Altered growth in male peroxisome proliferator-activated receptor gamma (PPARgamma) heterozygous mice: involvement of PPARgamma in a negative feedback regulation of growth hormone action.

The peroxisome proliferator-activated receptor gamma (PPARgamma) plays a major role in fat tissue development and physiology. Mutations in the gene encoding this receptor have been associated to disorders in lipid metabolism. A thorough investigation of mice in which one PPARgamma allele has been mutated reveals that male PPARgamma heterozygous (PPARgamma +/-) mice exhibit a reduced body size associated with decreased body weight, reflecting lean mass reduction. This phenotype is reproduced when treating the mice with a PPARgamma- specific antagonist. Monosodium glutamate treatment, which induces weight gain and alters body growth in wild-type mice, further aggravates the growth defect of PPARgamma +/- mice. The levels of circulating GH and that of its downstream effector, IGF-I, are not altered in mutant mice. However, the IGF-I mRNA level is decreased in white adipose tissue (WAT) of PPARgamma +/- mice and is not changed by acute administration of recombinant human GH, suggesting an altered GH action in the mutant animals. Importantly, expression of the gene encoding the suppressor of cytokine signaling-2, which is an essential negative regulator of GH signaling, is strongly increased in the WAT of PPARgamma +/- mice. Although the relationship between the altered GH signaling in WAT and reduced body size remains unclear, our results suggest a novel role of PPARgamma in GH signaling, which might contribute to the metabolic disorder affecting insulin signaling in PPARgamma mutant mice.

Sentinel lymph node involvement and a high Breslow index are independent factors of risk for early relapse of melanoma

Rapport de synthèse : Le ganglion sentinelle (GS) se défini comme le premier ganglion de la chaîne ganglionnaire qui draine le territoire anatomique où siège une tumeur et, par conséquent, celui ayant le plus de possibilités de recevoir des métastases. La combinaison des deux techniques de détection du GS existantes, lymphoscintigraphie et coloration, permettent de déceler le GS dans 95-100% des cas. Le taux d'attente métastatique du GS varie entre 16 et 21 % des patients. Dans 50 à 87% des cas, le GS est le seul site de métastase et la probabilité de trouver des micro-métastases dans des ganglions appartenant aux relais supérieurs sans atteinte du GS est estimée à moins de 2%. Ces chiffres relèvent l'importance de la détection du GS. L'emploi de cette technique offre de nombreux avantages par rapport à la lymphadénéctomie élective que nous décrirons. Selon Rousseau et al., il existe une probable association entre le statut du GS et la survie de la maladie. Cette interprétation et celles d'autres auteurs soulignent la pertinence clinique du statut du GS dans le mélanome. En ce qui concerne la survie sans maladie (DFS) et la survie globale (OS), aucune différence significative n'a été observée entre les patients ayant subi une résection complète immédiate des ganglions lymphatiques et ceux qui d'abord ont subi une résection chirurgicale et analyse du GS secondaire, suivies par une dissection élective en cas de positivité. L'objectif de cette étude prospective était d'évaluer la pertinence de la positivité tumorale du GS dans l'évaluation des risques de rechute du mélanome. Cette étude a confirmé l'intérêt de la scintigraphie des ganglions lymphatiques (associée à la technique de coloration par bleu et celle de détection par sonde portable) dans l'identification du GS comme approche thérapeutique au stade précoce du mélanome. Elle a montré, en autre, que le statut du GS et l'indice de Breslow sont des facteurs de risque indépendants importants de rechute chez des patients atteints d'un mélanome au stade précoce. La combinaison de ces deux paramètres a permis de créer des groupes de patients à risque de rechute différents qui pourraient conduire à l'adaptation des protocoles de thérapie en fonction de ces risques.

