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Arbuscular mycorrhizal (AM) fungi improve plant growth, nutrition, fitness and stress tolerance while AM fungi obtain carbohydrates and lipids from the host. This whole process of mutual benefit requires substantial alterations in the structural and functional aspects of the host root cells. These modifications ultimately culminate in the formation of arbuscules, which are specialized intraradical and highly branched fungal structures. Arbuscule-containing cells undergo massive reprogramming to hosting arbuscule and members of the GRAS transcription factor family have been characterized as AM inducible genes which play a pivotal role in these process. Here, we show a functional analysis for the GRAS transcription factor SCL3/SlGRAS18 in tomato. SlGRAS18 interacts with SlDELLA, a central regulator of AM formation. Silencing of SlGRAS18 positively impacts arbuscule development and the improvement in symbiotic status, favouring flowering and therefore progress in the formation and development of fruits in SlGRAS18 silenced plants which parallel to a discernible pattern of mineral nutrient redistribution in leaves. Our results advance the knowledge of GRAS transcription factors involved in the formation and establishment of AM symbiosis and provide experimental evidence for how specific genetic alterations can lead to more effective AM symbiosis.
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Video game addiction among adolescents, particularly those with ADHD, is a significant concern. To gather more insights into video game usage patterns in this population, we investigated levels of potentially problematic use, passion, motivations, and emotional/behavioral symptoms in adolescents with and without ADHD. Our cross-sectional, multicenter study involved 2513 subjects (Age M = 15.07; SD = 2.82) from 24 schools in Galicia (Spain), including 158 (6.3%) diagnosed with ADHD. We employed an ad hoc questionnaire covering sociodemographic data and ADHD diagnosis, the Questionnaire of Experiences Associated with Video Games (CERV), the scale of passion for video games, reasons for playing video games Questionaire (VMQ), and emotional/behavioral problems assessment (SDQ). Results indicated heightened vulnerability in adolescents with ADHD, manifesting in longer usage durations and higher problematic use scores. Interestingly, ADHD medication did not affect internet gaming disorder development. Motivations for gaming differed between groups, with the ADHD cohort showing distinctions in cognitive development, coping, and violent reward. Additionally, the ADHD group exhibited greater emotional/behavioral symptoms, hyperactivity, and reduced prosocial behavior.
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Taiwaniaquinoids are a unique family of diterpenoids predominantly isolated from Taiwania cryptomerioides Hayata. Previously, we evaluated the antiproliferative effect of several synthetic taiwaniaquinoids against human lung (A-549), colon (T-84), and breast (MCF-7) tumor cell lines. Herein, we report the in vitro and in vivo antitumor activity of the most potent compounds. Their cytotoxic activity against healthy peripheral blood mononuclear cells (PBMCs) has also been examined. We underscore the limited toxicity of compound C36 in PBMCs and demonstrate that it exerts its antitumor effect in MCF-7 cells (IC50 = 1.8 µM) by triggering an increase in reactive oxygen species, increasing the cell population in the sub-G1 phase of the cell cycle (90 %), and ultimately activating apoptotic (49.6 %) rather than autophagic processes. Western blot results suggested that the underlying mechanism of the C36 apoptotic effects was linked to caspase 9 activation and a rise in the Bax/Bcl-2 ratio. In vivo analyses showed normal behavior and hematological parameters in C57BL/6 mice post C36 treatment. Moreover, no significant impact was observed on the biochemical parameters of these animals, indicating that C36 did not induce liver toxicity. Furthermore, C36 demonstrated a significant reduction in tumor growth in immune-competent C57BL/6 mice implanted with E0771 mouse mammary tumor cells, effectively improving survival rates. These findings position taiwaniaquinoids, particularly compound C36, as promising therapeutic candidates for human breast cancer.
