Optimización de los protocolos de hiperestimulación ovárica controlada para FIV/ICSI en pacientes diagnosticadas de síndrome de ovarios poliquísticos

Objetivo principal Comprobar la eficacia y seguridad de la estimulación con FSHr bajo bloqueo gonadotropo hipofisario por administración de una antagonista de GnRH (Ganirelix) iniciando ésta al comienzo del ciclo menstrual, simultáneamente a la administración de FSHr en un grupo de estudio formado por mujeres estériles diagnosticadas de SOP. Material y Métodos Diseño: Estudio longitudinal prospectivo y comparativo, no randomizado, de 3 años de duración. Muestra: 278 pacientes diagnosticadas de SOP según criterios ESHRE para tratamiento FIV/ICSI divididas en dos grupos: • Grupo estudio: (Grupo Antagonista): 123 pacientes tratadas con Ganirelix 0,25 mg/d desde día 3. • Grupo control (Grupo Agonista): 155 pacientes Nafarelina 400 µg/d, desde el día 22 del ciclo previo. Intervenciones: - Hiperestimulación ovárica controlada - Punción-aspiración folicular - Cultivo y fecundación de los ovocitos - Transferencia de preembriones - Suplementación de la fase lutea - Diagnóstico de la gestación - Resultados perinatales - Estudio estadístico SPSS 11.0 - Estudio coste efectividad según ley de tasas. DOGV nº 4971 1/2005. Resultados Antagonista Agonista Valor p Magnitud asociación Días de estímulo 8(7-9)a 8(7-9) a 0,891 c 0,210e Total FSH (UI) 1400(1200-1625) a 1400(1150-1681) a 0,273 c -0,069e Estradiol -2 (pg/ml) 1879(1400-2500) a 2399(1537-3028) a 0,002 c 0,201e Estradiol 0 (pg/ml) 1340(1030-1842) a 1609(1206-2006) a 0,020 c 0,161e Estradiol +2 (pg/ml) 1120(800-1450) a 1123(859-1454) a 0,992 c 0,001e Grosor LE (mm) 11(10-13) a 12(11-13) a 0,282 c 0,67e Progesterona 0 (ng/ml) 9,6(6,0-15,5) a 7,4(5,2-10,1) a 0,014 c -0,189e Progesterona +2 (ng/ml) 49,9(37,2-71,1) a 51,2(35,5-68,0)a 0,692 c -0,26e Cancelación total ciclo 1,6 b 15,4 b 0,002d R hiperestimulación 1,6 b 13,3 b <0,001 d 9,41f Falta respuesta 0 b 3,2 b 0,709d 1,27f Folículos ≥16mm 8(6-11)a 9(6-12) a 0,205 c -0,22e Diámetro del folículo mayor (mm) 20(19-21)a 20(19-21) a 0,227 c -0,083e Ovocitos obtenidos 11(8-16)a 13(8-15) a 0,372 c 0,073e Ovocitos Metafase II 8(4-12)a 8(5-12) a 0,422 c -0,034e a mediana(rango intercuartil) b % c U-Mann Withney d Chi2 e Correlación de Spearman f RR Antagonistas (%) Agonistas (%) valorap RR IC95% Tasa de gestación 27,6 27,1 0,919d 1,028 0,605-1,747 Tasa de implantación 19,3 22,8 0,651d 0,878 0,499-1,543 Tasa de aborto 25,0 18,9 0,584d 1,385 0,501-3,834 Tasa de gestación múltiple 17,8 27,5 0,356d 0,573 0,174-1,885 Tasa de recién nacido 22,8 24,5 0,686d 0,884 0,487-1,606 Tasa de recién nacido sano a término 18,7 16,8 0,273 d 1,021 0,544-1,920 Tasa de prematuridad 4,1 7,8 0,597d 0,670 0,151-2,974 a Chi2 Estudio coste-efectividad Coste niño sano € Total 18018,5 Antagonista 16596,2 Agonista 19276,7 Conclusiones 1. La estimulación de mujeres SOP con FSHr con un antagonista de GnRH administrado simultáneamente a la FSHr representa un protocolo eficaz que proporciona tasas de gestación e implantación similares al bloqueo hipofisario con agonistas en protocolo largo. 2. El protocolo de empleo de antagonista utilizado es seguro tanto para la madre como para el nacido. En particular disminuye el riesgo de que se produzca un síndrome de hiperestimulación ovárica como consecuencia del tratamiento respecto a los protocolos en que se utiliza agonista en protocolo largo. 3. El uso de antagonista de GnRH desde el inicio de la estimulación no anula pero sí resulta efectivo en la prevención del síndrome de hiperestimulación ovárica 4. El coste de un ciclo de FIV es ligeramente más económico utilizando antagonistas que utilizando agonistas en protocolo largo. El coste de obtener un recién nacido sano a término (no así el de obtener un recién nacido) es sensiblemente menor utilizando agonista simultáneamente a las gonadotrofinas que utilizando agonista en protocolo largo.Main objective To determine the efficacy and safety of rFSH stimulation under pituitary gonadotropic blockade by administration of a GnRH antagonist (ganirelix) initiating it at the beginning of the menstrual cycle, simultaneously with the administration of rFSH in a study group composed of infertile women diagnosed with PCOS . Material and Methods Design: Prospective, comparative, non randomized study of 3 years. Sample: 278 patients diagnosed with PCOS according to ESHRE criteria for IVF / ICSI split into two groups: • Study group (antagonist group): Ganirelix 123 patients treated with 0.25 mg /day, from day 3. • Control group (Group Agonist): 155 patients nafarelin 400 mg /day, from day 22 of the previous cycle. Interventions: - Controlled ovarian hyperstimulation - Follicular puncture-aspiration - Culture and fertilization of oocytes - Transfer of pre-embryos - Supplementation of the luteal phase - Diagnosis of pregnancy Results: No difference observed in stimulating days, Total FSH consumed, follicles developed, oocytes retrieved, fecundation rates, pregnancy rates, implantation rates or abortion rates. Cycle cancellation for ovarian hyperstimulation risk 1,6%(antagonist) vs 13,3% (agonist) (p<0,001 RR 9,41 IC95% 2,18-41,28) was statistically different. Conclusions 1. Stimulation of PCOS women with rFSH with a GnRH antagonist rFSH administered simultaneously with an effective protocol that provides pregnancy and implantation rates similar to blocking agonist in pituitary long protocol. 2. The use of antagonist protocol used is safer for both mother and baby. In particular reduces the risk of occurrence of ovarian hyperstimulation syndrome from treatment with respect to the protocols used agonist long protocol. 3. The use of GnRH antagonist from the beginning of stimulation does not cancel but is effective in preventing ovarian hyperstimulation syndrome. 4. The cost of an IVF cycle is slightly more economical using agonists, antagonists that using long protocol. The cost of obtaining a healthy newborn at term (but not to obtain a newborn) is significantly less simultaneously using gonadotropins agonist that using agonist long protocol

