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Adverse pregnancy outcomes pose major health risks to pregnant women and increase maternal risk for cardiovascular disease, but mechanisms linking these two conditions are not well understood. The renin-angiotensin system (RAS) is a cardiovascular system comprised of two arms with opposing actions that plays a major role in cardiovascular adaptation to pregnancy. We investigated whether the normal activity of the RAS during pregnancy was dysregulated in pregnancies with adverse outcomes. In a study of 74 women followed prospectively for pregnancy-hypertension and related adverse outcomes, we used a novel LC-MS/MS-based methodology to quantify multiple components of the classical and alternative RAS at two time points in pregnancy. There were n=46 women meeting the primary endpoint (a composite of adverse outcomes) and n=28 women without adverse outcomes. Serum concentrations of the classical RAS, angiotensin peptides I and II, and renin activity, were increased in healthy pregnancy, but markedly suppressed in adverse outcome pregnancies. In contrast, components of the alternative RAS, ACE2, neprilysin, and angiotensin-1-5, were moderately increased in healthy pregnancies but robustly increased in adverse outcome pregnancies. Our results indicate that a shift in the activation of the classical to the alternative arm of the RAS portends development of adverse outcomes of pregnancy.

BACKGROUND: Preterm birth is a global health priority. Using a progestogen during high-risk pregnancy could reduce preterm birth and adverse neonatal outcomes.METHODS: We did a systematic review of randomised trials comparing vaginal progesterone, intramuscular 17-hydroxyprogesterone caproate (17-OHPC), or oral progesterone with control, or with each other, in asymptomatic women at risk of preterm birth. We identified published and unpublished trials that completed primary data collection before July 30, 2016, (12 months before data collection began), by searching MEDLINE, Embase, CINAHL, the Maternity and Infant Care Database, and relevant trial registers between inception and July 30, 2019. Trials of progestogen to prevent early miscarriage or immediately-threatened preterm birth were excluded. Individual participant data were requested from investigators of eligible trials. Outcomes included preterm birth, early preterm birth, and mid-trimester birth. Adverse neonatal sequelae associated with early births were assessed using a composite of serious neonatal complications, and individually. Adverse maternal outcomes were investigated as a composite and individually. Individual participant data were checked and risk of bias assessed independently by two researchers. Primary meta-analyses used one-stage generalised linear mixed models that incorporated random effects to allow for heterogeneity across trials. This meta-analysis is registered with PROSPERO, CRD42017068299.FINDINGS: Initial searches identified 47 eligible trials. Individual participant data were available for 30 of these trials. An additional trial was later included in a targeted update. Data were therefore available from a total of 31 trials (11 644 women and 16185 offspring). Trials in singleton pregnancies included mostly women with previous spontaneous preterm birth or short cervix. Preterm birth before 34 weeks was reduced in such women who received vaginal progesterone (nine trials, 3769 women; relative risk [RR] 0·78, 95% CI 0·68-0·90), 17-OHPC (five trials, 3053 women; 0·83, 0·68-1·01), and oral progesterone (two trials, 181 women; 0·60, 0·40-0·90). Results for other birth and neonatal outcomes were consistently favourable, but less certain. A possible increase in maternal complications was suggested, but this was uncertain. We identified no consistent evidence of treatment interaction with any participant characteristics examined, although analyses within subpopulations questioned efficacy in women who did not have a short cervix. Trials in multifetal pregnancies mostly included women without additional risk factors. For twins, vaginal progesterone did not reduce preterm birth before 34 weeks (eight trials, 2046 women: RR 1·01, 95% CI 0·84-1·20) nor did 17-OHPC for twins or triplets (eight trials, 2253 women: 1·04, 0·92-1·18). Preterm premature rupture of membranes was increased with 17-OHPC exposure in multifetal gestations (rupture INTERPRETATION: Vaginal progesterone and 17-OHPC both reduced birth before 34 weeks' gestation in high-risk singleton pregnancies. Given increased underlying risk, absolute risk reduction is greater for women with a short cervix, hence treatment might be most useful for these women. Evidence for oral progesterone is insufficient to support its use. Shared decision making with woman with high-risk singleton pregnancies should discuss an individual's risk, potential benefits, harms and practicalities of intervention. Treatment of unselected multifetal pregnancies with a progestogen is not supported by the evidence.FUNDING: Patient-Centered Outcomes Research Institute.

