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1.
Mol Cell ; 65(5): 900-916.e7, 2017 Mar 02.
Artículo en Inglés | MEDLINE | ID: mdl-28238654

RESUMEN

Protein post-translation modification plays an important role in regulating DNA repair; however, the role of arginine methylation in this process is poorly understood. Here we identify the arginine methyltransferase PRMT5 as a key regulator of homologous recombination (HR)-mediated double-strand break (DSB) repair, which is mediated through its ability to methylate RUVBL1, a cofactor of the TIP60 complex. We show that PRMT5 targets RUVBL1 for methylation at position R205, which facilitates TIP60-dependent mobilization of 53BP1 from DNA breaks, promoting HR. Mechanistically, we demonstrate that PRMT5-directed methylation of RUVBL1 is critically required for the acetyltransferase activity of TIP60, promoting histone H4K16 acetylation, which facilities 53BP1 displacement from DSBs. Interestingly, RUVBL1 methylation did not affect the ability of TIP60 to facilitate ATM activation. Taken together, our findings reveal the importance of PRMT5-mediated arginine methylation during DSB repair pathway choice through its ability to regulate acetylation-dependent control of 53BP1 localization.


Asunto(s)
Proteínas Portadoras/metabolismo , Roturas del ADN de Doble Cadena , ADN Helicasas/metabolismo , Histona Acetiltransferasas/metabolismo , Procesamiento Proteico-Postraduccional , Proteína-Arginina N-Metiltransferasas/metabolismo , Reparación del ADN por Recombinación , ATPasas Asociadas con Actividades Celulares Diversas , Acetilación , Animales , Arginina , Proteínas de la Ataxia Telangiectasia Mutada/metabolismo , Proteínas Portadoras/genética , ADN Helicasas/genética , Inestabilidad Genómica , Células HEK293 , Células HeLa , Histona Acetiltransferasas/genética , Histonas/metabolismo , Humanos , Lisina Acetiltransferasa 5 , Metilación , Ratones , Ratones Transgénicos , Proteína-Arginina N-Metiltransferasas/genética , Interferencia de ARN , Factores de Tiempo , Transfección , Proteína 1 de Unión al Supresor Tumoral P53/genética , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo
2.
Pacing Clin Electrophysiol ; 46(10): 1278-1286, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37695204

RESUMEN

BACKGROUND: Embolic cerebrovascular events that remain of unknown etiology after a thorough diagnostic evaluation, are known as Embolic Strokes of Undetermined Source (ESUS). Subclinical atrial fibrillation (AF) represents a significant underlying cause of ESUS. Our aims were to examine the overall diagnostic yield of a prolonged cardiac monitoring wearable system (PCMw) after an ESUS to detect AF and factors associated with it, including the time frame from the ESUS event to PCMw initiation. Additionally, to evaluate the frequency of unexpected arrhythmic events (UAE) and their prognostic implications. METHODS: We retrospectively analyzed 200 ECG recordings (3-leads, 30 days duration) by means of a PCMw in patients with an ESUS to detect AF lasting longer than 30 s, between 2017 and 2021. UAE were defined as arrhythmia events that were not correlated to the main reason of prolonged cardiac monitoring. RESULTS: AF was detected in 21 patients (10.5%). Patients with AF had more left atrial enlargement (OR = 4.22 [1.59-6.85]; p = .01) and atrial arrythmias in the initial 24-h Holter during hospitalization (OR = 5.73 [2.03-16.49]; p = .001). The detection of AF was significatively higher if the PCMw was worn within the first 30 days after the ESUS compared to beyond 30 days (17% vs. 10.3%; p = .002). Fifty three patients (26.5%) had UAE during PCMw. In six of them these findings led to targeted treatment. CONCLUSION: PCMw represents a feasible non-invasive device that could reliably detect subclinical AF episodes after an ESUS. Diagnostic yield was significatively higher when used within the first 30 days after the event, especially in selected patients. UAE were common, but did not impact prognosis.

