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Severe asthma patients with persistent airflow obstruction are characterized by functional obstruction due to mucus plugs containing mucins, fibrin, and eosinophil derived Charcot- Leyden crystals. The molecular mechanisms underlying this endotype are not clearly understood. Developing new models is crucial to respiratory research insofar as critical differences exist between human and rodent airway epithelium. We (and other teams) have shown that it is possible to reconstitute in vitro a complex and functional airway epithelium displaying all the features described in vivo from human-induced pluripotent stem cells (hiPSC). Our aim is to establish a human in vitro model of severe asthma that will recapitulate airway epithelium remodeling and mucus plugs.
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Asma , Células Madre Pluripotentes Inducidas , Humanos , Pulmón , MocoRESUMEN
Understanding the factors and processes that shape intra-specific sensitivity to heat stress is fundamental to better predicting the vulnerability of benthic species to climate change. Here, we investigate the response of a habitat-forming Mediterranean octocoral, the red gorgonian Paramuricea clavata (Risso, 1826) to thermal stress at multiple biological and geographical scales. Samples from eleven P. clavata populations inhabiting four localities separated by hundreds to more than 1500 km of coast and with contrasting thermal histories were exposed to a critical temperature threshold (25 °C) in a common garden experiment in aquaria. Ten of the 11 populations lacked thermotolerance to the experimental conditions provided (25 days at 25 °C), with 100% or almost 100% colony mortality by the end of the experiment. Furthermore, we found no significant association between local average thermal regimes nor recent thermal history (i.e., local water temperatures in the 3 months prior to the experiment) and population thermotolerance. Overall, our results suggest that local adaptation and/or acclimation to warmer conditions have a limited role in the response of P. clavata to thermal stress. The study also confirms the sensitivity of this species to warm temperatures across its distributional range and questions its adaptive capacity under ocean warming conditions. However, important inter-individual variation in thermotolerance was found within populations, particularly those exposed to the most severe prior marine heatwaves. These observations suggest that P. clavata could harbor adaptive potential to future warming acting on standing genetic variation (i.e., divergent selection) and/or environmentally-induced phenotypic variation (i.e., intra- and/or intergenerational plasticity).
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Respuesta al Choque TérmicoRESUMEN
Understanding the resilience of temperate reefs to climate change requires exploring the recovery capacity of their habitat-forming species from recurrent marine heatwaves (MHWs). Here, we show that, in a Mediterranean highly enforced marine protected area established more than 40 years ago, habitat-forming octocoral populations that were first affected by a severe MHW in 2003 have not recovered after 15 years. Contrarily, they have followed collapse trajectories that have brought them to the brink of local ecological extinction. Since 2003, impacted populations of the red gorgonian Paramuricea clavata (Risso, 1826) and the red coral Corallium rubrum (Linnaeus, 1758) have followed different trends in terms of size structure, but a similar progressive reduction in density and biomass. Concurrently, recurrent MHWs were observed in the area during the 2003-2018 study period, which may have hindered populations recovery. The studied octocorals play a unique habitat-forming role in the coralligenous assemblages (i.e. reefs endemic to the Mediterranean Sea home to approximately 10% of its species). Therefore, our results underpin the great risk that recurrent MHWs pose for the long-term integrity and functioning of these emblematic temperate reefs.
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Antozoos , Ecosistema , Animales , Cambio Climático , Arrecifes de Coral , Estudios Longitudinales , Mar MediterráneoRESUMEN
BACKGROUND AND PURPOSE: Childhood-onset autosomal dominant cerebellar ataxia type 7 (SCA7) is a severe disease which leads to premature loss of ambulation and death. Early diagnosis of SCA7 is of major importance for genetic counselling and still relies on specific genetic testing, driven by clinical expertise. However, the precise phenotype and natural history of paediatric SCA7 has not yet been fully described. Our aims were to describe the natural history of SCA7 in a large multicentric series of children of all ages, and to find correlates to variables defining this natural history. METHODS: We collected and analysed clinical data from 28 children with proven SCA7. All had clinical manifestations of SCA7 and either a definite number of CAG repeats in ATXN7 or a long expansion > 100 CAG. RESULTS: We identified four clinical presentation patterns related to age at onset. Children of all age groups had cerebellar atrophy and retinal dystrophy. Our data, combined with those in the literature, suggest that definite ranges of CAG repeats determine paediatric SCA7 subtypes. The number of CAG repeats inversely correlated to all variables of the natural history. Age at gait ataxia onset correlated accurately to age at loss of walking ability and to age at death. CONCLUSION: SCA7 in children has four presentation patterns that are roughly correlated to the number of CAG repeats. Our depiction of the natural history of SCA7 in children may help in monitoring the effect of future therapeutic trials.