Involvement of the extracellular signal-regulated kinase cascade for cocaine-rewarding properties

A central feature of drugs of abuse is to induce gene expression in discrete brain structures that are critically involved in behavioral responses related to addictive processes. Although extracellular signal-regulated kinase (ERK) has been implicated in several neurobiological processes, including neuronal plasticity, its role in drug addiction remains poorly understood. This study was designed to analyze the activation of ERK by cocaine, its involvement in cocaine-induced early and long-term behavioral effects, as well as in gene expression. We show, by immunocytochemistry, that acute cocaine administration activates ERK throughout the striatum, rapidly but transiently. This activation was blocked when SCH 23390 [a specific dopamine (DA)-D1 antagonist] but not raclopride (a DA-D2 antagonist) was injected before cocaine. Glutamate receptors of NMDA subtypes also participated in ERK activation, as shown after injection of the NMDA receptor antagonist MK 801. The systemic injection of SL327, a selective inhibitor of the ERK kinase MEK, before cocaine, abolished the cocaine-induced ERK activation and decreased cocaine-induced hyperlocomotion, indicating a role of this pathway in events underlying early behavioral responses. Moreover, the rewarding effects of cocaine were abolished by SL327 in the place-conditioning paradigm. Because SL327 antagonized cocaine-induced c-fos expression and Elk-1 hyperphosphorylation, we suggest that the ERK intracellular signaling cascade is also involved in the prime burst of gene expression underlying long-term behavioral changes induced by cocaine. Altogether, these results reveal a new mechanism to explain behavioral responses of cocaine related to its addictive properties.

A longitudinal study of environmental tobacco smoke exposure in children: parental self reports versus age dependent biomarkers

Background: Awareness of the negative effects of smoking on children's health prompted a decrease in the self-reporting of parental tobacco use in periodic surveys from most industrialized countries. Our aim is to assess changes between ETS exposure at the end of pregnancy and at 4 years of age determined by the parents' self-report and measurement of cotinine in age related biological matrices.Methods: The prospective birth cohort included 487 infants from Barcelona city (Spain). Mothers were asked about maternal and household smoking habit. Cord serum and children's urinary cotinine were analyzed in duplicate using a double antibody radioimmunoassay. Results: At 4 years of age, the median urinary cotinine level in children increased 1.4 or 3.5 times when father or mother smoked, respectively. Cotinine levels in children's urine statistically differentiated children from smoking mothers (Geometric Mean (GM) 19.7 ng/ml; 95% CI 16.83–23.01) and exposed homes (GM 7.1 ng/ml; 95% CI 5.61–8.99) compared with non-exposed homes (GM 4.5 ng/ml; 95% CI 3.71–5.48). Maternal self-reported ETS exposure in homes declined in the four year span between the two time periods from 42.2% to 31.0% (p < 0.01). Nevertheless, most of the children considered non-exposed by their mothers had detectable levels of cotinine above 1 ng/mL in their urine.Conclusion: We concluded that cotinine levels determined in cord blood and urine, respectively, were useful for categorizing the children exposed to smoking and showed that a certain increase in ETS exposure during the 4-year follow-up period occurred.

Predicting cancer involvement of genes from heterogeneous data

Background: Systematic approaches for identifying proteins involved in different types of cancer are needed. Experimental techniques such as microarrays are being used to characterize cancer, but validating their results can be a laborious task. Computational approaches are used to prioritize between genes putatively involved in cancer, usually based on further analyzing experimental data. Results: We implemented a systematic method using the PIANA software that predicts cancer involvement of genes by integrating heterogeneous datasets. Specifically, we produced lists of genes likely to be involved in cancer by relying on: (i) protein-protein interactions; (ii) differential expression data; and (iii) structural and functional properties of cancer genes. The integrative approach that combines multiple sources of data obtained positive predictive values ranging from 23% (on a list of 811 genes) to 73% (on a list of 22 genes), outperforming the use of any of the data sources alone. We analyze a list of 20 cancer gene predictions, finding that most of them have been recently linked to cancer in literature. Conclusion: Our approach to identifying and prioritizing candidate cancer genes can be used to produce lists of genes likely to be involved in cancer. Our results suggest that differential expression studies yielding high numbers of candidate cancer genes can be filtered using protein interaction networks.

