How do late terminations of pregnancy affect comparisons of stillbirth rates in Europe? Analyses of aggregated routine data from the Euro-Peristat Project.

OBJECTIVE: To describe how terminations of pregnancy at gestational ages at or above the limit for stillbirth registration are recorded in routine statistics and to assess their impact on comparability of stillbirth rates in Europe. DESIGN: Analysis of aggregated data from the Euro-Peristat project. SETTING: Twenty-nine European countries. POPULATION: Births and late terminations in 2010. METHODS: Assessment of terminations as a proportion of stillbirths and derivation of stillbirth rates including and excluding terminations. MAIN OUTCOME MEASURES: Stillbirth rates overall and excluding terminations. RESULTS: In 23 countries, it is possible to assess the contribution of terminations to stillbirth rates either because terminations are rare occurrences or because they can be distinguished from spontaneous stillbirths. Where terminations were reported, they accounted for less than 1.5% of stillbirths at 22+ weeks in Denmark, between 13 and 22% in Germany, Italy, Hungary, Finland and Switzerland, and 39% in France. Proportions were much lower at 24+ weeks, with the exception of Switzerland (7.4%) and France (39.2%). CONCLUSIONS: Terminations represent a substantial proportion of stillbirths at 22+ weeks of gestation in some countries. Countries where terminations occur at 22+ weeks should publish rates with and without terminations in order to improve international comparisons and the policy relevance of stillbirth statistics. TWEETABLE ABSTRACT: For valid comparisons of stillbirth rates, data about late terminations of pregnancy are needed.

Risk factors of preterm birth in France in 2010 and changes since 1995: Results from the French National Perinatal Surveys.

OBJECTIVES: To investigate risk factors of total, spontaneous and induced preterm birth in 2010 and differences between 1995 and 2010. MATERIAL AND METHODS: The national perinatal surveys are based on a representative sample of births in France. We selected live-born singletons (n=14,326 in 2010 and 12,885 in 1995) and used multiple regression analyses to calculate adjusted odds ratios (aOR) for maternal sociodemographic characteristics, obstetric history, prenatal care and smoking. RESULTS: The main risk factors in 2010 were parity 1 compared to parity 2 (aOR=1.9 [95% CI 1.5-1.3]), previous preterm delivery (aOR=6.6 [5.0-8.7]), pre-pregnancy body mass index<18.5 compared to 18.5-24.9kg/m2 (aOR=1.7 [1.4-2.2]), level of education completed: high school or less, inadequate prenatal care and cannabis use. Most risk factors of spontaneous and induced preterm births were similar. Compared to 1995, maternal age≥35 years and previous induced abortion were no longer associated with preterm birth in 2010. CONCLUSION: Identified risk factors for preterm birth in France in 2010 agree with the literature. Increases in baseline rates for maternal age and medically induced abortions may explain changes in certain preterm birth risk factors.

[Episiotomy in France in 2010: Variations according to obstetrical context and place of birth]. / L'épisiotomie en France en 2010 : variations des pratiques selon le contexte obstétrical et le lieu d'accouchement.

OBJECTIVES: To analyze episiotomy rates according to the characteristics of women and maternity units and to study the variability of rates between units and regions. MATERIALS AND METHODS: Our study included all vaginal deliveries in the National Perinatal Survey 2010 (n=11,322). We estimated the adjusted relative risk of episiotomy (aRR) according to women and maternity units characteristics, and we studied the variance between regions and hospitals using multilevel Poisson regressions, stratified on parity. RESULTS: In 2010, 44.7% of primiparous; 14.2% in multiparous had an episiotomy. The main associated factors were Asian origin (primiparae: aRR=1.32 [1.16-1.51]; multiparae: aRR=2.30 [1.67-3.16]), breech presentation (primiparae: aRR=2.14 [1.87-2.21]; multiparae: aRR=3.32 [2.52-4.38]) and operative vaginal delivery (primiparae: aRR=2.04 [1.89-2.11]; multiparae: aRR=3.19 [2.74-3.72]). Rates varied dramatically between regions (primiparae: 17 to 64%; multiparae: 3 to 21%). The variance was significant between regions and between maternity units after controlling for women and units characteristics. CONCLUSION: It would be useful to study the attitudes and views of obstetricians and midwives about the protection of the perineum to better understand these differences in practice.

