Mother's attachment representations of their premature infant at 6 and 18 months after birth.

The effects of premature birth on attachment have generally been examined from the infant's perspective. There is a lack of data concerning parental attachment representations toward a premature child. Because of the psychological stress engendered in parents confronted with a premature birth, we hypothesized that their attachment representations would be altered during the first months after the hospital discharge. Fifty families with a premature infant (25-33 gestation weeks) and a control group of 30 families with a full-term infant participated to the study. Perinatal risks were evaluated during hospitalization. To assess mothers' representations of their infant, the Working Model of the Child Interview (WMCI, Zeanah & Benoit, 1995 & Benoit, Zeanah, Parker, Nicholson, & Coolbear, 1997) were administered when their children were 6 and 18 months old. The severity of the perinatal risks was found to have an impact on the mothers' attachment representations. At six months, only 20% of the mothers of a prematurely born infant (30% at 18 months) had secure attachment representations, vs. 53% for the control group (57% at 18 months). Furthermore, mothers of low-risk premature infants more often had disengaged representations, whereas distorted representations were more frequent in the high-risk group of premature children. These findings suggest that the parental response to a premature birth is linked to the severity of postnatal risks. The fact that secure attachment representations are affected in mothers of low-risk infants just as much as they are in mothers of high-risk infants points to the need to conduct further studies aimed at evaluating whether preventive intervention for both low-risk and high-risk premature will be helpful.

Recent decrease in the prevalence of congenital heart defects in europe.

OBJECTIVES: To examine trends in the prevalence of congenital heart defects (CHDs) in Europe and to compare these trends with the recent decrease in the prevalence of CHDs in Canada (Quebec) that was attributed to the policy of mandatory folic acid fortification. STUDY DESIGN: We used data for the period 1990-2007 for 47 508 cases of CHD not associated with a chromosomal anomaly from 29 population-based European Surveillance of Congenital Anomalies registries in 16 countries covering 7.3 million births. We estimated trends for all CHDs combined and separately for 3 severity groups using random-effects Poisson regression models with splines. RESULTS: We found that the total prevalence of CHDs increased during the 1990s and the early 2000s until 2004 and decreased thereafter. We found essentially no trend in total prevalence of the most severe group (group I), whereas the prevalence of severity group II increased until about 2000 and decreased thereafter. Trends for severity group III (the most prevalent group) paralleled those for all CHDs combined. CONCLUSIONS: The prevalence of CHDs decreased in recent years in Europe in the absence of a policy for mandatory folic acid fortification. One possible explanation for this decrease may be an as-yet-undocumented increase in folic acid intake of women in Europe following recommendations for folic acid supplementation and/or voluntary fortification. However, alternative hypotheses, including reductions in risk factors of CHDs (eg, maternal smoking) and improved management of maternal chronic health conditions (eg, diabetes), must also be considered for explaining the observed decrease in the prevalence of CHDs in Europe or elsewhere.

Atrioventricular septal defects among infants in Europe: a population-based study of prevalence, associated anomalies, and survival.

OBJECTIVE: To describe the epidemiology of chromosomal and non-chromosomal cases of atrioventricular septal defects in Europe. METHODS: Data were obtained from EUROCAT, a European network of population-based registries collecting data on congenital anomalies. Data from 13 registries for the period 2000-2008 were included. RESULTS: There was a total of 993 cases of atrioventricular septal defects, with a total prevalence of 5.3 per 10,000 births (95% confidence interval 4.1 to 6.5). Of the total cases, 250 were isolated cardiac lesions, 583 were chromosomal cases, 79 had multiple anomalies, 58 had heterotaxia sequence, and 23 had a monogenic syndrome. The total prevalence of chromosomal cases was 3.1 per 10,000 (95% confidence interval 1.9 to 4.3), with a large variation between registers. Of the 993 cases, 639 cases were live births, 45 were stillbirths, and 309 were terminations of pregnancy owing to foetal anomaly. Among the groups, additional associated cardiac anomalies were most frequent in heterotaxia cases (38%) and least frequent in chromosomal cases (8%). Coarctation of the aorta was the most common associated cardiac defect. The 1-week survival rate for live births was 94%. CONCLUSION: Of all cases, three-quarters were associated with other anomalies, both chromosomal and non-chromosomal. For infants with atrioventricular septal defects and no chromosomal anomalies, cardiac defects were often more complex compared with infants with atrioventricular septal defects and a chromosomal anomaly. Clinical outcomes for atrioventricular septal defects varied between regions. The proportion of termination of pregnancy for foetal anomaly was higher for cases with multiple anomalies, chromosomal anomalies, and heterotaxia sequence.