3.
Molecules ; 28(18)2023 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-37764471

RESUMEN

Renewable hydrogen production by aqueous phase reforming (APR) over Ni/Al-Ca catalysts was studied using pure or refined crude glycerol as feedstock. The APR was carried out in a fixed bed reactor at 238 °C, 37 absolute bar for 3 h, using a solution of 5 wt.% of glycerol, obtaining gas and liquid products. The catalysts were prepared by the co-precipitation method, calcined at different temperatures, and characterized before and after their use by several techniques (XRD, ICP-OES, H2-TPR, NH3-TPD, CO2-TPD, FESEM, and N2-physisorption). Increasing the calcination temperature and adding Ca decreased the surface area from 256 to 188 m2/g, and its value after the APR changed depending on the feedstock used. The properties of the acid and basic sites of the catalysts influenced the H2 yield also depending on the feed used. The Ni crystallite was between 6 and 20 nm. In general, the incorporation of Ca into Ni-based catalysts and the increase of the calcination temperature improved H2 production, obtaining 188 mg H2/mol C fed during the APR of refined crude glycerol over Ni/AlCa-675 catalyst, which was calcined at 675 °C. This is a promising result from the point of view of enhancing the economic viability of biodiesel.

4.
Stroke ; 52(2): 552-562, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33406872

RESUMEN

BACKGROUND AND PURPOSE: The coronavirus disease 2019 (COVID-19) outbreak has added challenges to providing quality acute stroke care due to the reallocation of stroke resources to COVID-19. Case series suggest that patients with COVID-19 have more severe strokes; however, no large series have compared stroke outcomes with contemporary non-COVID-19 patients. Purpose was to analyze the impact of COVID-19 pandemic in stroke care and to evaluate stroke outcomes according to the diagnosis of COVID-19. METHODS: Retrospective multicenter cohort study including consecutive acute stroke patients admitted to 7 stroke centers from February 25 to April 25, 2020 (first 2 months of the COVID-19 outbreak in Madrid). The quality of stroke care was measured by the number of admissions, recanalization treatments, and time metrics. The primary outcome was death or dependence at discharge. RESULTS: A total of 550 acute stroke patients were admitted. A significant reduction in the number of admissions and secondary interhospital transfers was found. COVID-19 was confirmed in 105 (19.1%) patients, and a further 19 patients were managed as suspected COVID-19 (3.5%). No differences were found in the rates of reperfusion therapies in ischemic strokes (45.5% non-COVID-19, 35.7% confirmed COVID-19, and 40% suspected COVID-19; P=0.265). However, the COVID-19 group had longer median door-to-puncture time (110 versus 80 minutes), which was associated with the performance of chest computed tomography. Multivariate analysis confirmed poorer outcomes for confirmed or suspected COVID-19 (adjusted odds ratios, 2.05 [95% CI, 1.12-3.76] and 3.56 [95% CI, 1.15-11.05], respectively). CONCLUSIONS: This study confirms that patients with COVID-19 have more severe strokes and poorer outcomes despite similar acute management. A well-established stroke care network helps to diminish the impact of such an outbreak in stroke care, reducing secondary transfers and allowing maintenance of reperfusion therapies, with a minor impact on door-to-puncture times, which were longer in patients who underwent chest computed tomography.


Asunto(s)
COVID-19/epidemiología , Brotes de Enfermedades/prevención & control , SARS-CoV-2/patogenicidad , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/virología , Anciano , Anciano de 80 o más Años , COVID-19/complicaciones , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
5.
Eur J Neurol ; 28(12): 4078-4089, 2021 12.
Artículo en Inglés | MEDLINE | ID: mdl-34528353

RESUMEN

BACKGROUND AND PURPOSE: The experience gained during the first COVID-19 wave could have mitigated the negative impact on stroke care in the following waves. Our aims were to analyze the characteristics and outcomes of patients with stroke admitted during the second COVID-19 wave and to evaluate the differences in the stroke care provision compared with the first wave. METHODS: This retrospective multicenter cohort study included consecutive stroke patients admitted to any of the seven hospitals with stroke units (SUs) and endovascular treatment facilities in the Madrid Health Region. The characteristics of the stroke patients with or without a COVID-19 diagnosis were compared and the organizational changes in stroke care between the first wave (25 February to 25 April 2020) and second wave (21 July to 21 November 2020) were analyzed. RESULTS: A total of 550 and 1191 stroke patients were admitted during the first and second COVID-19 waves, respectively, with an average daily admission rate of nine patients in both waves. During the second wave, there was a decrease in stroke severity (median National Institutes of Health Stroke Scale 5 vs. 6; p = 0.000), in-hospital strokes (3% vs. 8.1%) and in-hospital mortality (9.9% vs. 15.9%). Furthermore, fewer patients experienced concurrent COVID-19 (6.8% vs. 19.1%), and they presented milder COVID-19 and less severe strokes. Fewer hospitals reported a reduction in the number of SU beds or deployment of SU personnel to COVID-19 dedicated wards during the second wave. CONCLUSIONS: During the second COVID-19 wave, fewer stroke patients were diagnosed with COVID-19, and they had less stroke severity and milder COVID-19.