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Antineoplásicos , Neoplasias de la Mama , Animales , Humanos , Ratones , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Leucocitos Mononucleares/metabolismo , Apoptosis , Ensayos de Selección de Medicamentos Antitumorales , Ratones Endogámicos C57BL , Línea Celular Tumoral , Células MCF-7 , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Proliferación CelularRESUMEN
PURPOSE: Tamoxifen is a drug used for hormone receptor-positive breast cancers, primarily metabolised by the CYP2D6 enzyme into active metabolites such as endoxifen. CYP2D6 displays varying degrees of activity depending on its genotype. This study aims to analyse the effect of an early increase in tamoxifen dose in poor metabolisers (PM) on survival. METHODS: We enrolled 220 patients diagnosed with breast cancer who were treated with tamoxifen. CYP2D6 polymorphisms were determined, and the phenotype was estimated according to the Clinical Pharmacogenetics Implementation Consortium. Disease-free survival (DFS) and overall survival (OS) were analysed considering the entire patient group, and a subgroup of 110 patients selected by Propensity Score Matching (PSM). All women were treated with 20 mg/day of tamoxifen for 5 years, except PM, who initially received 20 mg/day for 4 months, followed by 40 mg/day for 4 months and 60 mg/day for 4 months before returning to the standard dose of 20 mg/day until completing 5 years of treatment. RESULTS: The analysis of the influence of CYP2D6 polymorphisms in the complete group and in the PSM subgroup revealed no significant differences for DFS or OS. Furthermore, DFS and OS were analysed in relation to various covariates such as age, histological grade, nodal status, tumour size, HER-2, Ki-67, chemotherapy, and radiotherapy. Only age, histological grade, nodal status, and chemotherapy treatment demonstrated statistical significance. CONCLUSION: An early increase in tamoxifen dose in PM patients is not associated with survival differences among CYP2D6 phenotypes.
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Neoplasias de la Mama , Femenino , Humanos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Citocromo P-450 CYP2D6/genética , Puntaje de Propensión , Antineoplásicos Hormonales/uso terapéutico , Resultado del Tratamiento , Tamoxifeno/uso terapéutico , GenotipoRESUMEN
PURPOSE: Ascending aorta (AAo) acute pathology still has an open-surgery indication with a high mortality rate associated to cardiopulmonary bypass and circulatory arrest. In these cases, the endovascular aortic approach could be an excellent option. The aim of the present study is to detail an optimized technique for the endovascular treatment of AAo diseases, based on thoracic endovascular aortic repair (TEVAR) and transcatheter aortic valve implantation (TAVI) procedures. TECHNIQUE: The procedure implies the usual preparation for TEVAR and TAVI implants. A transient pacemaker lead is necessary to deliver the prosthesis under "rapid pacing." As in the TAVI technique, a final high-support guidewire is placed at the left ventricle. The proximal landing zone is the sinotubular junction (zone 0B). Transesophageal echocardiography is essential to ensure aortic valve function and patency in coronary arteries during the delivery. To assess a potential occlusion of the brachiocephalic artery, a guidewire is positioned in the descending aorta from the axillary artery. Finally, a noncovered stent is implanted to stabilize the AAo prosthesis. CONCLUSION: The technique presented here can standardize a safe and reproducible procedure to endovascular repair of AAo diseases. However, new devices specifically designed for the AAo could facilitate the transcatheter approach. CLINICAL IMPACT: Ascending aorta acute pathology still has an open-surgery indication with high mortality rate associated to cardiopulmonary bypass and circulatory arrest. Moreover, near 30% of patients are not considered suitable for surgery because of age, critical situation or the presence of severe comorbidities. The present study provides a detailed and optimized technique for the endovascular treatment of ascending aorta disease, based on TEVAR and TAVI procedures.
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For the establishment of the Arbuscular Mycorrhiza (AM) symbiosis it is essential that epidermis and cortical cells from plant roots suffer a strong reorganization to allow the penetration of intracellular fungal hyphae. In the same manner, the new formation of a periarbuscular membrane and a symbiotic interface with specific compositions are required for a functional symbiosis. It is believed that the cytoskeleton of the plant host plays an essential role in these processes, particularly the microtubule (MT) cytoskeleton, as huge modifications have been observed in the MT array of root cells accompanying the establishment of the AM symbiosis. Recent research has established a link between microtubule rearrangements and arbuscule functioning. However, further research is required to elucidate the specific functions of MT cytoskeleton along the different stages of the arbuscule life cycle and to unravel the signals triggering these changes.