Marine classification schemes based on abiotic surrogates often inform regional marine conservation planning in lieu of detailed biological data. However, these schemes may poorly represent ecologically relevant biological patterns required for effective design and management strategies. We used a community-level modeling approach to characterize and delineate representative mesoscale (tens to thousands of kilometers) assemblages of demersal fish and benthic invertebrates in the Northwest Atlantic. Hierarchical clustering of species occurrence data from four regional annual multispecies trawl surveys revealed three to six groupings (predominant assemblage types) in each survey region, broadly associated with geomorphic and oceanographic features. Indicator analyses identified 3-34 emblematic taxa of each assemblage type. Random forest classifications accurately predicted assemblage distributions from environmental covariates (AUC 0.95) and identified thermal limits (annual minimum and maximum bottom temperatures) as important predictors of distribution in each region. Using forecasted oceanographic conditions for the year 2075 and a regional classification model, we projected assemblage distributions in the southernmost bioregion (Scotian Shelf-Bay of Fundy) under a high emissions climate scenario (RCP 8.5). Range expansions to the northeast are projected for assemblages associated with warmer and shallower waters of the Western Scotian Shelf over the 21st century as thermal habitat on the relatively cooler Eastern Scotian Shelf becomes more favorable. Community-level modeling provides a biotic-informed approach for identifying broadscale ecological structure required for the design and management of ecologically coherent, representative, well-connected networks of Marine Protected Areas. When combined with oceanographic forecasts, this modeling approach provides a spatial tool for assessing sensitivity and resilience to climate change, which can improve conservation planning, monitoring, and adaptive management.

New findings What is the central question of this study? Is chemerin, an adipokine implicated in obesity, increased in neonates following in utero cigarette smoke exposure. What is the main finding and its importance? Chemerin mRNA expression was increased and chemerin DNA methylation was decreased in babies born to mothers who smoked during pregnancy. These data provide a potential mechanism that may be mediating the increased obesity risk in individuals that are born to mothers who smoked during pregnancy. Abstract It has been shown that in utero tobacco exposure increases offspring risk for obesity, but the mechanisms responsible for this increased risk are not well understood. Chemerin is an adipokine that regulates adipocyte differentiation. This chemokine is elevated in obese individuals and with smoke exposure, but its levels have not been measured in neonates exposed to cigarette smoke in utero. We examined chemerin gene expression [n = 31 non-smoker (NS) and 15 smoker (S)] and DNA methylation (n = 28 NS and n = 11 S) in skin collected from babies born to mothers who smoked during pregnancy as compared to non-smoking controls. Quality RNA and DNA were isolated from foreskin tissue following circumcision, and chemerin gene expression and DNA methylation were assessed. Further, in a second cohort, we utilized primary dermal foreskin fibroblasts as a functional measure of adipogenesis in living cells (n = 11 NS and n = 8 S). Cells were stimulated with an adipogenic cocktail, mRNA was isolated from cells after 14 days, and chemerin gene expression assessed via real-time PCR. Chemerin mRNA was elevated in both whole tissue (NS: 2409.20 ± 555.28 counts and S: 2966.72 ± 636.84 counts; P 0.55 2 Δ Δ C T and S: 2.13 ± 1.34 2 Δ Δ C T ; P = 0.04) collected from infants born to smoking mothers. Chemerin DNA methylation was reduced in whole tissue of offspring born to smokers (NS: 4.18 ± 1.28 and S: 3.07 ± 1.31%; P = 0.02), which may contribute to the increased gene expression. Neonates born to mothers who smoke during pregnancy exhibit distinct changes in chemerin gene expression in response to in utero tobacco smoke exposure which are regulated in part by epigenetic alterations.

