Developmental programming: rescuing disruptions in preovulatory follicle growth and steroidogenesis from prenatal testosterone disruption

Abstract Background Prenatal testosterone (T) excess from days 30-90 of gestation disrupts gonadotropin surge and ovarian follicular dynamics and induces insulin resistance and functional hyperandrogenism in sheep. T treatment from days 60-90 of gestation produces a milder phenotype, albeit with reduced fecundity. Using this milder phenotype, the aim of this study was to understand the relative postnatal contributions of androgen and insulin in mediating the prenatal T induced disruptions in ovarian follicular dynamics. Methods Four experimental groups were generated: 1) control (vehicle treatment), 2) prenatal T-treated (100 mg i.m. administration of T propionate twice weekly from days 60-90 of gestation), 3) prenatal T plus postnatal anti-androgen treated (daily oral dose of 15 mg/kg/day of flutamide beginning at 8 weeks of age) and 4) prenatal T and postnatal insulin sensitizer-treated (daily oral dose of 8 mg/day rosiglitazone beginning at 8 weeks of age). Follicular response to a controlled ovarian stimulation protocol was tested during their third breeding season. Main outcome measures included the determination of number and size of ovarian follicles and intrafollicular concentrations of steroids. Results At the end of the controlled ovarian stimulation, the number of follicles approaching ovulatory size (≥6 mm) were ~35 % lower in prenatal T-treated (6.5 ± 1.8) compared to controls (9.8 ± 2.0). Postnatal anti-androgen (10.3 ± 1.9), but not insulin sensitizer (5.0 ± 0.9), treatment prevented this decrease. Preovulatory sized follicles in the T group had lower intrafollicular T, androstenedione, and progesterone compared to that of the control group. Intrafollicular steroid disruption was partially reversed solely by postnatal insulin sensitizer treatment. Conclusions These results demonstrate that the final preovulatory follicular growth and intrafollicular steroid milieu is impaired in prenatal T-treated females. The findings are consistent with the lower fertility rate reported earlier in these females. The finding that final follicle growth was fully rescued by postnatal anti-androgen treatment and intrafollicular steroid milieu partially by insulin sensitizer treatment suggest that both androgenic and insulin pathway disruptions contribute to the compromised follicular phenotype of prenatal T-treated females.http://deepblue.lib.umich.edu/bitstream/2027.42/134597/1/13048_2016_Article_250.pd

A technique using a membrane flow-cell to determine average mass transfer coefficients and tortuosity factors in biofilms

Average mass transfer coefficients of an inert compound (LiCl) within denitrifying biofilms were monitored during biofilm growth in a membrane flow cell under different flow conditions, until the biofilm reached (pseudo-) steady state. Average effective diffusivities were found to increase with the decrease in tortuosity factors of the biofilm matrix. The lowest tortuosity factor corresponded to the biofilm formed under the highest liquid velocity

InterMiG: international differences in the therapeutic approach to migraine patients in specialized headache centers

Antidepressiu; Migranya; Tractament preventiuAntidepresivo; Migraña; Tratamiento preventivoAntidepressant; Migraine; Preventive treatmentBackground There is currently a wide therapeutic arsenal for migraine patients, without a single first-line preventive drug and we choose the different available alternatives taking into account comorbidities, national guidelines, previous treatments and personal experiences. Our objective was to evaluate the differences in the use of migraine treatments between neurologists from different countries. Methods This is a multi-centre observational study carried out by neurologists from specialized headache units in seven countries, retrospective with consecutive inclusion of all patients presenting with a migraine diagnosis, over a period of three months. Results A total of 734 patients were recruited but only 600 were considered in the analysis in order to homogenize the patient cohorts from countries: 200 Spain (ES), 100 Italy (IT), 85 Russia (RUS), 80 Germany (DE), 60 Portugal (PT), 45 Poland (PL) and 30 Australia (AU). 85.4 % of patients were women with a mean age of 42.6 ± 11.8 years. Considering previous and current preventive treatment, the order of use was: antidepressants (69.3 %), antiepileptic drugs (54.7 %), beta-blockers and antihypertensive drugs (49.7 %), OnabotulinumtoxinA (44.0 %) and others (36.2 %). Statistically significant differences were found between all pharmacological classes: antidepressants were commonly used in all countries, with the exception of Poland (AU: 76.7 %, IT: 71.0 %, DE: 60.0 %, PL: 31.1 %, PT: 71.7 %, RUS: 70.6 %, ES: 78.5 %; p < 0.0001); antiepileptic drugs were more frequently prescribed in Portugal, Australia and Spain (AU: 73.3 %, IT: 40.0 %, DE: 37.5 %, PL: 48.9 %, PT: 85.0 %, RUS: 29.4 % and ES: 69.0 %; p < 0.0001); beta-blockers and antihypertensive drugs were frequently used in all countries except Italy (AU: 60.0 %, IT: 14.0 %, DE: 53.8 %, PL: 48.9 %, PT: 68.3 %, RUS: 49.4 % and ES: 59.0 %; p < 0.0001); BTX-A were predominately used in Spain, Italy and Australia (AU:56.7 %, IT:58.0 %, DE:20.0 %, PL: 42.2 %, PT: 26.7 %, RUS: 24.7 % and ES: 58.5 %; p < 0.0001) and others were most frequently used in Poland (AU: 0.0 %, IT: 19.0 %, DE: 42.5 %, PL: 95.6 %, PT: 31.7 %, RUS: 3.5 % and ES: 49.5 %; p < 0.0001). If only patients without comorbidities are considered (200/600), statistically differences between countries persist in all preventive treatments. Conclusions There is heterogeneity in the choice of preventive treatment between different countries. Prospective comparative studies of the different oral and subcutaneous alternatives would help to create a global therapeutic algorithm that would guarantee the best option for our patients.This work did not receive any funds

