[Overview of induction of labor practices in France]. / État des lieux des pratiques de déclenchement en France.

OBJECTIVE: To describe induction of labor practices in France and to identify factors associated with the use of different methods. METHODS: The data came from the French prospective population-based cohort MEDIP (MEthodes de Déclenchement et Issues Périnatales), including consecutively during one month in 2015 all women with induction of labor and a live fetus in 7 perinatal networks. The characteristics of women, maternity units, gestational age, Bishop's score, decision mode, indication and methods of labor induction were described. Factors associated with the use of different methods were sought in univariate analyzes. RESULTS: The rate of induction of labor during the study was 21% and 3042 women were included (95.9% participation rate). The two main indications were prolonged pregnancy (28.7%) and premature rupture of the membranes (25.4%). More than one-third of women received intravenous oxytocin in first method, 57.3% prostaglandins, 4.5% balloon catheter and 1.4% another method. Among the prostaglandins, the vaginal device of dinoprostone was the most used (71.6%) then the gel (20.7%) and the vaginal misoprostol (6.7%). Women with a balloon were more often of higher body mass index and multiparous with scarred uterus. The balloon and misoprostol were mainly used in university public hospitals. CONCLUSIONS: The evolution of induction of labor methods, due to new data from the literature and the development of new drugs or devices, invites to regularly repeat population-based studies on induction of labor.

Risk of cesarean after induction of labor in twin compared to singleton pregnancies.

OBJECTIVE: To assess the risk of cesarean delivery after induction of labor in twin compared with singleton pregnancies. STUDY DESIGN: This retrospective multicenter study compared data from two nationwide prospective cohorts: one of twin pregnancies established from February 2014 through March 2015 (JUMODA cohort), and the other of singleton pregnancies in November and December 2015 (MEDIP cohort). This study includes all women in both cohorts who had labor induced at ≥ 35 weeks of gestation, with a live fetus in cephalic presentation (Twin 1 for the twin pregnancies). Multivariate analyses with multilevel logistic regression models were used to study twin pregnancy as an independent risk factor for cesarean delivery, overall and stratified for parity and Bishop score. RESULTS: The outcomes of 1995 twin births after induction of labor were compared to those of 2771 induced singleton births. The cesarean rate differed significantly between the two populations and was higher in twins (23% in twins vs 19.4% in singletons, P = 0.002). After adjustment for factors associated with cesareans, twin pregnancy was independently associated with it (aOR = 1.8, 95% CI 1.4-2.2). CONCLUSION: Twin pregnancy appears to be an independent risk factor for cesarean births after induction of labor, but more than three-quarters of inductions culminated in vaginal delivery.

Factors affecting rotation of occiput posterior position during the first stage of labor.

INTRODUCTION: Fetal occiput posterior (OP) positions account for 15 to 20% of cephalic presentations and are associated with poorer maternal and neonatal outcomes than occiput anterior (OA) positions. The aim of this study was to identify maternal, neonatal and obstetric factors associated with rotation from OP to OA position during the first stage of labor. MATERIAL AND METHODS: This secondary analysis of a multicenter randomized controlled trial (EVADELA) included 285 laboring women with ruptured membranes and a term fetus in OP position. After excluding women with cesarean deliveries before full dilatation, we compared two groups according to fetal head position at the end of the first stage of labor: those with and without rotation from OP to OA position. Factors associated with rotation were assessed with univariate and multivariate analyses using multilevel logistic regression models. RESULTS: The rate of anterior rotation during the first stage was 49.1%. Rotation of the fetal head was negatively associated with excessive gestational weight gain (adjusted odds ratio [aOR]: 0.37, 95% confidence interval [CI]: 0.17-0.80), macrosomia (aOR: 0.35, 95% CI: 0.14-0.90), direct OP position (aOR: 0.24, 95% CI: 0.09-0.65), and prelabor rupture of membranes (aOR: 0.40, 95% CI: 0.19-0.86). Oxytocin administration was the only factor positively associated with fetal head rotation (aOR: 2.17, 95% CI: 1.20-3.91). DISCUSSION: Oxytocin administration may affect rotation of OP positions during the first stage of labor. Further studies should be performed to assess the risks and benefits of its utilization for managing labor with a fetus in OP position.

Labour induction practices in France: A population-based declarative survey in 94 maternity units.