Reducing the risk of developing chronic disease, such as obesity and type 2 diabetes, is an important component of successful aging. Offspring born to mothers who exercise during pregnancy have improved body composition and metabolic profiles. However, mechanisms to explain this phenomenon are lacking.PurposeThis study examined whether maternal step counts were correlated with neonatal gene expression markers related to glucose metabolism and adipogenesis.MethodsPhysical activity levels were assessed in women with male neonates via Fitbit Flex® during the second and third trimester of pregnancy. The dartos and epidermal/dermal layers of the foreskin were collected following circumcision in full-term, singleton, neonates (n = 12 dartos and n = 14 dermal). Tissue was homogenized, RNA isolated, and a NanoString code set was run to quantify a panel of genes related to glucose metabolism and adipogenesis.ResultsTwelve genes were correlated to steps per day with a P-value of P-value < 0.10). Notably, glucose transporter 1, adiponectin receptor 1, and CCAAT/enhancer-binding protein alpha and beta were positively correlated with steps per day, while peroxisome proliferator-activated receptor alpha and peroxisome proliferator-activated receptor gamma coactivator 1- alpha were negatively correlated with steps per day.ConclusionMaternal physical activity is associated with offspring gene expression markers of adipogenesis, insulin sensitivity and glucose uptake. Future studies should aim to mechanistically examine whether these markers are driving increased adiposity in offspring born to sedentary mothers.

BackgroundAn indirect comparison meta-analysis published in 2013 reported that both vaginal progesterone and cerclage are equally efficacious for preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth and a sonographic short cervix. The efficacy of vaginal progesterone has been disputed after publication of the OPPTIMUM study.ObjectiveTo compare the efficacy of vaginal progesterone and cerclage in preventing preterm birth and adverse perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth and a midtrimester sonographic short cervix.Data SourcesMEDLINE, EMBASE, LILACS, and CINAHL (from their inception to March 2018); Cochrane databases, bibliographies, and conference proceedings.Study Eligibility CriteriaRandomized controlled trials comparing vaginal progesterone with placebo/no treatment or cerclage with no cerclage in women with a singleton gestation, previous spontaneous preterm birth and a sonographic cervical length Study Appraisal and Synthesis MethodsUpdated systematic review and adjusted indirect comparison meta-analysis of vaginal progesterone versus cerclage using placebo/no cerclage as the common comparator. The primary outcomes were preterm birth ResultsFive trials comparing vaginal progesterone versus placebo (265 women) and 5 comparing cerclage versus no cerclage (504 women) were included. Vaginal progesterone, compared with placebo, significantly reduced the risk of preterm birth ConclusionsVaginal progesterone and cerclage are equally effective for preventing preterm birth and improving perinatal outcomes in women with a singleton gestation, previous spontaneous preterm birth, and a midtrimester sonographic short cervix. The choice of treatment will depend on adverse events and cost-effectiveness of interventions, and patient/physician’s preferences.

Objective To assess differences in cytokine levels in cervicovaginal fluid (CVF) and serum across trimesters between women with preterm births (PTBs) and full-term births. Study Design This multicenter study enrolled 302 women with a singleton gestation. CVF and serum cytokines, interleukin 1α (IL-1α), IL-1β, IL-6, IL-8, IL-10, C-reactive protein (CRP), tumor necrosis factor (TNF)-α, and matrix metalloproteinase (MMP)-8, were measured. Women with at least one cytokine assessment and noted PTB status in their medical record were retained in the study (N = 272). Data were analyzed using mixed modeling (main effects of PTBs and time/trimester). Results For the CVF values of IL-6, IL-8, IL-10, TNF-α, and CRP, and serum MMP-8, those who delivered preterm had significantly higher values than the full-term group regardless of trimester. For the serum values of IL-1β, IL-6, and TNF-α, those delivering preterm had significantly lower values than those delivering full-term regardless of trimester. For IL-1β in CVF, the cytokine was significantly higher in the PTB group for second and third trimesters only, relative to the full-term group. Conclusion For each CVF cytokine that differed by birth status, values were higher for PTB than term, averaged over trimester. Numerous cytokine profiles varied across trimesters in women delivering term versus preterm in both CVF and serum.

Background The efficacy of vaginal progesterone for preventing preterm birth and adverse perinatal outcomes in singleton gestations with a short cervix has been questioned after publication of the OPPTIMUM study. Objective To determine whether vaginal progesterone prevents preterm birth and improves perinatal outcomes in asymptomatic women with a singleton gestation and a midtrimester sonographic short cervix. Study Design We searched MEDLINE, EMBASE, LILACS, and CINAHL (from their inception to September 2017); Cochrane databases; bibliographies; and conference proceedings for randomized controlled trials comparing vaginal progesterone vs placebo/no treatment in women with a singleton gestation and a midtrimester sonographic cervical length ≤25 mm. This was a systematic review and meta-analysis of individual patient data. The primary outcome was preterm birth Results Data were available from 974 women (498 allocated to vaginal progesterone, 476 allocated to placebo) with a cervical length ≤25 mm participating in 5 high-quality trials. Vaginal progesterone was associated with a significant reduction in the risk of preterm birth Conclusion Vaginal progesterone decreases the risk of preterm birth and improves perinatal outcomes in singleton gestations with a midtrimester sonographic short cervix, without any demonstrable deleterious effects on childhood neurodevelopment.

