25 research outputs found
Acid-sensing ion channel 1a contributes to the effect of extracellular acidosis on NLRP1 inflammasome activation in cortical neurons
A Variação do método de incremento de cargas não altera a determinação do limiar de lactato em exercÃcio resistido Variation in the incremental workload method does not change the lactate threshold determination in resistance exercise
Com o objetivo de analisar e comparar diferentes protocolos incrementais (PI) em exercÃcio resistido para a identificação do limiar de lactato (LL), 12 voluntários homens (23,3 ± 1,6 anos) adaptados ao exercÃcio resistido foram submetidos a dois testes incrementais realizados em leg press 45º (LP). Os PI's foram: 1) relativo ao teste da carga máxima (PI%1RM), com incrementos de 19, 28, 32, 37, 41, 45, 55 e 60% de 1RM; 2) relativo ao peso corporal (PI%PC), com incrementos de 17, 33, 50, 67, 83, 100, 117 e 133% do PC. Em ambos os PI's a duração de cada estágio foi de 1 min, sendo realizadas 30 repetições em cada. Durante os intervalos entre cada estágio (2 min para o PI%1RM e de 1 min para o PI%PC) foram coletados do lóbulo da orelha, 25µL de sangue capilarizado, os quais foram depositados em microtúbulos Eppendorff para posterior dosagem das concentrações de lactato sanguÃneo [Lac]. Foi possÃvel identificar o LL a partir da resposta das [Lac] nos diferentes protocolos. Não foram observadas diferenças significativas entre o LL determinado por cargas absolutas (PI%1RM - 72,3 ± 12,5 vs. PI%PC - 65,9 ± 11,5kg; p > 0,05) e relativas (PI%1RM - 32,3 ± 4,2 vs. PI%PC - 31,6 ± 4,3%; p > 0,05). Alta correlação foi observada entre os PI's, tanto para cargas absolutas (r = 0,90; p < 0,01) como relativas (r = 0,83; p < 0,01). Concluiu-se que, apesar de modificações realizadas nos protocolos adotados, foi possÃvel identificar o LL em LP na amostra estudada, em que as intensidades relativas e absolutas a esses limiares não diferiram e apresentaram correlação entre si. Sugere-se a identificação do LL em exercÃcio resistido através de protocolo com incrementos relativos ao PC, tendo em vista a vantagem de não ser necessário submeter o avaliado à aplicação prévia de um teste de carga máxima.<br>The aim of this investigation was to analyze and compare different incremental protocols (IP) to identify the lactate threshold (LT) in resistance exercise. 12 male volunteers (23.3 ± 1.6 years) adapted to resistance exercise were submitted to two incremental tests performed in leg-press 45º (LP). The IP were: 1) concerned with the maximum workload test (IP%1RM), with incremental load corresponding to 19, 28, 32, 37, 41, 45, 55 and 60% of 1RM; 2) concerned with the body weight (IP%BW), with incremental load of 17, 33, 50, 67, 83, 100, 117 and 133% of the BW. Both IP had stage duration of 1-min, each with 30 repetitions. During intervals between stages (2-min to IP%1RM and 1-min to IP%BW), 25 µL of blood were collected from ear lobe and then placed in Eppendorff microtubes for blood lactate concentration [Lac] dosing. It was possible to identify LT from the responses of the [Lac] in both protocols. No significant differences were observed between the LT intensities determined by absolute (IP%1RM - 72.3 ± 12.5 vs. IP%BW - 65.9 ± 11.5 kg; p > 0.05) and relative loads (IP%1RM - 32.3 ± 4.2 vs. IP%BW - 31.6 ± 4.3 %1-RM; p > 0.05). High correlation was observed between the IP%1RM and IP%BW both for absolute (r = 0.90; p < 0.01) as well as for relative loads (r = 0.83; p < 0.01). In conclusion, despite protocols modifications during the incremental test on resistance exercise, it was possible to identify the LT in LP in the studies sample in which relative and absolute intensities did not differ from each other and presented high correlation between them. The results suggest that LT in resistance exercise should be identified through a protocol with increments based on the BW %. Such procedure has the advantage of not submitting the participant to a previous 1 RM incremental test
Association Between Antihypertensive Medication Use and Non-cardiovascular Outcomes in Older Men
Rational design of mutations that change the aggregation rate of a protein while maintaining its native structure and stability
RNA structure drives interaction with proteins
The combination of high-throughput sequencing and in vivo crosslinking approaches leads to the progressive uncovering of the complex interdependence between cellular transcriptome and proteome. Yet, the molecular determinants governing interactions in protein-RNA networks are not well understood. Here we investigated the relationship between the structure of an RNA and its ability to interact with proteins. Analysing in silico, in vitro and in vivo experiments, we find that the amount of double-stranded regions in an RNA correlates with the number of protein contacts. This relationship -which we call structure-driven protein interactivity- allows classification of RNA types, plays a role in gene regulation and could have implications for the formation of phase-separated ribonucleoprotein assemblies. We validate our hypothesis by showing that a highly structured RNA can rearrange the composition of a protein aggregate. We report that the tendency of proteins to phase-separate is reduced by interactions with specific RNAs.The research leading to these results has been supported by European Research Council (RIBOMYLOME_309545 to G.G.T. and METAMETA_311522 to R.M.V.), Spanish Ministry of Economy and Competitiveness (BFU2014-55054-P and BFU2017-86970-P), ‘Fundació La Marató de TV3’ (PI043296) and the collaboration with Peter St. George-Hyslop financed by the Wellcome Trust. We acknowledge support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013-2017’. We also acknowledge the support of the CERCA Programme/Generalitat de Catalunya and of Spanish Ministry for Science and Competitiveness (MINECO) to the EMBL partnership