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Ataxias Espinocerebelosas , Ataxina-7 , Niño , Pruebas Genéticas , Humanos , Fenotipo , Ataxias Espinocerebelosas/diagnóstico , Ataxias Espinocerebelosas/genéticaRESUMEN
Magnetic resonance imaging (MRI) has become the reference imaging for the management of a large number of diseases. The number of MR examinations increases every year, simultaneously with the number of patients receiving a cardiac electronic implantable device (CEID). A CEID was considered an absolute contraindication for MRI for years. The progressive replacement of conventional pacemakers and defibrillators by MR-conditional CEIDs and recent data on the safety of MRI in patients with "MR-nonconditional" CEIDs have progressively increased the demand for MRI in patients with a CEID. However, some risks are associated with MRI in CEID carriers, even with "MR-conditional" devices because these devices are not "MR-safe". A specific programing of the device in "MR-mode" and monitoring patients during MRI remain mandatory for all patients with a CEID. A standardized patient workflow based on an institutional protocol should be established in each institution performing such examinations. This joint position paper of the Working Group of Pacing and Electrophysiology of the French Society of Cardiology and the Société française d'imagerie cardiaque et vasculaire diagnostique et interventionnelle (SFICV) describes the effect and risks associated with MRI in CEID carriers. We propose recommendations for patient workflow and monitoring and CEID programming in MR-conditional, "MR-conditional nonguaranteed" and MR-nonconditional devices.
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Cardiología , Desfibriladores Implantables , Marcapaso Artificial , Electrónica , Humanos , Imagen por Resonancia MagnéticaRESUMEN
Summary: Different phenotypes of allergic rhinitis have been identified based on the seasonality of the allergen involved. Within pollinosis, importance has to be paid to the responsible pollen species. Guidelines for clinical management are mostly based on studies performed in patients with grass pollen allergy. Only few data is available on tree pollen allergy and more specifically on cypress pollen allergy. We focused on the clinical and biological features of cypress pollen allergy to determine whether it is associated with a specific phenotype of allergic rhinitis or not. Our results suggest that cypress pollen can be responsible for two distinct phenotypes of rhinitis, both different from other pollinosis. In the most common phenotype, cypress pollen was not responsible for bronchial hyperresponsiveness or systemic inflammation. Close attention has to be paid to the allergen involved in allergic rhinitis. Different phenotypes leading to different pharmacological strategies may apply.
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Hiperreactividad Bronquial/inmunología , Cupressus/inmunología , Inflamación/inmunología , Rinitis Alérgica Estacional/inmunología , Rinitis Alérgica/inmunología , Adulto , Alérgenos/inmunología , Femenino , Humanos , Inmunoglobulina E/metabolismo , Masculino , Persona de Mediana Edad , Fenotipo , Poaceae/inmunología , Polen/inmunología , Guías de Práctica Clínica como Asunto , Estaciones del Año , Adulto JovenRESUMEN
OBJECTIVE: The posterior superior temporal sulcus (pSTS) plays a critical role in the 'social brain'. Its neurodevelopment and relationship with the social impairment in autism spectrum disorders (ASD) are not well understood. We explored the relationship between social cognition and the neurodevelopment of the pSTS in ASD. METHOD: We included 44 adults with high-functioning ASD and 36 controls. We assessed their performances on the 'Reading the mind in the eyes' test (for 34 of 44 subjects with ASD and 30 of 36 controls), their fixation time on the eyes with eye tracking (for 35 of 44 subjects with ASD and 30 of 36 controls) and the morphology of the caudal branches of the pSTS (length and depth), markers of the neurodevelopment, with structural MRI. RESULTS: The right anterior caudal ramus of the pSTS was significantly longer in patients with ASD compared with controls (52.6 mm vs. 38.3 mm; P = 1.4 × 10-3 ; Cohen's d = 0.76). Its length negatively correlated with fixation time on the eyes (P = 0.03) in the ASD group and with the 'Reading the mind in the eyes' test scores in both groups (P = 0.03). CONCLUSION: Our findings suggest that the neurodevelopment of the pSTS is related to the ASD social impairments.