[Customized and non-customized French intrauterine growth curves. I - Methodology]. / Courbes de croissance in utero ajustées et non ajustées adaptées à la population française. I - Méthodes de construction.

OBJECTIVES: We developed intrauterine growth references, called EPOPé curves, in line with recommendations for screening of intra-uterine growth restriction issued in 2013 by the French College of Obstetricians and Gynecologists. POPULATION AND METHODS: Using the French Perinatal Survey (FPS) 2010, we adapted the methodology developed by Gardosi (1) to model intrauterine growth and its distribution and (2) to adjust for physiological fetal and maternal factors influencing fetal weight. Based on this model, 3 reference curves (unadjusted, adjusted for fetal sex, and adjusted for fetal sex, and maternal height, weight and parity) were proposed. We applied these models to births in the 2010 FPS and the French hospital discharge database (PMSI) in 2011-2012. RESULTS: Among singleton live births in the FPS and the PMSI, the model adjusted for fetal sex identified 3.2 and 3.3% of births below the 3rd centile respectively, and 10.0 and 10.2% below the 10th. In model adjusted for maternal factors, 4.0% of births from the FPS 2010 were reclassified, but population rates remained at 3.0 and 10.0%. CONCLUSION: This growth model is appropriate for French births, and allows for the implementation of a homogeneous definition of small for gestational age infants during pregnancy and at birth.

[Customized and non-customized French intrauterine growth curves. II - Comparison with existing curves and benefits of customization]. / Courbes de croissance in utero ajustées et non ajustées adaptées à la population française. II - Comparaison à des courbes existantes et apport de l'ajustement.

OBJECTIVES: Our aim is to compare the new French EPOPé intrauterine growth curves, developed to address the guidelines 2013 of the French College of Obstetricians and Gynecologists, with reference curves currently used in France, and to evaluate the consequences of their adjustment for fetal sex and maternal characteristics. POPULATION AND METHODS: Eight intrauterine and birthweight curves, used in France were compared to the EPOPé curves using data from the French Perinatal Survey 2010. The influence of adjustment on the rate of SGA births and the characteristics of these births was analysed. RESULTS: Due to their birthweight values and distribution, the selected intrauterine curves are less suitable for births in France than the new curves. Birthweight curves led to low rates of SGA births from 4.3 to 8.5% compared to 10.0% with the EPOPé curves. The adjustment for maternal and fetal characteristics avoids the over-representation of girls among SGA births, and reclassifies 4% of births. Among births reclassified as SGA, the frequency of medical and obstetrical risk factors for growth restriction, smoking (≥10 cigarettes/day), and neonatal transfer is higher than among non-SGA births (P<0.01). CONCLUSION: The EPOPé curves are more suitable for French births than currently used curves, and their adjustment improves the identification of mothers and babies at risk of growth restriction and poor perinatal outcomes.

A global reference for caesarean section rates (C-Model): a multicountry cross-sectional study.