A receptor-like kinase mutant with absent endodermal diffusion barrier displays selective nutrient homeostasis defects.

The endodermis represents the main barrier to extracellular diffusion in plant roots, and it is central to current models of plant nutrient uptake. Despite this, little is known about the genes setting up this endodermal barrier. In this study, we report the identification and characterization of a strong barrier mutant, schengen3 (sgn3). We observe a surprising ability of the mutant to maintain nutrient homeostasis, but demonstrate a major defect in maintaining sufficient levels of the macronutrient potassium. We show that SGN3/GASSHO1 is a receptor-like kinase that is necessary for localizing CASPARIAN STRIP DOMAIN PROTEINS (CASPs)--major players of endodermal differentiation--into an uninterrupted, ring-like domain. SGN3 appears to localize into a broader band, embedding growing CASP microdomains. The discovery of SGN3 strongly advances our ability to interrogate mechanisms of plant nutrient homeostasis and provides a novel actor for localized microdomain formation at the endodermal plasma membrane.

Point defects and texture of Pd1-xInx sputtered intermetallic thin films

Pd1-xInx thin films (0.4 < x < 0.56) were prepared by radio frequency sputtering from a multi-zone target. The properties of these Hume-Rothery alloys were studied by X-ray diffractometry, electron probe microanalysis and scanning tunneling microscopy. The diffraction spectra were analyzed to obtain the intensity ratio of the (100) superlattice line to the (200) normal line, together with the variations of the lattice constant. The results ape explained quantitatively by a model based on point defects, i.e. Pd vacancies in In-rich films and Pd antisite atoms in Pd-rich films. In-rich films grow preferentially in the [100] direction while Pd-rich films grow preferentially in the [110] direction. The grains in indium-rich sputtered films appear to be enclosed in an atomically thick, indium-rich layer. The role of texture and the influence of point defects on electrical resistivity is also reported. (C) 1996 Elsevier Science Limited.

New insights into the role of microRNAs in pancreatic ß-cell maturation and plasticity

