Ustekinumab and vedolizumab for the prevention of postoperative recurrence of Crohn's disease: Results from the ENEIDA registry.

BACKGROUND: Anti-TNF agents are the only effective biological agents for the prevention of postoperative recurrence (POR) in Crohn's disease (CD). However, they are contraindicated or have been shown to fail in some patients. Although ustekinumab and vedolizumab were licensed for CD some years ago, data in this setting are scarce. METHODS: All CD patients in whom ustekinumab or vedolizumab was prescribed for the prevention of POR within three months of ileocolonic resection with anastomosis were identified from the ENEIDA registry. The development of endoscopic, clinical and surgical POR was registered. RESULTS: Forty patients were treated for the prevention of POR with ustekinumab and 25 were treated with vedolizumab. Eighty per cent had at least one risk factor for POR (prior resections, active smoking, perianal disease or penetrating disease behaviour). All the patients had been exposed to anti-TNF therapy. After a median follow-up of 17 and 26 months, the cumulative probability of clinical POR at 12 months after surgery was 32% and 30% for ustekinumab and vedolizumab, respectively. Endoscopic assessment within the first 18 months after surgery was available for 80% of the patients on ustekinumab and 70% for those on vedolizumab. The rate of endoscopic POR was 42% for ustekinumab and 40% for vedolizumab. One patient treated with ustekinumab and two with vedolizumab underwent a new intestinal resection. CONCLUSIONS: Ustekinumab and vedolizumab seem to be effective in the prevention of POR in patients at high risk. Our results warrant controlled trials comparing these drugs with conventional therapies.

Implementación del protocolo de recuperación acelerada en la histerectomía abdominal / Implementation of the accelerated recovery protocol in abdominal hysterectomy

Introducción: El perioperatorio en la cirugía electiva evoluciona para reducir el estrés inmunológico y metabólico causado por el trauma quirúrgico y lograr una recuperación temprana. Las enfermedades ginecológicas constituyen un problema de salud mundial, en la que la rehabilitación y reincorporación precoz a la cotidianeidad es fundamental en la disminución de la morbilidad. No existen guías y manuales en Cuba que brinden pautas metodológicas para la implementación de estos protocolos. Objetivo: Determinar la efectividad de la implementación de los protocolos de recuperación acelerada en pacientes sometidas a histerectomía abdominal. Métodos: Se realizó un estudio observacional analítico de casos-control, en pacientes sometidas a histerectomía abdominal en el Hospital General Docente Julio M. Aristegui Villamil en el año 2017. Se utilizaron las variables: grupos etáreos, tiempo de apertura de la vía oral, tiempo de inicio de la deambulación, tiempo de aparición del dolor, variación de la glicemia, presencia de náuseas, vómitos y complicaciones, estadía hospitalaria. Resultados: Predominó la edad entre 41 y 60 años en ambos grupos. En el grupo casos prevaleció la apertura de la vía oral en las primeras 4 h y la deambulación precoz según el esquema en las primeras 3 h. Se reportó mayor incidencia de dolor en el grupo control al igual que la variación de la glicemia, también reportándose náuseas, vómitos y complicaciones como fiebre e íleo paralítico. Se logró una estadía hospitalaria promedio de 24 h en el grupo de casos mientras que en el tradicional fue superior. Conclusiones: El protocolo de trabajo diseñado contribuyó a la recuperación precoz(AU)

Introduction: The perioperative period in elective surgery evolves up to reducing immune and metabolic stress caused by surgical trauma and achieving early recovery. Gynecological diseases are a global health concern in which rehabilitation and early return to daily life is essential in reducing morbidity. There are no guides and manuals in Cuba that provide methodological guidelines for the implementation of these protocols. Objective: To determine the effectiveness of implementing accelerated recovery protocols in patients undergoing abdominal hysterectomy. Methods: An analytical and observational case-control study was carried out in patients undergoing abdominal hysterectomy at Julio M. Aristegui Villamil General Teaching Hospital in 2017. The following variables were used: age groups, oral intake time, ambulation onset time, pain onset time, glycemic variation, presence of nausea, vomiting and complications, hospital stay. Results: Age between 41 and 60 years predominated in both groups. In the case group, there was a prevalence of oral intake time at four hours and of early ambulation, according to the scheme, within the first three hours. A higher incidence of pain was reported in the control group, together with glycemic variability, apart from reports of nausea, vomiting and complications such as fever and paralytic ileus. An average hospital stay of 24 hours was achieved in the case group, while it was longer in the traditional group. Conclusions: The designed work protocol contributed to early recovery(AU)

Regiospecific Synthesis and Structural Studies of 3,5-Dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-ones and Comparison with 1,3-Dihydro-2H-benzo[b][1,4]diazepin-2-ones.