Objective This study describes the normal variations in serum and cervicovaginal fluid (CVF) cytokine levels throughout pregnancy. Study Design This multicenter, prospective study examined trimester-specific maternal serum and CVF cytokines (interleukin [IL]-1α, IL-1β, IL-6, IL-8, IL-10, tumor necrosis factor-α, and C-reactive protein [CRP]). A two-factor linear mixed modeling approach compared cytokine distribution, while pairwise comparisons evaluated differences over time. Results Trimester-specific serum cytokine data were available for 288, 243, and 221 patients, whereas CVF cytokine data were available for 273, 229, and 198 patients. CVF had significantly higher concentrations of IL-1α, IL-1β, IL-6, IL-8, and matrix metalloproteinase-8 (p Conclusion Differences in cytokine distribution across different biological fluids are evident throughout pregnancy. These findings provide a framework for examining patterns of changes in cytokines throughout pregnancy.

Elevated birth weight is linked to glucose intolerance and obesity health-related complications later in life. No studies have examined if infant birth weight is associated with gene expression markers of obesity and inflammation in a tissue that comes directly from the infant following birth. We evaluated the association between birth weight and gene expression on fetal programming of obesity. Foreskin samples were collected following circumcision, and gene expression analyzed comparing the 15% greatest birth weight infants (n=7)v.the remainder of the cohort (n=40). Multivariate linear regression models were fit to relate expression levels on differentially expressed genes to birth weight group with adjustment for variables selected from a list of maternal and infant characteristics. Glucose transporter type 4 (GLUT4), insulin receptor substrate 2 (IRS2), leptin receptor (LEPR), lipoprotein lipase (LPL), low-density lipoprotein receptor-related protein 1 (LRP1), matrix metalloproteinase 2 (MMP2), plasminogen activator inhibitor-1 (PAI-1) and transcription factor 7-like 2 (TCF7L2) were significantly upregulated and histone deacetylase 1 (HDAC1) and thioredoxin (TXN) downregulated in the larger birth weight neonatesv. controls. Multivariate modeling revealed that the estimated adjusted birth weight group difference exceeded one standard deviation of the expression level for eight of the 10 genes. Between 25 and 50% of variation in expression level was explained by multivariate modeling for eight of the 10 genes. Gene expression related to glycemic control, appetite/energy balance, obesity and inflammation were altered in tissue from babies with elevated birth weight, and these genes may provide important information regarding fetal programming in macrosomic babies.

Objective To evaluate the efficacy of vaginal progesterone administration for preventing preterm birth and perinatal morbidity and mortality in asymptomatic women with a singleton gestation and a mid‐trimester sonographic cervical length (CL) ≤ 25 mm. Methods This was an updated systematic review and meta‐analysis of randomized controlled trials comparing the use of vaginal progesterone to placebo/no treatment in women with a singleton gestation and a mid‐trimester sonographic CL ≤ 25 mm. Electronic databases, from their inception to May 2016, bibliographies and conference proceedings were searched. The primary outcome measure was preterm birth ≤ 34 weeks of gestation or fetal death. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. Results Five trials involving 974 women were included. A meta‐analysis, including data from the OPPTIMUM study, showed that vaginal progesterone significantly decreased the risk of preterm birth ≤ 34 weeks of gestation or fetal death compared to placebo (18.1% vs 27.5%; RR, 0.66 (95% CI, 0.52–0.83); P = 0.0005; five studies; 974 women). Meta‐analyses of data from four trials (723 women) showed that vaginal progesterone administration was associated with a statistically significant reduction in the risk of preterm birth occurring at, This article has been selected for Journal Club. Click here to view slides and discussion points.