Le diabète est une maladie chronique caractérisée par une élévation du taux de sucre dans le sang aussi appelé « glycémie » reflétant un état pathologique. L'élévation de la glycémie au long cours a des répercussions délétères sur nombreux de nos tissus et organes d'où l'apparition de complications sévères chez les sujets diabétiques pouvant atteindre les yeux, les reins, le système nerveux, le système cardiovasculaire et les membres inférieurs. La carence en une hormone essentielle à notre organisme, l'insuline, est au coeur du développement de la maladie. L'insuline induit la captation du glucose circulant dans le sang en excès suite à une prise alimentaire riche en glucides et favorise son utilisation et éventuellement son stockage dans les tissus tels que le foie, le tissu adipeux et les muscles. Ainsi, l'insuline est vitale pour réguler et maintenir stable notre niveau de glycémie. Les cellules bêta du pancréas sont les seules entités de notre corps capables de produire de l'insuline et une perte de fonctionnalité associée à leur destruction ont été mises en cause dans le processus pathologique du diabète de type 2. Cependant la pleine fonctionnalité et la maturation des cellules bêta n'apparaissent qu'après la naissance lorsque le pancréas en développement a atteint sa masse adulte définitive. Enfin, une fois la masse des cellules bêta définitive établie, leur nombre et volume restent relativement constants au cours de la vie adulte chez un sujet sain. Néanmoins, au cours de périodes critiques les besoins en insuline sont augmentés tel qu'observé chez les femmes enceintes et les personnes obèses qui ont une perte de sensibilité à l'insuline qui se traduit par la nécessité de sécréter plus d'insuline afin de maintenir une glycémie normale. Dans l'hypothèse où la compensation n'a pas lieu ou n'est pas aboutie, le diabète se développe. Le processus de maturation postnatale ainsi que les événements compensatoires sont donc des étapes essentielles et de nombreuses questions sont encore non résolues concernant l'identification des mécanismes les régulant. Parmi les acteurs potentiels figurent de petites molécules d'ARN découvertes récemment appelées microARNs et qui ont été rapidement suggérées très prometteuses dans l'identification de nouvelles cibles thérapeutiques dans le cadre du diabète et d'autres pathologies. Les microARNs vont réguler l'expression de notre génome sans en modifier la séquence, phénomène également appelé épigénétique, ce qui résulte en des différences de comportement et de fonction cellulaires. Les microARNs sont donc susceptibles de jouer un rôle clé dans l'ensemble des processus biologiques et notre environnement associé à nos prédispositions génétiques peuvent grandement modifier leur niveau et donc leur action, qui à son tour se répercutera sur notre état physiologique. En effet nous avons identifié des changements de microARNs dans les cellules d'îlots pancréatiques de modèles animaux (rats et souris) associés à un état de résistance à l'insuline (grossesse et obésité). Par le biais d'expériences in vitro sur des cellules bêta extraites de rats et conservées en culture, nous avons pu analyser de plus près l'implication des microARNs dans la capacité des cellules bêta à sécréter de l'insuline mais aussi à se multiplier et à survivre au sein d'un environnement toxique. Ainsi, nous avons identifié des microARNs qui participent positivement à la compensation des cellules bêta, sous la direction d'hormones telles les estrogènes ou d'une hormone libérée par l'intestin au cours de la digestion (l'inerétine GLP1) et qui est largement utilisée comme agent thérapeutique dans la médication contre le diabète. Dans un second temps nous avons utilisé une stratégie similaire afin de déterminer le rôle de microARNs préalablement détectés comme étant changés au cours du développement postnatal des cellules bêta chez le rat. Cette étude a également mené à l'identification de microARNs participant à la maturation et à l'expansion de la masse des cellules bêta sous l'influence de la composition du régime alimentaire et des besoins en insuline adéquats qui en dépendent. Ces études apportent la vision de nouveaux mécanismes moléculaires impliquant les microARNs et démontrant leur importance pour le bon fonctionnement des cellules bêta et leur capacité d'adaptation à l'environnement. -- Les cellules bêta sont une composante des îlots pancréatiques de Langerhans et sont des cellules hautement différenciées qui ont l'unique capacité de sécréter de l'insuline sous l'influence des nutriments suite à une prise alimentaire. L'insuline facilite l'incorporation de glucose dans ses tissus cibles tels le foie, le tissu adipeux et les muscles. Bien que les besoins en insuline soient relativement constants au cours de la vie d'un individu sain, certaines conditions associées à un état de résistance à l'insuline, telles la grossesse ou l'obésité, requièrent une libération d'insuline majorée. En cas de résistance à l'insuline, une dysfonction des cellules bêta plus ou moins associée à leur mort cellulaire, conduisent à une sécrétion d'insuline insuffisante et au développement d'une hyperglycémie chronique, caractéristique du diabète de type 2. Jusqu'à présent, les mécanismes moléculaires sous- jacents à la compensation des cellules bêta ou encore menant à leur dysfonction restent peu connus. Découverts récemment, les petits ARNs non-codant appelés microARNs (miARNs), suscitent un intérêt grandissant de par leur potentiel thérapeutique pour la prise en charge et le traitement du diabète. Les miARNs sont de puissants régulateurs de l'expression génique qui lient directement le 3'UTR de leurs ARN messagers cibles afin