Search

Angewandte Chemie / International edition International edition 58(30), 10179 - 10183 (2019). doi:10.1002/anie.201903765, Published by Wiley-VCH, Weinheim

While chemoselectivities in Pd0-catalyzed coupling reactions are frequently non-intuitive and a result of a complex interplay of ligand/catalyst, substrate, and reaction conditions, we herein report a general method based on PdI that allows for an a priori predictable chemoselective Csp2 −Csp2 coupling at C−Br in preference to C−OTf and C−Cl bonds, regardless of the electronic or steric bias of the substrate. The C−C bond formations are extremely rapid (

International audience; BACKGROUND & AIMS: Programming of infant development and later health may depend on early-milk polyunsaturated fatty acids (PUFA) contents, that are very variable between women for reasons not well elucidated. Indeed, a high n-6/n-3 PUFA in milk was associated with higher adiposity, arterial pressure and lower psychomotor scores in childhood. We aimed to explore the respective contribution of several maternal and perinatal factors to the variability of linoleic (LA), α-linolenic (ALA), arachidonic (AA), and docosahexaenoic (DHA) acid levels in early milk. METHODS: Fatty acids of 934 colostrum samples from the EDEN mother-child cohort were analyzed by gas chromatography. The dietary intakes during the last trimester of pregnancy were estimated using a quantitative food frequency questionnaire. Relationship between milk PUFA and dietary fatty acids, and other maternal or pregnancy variables were analyzed by multiple linear regression.RESULTS: The means (±SD) of colostrum LA, ALA, AA and DHA levels were, respectively, 9.85 ± 1.85, 0.65 ± 0.22, 0.86 ± 0.16, and 0.64 ± 0.19% of total fatty acids. Obese mothers colostrum contained the highest level of LA and AA and the lowest level of ALA and DHA. Colostrum LA, AA and DHA levels were higher in primiparous women. Mother's age was positively associated with colostrum AA and DHA. Dietary n-6 PUFA were associated with higher LA and lower DHA levels in colostrum, while dietary n-3 PUFA were related to higher LA and lower AA levels. Contrary to what was observed for DHA, AA level in colostrum was not related to its dietary intake. High dietary AA/DHA and total n-6/n-3 ratios were critical for the content of DHA in colostrum lipids.CONCLUSIONS: Our study brings new insights in the understanding of the main maternal factors involved in PUFA levels variability in early milk. These data are important to consider for dietary counseling for women prior to and during pregnancy.

Disclosed herein is the first general chemo‐ and site‐selective alkylation of C−Br bonds in the presence of COTf, C−Cl and other potentially reactive functional groups, using the air‐, moisture‐, and thermally stable dinuclear PdI catalyst, [Pd(μ‐I)PtBu3]2. The bromo‐selectivity is independent of the substrate and the relative positioning of the competing reaction sites, and as such fully predictable. Primary and secondary alkyl chains were introduced with extremely high speed (

This study assessed the prevalence of personality disorders (PDs), according to DSM-IV criteria, in relation to depressive symptomatology at three different periods of life in female subjects. Depressive symptoms and personality disorders were assessed in a sample of 568 women from three different transitional stages: 134 students, 314 primiparous women after childbirth and 120 women diagnosed with breast cancer. Depressive symptoms were assessed by the Hospital Depression and Anxiety Scale in the first and third groups and by the Edinburgh Post-natal Depression Scale in the second group, whereas PDs were assessed by the French version of the Vragenlijst voor Kenmerken van de Persoonlijkheid. Depressive symptomatology and rates of PD (20.4% and 6.3%) were equivalent in the three groups. The prevalence of PD was higher in the depressed group compared with the non-depressed group, with more paranoid, borderline, avoidant, obsessive-compulsive, schizotypal, antisocial, dependent and histrionic PD. Our findings support the hypothesis that PDs are more frequently associated with depressive symptoms. Borderline and avoidant PDs were more prevalent among young women. All cluster C PD (dependent, avoidant and obsessive-compulsive) co-occurred significantly with depressive symptoms.