INTRODUCTION: In 2016, 22.0% of deliveries in France were induced. The current lack of high level of evidence data about the methods and indications for induction of labour has promoted heterogeneous and non-recommended practices. The extent of these different practices is not adequately known in France today, although they may influence perinatal outcomes. The objective of this study was to report current practices of induction of labour in France. MATERIAL AND METHODS: This study surveyed 94 maternity units in seven perinatal networks. A questionnaire was sent by email to either the department head or delivery room supervisor of these units to ask about their methods for induction and their attitudes in specific obstetric situations. RESULTS: The rate of induction varied between maternity units from 7.7% to 33% of deliveries. Most units used two (39.4%) or three or more (35.1%) agents for cervical ripening. In all, 87 (92.6%) units reported using dinoprostone as a vaginal slow-released insert, 59 units dinosprostone as a vaginal gel (62.8%) and 46 units a balloon catheter (48.9%). Only three units reported using vaginal misoprostol. Inductions without medical indication were reported by 71 (75.5%) maternity units, and 22 (23.4%) units even when the cervix was unfavourable. Obstetric attitudes in cases of breech presentation, previous caesareans, fetal growth restriction or macrosomia and prelabour rupture of the membranes varied widely. DISCUSSION: The variability of practices for induction of labour and the persistence of disapproved practices call for an assessment of the effectiveness and the safety of the different strategies.

[Switch of methoxy-polyethylene-glycol-epoetin beta to darbepoetin alfa in 263 dialysis patients]. / Étude de la conversion du méthoxypolyéthylèneglycol-époétine bêta vers la darbépoétine alfa chez 263 patients hémodialysés.

In early 2012, due to national supply disruption, the methoxy-polyethylene glycol-epoetin beta (CERA) was no longer available and has been replaced by darbepoetin alfa (DA) in all dialysis patients. Official recommendations for the replacement of one by the other is missing or unclear. On this occasion, we wanted to examine how the shift from CERA to DA was done in terms of dose conversion factor and the other factors that could have influenced the dose of DA prescribed (hemoglobin, patient weight, dose of CERA). This retrospective multicenter open conducted in six dialysis centers in Alsace is the first large study (n=263) that evaluated the switch from CERA to DA in all chronic hemodialysis patients. We found that the instantaneous ratio of dose adjustment is close to 1 and that nephrologists are mainly based on the dose of CERA for determining the DA dose, before hemoglobin and weight. However, establishing a true dose-response ratio between the two molecules requires a long term prospective study.

Indication of a cosmological variation of the proton-electron mass ratio based on laboratory measurement and reanalysis of H2 spectra.

Based on highly accurate laboratory measurements of Lyman bands of H2 and an updated representation of the structure of the ground X 1sigma(g)+ and excited B 1sigma(u)+ and C 1pi(u) states, a new set of sensitivity coefficients K(i) is derived for all lines in the H2 spectrum, representing the dependence of their transition wavelengths on a possible variation of the proton-electron mass ratio mu = m(p)/m(e). Included are local perturbation effects between B and C levels and adiabatic corrections. The new wavelengths and K(i) factors are used to compare with a recent set of highly accurate H2 spectral lines observed in the Q 0347-383 and Q 0405-443 quasars, yielding a fractional change in the mass ratio of deltamu/mu = (2.4 +/- 0.6) x 10(-5) for a weighted fit and deltamu/mu = (2.0 +/- 0.6) x 10(-5) for an unweighted fit. This result indicates, at a 3.5sigma confidence level, that mu could have decreased in the past 12 Gyr.

Short-term corticosteroids then lamivudine and plasma exchanges to treat hepatitis B virus-related polyarteritis nodosa.

