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1.
Front Med Technol ; 4: 881930, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35711385

RESUMEN

Luer slip is one of the gold standards for chip-to-world interface in microfluidics. They have outstanding mechanical and operational robustness in a broad range of applications using water and solvent-based liquids. Still, their main drawbacks are related to their size: they have relatively large dead volumes and require a significant footprint to assure a leak-free performance. Such aspects make their integration in systems with high microchannel density challenging. To date, there has been no geometrical optimization of the Luer slips to provide a solution to the mentioned drawbacks. This work aims to provide the rules toward downscaling the Luer slips. To this effect, seven variations of the Luer slip male connectors and five variations of Luer slip female connectors have been designed and manufactured focusing on the reduction of the size of connectors and minimization of the dead volumes. In all cases, female connectors have been developed to pair with the corresponding male connector. Characterization has been performed with a tailor-made test bench in which the closure force between male and female connectors has been varied between 7.9 and 55 N. For each applied closure force, the test bench allows liquid pressures to be tested between 0.5 and 2.0 bar. Finally, the analysis of a useful life determines the number of cycles that the connectors can withstand before leakage.

3.
Sci Total Environ ; 830: 154828, 2022 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-35346708

RESUMEN

A multiproxy approach was applied to a sediment core retrieved from the deep crater Lake Funda, located in the middle of the North Atlantic Ocean on Flores Island, Azores archipelago (Portugal). The purpose of this study was to determine how this ecosystem responded to natural and anthropogenic forces over the last millennium. We distinguished three main phases in lake evolution using multiproxy reconstructions and documentary sources. (A) Climate and lake catchment processes, as well as internal ones, were the main drivers of ecosystem variability before 1335 CE, when human disturbances were absent in the Lake Funda catchment. (B) The second phase is marked by unprecedented changes in all studied proxies between 1335 and 1560 CE, including abrupt changes in the composition and diversity of diatom and chironomid assemblages. Synergistic effects from high climate variability and the onset of human disturbances in the catchment (e.g., introduction of livestock) during the Medieval Climate Anomaly-Little Ice Age transition, led to an increase in lake trophic state from mesotrophic to eutrophic conditions. (C) In the last phase (1560 CE to the present), the eutrophic conditions in Lake Funda were maintained through a positive feedback loop between lake productivity and in-lake phosphorous recycling. Variability within the lake ecosystem was mainly associated with climate variability and internal lake dynamics (e.g., phosphorus remobilization). Our results show that a paleoecological approach is crucial to understanding lake ecological states in the present-day in order to develop locally adapted management and restoration strategies. A long-term perspective enables us to understand the harmful consequences of ongoing climate change and human disturbances on lake ecosystems.


Asunto(s)
Diatomeas , Ecosistema , Efectos Antropogénicos , Cambio Climático , Humanos , Lagos
5.
Proc Natl Acad Sci U S A ; 118(41)2021 10 12.
Artículo en Inglés | MEDLINE | ID: mdl-34607952

RESUMEN

Humans have made such dramatic and permanent changes to Earth's landscapes that much of it is now substantially and irreversibly altered from its preanthropogenic state. Remote islands, until recently isolated from humans, offer insights into how these landscapes evolved in response to human-induced perturbations. However, little is known about when and how remote systems were colonized because archaeological data and historical records are scarce and incomplete. Here, we use a multiproxy approach to reconstruct the initial colonization and subsequent environmental impacts on the Azores Archipelago. Our reconstructions provide unambiguous evidence for widespread human disturbance of this archipelago starting between 700-60+50 and 850-60+60 Common Era (CE), ca. 700 y earlier than historical records suggest the onset of Portuguese settlement of the islands. Settlement proceeded in three phases, during which human pressure on the terrestrial and aquatic ecosystems grew steadily (i.e., through livestock introductions, logging, and fire), resulting in irreversible changes. Our climate models suggest that the initial colonization at the end of the early Middle Ages (500 to 900 CE) occurred in conjunction with anomalous northeasterly winds and warmer Northern Hemisphere temperatures. These climate conditions likely inhibited exploration from southern Europe and facilitated human settlers from the northeast Atlantic. These results are consistent with recent archaeological and genetic data suggesting that the Norse were most likely the earliest settlers on the islands.