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Micorrizas , Micorrizas/metabolismo , Raíces de Plantas/metabolismo , Proteínas de Plantas/metabolismo , Simbiosis , Microtúbulos/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
BACKGROUND: Early identification of patients with COVID-19 who may develop critical illness is of great importance. METHODS: In this study a retrospective cohort of 264 COVID-19 cases admitted at Macarena University was used for development and internal validation of a risk score to predict the occurrence of critical illness in hospitalized patients with COVID-19. Backward stepwise logistic regression was used to derive the model, including clinical and laboratory variables predictive of critical illness. Internal validation of the final model used bootstrapped samples and the model scoring derived from the coefficients. External validation was performed in a cohort of 154 cases admitted at Valme and Virgen del Rocio University Hospital. RESULTS: A total of 62 (23.5%) patients developed a critical illness during their hospitalization stay, 21 (8.0%) patients needed invasive ventilation, 34 (12.9%) were admitted at the ICU and the overall mortality was of 14.8% (39 cases). 5 variables were included in the final model: age >59.5 years (OR: 3.11;95%CI 1.39-6.97), abnormal CRP results (OR: 5.76;95%CI 2.32-14.30), abnormal lymphocytes count (OR: 3.252;95%CI 1.56-6.77), abnormal CK results (OR: 3.38;95%CI 1.59-7.20) and abnormal creatinine (OR: 3.30;95%CI 1.42-7.68). The AUC of this model was 0.850 with sensitivity of 65% and specificity of 87% and the IDI and NRI were 0.1744 and 0.2785, respectively. The validation indicated a good discrimination for the external population. CONCLUSIONS: Biomarkers add prognostic information in COVID-19 patients. Our risk-score provides an easy to use tool to identify patients who are likely to develop critical illness during their hospital stay.
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Biomarcadores/sangre , COVID-19/etiología , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , COVID-19/mortalidad , COVID-19/terapia , Creatina Quinasa/sangre , Creatinina/sangre , Enfermedad Crítica , Femenino , Hospitalización , Humanos , Laboratorios , Recuento de Linfocitos , Masculino , Persona de Mediana Edad , Respiración Artificial , Estudios Retrospectivos , Medición de Riesgo , Sensibilidad y Especificidad , Adulto JovenRESUMEN
BACKGROUND: Trastuzumab is a drug used in HER2-positive breast cancer that increases patient survival. Due to cardiotoxicity is the most important side effect of trastuzumab treatment, cardiac monitoring should be a priority. The purpose of this study is to evaluate plasma NT-proBNP level and major cardiovascular risk factors as possible early predictors of trastuzumab-induced cardiotoxicity in HER2-positive breast cancer patients. METHODS: We conducted a retrospective observational study involving 66 patients with HER2-positive breast cancer treated with trastuzumab. Left ventricle ejection fraction (LVEF), NT-proBNP values, and the history of cardiovascular risk factors were collected. Cardiotoxicity was diagnosed considering a decrease of the LVEF from baseline or clinical manifestation of congestive heart failure. NT-proBNP cut-off points were considered to establish normal or abnormal values according to patient age. RESULTS: 27.3% of the patients suffered cardiotoxicity during trastuzumab treatment. Most cases were diagnosed due to the appearance of cardiac symptomatology (66.7%). Logistic regression analysis showed a significant association of diabetes mellitus (OR 5.9, 95% CI 1.2-28.5, p = 0.028) and high NT-proBNP levels (OR 22.0, 95% CI 5.7-85.4, p < 0.0001) with the development of trastuzumab-induced cardiotoxicity. CONCLUSION: NT-proBNP levels above the upper limit of the normal range adjusted to age or diabetes mellitus seem to be associated with a higher risk of developing cardiotoxicity. However, some limitations of the present study make necessary further studies aimed to clarify whether NT-proBNP and diabetes-associated markers determinations can be useful in the monitoring of cardiotoxicity risk in breast cancer patients undergoing trastuzumab therapy.