OBJECTIVE: To assess the efficacy and safety of lamivudine, an antiviral agent that strongly inhibits hepatitis B virus (HBV) DNA replication, combined with plasma exchanges after short-term corticosteroids for HBV-related polyartertitis nodosa (PAN). METHODS: Ten patients (8 men, 2 women, mean +/- SD age 50.4 +/- 14.4 years) with previously untreated HBV-related PAN were included in a multicenter, prospective, observational trial. Oral prednisone (1 mg/kg/day) was given for 1 week, then tapered and withdrawn within 1 week. Then, lamivudine (100 mg/day or less in the case of renal insufficiency) was started for a maximum of 6 months. Plasma exchanges were performed simultaneously and scheduled as follows: 3/week for 3 weeks, 2/week for 2 weeks, then 1/week until hepatitis B e antigen (HBeAg) to anti-HBe antibody (HBeAb) seroconversion was obtained or until 2-3 months of clinical recovery was sustained. The primary trial endpoint was clinical recovery from HBV-PAN at 6 months. The secondary endpoint was loss of detectable serum HBeAg and HBV DNA, and HBeAg to HBeAb seroconversion at 9 months. RESULTS: One death, attributed to catheter-related septicemia, was recorded. At 6 months, all 9 survivors had achieved clinical recovery and by 9 months, 6 of 9 (66%) had seroconverted. CONCLUSION: The strategy of short-term steroids followed by lamivudine and plasma exchanges effectively led to recovery from HBV-PAN. Because of its oral administration and good safety profile, lamivudine should henceforth be considered the antiviral agent of choice to treat HBV-related PAN.

Limits on the time variation of the electromagnetic fine-structure constant in the low energy limit from absorption lines in the spectra of distant quasars.

We present the results of a detailed many-multiplet analysis performed on a new sample of Mg ii systems observed in high quality quasar spectra obtained using the Very Large Telescope. The weighted mean value of the variation in alpha derived from our analysis over the redshift range 0.4

NMR structure of the HIV-1 regulatory protein VPR.

The human immunodeficiency virus type 1 (HIV-1) genome encodes a highly conserved regulatory gene product, Vpr (96 residues, 14kDa), which is incorporated into virions. In the infected cells, Vpr, expressed late in the virus cycle, is believed to function in the early phases of HIV-1 replication, such as nuclear migration of pre-integration complex, transcription of the proviral genome, viral multiplication by blocking cells in G2 phase and regulation of apoptosis phenomenon. Vpr has a critical role in long term AIDS disease by inducing infection in non-dividing cells such as monocytes and macrophages. To gain insight into the structure-function relationships of Vpr, the (1-96)Vpr protein was synthesized with 22 labeled amino acids. Its 3D structure was analyzed in the presence of CD(3)CN and in pure water at low pH and refined by restrained simulated annealing. The structure of the protein is characterized by three well-defined alpha-helices: 17-33, 38-50 and 56-77 surrounded by flexible N and C-terminal domains. In contrast to the structure obtained in the presence of TFE, the three alpha-helices are folded around a hydrophobic core constituted of Leu, Ile, Val and aromatic residues as illustrated by numerous long range NOEs. This structure accounts for the interaction of Vpr with different targets.

[The dilemma of the last vascular access]. / Le "dilemme" du dernier abord vasculaire.

Age and cardio-vascular pathologies in hemodialysis patients confront us with the increasing difficulties in finding vascular access. This implies the necessity to keep in place central venous catheters (CVC) and find alternative puncturing sites. CVC malfunction in dialysis is frequently encountered (87% of cases). A variety of salvage procedures are described in the literature amongst them the "stripping" and re-canalization methods. Stripping allows withdraw fibrin strands around the CVC with a success rate of 75 to 90% and a rather low complication rate, although this may not be well documented. Re-vascularization techniques allow the placement of a CVC even across a thrombosed vessel. Success rate here is 100% in a limited series of patients. In addition to the classical access sites, like internal jugular and subclavian vein exist, alternative sites such as the external jugular, femoral or even translumbar vein.

The cosmic microwave background radiation temperature at a redshift of 2.34.

The existence of the cosmic microwave background radiation is a fundamental prediction of hot Big Bang cosmology, and its temperature should increase with increasing redshift. At the present time (redshift z = 0), the temperature has been determined with high precision to be T(CMBR)(0) = 2.726 +/- 0.010 K. In principle, the background temperature can be determined using measurements of the relative populations of atomic fine-structure levels, which are excited by the background radiation. But all previous measurements have achieved only upper limits, thus still formally permitting the radiation temperature to be constant with increasing redshift. Here we report the detection of absorption lines from the first and second fine-structure levels of neutral carbon atoms in an isolated cloud of gas at z = 2.3371. We also detected absorption due to several rotational transitions of molecular hydrogen, and fine-structure lines of singly ionized carbon. These constraints enable us to determine that the background radiation was indeed warmer in the past: we find that T(CMBR)(z = 2.3371) is between 6.0 and 14 K. This is in accord with the temperature of 9.1 K predicted by hot Big Bang cosmology.