Nine 3,5-dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-ones (17-25), some of which contain fluoro-substituents, have been regiospecifically prepared by reaction of 2,3-diaminopyridines with ethyl aroylacetates. In two cases, open intermediates have been isolated and these are related to the reaction pathway. The X-ray crystal structure of 1-methyl-4-phenyl-3,5-dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-one (23) has been solved (formula, C15H13N3O; crystal system, monoclinic; space group, C2/c). This is an asymmetric unit constituted by a single nonplanar molecule and its conformational enantiomer due to the presence of the seven-membered diazepin-2-one moiety, which introduces a certain degree of torsion in the adjacent pyridine ring. The 1H, 13C, 15N, and 19F NMR spectra were obtained and the chemical shifts, together with those of the previously published 1,3-dihydro-2H-benzo[b][1,4]diazepin-2-ones (1-16), i.e., a total of 544 values, were successfully compared with the chemical shifts calculated at the gauge invariant atomic orbital (GIAO)/Becke, three-parameter, Lee-Yang-Parr (B3LYP)/6-311++G(d,p) level. The seven-membered ring inversion barrier in 5-benzyl-2-phenyl-3,5-dihydro-4H-pyrido[2,3-b][1,4]diazepin-4-one (25) was determined and, in conjunction with the data from the literature, compared with the B3LYP/6-311++G(d,p) computed values. This allowed the determination of several structural effects. The rotation about the exocyclic N1-CR bond was also calculated and its dynamic properties were discussed.

Protocolo de estudio cuasi-experimental para promover un estilo interpersonal de apoyo a la autonomía en docentes de educación física / Protocol quasi-experimental study to promote interpersonal style autonomy support in physical education teachers / Protocolo de estudo quase-experimental para promover um estilo interpessoal de apoio à autonomia em professores de educação física

Según la Teoría de la Autodeterminación (Deci y Ryan, 1985, 2002), el estilo interpersonal que utilice el educador puede tener un fuerte impacto en la motivación de los estudiantes. Los objetivos de este artículo fueron: (I) explicar la justificación y desarrollo de un programa de formación basado en esta teoría para promover el apoyo a la autonomía; (II) describir el protocolo de estudio y los procedimientos de evaluación del programa de formación; y (III) probar la integridad del protocolo de estudio para una futura intervención. De un total de 40 docentes de educación física, se asignarán 20 a un grupo de intervención o a un grupo control (n = 20). Durante un período de 8 semanas, los docentes del grupo de intervención completarán un programa de formación en apoyo a la autonomía a través de varias fases. Se evaluarán indicadores que caracterizan el estilo interpersonal de apoyo a la autonomía de forma cualitativa y cuantitativa, tanto al docente como al estudiante. La recogida de los datos de la línea base cuantitativa se llevará a cabo un mes antes del inicio de la intervención y un mes después de la finalización del período de intervención. Los datos cuantitativos se analizarán mediante análisis multinivel. Para explorar las percepciones del programa de formación, también se llevará a cabo un seguimiento a través de entrevistas semiestructuradas con docentes y miembros de la clase, de cuatro a seis semanas después del final de la intervención. Este estudio cuenta con la aprobación del Comité de Ética de las instituciones participantes. Los hallazgos del estudio se difundirán a través de revistas de impacto científico y presentaciones en conferencias sobre la temática de estudio de carácter internacional

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A high-throughput ratiometric method for imaging hypertrophic growth in cultured primary cardiac myocytes.