Small invertebrate grazers can disproportionately reduce plant fitness by discriminately consuming valuable tissues, but the context and attendant consequences of this activity at higher levels of ecological organization rarely are considered. To assess the impact of a gastropod mesograzer Lacuna vincta on fecundity and potential reproductive output of the habitat-forming kelp Saccharina latissima, we measured the intensity and distribution of grazing damage on kelp blades at five sites of varying kelp density, during the annual reproductive peak (October-November) in Nova Scotia. We found most grazing damage on reproductive individuals consisted of superficial excavations, and was concentrated on the central sorus (region where sporangia develop) compared to the vegetative blade margins. Grazing intensity on sori (percent grazed) averaged 29.6% across sites and sampling periods. The distribution of grazing on non-reproductive individuals was opposite to that of reproductive ones, indicating that snails shift feeding from blade margins to the center as sori develop. Choice and no-choice feeding assays in the laboratory revealed that focused grazing on sori is likely due to an active feeding preference for sporogenous over vegetative tissue. This preference was correlated with the distribution of chemical defense between tissues (phlorotannin content was ~2.5 times higher in vegetative tissue than sori), but not nutritional quality (no difference in C/N ratio). We deduce, with support from histological observations, that consumption of sorus tissue by L. vincta reduces fecundity of S. latissima. Extrapolating our results to estimate potential reproductive output within kelp beds suggests that spore supply and recruitment limitation may be predominantly imposed by the scarcity of reproductive individuals in the most degraded kelp beds. However, loss of reproductive output to grazing could extend recruitment limitations that impede recovery of waning kelp populations in Nova Scotia.

Low recruitment due to limitations of propagule supply or post-settlement survival reinforces dominance of turf algal assemblages that replace canopy algae following large-scale losses. However, post-recruitment processes that hinder juvenile growth and survival (epiphytic overgrowth, grazing, physical stress) also could impede recovery. To evaluate the contribution of recruitment, growth, and survival of young sporophytes to recovery of degraded kelp populations and key factors driving post-recruitment tissue loss and mortality, we followed cohorts of juvenile kelp Saccharina latissima at two defoliated sites in Nova Scotia. We also monitored kelp recruitment, abundance, size structure, and macroalgal composition for 5.5 years. Recruit densities were an order of magnitude lower compared to previous studies in the region. Large decreases in blade area of juveniles were related to cover by the invasive bryozoan Membranipora membranacea, grazing by small snails Lacuna vincta, and warm seawater temperatures. Cohort survival was low (time to 50% mortality 2.5–5.5 months) and increased risk of death was directly related to bryozoan encrustation. Modest seasonal or interannual gains in kelp abundance were lost during periods of peak temperature, which showed a warming trend during the study, favouring persistence of widespread turf-forming, opportunistic and invasive algae. We conclude that low recruitment success, high rate of tissue loss relative to growth, and high mortality, inhibited kelp recovery. Impacts of epiphytic overgrowth, grazing, and warm temperatures on these processes highlight the need to protect intact kelp populations, growing in favourable conditions, to maintain positive interactions that increase resilience to undesirable regime shifts.

What is the central question of this study? Is chemerin, an adipokine implicated in obesity, increased in neonates following in utero cigarette smoke exposure. What is the main finding and its importance? Chemerin mRNA expression was increased and chemerin DNA methylation was decreased in babies born to mothers who smoked during pregnancy. These data provide a potential mechanism that may be mediating the increased obesity risk in individuals that are born to mothers who smoked during pregnancy.It has been shown that in utero tobacco exposure increases offspring risk for obesity, but the mechanisms responsible for this increased risk are not well understood. Chemerin is an adipokine that regulates adipocyte differentiation. This chemokine is elevated in obese individuals and with smoke exposure, but its levels have not been measured in neonates exposed to cigarette smoke in utero. We examined chemerin gene expression [n = 31 non-smoker (NS) and 15 smoker (S)] and DNA methylation (n = 28 NS and n = 11 S) in skin collected from babies born to mothers who smoked during pregnancy as compared to non-smoking controls. Quality RNA and DNA were isolated from foreskin tissue following circumcision, and chemerin gene expression and DNA methylation were assessed. Further, in a second cohort, we utilized primary dermal foreskin fibroblasts as a functional measure of adipogenesis in living cells (n = 11 NS and n = 8 S). Cells were stimulated with an adipogenic cocktail, mRNA was isolated from cells after 14 days, and chemerin gene expression assessed via real-time PCR. Chemerin mRNA was elevated in both whole tissue (NS: 2409.20 ± 555.28 counts and S: 2966.72 ± 636.84 counts; P0.01) and primary fibroblasts (NS: 1.12 ±mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:mrowmml:mn0.55/mml:mnmml:mspace/mml:msupmml:mn2/mml:mnmml:mrowmml:miΔ/mml:mimml:miΔ/mml:mimml:msubmml:miC/mml:mimml:miT/mml:mi/mml:msub/mml:mrow/mml:msup/mml:mrow/mml:mathand S: 2.13 ±mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"mml:mrowmml:mn1.34/mml:mnmml:mspace/mml:msupmml:mn2/mml:mnmml:mrowmml:miΔ/mml:mimml:miΔ/mml:mimml:msubmml:miC/mml:mimml:miT/mml:mi/mml:msub/mml:mrow/mml:msup/mml:mrow/mml:math; P = 0.04) collected from infants born to smoking mothers. Chemerin DNA methylation was reduced in whole tissue of offspring born to smokers (NS: 4.18 ± 1.28 and S: 3.07 ± 1.31%; P = 0.02), which may contribute to the increased gene expression. Neonates born to mothers who smoke during pregnancy exhibit distinct changes in chemerin gene expression in response to in utero tobacco smoke exposure which are regulated in part by epigenetic alterations.