OBJECTIVE: To generate a global reference for caesarean section (CS) rates at health facilities. DESIGN: Cross-sectional study. SETTING: Health facilities from 43 countries. POPULATION/SAMPLE: Thirty eight thousand three hundred and twenty-four women giving birth from 22 countries for model building and 10,045,875 women giving birth from 43 countries for model testing. METHODS: We hypothesised that mathematical models could determine the relationship between clinical-obstetric characteristics and CS. These models generated probabilities of CS that could be compared with the observed CS rates. We devised a three-step approach to generate the global benchmark of CS rates at health facilities: creation of a multi-country reference population, building mathematical models, and testing these models. MAIN OUTCOME MEASURES: Area under the ROC curves, diagnostic odds ratio, expected CS rate, observed CS rate. RESULTS: According to the different versions of the model, areas under the ROC curves suggested a good discriminatory capacity of C-Model, with summary estimates ranging from 0.832 to 0.844. The C-Model was able to generate expected CS rates adjusted for the case-mix of the obstetric population. We have also prepared an e-calculator to facilitate use of C-Model (www.who.int/reproductivehealth/publications/maternal_perinatal_health/c-model/en/). CONCLUSIONS: This article describes the development of a global reference for CS rates. Based on maternal characteristics, this tool was able to generate an individualised expected CS rate for health facilities or groups of health facilities. With C-Model, obstetric teams, health system managers, health facilities, health insurance companies, and governments can produce a customised reference CS rate for assessing use (and overuse) of CS. TWEETABLE ABSTRACT: The C-Model provides a customized benchmark for caesarean section rates in health facilities and systems.

[Robson classification: A tool for assessment of caesarean practices in France]. / Classification de Robson : un outil d'évaluation des pratiques de césarienne en France.

OBJECTIVE: To give a description of caesarean rates in France in 2010 using Robson classification, to assess practices according to the level of care of the maternity units. MATERIALS AND METHODS: The study population was the sample of the French National Perinatal Survey in 2010 (n=14,165). Data were stratified by the level of care of the maternity unit (1, 2 or 3). Women were classified in 12 groups according to Robson classification, using maternal characteristics and obstetrical history. In each level of care, we calculated for each group, its relative size, its crude caesarean rate and its contribution to the overall caesarean rate. RESULTS: The overall rate of caesarean in 2010 in France was 20.8% in level 1, 21.1% in level 2 and 20.0% in level 3 maternity units. In the three levels, the main contributors to the overall caesarean rate were primiparous women in spontaneous labour (group 1; contribution: 3.5% in level 1 units, 2.2% in level 2 units, 2.7% in level 3 units) or with induced labour (group 2a; contribution: 2.9, 2.5 and 3.0%, respectively) and multiparous women with previous caesarean (group 5; contribution: 5.8, 5.3 and 6.0%, respectively). Premature singletons (group 10) contributed to 0.8% to the overall caesarean rate in level 1 units, 1.4% in level 2 units and 3.5% in level 3 units. CONCLUSION: The Robson classification is easy to use. Each maternity unit can compare its rates with those of units with similar level, to find whether some groups of women have very high rates of caesarean sections.

Prevalence and characteristics of women reporting poor mental health during pregnancy: Findings from the 2010 French National Perinatal Survey.

BACKGROUND: Self-rated mental health is a useful indicator to examine the positive dimension of mental health and psychological well-being. The primary objective of this study was to estimate the prevalence of poor self-rated mental health during pregnancy in a nationally representative population in France. The second objective was to assess the sociodemographic and medical characteristics associated with this condition and with a health professional's consultation for psychological problems. METHODS: The study was based on the 2010 French National Perinatal Survey, which included all singleton live births in French maternity units during a 1-week period (n=14,326 women). Self-rated mental health was assessed using the following single-item question: "During your pregnancy, how did you feel from a psychological point of view: good - fairly good - rather poor - poor?" Women were also asked if they had visited a healthcare professional for psychological problems. They were interviewed between delivery and discharge to collect information on mental health, sociodemographic and medical characteristics, the context of their pregnancy, and their prenatal care. RESULTS: Of the women interviewed, 8.9% [95% CI, 8.5-9.5%] reported poor self-rated mental health during pregnancy. Among them, 18.7% consulted a healthcare professional for psychological problems. Sociodemographic characteristics indicative of social disadvantage were associated with a higher-risk of poor self-rated mental health, and a social gradient was observed. However, more favorable social characteristics were associated with consultation with a healthcare professional for these psychological difficulties. The reaction to the discovery of pregnancy and prenatal care differed significantly depending on self-rated mental health. Women with poor mental health had more complicated pregnancies. CONCLUSION: This study showed strong associations between many socially disadvantaged characteristics and a positive dimension of mental health. The findings suggest that well-being measures such as self-rated mental health should be routinely assessed during pregnancy so that women can be offered more appropriate support.