Background According to the World Health Organization, mental health disorders are the leading causes of disease burden in women from 15 to 44 years. These conditions in pregnant women may affect the offspring. Aim To analyze the relation between depression and anxiety of pregnant women and neonatal outcomes including gestational age and birthweight. Study design Observational cohort study. Subjects 2002 women recruited before the 20th gestational week. Outcome measures Gestational age at delivery in completed weeks of amenorrhea and preterm delivery defined as birth before 37 completed weeks of gestation. Spontaneous preterm birth (PB) defined as either spontaneous preterm labor or preterm premature rupture of the membranes. Medically indicated preterm delivery defined as delivery that begins by induction or cesarean section. Birthweight as a continuous variable and centiles of the customized fetal weight norms for the French population. Results From the 1719 women included in the study, 7.9% (n = 135) were classified as “anxious”, 11.8% (n = 203) as “depressed”, 13.2% (n = 227) as “depressed and anxious”. After adjusting for potential confounders, depression combined with anxiety during pregnancy increased the risk of spontaneous PB (Odds Ratio: 2.46 [1.22–4.94]), but did not influence medically indicated PB nor birthweight. Conclusion In this study, comorbidity of depressive and anxiety symptoms was the worst condition during pregnancy. Further studies are needed to investigate depression and anxiety together to improve the comprehension of the biological modifications involved.

Objective In small-for-gestational-age neonates, parental and fetal characteristics can be used to distinguish between constitutionally small size and growth restriction, which is associated with a higher risk of morbidity and mortality. The aim of this study was to quantify relationships of parental and fetal characteristics with fetal ultrasound measurements. Methods The EDEN mother–child cohort included 2002 pregnant women with singleton pregnancies attending one of two university hospitals. Data from two routine ultrasound examinations for fetal biometry were recorded, at 20–25 and 30–35 weeks of gestation. Biparietal diameter (BPD), head circumference (HC), femur length (FL), abdominal circumference (AC) and estimated fetal weight (EFW) were studied as a function of prepregnancy maternal body mass index (BMI), maternal height, paternal height, fetal sex and gestational age. Results Data were obtained at the first scan from 1833 women and at the second scan from 1752 women. Parental anthropometric characteristics were significantly associated with ultrasound measurements at both scans. Maternal BMI was more strongly associated with AC and EFW, whereas both maternal and paternal height were more strongly associated with FL. An association was also found between fetal sex and all ultrasound measurements other than FL. Conclusion Maternal and paternal anthropometric characteristics are significantly associated with ultrasound measurements in mid to late pregnancy. These relationships provide support for the use of these characteristics in ultrasound fetal size reference charts. Copyright © 2011 ISUOG. Published by John Wiley & Sons, Ltd.

International audience; To study the relationship between pre-pregnancy body mass index (BMI) and weight gain during pregnancy with pregnancy and birth outcomes, with a focus on gestational diabetes and hypertension and their role in the association with fetal growth. We studied 1,884 mothers and offspring from the Eden mother-child cohort. Weight before pregnancy (W1) and weight after delivery (W2) were collected and we calculated BMI and net gestational weight gain (netGWG = (W2 - W1)/(weeks of gestation)). Gestational diabetes, hypertension gestational age and birth weight were collected. We used multivariate linear or logistic models to study the association between BMI, netGWG and pregnancy and birth outcomes, adjusting for center, maternal age and height, parity and average number of cigarettes smoked per day during pregnancy. High BMI was more strongly related to the risk of giving birth to a large-for-gestational-age (LGA) baby than high netGWG (odds ratio OR [95% CI] of 3.23 [1.86-5.60] and 1.61 [0.91-2.85], respectively). However, after excluding mothers with gestational diabetes or hypertension the ORs for LGA, respectively weakened (OR 2.57 [1.29-5.13]) for obese women and strengthened for high netGWG (OR 2.08 [1.14-3.80]). Low in comparison to normal netGWG had an OR of 2.18 [1.20-3.99] for pre-term birth, which became stronger after accounting for blood pressure and glucose disorders (OR 2.70 [1.37-5.34]). Higher net gestational weight gain was significantly associated with an increased risk of LGA only after accounting for blood pressure and glucose disorders. High gestational weight gain should not be neglected in regard to risk of LGA in women without apparent risk factors.

Maternal seafood intake is of great health interest since it constitutes an important source of n-3 fatty acids, but provides also an important pathway for fetal exposure to Hg. The objective of the present study was to determine associations between Hg contamination and both maternal seafood consumption and fetal growth in French pregnant women. Pregnant women included in the ‘EDEN mother–child’ cohort study answered FFQ on their usual diet in the year before and during the last 3 months of pregnancy, from which frequencies of seafood intake were evaluated. Total hair-Hg level was determined for the first 691 included women. Associations between Hg level, seafood intake and several neonatal measurements were studied using linear regressions adjusted for confounding variables. The median Hg level for mothers was 0·52 μg/g. Maternal seafood intake was associated with Hg level (r 0·33; P sd in seafood consumption; P = 0·008). Although seafood intake was associated with Hg contamination in French pregnant women, the contamination level was low. There was no consistent association between Hg level and fetal growth. Taking into account Hg level did not modify associations between seafood intake and fetal growth.