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Antineoplásicos/efectos adversos , Neoplasias de la Mama/tratamiento farmacológico , Insuficiencia Cardíaca/diagnóstico , Péptido Natriurético Encefálico/sangre , Fragmentos de Péptidos/sangre , Trastuzumab/efectos adversos , Adulto , Anciano , Biomarcadores Farmacológicos/análisis , Neoplasias de la Mama/sangre , Cardiotoxicidad/diagnóstico , Diabetes Mellitus/sangre , Monitoreo de Drogas , Femenino , Factores de Riesgo de Enfermedad Cardiaca , Insuficiencia Cardíaca/inducido químicamente , Humanos , Modelos Logísticos , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Volumen Sistólico/efectos de los fármacos , Función Ventricular Izquierda/efectos de los fármacosRESUMEN
BACKGROUND: The coexistence of other comorbidities confers poor outcomes in patients with acute heart failure. Our aim was to determine the characteristics of patients with acute heart failure and cardiorenal anaemia syndrome and the relationship between renal dysfunction and anaemia, alone or combined as cardiorenal anaemia syndrome, on short-term outcomes. METHODS: We analysed the Epidemiology of Acute Heart Failure in Emergency Departments registry (cohort of patients with acute heart failure in Spanish emergency departments). Renal dysfunction was defined by an estimated glomerular filtration rate <60 ml/min/m2, anaemia by haemoglobin values <12/<13 g/dl in women/men, and cardiorenal anaemia syndrome as the presence of both. Comparisons were made according to cardiorenal-anaemia syndrome positive (CRAS+) with respect to the rest of patients (CRAS-) and according the presence of renal dysfunction (RD+) and anaemia (A+), (alone, RD+/A-, RD-/A+) or in combination (RD+/A+; i.e. CRAS+) with respect to patients without renal dysfunction and anaemia (RD-/A-). The primary outcome was 30-day mortality, and the secondary outcomes were need for admission, prolonged hospitalisation (>10 days), in-hospital mortality during the index event, and reconsultation and the combination of 30-day post-discharge reconsultation/death. These short-term outcomes were compared and adjusted for differences among groups. RESULTS: Of the 13,307 patients analysed, CRAS+ (36.4%) was associated with older age, multiple comorbidities, chronic use of loop diuretics, oedemas and hypotension. The 30-day mortality in CRAS+ was greater than in CRAS- (hazard ratio = 1.46, 95% confidence interval = 1.26-1.68) and RD-/A- (hazard ratio = 1.83, 95% confidence interval = 1.46-2.28) control groups. The mortality level was also higher in RD+/A- (hazard ratio = 1.40, 95% confidence interval = 1.10-1.78) and higher, but not statistically significant, in RD-/A+ (hazard ratio = 1.28, 95% confidence interval = 0.99-1.63) with respect to RD-/A-. All of the secondary outcomes, when related to CRAS- and RD-/A- control groups, were worse for CRAS+ and to a lesser extent, RD+/A-, being more rarely observed in RD-/A+. CONCLUSIONS: Cardiorenal anaemia syndrome in acute heart failure is related to greater mortality and worse short-term outcomes, and the impact of renal dysfunction and anaemia seems to be additive.
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Anemia/complicaciones , Síndrome Cardiorrenal/complicaciones , Servicio de Urgencia en Hospital/estadística & datos numéricos , Insuficiencia Cardíaca/complicaciones , Sistema de Registros , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Síndrome Cardiorrenal/fisiopatología , Causas de Muerte/tendencias , Femenino , Estudios de Seguimiento , Tasa de Filtración Glomerular , Insuficiencia Cardíaca/mortalidad , Humanos , Masculino , Pronóstico , Estudios Prospectivos , España/epidemiología , Tasa de Supervivencia/tendenciasRESUMEN
Ralstonia solanacearum is a devastating soil borne vascular pathogen that can infect a large range of plant species, causing an important threat to agriculture. However, the Ralstonia model is considerably underexplored in comparison to other models involving bacterial plant pathogens, such as Pseudomonas syringae in Arabidopsis. Research targeted to understanding the interaction between Ralstonia and crop plants is essential to develop sustainable solutions to fight against bacterial wilt disease but is currently hindered by the lack of straightforward experimental assays to characterize the different components of the interaction in native host plants. In this scenario, we have developed a method to perform genetic analysis of Ralstonia infection of tomato, a natural host of Ralstonia. This method is based on Agrobacterium rhizogenes-mediated transformation of tomato roots, followed by Ralstonia soil-drenching inoculation of the resulting plants, containing transformed roots expressing the construct of interest. The versatility of the root transformation assay allows performing either gene overexpression or gene silencing mediated by RNAi. As a proof of concept, we used this method to show that RNAi-mediated silencing of SlCESA6 in tomato roots conferred resistance to Ralstonia. Here, we describe this method in detail, enabling genetic approaches to understand bacterial wilt disease in a relatively short time and with small requirements of equipment and plant growth space.
