Internal attention modulates the functional state of novel stimulus-response associations in working memory

Information in working memory (WM) is crucial for guiding behavior. However, not all WM representations are equally relevant simultaneously. Current theoretical frameworks propose a functional dissociation between ‘latent’ and ‘active’ states, in which relevant representations are prioritized into an optimal (active) state to face current demands, while relevant information that is not immediately needed is maintained in a dormant (latent) state. In this context, task demands can induce rapid and flexible prioritization of information from latent to active state. Critically, these functional states have been primarily studied using simple visual memories, with attention selecting and prioritizing relevant representations to serve as templates to guide subsequent behavior. It remains unclear whether more complex WM representations, such as novel stimulus-response associations, can also be prioritized into different functional states depending on their task relevance, and if so how these different formats relate to each other. In the present study, we investigated whether novel WM-guided actions can be brought into different functional states depending on current task demands. Our results reveal that planned actions can be flexibly prioritized when needed and show how their functional state modulates their influence on ongoing behavior. Moreover, they suggest the representations of novel actions of different functional states are maintained in WM via a non-orthogonal coding scheme, thus are prone to interference.German Research Foundation (Deutsche Forschungsgemeinschaft, DFG) under Germany's Excellence Strategy-EXC 2002/1Science of Intelligence (Project Ref.: 390523135)Einstein Foundation BerlinAndalusian Autonomic Government (Grant Ref.: PAIDI 21_00207)Research Foundation - Flanders (FWO-Vlaanderen, Project Ref: 11H5619N)Einstein Strategic Professorship (Einstein Foundation Berlin)Project PID2020-116342GA-I00 funded by MCIN/AEI/10.13039/501100011033Grant RYC2021-033536-I funded by MCIN/AEI/10.13039/501100011033 and by the European Union NextGenerationEU/PR

Estatus epiléptico refractario no convulsionante en postoperatorio de pancreatectomía total: A propósito de un caso

We present a clinical case of non-convulsive epileptic status in the post-operative of a 79-year-old patient with no history of epilepsy, and its probable relationship with scheduled antibiotic therapy. Then a discussion about the epileptic status and its appearance as a side effect of the treatment with certain antibiotics is made.Se presenta un caso clinico de Estatus Epileptico No convulsionante en el posopoeratorio de una paciente de 79 años sin antecedentes de epilepsia, y su probable relación con la antibioterapia pautada. Seguidamente se realiza una discusion acerca del estatus epileptico y su aparicion como efecto secundario del tratamiento con ciertos antibioticos.

Canonical template tracking: Measuring the activation state of specific neural representations

Multivariate analyses of neural data have become increasingly influential in cognitive neuroscience since they allow to address questions about the representational signatures of neurocognitive phenomena. Here, we describe Canonical Template Tracking: a multivariate approach that employs independent localizer tasks to assess the activation state of specific representations during the execution of cognitive paradigms. We illustrate the benefits of this methodology in characterizing the particular content and format of task-induced representations, comparing it with standard (cross-)decoding and representational similarity analyses. Then, we discuss relevant design decisions for experiments using this analysis approach, focusing on the nature of the localizer tasks from which the canonical templates are derived. We further provide a step-by-step tutorial of this method, stressing the relevant analysis choices for functional magnetic resonance imaging and magneto/electroencephalography data. Importantly, we point out the potential pitfalls linked to canonical template tracking implementation and interpretation of the results, together with recommendations to mitigate them. To conclude, we provide some examples from previous literature that highlight the potential of this analysis to address relevant theoretical questions in cognitive neuroscience

Purinergic P2X7 receptor expression increases in leukocytes from intra-abdominal septic patients

