Buoyant crystals halt the cooling of white dwarf stars.

White dwarfs are stellar remnants devoid of a nuclear energy source, gradually cooling over billions of years1,2 and eventually freezing into a solid state from the inside out3,4. Recently, it was discovered that a population of freezing white dwarfs maintains a constant luminosity for a duration comparable with the age of the universe5, signalling the presence of a powerful, yet unknown, energy source that inhibits the cooling. For certain core compositions, the freezing process is predicted to trigger a solid-liquid distillation mechanism, owing to the solid phase being depleted in heavy impurities6-8. The crystals thus formed are buoyant and float up, thereby displacing heavier liquid downward and releasing gravitational energy. Here we show that distillation interrupts the cooling for billions of years and explains all the observational properties of the unusual delayed population. With a steady luminosity surpassing that of some main-sequence stars, these white dwarfs defy their conventional portrayal as dead stars. Our results highlight the existence of peculiar merger remnants9,10 and have profound implications for the use of white dwarfs in dating stellar populations11,12.

A giant planet candidate transiting a white dwarf.

Astronomers have discovered thousands of planets outside the Solar System1, most of which orbit stars that will eventually evolve into red giants and then into white dwarfs. During the red giant phase, any close-orbiting planets will be engulfed by the star2, but more distant planets can survive this phase and remain in orbit around the white dwarf3,4. Some white dwarfs show evidence for rocky material floating in their atmospheres5, in warm debris disks6-9 or orbiting very closely10-12, which has been interpreted as the debris of rocky planets that were scattered inwards and tidally disrupted13. Recently, the discovery of a gaseous debris disk with a composition similar to that of ice giant planets14 demonstrated that massive planets might also find their way into tight orbits around white dwarfs, but it is unclear whether these planets can survive the journey. So far, no intact planets have been detected in close orbits around white dwarfs. Here we report the observation of a giant planet candidate transiting the white dwarf WD 1856+534 (TIC 267574918) every 1.4 days. We observed and modelled the periodic dimming of the white dwarf caused by the planet candidate passing in front of the star in its orbit. The planet candidate is roughly the same size as Jupiter and is no more than 14 times as massive (with 95 per cent confidence). Other cases of white dwarfs with close brown dwarf or stellar companions are explained as the consequence of common-envelope evolution, wherein the original orbit is enveloped during the red giant phase and shrinks owing to friction. In this case, however, the long orbital period (compared with other white dwarfs with close brown dwarf or stellar companions) and low mass of the planet candidate make common-envelope evolution less likely. Instead, our findings for the WD 1856+534 system indicate that giant planets can be scattered into tight orbits without being tidally disrupted, motivating the search for smaller transiting planets around white dwarfs.

Perinatal morbidity among women with a previous caesarean delivery (PRISMA trial): a cluster-randomised trial.

BACKGROUND: Women with a previous caesarean delivery face a difficult choice in their next pregnancy: planning another caesarean or attempting vaginal delivery, both of which are associated with potential maternal and perinatal complications. This trial aimed to assess whether a multifaceted intervention, which promoted person-centred decision making and best practices, would reduce the risk of major perinatal morbidity among women with one previous caesarean delivery. METHODS: We conducted an open, multicentre, cluster-randomised, controlled trial of a multifaceted 2-year intervention in 40 hospitals in Quebec among women with one previous caesarean delivery, in which hospitals were the units of randomisation and women the units of analysis. Randomisation was stratified according to level of care, using blocked randomisation. Hospitals were randomly assigned (1:1) to the intervention group (implementation of best practices and provision of tools that aimed to support decision making about mode of delivery, including an estimation of the probability of vaginal delivery and an ultrasound estimation of the risk of uterine rupture), or the control group (no intervention). The primary outcome was a composite risk of major perinatal morbidity. This trial was registered with ISRCTN, ISRCTN15346559. FINDINGS: 21 281 eligible women delivered during the study period, from April 1, 2016 to Dec 13, 2019 (10 514 in the intervention group and 10 767 in the control group). None were lost to follow-up. There was a significant reduction in the rate of major perinatal morbidity from the baseline period to the intervention period in the intervention group as compared with the control group (adjusted odds ratio [OR] for incremental change over time, 0·72 [95% CI 0·52-0·99]; p=0·042; adjusted risk difference -1·2% [95% CI -2·0 to -0·1]). Major maternal morbidity was significantly reduced in the intervention group as compared with the control group (adjusted OR 0·54 [95% CI 0·33-0·89]; p=0·016). Minor perinatal and maternal morbidity, caesarean delivery, and uterine rupture rates did not differ significantly between groups. INTERPRETATION: A multifaceted intervention supporting women in their choice of mode of delivery and promoting best practices resulted in a significant reduction in rates of major perinatal and maternal morbidity, without an increase in the rate of caesarean or uterine rupture. FUNDING: Canadian Institutes of Health Research (CIHR, MOP-142448).