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Trastorno del Espectro Autista/diagnóstico por imagen , Trastorno del Espectro Autista/fisiopatología , Percepción Social , Lóbulo Temporal/crecimiento & desarrollo , Adolescente , Adulto , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Lóbulo Temporal/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND: Type 1 myeloid dendritic cells (mDCs) contribute to inception of allergic asthma (AA) and are regulated by epithelial-derived cytokines. OBJECTIVES: To evaluate whether mDCs from AA patients are primed for thymic stromal lymphopoietin (TSLP)-driven responses. METHODS: mDCs from 18 AA patients and 15 controls were purified using immunomagnetic sorting. Cells were pulsed with TSLP or Dermatophagoides pteronyssinus (Der p) allergen, before FACS phenotyping and co-culture with allogeneic CD4+ T cells. Bronchial biopsies from 15 AA patients and four controls were immunostained for CD1c and TSLP receptor (TSLPR). RESULTS: Allergic asthma patients had a higher proportion of TSLPR+ mDCs, in blood and bronchial mucosa. When compared to mDCs from controls, both TSLP- and Der p-pulsed blood mDCs from AA patients induced increased polarization of CD4+ T cells into Th2 cells (IL-5, IL-13, and GATA3+), while only TSLP-mDCs promoted Th9 cells (IL-9 and PU.1+ /IRF4+). In addition, OX40L was induced upon TSLP stimulation and was required for the induction of Th2, but not Th9, cells. In contrast, development of Th9 cells in this model depended on TGF-ß1. CONCLUSIONS: Our data indicate overlapping but partially distinct effects of TSLP and Der p allergen pathways, showing that DCs are primed in human asthma for TSLP-driven induction of both Th2 and Th9 cells. This novel TSLP/mDC/Th9 axis operates through a distinct, OX40L-independent pathway. These data further highlight the TSLP pathway as a relevant target in human asthma.
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Asma/inmunología , Asma/metabolismo , Citocinas/metabolismo , Células Dendríticas/inmunología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Antígenos Dermatofagoides/inmunología , Proteínas de Artrópodos/inmunología , Asma/genética , Estudios de Casos y Controles , Cisteína Endopeptidasas/inmunología , Células Dendríticas/metabolismo , Expresión Génica , Humanos , Ligando OX40/antagonistas & inhibidores , Ligando OX40/metabolismo , Receptores de Citocinas/genética , Receptores de Citocinas/metabolismo , Subgrupos de Linfocitos T/inmunología , Subgrupos de Linfocitos T/metabolismo , Regulación hacia Arriba , Linfopoyetina del Estroma TímicoRESUMEN
INTRODUCTION: Glucose transporter type 1 deficiency syndrome is caused by heterozygous, mostly de novo, mutations in the SLC2A1 gene encoding the glucose transporter GLUT1. Mutations in this gene limit brain glucose availability and lead to cerebral energy deficiency. STATE OF THE ART: The phenotype is characterized by the variable association of mental retardation, acquired microcephaly, complex motor disorders, and paroxysmal manifestations including seizures and non-epileptic paroxysmal episodes. Clinical severity varies from mild motor dysfunction to severe neurological disability. In patients with mild phenotypes, paroxysmal manifestations may be the sole manifestations of the disease. In particular, the diagnosis should be considered in patients with paroxysmal exercise-induced dyskinesia or with early-onset generalized epilepsy. Low CSF level of glucose, relative to blood level, is the best biochemical clue to the diagnosis although not constantly found. Molecular analysis of the SLC2A1 gene confirms the diagnosis. Ketogenic diet is the cornerstone of the treatment and implicates a close monitoring by a multidisciplinary team including trained dieticians. Non-specific drugs may be used as add-on symptomatic treatments but their effects are often disappointing. CONCLUSION: Glucose transporter type 1 deficiency syndrome is likely under diagnosed due to its complex and pleiotropic phenotype. Proper identification of the affected patients is important for clinical practice since the disease is treatable.