Stabilising the caesarean rate: which target population?

OBJECTIVE: Caesarean rate increased in France between 1995 and 2003, but remained stable between 2003 and 2010. Our objective was to analyse these trends by identifying the groups of women who contributed to the increase and those who contributed to the stabilisation. DESIGN: Cross-sectional population-based study from the French national perinatal surveys. SETTING: All maternity units in France. POPULATION: Representative samples of women delivering in 1995 (n = 13 147), 2003 (n = 14 482), and 2010 (n = 14 681). METHODS: Robson classification, based on pregnancy and delivery characteristics, was used for each group. MAIN OUTCOME MEASURES: Caesarean rate for each group, its contribution to the overall caesarean rate, and the differences (Δ) in these contributions between 1995 and 2003 and between 2003 and 2010. RESULTS: Overall caesarean rates were 15.4% in 1995, 19.7% in 2003 and 20.5% in 2010. Between 1995 and 2003, the contribution to the overall caesarean rate of all groups but one rose. Between 2003 and 2010, the contribution of all groups but three stabilised or decreased: nulliparous women in spontaneous labour with singleton cephalic fetuses at term (Δ = + 0.5%, 95% CI 0.1-0.9%), an increase explained by their higher caesarean rate; nulliparous women with induced labour at term (Δ = + 1.1%, 95% CI 0.8-1.4%) caused by an increase in both the caesarean rate and the relative size of this group; and women with previous caesarean (Δ = + 0.8%, 95% CI 0.3-1.3%), because of the growing size of this group. CONCLUSION: Proposing and evaluating interventions for improving the management of labour in nulliparous women could help to maintain caesarean rates and mitigate increases among multiparous women in the future.

[Medical care and perinatal health in twin pregnancies: situation in 2010 and recent trends in France]. / Prise en charge et santé périnatale en cas de grossesse gémellaire : situation en 2010 et évolution récente en France.

OBJECTIVE: To compare medical care and health status of twins and singletons in 2010 and to describe the trends between 1995 and 2010 in metropolitan France. POPULATIONS AND METHODS: Data were derived from the national perinatal surveys from 1995 to 2010, on representative samples of births, and included 14,460 singletons and 440 twins in 2010. We compared prenatal care, childbirth and health status of children between twin and singleton pregnancies and between years. RESULTS: In 2010, mothers of twins had more intensive medical care than mothers of singletons. The preterm birth rate was higher (42.7% versus 6.3%). The medical care of twins has increased (for example 51% of women had 11 or more prenatal visits in 2010 versus 26% in 1995), often following the same trends as singletons. The proportion of non-spontaneous labors increased between 1998 and 2003. The cesarean section rate increased from 42.2% in 1995 to 54.8% in 2010 among twins, and from 15.2% to 19.9% among singletons. The preterm birth did not increase, but the proportion of twins born at 39 weeks of gestation or more declined significantly. CONCLUSION: Medical care takes into account the high risks of twin pregnancies. Twins are still a medical cause for concern because of their continued increase.

Cannabis use during pregnancy in France in 2010.

