Lidocaine effects on acetylcholine-elicited currents from mouse superior cervical ganglion neurons

Lidocaine is a commonly used local anaesthetic that, besides blocking voltage-dependent Na+ channels, has multiple inhibitory effects on muscle-type nicotinic acetylcholine (ACh) receptors (nAChRs). In the present study, we have investigated the effects of lidocaine on ACh-elicited currents (IAChs) from cultured mouse superior cervical ganglion (SCG) neurons, which mainly express heteromeric α3β4 nAChRs. Neurons were voltage-clamped by using the perforated-patch method and IAChs were elicited by fast application of ACh (100-300 μM), either alone or in presence of lidocaine at different concentrations. IAChs were reversibly blocked by lidocaine in a concentration-dependent way (IC50 = 41 μM; nH close to 1) and the inhibition was, at least partially, voltage-dependent, indicating an open-channel blockade. Besides, lidocaine blocked resting (closed) nAChRs, as evidenced by the increased inhibition caused by a 12 s lidocaine application just before its co-application with the agonist, and also enhanced IAChs desensitisation, at concentrations close to the IC50. These results indicate that lidocaine has diverse inhibitory actions on neuronal heteromeric nAChRs resembling those previously reported for Torpedo (muscle-type) nAChRs ( Alberola-Die et al., 2011). The similarity of lidocaine actions on different subtypes of heteromeric nAChRs differs with the specific effects of other compounds, restricted to particular subtypes of nAChRs.This work was supported by the following MICINN (Spanish government) grants: CONSOLIDER-INGENIO 2010 (CSD2008-00005), BFU2011-25371 and BFU2012-31359

Monitoring of an embankment dam in southern Spain based on Sentinel-1 Time-series InSAR

Sentinel-1A/B data were freely provided by ESA through Copernicus Programme. Data have been processed by SARPROZ (Copyright (c) 2009-2020 Daniele Perissin). The satellite orbits are from ESA Quality Control Group of Sentinel-1. Research was supported by: (a) ESA Research and Service Support for providing hardware resources employed in this work, (b) ReMoDams project ESP2017-89344-R (AEI/FEDER, UE) from Spanish Ministry of Economy, Industry and Competitiveness, PAIUJA-2019/2020 and CEACTEMA from University of Jaen (Spain), and RNM-282 research group from the Junta de Andalucia (Spain), (c) ERDF through the Operational Programme for Competitiveness and Internationalisation -COMPETE 2020 Programme within project >, and by National Funds through the FCT -Fundacao para a Ciencia e a Tecnologia (Portuguese Foundation for Science and Technology) as part of project UID/EEA/50014/2013, (d) The Ministry of Education, Youth and Sports from the National Programme of Sustainability (NPU II) project > (Czech Republic), and (e) Slovak Grant Agency VEGA under projects No. 2/0100/20.Deformation monitoring is a common practice in most of dams to ensure their structural health and safety status. Systematic monitoring is frequently carried out by means of geotechnical sensors and geodetic techniques that, although very precise an accurate, can be time-consuming and economically costly. Remote sensing techniques are proved to be very effective in assessing deformation. Changes in the structure, shell or associated infrastructures of dams, including adjacent slopes, can be efficiently recorded by using satellite Synthetic Aperture Radar Inteferometry (InSAR) techniques, in particular, Muti-Temporal InSAR time-series analyses. This is a mature technology nowadays but not very common as a routine procedure for dam monitoring. Today, thanks to the availability of spaceborne satellites with high spatial resolution SAR images and short revisit times, this technology is a powerful cost-effective way to monitor millimeter-level displacements of the dam structure and its surroundings. What is more, the potential of the technique is increased since the Copernicus C-band SAR Sentinel-1 satellites are in orbit, due to the high revisit time of 6 days and the free data availability. ReMoDams is a Spanish research project devoted to provide the deformation monitoring of several embankments dams using advances time-series InSAR techniques. One of these dams is The Arenoso dam, located in the province of Cordova (southern Spain). This dam has been monitored using Sentinel-1 SAR data since the beginning of the mission in 2014. In this paper, we show the processing of 382 SLC SAR images both in ascending and descending tracks until March 2019. The results indicate that the main displacement of the dam in this period is in the vertical direction with a rate in the order of -1 cm/year in the central part of the dam body.ESA Research and ServiceReMoDams project (AEI/FEDER, UE) from Spanish Ministry of Economy, Industry and Competitiveness ESP2017-89344-RCEACTEMA from University of Jaen (Spain)Junta de Andalucia European Commission RNM-282ERDF through the Operational Programme for Competitiveness and Internationalisation -COMPETE 2020 Programme POCI-01-0145FEDER-006961National Funds through the FCT -Fundacao para a Ciencia e a Tecnologia (Portuguese Foundation for Science and Technology) UID/EEA/50014/2013Ministry of Education, Youth and Sports from the National Programme of Sustainability (NPU II) project "IT4Innovations excellence in science" (Czech Republic) LQ1602Vedecka grantova agentura MSVVaS SR a SAV (VEGA) 2/0100/20PAIUJA-2019/202