Inflammation is a tightly coordinated response of the host immune system to bacterial and viral infections, triggered by the production of inflammatory cytokines. Sepsis is defined as a systemic inflammatory response followed by immunosuppression of the host and organ dysfunction. This imbalance of the immune response increases the risk of mortality of patients with sepsis, making it a major problem for critical care units worldwide. The P2X7 receptor plays a crucial role in activating the immune system by inducing the activation of peripheral blood mononuclear cells. In this study, we analyzed a cohort of abdominal origin septic patients and found that the expression of the P2X7 receptor in the plasma membrane is elevated in the different subsets of lymphocytes. We observed a direct relationship between the percentage of P2X7-expressing lymphocytes and the early inflammatory response in sepsis. Additionally, in patients whose lymphocytes presented a higher percentage of P2X7 surface expression, the total lymphocytes populations proportionally decreased. Furthermore, we found a correlation between elevated soluble P2X7 receptors in plasma and inflammasome-dependent cytokine IL-18. In summary, our work demonstrates that P2X7 expression is highly induced in lymphocytes during sepsis, and this correlates with IL-18, along with other inflammatory mediators such as IL-6, IL-8, and procalcitonin

Perception of level of knowledge, skills, and safety before and after training to perform videolaryngoscopy with the Intubox barrier system for airway management in patients with COVID-19.

©2020. This manuscript version is made available under the CC-BY4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ This document is the Published, version of a Published Work that appeared in final form in Emergencias.Objetivos. El objetivo principal fue describir el grado de percepción sobre el conocimiento, las habilidades y la seguridad antes y después de un programa de entrenamiento con videolaringoscopia y mecanismo de protección Intubox® en el manejo de la vía aérea de pacientes con COVID-19. El objetivo secundario fue evaluar la seguridad de los dispositivos de barrera en la intubación a través de un análisis visual de dispersión de partículas. Método. Ensayo clínico de un solo brazo basado en simulación. Los participantes fueron médicos que realizaron un programa de formación mediante simulación clínica de baja y alta fidelidad. Se usó un instrumento diseñado y validado específico para evaluar la percepción sobre el conocimiento, las habilidades y la seguridad antes y después del programa. Se realizó un análisis visual de la contaminación por gotas. Resultados. La muestra final estuvo compuesta por 27 médicos, con una edad media de 40 (DE 10,8) años y el 63% mujeres. Se obtuvo un incremento estadísticamente significativo en las dimensiones conocimiento, habilidad y seguridad tras el entrenamiento. Se observó una menor contaminación cuando se realizaron las técnicas de manejo de vía aérea con urna protectora. Conclusiones. Los urgenciólogos incrementaron su percepción sobre los conocimientos, habilidades y seguridad en el manejo de la vía aérea en pacientes con COVID-19 tras un programa de formación con simulación. El uso combinado de laringoscopia y dispositivo de barrera Intubox® causó menor dispersión de partículas durante la intubación.------------------------------Objectives. The main objective was to describe physicians’ perception of their knowledge, skill, and safety before and after training to perform videolaryngoscopy while using the Intubox barrier system when managing the airway of a patient with the coronavirus 2019 disease (COVID-19). The secondary objective was to assess the safety afforded by the barrier by means of visually evaluating particle dispersion during intubation. Methods. Single-arm clinical simulation trial. The participants were physicians who received training in both a lowfidelity and a high-fidelity simulation zone. The participants assessed their knowledge, skill, and safety when using the Intubox before and after training using a specially designed and validated questionnaire. Droplet contamination was estimated visually. Results. Twenty-seven physicians with a mean (SD) age of 40 (10.8) years participated; 63% were women. They perceived their knowledge, skill, and safety to be significantly higher after training. Droplet contamination was seen to decrease when airway management maneuvers were done with the barrier in place. Conclusions. After simulation training the emergency physicians judged their knowledge, skill, and safety to be greater when they used the barrier during airway management in patients with COVID-19. The combined use of a laryngoscope and the Intubox barrier resulted in less particle dispersion during intubation

P2X7 receptor induces mitochondrial failure in monocytes and compromises NLRP3 inflammasome activation during sepsis

