Is "option B+" also being adopted in pregnant women in high-income countries? Temporal trends from a national study in Italy

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SUMO modification of PCNA is controlled by DNA

Post-translational modification by the ubiquitin-like protein SUMO is often regulated by cellular signals that restrict the modification to appropriate situations. Nevertheless, many SUMO-specific ligases do not exhibit much target specificity, and—compared with the diversity of sumoylation substrates—their number is limited. This raises the question of how SUMO conjugation is controlled in vivo. We report here an unexpected mechanism by which sumoylation of the replication clamp protein, PCNA, from budding yeast is effectively coupled to S phase. We find that loading of PCNA onto DNA is a prerequisite for sumoylation in vivo and greatly stimulates modification in vitro. To our surprise, however, DNA binding by the ligase Siz1, responsible for PCNA sumoylation, is not strictly required. Instead, the stimulatory effect of DNA on conjugation is mainly attributable to DNA binding of PCNA itself. These findings imply a change in the properties of PCNA upon loading that enhances its capacity to be sumoylated

Pregnancy outcomes and cytomegalovirus DNAaemia in HIV infected pregnant women with CMV

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Rate , correlates and outcomes of repeat pregnancy in HIV-infected women

Objectives: The aim of the study was to assess the rate, determinants, and outcomes of repeat pregnancies in women with HIV infection. Methods: Data from a national study of pregnant women with HIV infection were used. Main outcomes were preterm delivery, low birth weight, CD4 cell count and HIV plasma viral load. Results: The rate of repeat pregnancy among 3007 women was 16.2%. Women with a repeat pregnancy were on average younger than those with a single pregnancy (median age 30 vs. 33 years, respectively), more recently diagnosed with HIV infection (median time since diagnosis 25 vs. 51 months, respectively), and more frequently of foreign origin [odds ratio (OR) 1.36; 95% confidence interval (CI) 1.10–1.68], diagnosed with HIV infection in the current pregnancy (OR: 1.69; 95% CI: 1.35–2.11), and at their first pregnancy (OR: 1.33; 95% CI: 1.06–1.66). In women with sequential pregnancies, compared with the first pregnancy, several outcomes showed a significant improvement in the second pregnancy, with a higher rate of antiretroviral treatment at conception (39.0 vs. 65.4%, respectively), better median maternal weight at the start of pregnancy (60 vs. 61 kg, respectively), a higher rate of end-of-pregnancy undetectable HIV RNA (60.7 vs. 71.6%, respectively), a higher median birth weight (2815 vs. 2885 g, respectively), lower rates of preterm delivery (23.0 vs. 17.7%, respectively) and of low birth weight (23.4 vs. 15.4%, respectively), and a higher median CD4 cell count (+47 cells/μL), with almost no clinical progression to Centers for Disease Control and Prevention stage C (CDC-C) HIV disease (0.3%). The second pregnancy was significantly more likely to end in voluntary termination than the first pregnancy (11.4 vs. 6.1%, respectively). Conclusions: Younger and foreign women were more likely to have a repeat pregnancy; in women with sequential pregnancies, the second pregnancy was characterized by a significant improvement in several outcomes, suggesting that women with HIV infection who desire multiple children may proceed safely and confidently with subsequent pregnancies

Amniocentesis and chorionic villus sampling in HIV-infected pregnant women: a multicentre case series.

Objectives: To assess in pregnant women with HIV the rates of amniocentesis and chorionic villus sampling (CVS), and the outcomes associated with such procedures. Design: Observational study. Data from the Italian National Program on Surveillance on Antiretroviral Treatment in Pregnancy were used. Setting: University and hospital clinics. Population: Pregnant women with HIV. Methods: Temporal trends were analysed by analysis of variance and by the Chi-square test for trend. Quantitative variables were compared by Student's t-test and categorical data by the Chi-square test, with odds ratios and 95% confidence intervals calculated. Main outcome measures: Rate of invasive testing, intrauterine death, HIV transmission. Results: Between 2001 and 2015, among 2065 pregnancies in women with HIV, 113 (5.5%) had invasive tests performed. The procedures were conducted under antiretroviral treatment in 99 cases (87.6%), with a significant increase over time in the proportion of tests performed under highly active antiretroviral therapy (HAART) (100% in 2011–2015). Three intrauterine deaths were observed (2.6%), and 14 pregnancies were terminated because of fetal anomalies. Among 96 live newborns, eight had no information available on HIV status. Among the remaining 88 cases with either amniocentesis (n = 75), CVS (n = 12), or both (n = 1), two HIV transmissions occurred (2.3%). No HIV transmission occurred among the women who were on HAART at the time of invasive testing, and none after 2005. Conclusions: The findings reinforce the assumption that invasive prenatal testing does not increase the risk of HIV vertical transmission among pregnant women under suppressive antiretroviral treatment. Tweetable abstract: No HIV transmission occurred among women who underwent amniocentesis or CVS under effective anti-HIV regimens. © 2016 Royal College of Obstetricians and Gynaecologist

Good prenatal detection rate of major birth defects in HIV-infected pregnant women in Italy

What's already known about this topic? Exposure to antiretroviral treatment in pregnancy does not seem to increase the risk of birth defects, but there is no information on the rate of prenatal detection of such defects. What does this study adds? We provide for the first time, in a national case series, information about prenatal detection rate in women with HIV (51.6% for any major defect, 66.7% for chromosomal abnormalities, and 85% for severe structural defect

Nucleosomes in gene regulation: theoretical approaches

This work reviews current theoretical approaches of biophysics and bioinformatics for the description of nucleosome arrangements in chromatin and transcription factor binding to nucleosomal organized DNA. The role of nucleosomes in gene regulation is discussed from molecular-mechanistic and biological point of view. In addition to classical problems of this field, actual questions of epigenetic regulation are discussed. The authors selected for discussion what seem to be the most interesting concepts and hypotheses. Mathematical approaches are described in a simplified language to attract attention to the most important directions of this field

Mother-to-child transmission of human immunodeficiency virus in Italy : temporal trends and determinants of infection

In order to analyse temporal trends in vertical transmission rates of human immunodeficiency virus (HIV) and determinant of congenital HIV infection in Italy, we have considered data from a network of hospitals co-operating in the Italian Collaborative Study on HIV infection in pregnancy, conducted between 1988 and 1995. A total of 1040 women entered the study. The HIV-1 status of the babies was known in 848 cases (81.5%). Transmission rates were highest in the period 1988\u20131991, then tended to decrease and in 1995 the rate was 9.7 per 100 children (this finding, however, was based on only six infected children and the trend was not statistically significant). Considering the overall series, the risk of vertical HIV transmission was higher in women with low CD4 count in pregnancy [odds ratio (OR) <400 versus \u2a7e400 1.8, 95% confidence interval (CI) 1.1\u20132.9]. In comparison with vaginal delivery the risk of transmission was 0.3 (95% CI 0.1\u20130.5) and 0.6 (95% CI 0.3\u20131.2) respectively for elective and emergency delivery. In comparison with women who delivered at term (\u2a7e37 gestation weeks) the OR of HIV infection of the babies for the whole series was 2.2 (95% CI 1.3\u20133.6) in women who delivered preterm. Similar findings emerged when the analysis was conducted considering, separately, subjects observed in the period 1988\u20131991 and 1992\u20131995. The frequency of Caesarean section increased from 26.5% of deliveries in 1988\u20131991 to 36.2% in 1992\u20131995. Consequently, most temporal differences disappeared after standardization for mode of delivery, but the rate in 1995 was still lower than in 1988\u20131994