Impact of Audits and Multifaceted Intervention on Vaginal Birth After Caesarean: Secondary Analysis of the QUARISMA Trial.

OBJECTIVES: This study estimated the effect that a multifaceted intervention aiming to improve the quality of obstetrical care and reduce Caesarean section (CS) had on the rate of vaginal birth after Caesarean (VBAC). METHODS: This is a secondary analysis of the cluster randomized controlled trial Quality of Care, Obstetrics Risk Management, and Mode of Delivery involving (1) audits regarding the indications for CS, (2) provision of feedback to health professionals, and (3) implementation of best practices to reduce CS rates in Quebec. The impact of intervention on VBAC, trial of labour (TOL), and maternal and neonatal morbidity was reported using adjusted odds ratios (ORs) with 95% confidence intervals (CIs). RESULTS: Out of 105 351 women who delivered during the pre- and postintervention period, 12 493 (11.9%) had a previous CS. We observed no significant impact of the multifaceted intervention on the rates of TOL (adjusted OR 1.22; 95% CI 0.96-1.56, P = 0.11) and VBAC (adjusted OR 1.20; 95% CI 0.97-1.48, P = 0.10) in women with one previous CS. However, the rate of TOL was reduced (adjusted OR 0.38; 95% CI 0.14-0.99) in women with more than one previous CS. The intervention has no influence on maternal and neonatal morbidity. CONCLUSIONS: A multifaceted intervention including audits, feedback to health professionals, and implementation of best practices did not affect VBAC rates or maternal and neonatal morbidity. Our results pointed out the need for decision-making processand risk management tools specific to women with previous CS.

Reporting Caesarean Delivery in Quebec Using the Robson Classification System.

OBJECTIVE: The increasing rates of Caesarean sections throughout the world is preoccupant, and a good understanding of which groups of women contribute the most to the CS rate represents an important question in public health. Therefore, we sought to report the CS rate according to the Robson's classification system in the Quebec population. METHOD: We performed a secondary analysis of the QUARISMA database, including all deliveries after 24 weeks' gestation from 32 maternity wards in the province of Quebec between 2008 and 2011 (n = 184 952 deliveries). CS rates were reported according to the modified Robson criteria from The Society of Obstetricians and Gynaecologists of Canada with the relative contribution to the total number of CSs. RESULTS: We observed a global CS rate of 22.9%. Women with previous CS and a fetus in cephalic presentation at term accounted for 35% of all Caesarean deliveries. Nulliparous women with cephalic presentation at term accounted for 30% of all CSs. Among nulliparous women with cephalic presentation, women with spontaneous labour contributed to 12% of all CSs, whereas women with an induction of labour contributed to 16% of all CSs. Non-cephalic fetal presentation accounted for 19% of all CSs. Other indications accounted for the remaining 16% of CSs. CONCLUSION: Most CSs are performed for multiparous women with previous CS; nulliparous women with a cephalic presentation at term, especially those undergoing labour induction; and non-cephalic fetal presentation.

"That was intense!" Spirituality during childbirth: a mixed-method comparative study of mothers' and fathers' experiences in a public hospital.