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Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Raíces de Plantas/microbiología , Ralstonia solanacearum/fisiología , Solanum lycopersicum/genética , Solanum lycopersicum/microbiología , Transformación Genética , Agrobacterium/metabolismo , Antibacterianos/farmacología , Arabidopsis/microbiología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Silenciador del Gen/efectos de los fármacos , Solanum lycopersicum/efectos de los fármacos , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Ralstonia solanacearum/efectos de los fármacos , Ralstonia solanacearum/crecimiento & desarrollo , Reproducibilidad de los Resultados , Suelo , Transformación Genética/efectos de los fármacosRESUMEN
OBJECTIVE: To investigate whether patients with an acute heart failure (AHF) episode triggered by infection present different outcomes compared to patients with no trigger and the effects of early antibiotic administration (EAA) and hospitalisation. METHODS: Two groups were made according to the AHF trigger: infection (G1) or none identified (G2). The primary outcome was 13-week (91-days) all-cause mortality, and secondary outcomes were 13-week post-discharge mortality, readmission or combined endpoint. Comparisons are presented as unadjusted and adjusted (MEESSI risk score) hazard ratios (uHR/aHR) for G1 compared to G2 patients, also estimated by weeks. Stratified analysis by EAA (provided/not provided) and patient disposition (discharged/hospitalised) was performed. RESULTS: We included 6727 patients (G1 = 3973; G2 = 2754). The 13-week mortality uHR was 1.11 (0.99-1.25; p = 0.06; with significant increases in the first 3 weeks), and the aHR was 0.91 (0.81-1.02; p = 0.11). There were no differences in unadjusted secondary post-discharge outcomes; however, G1 outcomes significantly improved after adjustment: aHR 0.83 (0.71-0.96; p = 0.01) for mortality, 0.92 (0.84-0.99; p = 0.04) for readmission, and 0.92 (0.85-0.99; p = 0.04) for the combined endpoint. We found a differentiated effect of hospitalisation (p < 0.05 for interaction; better post-discharge readmission and combined outcomes in G1), and a trend (p = 0.06) to lower mortality in G1 patients with EAA. Additionally, there were some differences between groups in baseline and acute episode characteristics. CONCLUSION: AHF triggered by infection is not associated with a higher mid-term mortality and has better post-discharge outcomes; however, the first 3 weeks are an extremely vulnerable period. Since hospitalisation could have a role in limiting adverse post-discharge events, and EAA in reducing mortality, these relationships should be prospectively explored in further studies.
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Antibacterianos/administración & dosificación , Insuficiencia Cardíaca/etiología , Hospitalización/estadística & datos numéricos , Infecciones/complicaciones , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Femenino , Insuficiencia Cardíaca/mortalidad , Humanos , Infecciones/tratamiento farmacológico , Masculino , Alta del Paciente , Readmisión del Paciente/estadística & datos numéricos , Sistema de Registros , Factores de TiempoRESUMEN
OBJECTIVES: This study investigated whether systemic corticosteroids (new onset) administered to patients with acute heart failure (AHF) have any association with outcomes, with differentiated analyses for patients with and without chronic obstructive pulmonary disease (COPD) as a comorbidity. BACKGROUND: Patients with undiagnosed dyspnea frequently receive corticosteroids in emergency departments while determining a final diagnosis, but their effect on the outcomes of patients with AHF without overt COPD exacerbation is unknown. METHODS: We selected patients with AHF from the EAHFE (Epidemiology of Acute Heart Failure in the Emergency Departments) registry, recording key data (new-onset corticosteroid therapy, COPD condition). Patients with and without COPD were analyzed separately. We calculated unadjusted and adjusted ratios for corticosteroid-treated compared with corticosteroid-untreated patients for 2 coprimary endpoints: 90-day all-cause mortality (from index episode) and 90-day post-discharge combined endpoint (all-cause mortality or readmission for AHF), with intermediate time-point estimations. Other secondary endpoints were calculated, and some sensitive and stratified analyses were performed. RESULTS: We analyzed 11,356 patients: 8,635 without COPD (841 corticosteroid-treated, 9.7%) and 2,721 with COPD (753 corticosteroid-treated, 27.7%). There were several differences between treated and untreated patients, essentially because corticosteroid-treated patients were sicker. Although unadjusted outcomes were worse in corticosteroid-treated patients, especially in patients without COPD, these differences disappeared after adjustment: hazard ratios for 90-day mortality (without/with COPD) were 0.91 (95% confidence interval (CI): 0.76 to 1.10)/0.99 (95% CI: 0.78 to 1.26), and 1.09 (95% CI: 0.93 to 1.28)/1.02 (95% CI: 0.86 to 1.21) for the post-discharge combined endpoint. Analyses of intermediate time-point coprimary endpoints and secondary outcomes rendered similar estimations. Sensitivity and stratified analysis did not significantly modify these results. CONCLUSIONS: There is no evidence of harm related to the new onset of systemic corticosteroid therapy during an episode of AHF, either in patients with or without concomitant COPD.
