Modelo holónico de la ingeniería del producto

En el presente trabajo se formula un modelo holónico de la Ingeniería del Producto,soportado por las siguientes entidades holónicas: Estrategia de Producto, Producto, Proceso, Entorno de Diseño y Desarrollo. Dicho modelo se fundamenta desde los principios holónicos propuestos por Koestler y la teoría de la variedad de Ashby. Esta formulación permite dar soporte a: los requerimientos de empresa y producto extendido y virtual, así como al diseño colaborativo y distribuido inteligente.The present work we formulated a holonic model of the Product Engineering, it is supported by the following holonics entities: Product Strategy, Product, Process, Design and Development Context. This model has a foundation from holonics principles proposed by Koestler and the Ashby theory of varieties. This formulation permits giving support to: Company's requests and extended and virtual product, furthermore the collaborative and distributed intelligent

Pentobarbital versus thiopental in the treatment of refractory intracranial hypertension in patients with traumatic brain injury: a randomized controlled trial

Introduction: Experimental research has demonstrated that the level of neuroprotection conferred by the various barbiturates is not equal. Until now no controlled studies have been conducted to compare their effectiveness, even though the Brain Trauma Foundation Guidelines recommend that such studies be undertaken. The objectives of the present study were to assess the effectiveness of pentobarbital and thiopental in terms of controlling refractory intracranial hypertension in patients with severe traumatic brain injury, and to evaluate the adverse effects of treatment. Methods: This was a prospective, randomized, cohort study comparing two treatments: pentobarbital and thiopental. Patients who had suffered a severe traumatic brain injury (Glasgow Coma Scale score after resuscitation ≤ 8 points or neurological deterioration during the first week after trauma) and with refractory intracranial hypertension (intracranial pressure > 20 mmHg) first-tier measures, in accordance with the Brain Trauma Foundation Guidelines. Results: A total of 44 patients (22 in each group) were included over a 5-year period. There were no statistically significant differences in ' baseline characteristics, except for admission computed cranial tomography characteristics, using the Traumatic Coma Data Bank classification. Uncontrollable intracranial pressure occurred in 11 patients (50%) in the thiopental treatment group and in 18 patients (82%) in the pentobarbital group (P = 0.03). Under logistic regression analysis - undertaken in an effort to adjust for the cranial tomography characteristics, which were unfavourable for pentobarbital - thiopental was more effective than pentobarbital in terms of controlling intracranial pressure (odds ratio = 5.1, 95% confidence interval 1.2 to 21.9; P = 0.027). There were no significant differences between the two groups with respect to the incidence of arterial hypotension or infection. Conclusions: Thiopental appeared to be more effective than pentobarbital in controlling intracranial hypertension refractory to first-tier measures. These findings should be interpreted with caution because of the imbalance in cranial tomography characteristics and the different dosages employed in the two arms of the study. The incidence of adverse effects was similar in both groups

Diagnóstico antenatal de la madurez pulmonar fetal en embarazos normales y patológicos

Hemos realizado un estudio de madurez fetal, en muestras de líquido amniótico obtenido en 112 mujeres en las que el parto se produjo antes de transcurridos 7 días tras la amniocentesis. Comparamos el test de Clements, el estudio de células naranaja, la DO a 650 y 400 NM y la determinación de creatinina, con el cociente lecitina/ esfingomielina. El test de Clements y la determinación de DO presentan una buena correlación con el cociente L/E

Traumatic brain injury and acute kidney injury - outcomes and associated risk factors

Our objective was to analyze the contribution of acute kidney injury (AKI) to the mortality of isolated TBI patients and its associated risk factors. Observational, prospective and multicenter registry (RETRAUCI) methods were used, from March 2015 to December 2019. Isolated TBI was defined as abbreviated injury scale (AIS) ≥ 3 head with no additional score ≥ 3. A comparison of groups was conducted using the Wilcoxon test, chi-square test or Fisher's exact test, as appropriate. A multiple logistic regression analysis was conducted to analyze associated risk factors in the development of AKI. For the result, overall, 2964 (30.2%) had AIS head ≥ 3 with no other area with AIS ≥ 3. The mean age was 54.7 (SD 19.5) years, 76% were men, and the ground-level falls was 49.1%. The mean ISS was 18.4 (SD 8). The in-hospital mortality was 22.2%. Up to 310 patients (10.6%) developed AKI, which was associated with increased mortality (39% vs. 17%, adjusted OR 2.2). Associated risk factors (odds ratio (OR) (95% confidence interval)) were age (OR 1.02 (1.01?1.02)), hemodynamic instability (OR 2.87 to OR 5.83 (1.79-13.1)), rhabdomyolysis (OR 2.94 (1.69-5.11)), trauma-associated coagulopathy (OR 1.67 (1.05-2.66)) and transfusion of packed red-blood-cell concentrates (OR 1.76 (1.12-2.76)). In conclusion, AKI occurred in 10.6% of isolated TBI patients and was associated with increased mortality

microRNA-based signatures obtained from endometrial fluid identify implantative endometrium