BACKGROUND: While spirituality is well described in end-of-life care literature, research on its place in the delivery room remains largely limited to mother-oriented qualitative studies focusing on life-threatening situations (e.g., high-risk pregnancies). Our aim was to compare mothers' and fathers' spirituality during childbirth. METHODS: A mixed methods questionnaire was developed from our childbirth-related spirituality categorization and distributed to all parents of newborns, 12-24 h postpartum, over 45 consecutive days. Paired-sample t-tests and qualitative thematic analysis were used to compare mothers and fathers. Multiple linear regressions identified factors associated with their respective global scores (vaginal and cesarean deliveries separately). RESULTS: The global scores for mothers (38.6/50) and fathers (37.2/50) were similarly high (N = 197; p = 0.001). Highest-ranked ("respect", "moral responsibility", "beauty of life", "gratitude") and lowest-ranked spiritual themes ("prayer", "greater than self") were in agreement. Fathers scored higher on "fragility of life" (p = 0.006) and mothers on "self-accomplishment" (p<0.001), "letting go" (p<0.001), and "meaningfulness" (p = 0.003). "Admission of baby in neonatal unit" was associated with higher global score for both mothers and fathers. Other factors also increased fathers' (witnessing a severe tear) and mothers' scores (birthplace outside Canada; for vaginal deliveries, religious belonging and longer pushing stage). CONCLUSION: These first quantitative data on the prevalence of spirituality during childbirth highlight a high score for both parents, among a non-selected public hospital population. Spirituality emerges not only from unordinary situations but from any childbirth as an "intensification of the human experience". Significant differences for some spiritual themes indicate the need to consider the spirituality of both parents.

Effect of endometrial ablation on premenstrual symptoms.

STUDY OBJECTIVE: To evaluate the effect of endometrial ablation on 6 premenstrual symptoms for up to 1 year after treatment. DESIGN: Prospective cohort of 59 women awaiting endometrial ablation (Canadian Task Force classification II-2). SETTING: University tertiary care hospital. PATIENTS: Adult women of childbearing age awaiting endometrial ablation for heavy menstrual bleeding were recruited through the gynecology clinic of the Centre Hospitalier Universitaire de Sherbrooke. Fifty-nine patients were recruited, of whom 9 were excluded. Women were eligible to participate after an initial self-evaluation of ≥ 3 out of 10 for at least 1 premenstrual symptom. INTERVENTIONS: Women underwent endometrial ablation using the microwave, impedance-controlled, or rollerball technique. MEASUREMENTS AND MAIN RESULTS: Women had to fill out 2 surveys at 3 time points: before surgery, 4 months after surgery, and 12 months after surgery. The first survey consisted of visual analog scales for self-evaluation of 6 premenstrual symptoms (i.e., irritability, agitation/anxiety, depression/sadness, headache, swelling/bloating, and breast tenderness), and the second evaluated the heaviness of menstrual bleeding. The severity of all 6 symptoms decreased significantly (p < .025) up to 1 year after endometrial ablation. The greatest improvement was seen in swelling/bloating, with mean decreases of 4.1 on a scale of 10 at the 4-month follow-up and 3.1 at the 12-month follow-up. Women who reported the most severe symptoms before surgery appeared to have greater improvement compared with women with milder symptoms. Significant improvements were nevertheless observed in the mild severity subgroup for 4 of the 6 symptoms studied (i.e., irritability, depression, swelling/bloating, and breast tenderness). CONCLUSION: Women reported significant improvement for the 6 premenstrual symptoms for up to 1 year following an endometrial ablation for heavy menstrual bleeding. The improvement of these symptoms appears to be linked to the efficacy of the procedure.

[Factors associated with breastfeeding continuation in young Canadian mothers]. / Les facteurs associés à la poursuite de l'allaitement maternel chez les jeunes mères canadiennes.

OBJECTIVES: Breastfeeding continuation rates are lower among young mothers, while few studies have specifically focused on this population. This study describes the factors related to continued breastfeeding beyond two months among young Canadian mothers. METHODS: A descriptive and correlational design was used to identify and quantify the impact offactors affecting continued breast-feeding beyond two months. Data were derived from a selection of mothers 15-19 years who responded to The Maternity Experiences Survey. RESULTS: The difference between subgroups (15-18 vs 19 years old) in terms of breastfeeding continuation was not significant, but non-smoking (OR 2.78, 95% C, 1.351 - 5.682), living with a partner (OR 1.96, 95% CI, 1.087 to 3.597), vaginal delivery (OR 2.22, 95% CI, 1.012 to 4.878) and experiencing a large number of stressful situations (RC 0.42, 95% CI, 0.221 to 0.788) promotes continued breastfeeding beyond two months. No significant relationship wasfound with pregnancy planning, prenatal preparation, the violence suffered, depressive symptoms and the availability of social support. CONCLUSION: Some factors related to pre-and postnatal periods, in addition to sociodemographic factors influence the choice of young Canadian mothers to continue or not continue breastfeeding beyond two months. Our results will be used to guide specific interventions for young mothers in breastfeeding protection, promotion and support programmes.