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Corticoesteroides/uso terapéutico , Broncodilatadores/uso terapéutico , Disnea/terapia , Insuficiencia Cardíaca/tratamiento farmacológico , Mortalidad Hospitalaria , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Diuréticos/uso terapéutico , Disnea/etiología , Intervención Médica Temprana , Servicio de Urgencia en Hospital , Femenino , Insuficiencia Cardíaca/complicaciones , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Mortalidad , Readmisión del Paciente , Pronóstico , Modelos de Riesgos Proporcionales , Enfermedad Pulmonar Obstructiva Crónica/complicacionesRESUMEN
OBJECTIVES: The decision about whether to use a biological or a mechanical prosthesis for aortic valve replacement remains controversial in patients between 50 and 65 years of age and has yet to be addressed in a Mediterranean population. This research aimed to analyse long-term survival and major morbidity rates (30-day mortality, stroke, any prosthetic reoperation and major bleeding) within this population. METHODS: Our multicentre observational retrospective study included all subjects aged 50-65 years who had a primary isolated aortic valve replacement due to severe aortic stenosis at 7 public hospitals from Andalusia (Spain) between 2000 and 2015. Concomitant surgery, reoperations and endocarditis were the exclusion criteria. A total of 1443 patients were enrolled in the study (272 with biological and 1171 with mechanical valves). Multivariate analyses including a 2:1 propensity score matching (506 mechanical and 257 biological prostheses) were conducted. RESULTS: Bioprostheses were implanted in 18.8% (n = 272): 35% were women; the mean EuroSCORE-I was 3%. The mean follow-up was 8.1 ± 4.9 years in a matched sample: 8.8 ± 4.9 years in those receiving a mechanical vs 7.1 ± 4.5 years in those receiving a biological prosthesis (P = 0.001). In the paired sample, the 15-year survival rate was 73% in those who had a biological vs 76% in those who had a mechanical valve [hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.54-1.20; P = 0.159]. No significant differences were observed in patients ≥55 years old (74% of 15-year survival in both groups: HR 0.88, 95% CI 0.56-1.34; P = 0.527). A higher rate of major bleeding was found in patients with a mechanical prosthesis (P = 0.004), whereas reoperation was more frequent among those with a biological prosthesis (P = 0.01). CONCLUSIONS: Long-term survival was comparable in patients above 55 years of age. Mechanical prostheses were associated with more major bleeding and bioprostheses, with more reoperations. A bioprosthesis in patients above 55 years old is a reasonable choice. CLINICAL TRIAL REGISTRATION NUMBER: NCT03239509.
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Válvula Aórtica/cirugía , Bioprótesis , Enfermedades de las Válvulas Cardíacas/cirugía , Implantación de Prótesis de Válvulas Cardíacas/métodos , Complicaciones Posoperatorias/epidemiología , Puntaje de Propensión , Factores de Edad , Anciano , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Pronóstico , Diseño de Prótesis , Estudios Retrospectivos , Factores de Riesgo , España/epidemiología , Tasa de Supervivencia/tendenciasRESUMEN
Left superior vena cava draining into the left atrium in the absence of coronary sinus is an anomaly that can appear in heterotaxy syndrome and unroofed coronary sinus syndrome. Regardless of the origin of these syndromes, biventricular repair can be done through rerouting by intracardiac procedures or through disconnection-reconnection of the left superior vena cava to the right atrium or right superior vena cava by extracardiac procedures. Different techniques can be used for this purpose, each of which has its own advantages and limitations. Therefore, appropriate selection is necessary to obtain the best results for each patient, and many factors, such as patient anatomy, age, associated cardiomyopathies, etc., have to be considered. In this review, we focus on heterotaxy and unroofed coronary sinus syndromes, associated cardiomyopathies, the state-of-the-art in their surgical treatment and our results in a sample of 10 patients. Our experience highlights the importance of accurate diagnosis and specific selection of surgical technique for the management of biventricular repair in patients with left superior vena cava draining into the left atrium in the absence of coronary sinus.