International audienceSepsis is characterized by a systemic inflammatory response followed by immunosuppres-sion of the host. Metabolic defects and mitochondrial failure are common in immunocom-promised patients with sepsis. The NLRP3 inflammasome is important for establishing an inflammatory response after activation by the purinergic P2X7 receptor. Here, we study a cohort of individuals with intra-abdominal origin sepsis and show that patient monocytes have impaired NLRP3 activation by the P2X7 receptor. Furthermore, most sepsis-related deaths are among patients whose NLRP3 activation is profoundly altered. In monocytes from sepsis patients, the P2X7 receptor is associated with mitochondrial dysfunction. Furthermore, activation of the P2X7 receptor results in mitochondrial damage, which in turn inhibits NLRP3 activation by HIF-1α. We show that mortality increases in a mouse model of sepsis when the P2X7 receptor is activated in vivo. These data reveal a molecular mechanism initiated by the P2X7 receptor that contributes to NLRP3 impairment during infection

NLRP3 inflammasome activation and symptom burden in KRAS-mutated CMML patients is reverted by IL-1 blocking therapy

Chronic myelomonocytic leukemia (CMML) is frequently associated with mutations in the rat sarcoma gene (RAS), leading to worse prognosis. RAS mutations result in active RAS-GTP proteins, favoring myeloid cell proliferation and survival and inducing the NLRP3 inflammasome together with the apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), which promote caspase-1 activation and interleukin (IL)-1(3 release. Here, we report, in a cohort of CMML patients with mutations in KRAS, a constitutive activation of the NLRP3 inflammasome in monocytes, evidenced by ASC oligomerization and IL-1(3 release, as well as a specific inflammatory cytokine signature. Treatment of a CMML patient with a KRASG12D mutation using the IL-1 receptor blocker anakinra inhibits NLRP3 inflammasome activation, reduces monocyte count, and improves the patient's clinical status, enabling a stem cell transplant. This reveals a basal inflammasome activation in RAS-mutated CMML patients and suggests potential therapeutic applications of NLRP3 and IL-1 blockers

Alteraciones hemodinámicas y metabólicas en el xenotrasplante ortotópico hepático : modelo de cerdo a babuino / Carlos García Palenciano ; dirección Pascual Parrilla Paricio, Pablo Ramírez Romero y Francisco Acosta Villegas

Tesis-Universidad de Murcia.MEDICINA ESPINARDO. DEPOSITO. MU-Tesis 765.Consulte la tesis en: BCA. GENERAL. ARCHIVO UNIVERSITARIO. T.M. 2634

The effect of task demands on the neural patterns generated by novel instruction encoding

This work was supported by the Spanish Ministry of Science and Innovation (PID2019-111187GB-I00 to M.R., and IJC2019-040208-I to C.G.G) , the European Union's Horizon 2020 research and innovation program under the Marie Sklodowska Curie (Ref. 835767, to C.G.G.) , and the Spanish Ministry of Education, Culture and Sports (FPU17/01627 to A.S.) . The open access charge was funded by the University of Granada and the CBUA.Verbal instructions allow fast and optimal implementation of novel behaviors. Previous research has shown that different control-related variables structure neural activity in frontoparietal regions during the encoding of novel instructed tasks. However, it is uncertain whether different task goals modulate the organizing effect of these variables. In this study, we investigated whether the neural encoding of three task-relevant variables (dimension integration, response set complexity and target category) is modulated by implementation and memorization demands. To do so, we combined functional Magnetic Resonance Imaging (fMRI), an instruction-following paradigm and multivariate analyses. We addressed how and where distributed activity patterns encoded the instructions' variables and the impact of the implementation and memorization demands on the fidelity of these representations. We further explored the nature of the neural code underpinning this process. Our results reveal, first, that the content of to-be-implemented and to-bememorized instructions is represented in overlapping brain regions, flexibly using a common neural code across tasks. Importantly, they also suggest that preparing to implement the instructions increases the decodability of task-relevant information in frontoparietal areas, in comparison with memorization demands. Overall, our work emphasizes both similarities and differences in task coding under the two contextual demands. These findings qualify the previous understanding of novel instruction processing, suggesting that representing task attributes in a generalizable code, together with the increase in encoding fidelity induced by the implementation goals, could be key mechanisms for proactive control in novel scenarios.Spanish Government PID2019-111187GB-I00 IJC2019-040208-IEuropean Commission 835767Spanish Government FPU17/01627University of Granad