Maladaptive hypertrophy of cardiac myocytes increases the risk of heart failure. The underlying signaling can be triggered and interrogated in cultured neonatal ventricular myocytes (NRVMs) using sophisticated pharmacological and genetic techniques. However, the methods for quantifying cell growth are, by comparison, inadequate. The lack of quantitative, calibratable and computationally-inexpensive high-throughput technology has limited the scope for using cultured myocytes in large-scale analyses. We present a ratiometric method for quantifying the hypertrophic growth of cultured myocytes, compatible with high-throughput imaging platforms. Protein biomass was assayed from sulforhodamine B (SRB) fluorescence, and image analysis calculated the quotient of signal from extra-nuclear and nuclear regions. The former readout relates to hypertrophic growth, whereas the latter is a reference for correcting protein-independent (e.g. equipment-related) variables. This ratiometric measure, when normalized to the number of cells, provides a robust quantification of cellular hypertrophy. The method was tested by comparing the efficacy of various chemical agonists to evoke hypertrophy, and verified using independent assays (myocyte area, transcripts of markers). The method's high resolving power and wide dynamic range were confirmed by the ability to generate concentration-response curves, track the time-course of hypertrophic responses with fine temporal resolution, describe drug/agonist interactions, and screen for novel anti-hypertrophic agents. The method can be implemented as an end-point in protocols investigating hypertrophy, and is compatible with automated plate-reader platforms for generating high-throughput data, thereby reducing investigator-bias. Finally, the computationally-minimal workflow required for obtaining measurements makes the method simple to implement in most laboratories.

Adalimumab or Infliximab for the Prevention of Early Postoperative Recurrence of Crohn Disease: Results From the ENEIDA Registry.

BACKGROUND: Anti-tumor necrosis factor agents (anti-TNFs) are efficacious at preventing the postoperative recurrence (POR) of Crohn disease, as demonstrated in 2 randomized controlled trials. However, real-life data for infliximab or adalimumab in this setting are scarce. Our aim was to assess both the efficiency of anti-TNFs at preventing early POR of Crohn disease in clinical practice and the associated risk factors for POR. METHODS: Patients in whom anti-TNFs were prescribed for the prevention of POR within 3 months after ileocolonic resection and who had an endoscopic assessment within 18 months were identified from the ENEIDA registry. Clinical and endoscopic features were collected within 18 months after surgery. RESULTS: In total, 152 patients were included (55 treated with infliximab, 97 with adalimumab, and 39% with concomitant immunosuppressants). Anti-TNF treatment was started after a median time of 29 days (IQR 13-44) after surgery. Eighty-two percent of patients had at least one risk factor for POR, and 82% had been exposed to anti-TNFs before the index surgery. Overall, 34% had endoscopic POR (as defined using a Rutgeerts endoscopic score > i1); 14% had advanced endoscopic POR (>i2); and 20% had clinical POR, with no differences between infliximab and adalimumab. In the multivariate analysis, only perianal disease (odds ratio 2.73, 95% confidence interval [CI] 1.26-5.91) and rectal involvement (odds ratio 2.79, 95% CI 1.09-7.14) were independent predictors of endoscopic POR. CONCLUSIONS: In clinical practice, anti-TNFs for the prevention of POR of Crohn disease are frequently used in patients experienced with anti-TNFs and with concomitant immunosuppressants. The efficacy of infliximab and adalimumab for POR prevention is similar and in accordance with the results obtained in randomized controlled trials.

Statistical Tools for Air Pollution Assessment: Multivariate and Spatial Analysis Studies in the Madrid Region.

The present work reports the distribution of pollutants in the Madrid city and province from 22 monitoring stations during 2010 to 2017. Statistical tools were used to interpret and model air pollution data. The data include the annual average concentrations of nitrogen oxides, ozone, and particulate matter (PM10), collected in Madrid and its suburbs, which is one of the largest metropolitan places in Europe, and its air quality has not been studied sufficiently. A mapping of the distribution of these pollutants was done, in order to reveal the relationship between them and also with the demography of the region. The multivariate analysis employing correlation analysis, principal component analysis (PCA), and cluster analysis (CA) resulted in establishing a correlation between different pollutants. The results obtained allowed classification of different monitoring stations on the basis of each of the four pollutants, revealing information about their sources and mechanisms, visualizing their spatial distribution, and monitoring their levels according to the average annual limits established in the legislation. The elaboration of contour maps by the geostatistical method, ordinary kriging, also supported the interpretation derived from the multivariate analysis demonstrating the levels of NO2 exceeding the annual limit in the centre, south, and east of the Madrid province.