Asunto(s)
Ecosistema , Ambiente , Actividades Humanas , Migración Humana , Agricultura , Azores , Cambio Climático , Modelos Climáticos , Heces/química , Humanos
6.
J Cardiovasc Pharmacol ; 78(3): 463-473, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34117181

RESUMEN

ABSTRACT: The aim of our study is to assess the impact of anemia, chronic kidney disease, and diabetes mellitus on platelet reactivity (PR) in patients with severe aortic stenosis, both at baseline and after transcatheter aortic valve implantation (TAVI). This study is a prespecified subanalysis of the REAC-TAVI prospective, multicenter trial that included patients pretreated with aspirin + clopidogrel before TAVI. PR was measured at baseline and at 5 different time points after TAVI with the VerifyNow assay (Accriva Diagnostics, San Diego, CA), over a 3-month follow-up period. Patients with high PR (HPR) at baseline, before TAVI (n = 48) were randomized to aspirin + clopidogrel or aspirin + ticagrelor for 3 months, whereas those with normal PR (NPR) (n = 20) were continued on aspirin + clopidogrel. A "raiser response" in PR was defined as an increase in PR units >20% of baseline after TAVI. Patients with HPR before TAVI presented concomitant anemia and chronic kidney disease more frequently than their counterparts with NPR. Anemia and higher body mass index were independently associated with HPR to clopidogrel at baseline. Moreover, anemic patients with baseline HPR who were continued on clopidogrel presented higher PR after TAVI than patients with HPR switched to ticagrelor. All patients with baseline NPR presented a "raiser response" after TAVI, which was nonexistent among patients with HPR managed with ticagrelor. In summary, anemia seems as a relevant factor associated with baseline HPR and higher PR after TAVI in patients with baseline HPR randomized to clopidogrel, whereas ticagrelor proved more effective than clopidogrel at attaining sustained reductions in PR during follow-up, regardless of baseline comorbidities.


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Aspirina/uso terapéutico , Plaquetas/efectos de los fármacos , Clopidogrel/uso terapéutico , Terapia Antiplaquetaria Doble , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticagrelor/uso terapéutico , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Anciano , Anciano de 80 o más Años , Anemia/sangre , Anemia/epidemiología , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/epidemiología , Aspirina/efectos adversos , Plaquetas/metabolismo , Clopidogrel/efectos adversos , Comorbilidad , Diabetes Mellitus/sangre , Diabetes Mellitus/epidemiología , Terapia Antiplaquetaria Doble/efectos adversos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/efectos adversos , Pruebas de Función Plaquetaria , Prevalencia , Estudios Prospectivos , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/epidemiología , Índice de Severidad de la Enfermedad , España/epidemiología , Ticagrelor/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
7.
Int J Mol Sci ; 22(2)2021 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-33440633

RESUMEN

Transforming growth factor ß (TGF-ß) signalling pathways are highly conserved across metazoa and play essential roles not only during development but also in adult tissue maintenance. Alterations of these pathways usually result in a plethora of pathologies. In the nematode Caenorhabditis elegans, the TGF-ß Sma/Mab (small/male abnormal) pathway regulates various worm phenotypes such as body size, immune response, ageing, matricide and reproductive span. SMA-10 has been described as a positive modulator of worm body size through the TGF-ß Sma/Mab pathway. To better understand if SMA-10 is a core component of the pathway, we use gene epistatic analysis to assess the contribution of SMA-10 to various phenotypes regulated by TGF-ß Sma/Mab. We confirm that SMA-10 controls body size and find that it also affects the matricide and reproductive span of the nematodes. However, neither male tail formation (previously reported) nor ageing appeared altered. Lastly, although null sma-10 worms are more susceptible to Pseudomonas aeruginosa infections than wild-types, this response does not depend on TGF-ß Sma/Mab but on the insulin receptor DAF-2. We also show that the expression of sma-10 in either hypodermis or intestine fully rescues the wild-type immune response. Our results contribute to understanding the role of SMA-10 as a context-dependent component of TGF-ß Sma/Mab, and reveal a function of SMA-10 in immunity in association to the Insulin/insulin-like growth factor signalling (IIS) pathway.


