Thymine starvation causes abortive initiation of chromosome replication critical for cell death in Escherichia coli

Presentado en: XXXVI Congreso SEBBM (Sociedad Española de Bioquímica y Biología Molecular), Madrid, 4-6 septiembre, 2013Thymineless death (TLD), a phenomenon in which thymine auxotrophy becomes lethal when cells are starved for thymine, can be prevented by rifampicin addition. In this work, we have obtained evidence indicating that among the effects of RNA polymerase inhibition by rifampicin, the inhibition of chromosomal replication initiation is the process responsible for TLD suppression. We show that diminishing, abolishing or increasing the transcription level around oriC alleviates TLD by limiting the chromosomal initiation capacity (ChIC) generated under thymine starvation. TLD suppression was eliminated by DnaA inactivation or the deletion in the left half of the replication origin or deletion of the DnaA-boxes located in the right half of the oriC region. In accordance with these data, two-dimensional DNA electrophoresis gels showed an accumulation of simple-Y and bubble arc replication intermediates, as well as recombination structures at the oriC region during thymine starvation. None of these structures were observed under genetic or physiological conditions that suppress TLD. These results demonstrate that abortive initiations of chromosome replication occur under thymine starvation, supporting the idea that these events are a critical target for the lethal damage caused by thymine starvation and that results in TLD.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tec

Heart disease risk prediction using deep learning techniques with feature augmentation

[EN] Cardiovascular diseases state as one of the greatest risks of death for the general population. Late detection in heart diseases highly conditions the chances of survival for patients. Age, sex, cholesterol level, sugar level, heart rate, among other factors, are known to have an influence on life-threatening heart problems, but, due to the high amount of variables, it is often difficult for an expert to evaluate each patient taking this information into account. In this manuscript, the authors propose using deep learning methods, combined with feature augmentation techniques for evaluating whether patients are at risk of suffering cardiovascular disease. The results of the proposed methods outperform other state of the art methods by 4.4%, leading to a precision of a 90%, which presents a significant improvement, even more so when it comes to an affliction that affects a large population.SIPublicación en abierto financiada por el Consorcio de Bibliotecas Universitarias de Castilla y León (BUCLE), con cargo al Programa Operativo 2014ES16RFOP009 FEDER 2014-2020 DE CASTILLA Y LEÓN, Actuación:20007-CL - Apoyo Consorcio BUCL

Relationship between Fork Progression and Initiation of Chromosome Replication in E. coli

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Buenas prácticas organizativas en Atención Primaria : una organización facilitadora de la seguridad clínica

En este capítulo se describen dos experiencias concretas de organización del trabajo en seguridad del paciente en dos áreas sanitarias de dos comunidades autónomas. Cada una tiene ventajas e inconvenientes en el despliegue de la estrategia de seguridad del paciente si bien, cada una tiene la virtud de adaptarse lo mejor posible a las circunstancias organizativas del medio en el que trabaja. La finalidad de ambas experiencias es poner sobre la mesa que la incorporación de la cultura de seguridad del paciente de una manera efectiva no se fundamenta creando estructuras nuevas sino consiguiendo adaptar la realidad existente para que se priorice mejorar la seguridad del paciente en el sistema sanitario

Relationship between Fork Progression and Initiation of Chromosome Replication in E. coli

post-print687 K

Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study

[EN] Matrix-assisted autologous chondrocyte implantation (MACI) has shown promising results for cartilage repair, combining cultured chondrocytes and hydrogels, including alginate. The ability of chondrocytes for MACI is limited by different factors including donor site morbidity, dedifferentiation, limited lifespan or poor proliferation in vitro. Mesenchymal stem cells could represent an alternative for cartilage regeneration. In this study, we propose a MACI scaffold consisting of a mixed alginate-agarose hydrogel in combination with human dental pulp stem cells (hDPSCs), suitable for cartilage regeneration. Scaffolds were characterized according to their rheological properties, and their histomorphometric and molecular biology results. Agarose significantly improved the biomechanical behavior of the alginate scaffolds. Large scaffolds were manufactured, and a homogeneous distribution of cells was observed within them. Although primary chondrocytes showed a greater capacity for chondrogenic differentiation, hDPSCs cultured in the scaffolds formed large aggregates of cells, acquired a rounded morphology and expressed high amounts of type II collagen and aggrecan. Cells cultured in the scaffolds expressed not only chondral matrix-related genes, but also remodeling proteins and chondrocyte differentiation factors. The degree of differentiation of cells was proportional to the number and size of the cell aggregates that were formed in the hydrogels.This work was funded by the Ministry of Economy and Competitiveness of the Spanish Government (PID2019-106099RB-C42, MM) and by the Generalitat Valenciana, Spain (PROMETEO/2020/069, CC). CIBER-BBN and CIBER-ER are financed by the VI National R&D&I Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and the Instituto de Salud Carlos III, with assistance of the European Regional Development Fund.Oliver-Ferrándiz, M.; Milián, L.; Sancho-Tello, M.; Martín De Llano, JJ.; Gisbert-Roca, F.; Martínez-Ramos, C.; Carda, C.... (2021). Alginate-Agarose Hydrogels Improve the In Vitro Differentiation of Human Dental Pulp Stem Cells in Chondrocytes. A Histological Study. Biomedicines. 9(7):1-22. https://doi.org/10.3390/biomedicines9070834S1229

Coocurrencia de trastornos de personalidad en pacientes con trastornos de ansiedad