BET inhibition as a new strategy for the treatment of gastric cancer.

Gastric cancer is one of the most common malignancies and a leading cause of cancer death worldwide. The prognosis of stomach cancer is generally poor as this cancer is not very sensitive to commonly used chemotherapies. Epigenetic modifications play a key role in gastric cancer and contribute to the development and progression of this malignancy. In order to explore new treatment options in this target area we have screened a library of epigenetic inhibitors against gastric cancer cell lines and identified inhibitors for the BET family of bromodomains as potent inhibitors of gastric cancer cell proliferations. Here we show that both the pan-BET inhibitor (+)-JQ1 as well as a newly developed specific isoxazole inhibitor, PNZ5, showed potent inhibition of gastric cancer cell growth. Intriguingly, we found differences in the antiproliferative response between gastric cancer cells tested derived from Brazilian patients as compared to those from Asian patients, the latter being largely resistant to BET inhibition. As BET inhibitors are entering clinical trials these findings provide the first starting point for future therapies targeting gastric cancer.

Discovery of a Chemical Tool Inhibitor Targeting the Bromodomains of TRIM24 and BRPF.

TRIM24 is a transcriptional regulator as well as an E3 ubiquitin ligase. It is overexpressed in diverse tumors, and high expression levels have been linked to poor prognosis in breast cancer patients. TRIM24 contains a PHD/bromodomain offering the opportunity to develop protein interaction inhibitors that target this protein interaction module. Here we identified potent acetyl-lysine mimetic benzimidazolones TRIM24 bromodomain inhibitors. The best compound of this series is a selective BRPF1B/TRIM24 dual inhibitor that bound with a KD of 137 and 222 nM, respectively, but exerted good selectivity over other bromodomains. Cellular activity of the inhibitor was demonstrated using FRAP assays as well as cell viability data.

Inflammatory status is different in relationship to insulin resistance in severely obese people and changes after bariatric surgery or diet-induced weight loss.

AIM: To assess if insulin resistance is related to a different inflammatory status (especially lymphocyte subpopulations) in severely obese people and to evaluate changes after weight loss either following a very-low calorie diet (VLCD) or bariatric surgery. RESEARCH METHODS & PROCEDURES: Severely obese patients were consecutively recruited in our Obesity Unit. Blood lymphocyte subpopulations and inflammatory parameters were measured baseline, after a VLCD during 6 weeks and one year after biliopancreatic diversion. Insulin resistance was evaluated by Homeostasis Model Assessment (HOMA) index. RESULTS: After excluding diabetic patients, 58 patients were studied. HOMA index classified 63.8% of them as insulin resistant (IR). Serum baseline levels of inflammatory cytokines were not significantly different between IR and insulinsensitive (IS) patients but, regarding lymphocyte subpopulations, Natural Killer (NK) cells were higher in IR patients [(305.0 (136.7) vs. 235.0 (80.7) cells/µL, p=0.047]. NK cells showed a significant positive correlation with HOMA index (r=0.484, p=0.000) and with the carbohydrate content of the diet (r=0.420, p=0.001). After VLCD, NK cells significantly decreased, but only in IR patients and in those losing more than 10% of their initial weight. After biliopancreatic diversion, total and CD8 T Lymphocytes, B lymphocytes and NK cells also decreased but only in IR individuals. CONCLUSION: NK cells are significantly increased in IR severely obese people in respect to IS, suggesting a slightly different immune status in these patients with a probable dietary relationship. Weight loss could reverse this increase either after VLCD or after bariatric surgery.

Aerosol delivery of DNA/liposomes to the lung for cystic fibrosis gene therapy.