Cardiovascular morbidity and endothelial dysfunction in chronic haemodialysis patients: is homocyst(e)ine the missing link?

BACKGROUND: Haemodialysis patients exhibit an excessive burden of atherothrombotic disease, which is not explained adequately by traditional risk factors. Hyperhomocyst(e)inaemia, a consistent finding in uraemic patients, is now widely recognized as an independent risk factor for vascular disease. The aim of this study was to examine the hypothesis that hyperhomocyst(e)inaemia is associated with cardiovascular complications in dialysed patients. METHODS: In a cohort of 63 stable chronic haemodialysis patients, we examined the causal relationship between hyperhomocyst(e)inaemia and vascular endothelial and haemostatic function. All their markers were determined before and after an 8-week course of a 10 mg per day oral folate supplementation, a manoeuvre known to decrease hyperhomocyst(e)inaemia in uraemic patients. RESULTS: History of at least one cardiovascular atherothrombotic event was present in 47.6% of the haemodialysed patients, and radiographic evidence of vascular calcifications in 70%. Hyperhomocyst(e)inaemia was found in all patients, averaging 3.5-fold the upper limit of normal values (P<0.001), despite the lack of clinical and biological evidence of malnutrition. Fibrinogen, von Willebrand factor and plasminogen activator inhibitor type 1, but not endothelin 1, were significantly higher in haemodialysis patients than in controls. After adjustment for all variables, past history of cardiovascular events was independently associated with higher levels of homocyst(e)inaemia only (odds ratio (OR) 1.06; 95% confidence interval (CI) 1.01-1.12; P<0.026). The presence of aortic calcifications was independently and significantly associated with age (OR 1.37; 95% CI 1.07-1.75; P<0.025), homocyst(e)inaemia (OR 1.14; 95% CI 1.02-1.27; P<0.05) and fibrinogen concentration only (OR 9.74; 95% CI 1.25-75.2; P<0.05). None of the endothelial haemostatic factors was, however, related to homocyst(e)ine levels. Mid-term folate supplementation decreased plasma homocyst(e)ine levels significantly without achieving normal values. No significant change of endothelial-haemostatic markers was observed, however, despite the drop in plasma homocyst(e)ine. CONCLUSIONS: Hyperhomocyst(e)inaemia is associated with increased cardiovascular risk in haemodialysis patients. Folate supplementation was partially effective in lowering hyperhomocyst(e)inaemia, but its usefulness in terms of reduction in cardiovascular morbidity and mortality remains to be determined in prospective trials.

Abysmal prognosis of patients with type 2 diabetes entering dialysis.

INTRODUCTION: The importance of non-insulin-dependent diabetes mellitus (type II diabetes) as a leading cause of end-stage renal disease is now widely recognized. The purpose of this study was to assess life-prognosis and its predictors in a cohort of patients newly entering dialysis. MATERIAL AND METHODS: Eighty-four consecutive type II diabetes patients (40% of all patients) starting dialysis between 01/01/95 and 31/12/96 were studied retrospectively, focusing on clinical data at inception and life-prognosis after a mean follow-up of 211 days. Patients were divided into three groups, according to onset of renal failure: acute 11% (9/84), chronic 61% (51/84) and acutely aggravated chronic renal failure 28% (25/84). RESULTS: Patients (mean age 67 years) had long-standing diabetes (mean duration approximately 15 years), heavy proteinuria (approximately 3 g/24h) and diabetic retinopathy (67%). The average creatinine clearance (Cockcroft's formula) was 13 ml/min. Cardiovascular diseases were highly prevalent at the start of dialysis: history of myocardial infarction (26%), angina (36%) and acute left ventricular dysfunction (67%). More than 80% of the patients underwent the first session dialysis under emergency conditions, a situation in part related to late referral to the nephrology division (63% for chronic patients). A great majority of the patients were overhydrated when starting dialysis, as evidenced by the average weight loss of 6 kg, during the first month of dialysis, required to reach dry weight. Nearly 64% of the patients presented high blood pressure (> 140/90 mmHg) when starting dialysis despite antihypertensive therapy (mean: 2.3 drugs). The outcome of this type II diabetes population was dramatic: 32% (27/84) died after a mean follow-up of 211 days, mostly from cardiovascular diseases. The rate of recovery of renal function was low in both the acute and the acutely aggravated renal failure group (30% and 24%, respectively). Of note, iatrogenic nephrotoxic agents accounted for renal function impairment in nearly 30% of patients. CONCLUSION: Our observational study illustrates the high burden of cardiovascular diseases contrasting with sub-optimal cardiovascular therapeutic interventions in type II diabetes patients entering dialysis. Factors aggravating renal failure were mainly iatrogenic, and therefore largely avoidable. Late referral generally implied a poor clinical condition at the start of dialysis.