The co-occurrence between personality disorders and anxiety disorders may have important implications. Multiple diagnoses can give us an idea of the severity of the disorder, functioning impairment and prognosis. The aim of this study was two-fold, to analyze the co-occurrence between personality disorders and anxiety disorders, and to identify personality disorder profiles in different anxiety disorders. A total of 31 patients with anxiety disorders participated in the study. They were divided into four groups: specific phobia, social phobia, generalized anxiety and panic with or without the presence of agoraphobia. The assessment instruments used were The Millon Clinical Multiaxial Inventory II and the Anxiety Disorders Interview according to the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders. The specific phobia group presented lower scores on the different scales and lower frequency of personality disorders. On the contrary, the generalized anxiety group had a higher rate of multiple diagnoses of personality disorders. Higher scores were observed in the schizoid, dependent, self-defeating, avoidant and compulsive scales. Each anxiety disorder presented a profile of personality disorders. Co-occurrence between disorders may help to understand the success or failure of a treatment, so the systematic evaluation of pathological personality in the clinical setting is recommended.    La coocurrencia entre los trastornos de personalidad y los trastornos de ansiedad puede tener implicaciones importantes. Los diagnósticos múltiples nos pueden dar idea de la gravedad de la alteración, el deterioro del funcionamiento y el pronóstico. El objetivo de este estudio fue doble, analizar la coocurrencia entre trastornos de personalidad y trastornos de ansiedad, e identificar perfiles de trastornos de personalidad en los diferentes trastornos de ansiedad. En este estudio participaron 31 pacientes con trastornos de ansiedad, distribuidos en cuatro grupos: fobia específica, fobia social, ansiedad generalizada y pánico, con y sin presencia de agorafobia. Los instrumentos de evaluación utilizados fueron El Inventario Clínico Multiaxial de Millon II y la Entrevista para los Trastornos de Ansiedad según el Manual diagnóstico y estadístico de los trastornos mentales IV. El grupo de fobia específica presenta puntuaciones más bajas en las distintas escalas y menor frecuencia de trastornos de personalidad. Por el contrario, el grupo de ansiedad generalizada presenta mayor tasa de diagnósticos múltiples de trastornos de personalidad. Las puntuaciones más altas se observan en las escalas esquizoide, dependiente, autodestructiva, evitativa y compulsiva. Cada trastorno de ansiedad presenta un perfil de trastornos de personalidad. Tener en cuenta la coocurrencia entre trastornos puede ayudar a comprender el éxito o no de un tratamiento, por lo que la evaluación sistemática de la personalidad patológica en el ámbito clínico es recomendable.&nbsp

Human predecidual stromal cells are mesenchymal stromal/stem cells and have a therapeutic effect in an immune-based mouse model of recurrent spontaneous abortion

Las células estromales deciduales humanas (Decidual Stromal Cells, DSCs) son un tipo celular localizado en la decidua (endometrio gestante) y que están involucradas en el mantenimiento y desarrollo del embarazo al jugar un papel clave en la inducción de la tolerancia materno fetal. Los precursores de DSCs (preDSC) están localizados alrededor de los vasos y han sido relacionados con los pericitos y con las células madre mesenquimales (MSCs). Puesto que las MSCs tienen numerosas propiedades funcionales que les han permitido ser utilizadas como herramienta terapéutica para enfermedades proinflamatorias y/o autoinmunes. En este estudio se pretendió determinar la existencia de un efecto terapéutico de las preDSCs en un modelo murino de aborto de repetición para su posterior uso en enfermedades con un componente inmunitario y/o proinflamatorio. Los resultados mostraron la capacidad de las DSCs en modular el sistema inmunitario al permitir la implantación embrionaria en un cruce abortivo, lo que sugiere la modulación del sistema inmunitario hacia la tolerancia materno-fetal

Clinical implementation of pharmacogenetics and personalized drug prescription based on e-health: the MedeA initiative

There is a growing demand for the clinical implementation of pharmacogenetics (PGx), personalized and precision medicine (PPM) for drug prescription to reduce adverse drug reactions (ADRs), drug failure, and ultimately health care costs. However, it is convenient to clarify the concept of clinical implementation to realize its benefits. Advances on PGx clinical implementation depend on the integration of genetic along with other relevant biomarkers and clinical information influencing variability in drug response for being interpreted and translated into clinical decisionmaking to optimize drug treatment choice during routine clinical practice

Incidence of long-term cardiotoxicity and evolution of the systolic function in patients with breast cancer treated with anthracyclines

Background: Anthracycline cardiotoxicity (AC) may manifest years after treatment (long-term cardiotoxicity). There is little data on the incidence and natural history of AC in the current context, with protocols including lower anthracycline doses. The present study prospectively evaluated the incidence, time of occurrence and clinical correlates of long-term cardiotoxicity and the evolution of systolic function in patients with breast cancer treated with anthracyclines. Methods: This study prospectively included 85 consecutive patients undergoing chemotherapy (CHT) with anthracyclines without trastuzumab. All patients underwent evaluation at baseline, at the end of CHT, 3 months after the end of CHT and 1 and 4 years subsequent to the beginning of CHT. Clinical data and echocardiographic parameters were evaluated in all examinations. Results: The mean dose of doxorubicin used was 243.53 mg/m2. Median follow-up of the current cohort was 4.5 years. At 1 year the incidence of AC was 1% and at the end of the follow-up 16.5% (14 of 85 patients). Therefore, the incidence of long-term cardiotoxicity was 15%. Of these 14 patients with AC, 12 had asymptomatic systolic dysfunction, 1 had heart failure and 1 suffered sudden death. Fifteen percent developed systolic dysfunction during follow–up. An early decline in strain was observed in patients who developed long-term AC. Conclusions: The incidence of long-term cardiotoxicity in patients treated with low-cumulative dose of anthracyclines is high, 16.5% at 4.5 years. This was observed in almost all cases after the first year of follow-up. Therefore, long-term monitoring may be advisable