Multipactor radiation analysis within a waveguide region based on a frequency-domain representation of the dynamics of charged particles

A technique for the accurate computation of the electromagnetic fields radiated by a charged particle moving within a parallel-plate waveguide is presented. Based on a transformation of the time-varying current density of the particle into a time-harmonic current density, this technique allows the evaluation of the radiated electromagnetic fields both in the frequency and time domains, as well as in the near- and far-field regions. For this purpose, several accelerated versions of the parallel-plate Green’s function in the frequency domain have been considered. The theory has been successfully applied to the multipactor discharge occurring within a two metal-plates region. The proposed formulation has been tested with a particle-in-cell code based on the finite- difference time-domain method, obtaining good agreement.The authors would like to thank ESA/ESTEC for having funded this research activity through the Contract “RF Breakdown in Multicarrier Systems” ͑Contract No. 19918/06/NL/GLC͒

An analytical model to evaluate the radiated power spectrum of a multipactor discharge in a parallel-plate region

This paper is aimed at studying the electromagnetic radiation pattern of a multipactor discharge occurring in a parallel-plate waveguide. The proposed method is based on the Fourier expansion of the multipactor current in terms of timeharmonic currents radiating in the parallel-plate region. Classical radiation theory combined with the frequency domain Green’s function of the problem allows the calculation of both the electric and the magnetic radiated fields. A novel analytical formula for the total radiated power of each multipactor harmonic has been derived. This formula is suitable for predicting multipactor with the third-harmonic technique. The proposed formulation has been successfully tested with a particle-in-cell code

Highly efficient full-wave electromagnetic analysis of 3D arbitrarily-shaped waveguide microwave devices using an integral equation technique