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Errores Innatos del Metabolismo de los Carbohidratos , Proteínas de Transporte de Monosacáridos/deficiencia , Errores Innatos del Metabolismo de los Carbohidratos/diagnóstico , Errores Innatos del Metabolismo de los Carbohidratos/genética , Errores Innatos del Metabolismo de los Carbohidratos/terapia , Dieta Cetogénica/métodos , Transportador de Glucosa de Tipo 1/genética , Humanos , Proteínas de Transporte de Monosacáridos/genética , Fenotipo , Ácido Tióctico/uso terapéutico , Triglicéridos/uso terapéuticoRESUMEN
TGF-beta-targeting structural and inflammatory cells has been implicated in the mechanisms leading to the inflammatory and restructuring processes in asthma, suggesting an impact of TGF-beta1 signaling on the development and persistency of this disease. We investigated the potential early involvement of TGF-beta1 activity in the immunological and molecular mechanisms underlying progression of inflammation in childhood asthma. We evaluated the levels of TGF-beta1 in induced sputum supernatants (ISSs) and the expression of small mother cell against decapentaplegic (Smad) 2 and Smad7 proteins in induced sputum cells (ISCs) from children with intermittent asthma (IA), moderate asthma (MA) and control subjects (C). Furthermore, we investigated the regulatory role of TGF-beta1 activity on eosinophil and neutrophil adhesion to epithelial cells using adhesion assay, and on the granulocyte expression of adhesion molecule CD11b/CD18 Macrophage-1 antigen (MAC-1), by flow cytometry. We found that the levels of TGF-beta1 are increased in ISSs of IA and MA in comparison to C, concomitantly to the activation of intracellular signaling TGFbeta/Smads pathway in ISCs. In MA, TGF-beta1 levels correlated with the number of sputum eosinophils and neutrophils. Furthermore, we showed the ability of sputum TGF-beta1 to promote eosinophil and neutrophil adhesion to epithelial cells, and to increase the expression of MAC-1 on the granulocyte surface. This study shows the activation of TGFbeta/Smad signaling pathway in the airways of children with IA and, despite the regular ICS treatment, in children with MA, and provides evidence for the contribution of TGF-beta1 in the regulation of granulocyte activation and trafficking.
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Asma/metabolismo , Pulmón/metabolismo , Transducción de Señal , Factor de Crecimiento Transformador beta1/metabolismo , Administración por Inhalación , Adolescente , Corticoesteroides/administración & dosificación , Factores de Edad , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/inmunología , Asma/fisiopatología , Broncodilatadores/administración & dosificación , Estudios de Casos y Controles , Adhesión Celular , Línea Celular , Niño , Eosinófilos/inmunología , Eosinófilos/metabolismo , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Femenino , Granulocitos/inmunología , Granulocitos/metabolismo , Humanos , Pulmón/efectos de los fármacos , Pulmón/inmunología , Pulmón/fisiopatología , Antígeno de Macrófago-1/metabolismo , Masculino , Neutrófilos/inmunología , Neutrófilos/metabolismo , Fosforilación , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/metabolismo , Índice de Severidad de la Enfermedad , Transducción de Señal/efectos de los fármacos , Proteína Smad2/metabolismo , Proteína smad7/metabolismo , Esputo/metabolismoRESUMEN
The bronchoalveolar epithelium is submitted to numerous mechanical strains. These strains induce a specific cellular activity at the tissue level. This type of activation has been studied in respiratory medicine, mainly in the context of mechanical ventilation and asthma. The phenomenon of mechanotransduction is linked to various epithelial cellular activities such as epithelium repair, extracellular matrix remodelling, inflammatory mediator release and mucociliary regulation. In this review, the main studies related to bronchoalveolar epithelial mechanotransduction are reported to bring a new perspective on this little known biological phenomenon. A better understanding of the physiological and pathological aspects will potentially offer new treatment approaches for bronchial diseases.
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Bronquios/citología , Células Epiteliales/fisiología , Mecanotransducción Celular/fisiología , Alveolos Pulmonares/citología , Apoptosis , Asma/metabolismo , Asma/patología , Asma/fisiopatología , Cilios/fisiología , Colágeno/metabolismo , Citocinas/metabolismo , Epitelio/fisiología , Receptores ErbB/metabolismo , Matriz Extracelular/metabolismo , Perfilación de la Expresión Génica , Inflamación , Mediadores de Inflamación/metabolismo , Interleucina-8/metabolismo , Moco/metabolismo , Especies Reactivas de Oxígeno , Respiración ArtificialRESUMEN
AIMS: Little is known about the incidence of paroxysmal atrial tachycardias (PAT) in patients with heart failure (HF). The availability of cardiac resynchronization therapy (CRT) devices with extended diagnostics for AT enables continuous monitoring of PAT episodes. The aim of the study was to assess the incidence over time of PAT in HF patients treated with CRT. METHODS AND RESULTS: Consecutive patients in NYHA functional class III or IV despite optimal drug therapy, QRS duration > or = 130 ms, left ventricular ejection fraction < or = 35%, and left ventricular end-diastolic dimension > or = 55 mm were eligible for enrolment. Patients with permanent or persistent atrial fibrillation (AF) were not included in the study. The first follow-up examination was performed 2 weeks after implantation, to optimize atrial sensing and CRT. Subsequent follow-up examinations were carried out 15 and 28 weeks after implantation, to collect the telemetric data. A total of 173 patients (67 +/- 11 years, M 116) were enrolled. Complete arrhythmia monitoring data were available from 120 patients over a mean follow-up of 183 +/- 23 days. Atrial tachycardia episodes were detected through telemetry in 25 of 120 patients (21%) during at least one follow-up examination. Atrial tachycardia episodes were recorded in 29 and 17% (P = NS) of patients with and without previous history of AF, respectively. CONCLUSION: More than 20% of the overall HF patient population treated with CRT suffer PAT episodes. Paroxysmal atrial tachycardia may interfere with response to CRT. Therefore, telemetric data may be relevant to drive the appropriate therapy in each patient.
