Site-Selective, Modular Diversification of Polyhalogenated Aryl Fluorosulfates (ArOSO2 F) Enabled by an Air-Stable PdI Dimer.

Since 2014, the interest in aryl fluorosulfates (ArOSO2 F) as well as their implementation in powerful applications has continuously grown. In this context, the enabling capability of ArOSO2 F 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-OSO2 F, C-Br, and C-Cl sites, which makes it possible to diversify the arene in the presence of OSO2 F or utilize OSO2 F 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.

Selective ortho-Functionalization of Adamantylarenes Enabled by Dispersion and an Air-Stable Palladium(I) Dimer.

Contrary to the general belief that Pd-catalyzed cross-coupling at sites of severe steric hindrance are disfavored, we herein show that the oxidative addition to C-Br ortho to an adamantyl group is as favored as the corresponding adamantyl-free system due to attractive dispersion forces. This enabled the development of a fully selective arylation and alkylation of C-Br ortho to an adamantyl group, even if challenged with competing non-hindered C-OTf or C-Cl sites. The method makes use of an air-stable PdI dimer and enables straightforward access to diversely substituted therapeutically important adamantylarenes in 5-30 min.

A General and Air-tolerant Strategy to Conjugated Polymers within Seconds under Palladium(I) Dimer Catalysis.

While current M0 /MII based polymerization strategies largely focus on fine-tuning the catalyst, reagents and conditions for each and every monomer, this report discloses a single method that allows access to a variety of different conjugated polymers within seconds at room temperature. Key to this privileged reactivity is an air- and moisture stable dinuclear PdI catalyst. The method is operationally simple, robust and tolerant to air.

Rapid Room-Temperature, Chemoselective Csp2 -Csp2 Coupling of Poly(pseudo)halogenated Arenes Enabled by Palladium(I) Catalysis in Air.

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 (<5 min at RT) and are catalyzed by an air- and moisture-stable PdI dimer under open-flask conditions.

Palladium(I) Dimer Enabled Extremely Rapid and Chemoselective Alkylation of Aryl Bromides over Triflates and Chlorides in Air.

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 (<5 min reaction time) at room temperature and under open-flask reaction conditions.

Major depressive disorder, personality disorders, and coping strategies are independent risk factors for lower quality of life in non-metastatic breast cancer patients.

OBJECTIVE: Our aim was to identify risk factors for lower quality of life (QOL) in non-metastatic breast cancer patients. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 Wiley & Sons, Ltd.

Results of the GYNECO 02 study, an FNCLCC phase III trial comparing hysterectomy with no hysterectomy in patients with a (clinical and radiological) complete response after chemoradiation therapy for stage IB2 or II cervical cancer.

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).

Prenatal mercury contamination: relationship with maternal seafood consumption during pregnancy and fetal growth in the 'EDEN mother-child' cohort.

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 < 0.0001). There was no association between Hg level and fetal growth in the whole sample of women, except for an early negative relationship with biparietal diameter. A positive association was found between seafood intake and fetal growth in overweight women only which remained unchanged after adjustment for Hg level (birth weight: +101 g for a difference of 1 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.

Very preterm birth: who has access to antenatal corticosteroid therapy?

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.

Maternal fatty acid intake and fetal growth: evidence for an association in overweight women. The 'EDEN mother-child' cohort (study of pre- and early postnatal determinants of the child's development and health).

Recent studies suggest a benefit of seafood and n-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 (n 1439). 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 (n 366), a high pre-pregnancy n-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<0.04). A substitution of 1% of 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 with n-3 fatty acid intake at the end of pregnancy were weaker and not significant. We concluded that a high pre-pregnancy n-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.

Association between maternal seafood consumption before pregnancy and fetal growth: evidence for an association in overweight women. The EDEN mother-child cohort.

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.

Personality disorders, but not cancer severity or treatment type, are risk factors for later generalised anxiety disorder and major depressive disorder in non metastatic breast cancer patients.

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.

[Acute salpingitis]. / Salpingites aiguës.

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.

Comorbidity between personality disorders and depressive symptomatology in women: A cross-sectional study of three different transitional life stages.

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.

Depression and anxiety in women during pregnancy and neonatal outcome: data from the EDEN mother-child cohort.

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.

Maternal blood lead levels and the risk of pregnancy-induced hypertension: the EDEN cohort study.

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 microg/dL) than in normotensive patients (1.9 +/- 1.2 microg/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.

Maternal personal exposure to airborne benzene and intrauterine growth.

BACKGROUND: Studies relying on outdoor pollutants measures have reported associations between air pollutants and birth weight. OBJECTIVE: Our aim was to assess the relation between maternal personal exposure to airborne benzene during pregnancy and fetal growth. METHODS: We recruited pregnant women in two French maternity hospitals in 2005-2006 as part of the EDEN mother-child cohort. A subsample of 271 nonsmoking women carried a diffusive air sampler for a week during the 27th gestational week, allowing assessment of benzene exposure. We estimated head circumference of the offspring by ultrasound measurements during the second and third trimesters of pregnancy and at birth. RESULTS: Median benzene exposure was 1.8 microg/m(3) (5th, 95th percentiles, 0.5, 7.5 microg/m(3)). Log-transformed benzene exposure was associated with a gestational age-adjusted decrease of 68 g in mean birth weight [95% confidence interval (CI), -135 to -1 g] and of 1.9 mm in mean head circumference at birth (95% CI, -3.8 to 0.0 mm). It was associated with an adjusted decrease of 1.9 mm in head circumference assessed during the third trimester (95% CI, -4.0 to 0.3 mm) and of 1.5 mm in head circumference assessed at the end of the second trimester of pregnancy (95% CI, -3.1 to 0 mm). CONCLUSIONS: Our prospective study among pregnant women is one of the first to rely on personal monitoring of exposure; a limitation is that exposure was assessed during 1 week only. Maternal benzene exposure was associated with decreases in birth weight and head circumference during pregnancy and at birth. This association could be attributable to benzene and a mixture of associated traffic-related air pollutants.