Asunto(s)
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/inmunología , Caenorhabditis elegans/metabolismo , Inmunomodulación , Proteínas de la Membrana/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta/metabolismo , Alelos , Animales , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Endorreduplicación/inmunología , Inmunidad Innata , Longevidad , Mutación con Pérdida de Función , Proteínas de la Membrana/genética , Mutación , Receptor de Insulina/metabolismo
8.
Ann Surg Oncol ; 28(7): 3714-3721, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33247362

RESUMEN

INTRODUCTION: The diagnosis or treatment of breast cancer is sometimes delayed. A lengthy delay may have a negative psychological impact on patients. The aim of our study was to evaluate the sociodemographic, clinical and pathological factors associated with delay in the provision of surgical treatment for localised breast cancer, in a prospective cohort of patients. METHODS: This observational, prospective, multicentre study was conducted in ten hospitals belonging to the Spanish national public health system, located in four Autonomous Communities (regions). The study included 1236 patients, diagnosed through a screening programme or found to be symptomatic, between April 2013 and May 2015. The study variables analysed included each patient's personal history, care situation, tumour history and data on the surgical intervention, pathological anatomy, hospital admission and follow-up. Treatment delay was defined as more than 30 days elapsed between biopsy and surgery. RESULTS: Over half of the study population experienced surgical treatment delay. This delay was greater for patients with no formal education and among widows, persons not requiring assistance for usual activities, those experiencing anxiety or depression, those who had a high BMI or an above-average number of comorbidities, those who were symptomatic, who did not receive NMR spectroscopy, who presented a histology other than infiltrating ductal carcinoma or who had poorly differentiated carcinomas. CONCLUSIONS: Certain sociodemographic and clinical variables are associated with surgical treatment delay. This study identifies factors that influence surgical delays, highlighting the importance of preventing these factors and of raising awareness among the population at risk and among health personnel.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/cirugía , Comorbilidad , Femenino , Hospitales , Humanos , Estudios Prospectivos , Tiempo de Tratamiento
9.
J Invasive Cardiol ; 32(12): 446-452, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32771996

RESUMEN

OBJECTIVES: Ticagrelor has proven more effective than clopidogrel at attaining a maintained suppression of high platelet reactivity (HPR) in aortic stenosis patients undergoing transcatheter aortic valve implantation (TAVI). This study aims to assess the influence of implanted valve type on the degree of platelet reactivity (PR) after TAVI. METHODS: This study is a prespecified analysis of REAC-TAVI, a prospective, multicenter study that included patients on dual-antiplatelet therapy with aspirin and clopidogrel before TAVI. Patients with HPR (n = 48) were randomized to aspirin and clopidogrel or aspirin and ticagrelor for 3 months, while those without HPR (n = 20) were continued on aspirin and clopidogrel. PR was measured 6 hours, 24 hours, 5 days, 30 days, and 90 days after TAVI with VerifyNow assay. Bioprosthetic valves were classified as balloon-expandable valve (BEV), self-expandable valve (SEV), or other. RESULTS: Sixty-eight patients comprising 32 BEVs, 28 SEVs, and 8 other valves were included. Devices were larger and postdilation was more frequent in the SEV group. Follow-up PR was lower in patients treated with ticagrelor vs those treated with clopidogrel at all time points after TAVI, including patients without baseline HPR (P<.001). PR after TAVI was similar in the three groups. Major cardiovascular adverse events, stroke, and hemorrhagic complications were comparable across the different bioprosthesis groups at 4-month follow-up. CONCLUSIONS: The effect of valve type on PR after TAVI is similar across the spectrum of most transcatheter valves. In our sample, ticagrelor achieved a faster and more effective reduction in PR than clopidogrel in patients with HPR undergoing TAVI, irrespective of valve type.