Abstract Lung gene therapy is being evaluated for a range of acute and chronic diseases, including cystic fibrosis (CF). As these therapies approach clinical realization, it is becoming increasingly clear that the ability to efficiently deliver gene transfer agents (GTAs) to target cell populations within the lung may prove just as critical as the gene therapy formulation itself in terms of generating positive clinical outcomes. Key to the success of any aerosol gene therapy is the interaction between the GTA and nebulization device. We evaluated the effects of aerosolization on our preferred formulation, plasmid DNA (pDNA) complexed with the cationic liposome GL67A (pDNA/GL67A) using commercially available nebulizer devices. The relatively high viscosity (6.3±0.1 cP) and particulate nature of pDNA/GL67A formulations hindered stable aerosol generation in ultrasonic and vibrating mesh nebulizers but was not problematic in the jet nebulizers tested. Aerosol size characteristics varied significantly between devices, but the AeroEclipse II nebulizer operating at 50 psi generated stable pDNA/GL67A aerosols suitable for delivery to the CF lung (mass median aerodynamic diameter 3.4±0.1 µm). Importantly, biological function of pDNA/GL67A formulations was retained after nebulization, and although aerosol delivery rate was lower than that of other devices (0.17±0.01 ml/min), the breath-actuated AeroEclipse II nebulizer generated aerosol only during the inspiratory phase and as such was more efficient than other devices with 83±3% of generated aerosol available for patient inhalation. On the basis of these results, we have selected the AeroEclipse II nebulizer for the delivery of pDNA/GL67A formulations to the lungs of CF patients as part of phase IIa/b clinical studies.

Rapid identification of novel functional promoters for gene therapy.

Transcriptional control of transgene expression is crucial to successful gene therapy, yet few promoter/enhancer combinations have been tested in clinical trials. We created a simple, desktop computer database and populated it with promoter sequences from publicly available sources. From this database, we rapidly identified novel CpG-free promoter sequences suitable for use in non-inflammatory, non-viral in vivo gene transfer. In a simple model of lung gene transfer, five of the six promoter elements selected, chosen without prior knowledge of their transcriptional activities, directed significant transgene expression. Each of the five novel promoters directed transgene expression for at least 14 days post-delivery, greatly exceeding the duration achieved with the commonly used CpG-rich viral enhancer/promoters. Novel promoter activity was also evaluated in a more clinically relevant model of aerosol-mediated lung gene transfer and in the liver following delivery via high-pressure tail vein injection. In each case, the novel CpG-free promoters exhibited higher and/or more sustained transgene expression than commonly used CpG-rich enhancer/promoter sequences. This study demonstrates that novel CpG-free promoters can be readily identified and that they can direct significant levels of transgene expression. Furthermore, the database search criteria can be quickly adjusted to identify other novel promoter elements for a variety of transgene expression applications.

CpG-free plasmid expression cassettes for cystic fibrosis gene therapy.

Clinical studies are underway for the aerosol delivery of plasmid DNA complexed with Genzyme Lipid GL67A to the lungs of patients with cystic fibrosis (CF). Plasmid vectors contain several functional elements all of which play a role in determining the efficacy of the final clinical product. To optimise the final plasmid, variations of CpG-free 5' enhancer elements and 3'UTR regions were inserted into a common CpG-free, plasmid backbone containing Luciferase or CFTR transgenes. Plasmids were compared in immortalised cell culture, human airway liquid interface primary cell cultures, and mouse lung models to determine which design directed optimal transgene expression. Following aerosol delivery to mouse lung, plasmids containing the murine CMV enhancer showed higher peak Luciferase activity than the human CMV enhancer, but the human version resulted in persistent expression. In cell culture, the SV40 3'UTR and a novel BGH2 3'UTR exhibited up to 20-fold higher Luciferase activity than the commonly used BGH 3'UTR, but in mouse lung aerosol studies the activity and duration was greater for BGH 3'UTR. Systematic evaluation of each functional component of the plasmid has resulted in an improved design, exhibiting superior levels and duration of lung gene expression.