STUDY QUESTION Is it possible to use free and extracellular vesicle-associated microRNAs (miRNAs) from human endometrial fluid (EF) samples as non-invasive biomarkers for implantative endometrium? SUMMARY ANSWER The free and extracellular vesicle-associated miRNAs can be used to detect implantative endometrium in a non-invasive manner. WHAT IS KNOWN ALREADY miRNAs and extracellular vesicles (EVs) from EF have been described as mediators of the embryo-endometrium crosstalk. Therefore, the analysis of miRNA from this fluid could become a non-invasive technique for recognizing implantative endometrium. This analysis could potentially help improve the implantation rates in ART. STUDY DESIGN, SIZE, DURATION In this prospective study, we first optimized different protocols for EVs and miRNA analyses using the EF of a setup cohort (n = 72). Then, we examined differentially expressed miRNAs in the EF of women with successful embryo implantation (discovery cohort n = 15/validation cohort n = 30) in comparison with those for whom the implantation had failed (discovery cohort n = 15/validation cohort n = 30). Successful embryo implantation was considered when pregnancy was confirmed by vaginal ultrasound showing a gestational sac 4 weeks after embryo transfer (ET). PARTICIPANTS/MATERIALS, SETTING, METHODS The EF of the setup cohort was obtained before starting fertility treatment during the natural cycle, 16-21 days after the beginning of menstruation. For the discovery and validation cohorts, the EF was collected from women undergoing frozen ET on Day 5, and the samples were collected immediately before ET. In this study, we compared five different methods; two of them based on direct extraction of RNA and the other three with an EV enrichment step before the RNA extraction. Small RNA sequencing was performed to determine the most efficient method and find a predictive model differentiating between implantative and non-implantative endometrium. The models were confirmed using quantitative PCR in two sets of samples (discovery and validation cohorts) with different implantation outcomes. MAIN RESULTS AND THE ROLE OF CHANCE The protocols using EV enrichment detected more miRNAs than the methods based on direct RNA extraction. The two most efficient protocols (using polymer-based precipitation (PBP): PBP-M and PBP-N) were used to obtain two predictive models (based on three miRNAs) allowing us to distinguish between an implantative and non-implantative endometrium. The first Model 1 (PBP-M) (discovery: AUC = 0.93; P-value = 0.003; validation: AUC = 0.69; P-value = 0.019) used hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-148b-3p. Model 2 (PBP-N) (discovery: AUC = 0.92; P-value = 0.0002; validation: AUC = 0.78; P-value = 0.0002) used hsa-miR-200b-3p, hsa-miR-24-3p and hsa-miR-99b-5p. Functional analysis of these miRNAs showed strong association with key implantation processes such as in utero embryonic development or transforming growth factor-beta signaling. LARGE SCALE DATA The FASTQ data are available in the GEO database (access number GSE178917). LIMITATIONS, REASONS FOR CAUTION One important factor to consider is the inherent variability among the women involved in the trial and among the transferred embryos. The embryos were pre-selected based on morphology, but neither genetic nor molecular studies were conducted, which would have improved the accuracy of our tests. In addition, a limitation in miRNA library construction is the low amount of input RNA. WIDER IMPLICATIONS OF THE FINDINGS We describe new non-invasive protocols to analyze miRNAs from small volumes of EF. These protocols could be implemented in clinical practice to assess the status of the endometrium before attempting ET. Such evaluation could help to avoid the loss of embryos transferred to a non-implantative endometrium. STUDY FUNDING/COMPETING INTEREST(S) J.I.-P. was supported by a predoctoral grant from the Basque Government (PRE_2017_0204). This study was partially funded by the Grant for Fertility Innovation (GFI, 2011) from Merck (Darmstadt, Germany). It was also supported by the Spanish Ministry of Economy and Competitiveness MINECO within the National Plan RTI2018-094969-B-I00, the European Union's Horizon 2020 research and innovation program (860303), the Severo Ochoa Centre of Excellence Innovative Research Grant (SEV-2016-0644) and the Instituto de Salud Carlos III (PI20/01131). The funding entities did not play any role in the study design, collection, analysis and interpretation of data, writing of the report or the decision to submit the article for publication. The authors declare no competing interests.J.I.-P. was supported by a predoctoral grant from the Basque Government (PRE_2017_0204). This study was partially funded by the Grant for Fertility Innovation (GFI, 2011) from Merck (Darmstadt, Germany). The project was also supported by the Spanish Ministry of Economy and Competitiveness MINECO within the national plan RTI2018-094969-B-I00, the European Union's Horizon 2020 research and innovation program (860303), the Severo Ochoa Centre of Excellence Innovative Research Grant (SEV-2016-0644) and the Instituto de Salud Carlos III (PI20/01131). The funding entities did not have any role in study design, sample collection, analysis and interpretation of data, report writing or decision to submit the article for publication