Asunto(s)
COVID-19 , Accidente Cerebrovascular , Prueba de COVID-19 , Estudios de Cohortes , Humanos , Estudios Retrospectivos , SARS-CoV-2 , Accidente Cerebrovascular/epidemiología
6.
FASEB J ; 31(7): 2925-2936, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28360195

RESUMEN

Polo-like kinase 1 (PLK1) is a serine/threonine kinase involved in several stages of the cell cycle, including the entry and exit from mitosis, and cytokinesis. Furthermore, it has an essential role in the regulation of DNA replication. Together with cyclin A, PLK1 also promotes CDH1 phosphorylation to trigger its ubiquitination and degradation, allowing cell cycle progression. The PLK1 levels in different type of tumors are very high compared to normal tissues, which is consistent with its role in promoting proliferation. Therefore, several PLK1 inhibitors have been developed and tested for the treatment of cancer. Here, we further analyzed PLK1 degradation and found that cytoplasmic PLK1 is ubiquitinated and subsequently degraded by the SCFßTrCP/proteasome. This procedure is triggered when heat shock protein (HSP) 90 is inhibited with geldanamycin, which results in misfolding of PLK1. We also identified CDK1 as the major kinase involved in this degradation. Our work shows for the first time that HSP90 inhibition arrests cell cycle progression at the G1/S transition. This novel mechanism inhibits CDH1 degradation through CDK1-dependent PLK1 destruction by the SCFßTrCP/proteasome. In these conditions, CDH1 substrates do not accumulate and cell cycle arrests, providing a novel pathway for regulation of the cell cycle at the G1-to-S boundary.-Giráldez, S., Galindo-Moreno, M., Limón-Mortés, M. C., Rivas, A. C., Herrero-Ruiz, J., Mora-Santos, M., Sáez, C., Japón, M. Á., Tortolero, M., Romero, F. G1/S phase progression is regulated by PLK1 degradation through the CDK1/ßTrCP axis.


Asunto(s)
Proteína Quinasa CDC2/metabolismo , Proteínas de Ciclo Celular/metabolismo , Puntos de Control de la Fase G1 del Ciclo Celular/fisiología , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Puntos de Control de la Fase S del Ciclo Celular/fisiología , Proteínas con Repetición de beta-Transducina/metabolismo , Animales , Proteína Quinasa CDC2/genética , Proteínas de Ciclo Celular/genética , Línea Celular , Clonación Molecular , Regulación Enzimológica de la Expresión Génica/fisiología , Técnicas de Silenciamiento del Gen , Humanos , Plásmidos , Mutación Puntual , Proteínas Serina-Treonina Quinasas/genética , Proteínas Proto-Oncogénicas/genética , Técnicas del Sistema de Dos Híbridos , Proteínas con Repetición de beta-Transducina/genética , Quinasa Tipo Polo 1
7.
Bioengineering (Basel) ; 11(3)2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38534503

RESUMEN

Edentulism can generate negative impacts on self-esteem, interpersonal relationships, and oral functions. Removable prostheses are commonly used for tooth replacement, but they may cause discomfort due to micromovements during mastication. Objective and quantifiable methods are needed to evaluate these micromovements. A pilot study was conducted to determine the micromovements in removable prostheses during mastication using a 3D electromagnetic articulography (EMA-3D) system. One elderly participant wearing lower removable prostheses and an upper total well-fitting removable prosthesis was studied. The EMA-3D system was used to record movements in three spatial planes. Peanuts were given as test food, and the participant was instructed to chew normally while recordings were carried out until feeling the need to swallow. Analyses of the upper total prosthesis show micromovements ranging from 0.63 ± 0.11 to 1.02 ± 0.13 mm. During simultaneous analyses of the upper prosthesis and lower partial prosthesis, interference was not observed. This pilot study demonstrated the feasibility of using the EMA-3D system to evaluate micromovements in removable prostheses during mastication. Further research is needed to evaluate a larger sample and assess the clinical implications of these micromovements.