Asunto(s)
Estenosis de la Válvula Aórtica , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/cirugía , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del Tratamiento
10.
Rev. esp. cardiol. (Ed. impr.) ; 73(7): 536-545, jul. 2020. tab, graf
Artículo en Español | IBECS | ID: ibc-197833

RESUMEN

INTRODUCCIÓN Y OBJETIVOS: El objetivo es evaluar el impacto del acceso vascular en las complicaciones hemorrágicas tras una intervención coronaria percutánea en pacientes con alto riesgo de sangrado (ARS) a los 30 días y a los 2 años. MÉTODOS: El presente estudio es un subanálisis predefinido del estudio LEADERS FREE, que incluyó a 2.432 pacientes con ARS y en el que el stent farmacoactivo Biolimus A9 resultó superior al stent convencional en seguridad y eficacia. RESULTADOS: El acceso radial (AR) se utilizó en 1.454 pacientes (59,8%) y el femoral (AF), en 978 (40,2%), ambos a elección del operador. La seguridad y los beneficios del stent farmacoactivo sobre el convencional fueron independientes del acceso vascular. A los 30 días y a los 2 años, habían sufrido un sangrado mayor el 2,4 y el 7,5% de los pacientes con AR y el 4,6 y el 10,9% de los pacientes con AF (p = 0,003), la mayoría en ambos grupos (el 2,1 y el 7,0% del de AR; el 3,2 y el 9,4% del de AF) no relacionados con el sitio de acceso vascular. El AR se asoció con una reducción significativa en las tasas ajustadas de sangrado mayor tanto a 30 días (HR=1,98; IC95%, 1,25-3,11; p = 0,003) como a 2 años de seguimiento (HR=1,51; IC95%, 1,14-2,01; p = 0,003). CONCLUSIONES: Los operadores prefirieron el AR en la mayoría de los pacientes con ARS, lo cual se asoció con una reducción significativa del sangrado mayor. Asimismo, un número significativo de sangrados en el seguimiento de esta población son no relacionados con el acceso vascular


INTRODUCTION AND OBJECTIVES: The prognostic impact of bleeding in high bleeding risk (HBR) patients depending on the location of bleeding and prognosis in nonaccess site bleeding is unknown. We aimed to assess the impact of vascular access site on bleeding complications after percutaneous coronary interventions for HBR patients at 30-day and 2-year follow-up. METHODS: The LEADERS FREE trial included 2432 HBR PCI patients. A Biolimus A9 drug-coated stent was superior to a bare-metal stent for safety and efficacy. This is a predefined sub-analysis of the LEADERS FREE trial. RESULTS: Transradial access (TRA) was used in 1454 patients (59.8%) and transfemoral access (TFA) in 978 (40.2%), according to operator preference. The safety and benefits of drug-coated stents over bare-metal stents were independent of vascular access. At 30 days and 2 years, major bleeding had occurred in 2.4% and 7.5% of TRA patients and 4.6% and 10.9% of TFA patients (P=.003), respectively. Most of these events in both groups (2.1% and 7.0% for TRA; 3.2% and 9.4% for TFA, respectively) were nonaccess site-related. TRA was associated with a significant reduction in adjusted rates of major bleeding both at 30 days (HR, 1.98; 95%CI, 1.25-3.11; P=.003) and at 2 years of follow-up (HR, 1.51; 95%CI, 1.14-2.01; P=.003). This difference was driven by both access and nonaccess bleeding. CONCLUSIONS: Operators preferred TRA for most HBR patients, which was associated with a significant reduction in major bleeding events. However, most of these events in this population are unrelated to vascular access