Parental care time in four European countries: comparing types and contexts

The intensity of parental investments in child care time is expected to vary across families with different norms and time-constraints. Additionally, it should also differ across countries, since the abilities of parents to harmonize family and work vary by national context. In our opinion, however, this question remains inconclusive for two main reasons: 1) only some countries have been studied from a comparative approach; 2) previous studies have not paid enough attention to the analysis of how the conditional effects of education and employment affect parental investments.In this paper we used nationally representative time-use data from Denmark, Flanders, Spain and the United Kingdom (N=4,031) to explore how employment and education predict variations in child care time. IN Britain and Spain employment has a strong negative effect on fathers’ child care, but a weaker one in Flanders and particularly in Denmark. In contrast, maternal employment has a strong negative impact in all four countries. Education increases child care time significantly only among Spanish mothers and fathers, as well as British mothers. Nonetheless, we find that college-educated mothers under similar time-constraints increase substantially their expected child care time in Britain, Flanders and Spain; for fathers we find a more mixed picture. Routine child care activities are more sensitive to both maternal and paternal employment than interactive child care activities. Finally, we observe that working a public sector job generally increases a total time allocated to parental care, controlling for several demographic and socioeconomic variables.

Who benefits from parental leave in Spain? : a life course analysis

This paper analyses the extent to which individual and workplacecharacteristics and regional policies influence the use and duration ofparental leave in Spain. The research is based on a sample of 125,165people, and 6,959 parental leaves stemming from the ‘Sample ofWorking Life Histories’ (SWLH), 2006. The SWLH consists of administrative register data which include information from threedifferent sources: Social Security, Municipality and Income TaxRegisters. We adopt a simultaneous equations approach to analyse theuse (logistic regression) and duration (event history analysis) ofparental leave, which allows us to control for endogeneity and censoredobservations. We argue that the Spanish parental leave scheme increases gender and social inequalities insofar as reinforces genderrole specialization, and only encourages the reconciling of work andfamily life among workers with a good position in the labour market(educated employees with high and stable working status).

Paternal involvement and children's developmental stages in Spain

How does fathering change across children’s developmental stages and how do these changes vary by educational levels and women’s employment? To investigate this, I use the „2003 Spanish Time Use Survey‟ (N = 2,941) for a sample of heterosexual couples with children of different ages. I differentiate between physical (i.e. feeding, supervising, putting children to bed) and interactive child care activities (i.e. speaking to, playing with, teaching the child). Fathers‟ education strongly influences how much fathers participate in physical care in families with preschoolers, a stage in which these activities are particularly important for children’s physical, social, and emotional development. For interactive care, a significant education gradient emerges when the youngest child is aged 3 to 5, when the acquisition of complex linguistic, conceptual, and social skills is critical for later school success. Mother’s employment significantly influences father’s physical child care with preschoolers. This suggests that empowering Spanish women to participate in the labor market promotes gender equity in the household division of child care.

Productivities, preferences, and parental child care

We study the interplay of preferences and market productivities on parenting, and show the preferences, when identified, provide a better explanation of caring decisions than has, so far, been demonstrated in the literature. We qualify the standard finding the parental education in a key determinant of care by showing important interaction effects with marital homogamy. We find that homogamy has opposite effects on child care and couple specialization for high and low educated parents. Identification has been made possible by a unique couple-based time diary study for Denmark

Explaining parental dedication to child care in Spain

The quality of the time dedicated to child care has potential positive effects on children’s life chances. However, the determinants of parental time allocation to child care remain largely unexplored, particularly in context undergoing rapid family change such as Spain. We assess two alternative explanations for differences between parents in the amount of time spent with children. The first, based in the relative resources hypothesis, links variation in time spent with children to the relative attributes (occupation, education or income) of one partner to the other. The second, derived from the social status hypothesis, suggests that variation in time spent with children is attributable to the relative social position of the pair (i.e. higher status couples spend more time with children regardless of within-couple difference).To investigate theses questions, we use a sample of adults (18-50) from the Spanish Time Use Survey (STUS) 2002-2003 (n=7,438). Limiting the analysis to adults who are married or in consensual unions, the STUS allows to assess both the quantity and quality of parental time spent with children. We find little support for the “relative resources hypothesis”. Instead, consistent with the “social status hypothesis”, we find that time spent on child care is attributable to the social position of the couple, regardless of between-parent differences in income of education.