Dystrophinopathy Phenotypes and Modifying Factors in Exon 45-55 Deletion

Duchenne muscular dystrophy (DMD) exon 45-55 deletion (del45-55) has been postulated as a model that could treat up to 60% of DMD patients, but the associated clinical variability and complications require clarification. We aimed to understand the phenotypes and potential modifying factors of this dystrophinopathy subset. This cross-sectional, multicenter cohort study applied clinical and functional evaluation. Next generation sequencing was employed to identify intronic breakpoints and their impact on the Dp140 promotor, intronic long noncoding RNA, and regulatory splicing sequences. DMD modifiers (SPP1, LTBP4, ACTN3) and concomitant mutations were also assessed. Haplotypes were built using DMD single nucleotide polymorphisms. Dystrophin expression was evaluated via immunostaining, Western blotting, reverse transcription polymerase chain reaction (PCR), and droplet digital PCR in 9 muscle biopsies. The series comprised 57 subjects (23 index) expressing Becker phenotype (28%), isolated cardiopathy (19%), and asymptomatic features (53%). Cognitive impairment occurred in 90% of children. Patients were classified according to 10 distinct index-case breakpoints; 4 of them were recurrent due to founder events. A specific breakpoint (D5) was associated with severity, but no significant effect was appreciated due to the changes in intronic sequences. All biopsies showed dystrophin expression of >67% and traces of alternative del45-57 transcript that were not deemed pathogenically relevant. Only the LTBP4 haplotype appeared associated the presence of cardiopathy among the explored extragenic factors. We confirmed that del45-55 segregates a high proportion of benign phenotypes, severe cases, and isolated cardiac and cognitive presentations. Although some influence of the intronic breakpoint position and the LTBP4 modifier may exist, the pathomechanisms responsible for the phenotypic variability remain largely unresolved. ANN NEUROL 2022;92:793-80

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.Supported by grants from the Spanish Ministry of Science, Innovation and Universities (MCIU) co-financed with FEDER funds (SAF2015-65327-R and RTI2018-096494-B-100 to JA; BFU2016-76872-R to EB, AGL2017-86757-R to LA, SAF2017-87301-R to MLMC, SAF2015-64111-R to AP, SAF2015-73549-JIN to HR), Instituto de Salud Carlos III (PIE13/0004 to AP), the Basque Government Department of Health (2015111117 to LA), the Basque Foundation for Innovation and Health Research (BIOEF), through the EiTB Maratoia grant BIO15/CA/016/BS to MLMC, the regional Government of Andalusia co-funded by CEC and FEDER funds (Proyectos de Excelencia P12-CTS-2232) and Fundación Domingo Martínez (to AP). LA is supported by the Ramon y Cajal program (RYC-2013-13666). DB, MMR and TMM are recipients of MCIU FPI fellowships. ACG and AP are recipients of fellowships form the Basque Government. APC is a recipient of a fellowship from the University of the Basque Country. We thank the MCIU for the Severo Ochoa Excellence accreditation (SEV-2016-0644), the Basque Department of Industry, Tourism and Trade (Etortek and Elkartek programs), the Innovation Technology Department of the Bizkaia Province and the CIBERehd network. DB and JA are supported by a grant from the Jesús de Gangoiti Barrera Foundation

Use of interactive response devices for the improvement of teaching in the degrees of the Faculty of Sciences