Asunto(s)
Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Angioplastia Coronaria con Balón/métodos , Dispositivos de Acceso Vascular/clasificación , Pérdida de Sangre Quirúrgica/prevención & control , Intervención Coronaria Percutánea/métodos , Angioplastia Coronaria con Balón/estadística & datos numéricos , Pronóstico , Factores de Riesgo , Stents Liberadores de Fármacos/estadística & datos numéricos , Intervención Coronaria Percutánea/estadística & datos numéricos
11.
Rev Esp Cardiol (Engl Ed) ; 73(7): 536-545, 2020 Jul.
Artículo en Inglés, Español | MEDLINE | ID: mdl-31563471

RESUMEN

INTRODUCTION AND OBJECTIVES: The prognostic impact of bleeding in high bleeding risk (HBR) patients depending on the location of bleeding and prognosis in nonaccess site bleeding is unknown. We aimed to assess the impact of vascular access site on bleeding complications after percutaneous coronary interventions for HBR patients at 30-day and 2-year follow-up. METHODS: The LEADERS FREE trial included 2432 HBR PCI patients. A Biolimus A9 drug-coated stent was superior to a bare-metal stent for safety and efficacy. This is a predefined sub-analysis of the LEADERS FREE trial. RESULTS: Transradial access (TRA) was used in 1454 patients (59.8%) and transfemoral access (TFA) in 978 (40.2%), according to operator preference. The safety and benefits of drug-coated stents over bare-metal stents were independent of vascular access. At 30 days and 2 years, major bleeding had occurred in 2.4% and 7.5% of TRA patients and 4.6% and 10.9% of TFA patients (P=.003), respectively. Most of these events in both groups (2.1% and 7.0% for TRA; 3.2% and 9.4% for TFA, respectively) were nonaccess site-related. TRA was associated with a significant reduction in adjusted rates of major bleeding both at 30 days (HR, 1.98; 95%CI, 1.25-3.11; P=.003) and at 2 years of follow-up (HR, 1.51; 95%CI, 1.14-2.01; P=.003). This difference was driven by both access and nonaccess bleeding. CONCLUSIONS: Operators preferred TRA for most HBR patients, which was associated with a significant reduction in major bleeding events. However, most of these events in this population are unrelated to vascular access.


Asunto(s)
Procedimientos Quirúrgicos Cardíacos/métodos , Cateterismo Periférico , Arteria Femoral/cirugía , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Arteria Radial/cirugía , Anciano , Anciano de 80 o más Años , Stents Liberadores de Fármacos , Femenino , Hemorragia/etiología , Hemorragia/prevención & control , Humanos , Masculino , Factores de Riesgo , Resultado del Tratamiento
12.
ACS Earth Space Chem ; 3(9): 1873-1883, 2019 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-31799490

RESUMEN

The rate coefficient, k(T), for the gas-phase reaction between OH radicals and acetone CH3C(O)CH3, has been measured using the pulsed CRESU (French acronym for Reaction Kinetics in a Uniform Supersonic Flow) technique (T = 11.7-64.4 K). The temperature dependence of k(T = 10-300 K) has also been computed using a RRKM-Master equation analysis after partial revision of the potential energy surface. In agreement with previous studies we found that the reaction proceeds via initial formation of two pre-reactive complexes both leading to H2O + CH3C(O)CH2 by H-abstraction tunneling. The experimental k(T) was found to increase as temperature was lowered. The measured values have been found to be several orders of magnitude higher than k(300 K). This trend is reproduced by calculations, with a special good agreement with experiments below 25 K. The effect of total gas density on k(T) has been explored. Experimentally, no pressure dependence of k(20 K) and k(64 K) was observed, while k(50 K) at the largest gas density 4.47×1017 cm-3 is twice higher than the average values found at lower densities. The computed k(T) is also reported for 103 cm-3 of He (representative of the interstellar medium). The predicted rate coefficients at 10 K surround the experimental value which appears to be very close to the low pressure regime prevailing in the interstellar medium. For gas-phase model chemistry of interstellar molecular clouds, we suggest using the calculated value of 1.8×10-10 cm3 molecule-1 s-1 at 10 K and the reaction products are water and CH3C(O)CH2 radicals.