Comparative study between transcriptionally- and translationally-acting adenine riboswitches reveals key differences in riboswitch regulatory mechanisms.

Many bacterial mRNAs are regulated at the transcriptional or translational level by ligand-binding elements called riboswitches. Although they both bind adenine, the adenine riboswitches of Bacillus subtilis and Vibrio vulnificus differ by controlling transcription and translation, respectively. Here, we demonstrate that, beyond the obvious difference in transcriptional and translational modulation, both adenine riboswitches exhibit different ligand binding properties and appear to operate under different regulation regimes (kinetic versus thermodynamic). While the B. subtilis pbuE riboswitch fully depends on co-transcriptional binding of adenine to function, the V. vulnificus add riboswitch can bind to adenine after transcription is completed and still perform translation regulation. Further investigation demonstrates that the rate of transcription is critical for the B. subtilis pbuE riboswitch to perform efficiently, which is in agreement with a co-transcriptional regulation. Our results suggest that the nature of gene regulation control, that is transcription or translation, may have a high importance in riboswitch regulatory mechanisms.

Chronic levothyroxine and acute T3 treatments enhance the amplitude and time course of uterine contractions in human.

This study compares the functional consequences of levothyroxine (T4) treatment during pregnancy as well as the acute affects of triiodothyronine (T3) on spontaneous uterine contractile activities observed in vitro. Uterine biopsies were obtained from consenting women undergoing elective caesarean at term (n = 28). Spontaneous contractile activities from T4-treated pregnant women (n = 8) were compared with control patients (n = 20) by isometric tension measurements. Effects of acute T3 and T4 on control tissues were also monitored. Area under the curve, amplitude, time to peak, duration, and frequency were quantified. In uterine strips from women treated for hypothyroidism, phasic uterine contractions of larger amplitude (+77%) were observed, with a prolonged duration at 90% relaxation (+138%) and reduced frequency (-55%) compared with values of the control group. The addition of exogenous T3 in vitro on control strips induced a significant increase in the duration of the contractions and a significant decrease in frequency (P < 0.05), which partially mimics the results obtained in strips from T4-treated women. Significant modifications of contractile properties were observed in strips from pregnant women treated with levothyroxine, consistent with those observed with the addition of exogenous T3. Clinical practices of modern obstetrics should take into account the effect of thyroid hormones on uterine contractions' time course to ensure a tighter followup at the end of pregnancy to achieve safer delivery.

Molecular insights into the ligand-controlled organization of the SAM-I riboswitch.

S-adenosylmethionine (SAM) riboswitches are widespread in bacteria, and up to five different SAM riboswitch families have been reported, highlighting the relevance of SAM regulation. On the basis of crystallographic and biochemical data, it has been postulated, but never demonstrated, that ligand recognition by SAM riboswitches involves key conformational changes in the RNA architecture. We show here that the aptamer follows a two-step hierarchical folding selectively induced by metal ions and ligand binding, each of them leading to the formation of one of the two helical stacks observed in the crystal structure. Moreover, we find that the anti-antiterminator P1 stem is rotated along its helical axis upon ligand binding, a mechanistic feature that could be common to other riboswitches. We also show that the nonconserved P4 helical domain is used as an auxiliary element to enhance the ligand-binding affinity. This work provides the first comprehensive characterization, to our knowledge, of a ligand-controlled riboswitch folding pathway.

Folding of the lysine riboswitch: importance of peripheral elements for transcriptional regulation.

