a place where they can socialize in a healthy environment with a lot of variety Despite the increase in brunch spots, the locals have not followed suit. In fact, some have taken an initiative to reclaim the traditional Catalan equivalent of brunch, the 'esmorzar de forquilla,' or fork breakfast. "We're not coming to take away the local culture. If you come to Billy Brunch and ask for 'pa am tomaquet' or a simple 'tortilla', you will get it. We understand Catalan and everyone is welcome," says Billy, encouraging locals to try brunch. To learn more about Barcelona's brunch scene and its local equivalent, the esmorzar de forquilla, listen to this episode of our podcast Filling the Sink.