OBJECTIVE: The aim was to estimate the proportion of women who reported cannabis use during pregnancy, to analyse the demographic and social characteristics of users, and the link between cannabis use and either preterm or small-for-gestational-age birth. DESIGN: Data were obtained from interviews of a representative sample of women giving birth in France in 2010 in the days after delivery, and from their medical records. SETTING: All maternity units in France. SAMPLE: The analysis includes women with live singleton births in metropolitan France who responded to the question about cannabis use during pregnancy: in total, 13 545 women. METHODS: The percentage of cannabis users during pregnancy was estimated, and variations according to social characteristics were described. Logistic regression analyses were used to investigate any associations between cannabis use and preterm birth or small-for-gestational-age status. MAIN OUTCOME MEASURES: Percentage of cannabis use, preterm birth rate, and small-for-gestational-age rate. RESULTS: In all, 1.2% of women reported having used cannabis during pregnancy. This percentage was higher among younger women, women living alone, or women who had a low level of education or low income. It was also associated with tobacco use and drinking alcohol. Cannabis users had higher rates of spontaneous preterm births: 6.4 versus 2.8%, for an adjusted odds ratio (aOR) of 2.15 (95% CI 1.10-4.18). The corresponding aOR was 2.64 (95% CI 1.12-6.22) among tobacco smokers and 1.22 (95% CI 0.29-5.06) among non-tobacco smokers. CONCLUSIONS: Although the reported rate of cannabis use during pregnancy in France is low, efforts should be continued to inform women and healthcare providers about the potential consequences of its use.

[Quality of perinatal statistics from hospital discharge data: comparison with civil registration and the 2010 National Perinatal Survey]. / Qualité des données périnatales issues du PMSI: comparaison avec l'état civil et l'enquête nationale périnatale 2010.

OBJECTIVE: To compare hospital discharge data (PMSI) with data in the reference databases: vital statistics and National Perinatal Surveys (NPS) for the principal perinatal indicators. METHODS: Data concerning hospitalizations for delivery and childbirth were extracted from the PMSI 2010 database. The exhaustiveness was assessed by comparing discharge data with data from birth certificates. Indicators were compared with those in the 2010 NPS, which was based on a representative sample of births (n=15,000), using 95% confidence intervals. RESULTS: About 823,360 hospital abstracts with delivery and 829,351 hospital abstracts with live births were considered. The exhaustiveness of the PMSI was 99.6% for live births in Metropolitan France. The distribution of maternal age, mode of delivery, birth weight and gestational age in the PMSI and NPS were very similar. In Metropolitan France, the prematurity rate was 6.9% (PMSI) vs. 6.6% [6.2-7.0] (NPS) and the rate of caesarean was 20.6% vs. 20.4% [19.8-21.1]. There were marked differences for the percentage of birth weights<2500g and for maternal diseases. CONCLUSION: The routine use of the PMSI for some indicators for follow-up purposes is foreseeable. Validation studies are still necessary for maternal diseases, for which recording is less standardized.

Maternal and health care determinants of preconceptional use of folic acid supplementation in France: results from the 2010 National Perinatal Survey.

OBJECTIVES: To estimate the national prevalence and analyse the factors associated with preconceptional folic acid supplementation, including maternal sociodemographic characteristics, region of residence, birth control use and chronic diseases requiring medical care before conception. DESIGN: Cross-sectional population-based study. SETTING: All maternity units in France. POPULATION: A nationally representative sample of women giving birth in 2010 (n = 12,646). METHODS: Data came from mothers' interviews 2-3 days after delivery. Statistical analyses included multivariable logistic regressions. MAIN OUTCOME MEASURE: Folic acid supplementation starting at least 1 month before conception. RESULTS: 14.8% (95% confidence interval [95% CI] 14.2-15.4) of women used folic acid before pregnancy; this percentage varied from 10.4% to 18.7% across regions. Supplementation was more frequent in primiparae, French citizens, women with higher educational levels and those needing medical monitoring or treatment before conception. Women who stopped contraception to become pregnant (75% of our population) used folic acid more often (intrauterine device or implant: 19%, pill: 17%, other methods which did not need medical monitoring: 17%) than other women (7%). The adjusted odds ratios were 3.3 (95% CI 2.6-4.3) for intrauterine device and implant, 2.2 (95% CI 1.8-2.6) for pill and 1.9 (95% CI 1.5-2.4) for other methods, compared with women who did not use birth control. CONCLUSION: The absence of preconceptional folic acid supplementation for most women, even those needing consultations with healthcare professionals before pregnancy, shows that campaigns to promote folic acid supplementation should address not only women but also healthcare professionals involved in birth control and obstetric care before pregnancy.