8.
Scand J Infect Dis ; 45(9): 664-71, 2013 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-23808723

RESUMEN

BACKGROUND: Coagulase-negative staphylococci (CoNS) are common contaminants in blood cultures (BC). A prospective study of patients with ≥ 2 blood culture sets and at least 1 positive CoNS BC was performed to develop an algorithm to assist in determining the clinical significance of CoNS bacteraemia. METHODS: A single reviewer examined the medical records of patients with CoNS bacteraemia (January-June 2010). The determination of clinical significance was made according to CDC/NHSN (US Centers for Disease Control and Prevention/National Healthcare Safety Network) criteria. To explore risk factors associated with clinical significance, a multivariate analysis was performed. The performances of various algorithms were then compared. An algorithm to assist in determining clinical significance was developed. RESULTS: Two hundred and sixty-nine cases were included; 97 (36%) were considered clinically significant bacteraemia (CSB). Predictors of CSB in the multivariate analysis were: time to positivity < 16 h (odds ratio (OR) 4.540, 95% confidence interval (CI) 1.734-11.884), identification of Staphylococcus epidermidis (OR 4.273, 95% CI 2.124-5.593), central venous catheter (OR 4.932, 95% CI 2.467-9.858), > 2 CoNS-positive bottles from different BC sets (OR 1.957, 95% CI 1.401-2.733), and Charlson score ≥ 3 (OR 2.102, 95% CI 1.078-4.099). The algorithm with best sensitivity (62%) and specificity (93%) for determining clinical significance of CoNS included Charlson score ≥ 3, Pitt score ≥ 1, neutropenic patients, presence of central venous catheter, identification of S. epidermidis, and time to positivity < 16 h. The positive predictive value was 83% and the negative predictive value was 81% (likelihood ratio 8.87). CONCLUSION: The use of this algorithm could potentially reduce the misclassification of nosocomial bloodstream infections and inappropriate antibiotic treatment in patients for whom a positive CoNS does not represent a CSB.


Asunto(s)
Bacteriemia/microbiología , Infecciones Estafilocócicas/microbiología , Staphylococcus epidermidis/aislamiento & purificación , Algoritmos , Análisis de Varianza , Bacteriemia/sangre , Bacteriemia/epidemiología , Femenino , Hospitalización , Humanos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Estudios Prospectivos , Factores de Riesgo , Índice de Severidad de la Enfermedad , España/epidemiología , Infecciones Estafilocócicas/sangre , Infecciones Estafilocócicas/epidemiología , Staphylococcus epidermidis/enzimología
9.
Scand J Infect Dis ; 45(8): 623-8, 2013 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-23596976

RESUMEN

OBJECTIVE: To evaluate the influence of a rapid diagnostic test (RDT) in antibiotic therapeutic decisions in non-paediatric patients with Gram-negative bacteraemia (GNB). PATIENTS AND METHODS: A RDT consisting of a direct antibiogram was used on blood isolates of GNB. GNB were also identified and sensitivity tests were performed according to standard criteria. Information on empirical treatment was registered (T1), as well as the antibiotic administered once the results of the RDT were available (T2). Finally, we noted the ideal antibiotic that the infectious diseases specialist (IDS) would have prescribed (T3). The decision regarding T2 was always taken by the patient's physician or the physician on duty. RESULTS: A RDT was performed for 248 patients. The most frequently isolated bacterium was Escherichia coli (13% producing extended-spectrum beta-lactamase). T1 was considered appropriate in 74% and appropriate but optimizable in 43%. T2 was considered appropriate in 95%, appropriate but optimizable in 36%, and inappropriate in 5%. The cost of the optimizable treatment (T2) was € 2210, while the cost of the ideal treatment would have been € 416; the saving in antibiotic cost of 1 day of treatment would have been € 1694. CONCLUSIONS: Treatment prescribed by a non-IDS after a RDT was inappropriate in 5% and optimizable in 36%. It is our recommendation that information provided by a RDT should be interpreted by an IDS to make the information more beneficial both economically and 'ecologically'.


Asunto(s)
Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacterias Gramnegativas/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/diagnóstico , Bacteriemia/microbiología , Sangre/microbiología , Niño , Femenino , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Estudios Prospectivos , Factores de Tiempo , Adulto Joven
10.
RSC Adv ; 13(8): 5483-5495, 2023 Feb 06.
Artículo en Inglés | MEDLINE | ID: mdl-36798615

RESUMEN

The present work studied the influence of the calcination temperature on the aqueous phase hydrogenolysis of glycerol with in situ generated hydrogen over a Ni/Al3Fe1 catalyst. The Ni/Al3Fe1 catalyst was synthesized by the co-precipitation method at 28 mol% of Ni (Ni/(Ni + Al + Fe)) and a molar ratio of Al/Fe of 3/1. The prepared catalyst was calcined at different temperatures (500-750 °C). The obtained samples were tested for the aqueous phase hydrogenolysis (APH) of glycerol and characterized by several analytical techniques (ICP-OES, H2-TPR, XRD, N2-physisorption, NH3-TPD, STEM, FESEM, and TGA). The catalyst calcined at 625 °C was selected as the best sample due to its high acidity, metal dispersion, and catalytic activity; 1,2-propanediol was the highest carbon selectivity product. In addition, it experienced lower metal leaching than the catalyst calcined at 500 °C.