A novel technique for the full-wave analysis of 3-D complex waveguide devices is presented. This new formulation, based on the Boundary Integral-Resonant Mode Expansion (BI-RME) method, allows the rigorous full-wave electromagnetic characterization of 3-D arbitrarily shaped metallic structures making use of extremely low CPU resources (both time and memory). The unknown electric current density on the surface of the metallic elements is represented by means of Rao-Wilton-Glisson basis functions, and an algebraic procedure based on a singular value decomposition is applied to transform such functions into the classical solenoidal and nonsolenoidal basis functions needed by the original BI-RME technique. The developed tool also provides an accurate computation of the electromagnetic fields at an arbitrary observation point of the considered device, so it can be used for predicting high-power breakdown phenomena. In order to validate the accuracy and efficiency of this novel approach, several new designs of band-pass waveguides filters are presented. The obtained results (S-parameters and electromagnetic fields) are successfully compared both to experimental data and to numerical simulations provided by a commercial software based on the finite element technique. The results obtained show that the new technique is specially suitable for the efficient full-wave analysis of complex waveguide devices considering an integrated coaxial excitation, where the coaxial probes may be in contact with the metallic insets of the component.This work was supported by the Ministerio de Economia y Competitividad, Spanish Government, under the Research Projects TEC2013-47037-C5-1-R and TEC2013-47037-C5-4-R.Vidal Pantaleoni, A.; San Blas Oltra, ÁA.; Quesada Pereira, FD.; Pérez Soler, FJ.; Gil Raga, J.; Vicente Quiles, CP.; Gimeno Martinez, B.... (2015). Highly efficient full-wave electromagnetic analysis of 3D arbitrarily-shaped waveguide microwave devices using an integral equation technique. Radio Science. 50(7):642-655. https://doi.org/10.1002/2015RS005685S64265550

Naturalization of the microbiota developmental trajectory of Cesarean-born neonates after vaginal seeding

Early microbiota perturbations are associated with disorders that involve immunological underpinnings. Cesarean section (CS)-born babies show altered microbiota development in relation to babies born vaginally. Here we present the first statistically powered longitudinal study to determine the effect of restoring exposure to maternal vaginal fluids after CS birth.This work was partially supported by the C&D Research Fund, the Emch Fund for Human Microbiome Studies, and CIFAR FS20-078 #125869 (to M.G.D.-B.); Chilean CONICYT PIA/ANILLO grant ACT172097 and Chilean SOCHIPE Project 022019 (to P.R.H.); and the Norwegian Institute of Public Health (2019-0350), the Emerald Foundation, an NIH Pioneer award (1DP1AT010885), the National Institute of Justice (2016-DN-BX-4194), the San Diego Digestive Diseases Research Center (NIDDK 1P30DK120515), Janssen Pharmaceuticals (20175015)Peer reviewe

Efecto de Prostaglandina E2 en la expresión de proteínas en los estómagos de mosquitos hembras de Anopheles albimanus

La malaria es la enfermedad parasitaria más importante del mundo; en México hay casos producidos por Plasmodium vivax transmitido por mosquitos Anopheles albimanus. Mediante electroforesis bidimensional se analizó el cambio en expresión de proteínas de estómagos de An. albimanus hembra por efecto de prostaglandina E2 (PGE2) y seis de ellas se identificaron por espectrometría de masas. La ATPasa mitocondrial y la calreticulina disminuyeron su concentración, sugiriendo cambios del metabolismo energético y señalización celular. Tres isoformas de actina y una serina proteasa aumentaron, indicando modificaciones en citoesqueleto y respuesta inmune.Malaria is the most important parasitic disease in the world; in México there are cases produced by Plasmodium vivax transmitted by Anopheles albimanus mosquitoes. In this work, the effect of prostaglandin E2 (PGE2) on protein profiles of An. albimanus female mosquito midguts was studied by mean of bidimensional electrophoresis and six of them were mass spectrometry identified. Mitochondrial ATPase and calreticulin diminished their concentration suggesting effect on energetic metabolism and cell signaling. Three actin isoforms and one serine protease increased their expression suggesting cytoskeleton rearrangements and activation of immune response

Multimodal Characterization of the Multipactor Effect in Microwave Waveguide Components

Multipactor effect is a resonant avalanche of secondary electrons induced by an RF electromagnetic field, which endangers high-power payloads on satellites and particle accelerator structures. The main goal of this letter is to present a multimodal network characterization of a multipactor discharge occurring in a bounded waveguide region. This will allow to perform a rigorous analysis of a complete passive component considering the presence of a discharge. In order to verify the present formulation, we have measured the power spectrum generated by a multipactor event excited in a simple microwave circuit based on rectangular waveguides, which has been compared with the theoretical results, obtaining good agreement.This work was supported by ESA/ESTEC through the NPI program and through the contract 20841/08/NL/GLC.Jimenez, M.; Gimeno Martinez, B.; Raboso García-Baquero, D.; Anza Hormigo, S.; Alvarez Melcon, A.; Quesada Pereira, FD.; Boria Esbert, VE.... (2012). Multimodal Characterization of the Multipactor Effect in Microwave Waveguide Components. IEEE Microwave and Wireless Components Letters. 22(2):61-63. doi:10.1109/LMWC.2011.2181831S616322