[Medical care organization in analgesia, anaesthesia and intensive care in maternity units: results from the National Perinatal Surveys in 2003 and 2010]. / Organisation des soins en analgésie, anesthésie et réanimation en maternité en France métropolitaine: résultats comparés des enquêtes nationales périnatales 2003 et 2010.

OBJECTIVE: The equipment and practices in obstetric analgesia, anaesthesia and intensive care, as well as their evolution between 2003 and 2010 in metropolitan France, were described. POPULATION AND METHODS: Data were derived from two representative samples of births in 2003 and 2010, based on all births in France during one week. The sample included 534 maternity units and 14,903 births in 2010 and 618 maternity units and 14,737 births in 2003. RESULTS: The caesarean operating room was adjacent or inside the labour ward in 66% of maternity units in 2010 vs 56% in 2003. An anaesthetist was appointed permanently to the labour ward in 38.9% of maternity units in 2010 vs 21.5% in 2003. Locoregional analgesia or anaesthesia rate increased significantly: 81.5% in 2010 compared to 74.9% in 2003. Almost all operative vaginal deliveries were performed under epidural anesthesia in 2010. Patient controlled epidural analgesia (PCEA) was available in 58% of the units in 2010 but only 34.2% of women had PCEA. Newborn's resuscitations were performed mainly by paediatricians in 2010, but 11.4% of children were resuscitated by an anaesthetist in level 1 maternity units. CONCLUSION: The conditions required to ensure anaesthetic care safety in maternity units has improved since 2003. Improvements in quality of care are still possible.

High circulating levels of 7beta- and 7alpha-hydroxycholesterol and presence of apoptotic and oxidative markers in arterial lesions of normocholesterolemic atherosclerotic patients undergoing endarterectomy.

In previous investigations, we found that 7beta-hydroxycholesterol had potent pro-apoptotic, and pro-oxidative properties. So, we asked whether the circulating level of this oxysterol was enhanced in atherosclerotic patients undergoing endarterectomy of the superficial femoral artery. To this end, 7beta-hydroxycholesterol serum concentrations were determined and compared with common lipid parameters in atherosclerotic patients, and in healthy subjects. 7alpha-hydroxycholesterol was simultaneously measured to evaluate the reliability of the method used for oxysterol analysis. On normal and atherosclerotic arterial fragments from patients, markers of oxidation (4-hydroxynonenal (4-HNE) adducts), and apoptosis (activated caspase-3; condensed/fragmented nuclei) were studied. Interestingly, high serum concentrations of 7beta- and 7alpha-hydroxycholesterol were found in normocholesterolemic atherosclerotic patients. However, in statin-treated patients, the circulating levels of 7beta- and 7alpha-hydroxycholesterol tend towards normal values. Therefore, 7beta- as well as 7alpha-hydroxycholesterol could be more appropriate markers of lipid metabolism disorders than cholesterol or LDL in normocholesterolemic patients with atherosclerosis of the lower limbs, and statins could normalize their serum concentrations. At the arterial level, apoptotic cells were mainly identified in low grade lesions and no statin effects were found on oxidation and apoptosis.

Comparison of the cytotoxic, pro-oxidant and pro-inflammatory characteristics of different oxysterols.