Background Prior studies revealed associations of environmental lead exposure with risks of hypertension and elevated blood pressure. Objective We examined the effect of blood lead levels on blood pressure and the incidence of pregnancy-induced hypertension (PIH) in the second and third trimesters of pregnancy. Methods One thousand seventeen pregnant women were enrolled in two French municipalities between 2003 and 2005 for the EDEN (Etude des Déterminants pré et post natals du développement et de la santé de l′ Enfant) cohort study. Blood lead concentrations were measured by atomic absorption spectrometry in mothers between 24 and 28 weeks of gestation. Results PIH was diagnosed in 106 subjects (10.9%). Age, parity, weight gain, alcohol, smoking habits, and calcium supplementation were comparable between hypertensive and nonhypertensive women. Lead levels were significantly higher in PIH cases (mean ± SD, 2.2 ± 1.4 μg/dL) than in normotensive patients (1.9 ± 1.2 μg/dL; p = 0.02). Adjustment for potential confounder effects slightly attenuated but did not eliminate the significant association between blood lead levels and the risk of PIH (adjusted odds ratio of PIH = 3.3; 95% confidence interval, 1.1–9.7). We also observed geographic differences in lead exposure and in the incidence of PIH and found significant correlations between blood lead levels and unadjusted as well as adjusted systolic and diastolic blood pressures after 24 weeks of gestation. Conclusions These findings confirm the relationship between blood lead levels at mid-pregnancy and blood pressure and suggest that environmental lead exposure may play an etiologic role in PIH.

Recent studies suggest a benefit of seafood andn-3 fatty acid intake on fetal growth and infant development. The objective was to study the association between fatty acid intake and fetal growth in pregnant French women. Pregnant women included in the EDEN mother–child cohort study completed FFQ on their usual diet: (1) in the year before pregnancy and (2) during the last 3 months of pregnancy (n1439). Conversion into nutrient intakes was performed using data on portion size and a French food composition table. Associations between maternal fatty acid intakes and several neonatal anthropometric measurements were studied using linear regressions adjusted for centre, mother's age, smoking habits, height, parity, gestational age and newborn's sex. Due to significant interaction, analyses were stratified according to maternal pre-pregnancy overweight status. Neither total lipid nor SFA, MUFA or PUFA intake was significantly associated with newborn size. In overweight women only (n366), a high pre-pregnancyn-3 fatty acid intake (% PUFA) was positively associated with the newborn's birth weight (P = 0·01), head, arm and wrist circumferences and sum of skinfolds (P n-3 fatty acids per d before pregnancy by other PUFA was related to an average decrease in birth weight of 60 g (P = 0·01). Relationships withn-3 fatty acid intake at the end of pregnancy were weaker and not significant. We concluded that a high pre-pregnancyn-3 fatty acid:PUFA ratio may sustain fetal growth in overweight women. Follow-up of the children may help determine whether this has beneficial consequences for the child's health and development.

International audience; This study aimed to determine whether personality disorders were associated with later Major Depressive Disorder (MDD) or Generalised Anxiety Disorder (GAD) in breast cancer patients. This longitudinal and multicentric study included 120 French non-metastatic breast cancer patients. After cancer diagnosis (T1) and 7 months after diagnosis (T3), we assessed MDD and GAD (Mini International Neuropsychiatric Interview 5.0). We assessed personality disorders 3 months after diagnosis (VKP). We used multiple logistic regression analysis to determine what were the factors associated with GAD and MDD at T3. At T3, prevalence rate was 10.8% for MDD and 19.2% for GAD. GAD at T3 was significantly and independently associated with GAD at T1 and with existence of a personality disorder, no matter the cluster type. MDD at T3 was significantly and independently associated with MDD at T1 and with the existence of a cluster C personality disorder. Initial cancer severity and the type of treatment used were not associated with GAD or MDD at T3. Breast cancer patients with personality disorders are at higher risk for GAD and MDD at the end of treatment. Patients with GAD should be screened for personality disorders. Specific interventions for patients with personality disorders could prevent psychiatric disorders.