Objective To evaluate the association of biochemically validated prenatal tobacco use with serum progesterone and estradiol in the second trimester of pregnancy, controlling for demographic and personal factors. Study design This secondary analysis of a multicenter longitudinal study included 114 women with singleton pregnancies. Multiple regression analysis assessed whether prenatal tobacco use was related to hormone levels during the second trimester, controlling for covariates (age, body mass index, and race or ethnicity, with gestational age added to subsequent models). Result In the initial regressions, tobacco users had significantly lower progesterone level compared with nonsmokers ( p = .037), while estradiol was unrelated to prenatal tobacco use. Women with greater body mass index also had significantly lower progesterone ( p = .028), but body mass index was unrelated to estradiol. With gestational age as an additional covariate, prenatal tobacco use was no longer a significant predictor of progesterone, but both body mass index and gestational age were significant ( F = 10.6, p 2 = 0.35). For estradiol, the overall regression of estradiol on age, body mass index, and race or ethnicity was not significant ( F = 1.2, p = .31). With gestational age added to the model, the overall model was significant ( F = 7.2, p 2 = 0.27). Conclusion This study provides additional evidence that prenatal tobacco use may influence lower serum progesterone during the second trimester. This is of particular concern given the link between depressed progesterone activity and risk for preterm birth.

This paper gives a general algorithm for computing the character table of any Renner monoid Hecke algebra, by adapting and generalizing techniques of Solomon used to study the rook monoid. The character table of the Hecke algebra of the rook monoid (i.e. the Cartan type [Formula: see text] Renner monoid) was computed earlier by Dieng et al. [2], using different methods. Our approach uses analogues of so-called A- and B-matrices of Solomon. In addition to the algorithm, we give explicit combinatorial formulas for the A- and B-matrices in Cartan type [Formula: see text] and use them to obtain an explicit description of the character table for the type [Formula: see text] Renner monoid Hecke algebra.

We examined how large-scale distur- bances that defoliate kelp beds (outbreaks of an invasive bryozoan, hurricanes) alter local-scale grazing dynamics of an abundant herbivore, the gastropod Lacuna vincta, on the Atlantic coast of Nova Scotia, Canada. From field observations and a 5 wk kelp-thinning experiment that simulated dis- turbance, we found that snail density and grazing intensity on the kelp Saccharina latissima increased non-linearly with decreasing kelp biomass, as it varied within a site. Grazing intensity on S. latissima also increased non-linearly with decreasing stand- ing kelp biomass across 5 sites spanning 40 km (linear distance) of coast and 2 yr, but we did not find strong support for this relationship for the kelp Laminaria digitata. Intensification of grazing aug- ments the indirect effect of L. vincta on S. latissima (increased blade erosion and fragmentation), and drives it beyond a threshold for further losses of kelp biomass with subsequent storms. This positive feedback between large-scale disturbances and local-scale grazing could reinforce the depletion of kelp and facilitate the establishment of turf-forming algae on Nova Scotian rocky reefs. We conclude that interactions of large external perturbations with local natural perturbations must be considered to under stand how drivers of ecosystem change collec- tively disrupt the balance of top-down and bottom- up forces to cause shifts to unexpected community states.