Oxidized low-density lipoproteins play important roles in the development of atherosclerosis and contain several lipid-derived, bioactive molecules which are believed to contribute to atherogenesis. Of these, some cholesterol oxidation products, referred to as oxysterols, are suspected to favor the formation of atherosclerotic plaques involving cytotoxic, pro-oxidant and pro-inflammatory processes. Ten commonly occurring oxysterols (7alpha-, 7beta-hydroxycholesterol, 7-ketocholesterol, 19-hydroxycholesterol, cholesterol-5alpha,6alpha-epoxide, cholesterol-5beta,6beta-epoxide, 22R-, 22S-, 25-, and 27-hydroxycholesterol) were studied for both their cytotoxicity and their ability to induce superoxide anion production (O2*-) and IL-8 secretion in U937 human promonocytic leukemia cells. Cytotoxic effects (phosphatidylserine externalization, loss of mitochondrial potential, increased permeability to propidium iodide, and occurrence of cells with swollen, fragmented and/or condensed nuclei) were only identified with 7beta-hydroxycholesterol, 7-ketocholesterol and cholesterol-5beta,6beta-epoxide, which also induce lysosomal destabilization associated or not associated with the formation of monodansylcadaverine-positive cytoplasmic structures. No relationship between oxysterol-induced cytotoxicity and HMG-CoA reductase activity was found. In addition, the highest O2*- overproduction quantified with hydroethidine was identified with 7beta-hydroxycholesterol, 7-ketocholesterol and cholesterol-5beta,6beta-epoxide, with cholesterol-5alpha, 6alpha-epoxide and 25-hydroxycholesterol. The highest capacity to simultaneously stimulate IL-8 secretion (quantified by ELISA and by using a multiplexed, particle-based flow cytometric assay) and enhance IL-8 mRNA levels (determined by RT-PCR) was observed with 7beta-hydroxycholesterol and 25-hydroxycholesterol. None of the effects observed for the oxysterols were detected for cholesterol. Therefore, oxysterols may have cytotoxic, oxidative, and/or inflammatory effects, or none whatsoever.

Involvement of a calcium-dependent dephosphorylation of BAD associated with the localization of Trpc-1 within lipid rafts in 7-ketocholesterol-induced THP-1 cell apoptosis.

7-Ketocholesterol is a component of oxidized LDL, which plays a central role in atherosclerosis. It is a potent inducer of cell death towards a wide number of cells involved in atherosclerosis. In this study, it is reported that 7-ketocholesterol treatment induces an increase of cytosolic-free Ca(2+) in THP-1 monocytic cells. This increase is correlated with the induction of cytotoxicity as suggested from experiments using the Ca(2+) channel blockers verapamil and nifedipine. This 7-ketocholesterol-induced apoptosis appears to be associated with the dephosphorylation of serine 75 and serine 99 of the proapoptotic protein Bcl-2 antagonist of cell death (BAD). We demonstrated that this dephosphorylation results mainly from the activation of calcium-dependent phosphatase calcineurin by the oxysterol-induced increase in Ca(2+). Moreover, this Ca(2+) increase appears related to the incorporation of 7-ketocholesterol into lipid raft domains of the plasma membrane, followed by the translocation of transient receptor potential calcium channel 1, a component of the store operated Ca(2+) entry channel, to rafts.

[Microspheres, nanospheres and flow cytometry: from cellular to molecular analysis]. / Microbilles, nanobilles et cytométrie en flux: de l'analyse cellulaire à l'analyse moléculaire.

Micro- and nanospheres are tightly associated with the development of flow cytometry. They are indispensable tools to optimize diffraction and fluorescence signals as well as for fluorescence calibration and cellular purification (magnetic micro- and nanospheres). They are also usefull to evaluate phagocytosis and to detect slightly expressed antigens. Recently, developments of microspheres-based flow cytometric assays have raised to quantify soluble analytes in biological fluids, cellular and tissue samples. The technology utilizes spectrally distinct fluorescent microspheres as a solid support for a conventional immunoassay, affinity assay or DNA hybridisation assay which is subsequently analyzed on a flow cytometer. Several multiplexed bead systems are now available facilitating the development of multiplexed assays that simultaneously measure many different analytes in few microliters of sample. Some recent applications with fluorescent microspheres coated with antibodies or oligonucleotides include cytokines and PCR products quantitation and single nucleotide polymorphism genotyping. Thus, multiplex assays using microspheres and flow cytometry technologies are exciting techniques which have the potential to contribute to the development of efficient diagnostic and research methods.