Our aim was to identify risk factors for lower quality of life (QOL) in non-metastatic breast cancer patients.Our study included 120 patients from the University Hospital Centers of Tours and Poitiers. This cross-sectional study was conducted 7 months after patients' breast cancer diagnosis and assessed QOL (Quality of Life Questionnaire Core 30 = QLQ-C30), socio-demographic characteristics, coping strategies (Brief-COPE), physiological and biological variables (e.g., initial tumor severity and types of treatment received), the existence of major depressive disorder (Mini International Neuropsychiatric Interview), and pain severity (Questionnaire de Douleur Saint Antoine). We assessed personality disorders 3 months after diagnosis (Vragenlijst voor Kenmerken van de Persoonlijkheid questionnaire). We used multiple linear regression models to determine which factors were associated with physical, emotional, and global QOL.Lower physical QOL was associated with major depressive disorder, younger age, a more severe initial tumor stage, and the use of the behavioral disengagement coping. Lower emotional QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self-blame, and lower use of acceptance coping strategies. Lower global QOL was associated with major depressive disorder, the existence of a personality disorder, a more severe pain level, higher use of self-blame, lower use of positive reframing coping strategies, and an absence of hormone therapy.Lower QOL scores were more strongly associated with variables related to the individual's premorbid psychological characteristics and the manner in which this individual copes with the cancer (e.g., depression, personality, and coping) than to cancer-related variables (e.g., treatment types and cancer severity). Copyright © 2015 John WileySons, Ltd.

This study assessed the prevalence of personality disorders (PDs), according to DSM-IV criteria, in relation to depressive symptomatology at three different periods of life in female subjects. Depressive symptoms and personality disorders were assessed in a sample of 568 women from three different transitional stages: 134 students, 314 primiparous women after childbirth and 120 women diagnosed with breast cancer. Depressive symptoms were assessed by the Hospital Depression and Anxiety Scale in the first and third groups and by the Edinburgh Post-natal Depression Scale in the second group, whereas PDs were assessed by the French version of the Vragenlijst voor Kenmerken van de Persoonlijkheid. Depressive symptomatology and rates of PD (20.4% and 6.3%) were equivalent in the three groups. The prevalence of PD was higher in the depressed group compared with the non-depressed group, with more paranoid, borderline, avoidant, obsessive-compulsive, schizotypal, antisocial, dependent and histrionic PD. Our findings support the hypothesis that PDs are more frequently associated with depressive symptoms. Borderline and avoidant PDs were more prevalent among young women. All cluster C PD (dependent, avoidant and obsessive-compulsive) co-occurred significantly with depressive symptoms.

Learning Objectives After completing this course, the reader will be able to: Evaluate the therapeutic impact of hysterectomy after chemoradiation therapy in locally advanced cervical cancer.Evaluate the rate of histologic residual disease in patients with complete clinical and radiologic response after chemoradiation therapy. This article is available for continuing medical education credit at CME.TheOncologist.com Background. Concomitant chemoradiation (CRT) (including brachytherapy) is considered the standard management for stage IB2 or II cervical cancer in many countries. Nevertheless, some of them discuss completion surgery (hysterectomy [HT]) after CRT. The aim of this study was to investigate the therapeutic impact of such surgery. Methods. A randomized trial was opened in France in 2003 to evaluate the interest in HT after CRT. Inclusion criteria were: (a) stage IB2 or II cervical cancer without extrapelvic disease on conventional imaging; (b) pelvic external radiation therapy (45 Gy with or without parametrial or nodal boost) with concomitant cisplatin chemotherapy (40 mg/m2 per week) followed by uterovaginal brachytherapy (15 Gy to the intermediate risk clinical target volume); and (c) complete clinical and radiological response 6–8 weeks after brachytherapy. Patients were randomized between HT (arm A) and no HT (arm B). Unfortunately this trial was closed because of poor accrual: 61 patients were enrolled (in 2003–2006) and are reported on here. Results. Thirty one and 30 patients were enrolled, respectively, in arm A and arm B. Twelve patients recurred (five of them died): respectively, eight and four in arm A and arm B. The 3-year event-free survival rates were 72% (standard error [SE], 9%) and 89% (SE, 6%) (not significant [NS]) in arm A and arm B, respectively. The 3-year overall survival rates were 86% (SE, 6%) and 97% (SE, 3%) (NS) in arm A and arm B, respectively. Conclusions. Results of the current trial seem to suggest that completion HT had no therapeutic impact in patients with clinical and radiological complete response after CRT (but this conclusion is limited by the lack of power).