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Fibrilación Atrial/epidemiología , Fibrilación Atrial/prevención & control , Estimulación Cardíaca Artificial/estadística & datos numéricos , Electrocardiografía Ambulatoria/estadística & datos numéricos , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/prevención & control , Anciano , Fibrilación Atrial/diagnóstico , Comorbilidad , Europa (Continente)/epidemiología , Femenino , Insuficiencia Cardíaca/diagnóstico , Humanos , Incidencia , Masculino , Medición de Riesgo/métodos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Congenital myasthenic syndromes (CMSs) are a heterogeneous group of diseases caused by genetic defects affecting neuromuscular transmission. Mutations of DOK7 have recently been described in recessive forms of CMS. Dok-7 is a cytoplasmic post-synaptic protein co-activator of the muscle-specific receptor-tyrosine kinase (MuSK) involved in neuromuscular synaptogenesis and maintenance. We report clinical, morphological and molecular data on 15 patients with mutations in DOK7. Eleven different mutations (5 novel) were identified and all patients but one were found to carry at least the common c.1124_1127dupTGCC mutation. Patients with DOK7 mutations have a particular limb-girdle pattern, without tubular aggregates but a frequent lipidosis on the muscle biopsy. Changes in pre- and post-synaptic compartments of the neuromuscular junction were also observed in muscle biopsies: terminal axons showed defective branching which resulted in a unique terminal axon contacting en passant postsynaptic cups. Clinical features, muscle biopsy findings or response to therapy were confusing in several patients. Characterization of this distinct phenotype is essential to provide clues for targeted genetic screening and to predict the therapeutic response to anticholinesterase treatments or ephedrine as has been suggested.
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Genotipo , Proteínas Musculares/genética , Mutación , Síndromes Miasténicos Congénitos/genética , Fenotipo , Axones/patología , Axones/fisiología , Niño , Preescolar , Estudios de Cohortes , Femenino , Estudios de Asociación Genética , Humanos , Lactante , Recién Nacido , Masculino , Músculo Esquelético/patología , Músculo Esquelético/fisiopatología , Síndromes Miasténicos Congénitos/patología , Síndromes Miasténicos Congénitos/terapia , Unión Neuromuscular/patología , Unión Neuromuscular/fisiopatología , Embarazo , Tomografía Computarizada por Rayos XRESUMEN
The relationship between allergic rhinitis and asthma is now established, and most of the clinical, epidemiological and biological data recommend integrated management. Epithelial cells represent the first barrier of the upper and lower respiratory tracts and thus are logical targets for a comprehensive integrated therapeutic approach. This review discusses rhinosinusitis as a co-morbid condition, a precipitating or triggering condition, and an epiphenomenon as an integrated part of the disease. A better understanding and a more pragmatic method of diagnosis and management is needed using cost-effective long-term strategies.