The complex interactions between genes and the environment yield multiple pathophysiologies for the great obstetrical diseases such as preterm birth (Romero R et al, Science, 2014, 345,760-765). Our current, limited capacity to define when and to what extent any number of these pathophysiologies are in effect in individual pregnant patients has resulted in therapeutic strategies being aimed preferentially toward populations defined by risk factors, particularly obstetrical history. However, strategies such as prophylactic progestogen administration indicated for a prior preterm birth necessarily overtreat pregnant women exposing them and their children to potential, possibly unforeseen, harm (O'Brien JM, BJOG 2015;122:610-614). This article is protected by copyright. All rights reserved.

Objective We hypothesized that, as has been shown outside of pregnancy, endothelial dysfunction would be seen in a dose-dependent fashion among women who smoke in the midtrimester of pregnancy. Study Design Endothelial function in women with singleton pregnancies between 16 and 23 weeks was analyzed utilizing the Endo-PAT2000 device (Itamar Medical Ltd., Caesarea, Israel) and expressed as a reactive hyperemia ratio (RHI). Serum was drawn to check cotinine and high-sensitivity C-reactive protein (CRP) levels. SAS 9.2 (SAS Institute, Cary, NC) was used to perform statistical tests including Student t test, analysis of variance, Fisher exact test, and Pearson coefficient. Results Endothelial function was noninvasively examined in 29 smokers and 31 nonsmokers. Demographics including age, race, and parity were similar between groups. Mean RHI was not significantly different between smokers and nonsmokers (1.43 ± 0.32 versus 1.53 ± 0.39, p = 0.27). No correlation was noted when cotinine values were plotted against RHI or CRP values in smokers (rho = 0.24, p = 0.21 and rho = 0.26, p = 0.18, respectively). RHI did correlate with diastolic blood pressure (rho = −0.40, p = 0.002), systolic blood pressure (rho = −0.35, p = 0.006), and heart rate (rho = −0.37, p = 0.004). Conclusion We did not find an association between smoking status and endothelial dysfunction in the midtrimester utilizing a noninvasive methodology.

The epiphytic bryozoan Membranipora membranacea encrusts the surface of kelp blades, causing recurrent large-scale defoliation events in kelp beds off the Atlantic coast of Nova Scotia, Canada. The gastropod Lacuna vincta grazes kelp, creating perforations that weaken blade tissues and increase the fragmentation rate. We assess the interaction between M. membranacea and L. vincta by measuring the grazing rate of snails on bryozoan-encrusted and non-encrusted kelp (Saccharina latissima) in no-choice and choice experiments in the laboratory conducted in November and December 2010. There was no effect of diet on grazing rate in no-choice experiments. In choice experiments, however, L. vincta grazed significantly more non-encrusted than encrusted kelp (7.1 versus 1.1 mg snail−1 d−1), and grazing rate of non-encrusted kelp was almost twice that in the no-choice experiment (3.8 mg snail−1 d−1), indicating that snails may avoid colonies of M. membranacea on partially encrusted kelp blades. We found no effect of diet on growth, reproduction and survival of snails maintained for four weeks on encrusted or non-encrusted kelp. By concentrating grazing damage on non-encrusted areas of blades, L. vincta may act synergistically with M. membranacea to increase the likelihood of blade breakage and canopy loss. This indirect effect of the invasive bryozoan could augment its direct effect on the standing biomass of native kelp beds and detrital export to adjacent communities.

Background The likelihood of cesarean is in part related to maternal body mass index (BMI). Myometrial changes may be responsible. Methods Myometrial biopsies were collected from the upper edge of the hysterotomy from women undergoing scheduled cesarean with term, singleton gestations. Oxytocin receptor and connexin-43 mRNA protein expression was quantified with real-time polymerase chain reaction and Western blot. Results Twenty subjects were recruited: 13 repeat and 7 primary cesareans. Oxytocin receptor mRNA was associated with BMI among women undergoing primary ( r = 0.75; p = 0.05) but not repeat cesarean ( p > 0.05). Controlling for gestational age, this association strengthened ( p = 0.004). Receptor protein expression showed a linear correlation with BMI in the primary cesarean group ( p = 0.002). Connexin-43 mRNA expression was not related to BMI in women undergoing primary ( r = −0.14, p = 0.76) or repeat ( r = −0.01, p = 0.86) cesarean. Conclusions Oxytocin receptor, but not connexin-43, expression is related to BMI, suggesting an alteration in oxytocin receptor expression or function related to obesity.