11.
Int J Drug Policy ; 112: 103946, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36696869

RESUMEN

BACKGROUND: Adolescent substance use has been widely related to different individual, school, family and community factors. Yet, the number of studies with all these variables together in a model from an ecological perspective is still low, and they rarely used a longitudinal design. The aim of this study was to explore, from an ecological perspective, the prospective impact of different individual, school, family and neighbourhood factors on adolescent substance use. METHODS: This was a longitudinal study with a one-year follow up. There were 881 participants (Mage = 12.57; 48.1% females) at wave 1, of which 686 (Mage = 13.51; 51.8% females) were followed-up at wave 2. Validated questionnaires were used for data collection. RESULTS: Regression analyses showed that higher substance use was predicted by high family socio-economic status cross-sectionally and longitudinally, and it was related to low neighbourhood socio-economic status cross-sectionally only. Participants who disliked school and had a poor academic performance were more likely to use substances, both cross-sectionally and longitudinally. CONCLUSIONS: The inclusion of families in substance use prevention programmes could be a key component in these interventions. Moreover, promotion of a positive school climate could protect adolescents from using substances.


Asunto(s)
Trastornos Relacionados con Sustancias , Femenino , Humanos , Adolescente , Niño , Masculino , Estudios Longitudinales , Factores Protectores , Estudios Prospectivos , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/prevención & control , Encuestas y Cuestionarios
12.
Cell Death Differ ; 30(2): 488-499, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36477079

RESUMEN

Cisplatin and other platinum-based anticancer agents are among the most widely used chemotherapy drugs in the treatment of different types of cancer. However, it is common to find patients who respond well to treatment at first but later relapse due to the appearance of resistance to cisplatin. Among the mechanisms responsible for this phenomenon is the increase in DNA damage repair. Here, we elucidate the effect of cisplatin on the MRN (MRE11-RAD50-NBS1) DNA damage sensor complex. We found that the tumor suppressor FBXW7 is a key factor in controlling the turnover of the MRN complex by inducing its degradation through lysosomes. Inhibition of lysosomal enzymes allowed the detection of the association of FBXW7-dependent ubiquitylated MRN with LC3 and the autophagy adaptor p62/SQSTM1 and the localization of MRN in lysosomes. Furthermore, cisplatin-induced cell death increased MRN degradation, suggesting that this complex is one of the targets that favor cell death. These findings open the possibility of using the induction of the degradation of the MRN complex after genotoxic damage as a potential therapeutic strategy to eliminate tumor cells.


Asunto(s)
Cisplatino , Enzimas Reparadoras del ADN , Humanos , Cisplatino/farmacología , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína Homóloga de MRE11 , Enzimas Reparadoras del ADN/genética , Proteínas de Ciclo Celular/genética , Proteínas Nucleares/metabolismo , Proteínas de Unión al ADN/metabolismo , Ácido Anhídrido Hidrolasas/metabolismo
13.
Br J Pharmacol ; 180(4): 459-478, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36181002

RESUMEN

BACKGROUND AND PURPOSE: Reperfusion therapy is the standard of care for ischaemic stroke; however, there is a need to identify new therapeutic targets able to ameliorate cerebral damage. Neutrophil ß1 adrenoceptors (ß1AR) have been linked to neutrophil migration during exacerbated inflammation. Given the central role of neutrophils in cerebral damage during stroke, we hypothesize that ß1AR blockade will improve stroke outcomes. EXPERIMENTAL APPROACH: Rats were subjected to middle cerebral artery occlusion-reperfusion to evaluate the effect on stroke of the selective ß1AR blocker metoprolol (12.5 mg·kg-1 ) when injected i.v. 10 min before reperfusion. KEY RESULTS: Magnetic resonance imaging and histopathology analysis showed that pre-reperfusion i.v. metoprolol reduced infarct size. This effect was accompanied by reduced cytotoxic oedema at 24 h and vasogenic oedema at 7 days. Metoprolol-treated rats showed reduced brain neutrophil infiltration and those which infiltrated displayed a high proportion of anti-inflammatory phenotype (N2, YM1+ ). Additional inflammatory models demonstrated that metoprolol specifically blocked neutrophil migration via ß1AR and excluded a significant effect on the glia compartment. Consistently, metoprolol did not protect the brain in neutrophil-depleted rats upon stroke. In patients suffering an ischaemic stroke, ß1AR blockade by metoprolol reduced circulating neutrophil-platelet co-aggregates. CONCLUSIONS AND IMPLICATIONS: Our findings describe that ß1AR blockade ameliorates cerebral damage by targeting neutrophils, identifying a novel therapeutic target to improve outcomes in patients with stroke. This therapeutic strategy is in the earliest stages of the translational pathway and should be further explored.