d'inhiber leur traduction ou d'induire leur dégradation, ce qui leur permet de contrôler des fonctions biologiques multiples. Ainsi, nous avons pris pour hypothèse que les miARNs pourraient jouer un rôle essentiel en maintenant la fonction des cellules bêta et des processus compensatoires afin de prévenir le développement du diabète. Lors d'une première étude, une analyse transcriptomique a permis l'identification de miARNs différemment exprimés au sein d'îlots pancréatiques de rattes gestantes. Parmi eux, le miR-338-3p a démontré la capacité de promouvoir la prolifération et la survie des cellules bêta exposées à des acides gras saturés et des cytokines pro-inflammatoires, sans altérer leur propriété sécrétrice d'insuline. Nous avons également identifié deux hormones reconnues pour leurs propriétés bénéfiques pour la physiologie de la cellule bêta, l'estradiol et l'incrétine GLP1, qui régulent les niveaux du miR-338-3p. Ce miARN intègre parfaitement les voies de signalisation de ces deux hormones dépendantes de l'AMP cyclique, afin de contrôler l'expression de nombreux gènes conduisant à son action biologique. Dans un projet ultérieur, notre objectif était de déterminer la contribution de miARNs dans l'acquisition de l'identité fonctionnelle des cellules bêta en période postnatale. En effet, directement après la naissance les cellules bêta sont reconnues pour être encore immatures et incapables de sécréter de l'insuline spécifiquement en réponse à l'élévation de la glycémie. Au contraire, la réponse insulinique induite par les acides aminés ainsi que la biosynthèse d'insuline sont déjà fonctionnelles. Nos recherches ont permis de montrer que les changements de miARNs corrélés avec l'apparition du phénotype sécrétoire en réponse au glucose, sont régis par la composition nutritionnelle du régime alimentaire et des besoins en insuline qui en découlent. En parallèle, le taux de prolifération des cellules bêta est considérablement réduit. Les miARNs que nous avons étudiés coordonnent des changements d'expression de gènes clés impliqués dans l'acquisition de propriétés vitales de la cellule bêta et dans la maintenancé de son identité propre. Enfin, ces études ont permis de clairement démontrer l'importance des miARNs dans la régulation de la fonction des cellules bêta pancréatiques. -- Beta-cells are highly differentiated cells localized in the pancreatic islets and are characterized by the unique property of secreting insulin in response to nutrient stimulation after meal intake. Insulin is then in charge of facilitating glucose uptake by insulin target tissues such as liver, adipose tissue and muscles. Despite insulin needs stay more or less constant throughout life of healthy individuals, there are circumstances such as during pregnancy or obesity which are associated to insulin resistance, where insulin needs are increased. In this context, defects in beta-cell function, sometimes associated with beta-cell loss, may result in the release of inappropriate amounts of insulin leading to chronic hyperglycemia, properly defined as type 2 diabetes mellitus. So far, the mechanisms underlying beta- cell compensation as well as beta-cell failure remain to be established. The recently discovered small non-coding RNAs called microRNAs (miRNAs) are emerging as interesting therapeutic targets and are bringing new hope for the treatment of diabetes. miRNAs display a massive potential in regulating gene expression by directly binding to the 3'UTR of messenger RNAs and by inhibiting their translation and/or stability, enabling them to modify a wide range of biological functions. In view of this, we hypothesized that miRNAs may play an essential role in preserving the functional beta-cell mass and permitting to fight against beta-cell exhaustion and decompensation that can lead to diabetes development. In a first study, global profiling in pancreatic islets of pregnant rats, a model of insulin resistance, led to the identification of a set of differentially expressed miRNAs. Among them, miR-338- 3p was found to promote beta-cell proliferation and survival upon exposure of islet cells to pro- apoptotic stimuli such as saturated fatty acids or pro-inflammatory cytokines, without impairment in their capacity to release insulin. We also discovered that miR-338-3p changes are driven by two hormones, the estradiol and the incretin GLP1, both well known for their beneficial impact on beta- cell physiology. Consistently, we found that miR-338-3p integrates the cAMP-dependent signaling pathways regulated by these two hormones in order to control the expression of numerous genes and execute its biological functions. In a second project, we aimed at determining whether miRNAs contribute to the acquisition of beta-cell identity. Indeed, we confirmed that right after birth beta-cells are still immature and are unable to secrete insulin specifically in response to elevated concentrations of glucose. In contrast, amino acid-stimulated insulin release as well as insulin biosynthesis are already fully functional. In parallel, newborn beta-cells are proliferating intensively within the expanding pancreas. Interestingly, we demonstrated that the miRNA changes and the subsequent acquisition of glucose responsiveness is influenced by the diet composition and the resulting insulin needs. At the same time, beta-cell proliferation declines. The miRNAs that we have identified orchestrate expression changes of essential genes involved in the acquisition of specific beta-cell properties and in the maintenance of a mature beta-cell identity. Altogether, these studies clearly demonstrate that miRNAs play important roles in the regulation of beta-cell function.

