Seizure frequency and sex steroids in women with partial epilepsy on antiepileptic therapy

PURPOSE: Neuroactive sex steroids influence neuron excitability, which is enhanced by estradiol (E2) and decreased by progesterone (Pg). In epilepsy, the production, metabolism, biologic availability, and activity of sex hormones may be affected by seizures themselves or by antiepileptic drugs (AEDs). This cross-sectional observational study was aimed at evaluating the relationships between sex steroids, seizure frequency, and other clinical parameters in women with partial epilepsy (PE) on AED treatments. METHODS: Serum E2, Pg, sex hormone binding globulin (SHBG) levels, free E2 (fE2), and E2/Pg ratios were determined during the follicular and luteal phases in 72 adult women with PE, and in 30 healthy controls. Hormonal data were correlated with seizure frequency, age, body weight, body mass index (BMI), disease onset and duration, and AED therapies. RESULTS: In patients, E2, fE2, and Pg levels were lower in both ovarian phases, whereas those of SHBG were higher than in controls. No significant changes in hormone levels and in prevalence of anovulatory cycles were observed between patients grouped according to their seizure frequency. However, when compared with those in healthy controls, luteal fE2 and Pg levels were chiefly impaired in women with more frequent seizures, mostly undergoing AED polytherapies, but not in those with absent or rarer seizures. CONCLUSIONS: The actual changes in sex steroid levels and E2/Pg ratios did not explain an increased seizure frequency in adult women with AED-treated PE, but patients with more severe disease showed more relevant changes in their sex hormone profile and impaired Pg levels during the luteal phase

Decoding Polo-like kinase 1 signaling along the kinetochore–centromere axis

Protein kinase signaling along the kinetochore-centromere axis is crucial to assure mitotic fidelity, yet its spatial coordination is obscure. Here, we examined how pools of human Polo-like kinase 1 (Plk1) within this axis control signaling events to elicit mitotic functions. To do this, we restricted active Plk1 to discrete subcompartments within the kinetochore-centromere axis using chemical genetics and decoded functional and phosphoproteomic signatures of each. We observe distinct phosphoproteomic and functional roles, suggesting that Plk1 exists and functions in discrete pools along this axis. Deep within the centromere, Plk1 operates to assure proper chromosome alignment and segregation. Thus, Plk1 at the kinetochore is a conglomerate of an observable bulk pool coupled with additional functional pools below the threshold of microscopic detection/resolution. Although complex, this multiplicity of locales provides an opportunity to decouple functional and phosphoproteomic signatures for a comprehensive understanding of Plk1’s kinetochore functions

Survey of neonatal respiratory care and surfactant administration in very preterm infants in the Italian Neonatal Network.

INTRODUCTION: Variation of respiratory care is described between centers around the world. The Italian Neonatal Network (INN), as a national group of the Vermont-Oxford Network (VON) allows to perform a wide analysis of respiratory care in very low birth weight infants. METHODS: We analyzed the dataset of infants enrolled in the INN in 2009 and 2010 and, for surfactant administration only, from 2006 to 2010 from 83 participating centers. All definitions are those of the (VON). A questionnaire analysis was also performed with a questionnaire on centers practices. RESULTS: We report data for 8297 infants. Data on ventilator practices and outcomes are outlined. Variation for both practices and outcome is found. Trend in surfactant administration is also analyzed. CONCLUSIONS. The great variation across hospitals in all the surveyed techniques points to the possibility of implementing potentially better practices with the aim of reducing unwanted variation. These data also show the power of large neonatal networks in identifying areas for potential improvement

The mode of delivery and the risk of vertical transmission of human immunodeficiency virus type 1--a meta-analysis of 15 prospective cohort studies. The International Perinatal HIV Group.

To evaluate the relation between elective cesarean section and vertical transmission of human immunodeficiency virus type 1 (HIV-1), we performed a meta-analysis using data on individual patients from 15 prospective cohort studies. North American and European studies of at least 100 mother-child pairs were included in the meta-analysis. Uniform definitions of modes of delivery were used. Elective cesarean sections were defined as those performed before onset of labor and rupture of membranes. Multivariate logistic-regression analysis was used to adjust for other factors known to be associated with vertical transmission. The primary analysis included data on 8533 mother-child pairs. After adjustment for receipt of antiretroviral therapy, maternal stage of disease, and infant birth weight, the likelihood of vertical transmission of HIV-1 was decreased by approximately 50 percent with elective cesarean section, as compared with other modes of delivery (adjusted odds ratio, 0.43; 95 percent confidence interval, 0.33 to 0.56). The results were similar when the study population was limited to those with rupture of membranes shortly before delivery. The likelihood of transmission was reduced by approximately 87 percent with both elective cesarean section and receipt of antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, as compared with other modes of delivery and the absence of therapy (adjusted odds ratio, 0.13; 95 percent confidence interval, 0.09 to 0.19). Among mother-child pairs receiving antiretroviral therapy during the prenatal, intrapartum, and neonatal periods, rates of vertical transmission were 2.0 percent among the 196 mothers who underwent elective cesarean section and 7.3 percent among the 1255 mothers with other modes of delivery. The results of this meta-analysis suggest that elective cesarean section reduces the risk of transmission of HIV-1 from mother to child independently of the effects of treatment with zidovudine