International audience; We describe the administration of antenatal corticosteroid therapy (ACT) for liveborn very preterm neonates in a population-based study. A total of 790 very preterm neonates (between 24 and 31 full weeks of gestation) were included in this regionally defined population of very preterm neonates in France. The main outcome measure was non-access to ACT. Data were analysed using logistic and polytomous models to control for neonatal and sociodemographic characteristics, mechanisms of very preterm birth and neonatal network organisation. As compared with level III, births in levels I-II maternity units were closely related to non-access to ACT (60.1% vs. 8.8%), but not to pregnancy follow-up (19.7% vs. 17.8%). Only 6.3% of very preterm neonates that benefited from antepartum referral did nor receive ACT. Births associated with rupture of membranes and gestational hypertension were significantly more often transferred to level-III units (73.8% and 68.3% respectively) than those due to maternal bleeding and spontaneous labour (57.0% and 50.7% respectively), and the neonates had a lower probability of not receiving ACT (8.5%, 11.5%, 23.0%, 31.2% respectively). Very preterm neonates referred in utero to a level-III unit came from a more favourable socio-economic environment. Non-access to ACT was more often observed in neonates born to 14- to 24-year-old mothers, smokers, of low socio-economic status, and preterm birth resulting from maternal bleeding or spontaneous labour. These data from a French regional study show that access to ACT is not only explained by practitioners' support of recommendations. In our population-based study, ACT access was related to socio-economic factors and to the mechanisms of very preterm birth. Improving the rate of access to ACT should take these organisational, medical and socio-economic dimensions into account.

International audience; Summary Drouillet P, Kaminski M, De Lauzon-Guillain B, Forhan A, Ducimeti? P, Schweitzer M, Magnin G, Goua V, Thi?ugeorges O, Charles M-A. Association between maternal seafood consumption before pregnancy and fetal growth: evidence for an association in overweight women. The EDEN mother-child cohort. Paediatric and Perinatal Epidemiology 2009; 23: 76-86.Studies in countries with high seafood consumption have shown a benefit on fetal growth and child development. The objective of our study was to determine the association between seafood consumption in French pregnant women and fetal growth. Pregnant women included in the EDEN mother-child cohort study completed two food frequency questionnaires on their usual diet in the year before and during the last 3 months of pregnancy (n = 1805). Fetal circumferences were measured by ultrasound and anthropometry at birth. Variables were compared across tertiles of the mother's seafood consumption using multiple linear regression to adjust for confounding variables. Analyses were stratified by maternal overweight status because of an interaction between maternal seafood consumption and her body mass index (P < 0.01). There was no association between seafood intake and fetal growth in the whole sample of women. For overweight women (n = 464), higher consumption of seafood before pregnancy was associated with higher fetal biparietal and abdominal circumferences and anthropometric measures. From the lowest to the highest tertiles, mean birthweight was 167 g higher (P = 0.002). No significant association was found with consumption at the end of pregnancy. In conclusion, high seafood consumption before pregnancy is positively associated with fetal growth in overweight women.

The incidence of acute salpingitis which are only one aspect of pelvic inflammatory disease has decreased during the last 20 years and more and more patients have mild symptoms. Consequences of this evolution are uncertainty for the diagnosis without laparoscopic proof of the pelvic inflammatory disease, ambulatory treatment with inappropriate regimen increasing the risk of chronical disease and long term sequelae. So laparoscopy must remain a standard in diagnosis and treatment especially in young childless women. Follow up of the medical treatment is necessary to assess its effectiveness and its compliance, to treat the sexual partner, and to provide informations about preventive measures to avoid relaps.

While chemoselectivities in Pd0‐catalyzed coupling reactions are frequently non‐intuitive and a result of a complex interplay of ligand/catalyst, substrate, and reaction conditions, we herein report a general method based on PdI that allows for an a priori predictable chemoselective Csp2 −Csp2 coupling at C−Br in preference to C−OTf and C−Cl bonds, regardless of the electronic or steric bias of the substrate. The C−C bond formations are extremely rapid (

Since 2014, the interest in aryl fluorosulfates (ArOSO2F) as well as their implementation in powerful applications has continuously grown. In this context, the enabling capability of ArOSO2F will strongly depend on the substitution pattern of the arene, which ultimately dictates its overall function as drug candidate, material, or bio‐linker. This report showcases the modular, substrate‐independent, and fully predictable, selective functionalization of polysubstituted arenes bearing C−OSO2F, C−Br, and C−Cl sites, which makes it possible to diversify the arene in the presence of OSO2F or utilize OSO2F as a triflate surrogate. Sequential and triply selective arylations and alkylations were realized within minutes at room temperature, using a single and air‐stable PdI dimer., Diversity: The rapid, modular, substrate‐independent and fully predictable functionalization of polysubstituted arenes bearing C−OSO2F, C−Br, and C−Cl sites at room temperature is showcased. In this way the arene unit can be functionalized in the presence of a fluorosulfate group or the latter can serve as a triflate surrogate.