The use of methotrexate in conservative treatment of placenta accreta spectrum disorders.

Aim of the study: This article reports on a series of patients with placenta accreta spectrum (PAS) disorder who were treated conservatively with Methotrexate (MTX) administration with or without embolization. We investigate whether there is a place for MTX in conservative treatment of PAS.Methods: We present a single-center retrospective case series of five patients. In all patients, diagnosis was unexpected and not made prenatally.Conclusion: The benefits should be weighed against the possible drug toxicity. Today high-quality evidence is lacking. PAS covers a broad spectrum of pathology, standardization in prenatal and postnatal diagnosis can help to compare evidence on treatment.

Gestational weight gain and postpartum weight retention after bariatric surgery: data from a prospective cohort study.

BACKGROUND: It is unknown whether international guidelines on gestational weight gain can be used in pregnancies after bariatric surgery. OBJECTIVES: To investigate gestational weight gain, intrauterine growth, and postpartum weight retention in postbariatric women. SETTING: 8 Belgian hospitals. METHODS: Prospective data from 127 postbariatric pregnancies from September 2014 through October 2018. Patients were grouped according to achievement of 2009 Institute of Medicine (IOM) guidelines. RESULTS: In 127 patients with a mean age of 30.2 years (standard deviation [SD], 4.7), the mean gestational weight gain was 12.5 kg (SD, 6.7). Of these patients, 24% (30 of 127) showed insufficient weight gain, 20% (26 of 127) showed adequate weight gain, and 56% (71 of 127) showed excessive weight gain. Of 127 patients, 27 (21%) had small-for-gestational-age infants. This peaked in the group with insufficient weight gain (47%; 95% confidence interval [CI], 29%-65%; P < .001). The prevalence of large-for-gestational-age infants was comparable between groups, although highest in the group with excessive weight gain (0% in those with insufficient weight gain, 4% in those with adequate weight gain, and 8% in those with excessive weight gain). Preterm births were recorded more in patients with insufficient weight gain (23%; 95% CI, 8%-38%; P = .048). The mean amounts of postpartum weight retained were 4.0 kg (SD, 7.4) at 6 weeks and 3.0 kg (SD, 9.1) at 6 months. Weight retention at 6 weeks (7.1 kg; 95% CI, 5.5-8.7; P < .001) and 6 months (8.3 kg; 95% CI, 4.5-12.2; P < .001) was highest in women gaining excessive weight. CONCLUSION: Achievement of IOM guidelines is low in postbariatric pregnancies. Insufficient weight gain increases the risk for small-for-gestational-age babies. Excessive weight gain increases weight retention after delivery and could precipitate weight regain. After bariatric surgery, women should be encouraged to achieve IOM recommendations.

Depression and Anxiety: Lack of Associations with an Inadequate Diet in a Sample of Pregnant Women with a History of Bariatric Surgery-a Multicenter Prospective Controlled Cohort Study.

BACKGROUND: Anxiety and depression levels are higher in obese compared to those in normal weight pregnant women. The aims of this study are to examine anxiety and depression in pregnancy following bariatric surgery and to compare with obese pregnant controls considering the dietary intake of polyunsaturated fatty acids (PUFA), folate, and vitamin B12. METHODS: Anxiety (State-Trait Anxiety Inventory) and depression (Edinburgh Postnatal Depression Scale) were examined in the first (T1) and third (T3) pregnancy trimester in 54 women with bariatric surgery and 25 obese. T1 and T3 dietary intake of PUFA, folate, and vitamin B12 intake was assessed using a 3-day food record. Mixed models with a compound symmetry covariance structure and regression models were applied. RESULTS: About half of the women with surgery had high state and trait anxiety scores (≥ 40), which did not significantly change during pregnancy. Every 10-kg postoperative weight loss was associated with an increase in T1 state and trait anxiety with respectively 2.7 and 2.3 points. A smoking woman had a 8.6-point higher state anxiety score than a non-smoking woman in T1. In T3, every additional hour of sleep was associated with a decrease in trait anxiety score with 1.59 points. Anxiety and depression scores were not associated with and could not be explained by inadequate PUFAs, folate, and vitamin B12 intakes. Anxiety scores were higher following surgery than those in untreated obesity at both time points. CONCLUSION: Pregnancy following bariatric surgery induces high levels of anxiety that are not associated with an inadequate maternal diet.

AURORA: bariatric surgery registration in women of reproductive age - a multicenter prospective cohort study.