13.
Molecules ; 24(17)2019 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-31438557

RESUMEN

Amaranthus hypochondriacus spp. is a commonly grown cereal in Latin America, known for its high protein content. The objective of this study was to separate and identify bioactive peptides found in amaranth seeds through enzymatically-assisted hydrolysis using alcalase and flavourzyme. Hydrolysis was carried out for each enzyme separately and compared to two-step continuous process where both enzymes were combined. The biological activity of the resulting three hydrolysates was analyzed, finding, in general, higher bioactive potential of the hydrolysate obtained in a continuous process (combined enzymes). Its fractions were separated by RP-HPLC, and their bioactivity was analyzed. In particular, two fractions showed the highest biological activity as ACE inhibitors with IC50 at 0.158 and 0.134, thrombin inhibitors with IC50 of 167 and 155, and antioxidants in ABTS assay with SC50 at 1.375 and 0.992 mg/L, respectively. Further sequence analysis of the bioactive peptides was carried out using MALDI-TOF, which identified amino acid chains that have not been reported as bioactive so far. Bibliographic survey allowed identification of similarities between peptides reported in amaranth and other proteins. In conclusion, amaranth proteins are a potential source of peptides with multifunctional activity.


Asunto(s)
Amaranthus/química , Péptidos/química , Proteínas de Plantas/química , Semillas/química , Endopeptidasas/metabolismo , Subtilisinas/metabolismo
14.
J Med Food ; 22(10): 976-981, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31211650

RESUMEN

Fermentation has shown to be an effective technique in bioactive peptides release. That is why in this study antihypertensive, antithrombotic, and antioxidant activity was evaluated during amaranth proteins fermentation with Lactobacillus casei Shirota and Streptococcus thermophilus 54102 in mono and combined culture. During fermentation an increase of free amine groups was observed, and no statistical differences among monocultures were shown, getting higher concentration in combined culture. This was related to antihypertensive and antioxidant activities, where the highest values were also found in the combined process (45% of angiotensin-converting enzyme inhibition, and 168 µmol Trolox equivalents per liter [TE/L] for 2,2-diphenyl-1-picrylhydrazyl, 268 µmol TE/L for 2,2'-azino-bis 3-ethylbenzothiazoline-6-sulfonic acid, and 381 µmol Fe2E/L for ferric reducing ability of plasma). On the contrary, antithrombotic activity was not related to free amine groups during fermentation, having the highest bioactivity in different moments in each experiment. L. casei Shirota and S. thermophilus 54102 are strains that are able to release bioactive peptides from amaranth protein, although amaranth is not a common matrix for the development of lactic acid bacteria. In addition, in this study it was observed for the first time that lactic acid strains are able to release bioactive peptides from amaranth protein. In addition, this methodology could be part for the development of fermented beverages, different from fermented milk, to diversify matrix to obtain a novel functional food.


Asunto(s)
Amaranthus/química , Fermentación , Lactobacillales/metabolismo , Péptidos/farmacología , Proteínas de Plantas/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Antihipertensivos/farmacología , Antioxidantes/farmacología , Antitrombinas/farmacología , Ácido Láctico/metabolismo , Lacticaseibacillus casei , Semillas/química , Streptococcus thermophilus
15.
JACC Cardiovasc Interv ; 12(1): 22-32, 2019 01 14.
Artículo en Inglés | MEDLINE | ID: mdl-30621974

RESUMEN

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).