Asociación entre la adquisición de síndrome gripal y el uso frecuente del transporte público / Association between the acquisition of influenza-like illness and the frequent use of public transport

Introducción. El transporte público en ciudades grandes como Lima puede favorecer el contagio de enfermedades transmitidas por aire, debido al hacinamiento, falta de ventilación y una permanencia prolongada en espacios reducidos. Materiales y métodos. Se realizó un estudio transversal en 592 universitarios de Lima para evaluar la relación entre el uso frecuente de transporte público y la presencia de síndrome gripal. Se definió síndrome gripal como el autorreporte de fiebre más dolor de garganta o tos en las últimas dos semanas, se evaluó el tipo de transporte más usado para acudir a la universidad. Se calculó los OR crudos y ajustados usando regresión logística simple y múltiple. Resultados. El 12,0% (71/592) presentó síndrome gripal en las últimas dos semanas. Se encontró asociación con el uso de transporte público (OR=3,6; IC95% 1,2- 10,2) y con tener contacto en la casa con alguien con síndrome gripal (OR=1,8; IC95% 1,1- 3,1) en el modelo de regresión logística múltiple. No se encontró asociación con la edad, vacunación frente a la influenza, vivir con niños, fumar cigarrillo y antecedentes patológicos. Conclusión. El uso de transporte público está asociado con la presencia de síndrome gripal en un grupo de estudiantes universitarios de Lima.

Background: Public transport in big cities like Lima may favor the spread of air-borne diseases due to overcrowding, poor ventilation and a prolonged stay in confined spaces. Material and methods: We performed a cross-sectional study in 592 students from a private university in Lima to evaluate the relationship between the frequent use of public transport and the presence of influenza-like illness (ILI). Self-report of ILI was defined as fever plus cough or sore throat in last two weeks, most used type of transport to go to university. OR crude and adjusted were calculated used simple and multiple logistic regression. Results: 12.0% (71/592) had ILI in the past two weeks. Use of public transport (OR = 3.6; 95% CI 1.2 to 10.2) and have contact with someone with ILI at home (OR = 1.8; 95% CI 1.1 to 3.1) were found associated in multiple logistic regression model. No association with age, vaccination against influenza, living with children, smoke and pathological history. In conclusion, the use of public transport is associated with the presence of ILI in a group of university students from Lima.

The use of CpG-free plasmids to mediate persistent gene expression following repeated aerosol delivery of pDNA/PEI complexes.

Aerosol gene therapy offers great potential for treating acquired and inherited lung diseases. For treatment of chronic lung diseases such as cystic fibrosis, asthma and emphysema, non-viral gene therapy will likely require repeated administration to maintain transgene expression in slowly dividing, or terminally differentiated, lung epithelial cells. When complexed with plasmid DNA (pDNA), the synthetic polymer, 25 kDa branched Polyethylenimine (PEI), can be formulated for aerosol delivery to the lungs. We show that pDNA/PEI aerosol formulations can be repeatedly administered to airways of mice on at least 10 occasions with no detectable toxicity. Interestingly, peak reporter gene activity upon repeated delivery was significantly reduced by up to 75% compared with a single administration, despite similar pDNA lung deposition at each subsequent aerosol exposure. Although the precise mechanism of inhibition is unknown, it is independent of mouse strain, does not involve an immune response, and is mediated by PEI. Importantly, using a dosing interval of 56 days, delivery of a fourth-generation, CpG-free plasmid generated high-level, sustained transgene expression, which was further boosted at subsequent administrations. Together these data indicate that pDNA/PEI aerosol formulations offer a versatile platform for gene delivery to the lung resulting in sustained transgene expression suitable for treatment of chronic lung diseases.

A novel mixing device for the reproducible generation of nonviral gene therapy formulations.

Nonviral gene therapy utilizing plasmid DNA (pDNA) complexed with cationic lipids (lipoplexes) or cationic polymers (polyplexes) has demonstrated considerable potential for the treatment of a variety of diseases. However, progress toward clinical application is often delayed by the lack of reliable and scalable mixing of components sufficient to guarantee consistent performance in vivo. Attempts to improve and standardize mixing have been limited by the sensitivity of pDNA to shear-related degradation. Here we describe a simple pneumatic mixing device that enables the rapid and reproducible production of large volumes of nonviral gene therapy formulations and demonstrate its suitability for use with shear-sensitive pDNA.

CpG-free plasmids confer reduced inflammation and sustained pulmonary gene expression.

