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.

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

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

Exploring the link between novel task proceduralization and motor simulation

Our ability to generate efficient behavior from novel instructions is critical for our adaptation to changing environments. Despite the absence of previous experience, novel instructed content is quickly encoded into an action-based or procedural format, facilitating automatic task processing. In the current work, we investigated the link between proceduralization and motor simulation, specifically, whether the covert activation of the task-relevant responses is used during the assembly of action-based instructions representations. Across three online experiments, we used a concurrent finger-tapping task to block motor simulation during the encoding of novel stimulus-response (S-R) associations. The overlap between the mappings and the motor task at the response level was manipulated. We predicted a greater impairment at mapping implementation in the overlapping condition, where the mappings' relevant response representations were already loaded by the motor demands, and thus, could not be used in the upcoming task simulation. This hypothesis was robustly supported by the three datasets. Nonetheless, the overlapping effect was not modulated by further manipulations of proceduralization-related variables (preparation demands in Exp.2, mapping novelty in Exp.3). Importantly, a fourth control experiment ruled out that our results were driven by alternative accounts as fatigue or negative priming. Overall, we provided strong evidence towards the involvement of motor simulation during anticipatory task reconfiguration. However, this involvement was rather general, and not restricted to novelty scenarios. Finally, these findings can be also integrated into broader models of anticipatory task control, stressing the role of the motor system during preparation

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

This repository contains all the relevant code and data from our work “Internal attention modulates the functional state of novel stimulus-response associations in working memory”. The /Materials folder contains the main script (exp.html) and functions (bowser.js, write_data.php, and files included in the /plugins subfolder) used for task presentation. The experiment was coded using JsPsych (v 6.1.0), an open-source software that is not included in this repository, but that can be downloaded from this link: https://github.com/jspsych/jsPsych/releases. The /Stimulus folder contains all the stimuli employed in the Encoding screen (/shapes, /colors) and Probe 1 and 2 (target.zip, /colors_neutral, /shapes_neutral). The file target.zip contains the bivalent stimuli used in the congruent and incongruent condition (the folder was compressed due to its large size). The subfolders /colors_neutral and /shapes_neutral contain the univalent stimuli used in the neutral condition and Probe 2. The experiment instructions (/instr) are also available. Originally, the experiment code and materials were uploaded to an online server and executed from the participant’s browser. Nonetheless, the version available in OSF was modified to be executed locally. To do so, download the Materials folder and JsPsych v6.1.0. After unzipping JsPsych, locate the jspsych-6.1.0 folder within the Materials one. The subfolder Target.zip located in /Stimulus should be also uncompressed. Then, execute the exp.html script using your browser (preferably, Google Chrome). The /Data folder contains the raw dataset, with .csv files for each participant and experimental block (12 per participant). Each file name indicates the participant ID and the block number. There is a codebook available detailing all the variables contained in these datasets. Finally, within the /Analysis folder, the script data_analysis.py contains the Python code to preprocess the data and perform the error rate analyses and the exploratory reaction time analyses using the Pingouin package (v 0.5.3). The script hddm_analysis.py contains the Python code to perform the drift diffusion modeling using the hierarchical drift diffusion model (HDDM) toolbox. The subfolder /distributional_analysis contains the main R script (analysis_brms.R) and functions (within the subfolder /R) used to perform the exploratory distributional analyses

Exploring the link between novel task proceduralization and motor simulation

Our ability to generate efficient behavior from novel instructions is critical for our adaptation to changing environments. Despite the absence of previous experience, novel instructed content is quickly encoded into an action-based or procedural format, facilitating automatic task processing. In the current work, we investigated the link between proceduralization and motor simulation, specifically, whether the covert activation of the task-relevant responses is used during the assembly of action-based instructions representations. Across three online experiments, we used a concurrent finger-tapping task to block motor simulation during the encoding of novel stimulus-response (S-R) associations. The overlap between the mappings and the motor task at the response level was manipulated. We predicted a greater impairment at mapping implementation in the overlapping condition, where the mappings' relevant response representations were already loaded by the motor demands, and thus, could not be used in the upcoming task simulation. This hypothesis was robustly supported by the three datasets. Nonetheless, the overlapping effect was not modulated by further manipulations of proceduralization-related variables (preparation demands in Exp.2, mapping novelty in Exp.3). Importantly, a fourth control experiment ruled out that our results were driven by alternative accounts as fatigue or negative priming. Overall, we provided strong evidence towards the involvement of motor simulation during anticipatory task reconfiguration. However, this involvement was rather general, and not restricted to novelty scenarios. Finally, these findings can be also integrated into broader models of anticipatory task control, stressing the role of the motor system during preparation