La implantación de los nuevos Grados dentro del EEES supone un nuevo enfoque metodológico, pero sobre todo evaluador. El profesor debe esforzarse en ser capaz de valorar no sólo el nivel de conocimientos del alumnado sobre los contenidos, ya que la sociedad actual demanda un perfil de los egresados más completo basado en la formación por competencias. La adquisición de ambas facetas por parte del alumnado se basa principalmente en actividades presenciales y metodologías docentes aplicadas en el desarrollo de las asignaturas, tanto en grupo reducido como en grupo completo. Por tanto, cualquier herramienta adicional que ayude al docente a facilitar esta doble tarea es bien recibida, pues permitirá evaluar el rendimiento académico global del alumnado. Recientemente la Facultad de Ciencias ha puesto en marcha una experiencia piloto mediante la cual un nutrido grupo de profesores ha incorporado en su docencia un sistema de mandos inalámbricos de respuesta. Actualmente, la Facultad de Ciencias dispone de un total de 82 mandos inalámbricos de respuesta y tres antenas receptoras. Esta nueva tecnología ha permitido al docente realizar, de forma interactiva, preguntas colectivas al alumnado y recoger las respuestas individuales de forma inmediata. Los resultados obtenidos en este proyecto nos permiten ser muy optimistas con el uso de esta herramienta y nos animan a continuar en la misma línea. El profesorado participante se ha mostrado dispuesto a continuar empleando esta TIC en su docencia, tratando de abarcar más asignaturas, diversificar el tipo de pruebas, y emplear los mandos de respuesta en grupo completo, cuando el número de alumnos lo permita. La puesta en común de los resultados revela que, de forma general, este tipo de sistemas de respuesta incrementa el nivel de atención del alumnado, ya que se les demanda de forma continuada su participación activa durante la sesión. Se potencia la retención de conceptos, al suministrar en el acto la respuesta correcta a cada pregunta realizada. Permite también al profesorado conocer el nivel previo de conocimientos sobre la materia a impartir, ya que se puede realizar este tipo de preguntas al comienzo de la sesión y enfocar entonces su atención en las debilidades manifestadas. Asimismo se puede testar el grado de adquisición de dichos conocimientos, realizando este tipo de cuestionarios después de la sesión. Además, el tratamiento posterior de los resultados, de forma individualizada, permite gestionar de forma ágil el nivel de conocimientos y adquisición de competencias en lo que es un sistema de evaluación continua, tan necesario en los nuevos enfoques metodológicos nacidos de la implantación del EEES. Por último destacar que el profesorado participante ha considerado que se trata de una herramienta de gran utilidad para la consecución del objetivo de excelencia en la docencia, que además es eficaz y de fácil manejo, y entiende que no debe ser una actividad puntual, sino un proceso transformador en la actividad docente e interacción alumno-profesor, configurándose como una herramienta habitual en los sistemas de enseñanza-aprendizaje.Implementation of the new degrees in the EHEA involve a new methodological approach, but above all evaluation. The teacher should strive to be able to assess not only the level of knowledge of the students on the content, as the current society demands a profile of the most complete graduates based on training by competencies. The acquisition of both facets by students is based mainly on face-to-face activities and teaching methodologies applied in the development of the subjects, both in small group and in whole group. Therefore, any additional tool that helps the teacher to facilitate this double task is well received, since it will allow to evaluate the overall academic performance of the students. Recently the Faculty of Sciences has launched a pilot experience through which a large group of teachers has incorporated into their teaching a system of interactive response devices. Currently, the Faculty of Sciences has a total of 82 wireless response controllers and three receiving antennas. This new technology has enabled the teacher to interact interactively with the students and collect the individual answers immediately. The results obtained in this project allow us to be very optimistic with the use of this tool and encourage us to continue in the same line. The participating teachers have been willing to continue using this ICT in their teaching, trying to cover more subjects, diversify the type of tests, and use the full group response commands, when the number of students allows. The sharing of results reveals that, in a general way, this type of response systems increases the level of attention of the students, since they are continuously demanded their active participation during the session. The retention of concepts is strengthened by providing the correct answer to every question asked. It also allows the faculty to know the previous level of knowledge about the subject to be taught, since this type of questions can be asked at the beginning of the session and then focus their attention on the weaknesses manifested. It is also possible to test the degree of acquisition of this knowledge, performing this type of questionnaire after the session. In addition, the subsequent treatment of the results, in an individualized way, allows to manage in an agile way the level of knowledge and acquisition of competences in what is a system of continuous evaluation, so necessary in the new methodological approaches born from the implantation of the EHEA. Finally, it should be pointed out that the participating teachers have considered that this is a very useful tool for achieving the objective of excellence in teaching, which is also efficient and easy to use and understands that it should not be a specific activity, but a transforming process in the teaching activity and student-teacher interaction, being configured as a habitual tool in the teaching-learning systems