Parental investments in children: how bargaining and educational homogamy affect time allocation

This study examines parental time investment in their children, distinguishing between developmental and non-developmental care. Our analyses centre on three influential determinants: educational background, marital homogamy, and spouses' relative bargaining power. We find that the emphasis on quality care time is correlated with parents' education, and that marital homogamy reduces couple specialization, but only among the highly educated. In line with earlier research, we identify gendered parental behaviour. The presence of boys is an important condition for fathers' time dedication, but primarly among lower educated fathers. To the extent that parental stimulation is decisive for child outcomes, our findings suggest the persistence of important inequalities. This emerges through our special attention to behavioural differences across the educational distribution among households.

Paternal involvement in child caregiving and infant sociability

In this study, the influence of paternal involvement in caregiving on infant sociability was assessed using a strange situation paradigm adapted from the work of Ainsworth, Blehar, Waters, and Wall (1978). Thirty-seven families participated with their firstborn child (aged 12-14 months). According to the questionnaire, 20 nontraditional fathers were very involved in caretaking, and 17 fathers were less or not at all involved. Infant sociability was assessed using three of Ainsworth et al.'s rating scales: proximity or contact-seeking, avoidance, and distance interaction. Results indicated that infants of nontraditional fathers were globally more sociable with all their partners (father, mother, and stranger) than infants of traditional fathers. Furthermore, results suggested that it was not only the father-infant relationship or infant development which were affected by the amount of paternal involvement in daily caretaking but the family system as a whole. Indeed, infants from nontraditional families appeared to interact equally with their fathers and mothers in direct interaction. In addition, these infants interacted at a distance with a stranger as much in the presence of their fathers as in the presence of their mothers, thereby suggesting that both parents represented an equally secure base.

Influence d'une hospitalisation prénatale sur les facteurs de stress parentaux lors d'une naissance prématurée [Influence of prenatal hospitalization on parental stressful experience in the case of a premature birth].

OBJECTIVES: To investigate the influence of prenatal hospitalization before a premature birth, on the parental stressful experience, parental symptoms of post-traumatic stress and quality of parent-infant interaction during the hospitalization in neonatology. POPULATION AND METHODS: Population: 51 preterm infants born and 25 full term infants control. Four groups: controls, premature without prenatal hospitalization, premature with a short (<8 days) prenatal hospitalization and premature with a long (≥8 days) prenatal hospitalization. Instruments: the Parental Stressor Scale: Neonatal Intensive Care Unit (PSS: NICU, Miles et al., 1993 [14]) and the Perinatal PTSD Questionnaire (PPQ, Quinnell and Hynan, 1999 [16]). RESULTS: When prenatal hospitalization of the mother occurred, parents acknowledged increased stress induced by the environmental factors during the infant's hospitalization. Furthermore, mothers from the group with a short prenatal hospitalization presented significantly more symptoms of post-traumatic stress. Parents presenting more symptoms of post-traumatic stress describe a significantly more difficult interaction with their infant in neonatology. CONCLUSION: This study highlights the necessity to deliver special care to women hospitalized shortly (<8 days) prior to the delivery of their premature baby. This group is at high risk of presenting post-traumatic stress symptoms, which could have a negative impact on the quality of parent-infant interactions.

Study of parental models: building an instrument for their exploration

Objective: This research presents the construction of an attributional questionnaire concerning the different parental models and factors that are involved in family interactions. Method: A mixed methodology was used as a foundation to develop items and respective pilots that allowed checking the validity and internal consistency of the instrument using expert judgment. Results: An instrument of 36 statements was organized into 12 categories to explore the parental models according to the following factors: parental models, breeding patterns, attachment bonds and guidelines for success, and promoted inside family contexts. Analyzing these factors contributes to the children’s development within the familiar frown, and the opportunity for socio-educational intervention. Conclusion: It is assumed that the family context is as decisive as the school context; therefore, exploring the nature of parental models is required to understand the features and influences that contribute to the development of young people in any social context.