Pulmonary delivery of plasmid DNA (pDNA)/cationic liposome complexes is associated with an acute unmethylated CG dinucleotide (CpG)-mediated inflammatory response and brief duration of transgene expression. We demonstrate that retention of even a single CpG in pDNA is sufficient to elicit an inflammatory response, whereas CpG-free pDNA vectors do not. Using a CpG-free pDNA expression vector, we achieved sustained (>or=56 d) in vivo transgene expression in the absence of lung inflammation.

Adenovirus-mediated in utero expression of CFTR does not improve survival of CFTR knockout mice.

Gene therapy is being investigated in the treatment of lung-related aspects of the genetic disease, Cystic fibrosis (CF). Clinical studies have demonstrated CF transmembrane conductance regulator (CFTR) expression in the airways of adults with CF using a variety of gene transfer agents. In utero gene therapy is an alternative approach that facilitates vector transduction of rapidly expanding populations of target cells while avoiding immune recognition of the vector. In CF, in utero gene transfer could potentially delay the onset of disease symptoms in childhood and compensate for the role, if any, that CFTR plays in the developing organs. Previously published studies have suggested that transient expression of CFTR in utero was sufficient to rescue the fatal intestinal defect in S489X Cftr(tm1Unc)/Cftr(tm1Unc) knockout mice. We replicated these studies using an identical CFTR-expressing adenoviral vector and CF mouse strain in sufficiently large numbers to provide robust Kaplan-Meier survival data. Although each step of the procedure was carefully controlled and vector-specific CFTR expression was confirmed in the fetal organs after treatment, there was statistically no significant improvement in the survival of mice treated in utero with AdCFTR, compared with contemporaneous control animals.

Validación de la Escala de Motivación Educativa (EME) en Paraguay / Validation of the Academic Motivation Scale (AMS) in Paraguay

El propósito de esta investigación ha sido validar en Paraguay la Escala de Motivación Educativa (EME) utilizando una muestra de estudiantes universitarios. Los resultados del análisis factorial confirmatorio y de las correlaciones entre las subescalas de la EME y el autoconcepto académico apoyan la validez de constructo de la escala. Asimismo, la consistencia interna ha sido aceptable en todas las subescalas. Finalmente, se han obtenido diferencias de género que indican que las mujeres presentan, en general, un perfil más autodeterminado que los hombres. Estos resultados apoyan el uso de la EME para evaluar la motivación en educación en Paraguay.(AU)

The aim of the present research has been to validate the Academic Motivation Scale (AMS) in Paraguay using a sample of university students. The results of the confirmatory factor analysis and the correlations between the AMS subscales and the academic self-concept partially support the construct validity of the scale. Likewise, the internal consistency has been acceptable in all subscales. Finally, gender differences were obtained which indicate that, in general, females have shown a more self-determinated profile than males. In conclusion, these results support the use of the AMS to assess the motivation in education in Paraguay.(AU)

Validación de la versión española de la Échelle de Motivation en Éducation / Validity of the Spanish version of the Échelle de Motivation en Éducation

En el contexto educativo se ha desarrollado en francés una escala de medida de la motivación basada en los principios de la teoría de la autodeterminación denominada Échelle de Motivation en Éducation (EME). El propósito de esta investigación ha sido traducir y validar al español la EME utilizando una muestra de estudiantes universitarios. Los resultados indican que la versión en español de la escala denominada Escala de Motivación Educativa (EME-E) ha mostrado niveles satisfactorios de consistencia interna y estabilidad temporal tras un período de siete semanas. Los resultados del análisis factorial confirmatorio confirman la estructura de siete factores de la EME-E. Finalmente, se han obtenido diferencias de género significativas. Estos resultados apoyan el uso de la EME-E para evaluar la motivación en educación

A measure of motivation toward education has been developed in French, namely the Échelle de Motivation en Éducation (EME) and based on the principles of self-determination theory. The aim of this study was to translate in Spanish and to validate the EME completed by 636 university students. The Spanish version of the scale renamed Escala de Motivación Educativa (EME-E) has showed satisfactory levels of internal consistency and temporal stability over a seven weeks period. The results of a confirmatory factor analysis confirmed the seven-factor structure of the EME-E. Finally, gender differences were obtained. These findings support the use of the Spanish version of the EME for the assessment of motivation in education