Automated Extraction Improves Multiplex Molecular Detection of Infection in Septic Patients

Sepsis is one of the leading causes of morbidity and mortality in hospitalized patients worldwide. Molecular technologies for rapid detection of microorganisms in patients with sepsis have only recently become available. LightCycler SeptiFast test Mgrade (Roche Diagnostics GmbH) is a multiplex PCR analysis able to detect DNA of the 25 most frequent pathogens in bloodstream infections. The time and labor saved while avoiding excessive laboratory manipulation is the rationale for selecting the automated MagNA Pure compact nucleic acid isolation kit-I (Roche Applied Science, GmbH) as an alternative to conventional SeptiFast extraction. For the purposes of this study, we evaluate extraction in order to demonstrate the feasibility of automation. Finally, a prospective observational study was done using 106 clinical samples obtained from 76 patients in our ICU. Both extraction methods were used in parallel to test the samples. When molecular detection test results using both manual and automated extraction were compared with the data from blood cultures obtained at the same time, the results show that SeptiFast with the alternative MagNA Pure compact extraction not only shortens the complete workflow to 3.57 hrs., but also increases sensitivity of the molecular assay for detecting infection as defined by positive blood culture confirmation

The Role of Faults as Barriers in Confined Seismic Sequences: 2021 Seismicity in the Granada Basin (Betic Cordillera)

Fault barriers are key structures for studying seismic hazard in regions of intense brittle deformation. The interaction between fault sets affects their seismogenic behavior, if some of them act as barriers. The Granada Basin, in the Betic Cordillera, is a region affected by shallow brittle deformation, as it was the scenario for the recent Granada 2021 seismic sequence. This seismicity presented a swarm behavior at the beginning of the sequence, followed by mainshock-aftershock features. Geological and gravity data presented here reveal that the basement is affected by two sets of NW-SE and NE-SW normal faults and intensely deformed by vertical NW-SE joints. Improved relocation of the Granada 2021 seismicity reveals a confined chimney-shape seismicity caused by the activity of a 2 km long NW-SE normal fault segment. The confinement of the sequence is associated with the NE-SW fault set acting as a barrier that restricts the rupture area, limiting the maximum magnitude, and favoring the recurrence of events with smaller magnitude. The chimney-shape of the seismic sequence suggests that the deformation is propagated vertically to the surface, facilitated by preexisting fractures. The shallow extensional deformation during the uplift of the central Betic Cordillera drove the activity of the local structures obliquely to the regional extensional trends, as evidenced by the seismic sequence. This multidisciplinary study improves the knowledge on the origin of the Granada Basin and underlies the important role of preexisting fractures on fault segmentation and seismic propagation, decreasing the seismic potential of this area.Spanish projects Evaluación de la Peligrosidad de Inestabilidades de Laderas Asociadas a Terremotos (CGL2015-65602-R AEI-FEDER)B-RNM-301-UGR18 (Junta de Andalucía/FEDER);P18-RT-3275 (Junta de Andalucía/FEDER)Programa Operativo FEDER Andalucía 2014–2020 – call made by the University of Jaén (Ref. 126344)POAIUJA 2021/2022 from the University of JaénAndalusian research groups RNM-148Andalusian research groups RNM-282Andalusian research groups RNM-37

