Cycle scheduling for in vitro fertilization with oral contraceptive pills versus oral estradiol valerate: a randomized, controlled trial

BACKGROUND: Both oral contraceptive pills (OCPs) and estradiol (E(2)) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E(2) valerate. METHODS: Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E(2) pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 μg ethinyl E(2)/150 μg levonorgestrel) for 12–16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E(2) valerate from day 20 for 5–12 days, until the day before starting stimulation. RESULTS: Pretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E(2) (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, –2.0% [95% CI –21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups. CONCLUSIONS: This is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E(2) for IVF with the GnRH antagonist protocol. Although the study is limited by its sample size, our results may contribute to a future meta-analysis. An interesting future direction would be to extend our study to women with decreased ovarian reserve, as these are the patients in whom an increase in oocyte yield—due to the hypothetical beneficial effect of steroid pretreatment on follicular synchronization—could more easily be demonstrated. TRIAL REGISTRATION: ClinicalTrials.gov http://NCT01501448

Regulation of Dendritic Cell Migration to the Draining Lymph Node: Impact on T Lymphocyte Traffic and Priming

Antigen-pulsed dendritic cells (DCs) are used as natural adjuvants for vaccination, but the factors that influence the efficacy of this treatment are poorly understood. We investigated the parameters that affect the migration of subcutaneously injected mouse-mature DCs to the draining lymph node. We found that the efficiency of DC migration varied with the number of injected DCs and that CCR7+/+ DCs migrating to the draining lymph node, but not CCR7−/− DCs that failed to do so, efficiently induced a rapid increase in lymph node cellularity, which was observed before the onset of T cell proliferation. We also report that DC migration could be increased up to 10-fold by preinjection of inflammatory cytokines that increased the expression of the CCR7 ligand CCL21 in lymphatic endothelial cells. The magnitude and quality of CD4+ T cell response was proportional to the number of antigen-carrying DCs that reached the lymph node and could be boosted up to 40-fold by preinjection of tumor necrosis factor that conditioned the tissue for increased DC migration. These results indicate that DC number and tissue inflammation are critical parameters for DC-based vaccination

RNA stabilizes transcription-Dependent Chromatin Loops Induced By Nuclear Hormones

We show that transcription induced by nuclear receptors for estrogen (e2) or retinoic acid (RA) is associated with formation of chromatin loops that juxtapose the 5’ end (containing the promoter) with the enhancer and the 3′ polyA addition site of the target gene. We nd three loop con gurations which change as a function of time after induction: 1. RA or E2-induced loops which connect the 5′ end, the enhancer and the 3′ end of the gene, and are stabilized by RNA early after induction; 2. E2-independent loops whose stability does not require RNA; 3. Loops detected only by treatment of chromatin with RNAse H1 prior to hormonal induction. RNAse H1 digests RNA that occludes the relevant restriction sites, thus preventing detection of these loops. R-loops at the 5′ and 3′ ends of the RA or e2-target genes were demonstrated by immunoprecipitation with anti-DNA-RNA hybrid antibodies as well as by sensitivity to RNAse H1. The cohesin RAD21 subunit is preferentially recruited to the target sites upon RA or e2 induction of transcription. R21 binding to chromatin is eliminated by RNAse H1. We identi ed e2-induced and RNase H1-sensitive antisense RNAs located at the 5′ and 3′ ends of the e2-induced transcription unit which stabilize the loops and RAD21 binding to chromatin. This is the rst report of chromatin loops that form after gene induction that are maintained by RNA:DNA hybrids

El forage descompresivo en la necrosis isquémica de la cabeza femoral : experiencia clínica en 34 casos

Se analizan los resultados obtenidos mediante el forage descompresivo de caderas afectas de necrosis isquémica de la cabeza femoral. Se efectuaron 34 forages en 27 pacientes, siendo la edad media de 44 años. Veintitrés caderas se clasificaron como estadio I de Ficat y 11 como estadio II. En cuanto a su etiología 17 caderas se consideraron idiopáticas, en 15 había antecedentes de ingesta elevada de alcohol, 1 presentaba antecedentes de ingesta de corticoides y otra había sufrido una fractura luxación de cadera 6 meses antes. Tras un seguimiento medio de 74 meses, el 74% de pacientes en estadio I permanecen asintomáticos y estabilizados radiológicamente y sólo en el 18% del estadio II se obtuvo dicha estabilización. Se concluye que el forage descompresivo estaría sólo indicado en el estadio I de Ficat; en el estadio II los malos resultados obtenidos nos hacen dudar de su eficacia, máxime si la etiología es alcohólica.We analysed the results obtained using the core decompression technique in hips with avascular necrosis of the femoral head. Thirty four core decompression were performed on 27 patients. The average age was 44. Twenty three hips were found to be Ficat stage I and 11 were stage II. As to the ethiology, 17 hips were idiopathic, 15 had a history of high alcohol intake, 1 had been treated with steroids and another one underwent a fracture-dislocation of the hip previously. After an average follow-up of 74 months, 74% stage I patients were asymptomatic and radiologically stable, whilst only 18% of stage II patients could be considered as radiologically stable. In conclusion, core decompression tecnique should be indicated only in stage I patients. The reliability of this technique in stage II patients is doubtful, specially in alcoholic patients as is shown by own poor results