The Bacillus subtilis lysC lysine riboswitch modulates its own gene expression upon lysine binding through a transcription attenuation mechanism. The riboswitch aptamer is organized around a single five-way junction that provides the scaffold for two long-range tertiary interactions (loop L2-loop L3 and helix P2-loop L4)--all of this for the creation of a specific lysine binding site. We have determined that the interaction P2-L4 is particularly important for the organization of the ligand-binding site and for the riboswitch transcription attenuation control. Moreover, we have observed that a folding synergy between L2-L3 and P2-L4 allows both interactions to fold at lower magnesium ion concentrations. The P2-L4 interaction is also critical for the close juxtaposition involving stems P1 and P5. This is facilitated by the presence of lysine, suggesting an active role of the ligand in the folding transition. We also show that a previously uncharacterized stem-loop located in the expression platform is highly important for the riboswitch activity. Thus, folding elements located in the aptamer and the expression platform both influence the lysine riboswitch gene regulation.

Constitutive regulatory activity of an evolutionarily excluded riboswitch variant.

The exquisite specificity of the adenine-responsive riboswitch toward its cognate metabolite has been shown to arise from the formation of a Watson-Crick interaction between the adenine ligand and residue U65. A recent crystal structure of a U65C adenine aptamer variant has provided a rationale for the phylogenetic conservation observed at position 39 for purine aptamers. The G39-C65 variant adopts a compact ligand-free structure in which G39 is accommodated by the ligand binding site and is base-paired to the cytosine at position 65. Here, we demonstrate using a combination of biochemical and biophysical techniques that the G39-C65 base pair not only severely impairs ligand binding but also disrupts the functioning of the riboswitch in vivo by constitutively activating gene expression. Folding studies using single-molecule FRET revealed that the G39-C65 variant displays a low level of dynamic heterogeneity, a feature reminiscent of ligand-bound wild-type complexes. A restricted conformational freedom together with an ability to significantly fold in monovalent ions are exclusive to the G39-C65 variant. This work provides a mechanistic framework to rationalize the evolutionary exclusion of certain nucleotide combinations in favor of sequences that preserve ligand binding and gene regulation functionalities.

Understanding the role of flux, pressure and temperature on polymorphism in ThB2O5.

A novel polymorph of ThB2O5, denoted as ß-ThB2O5, was synthesised under high-temperature high-pressure (HT/HP) conditions. Via single crystal X-ray diffraction measurements, ß-ThB2O5 was found to form a three-dimensional (3D) framework structure where thorium atoms are ten-fold oxygen coordinated forming tetra-capped trigonal prisms. The only other known polymorph of ThB2O5, denoted α, synthesised herein using a known borax, B2O3-Na2B4O7, high temperature solid method, was found to transform to the ß polymorph when exposed to conditions of 4 GPa and ∼900 °C. Compared to the α polymorph, ß-ThB2O5 has smaller molar volume by approximately 12%. Exposing a mixture of the α and ß polymorphs to HT/HP conditions ex situ further demonstrated the preferred higher-pressure phase being ß, with no α phase material being observed via Rietveld refinements against laboratory X-ray powder diffraction (PXRD) measurements. In situ heating PXRD measurements on α-ThB2O5 from RT to 1030 °C indicated that α-ThB2O5 transforms to the ß variant at approximately 900 °C via a 1st order mechanism. ß-ThB2O5 was found to exist only over a narrow temperature range, decomposing above 1050 °C. Ab initio calculations using density functional theory (DFT) with the Hubbard U parameter indicated, consistent with experimental observations, that ß is both the preferred phase at higher temperatures and high pressures. Interestingly, it was found by switching from B2O3-Na2B4O7 to H3BO3-Li2CO3 flux using consistent high temperature solid state conditions for the synthesis of the α variant, ß-ThB2O5 could be generated. Comparison of their single crystal measurements showed this was identical to that obtained from HT/HP conditions.

Direct evaluation of the phase diagrams of dense multicomponent plasmas by integration of the Clapeyron equations.