Trajectory mapping: A tool for validation of trace gas observations

We investigate the effectiveness of trajectory mapping(TM) as a data validation tool. TM combines a dynamical model of the atmosphere with trace gas observations to provide more statistically robust estimates of instrument performance over much broader geographic areas than traditional techniques are able to provide. We present four detailed case studies selected so that the traditional techniques are expected to work well. In each case the TM results are equivalent to or improve upon the measurement comparisons performed with traditional approaches. The TM results are statistically more robust than those achieved using traditional approaches since the TM comparisons occur over a much larger range of geophysical variability. In the first case study we compare ozone data from the Halogen Occultation Experiment (HALOE) with Microwave Limb Sounder(MLS). TM comparisons appear to introduce little to no error as compared to the traditional approach. In the second case study we compare ozone data from HALOE with that from the Stratospheric Aerosol and Gas Experiment TT(SAGE TT). TM results in differences of less than 5% as compared to the traditional approach at altitudes between 18 and 25 km and less than 10% at altitudes between 25 and 40 km.In the third case study we show that ozone profiles generated from HALOE data using TM compare well with profiles from five European ozonesondes. In the fourth case study we evaluate the precision of MLS H20 using TM and find typical precision uncertainties of 3-7% at most latitudes and altitudes. The TM results agree well with previous estimates but are the result of a global analysis of the data rather than an analysis in the limited latitude bands in which traditional approaches work. Finally, sensitivity studies using the MLS H20 data show the following: (1) a combination of forward and backward trajectory calculations minimize uncertainties in isentropic TM; (2) although the uncertainty of the technique increases with trajectory duration,TM calculations of up to 14 days can provide reliable information for use in data validation studies; (3) a correlation coincidence criterion of 400 km produces the best TM results under most circumstances; (4) TM performs well compared to (and sometimes better than) traditional approaches at all latitudes and in most seasons and; (5) TM introduces no statistically significant biases at altitudes between 22 and 40 km

Anisotropy studies around the galactic centre at EeV energies with the Auger Observatory

Data from the Pierre Auger Observatory are analyzed to search for anisotropies near the direction of the Galactic Centre at EeV energies. The exposure of the surface array in this part of the sky is already significantly larger than that of the fore-runner experiments. Our results do not support previous findings of localized excesses in the AGASA and SUGAR data. We set an upper bound on a point-like flux of cosmic rays arriving from the Galactic Centre which excludes several scenarios predicting sources of EeV neutrons from Sagittarius $A$. Also the events detected simultaneously by the surface and fluorescence detectors (the `hybrid' data set), which have better pointing accuracy but are less numerous than those of the surface array alone, do not show any significant localized excess from this direction.Comment: Matches published versio

Discovering and linking public omics data sets using the Omics Discovery Index.

Biomedical data are being produced at an unprecedented rate owing to the falling cost of experiments and wider access to genomics, transcriptomics, proteomics and metabolomics platforms1, 2. As a result, public deposition of omics data is on the increase. This presents new challenges, including finding ways to store, organize and access different types of biomedical data stored on different platforms. Here, we present the Omics Discovery Index (OmicsDI; http://www.omicsdi.org), an open-source platform that enables access, discovery and dissemination of omics data sets