Nuclear cardiology practice and associated radiation doses in Europe: results of the IAEA Nuclear Cardiology Protocols Study (INCAPS) for the 27 European countries
Purpose: Nuclear cardiology is widely used to diagnose coronary artery disease and to guide patient management, but data on current practices, radiation dose-related best practices, and radiation doses are scarce. To address these issues, the IAEA conducted a worldwide study of nuclear cardiology practice. We present the European subanalysis. Methods: In March 2013, the IAEA invited laboratories across the world to document all SPECT and PET studies performed in one week. The data included age, gender, weight, radiopharmaceuticals, injected activities, camera type, positioning, hardware and software. Radiation effective dose was calculated for each patient. A quality score was defined for each laboratory as the number followed of eight predefined best practices with a bearing on radiation exposure (range of quality score 0 – 8). The participating European countries were assigned to regions (North, East, South, and West). Comparisons were performed between the four European regions and between Europe and the rest-of-the-world (RoW). Results: Data on 2,381 European patients undergoing nuclear cardiology procedures in 102 laboratories in 27 countries were collected. A cardiac SPECT study was performed in 97.9 % of the patients, and a PET study in 2.1 %. The average effective dose of SPECT was 8.0 ± 3.4 mSv (RoW 11.4 ± 4.3 mSv; P < 0.001) and of PET was 2.6 ± 1.5 mSv (RoW 3.8 ± 2.5 mSv; P < 0.001). The mean effective doses of SPECT and PET differed between European regions (P < 0.001 and P = 0.002, respectively). The mean quality score was 6.2 ± 1.2, which was higher than the RoW score (5.0 ± 1.1; P < 0.001). Adherence to best practices did not differ significantly among the European regions (range 6 to 6.4; P = 0.73). Of the best practices, stress-only imaging and weight-adjusted dosing were the least commonly used. Conclusion: In Europe, the mean effective dose from nuclear cardiology is lower and the average quality score is higher than in the RoW. There is regional variation in effective dose in relation to the best practice quality score. A possible reason for the differences between Europe and the RoW could be the safety culture fostered by actions under the Euratom directives and the implementation of diagnostic reference levels. Stress-only imaging and weight-adjusted activity might be targets for optimization of European nuclear cardiology practice
Current worldwide nuclear cardiology practices andradiationexposure: results from the 65 country IAEA nuclear cardiology protocols cross-sectional study (INCAPS)
Aims To characterize patient radiation doses from nuclear myocardial perfusion imaging (MPI) and the use of radiationoptimizing 'best practices' worldwide, and to evaluate the relationship between laboratory use of best practices and patient radiation dose. Methods and results We conducted an observational cross-sectional study of protocols used for all 7911 MPI studies performed in 308 nuclear cardiology laboratories in 65 countries for a single week in March-April 2013. Eight 'best practices' relating to radiation exposurewere identified a priori by an expert committee, and a radiation-related quality index (QI) devised indicating the number of best practices used by a laboratory. Patient radiation effective dose (ED) ranged between 0.8 and 35.6 mSv (median 10.0 mSv). Average laboratory ED ranged from 2.2 to 24.4 mSv (median 10.4 mSv); only 91 (30%) laboratories achieved the median ED ≤ 9 mSv recommended by guidelines. Laboratory QIs ranged from 2 to 8 (median 5). Both ED and QI differed significantly between laboratories, countries, and world regions. The lowest median ED (8.0 mSv), in Europe, coincided with high best-practice adherence (mean laboratory QI 6.2). The highest doses (median 12.1 mSv) and low QI (4.9) occurred in Latin America. In hierarchical regression modelling, patients undergoing MPI at laboratories following more 'best practices' had lower EDs Conclusion Marked worldwide variation exists in radiation safety practices pertaining to MPI, with targeted EDs currently achieved in a minority of laboratories. The significant relationship between best-practice implementation and lower doses indicates numerous opportunities to reduce radiation exposure from MPI globally
Contributing role of extracellular vesicles on vascular endothelium haemostatic balance in cancer.
Extracellular vesicles (EVs) generated during tumourigenesis are thought to play a major role in the hypercoagulant state observed in cancer patients. They exhibit negatively charged phospholipids and tissue factor (TF) that promote coagulation cascade activation. In addition, they contain surface proteins and cytoplasmic molecules, both originating from the producing cell that can impact target cells' expression. By targeting endothelial cells of blood vessels, these EVs could disturb the physiological anticoagulant properties of these cells and be partly responsible for the vascular endothelium activation observed in cancer patients. Indeed, vascular endothelium naturally exhibits heparin-like proteoglycan, TF pathway inhibitor and protein C anticoagulant pathway that prevent thrombosis in physiological condition. An overexpression of TF and a decreased expression of coagulation cascade inhibitors have been reported after EVs' treatment of endothelial cells. The induction of apoptosis and an increased expression of platelet adhesion molecules have also been highlighted. These events may promote thrombus formation in cancer. The aim of this paper is to provide a targeted review on the current evidence and knowledge of roles and impact of EVs on endothelial surface anticoagulant and procoagulant factors and cellular adhesion molecules expression