Accurate phase diagrams of multicomponent plasmas are required for the modeling of dense stellar plasmas, such as those found in the cores of white dwarf stars and the crusts of neutron stars. Those phase diagrams have been computed using a variety of standard techniques, which suffer from physical and computational limitations. Here we present an efficient and accurate method that overcomes the drawbacks of previously used approaches. In particular, finite-size effects are avoided as each phase is calculated separately; the plasma electrons and volume changes are explicitly taken into account; and arbitrary analytic fits to simulation data as well as particle insertions are avoided. Furthermore, no simulations at "uninteresting" state conditions, i.e., away from the phase coexistence curves, are required, which improves the efficiency of the technique. The method consists of an adaptation of the so-called Gibbs-Duhem integration approach to electron-ion plasmas, where the coexistence curve is determined by direct numerical integration of its underlying Clapeyron equation. The thermodynamics properties of the coexisting phases are evaluated separately using Monte Carlo simulations in the isobaric semigrand canonical ensemble (NPTΔµ). We describe this Monte Carlo-based Clapeyron integration method, including its basic physical and numerical principles, our extension to electron-ion plasmas, and our numerical implementation. We illustrate its applicability and benefits with the calculation of the melting curve of dense carbon-oxygen plasmas under conditions relevant for the cores of white dwarf stars and provide analytic fits to implement this new melting curve in white dwarf models. While this work focuses on the liquid-solid phase boundary of dense two-component plasmas, a wider range of physical systems and phase boundaries are within the scope of the Clapeyron integration method, which had until now only been applied to simple model systems of neutral particles.

Riboswitches: ancient and promising genetic regulators.

BAIT AND SWITCH: Metabolite-sensing riboswitches make use of RNA structural modulation to regulate gene expression, as illustrated in the scheme, in response to subtle changes in metabolite concentrations. This review describes the current knowledge about naturally occurring riboswitches and their growing potential as antibacterial cellular targets and as molecular biosensors. Newly discovered metabolite-sensing riboswitches have revealed that cellular processes extensively make use of RNA structural modulation to regulate gene expression in response to subtle changes in metabolite concentrations. Riboswitches are involved at various regulation levels of gene expression, such as transcription attenuation, translation initiation, mRNA splicing and mRNA processing. Riboswitches are found in the three kingdoms of life, and in various cases, are involved in the regulation of essential genes, which makes their regulation an essential part of cell survival. Because riboswitches operate without the assistance of accessory proteins, they are believed to be remnants of an ancient time, when gene regulation was strictly based on RNA, from which are left numerous "living molecular fossils", as exemplified by ribozymes, and more spectacularly, by the ribosome. Due to their nature, riboswitches hold high expectations for the manipulation of gene expression and the detection of small metabolites, and also offer an unprecedented potential for the discovery of novel classes of antimicrobial agents.

Functional studies of DNA-protein interactions using FRET techniques.

Protein-DNA interactions underpin life and play key roles in all cellular processes and functions including DNA transcription, packaging, replication, and repair. Identifying and examining the nature of these interactions is therefore a crucial prerequisite to understand the molecular basis of how these fundamental processes take place. The application of fluorescence techniques and in particular fluorescence resonance energy transfer (FRET) to provide structural and kinetic information has experienced a stunning growth during the past decade. This has been mostly promoted by new advances in the preparation of dye-labeled nucleic acids and proteins and in optical sensitivity, where its implementation at the level of individual molecules has opened a new biophysical frontier. Nowadays, the application of FRET-based techniques to the analysis of protein-DNA interactions spans from the classical steady-state and time-resolved methods averaging over large ensembles to the analysis of distances, conformational changes, and enzymatic reactions in individual Protein-DNA complexes. This chapter introduces the practical aspects of applying these methods for the study of Protein-DNA interactions.

Impact of tamsulosin and nifedipine on contractility of pregnant rat ureters in vitro.