Asunto(s)
Isquemia Encefálica , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Ratas , Animales , Metoprolol/farmacología , Metoprolol/uso terapéutico , Metoprolol/metabolismo , Neutrófilos/metabolismo , Enfermedades Neuroinflamatorias , Isquemia Encefálica/metabolismo , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular Isquémico/metabolismo , Receptores Adrenérgicos/metabolismo
14.
Stroke Res Treat ; 2023: 6655772, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38099264

RESUMEN

Introduction: The screening for atrial fibrillation (AF) scale (SAFE score) was recently developed to provide a prediction of the diagnosis of AF after an ischemic stroke. It includes 7 items: age ≥ 65 years, bronchopathy, thyroid disease, cortical location of stroke, intracranial large vessel occlusion, NT-ProBNP ≥250 pg/mL, and left atrial enlargement. In the internal validation, a good performance was obtained, with an AUC = 0.88 (95% CI 0.84-0.91) and sensitivity and specificity of 83% and 80%, respectively, for scores ≥ 5. The aim of this study is the external validation of the SAFE score in a multicenter cohort. Methods: A retrospective multicenter study, including consecutive patients with ischemic stroke or transient ischemic attack between 2020 and 2022 with at least 24 hours of cardiac monitoring. Patients with previous AF or AF diagnosed on admission ECG were excluded. Results: Overall, 395 patients were recruited for analysis. The SAFE score obtained an AUC = 0.822 (95% CI 0.778-0.866) with a sensitivity of 87.2%, a specificity of 65.4%, a positive predictive value of 44.1%, and a negative predictive value of 94.3% for a SAFE score ≥ 5, with no significant gender differences. Calibration analysis in the external cohort showed an absence of significant differences between the observed values and those predicted by the model (Hosmer-Lemeshow's test 0.089). Conclusions: The SAFE score showed adequate discriminative ability and calibration, so its external validation is justified. Further validations in other external cohorts or specific subpopulations of stroke patients might be required.

15.
J Biol Chem ; 286(34): 30047-56, 2011 Aug 26.
Artículo en Inglés | MEDLINE | ID: mdl-21757741

RESUMEN

PTTG1, also known as securin, is an inactivating partner of separase, the major effector for chromosome segregation during mitosis. At the metaphase-to-anaphase transition, securin is targeted for proteasomal destruction by the anaphase-promoting complex or cyclosome, allowing activation of separase. In addition, securin is overexpressed in metastatic or genomically instable tumors, suggesting a relevant role for securin in tumor progression. Stability of securin is regulated by phosphorylation; some phosphorylated forms are degraded out of mitosis, by the action of the SKP1-CUL1-F-box protein (SCF) complex. The kinases targeting securin for proteolysis have not been identified, and mechanistic insight into the cause of securin accumulation in human cancers is lacking. Here, we demonstrate that glycogen synthase kinase-3ß (GSK3ß) phosphorylates securin to promote its proteolysis via SCF(ßTrCP) E3 ubiquitin ligase. Importantly, a strong correlation between securin accumulation and GSK3ß inactivation was observed in breast cancer tissues, indicating that GSK3ß inactivation may account for securin accumulation in breast cancers.


Asunto(s)
Neoplasias de la Mama/metabolismo , Glucógeno Sintasa Quinasa 3/metabolismo , Mitosis , Proteínas de Neoplasias/metabolismo , Animales , Neoplasias de la Mama/genética , Células COS , Chlorocebus aethiops , Femenino , Glucógeno Sintasa Quinasa 3/genética , Glucógeno Sintasa Quinasa 3 beta , Células HeLa , Humanos , Proteínas de Neoplasias/genética , Fosforilación , Estabilidad Proteica , Proteínas Ligasas SKP Cullina F-box/genética , Proteínas Ligasas SKP Cullina F-box/metabolismo , Securina
16.
Biochem Cell Biol ; 90(3): 412-6, 2012 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-22397495