Asunto(s)
Estenosis de la Válvula Aórtica/cirugía , Válvula Aórtica/cirugía , Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Clopidogrel/administración & dosificación , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticagrelor/administración & dosificación , Anciano , Anciano de 80 o más Años , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/fisiopatología , Estenosis de la Válvula Aórtica/sangre , Estenosis de la Válvula Aórtica/diagnóstico por imagen , Estenosis de la Válvula Aórtica/fisiopatología , Aspirina/efectos adversos , Plaquetas/metabolismo , Clopidogrel/efectos adversos , Resistencia a Medicamentos , Quimioterapia Combinada , Femenino , Humanos , Masculino , Persona de Mediana Edad , Proyectos Piloto , Inhibidores de Agregación Plaquetaria/efectos adversos , Estudios Prospectivos , Sistema de Registros , España , Ticagrelor/efectos adversos , Factores de Tiempo , Resultado del Tratamiento
16.
Sci Total Environ ; 624: 114-132, 2018 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-29248702

RESUMEN

The Cordillera de la Costa is located along the coastline of northern Chile, in the hyperarid Atacama Desert area. Chemical and isotopic analyses of several small coastal springs and groundwater reservoirs between 22.5 °S and 25.5 °S allow understanding groundwater origin, renewal time and the probable timing of recharge. The aquifers are mostly in old volcanic rocks and alluvial deposits. All spring waters are brackish, of the sodium chloride type due to intensive concentration of precipitation due aridity and for deep groundwater to additional water-rock interaction in slowly renewed groundwater and mixing with deep seated brines. The heavy δ18O and δ2H values in spring water are explained by recharge by the arrival of moist air masses from the Pacific Ocean and the originally lighter values in the deep wells can be associated to past recharge by air masses coming from the Atlantic Ocean. Current recharge is assumed almost nil but it was significant in past wetter-than-present periods, increasing groundwater reserves, which are not yet exhausted. To explain the observed chloride content and radiocarbon (14C) activity, a well-mixed (exponential) flow model has been considered for aquifer recharge. The average residence time of groundwater feeding the springs has been estimated between 1 and 2kyr, up to 5kyr and between 7 and 13kyr for deep well water, assuming that current recharge is much less than during the previous wetter period. The recharge period feeding the coastal springs could have been produced 1 to 5kyr BP, when the area was already inhabited, and recharge in the Michilla mine was produced during the 10 to 14.5kyr BP CAPE (Central Andean Pluvial Event) pluvial events of the central Andes. The approximate coincidence of turnover time with the past wet periods, as revealed by paleoclimate data, points to significant recharge during them.

17.
BMC Genomics ; 18(1): 768, 2017 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-29020939

RESUMEN

BACKGROUND: The impact of nutritional status and diet composition on mitochondrial oxidative phosphorylation (OXPHOS) in fish remains largely unknown. To identify biomarkers of interest in nutritional studies, herein we obtained a deep-coverage transcriptome by 454 pyrosequencing of liver and skeletal muscle cDNA normalised libraries from long-term starved gilthead sea bream (Sparus aurata) and fish fed different diets. RESULTS: After clean-up of high-throughput deep sequencing reads, 699,991 and 555,031 high-quality reads allowed de novo assembly of liver and skeletal muscle sequences, respectively (average length: 374 and 441 bp; total megabases: 262 and 245 Mbp). An additional incremental assembly was completed by integrating data from both tissues (hybrid assembly). Assembly of hybrid, liver and skeletal muscle transcriptomes yielded, respectively, 19,530, 11,545 and 10,599 isotigs (average length: 1330, 1208 and 1390 bp, respectively) that were grouped into 15,954, 10,033 and 9189 isogroups. Following annotation, hybrid transcriptomic data were used to construct an oligonucleotide microarray to analyse nutritional regulation of the expression of 129 genes involved in OXPHOS in S. aurata. Starvation upregulated cytochrome c oxidase components and other key OXPHOS genes in the liver, which exhibited higher sensitive to food deprivation than the skeletal muscle. However, diet composition affected OXPHOS in the skeletal muscle to a greater extent than in the liver: most of genes upregulated under starvation presented higher expression among fish fed a high carbohydrate/low protein diet. CONCLUSIONS: Our findings indicate that the expression of coenzyme Q-binding protein (COQ10), cytochrome c oxidase subunit 6A2 (COX6A2) and ADP/ATP translocase 3 (SLC25A6) in the liver, and cytochrome c oxidase subunit 5B isoform 1 (COX5B1) in the liver and the skeletal muscle, are sensitive markers of the nutritional condition that may be relevant to assess the effect of changes in the feeding regime and diet composition on fish farming.