MAMI: a birth cohort focused on maternal-infant microbiota during early life

Early microbial colonization is a relevant aspect in human health. Altered microbial colonization patterns have been linked to an increased risk of non-communicable diseases (NCDs). Advances in understanding host-microbe interactions highlight the pivotal role of maternal microbiota on infant health programming. This birth cohort is aimed to characterize the maternal microbes transferred to neonates during the first 1000 days of life, as well as to identify the potential host and environmental factors, such as gestational age, mode of delivery, maternal/infant diet, and exposure to antibiotics, which affect early microbial colonization.This study is supported through a five-year grant from European Research Council (ERC) - European Union’s Horizon 2020 Framework - with an ERC Starting Grant (ref. 639226). Funding received from this grant supports direct research costs and research assistant salaries. The ERC had no direct role in the design of this study and will not in the collection, analysis or interpreting of data, or manuscript writing

Fibrinogen nitrotyrosination after ischemic stroke impairs thrombolysis and promotes neuronal death

Ischemic stroke is an acute vascular event that compromises neuronal viability, and identification of the pathophysiological mechanisms is critical for its correct management. Ischemia produces increased nitric oxide synthesis to recover blood flow but also induces a free radical burst. Nitric oxide and superoxide anion react to generate peroxynitrite that nitrates tyrosines. We found that fibrinogen nitrotyrosination was detected in plasma after the initiation of ischemic stroke in human patients. Electron microscopy and protein intrinsic fluorescence showed that in vitro nitrotyrosination of fibrinogen affected its structure. Thromboelastography showed that initially fibrinogen nitrotyrosination retarded clot formation but later made the clot more resistant to fibrinolysis. This result was independent of any effect on thrombin production. Immunofluorescence analysis of affected human brain areas also showed that both fibrinogen and nitrotyrosinated fibrinogen spread into the brain parenchyma after ischemic stroke. Therefore, we assayed the toxicity of fibrinogen and nitrotyrosinated fibrinogen in a human neuroblastoma cell line. For that purpose we measured the activity of caspase-3, a key enzyme in the apoptotic pathway, and cell survival. We found that nitrotyrosinated fibrinogen induced higher activation of caspase 3. Accordingly, cell survival assays showed a more neurotoxic effect of nitrotyrosinated fibrinogen at all concentrations tested. In summary, nitrotyrosinated fibrinogen would be of pathophysiological interest in ischemic stroke due to both its impact on hemostasis - it impairs thrombolysis, the main target in stroke treatments - and its neurotoxicity that would contribute to the death of the brain tissue surrounding the infarcted area.This work was supported by the Spanish Ministry of Science and Innovation (SAF2012-38140; SAF 2009-10365); Fondo de Investigación Sanitaria (FIS PI13/00408, FIS PI13/00864, CP04-00112, PS09/00664 and Red HERACLESRD12/0042/0014, RD12/0042/0016 and RD12/0042/0020); FEDER Funds; Generalitat de Catalunya (SGR09-1369); and Fundació la Marató de TV3 (100310). Dr. A.M. Galán belongs to the Miguel Servet stabilization program of the Spanish Government's ISCIII research institute and “Direcció d'Estratègia i Coordinació del Departament de Salut” of the Generalitat de Catalunya

ENGIU: Encuentro Nacional de Grupos de Investigación de UNIMINUTO.

El desarrollo del prototipo para el sistema de detección de Mina Antipersona (MAP), inicia desde el semillero ADSSOF perteneciente al programa de Administración en Seguridad y Salud en el trabajo de la UNIMINUTO, se realiza a partir de un detector de metales que emite una señal audible, que el usuario puede interpretar como aviso de presencia de un objeto metálico, en este caso una MAP. La señal audible se interpreta como un dato, como ese dato no es perceptible a 5 metros de distancia, se implementa el transmisor de Frecuencia Modulada FM por la facilidad de modulación y la escogencia de frecuencia de transmisión de acuerdo con las normas y resolución del Ministerio de Comunicaciones; de manera que esta sea la plataforma base para enviar los datos obtenidos a una frecuencia establecida. La idea es que el ser humano no explore zonas peligrosas y buscar la forma de crear un sistema que permita eliminar ese riesgo, por otro lado, buscar la facilidad de uso de elementos ya disponibles en el mercado