RESUMEN

Here, we determined the effect of bovine lactoferrin (bLF) on the minimum inhibitory concentration (MIC) of ampicillin and trimethoprim-sulfamethoxazole in Shigella . Using a microdilution method, the MIC was determined in the presence or absence of bovine lactoferrin (10 mg/mL) on 88 Shigella strains (56 Shigella flexneri , 15 Shigella boydii , 13 Shigella sonnei , and 4 Shigella dysenteriae ) previously isolated from peruvian children <2 years old. A fold change of 2 or more in MIC values was considered significant. For ampicillin, 67 (76%) strains were highly resistant; one-third of the strains (32%) showed a decrease in ampicillin MIC in the presence of LF. This was more typical of MIC values in less resistant strains. For 7 (8%) ampicillin-resistant strains, the decrease in the MIC resulted in the strains reaching the cutoff for susceptible in the presence of bLF. For trimethoprim-sulfamethoxazole, 93% of the isolates (n = 82) were highly resistant and only 4 isolates (5%) decreased their MIC in the presence of bLF. None of the trimethoprim-sulfamethoxazole resistant strains became susceptible in the presence of LF. The decrease in the MIC in the presence of bLF seems to depend on the mechanisms of action of each antibiotic. In vivo studies are needed to further evaluate bLF as a coadjuvant to antibiotic treatment of resistant Shigella.


Asunto(s)
Ampicilina/farmacología , Antibacterianos/farmacología , Lactoferrina/farmacología , Shigella/efectos de los fármacos , Combinación Trimetoprim y Sulfametoxazol/farmacología , Animales , Bovinos , Farmacorresistencia Bacteriana , Quimioterapia Combinada , Pruebas de Sensibilidad Microbiana , Shigella/crecimiento & desarrollo
17.
Int J Ment Health Addict ; : 1-12, 2022 Jan 13.
Artículo en Inglés | MEDLINE | ID: mdl-35043047

RESUMEN

Prevalence rates of compliance with anti-COVID measures have been widely studied, but little is known about this issue in early adolescence. Moreover, the relation between substance use and compliance with anti-COVID regulations is still unexplored. Thus, this study aimed to determine the level of compliance with anti-COVID measures by adolescents and the link between substance use and compliance with anti-COVID regulations. This was a cross-sectional study including 909 participants (M age = 12.57; SD = 0.81). The most complied measure was mask-wearing, followed by avoiding hug/kiss friends and, finally, social distancing. All substance use negatively correlated with compliance with measures. However, strong alcohol and tobacco were the only substances significantly related to less compliance of anti-COVID measures after controlling for covariates. These results provide evidence about the relation between substance use and compliance with anti-COVID measures. Strategies addressed to decrease substance use could be effective to reduce behaviours associated with coronavirus transmission.

18.
Sci Total Environ ; 846: 157395, 2022 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-35843337

RESUMEN

Biogas generation through anaerobic digestion provides an interesting opportunity to valorize some types of animal waste materials whose management is increasingly complicated by legal and environmental restrictions. To successfully expand anaerobic digestion in livestock areas, operational issues such as digestate management must be addressed in an economical and environmentally sustainable way. Biogas upgrading is another necessary stage before intending it to add-value applications. The high concentration of CO2 in biogas results in a reduced caloric value, so the removal of CO2 would be beneficial for most end-users. The current work evaluates the CO2 uptake properties (thermogravimetry study) of low-cost adsorbent materials produced from the animal wastes generated in the livestock area itself, specifically via pyrolysis of poorly biodegradable materials, such as meat and bone meal, and the digestate from manure anaerobic digestion. Therefore, the new element in this study with respect to other studies found in the literature related to biochar-based CO2 adsorption performance is the presence of high content of pyrolyzed proteins in the adsorbent material. In this work, pyrolyzed chars from both meat and bone meal and co-digested manure have been proven to adsorb CO2 reversibly, and also the chars produced from their representative pure proteins (collagen and soybean protein), which were evaluated as model compounds for a better understanding of the individual performance of proteins. The ultra-microporosity developed in the protein chars during pyrolysis seems to be the main explanation for such CO2 uptake capacities, while neither the BET surface area nor N-functionalities on the char surface can properly explain the observed results. Although the CO2 adsorption capacities of these pristine chars (6-41.0 mg CO2/g char) are far away from data of commercially activated carbons (~80 mg CO2/g char), this application opens a new via to integrate and valorize these wastes in the circular economy of the primary sector.