Birth and rapid subcellular adaptation of a hominoid-specific CDC14 protein

Gene duplication was prevalent during hominoid evolution, yet little is known about the functional fate of new ape gene copies. We characterized the CDC14B cell cycle gene and the functional evolution of its hominoid-specific daughter gene, CDC14Bretro. We found that CDC14B encodes four different splice isoforms that show different subcellular localizations (nucleus or microtubule-associated) and functional properties. A microtubular CDC14B variant spawned CDC14Bretro through retroposition in the hominoid ancestor 18-25 million years ago (Mya). CDC14Bretro evolved brain-/testis-specific expression after the duplication event and experienced a short period of intense positive selection in the African ape ancestor 7-12 Mya. Using resurrected ancestral protein variants, we demonstrate that by virtue of amino acid substitutions in distinct protein regions during this time, the subcellular localization of CDC14Bretro progressively shifted from the association with microtubules (stabilizing them) to an association with the endoplasmic reticulum. CDC14Bretro evolution represents a paradigm example of rapid, selectively driven subcellular relocalization, thus revealing a novel mode for the emergence of new gene function

Dosage-dependent effects of Akt1/protein kinase Balpha (PKBalpha) and Akt3/PKBgamma on thymus, skin, and cardiovascular and nervous system development in mice.

Akt/protein kinase B (PKB) plays a critical role in the regulation of metabolism, transcription, cell migration, cell cycle progression, and cell survival. The existence of viable knockout mice for each of the three isoforms suggests functional redundancy. We generated mice with combined mutant alleles of Akt1 and Akt3 to study their effects on mouse development. Here we show that Akt1-/- Akt3+/- mice display multiple defects in the thymus, heart, and skin and die within several days after birth, while Akt1+/- Akt3-/- mice survive normally. Double knockout (Akt1-/-) Akt3-/-) causes embryonic lethality at around embryonic days 11 and 12, with more severe developmental defects in the cardiovascular and nervous systems. Increased apoptosis was found in the developing brain of double mutant embryos. These data indicate that the Akt1 gene is more essential than Akt3 for embryonic development and survival but that both are required for embryo development. Our results indicate isoform-specific and dosage-dependent effects of Akt on animal survival and development.

Parental post-traumatic reactions after premature birth: implications for sleeping and eating problems in the infant.

BACKGROUND: Progress in perinatal medicine has made it possible to increase the survival of very or extremely low birthweight infants. Developmental outcomes of surviving preterm infants have been analysed at the paediatric, neurological, cognitive, and behavioural levels, and a series of perinatal and environmental risk factors have been identified. The threat to the child's survival and invasive medical procedures can be very traumatic for the parents. Few empirical reports have considered post-traumatic stress reactions of the parents as a possible variable affecting a child's outcome. Some studies have described sleeping and eating problems as related to prematurity; these problems are especially critical for the parents. OBJECTIVE: To examine the effects of post-traumatic reactions of the parents on sleeping and eating problems of the children. DESIGN: Fifty families with a premature infant (25-33 gestation weeks) and a control group of 25 families with a full term infant participated in the study. Perinatal risks were evaluated during the hospital stay. Mothers and fathers were interviewed when their children were 18 months old about the child's problems and filled in a perinatal post-traumatic stress disorder questionnaire (PPQ). RESULTS: The severity of the perinatal risks only partly predicts a child's problems. Independently of the perinatal risks, the intensity of the post-traumatic reactions of the parents is an important predictor of these problems. CONCLUSIONS: These findings suggest that the parental response to premature birth mediates the risks of later adverse outcomes. Preventive intervention should be promoted.