OBJECTIVES: To evaluate the in vitro effect of tamsulosin and nifedipine on the contractility of pregnant rat ureters and to perform quantitative analysis of the pharmacological effects. Medical expulsive therapy (MET) is commonly used to treat urolithiasis. However, this treatment is seldom used in pregnant women since no studies support this practice. METHODS: This was an in vitro study on animal tissue derived from pregnant Sprague-Dawley rats. A total of 124 ureteral segments were mounted in an organ bath system and contractile response to methacholine (MCh) was assessed. Tamsulosin or nifedipine were added at cumulative concentrations (0.001-1 µM). The area under the curve (AUC) from isometric tension measurements was calculated. The effect of pharmacological agents and the respective controls were assessed by calculating the AUC for each 5-min interval. Statistical analyses were performed using the Mann-Whitney-Wilcoxon nonparametric test. RESULTS: Both drugs displayed statistically significant inhibitory activity at concentrations of 0.1 and 1 µM for tamsulosin and 1 µM for nifedipine when calculated as the AUC as compared to DMSO controls. CONCLUSION: Tamsulosin and nifedipine directly inhibit MCh-induced contractility of pregnant rat ureters. Further work is needed to determine the clinical efficacy of these medications for MET in pregnancy.

Neuroprotective effects of antenatal magnesium sulfate under inflammatory conditions in a Sprague-Dawley pregnant rat model.

OBJECTIVE: Antenatal magnesium sulfate (MgSO4) is recommended for fetal neuroprotection. The aim of this animal study was to assess the neuroprotective effect of in utero exposure to MgSO4, under inflammatory conditions. METHODS: Timed pregnant Sprague-Dawley (SD) rats (n = 29) received four intra-peritoneal (IP) injections of lipopolysaccharides (LPS; 200 µg/kg), combined with increasing concentrations of MgSO4 (25, 50 or 100 mg/kg, n = 19) or saline solution (SS; n = 10). In the second set of experiments, animals (n = 8) received a single IP injection of i) LPS (500 µg/kg), MgSO4 (50 mg/kg) and SS (n = 4) or ii) LPS (500 µg/kg), MgSO4 (50 mg/kg) and IL-6 (12 µg/kg) (n = 4). Neurodevelopmental outcomes of surviving pups (n = 212) were assessed by the open field and the rotarod tests. RESULTS: Pups' average weight at postnatal day (P) 25 was 75.77 g and 89.08 g in MgSO4 and control groups, respectively (p = 0.02). Pups in MgSO4 group have traveled a shorter distance and have shown reduced motor balance and coordination (p < 0.01). Average weight of pups receiving (LPS + MgSO4+ IL-6) was 92.26 g at P25, compared to 75.86 g in (LPS + MgSO4+SS) group (p < 0.05). CONCLUSIONS: In our model, MgSO4 induces pup's growth retardation and motor deficits, which may partly be related to a lower IL-6 circulating concentration.

Antenatal montelukast treatment reduces uterine activity associated with inflammation in a pregnant rat model.

OBJECTIVE: The potency of acute montelukast treatment, a leukotriene receptor antagonist, has been demonstrated as tocolytic on in vitro myometrial contractility. This study assessed the ability of a 48h montelukast treatment to modify in vitro contractions under inflammatory conditions in a pregnant rat model. STUDY DESIGN: Pregnant Sprague-Dawley rats were injected intraperitoneally (gestational days 20-22) with lipopolysaccharides (LPS) 200µg/kg (4 treatments at 12h intervals) alone or combined with montelukast 10mg/kg/day or a saline solution for a 48h period. Uterine rings (n=72) were obtained by median laparotomy at day 22. Spontaneous contractile activities were compared using pharmacological compounds (oxytocin, nifedipine) along with assessment of contractile parameters. Myometrial subcellular fractions were also analyzed by Western blot to quantify oxytocin, cysteinyl leukotriene receptors and inflammation markers. RESULTS: In in vitro experiments, the area under the curve, the amplitude and the duration of phasic contractions were significantly reduced following 48h of LPS+montelukast treatment comparatively to the LPS group. Moreover, in this same group, oxytocin (10-9-10-7M) largely decreased uterine sensitivity (p=0.04). Following LPS and montelukast treatment, the tocolytic effectiveness of nifedipine (10-9-10-7M) was increased (p<0.01). Western blot analysis confirmed the presence of type 1 CysLT receptors in all treated groups. Hence, montelukast treatment restored TNF-α and COX-2 basal levels. CONCLUSION: Our results strongly suggest that montelukast treatment could facilitate a relative uterine quiescence by decreasing its sensitivity to uterotonic agent or by increasing tocolytic efficiency under proinflammatory conditions.