Asunto(s)
Dieta , Perfilación de la Expresión Génica , Genes Mitocondriales/genética , Fosforilación Oxidativa , Dorada/genética , Inanición/genética , Animales , Ontología de Genes , Anotación de Secuencia Molecular , Factores de Tiempo
19.
Farm. comunitarios (Internet) ; 9(1): 14-27, mar. 2017. tab
Artículo en Español | IBECS | ID: ibc-161764

RESUMEN

Se ha elaborado la primera guía clínica española que permitirá a los farmacéuticos comunitarios y demás profesionales de la salud seleccionar, para cada indicación específica, el producto con probióticos adecuado, la dosis y la vía de administración. Con ello se pretende lograr que la práctica diaria de indicación farmacéutica de los suplementos probióticos esté basada en las mejores evidencias científicas disponibles


We have developed the first Spanish clinical guide that will allow the community pharmacists and other health care professionals easily select the right product with probiotics, dosage and format for each specific indication. With the proposed guide, it is our goal that the daily pharmaceutical practice of probiotics supplementation in community pharmacy is based on the best scientific evidence available (AU)


Asunto(s)
Humanos , Probióticos/administración & dosificación , Servicios Comunitarios de Farmacia/normas , Suplementos Dietéticos , Pautas de la Práctica en Medicina , Práctica Clínica Basada en la Evidencia/tendencias , Microbioma Gastrointestinal
20.
Gen Comp Endocrinol ; 240: 121-128, 2017 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-27725144

RESUMEN

Endocrine factors released from the central nervous system, gastrointestinal tract, adipose tissue and other peripheral organs mediate the regulation of food intake. Although many studies have evaluated the effect of fed-to-starved transition on the expression of appetite-related genes, little is known about how the expression of appetite-regulating peptides is regulated by the macronutrient composition of the diet. The aim of the present study was to examine the effect of diet composition and nutritional status on the expression of four peptides involved in food intake control in gilthead sea bream (Sparus aurata): neuropeptide Y (NPY), ghrelin, cholecystokinin (CCK) and leptin. Quantitative real-time RT-PCR showed that high protein/low carbohydrate diets stimulated the expression of CCK and ghrelin in the intestine and leptin in the adipose tissue, while downregulation of ghrelin and NPY mRNA levels was observed in the brain. Opposite effects were found for the expression of the four genes in fish fed low protein/high carbohydrate diets or after long-term starvation. Our findings indicate that the expression pattern of appetite-regulating peptides, particularly CCK and ghrelin, is modulated by the nutritional status and diet composition in S. aurata.


Asunto(s)
Colecistoquinina/genética , Dieta , Regulación de la Expresión Génica , Ghrelina/genética , Leptina/genética , Neuropéptido Y/genética , Dorada/genética , Animales , Composición Corporal , Peso Corporal , Colecistoquinina/metabolismo , Ghrelina/metabolismo , Leptina/metabolismo , Modelos Lineales , Neuropéptido Y/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Inanición/genética
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