BACKGROUND: The expansion of the obesity epidemic is accompanied with an increase in bariatric procedures, in particular in women of reproductive age. The weight loss induced by the surgery is believed to reverse the negative impact of overweight and obesity on female reproduction, however, research is limited to in particular retrospective cohort studies and a growing number of small case-series and case-(control) studies. METHODS/DESIGN: AURORA is a multicenter prospective cohort study. The main objective is to collect long-term data on reproductive outcomes before and after bariatric surgery and in a subsequent pregnancy. Women aged 18-45 years are invited to participate at 4 possible inclusion moments: 1) before surgery, 2) after surgery, 3) before 15 weeks of pregnancy and 4) in the immediate postpartum period (day 3-4). Depending on the time of inclusion, data are collected before surgery (T1), 3 weeks and 3, 6, 12 or x months after surgery (T2-T5) and during the first, second and third trimester of pregnancy (T6-T8), at delivery (T9) and 6 weeks and 6 months after delivery (T10-T11). Online questionnaires are send on the different measuring moments. Data are collected on contraception, menstrual cycle, sexuality, intention of becoming pregnant, diet, physical activity, lifestyle, psycho-social characteristics and dietary supplement intake. Fasting blood samples determine levels of vitamin A, D, E, K, B-1, B-12 and folate, albumin, total protein, coagulation parameters, magnesium, calcium, zinc and glucose. Participants are weighted every measuring moment. Fetal ultrasounds and pregnancy course and complications are reported every trimester of pregnancy. Breastfeeding is recorded and breast milk composition in the postpartum period is studied. DISCUSSION: AURORA is a multicenter prospective cohort study extensively monitoring women before undergoing bariatric surgery until a subsequent pregnancy and postpartum period. TRIAL REGISTRATION: Retrospectively registered (July 2015 - NCT02515214 ).

Mutation of C. elegans demethylase spr-5 extends transgenerational longevity.

Complex organismal properties such as longevity can be transmitted across generations by non-genetic factors. Here we demonstrate that deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase, spr-5, causes a trans-generational increase in lifespan. We identify a chromatin-modifying network, which regulates this lifespan extension. We further show that this trans-generational lifespan extension is dependent on a hormonal signaling pathway involving the steroid dafachronic acid, an activator of the nuclear receptor DAF-12. These findings suggest that loss of the demethylase SPR-5 causes H3K4me2 mis-regulation and activation of a known lifespan-regulating signaling pathway, leading to trans-generational lifespan extension.

DRE-1/FBXO11-dependent degradation of BLMP-1/BLIMP-1 governs C. elegans developmental timing and maturation.

Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1. blmp-1 also opposed dre-1 for other life history traits, including entry into the dauer diapause and longevity. BLMP-1 protein was strikingly elevated upon dre-1 depletion and dysregulated in a stage- and tissue-specific manner. The role of DRE-1 in regulating BLMP-1 stability is evolutionary conserved, as we observed direct protein interaction and degradation function for worm and human counterparts. Taken together, posttranslational regulation of BLMP-1/BLIMP-1 by DRE-1/FBXO11 coordinates C. elegans developmental timing and other life history traits, suggesting that this two-protein module mediates metazoan maturation processes.

Regulation of genes involved in nitrogen utilization on different C/N ratios and nitrogen sources in the model ectomycorrhizal fungus Hebeloma cylindrosporum.

Nitrogen (N) utilization by ectomycorrhizal fungi is an essential aspect of their ecosystem function. N deposition changes both the N pools and the carbon/nitrogen (C/N) ratio of the substrates where ectomycorrhizal fungi are found, and it is important to understand how these changes affect the N forms used by ectomycorrhizal fungi. To overcome the difficulties of studying ectomycorrhizal fungi in situ, we investigated all known N genes in the model fungus, Hebeloma cylindrosporum in a culture study. In addition to studying the regulation of all known N utilization genes, we aimed to understand whether there are gene clusters that undergo similar regulation. Lastly we studied how C/N ratio, N transporter type, and N source affected relative gene expression levels. We grew the D2 strain of H. cylindrosporum on a range of inorganic and organic N sources under low, medium, and high C/N ratios. We found three gene clusters that were regulated in a similar pattern. Lastly, we found C/N ratio, N source and N transporter type all affected gene expression levels. Relative expression levels were highest on the high C/N ratio, BSA and diLeucine N sources, and inorganic N transporters were always expressed at higher levels than organic N transporters. These results suggest that inorganic N sources may always the default preference for H. cylindrosporum, regardless of both the N sources and the C/N ratio of the substrate.