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Procedimientos Quirúrgicos Cardíacos/métodos , Atrios Cardíacos/cirugía , Síndrome de Heterotaxia/cirugía , Vena Cava Superior/cirugía , Adolescente , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Niño , Preescolar , Angiografía Coronaria , Seno Coronario/anomalías , Ecocardiografía Doppler en Color , Femenino , Atrios Cardíacos/anomalías , Atrios Cardíacos/diagnóstico por imagen , Síndrome de Heterotaxia/diagnóstico por imagen , Humanos , Lactante , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Vena Cava Superior/anomalías , Vena Cava Superior/diagnóstico por imagenRESUMEN
Saponins are potential wide-spectrum antitumor drugs, and copper(I) catalyzed azide-alkyne 1,3-dipolar cycloaddition is a suitable approach to synthesizing saponin-like compounds by regioselective glycosylation of the C2/C3 hydroxyl and C28 carboxylic groups of triterpene aglycones maslinic acid (MA) and oleanolic acid (OA). Biological studies on the T-84 human colon carcinoma cell line support the role of the hydroxyl groups at C2/C3, the influence of the aglycone, and the bulky nature of the substituents in C28. OA bearing a α-d-mannose moiety at C28 (compound 18) focused our interest because the estimated inhibitory concentration 50 was similar to that reported for ginsenoside Rh2 against colon cancer cells and it inhibits the G1-S phase transition affecting the cell viability and apoptosis. Considering that triterpenoids from natural sources have been identified as inhibitors of nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling, docking studies were conducted to evaluate whether NF-κB may be a potential target. Results are consistent with the biological study and predict a similar binding mode of MA and compound 18 to the p52 subunit from NF-κB but not for OA. The fact that the binding site is shared by the NF-κB inhibitor 6,6-dimethyl-2-(phenylimino)-6,7-dihydrobenzo[d][1,3]oxathiol-4(5H)-one supports the result and points to NF-κB as a potential target of both MA and compound 18.
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BACKGROUND: Solanum lycopersicum, an economically important crop grown worldwide, has been used as a model for the study of arbuscular mycorrhizal (AM) symbiosis in non-legume plants for several years and several cDNA array hybridization studies have revealed specific transcriptomic profiles of mycorrhizal tomato roots. However, a method to easily screen candidate genes which could play an important role during tomato mycorrhization is required. RESULTS: We have developed an optimized procedure for composite tomato plant obtaining achieved through Agrobacterium rhizogenes-mediated transformation. This protocol involves the unusual in vitro culture of composite plants between two filter papers placed on the culture media. In addition, we show that DsRed is an appropriate molecular marker for the precise selection of cotransformed tomato hairy roots. S. lycopersicum composite plant hairy roots appear to be colonized by the AM fungus Rhizophagus irregularis in a manner similar to that of normal roots, and a modified construct useful for localizing the expression of promoters putatively associated with mycorrhization was developed and tested. CONCLUSIONS: In this study, we present an easy, fast and low-cost procedure to study AM symbiosis in tomato roots.
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Exosomes are extracellular microvesicles released from cells, which are involved in many biological and pathological processes, mainly because of their role in intercellular communication. Exosomes derived from colorectal cancer (CRC) cells are related to oncogenesis, tumor cell survival, chemo-resistance, and metastasis. The role of the exosomes in these processes involves the transfer of proteins, RNAs, or mutant versions of proto-oncogenes to the target cells. In recent years, great efforts have been made to identify useful biomarkers in CRC exosomes for diagnosis, prediction of prognosis, and treatment response. This review focuses on recent studies on CRC exosomes, considering isolation, cargo, biomarkers, and the effects of exosomes on the development and progression of CRC, including resistance to antitumor therapy.
Asunto(s)
Neoplasias Colorrectales/patología , Exosomas/fisiología , Biomarcadores de Tumor , Carcinogénesis , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Humanos , Mutación , Proteínas de Neoplasias/metabolismo , Pronóstico , Transporte de Proteínas , Proto-Oncogenes/genética , ARN Neoplásico/metabolismoRESUMEN
Plant hormones have become appropriate candidates for driving functional plant mycorrhization programs, including the processes that regulate the formation of arbuscules in arbuscular mycorrhizal (AM) symbiosis. Here, we examine the role played by ABA/GA interactions regulating the formation of AM in tomato. We report differences in ABA and GA metabolism between control and mycorrhizal roots. Active synthesis and catabolism of ABA occur in AM roots. GAs level increases as a consequence of a symbiosis-induced mechanism that requires functional arbuscules which in turn is dependent on a functional ABA pathway. A negative interaction in their metabolism has been demonstrated. ABA attenuates GA-biosynthetic and increases GA-catabolic gene expression leading to a reduction in bioactive GAs. Vice versa, GA activated ABA catabolism mainly in mycorrhizal roots. The negative impact of GA3 on arbuscule abundance in wild-type plants is partially offset by treatment with ABA and the application of a GA biosynthesis inhibitor rescued the arbuscule abundance in the ABA-deficient sitiens mutant. These findings, coupled with the evidence that ABA application leads to reduce bioactive GA1, support the hypothesis that ABA could act modifying bioactive GA level to regulate AM. Taken together, our results suggest that these hormones perform essential functions and antagonize each other by oppositely regulating AM formation in tomato roots.