Asunto(s)
Dióxido de Carbono , Pirólisis , Adsorción , Animales , Biocombustibles , Carbón Orgánico , Ganado , Estiércol
19.
BMC Fam Pract ; 12: 125, 2011 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-22054017

RESUMEN

BACKGROUND: The non-pharmacological approach to cholesterol control in patients with hyperlipidemia is based on the promotion of a healthy diet and physical activity. Thus, to help patients change their habits, it is essential to identify the most effective approach. Many efforts have been devoted to explain changes in or adherence to specific health behaviors. Such efforts have resulted in the development of theories that have been applied in prevention campaigns, and that include brief advice and counseling services. Within this context, Motivational Interviewing has proven to be effective in changing health behaviors in specific cases. However, more robust evidence is needed on the effectiveness of Motivational Interviewing in treating chronic pathologies -such as dyslipidemia- in patients assisted by general practitioners. This article describes a protocol to assess the effectiveness of MI as compared with general practice (brief advice), with the aim of improving lipid level control in patients with dyslipidemia assisted by a general practitioner. METHODS/DESIGN: An open, two-arm parallel, multicentre, cluster, controlled, randomized, clinical trial will be performed. A total of 48-50 general practitioners from 35 public primary care centers in Spain will be randomized and will recruit 436 patients with dyslipidemia. They will perform an intervention based either on Motivational Interviewing or on the usual brief advice. After an initial assessment, follow-ups will be performed at 2, 4, 8 and 12 months. Primary outcomes are lipid levels (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and cardiovascular risk. The study will assess the degree of dietary and physical activity improvement, weight loss in overweight patients, and adherence to treatment guidelines. DISCUSSION: Motivational interview skills constitute the primary strategies GPs use to treat their patients. Having economical, simple, effective and applicable techniques is essential for primary care professionals to help their patients change their lifestyle and improve their health. This study will provide scientific evidence on the effectiveness of Motivational interviewing, and will be performed under strict control over the data collected, ensuring the maintenance of therapeutic integrity. TRIALS REGISTRATION: ClinicalTrials.gov (NCT01282190).


Asunto(s)
Dislipidemias/terapia , Medicina General , Entrevistas como Asunto/métodos , Motivación , Adulto , Anciano , Colesterol/sangre , Dislipidemias/sangre , Dislipidemias/tratamiento farmacológico , Femenino , Humanos , Hipolipemiantes/uso terapéutico , Masculino , Persona de Mediana Edad , Encuestas y Cuestionarios , Triglicéridos/sangre
20.
Int J Clin Health Psychol ; 21(3): 100251, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34527057

RESUMEN

Substance use is one of the main risks for adolescent health. Many research projects have studied longitudinal patterns of use and risk/protective factors, but the number of studies focused on within-individual stability and change is low. The objective of this study was to discover specific longitudinal profiles of drug use and explore the role of social and emotional competencies, and empathy as possible protective factors against substance use. Method: This was a longitudinal study with 879 students (9-17 years at wave 1, 10-18 at wave 2). Substance use, social and emotional competencies, and empathy were measured with a survey. Results: Nine longitudinal profiles of substance use were found in this sample. Multinomial regression analysis found that low responsible decision making, self-management and affective empathy predicted the profiles of ascending user, chronic user and experiencer, respectively. Experiencer was also predicted by a low level of social awareness. Conclusions: The trend to a higher use over time can increase the odds of addiction in future. Some personal variables were found as protective factors against drug use. Thus, school interventions addressed to promote social and emotional competencies, and empathy seem necessary in order to decrease the adolescent drug use.


El consumo de sustancias es uno de los mayores riesgos para la salud de los adolescentes. Numerosas investigaciones han estudiado el patrón longitudinal de consumo y factores de riesgo/protección, pero pocas han estudiado la estabilidad y el cambio a nivel intraindividual. El objetivo de este estudio fue descubrir patrones longitudinales específicos de consumo de drogas y explorar el papel de las competencias sociales y emocionales, y la empatía como posibles factores protectores. Método: Un estudio longitudinal con 879 participantes (9-17 años en tiempo 1; 10-18 en tiempo 2). El consumo de sustancias, las competencias socioemocionales y la empatía se midieron con una encuesta. Resultados: Se encontraron nueve perfiles longitudinales de consumo. Los análisis de regresión encontraron que baja toma de decisiones responsables, autocontrol y empatía afectiva predijeron los perfiles de consumidor ascendente, consumidor crónico y experimentador, respectivamente. Experimentador también fue predicho por bajos niveles de conciencia social. Conclusiones: La tendencia a aumentar el consumo a través del tiempo puede incrementar el riesgo de adicción en el futuro. Algunas variables personales actúan como factores de protección. Por ello, parecen necesarias intervenciones escolares dirigidas a promocionar las competencias sociales y emocionales, y la empatía para disminuir el consumo de sustancias.

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