Model of the complex formed between the H2 domain of the TATA box binding protein and the L(281-301) fragment of the human transcription factor TFIIA.

Additional interactions possibly involving the well-exposed H2 helical domain of hTBP and the acidic fragment L(281-301) of the non-conserved domain of hTFIIA have been proposed to account for the apparent discrepancies between the results of mutagenesis experiments on human proteins and the structure of the ternary complex TBP/TATA box/TFIIA established from yeast proteins by X-ray crystallography. To verify this hypothesis both peptides were synthesized and their structures studied by circular dichroism (CD), NMR and molecular modelling. These peptides exist preferentially under helical conformations in solution (30% TFE in H2O). An interaction between the two peptides was observed by fluorescence (Kapp 170 microM), CD and NMR techniques. Molecular modelling studies indicate that this complex could be stabilized by electrostatic interactions involving the glutamate Glu287 and aspartates (Asp290, Asp294, Asp297 and Asp298) of L(281-301)TFIIA and lysine residues (Lys133, Lys138 and Lys145) and arginine residues (Arg137, Arg140) of H2(TBP) in agreement with mutagenesis experiments. Similar studies could now be carried out with human proteins to demonstrate the biological relevance of this interaction.

Roles of the human immunodeficiency virus type 1 nucleocapsid protein in annealing and initiation versus elongation in reverse transcription of viral negative-strand strong-stop DNA.

To study the initiation of human immunodeficiency virus type 1 reverse transcription, we have used the viral nucleocapsid protein (NC7) to anneal tRNA3Lys primer onto viral genomic RNA and have then eliminated NC7 from this primer-template complex by digestion with proteinase K and phenol-chloroform extraction of residual protein. Our data show that saturating concentrations of NC7 resulted in the formation of an active tRNA-template complex that yielded enhanced production of full-length negative-strand strong-stop DNA [(-)ssDNA] and that this complex remained active even after the elimination of NC7. While both of the two Zn finger motifs found within NC7 were essential for efficient elongation, NC protein that contained a point mutation in the first Zn finger or that was devoid of both Zn fingers yielded primer-template complexes that could still be initiated in 1-base-extension assays. In contrast, the use of heat annealing to produce primer-template complexes resulted in proportions of full-length (-)ssDNA lower than those seen with NC protein, and the addition of NC protein to such preformed primer-template complexes was able to reverse this defect only to a marginal extent.

The annealing of tRNA3Lys to human immunodeficiency virus type 1 primer binding site is critically dependent on the NCp7 zinc fingers structure.

The nucleocapsid protein NCp7 of the human immunodeficiency virus type 1 contains two zinc fingers of the CX2CX4HX4C type, flanked by several basic residues, and plays a major role in viral infectivity. Thus, NCp7 was shown to promote annealing of the tRNA3Lys to the primer binding site, a key step in reverse transcription. However, previous in vitro experiments were unable to clarify the role of the zinc fingers in this process, due to nucleic acid aggregation induced by the basic N- and C-terminal domains of NCp7. We show here that deletion of these sequences in (12-53)NCp7 strongly reduces the formation of aggregates and allows a direct visualization of the binary or ternary complexes between NCp7 and nucleic acids by gel electrophoresis. (12-53)NCp7 is able to induce hybridization of the 33P tRNA3Lys and the human immunodeficiency virus type 1 viral RNA-(77-257), which contains the primer binding site. Modification of the proximal zinc finger conformation in Cys23(12-53)NCp7 led to a large reduction in this hybridization process, while replacement of Trp37 by Leu in the distal zinc fingers resulted in a complete absence of annealing activity. These data account for the in vivo loss of viral infectivity following these mutations and emphasize the critical role of the structure of the zinc finger domain of NCp7. This could facilitate a rational approach to new antiviral agents directed toward NCp7.