RESUMEN
Fundamento y objetivo: Evaluar si una intervención educativa en mujeres perimenopáusicas con hipertensión, diabetes mellitus y/o dislipidemia sería capaz de mejorar la adherencia a un patrón de dieta mediterráneo y conseguir cambios en parámetros antropométricos. Pacientes: Ensayo clínico aleatorizado de grupos paralelos: 320 mujeres (45-60 años) de 2 servicios de atención primaria urbanos. Variables a estudio: perímetro abdominal y de cadera, índice de masa corporal (IMC), grasa corporal total, visceral y de tronco (medidas con bioimpedancia) y adherencia a dieta mediterránea (cuestionario MEDAS-14). Grupo intervención: 3 talleres interactivos sobre prevención de enfermedad cardiovascular, y grupo control: información por correo. Resultados: Concluyeron el estudio 230 mujeres (113 en el grupo control y 117 en el grupo intervención). Un año después, las diferencias entre grupos fueron significativas en todos los parámetros. En la comparación intragrupos, las mujeres del grupo intervención mantuvieron el IMC y mejoraron la adherencia a la dieta mediterránea. El grupo control aumentó el IMC, el perímetro abdominal y de cadera y los parámetros de grasa (corporal total, visceral y tronco). Conclusiones: Una sencilla intervención educativa en mujeres perimenopáusicas con riesgo cardiovascular puede mejorar sus hábitos saludables (AU)
Background and objective: To assess whether an educational intervention in perimenopausal women with hypertension, diabetes mellitus and/or dyslipidaemia would improve adherence to a Mediterranean diet pattern and achieve changes in anthropometric parameters. Patients: Randomized clinical trial of parallel groups: 320 women (45-60 years) in 2 urban primary care services. Variables studied: hip and waist circumference, body mass index (BMI), total, visceral and trunk fat (bioimpedance measures) and adherence to Mediterranean diet (MEDAS-14 questionnaire). Intervention group: 3 interactive workshops on prevention of cardiovascular disease, and control group: information by post. Results: Two hundred and thirty women completed the study (113 control group and 117 intervention group). The differences between groups were significant in all parameters one year later. In the intragroup comparison, the intervention group maintained their BMI and improved adherence to the Mediterranean diet. The control group increased their BMI, abdominal and hip circumference and fat parameters (total, visceral and trunk fat). Conclusions: A simple educational intervention in perimenopausal women with cardiovascular risk can improve their healthy habits (AU)
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Anciano , Educación en Salud/métodos , Educación en Salud/tendencias , Educación en Salud , Mujeres/educación , Menopausia/metabolismo , Menopausia/fisiología , Enfermedades Cardiovasculares/prevención & control , Enfermedades Cardiovasculares/mortalidad , Dieta Mediterránea , Antropometría/instrumentación , Antropometría/métodos , Cumplimiento de la Medicación , Conducta Alimentaria/fisiología , Ensayos Clínicos Controlados Aleatorios como Asunto/instrumentación , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
BACKGROUND AND OBJECTIVE: To assess whether an educational intervention in perimenopausal women with hypertension, diabetes mellitus and/or dyslipidaemia would improve adherence to a Mediterranean diet pattern and achieve changes in anthropometric parameters. PATIENTS: Randomized clinical trial of parallel groups: 320 women (45-60 years) in 2 urban primary care services. VARIABLES STUDIED: hip and waist circumference, body mass index (BMI), total, visceral and trunk fat (bioimpedance measures) and adherence to Mediterranean diet (MEDAS-14 questionnaire). Intervention group: 3 interactive workshops on prevention of cardiovascular disease, and control group: information by post. RESULTS: Two hundred and thirty women completed the study (113 control group and 117 intervention group). The differences between groups were significant in all parameters one year later. In the intragroup comparison, the intervention group maintained their BMI and improved adherence to the Mediterranean diet. The control group increased their BMI, abdominal and hip circumference and fat parameters (total, visceral and trunk fat). CONCLUSIONS: A simple educational intervention in perimenopausal women with cardiovascular risk can improve their healthy habits.