Leukotriene D4-induced Caco-2 cell proliferation is mediated by prostaglandin E2 synthesis

Leukotriene D4 (LTD4) is a pro-inflammatory mediator formed from arachidonic acid through the action of 5-lipoxygenase (5-LOX). Its biological effects are mediated by at least two G-coupled plasmatic cysteinyl LT receptors (CysLT1-2R). It has been reported an upregulation of the 5-LOX pathway in tumor tissue unlike in normal colon mucosa. Colon tumors generally have an increased expression of CysLT1R and colon cancer patients with high expression levels of CysLT1R have poor prognosis. We previously observed that the cyclooxygenase pathway is involved in the control of intestinal epithelial cancer cell growth through PGE2 production. The aim of this study was therefore to assess the effect of LTD4 binding with CysLT1R on Caco-2 cell growth. We note a number of key findings from this research. We observed that at a concentration similar to that found under inflammatory conditions, LTD4 was able to induce Caco-2 cell proliferation and DNA synthesis. Moreover, with the use of a specific receptor antagonist this study has demonstrated that the effect of LTD4 is a result of its interaction with CystLT1R. We also note the possible participation of the PLC-IP3-Ca2+/DAG-PKC signaling pathways in cytosolic PLA2 and [3H]AA release induced by LTD4-CystLT1R interaction. Finally, we found that the resulting activation of the AA cascade and the production of PGE2 eicosanoid could be related to the activation of cell signaling pathways such as ERK and CREB. These findings will help facilitate our understanding of how inflammatory mediators can affect the survival and dissemination of intestinal carcinoma cells

Dual Behavior of Long-Chain Fatty Acids and Their Cyclooxygenase/Lipoxygenase Metabolites on Human Intestinal Caco-2 Cell Growth

Etiology of colorectal cancer (CRC) is related, at least in part, with nutritional profile and epidemiological data indicating a key role of dietary fat on CRC pathogenesis. Moreover, inflammation and eicosanoids produced from arachidonic acid might have a pivotal role in CRC development. However, the effect of specific fatty acids (FAs) on intestinal epithelial cell growth is not completely studied now. By this reason, the aim of this work is to unravel the effect of different saturated and unsaturated long-chain fatty acids (LCFA) and some LCFA metabolites on CRC cell line growth and their possible mechanisms of action. Our results demonstrated that oleic acid is a potent mitogenic factor to Caco-2 cells, at least in part, through 10-hydroxy-8-octadecenoic synthesized by lipoxigenase pathway, whereas polyunsaturated FAs such as eicosapentaenoic (EPA) acid has a dual behavior effect depending on its concentration. A high concentration, EPA induced apoptosis through intrinsic pathway, whereas at low concentration induced cell proliferation that could be related to the synthesis of eicosanoids such as prostaglandin E3 and 12-hydroxyeicosapentaenoic acid and the subsequent induction of mitogenic cell signaling pathways (ERK 1/2, CREB, p38α). Thus, this study contributes to understand the complicated relationship between fat ingest and CRC

Using Bayesian optimization and wavelet decomposition in GPU for arterial blood pressure estimation

Continuous monitoring of arterial blood pressure (ABP) of patients in hospital is currently carried out in an invasive way, which could represent a risk for them. In this paper, a noninvasive methodology to optimize ABP estimators using electrocardiogram and photoplethysmography signals is proposed. For this, the XGBoost machine learning model, optimized with Bayesian techniques, is executed in a Graphics Processing Unit, which drastically reduces execution time. The methodology is evaluated using the MIMIC-III Waveform Database. Systolic and diastolic pressures are estimated with mean absolute error values of 15.85 and 11.59 mmHg, respectively, similar to those of the state of the art. The main advantage of the proposed methodology with respect to others of the current state of the art is that it allows the optimization of the estimator model to be performed automatically and more efficiently at the computational level for the data available. Clinical Relevance— This approach has the advantage of using noninvasive methods to continuously monitor patient's arterial blood pressure, reducing the risk for patientsAgencia Gallega de Innovación | Ref. IN845D-2020/29Agencia Gallega de Innovación | Ref. IN607B-2021/1

Fragmento de una publicación periódica

Final de una comunicación de Juan Facundo Quiroga con el respectivo comentario y carta de Toribio SalvadoresFragment

Cochlear implant in far advanced otosclerosis. Performance complications-long term results