Genetic parameters of biokinematic variables of the trot in Spanish Purebred horses under experimental treadmill conditions

The purpose of this study was to estimate the genetic parameters of biokinematic variables in Spanish Purebred (SPB) horses in order to select those of sufficient interest to be measured in the pre-selection of the animals for possible inclusion in the breeding programme. Kinematic analysis of 130 SPB horses 4.6 ± 1.5 years old were recorded at the trot (4 m/s) on a treadmill. Genetic parameters were estimated using VCE software and a bivariate mixed animal model including age and stud as fixed effects and animal additive genetic effect and residual error as random effects. In general, heritabilities were high (0.33–0.88). The angular variables presented the lowest heritabilities, whereas the maximum height of the fore-hoof and the duration of swing phase in the hindlimb gave the highest scores. Genetic correlations were also very high, so it was possible to reduce the number of breeding programme characteristics to stride duration, hindlimb swing phase duration, range of stifle and elbow angles, minimal angle of carpus, and minimal retraction-protraction angle of the hindlimb.Unión Europea 1FD97-089

High-coverage methylation data of a gene model before and after DNA damage and homologous repair

Genome-wide methylation analysis is limited by its low coverage and the inability to detect single variants below 10%. Quantitative analysis provides accurate information on the extent of methylation of single CpG dinucleotide, but it does not measure the actual polymorphism of the methylation profiles of single molecules. To understand the polymorphism of DNA methylation and to decode the methylation signatures before and after DNA damage and repair, we have deep sequenced in bisulfite-treated DNA a reporter gene undergoing site-specific DNA damage and homologous repair. In this paper, we provide information on the data generation, the rationale for the experiments and the type of assays used, such as cytofluorimetry and immunoblot data derived during a previous work published in Scientific Reports, describing the methylation and expression changes of a model gene (GFP) before and after formation of a double-strand break and repair by homologous-recombination or non-homologous-end-joining. These data provide: 1) a reference for the analysis of methylation polymorphism at selected loci in complex cell populations; 2) a platform and the tools to compare transcription and methylation profiles

Mechanical behavior and microstructural changes in polyurethane exposed to high doses of X rays, gamma rays or neutron irradiation

Polymeric materials are widely used in applications where the environmental conditions entail their exposure to different sources of irradiation (in most cases ultraviolet or low dose of electromagnetic irradiation for sterilization). In contrast, in this study we have assessed the modifications undergone by a series of polyurethane joints exposed to high radioactive doses of either X-rays or gamma rays (with doses of 20.5, 100, 300 and 900?kGy) or neutron irradiation (with a fluence of 7.23·1010 n/cm2) which are typical of the environment of nuclear reactors. Tensile tests were carried out to assess the change in mechanical properties derived from the radioactive exposure. Three mechanical parameters were used to monitor the evolution of strength, ductility and toughness: the tensile strength (?max), the strain corresponding to ?max (??max) and the density of energy absorbed prior to maximum load (U?max). With regards to X and gamma rays, a negative impact of radiation on strength, ductility and toughness was observed. The detailed statistical analysis of the results has shown that a threshold dose of 300?kGy must be overcome to trigger the damage process. For the fluence employed in this study, neutron irradiation produced very little change in the mechanical properties. The SEM fractographic study has allowed the influence of irradiation on the material failure mechanisms to be identified. Thus, the fracture surface of unirradiated samples shows evidence of plastic deformation and ductile tearing. In contrast, the fracture surface of those samples exposed to a dose of 900?kGy corresponds to brittle fracture. In a consistent way, samples exposed to neutron irradiation have a fracture surface similar to that of the non-irradiated material. In summary, electromagnetic radiation for doses above the threshold leads to the embrittlement of polyurethane. Raman spectroscopy was employed to identify the microstructural changes induced by the different sources of radiation at the molecular level. The band corresponding to the vibration of the C-H bending bonds present in the polyurethane was measured as a function of the dose, finding a strong correlation between its vibration frequency and the dose of exposure to electromagnetic radiation. This shift is more sensitive than the mechanical material response since the frequency is affected at doses of 100?kGy, below the threshold previously identified for any of the mechanical properties. This correlation opens the door for the use of Raman spectroscopy as a novel non-destructive tool to characterize the microstructural effect of irradiation on polyurethane

Alpha-synuclein gene duplication: Marked intrafamilial variability in two novel pedigrees

n/