Circadian and circaseptan patterns of natality and perinatal mortality of infants with different birth weights

OBJECTIVE. Data on human natality, stillbirth and perinatal mortality from Switzerland (1979-1987), available in four birthweight categories, are reexamined to assess any about-weekly (circaseptan) and changes in about-daily (circadian) patterns in central Europe over a century and a halfDESIGN. Retrospective analyses on archived data.SETTING. Federal Office of Statistics for Switzerland.RESULTS. In addition to prominent circadians, weekly patterns are also documented.CONCLUSION. Exogenous variations, prominent in early extrauterine life, such as changes of scheduling in obstetrics, may contribute to circadian and cireaseptan natality patterns. Information on these patterns serves in the optimization of neonatal care. Partly endogenous, partly physical environmental aspects, at least of about-weekly patterns, remain to be elucidated in series consisting exclusively of spontaneous parturitions.

Descriptive epidemiology of Cornelia de Lange syndrome in Europe.

Cornelia de Lange syndrome (CdLS) is a multiple congenital anomaly/mental retardation syndrome consisting of characteristic dysmorphic features, microcephaly, hypertrichosis, upper limb defects, growth retardation, developmental delay, and a variety of associated malformations. We present a population-based epidemiological study of the classical form of CdLS. The data were extracted from the database of European Surveillance of Congenital Anomalies (EUROCAT) database, a European network of birth defect registries which follow a standard methodology. Based on 23 years of epidemiologic monitoring (8,558,346 births in the 1980-2002 period), we found the prevalence of the classical form of CdLS to be 1.24/100,000 births or 1:81,000 births and estimated the overall CdLS prevalence at 1.6-2.2/100,000. Live born children accounted for 91.5% (97/106) of cases, fetal deaths 2.8% (3/106), and terminations of pregnancy following prenatal diagnosis 5.7% (6/106). The most frequent associated congenital malformations were limb defects (73.1%), congenital heart defects (45.6%), central nervous system malformations (40.2%), and cleft palate (21.7%). In the last 11 years, as much as 68% of cases with major malformations were not detected by routine prenatal US. Live born infants with CdLS have a high first week survival (91.4%). All patients were sporadic. Maternal and paternal age did not seem to be risk factors for CdLS. Almost 70% of patients, born after the 37th week of gestation, weighed <or=2,500 g. Low birth weight correlated with a more severe phenotype. Severe limb anomalies were significantly more often present in males.

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

Effects of age, birth cohort and period of death on Swiss cancer mortality, 1951-1984.

Swiss death certification data over the period 1951-1984 for total cancer mortality and 30 major cancer sites in the population aged 25 to 74 years were analysed using a log-linear Poisson model with arbitrary constraints on the parameters to isolate the effects of birth cohort, calendar period of death and age. The overall pattern of total cancer mortality in males was stable for period values and showed some moderate decreases in cohort values restricted to the generations born after 1930. Cancer mortality trends were more favourable in females, with steady, though moderate, declines in both cohort and period values. According to the estimates from the model, the worst affected generation for male lung cancer was that born around 1910, and a flattening of trends or some moderate decline was observed for more recent cohorts, although this decline was considerably more limited than in other European countries. There were decreases in cohort and period values for stomach, intestine and oesophageal cancer in both sexes and (cervix) uteri in females. Increases were observed in both cohort and period trends for pancreas and liver in males and for several other neoplasms, including prostate, brain, leukaemias and lymphomas, restricted, however, for the latter sites, to the earlier cohorts and hence partly attributable to improved diagnosis and certification in the elderly. Although age values for lung cancer in females were around 10-times lower than in males, upward trends in female lung cancer cohort values were observed in subsequent cohorts and for period values from the late 1960's onwards. Therefore, future trends in female lung cancer mortality should continue to be monitored. The application of these age/period/cohort models thus provides a summary guide for the reading and interpretation of cancer mortality trends, although it cannot replace careful inspection of single age-specific rates.