Properties and growth mechanism of the ordered aggregation of a model RNA by the HIV-1 nucleocapsid protein: an electron microscopy investigation.

NCp7, the nucleocapsid protein of the human immunodeficiency virus type 1, induces an ordered aggregation of RNAs, a mechanism that is thought to be involved in the NCp7-induced promotion of nucleic acid annealing. To further investigate this aggregation the morphology and the properties of the NCp7-induced aggregates of the model RNA homoribopolymer, polyA, were investigated by electron microscopy in various conditions. In almost all the tested conditions, the aggregates were spherical and consisted of a central dense core surrounded by a less dense halo made of NCp7-covered polyA molecules. The formation of these aggregates with a narrow distribution of sizes constitutes a distinctive feature of NCp7 over other single-stranded nucleic acid binding proteins. In most conditions, at the shortest times that can be reached experimentally, all the polyA molecules were already incorporated in small aggregates, suggesting that the nucleation step and the first aggregation events took place rapidly. The aggregates then orderly grew with time by fusion of the smaller aggregates to give larger ones. The aggregate halo was important in the fusion process by initiating the bridging between the colliding aggregates. In the presence of an excess of protein, the aggregates grew rapidly but were loosely packed and dissociated easily, suggesting adverse protein-protein interactions in the aggregates obtained in these conditions. In the presence of an excess of nucleotides, the presence of both amorphous nonspherical and slowly growing spherical aggregates suggested some changes in the mechanism of aggregate growth due to an incomplete covering of polyA molecules by NCp7. Finally, we showed that in the absence of added salt, the aggregate fusions were unfavored but not the initial events giving the first aggregates, the reverse being true in the presence of high salt concentrations (> or = 300 mM).

[Kidney and nitric oxide]. / Rein et monoxyde d'azote.

Nitric oxide (NO) pathway is involved in various physiological and pathophysiological processes. NO is synthesised by NO synthase. Three isoforms, ecNOS, nNOS, iNOS have been identified to date, that are encoded by 3 distinct genes on chromosome 7, 12 and 17 respectively. L-arginine is likely involved in the control of NO synthesis. In the kidney, NO regulates glomerular hemodynamics by modulating the ultrafiltration coefficient and afferent and efferent renal arteriolar resistance. NO is further involved in the pressure-natriuresis mechanism and in the tubuloglomerular feedback. Several physiopathological models have underlined the importance of the NO in arterial hypertension and in glomerular inflammation.

The zinc fingers of HIV nucleocapsid protein NCp7 direct interactions with the viral regulatory protein Vpr.

The 96-amino acid protein Vpr functions as a regulator of cellular processes involved in human immunodeficiency virus, type 1 (HIV-1) life cycle, in particular by interrupting cells division in the G2 phase. Incorporation of Vpr in the virion was reported to be mediated by the C-terminal domain of the Pr55(Gag) polyprotein precursor, which includes NCp7, a protein involved in the genomic RNA encapsidation and p6, a protein required for particle budding. To precisely define the Gag and Vpr sequences involved in this protein-protein interaction, NCp7, p6, and Vpr as well as a series of derived peptides were synthesized using Fmoc (N-(9-fluorenyl)methoxycarbonyl) chemistry. Binding assays were carried out by Far Western experiments and by competition studies using (52-96)Vpr immobilized onto agarose beads. The results show that interaction between NCp7 and Vpr occurs in vitro by a recognition mechanism requiring the zinc fingers of NCp7 and the last 16 amino acids of Vpr. Moreover, NCp10, the equivalent of NCp7 in Moloney murine leukemia virus but not polysine inhibits Vpr-NCp7 complexation. Interestingly enough, Vpr was found to interact with Gag, NCp15, and NCp7 but not with mature p6 in vitro. In vivo mutations in NCp7 zinc fingers in an HIV-1 molecular clone led to viruses with important defects in Vpr encapsidation. Together, these results suggest that NCp7 cooperates with p6 to induce Vpr encapsidation in HIV-1 mature particles. The NCp7-Vpr complex could also be important for interaction of Vpr with cellular proteins involved in cell division.