Gelsilox: a novel strategy for the study of dynamics alteration in the thiol redox proteome

Comunicaciones a congreso

The Role of Faults as Barriers in Confined Seismic Sequences: 2021 Seismicity in the Granada Basin (Betic Cordillera)

Fault barriers are key structures for studying seismic hazard in regions of intense brittle deformation. The interaction between fault sets affects their seismogenic behavior, if some of them act as barriers. The Granada Basin, in the Betic Cordillera, is a region affected by shallow brittle deformation, as it was the scenario for the recent Granada 2021 seismic sequence. This seismicity presented a swarm behavior at the beginning of the sequence, followed by mainshock-aftershock features. Geological and gravity data presented here reveal that the basement is affected by two sets of NW-SE and NE-SW normal faults and intensely deformed by vertical NW-SE joints. Improved relocation of the Granada 2021 seismicity reveals a confined chimney-shape seismicity caused by the activity of a 2 km long NW-SE normal fault segment. The confinement of the sequence is associated with the NE-SW fault set acting as a barrier that restricts the rupture area, limiting the maximum magnitude, and favoring the recurrence of events with smaller magnitude. The chimney-shape of the seismic sequence suggests that the deformation is propagated vertically to the surface, facilitated by preexisting fractures. The shallow extensional deformation during the uplift of the central Betic Cordillera drove the activity of the local structures obliquely to the regional extensional trends, as evidenced by the seismic sequence. This multidisciplinary study improves the knowledge on the origin of the Granada Basin and underlies the important role of preexisting fractures on fault segmentation and seismic propagation, decreasing the seismic potential of this area

Characterization of triple‐negative breast cancer preclinical models provides functional evidence of metastatic progression

Triple‐negative breast cancer (TNBC), an aggressive, metastatic and recurrent breast cancer (BC) subtype, currently suffers from a lack of adequately described spontaneously metastatic preclinical models that faithfully reproduce the clinical scenario. We describe two preclinical spontaneously metastatic TNBC orthotopic murine models for the development of advanced therapeutics: an immunodeficient human MDA‐MB‐231‐Luc model and an immunocompetent mouse 4T1 model. Furthermore, we provide a broad range of multifactorial analysis for both models that could provide relevant information for the development of new therapies and diagnostic tools. Our comparisons uncovered differential growth rates, stromal arrangements and metabolic profiles in primary tumors, and the presence of cancer‐associated adipocyte infiltration in the MDA‐MB‐231‐Luc model. Histopathological studies highlighted the more rapid metastatic spread to the lungs in the 4T1 model following a lymphatic route, while we observed both homogeneous (MDA‐MB‐231‐Luc) and heterogeneous (4T1) metastatic spread to axillary lymph nodes. We encountered unique metabolomic signatures in each model, including crucial amino acids and cell membrane components. Hematological analysis demonstrated severe leukemoid and lymphoid reactions in the 4T1 model with the partial reestablishment of immune responses in the immunocompromised MDA‐MB‐231‐Luc model. Additionally, we discovered β‐immunoglobulinemia and increased basal levels of G‐CSF correlating with a metastatic switch, with G‐CSF also promoting extramedullary hematopoiesis (both models) and causing hepatosplenomegaly (4T1 model). Overall, we believe that the characterization of these preclinical models will foster the development of advanced therapeutic strategies for TNBC treatment, especially for the treatment of patients presenting both, primary tumors and metastatic spread

Relevance of the extraction stage on the anti-inflammatory action of fucoidans

The anti-inflammatory action of fucoidans is well known, based on both in vitro and some in vivo studies. The other biological properties of these compounds, their lack of toxicity, and the possibility of obtaining them from a widely distributed and renewable source, makes them attractive novel bioactives. However, fucoidans’ heterogeneity and variability in composition, structure, and properties depending on seaweed species, biotic and abiotic factors and processing conditions, especially during extraction and purification stages, make it difficult for standardization. A review of the available technologies, including those based on intensification strategies, and their influence on fucoidan composition, structure, and anti-inflammatory potential of crude extracts and fractions is presented.Xunta de Galicia | Ref. EDC431C/2022/08Xunta de Galicia | Ref. ED431F 2020/01Xunta de Galicia | Ref. ED481D-2022/018Ministerio de Ciencia e Innovación | Ref. CTM2012-38095Ministerio de Ciencia e Innovación | Ref. RYC2018-024454-