Patients with far advanced otosclerosis demonstrated good performance with CI in 26/32 cases. In the cases with otosclerosis type 3, 5/6 patients had more difficulty in the insertion of electrodes, 1 of them with 2 electrodes within the IAC and leakage of LCR, and 5 of these recipients with tinnitus and poorer auditory outcome, with greater number of calibrations and adjustments inlevels T and C. Only two patient, 2/32 had FNS and were in otosclerosis type 3 with straight electrodes. None with perimodiolars electrodes.https://www.medigraphic.com/pdfs/audiologia/fon-2013/fon131b.pdfFil: Curet, Carlos Augusto. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Unidad Hospitalaria San Roque. Cátedra II de Otorrinolaringología; Argentina.Fil: Curet, Carlos Augusto. Centro Odontológico de Clínica Privada Curet SRL; Argentina.Fil: Curet, Carlos Augusto. Centro de Garganta, Nariz y Oído Dr. Hector Ruiz; Argentina.Fil: Ruíz, Héctor. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Salvadores, María Inés. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas. Unidad Hospitalaria San Roque. Cátedra II de Otorrinolaringología ; Argentina.Fil: Salvadores, María Inés. Centro Odontológico de Clínica Privada Curet SRL; Argentina.Fil: Romani, Claudia. Centro Odontológico de Clínica Privada Curet SRL; Argentina.Fil: Dotto, Gabriela. Centro de Garganta, Nariz y Oído Dr. Hector Ruiz; Argentina.Fil: Queirolo, Adriana. Centro de Garganta, Nariz y Oído Dr. Hector Ruiz; Argentina.Fil: Fil: Chailé, Iván David. Universidad Nacional de Córdoba. Facultad de Ciencias Médicas; Argentina.Fil: Chailé, Iván David. Centro Odontológico de Clínica Privada Curet SRL; Argentina.Fil: Robledo, Hugo. Centro Odontológico de Clínica Privada Curet SRL; Argentina.Fil: Muiño, Juan Carlos. Centro Odontológico de Clínica Privada Curet SRL; Argentina.Otorrinolaringologí

Automatic assessment of transcatheter aortic valve implantation results on four-dimensional computed tomography images using artificial intelligence

Transcatheter aortic valve implantation (TAVI) is a procedure to treat severe aortic stenosis. There are several clinical concerns related to potential complications after the procedure, which demand the analysis of computerized tomography (CT) scans after TAVI to assess the implant’s result. This work introduces a novel, fully automatic method for the analysis of post-TAVI 4D-CT scans to characterize the prosthesis and its relationship with the patient’s anatomy. The method enables measurement extraction, including prosthesis volume, center of mass, cross-sectional area (CSA) along the prosthesis axis, and CSA difference between the aortic root and prosthesis, all the variables studied throughout the cardiac cycle. The method has been implemented and evaluated with a cohort of 13 patients with five different prosthesis models, successfully extracting all the measurements from each patient in an automatic way. For Allegra patients, the mean of the obtained inner volume values ranged from 10,798.20 mm3 to 18,172.35 mm3, and CSA in the maximum diameter plane varied from 396.35 mm2 to 485.34 mm2. The implantation of this new method could provide information of the important clinical value that would contribute to the improvement of TAVI, significantly reducing the time and effort invested by clinicians in the image interpretation process.Xunta de Galicia | Ref. IN607B-2021/1

Assessment of Platelet REACtivity After Transcatheter Aortic Valve Replacement: The REAC-TAVI Trial

OBJECTIVES: The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. BACKGROUND: Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. METHODS: This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y12 reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. RESULTS: A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. CONCLUSIONS: HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066)

Assessment of platelet REACtivity after transcatheter aortic valve replacement

OBJECTIVES: The REAC-TAVI (Assessment of platelet REACtivity after Transcatheter Aortic Valve Implantation) trial enrolled patients with aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) pre-treated with aspirin + clopidogrel, aimed to compare the efficacy of clopidogrel and ticagrelor in suppressing high platelet reactivity (HPR) after TAVI. BACKGROUND: Current recommendations support short-term use of aspirin + clopidogrel for patients with severe AS undergoing TAVR despite the lack of compelling evidence. METHODS: This was a prospective, randomized, multicenter investigation. Platelet reactivity was measured at 6 different time points with the VerifyNow assay (Accriva Diagnostics, San Diego, California). HPR was defined as (P2Y12 reaction units (PRU) ≥208. Patients with HPR before TAVR were randomized to either aspirin + ticagrelor or aspirin + clopidogrel for 3 months. Patients without HPR continued with aspirin + clopidogrel (registry cohort). The primary endpoint was non-HPR status (PRU <208) in ≥70% of patients treated with ticagrelor at 90 days post-TAVR. RESULTS: A total of 68 patients were included. Of these, 48 (71%) had HPR (PRU 273 ± 09) and were randomized to aspirin + ticagrelor (n = 24, PRU 277 ± 08) or continued with aspirin + clopidogrel (n = 24, PRU 269 ± 49). The remaining 20 patients (29%) without HPR (PRU 133 ± 12) were included in the registry. Overall, platelet reactivity across all the study time points after TAVR was lower in patients randomized to ticagrelor compared with those treated with clopidogrel, including those enrolled in the registry (p < 0.001). The primary endpoint was achieved in 100% of patients with ticagrelor compared with 21% with clopidogrel (p < 0.001). Interestingly, 33% of clopidogrel responder patients at baseline developed HPR status during the first month after TAVR. CONCLUSIONS: HPR to clopidogrel is present in a considerable number of patients with AS undergoing TAVR. Ticagrelor achieves a better and faster effect, providing sustained suppression of HPR to these patients. (Platelet Reactivity After TAVI: A Multicenter Pilot Study [REAC-TAVI]; NCT02224066)

Actualización e internacionalización del catálogo "OSCAR" de experiencias de Física General

En convocatorias anteriores de la convocatorias de Proyectos de Innovación Docente de l UCM, la última de ellas correspondiente a 2014, desarrollamos un Catálogo de experiencias de cátedra para la docencia de Física General, OSCAR. En esta edición los hemos ampliado con nuevas experiencias. Asimismo se ha desarrollado un programa de visitas de colegios a la Facultad de Ciencias Físicas de la UCM