The safety of supplemental progestin therapy during pregnancy reflects whether an agent exclusively promotes or potentially inhibits progestational cellular functions and whether treatment incites a metabolic derangement or other pathophysiology to initiate rare untoward events. No safety signal has been identified from intravaginal administration of natural progesterone from phase III clinical trials. The Food and Drug Administration has identified a legitimate safety signal regarding second-trimester miscarriage and stillbirth with exposure to 17-hydroxyprogesterone caproate (17-OHPC). Results from recent phase II and III trials in multiples also demonstrates concern with exposure to this synthetic for fetal loss and increased severe respiratory distress in neonates (one study each), as well as repeated significant associations for shorter duration of pregnancy and poorer fetal growth in others. The biological plausibility for 17-OHPC to be associated with adverse outcomes can be suggested from pharmacogenomic observations, ex vivo experimentation, and clinical observations. Further data are needed interrogating the potential for rare fetal or maternal adverse events/safety outcomes with exposure to progestins. Safety concerns should be incorporated into prescribing decisions.

L’EMDR (désensibilisation et retraitement par les mouvements oculaires) est une thérapie qui a démontré son efficacité dans le traitement de l’état de stress post-traumatique (ESPT). Une littérature clinique encore relativement réduite, mais croissante, montre que l’EMDR peut aussi être un traitement complémentaire efficace de la toxicomanie. Le présent article passe en revue les divers protocoles qui ont été développés dans ce but, avec les protocoles de Vogelmann-Sine et al., Omaha, Popky et Hase. Une étude de cas intégrant certaines de ces interventions est présentée afin d’illustrer la réussite du traitement par l’EMDR d’une femme souffrant de longue date d’une dépendance à l’alcool et d’un ESPT comorbides. Le suivi, deux ans plus tard, a montré que cette femme restait sobre et que l’ESPT était en rémission complète. Après une discussion des aspects importants de ce cas, les auteurs explorent de futures directions de recherche.

Women with a sonographic short cervix in the mid-trimester are at increased risk for preterm delivery. This study was undertaken to determine the efficacy and safety of using micronized vaginal progesterone gel to reduce the risk of preterm birth and associated neonatal complications in women with a sonographic short cervix.This was a multicenter, randomized, double-blind, placebo-controlled trial that enrolled asymptomatic women with a singleton pregnancy and a sonographic short cervix (10-20 mm) at 19 + 0 to 23 + 6 weeks of gestation. Women were allocated randomly to receive vaginal progesterone gel or placebo daily starting from 20 to 23 + 6 weeks until 36 + 6 weeks, rupture of membranes or delivery, whichever occurred first. Randomization sequence was stratified by center and history of a previous preterm birth. The primary endpoint was preterm birth before 33 weeks of gestation. Analysis was by intention to treat.Of 465 women randomized, seven were lost to follow-up and 458 (vaginal progesterone gel, n=235; placebo, n=223) were included in the analysis. Women allocated to receive vaginal progesterone had a lower rate of preterm birth before 33 weeks than did those allocated to placebo (8.9% (n=21) vs 16.1% (n=36); relative risk (RR), 0.55; 95% CI, 0.33-0.92; P=0.02). The effect remained significant after adjustment for covariables (adjusted RR, 0.52; 95% CI, 0.31-0.91; P=0.02). Vaginal progesterone was also associated with a significant reduction in the rate of preterm birth before 28 weeks (5.1% vs 10.3%; RR, 0.50; 95% CI, 0.25-0.97; P=0.04) and 35 weeks (14.5% vs 23.3%; RR, 0.62; 95% CI, 0.42-0.92; P=0.02), respiratory distress syndrome (3.0% vs 7.6%; RR, 0.39; 95% CI, 0.17-0.92; P=0.03), any neonatal morbidity or mortality event (7.7% vs 13.5%; RR, 0.57; 95% CI, 0.33-0.99; P=0.04) and birth weight1500 g (6.4% (15/234) vs 13.6% (30/220); RR, 0.47; 95% CI, 0.26-0.85; P=0.01). There were no differences in the incidence of treatment-related adverse events between the groups.The administration of vaginal progesterone gel to women with a sonographic short cervix in the mid-trimester is associated with a 45% reduction in the rate of preterm birth before 33 weeks of gestation and with improved neonatal outcome.