Impact of occlusion duration on the success rate and outcomes of percutaneous coronary intervention in chronic total occlusions

ABSTRACTBackgroundInitial studies have shown that old occlusions or those with indeterminate occlusion duration have been associated with percutaneous coronary intervention (PCI) failure and a worse prognosis. This study aimed to determine the impact of occlusion duration on the success and outcomes of contemporary PCI on chronic total occlusion (CTO).MethodsThe authors analyzed a retrospective cohort of consecutive patients submitted to PCI in CTO, who were compared according to the confirmed occlusion duration (COD) < 12 months, ≥ 12 months, or indeterminate occlusion duration (IOD).ResultsA total of 168 patients were treated, 122 (72.6%) with COD (80 < 12 months, 42 ≥ 12 months) and 46 (24.7%) with an IOD. Lesion extension was 17.0 ± 13.6mm, in 2.90 ± 0.58mm vessels, and the anterograde approach was used in 98.8% of cases. Angiographic success was attained in 79.2% of patients (80.0% vs. 73.8% vs. 82.6%; p = 0.73). The main cause of failure was the inability to cross the lesion with the guidewire (68.6%). Occlusion duration had no impact on in-hospital events (4.8% vs. 7.1% vs. 6.0%; p = 0.73), which were almost entirely explained by periprocedural myocardial infarction, or on late outcomes (18.8% vs. 7.1% vs. 15.3%; p = 0.23). At the multivariate analysis, lesion length ≥ 20mm (odds ratio - OR = 7.27; 95% confidence interval - 95% IC 1.94-29.1; p = 0.003), calcification (OR = 4.72; 95% CI 1.19-19.1; p = 0.02), and tortuosity of the occluded segment (OR = 15.98; 95% CI 2.18-144.7; p = 0.007) were predictors of failure.ConclusionsOcclusion duration was not associated with increased failure rate of the procedure or worse PCI outcomes in CTO

Aceitação da instituição universitária do ponto de vista do aluno

Este artículo aborda la percepción de los estudiantes sobre la institución universitaria. Los estudiantes universitarios muestran una aceptación percibida de carácter institucional, académico y personal, según las evidencias empíricas obtenidas a través de un cuestionario sobre la percepción de la institución universitaria realizado en la Universidad de Granada, España. La percepción de los estudiantes contiene actitudes relacionadas con cierta conformidad institucional y adopta formas cercanas al pragmatismo académico. Los estudiantes universitarios encuestados, de diferentes Grados, género y edad, revelan una actitud general de conformidad con la institución de educación superior, con las acciones de enseñanza y los recursos y un sentimiento de pertenencia institucional sustentado en motivaciones internas y externas dentro de la misma institución de educación superior.This study analyzes students’ perception of university institutions. According to empirical evidence obtained from a questionnaire on perception of university institutions performed at the University of Granada, Spain, university students show perceived acceptance that is institutional, academic, and personal. Students’ perceptions contain attitudes involving a certain institutional conformity and adopt forms close to academic pragmatism. The university students surveyed, who are from different undergraduate degree programs and differ in gender and age, show a general attitude of conformity toward higher education institutions, their instructional practice, and their resources, as well as a feeling of belonging to the institution based on internal and external motivations within the higher education.Este trabalho aborda a percepção dos estudantes relativamente à instituição universitária. Os estudantes universitários revelam uma aceitação de carácter institucional, académico e pessoal, segundo as evidências empíricas recolhidas através de um questionár io sobre a percepção da instituição universitária, realizado na Universidade de Granada, Espanha. A percepção dos estudantes revela atitudes relacionadas com alguma conformidade institucional e adopta formas próximas de uma pragmatismo académico. Os estudantes universitários inquiridos são de graus de ensino, género e idades diferentes e revelam na sua generalidade uma atitude de conformidade com a instituiçao de ensino superior, com as práticas de ensino e os recursos, assim como, um sentimento de pertença institucional sustentado em motivações internas e externas, dentro da própria instituição de ensino superior