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Asma , Rinitis , Sinusitis , Antiinflamatorios/uso terapéutico , Asma/diagnóstico , Asma/tratamiento farmacológico , Asma/epidemiología , Bronquios/inmunología , Bronquios/patología , Comorbilidad , Células Epiteliales/inmunología , Células Epiteliales/patología , Humanos , Nariz/patología , Rinitis/diagnóstico , Rinitis/tratamiento farmacológico , Rinitis/epidemiología , Sinusitis/diagnóstico , Sinusitis/tratamiento farmacológico , Sinusitis/epidemiologíaRESUMEN
MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression and hence play important roles in metabolic pathways. Recent studies have evidenced the interrelation of miRNAs with cell proliferation, differentiation, development, and diseases. Since they are involved in gene regulation, they are intrinsically related to metabolic pathways. This leads to questions that are particularly interesting for investigating medical and laboratorial applications. We developed an miRNApath online database that uses miRNA target genes to link miRNAs to metabolic pathways. Currently, databases about miRNA target genes (DIANA miRGen), genomic maps (miRNAMap) and sequences (miRBase) do not provide such correlations. Additionally, miRNApath offers five search services and a download area. For each search, there is a specific type of input, which can be a list of target genes, miRNAs, or metabolic pathways, which results in different views, depending upon the input data, concerning relationships between the target genes, miRNAs and metabolic pathways. There are also internal links that lead to a deeper analysis and cross-links to other databases with more detailed information. miRNApath is being continually updated and is available at http://lgmb.fmrp.usp.br/mirnapath.
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Biología Computacional/métodos , Bases de Datos de Ácidos Nucleicos , Redes y Vías Metabólicas , MicroARNs/genética , Programas Informáticos , Animales , HumanosRESUMEN
AIMS: To assess procedural characteristics and adjudicated procedure-related (
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Estimulación Cardíaca Artificial , Desfibriladores Implantables , Anciano , Estimulación Cardíaca Artificial/efectos adversos , Estimulación Cardíaca Artificial/mortalidad , Femenino , Insuficiencia Cardíaca/mortalidad , Insuficiencia Cardíaca/terapia , Humanos , Masculino , Persona de Mediana Edad , Marcapaso Artificial , Complicaciones Posoperatorias , Análisis de Supervivencia , Resultado del TratamientoRESUMEN
MicroRNAs (miRNAs) are small non-coding RNAs that regulate target gene expression and hence play important roles in metabolic pathways. Recent studies have evidenced the interrelation of miRNAs with cell proliferation, differentiation, development, and diseases. Since they are involved in gene regulation, they are intrinsically related to metabolic pathways. This leads to questions that are particularly interesting for investigating medical and laboratorial applications. We developed an miRNApath online database that uses miRNA target genes to link miRNAs to metabolic pathways. Currently, databases about miRNA target genes (DIANA miRGen), genomic maps (miRNAMap) and sequences (miRBase) do not provide such correlations. Additionally, miRNApath offers five search services and a download area. For each search, there is a specific type of input, which can be a list of target genes, miRNAs, or metabolic pathways, which results in different views, depending upon the input data, concerning relationships between the target genes, miRNAs and metabolic pathways. There are also internal links that lead to a deeper analysis and cross-links to other databases with more detailed information. miRNApath is being continually updated and is available at http://lgmb.fmrp.usp.br/mirnapath.
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Humanos , Animales , Bases de Datos de Ácidos Nucleicos , MicroARNs/genética , Programas Informáticos , Biología Computacional/métodosRESUMEN
BACKGROUND: Cardiac resynchronization therapy (CRT) is a promising new treatment for patients with heart failure and cardiac dyssynchrony. The CARE-HF study is a morbidity/mortality trial designed to provide conclusive evidence of the effects of CRT in patients with moderate to severe heart failure. METHODS: A description of the baseline characteristics of patients randomised in the CARE-HF trial. RESULTS: 813 Patients with predominantly NYHA class III (94%) heart failure were randomised in 82 centres. Their mean age was 65 (interquartile range [IQR] 59 to 72) years, 34% were aged >70 years and 27% were women. Thirty-eight percent of the patients had ischaemic heart disease. Mean heart rate was adequately controlled at 70 (IQR 60 to 78) bpm consistent with the use of beta-blockers. Supine systolic blood pressure was low at 117 (IQR 105 to 130) mm Hg. Eighty-eight percent of patients had a QRS > or =150 ms. Mean LV ejection fraction was 26% (IQR 22 to 29) and end-diastolic dimension was 7.2 (IQR 6.4 to 7.8) cm. Ninety-four percent of patients were receiving loop diuretics, 95% an ACE inhibitor or angiotensin receptor blocker (ARB), 72% a beta-blocker and 56% were taking spironolactone. CONCLUSIONS: The patients enrolled in CARE-HF had moderately severe heart failure and cardiac dysfunction with evidence of cardiac dyssynchrony. The population appears at high risk of events despite pharmacological therapy and therefore appropriate for a trial of CRT.