Early dyadic patterns of mother-infant interactions and outcomes of prematurity at 18 months.

OBJECTIVE: With the increased survival of very preterm infants, there is a growing concern for their developmental and socioemotional outcomes. The quality of the early mother-infant relationship has been noted as 1 of the factors that may exacerbate or soften the potentially adverse impact of preterm birth, particularly concerning the infant's later competencies and development. The first purpose of the study was to identify at 6 months of corrected age whether there were specific dyadic mother-infant patterns of interaction in preterm as compared with term mother-infant dyads. The second purpose was to examine the potential impact of these dyadic patterns on the infant's behavioral and developmental outcomes at 18 months of corrected age. METHODS: During a 12-month period (January-December 1998), all preterm infants who were <34 weeks of gestational age and hospitalized at the NICU of the Lausanne University Hospital were considered for inclusion in this longitudinal prospective follow-up study. Control healthy term infants were recruited during the same period from the maternity ward of our hospital. Mother-infant dyads with preterm infants (n = 47) and term infants (n = 25) were assessed at 6 months of corrected age during a mother-infant play interaction and coded according to the Care Index. This instrument evaluates the mother's interactional behavior according to 3 scales (sensitivity, control, and unresponsiveness) and the child's interactional behavior according to 4 scales (cooperation, compliance, difficult, and passivity). At 18 months, behavioral outcomes of the children were assessed on the basis of a semistructured interview of the mother, the Symptom Check List. The Symptom Check List explores 4 groups of behavioral symptoms: sleeping problems, eating problems, psychosomatic symptoms, and behavioral and emotional disorders. At the same age, developmental outcomes were evaluated using the Griffiths Developmental Scales. Five areas were evaluated: locomotor, personal-social, hearing and speech, eye-hand coordination, and performance. RESULTS: Among the possible dyadic patterns of interaction, 2 patterns emerge recurrently in mother-infant preterm dyads: a "cooperative pattern" with a sensitive mother and a cooperative-responsive infant (28%) and a "controlling pattern" with a controlling mother and a compulsive-compliant infant (28%). The remaining 44% form a heterogeneous group that gathers all of the other preterm dyads and is composed of 1 sensitive mother-passive infant; 10 controlling mothers with a cooperative, difficult, or passive infant; and 10 unresponsive mothers with a cooperative, difficult, or passive infant. Among the term control subjects, 68% of the dyads are categorized as cooperative pattern dyads, 12% as controlling pattern dyads, and the 20% remaining as heterogeneous dyads. At 18 months, preterm infants of cooperative pattern dyads have similar outcomes as the term control infants. Preterm infants of controlling pattern dyads have significantly fewer positive outcomes as compared with preterm infants of cooperative pattern dyads, as well as compared with term control infants. They display significantly more behavioral symptoms than term infants, including more eating problems than term infants as well as infants from cooperative preterm dyads. Infants of the controlling preterm dyads do not differ significantly for the total development quotient but have worse personal-social development than term infants and worse hearing-speech development than infants from cooperative preterm dyads. The preterm infants of the heterogeneous group have outcomes that can be considered as intermediate with no significant differences compared with preterm infants from the cooperative pattern or the controlling pattern dyads. CONCLUSION: Among mother-preterm infant dyads, we identified 2 specific patterns of interaction that could play either a protective (cooperative pattern) or a risk-precipitating (controlling pattern) role on developmental and behavioral outcome, independent of perinatal risk factors and of the family's socioeconomic background. The controlling pattern is much more prevalent among preterm than term dyads and is related to a less favorable infant outcome. However, the cooperative pattern still represents almost 30% of the preterm dyads, with infants' outcome comparable to the ones of term infants. These results point out the impact of the quality of mother-infant relationship on the infant's outcome. The most important clinical implication should be to support a healthy parent-infant relationship already in the NICU but also in the first months of the infant's life. Early individualized family-based interventions during neonatal hospitalization and transition to home have been shown to reduce maternal stress and depression and increase maternal self-esteem and to improve positive early parent-preterm infant interactions.

Manipulating the sensitivity of signal-induced repression: quantification and consequences of altered brinker gradients.

Traditionally, the analysis of gene regulatory regions suffered from the caveat that it was restricted to artificial contexts (e.g. reporter constructs of limited size). With the advent of the BAC recombineering technique, genomic constructs can now be generated to test regulatory elements in their endogenous environment. The expression of the transcriptional repressor brinker (brk) is negatively regulated by Dpp signaling. Repression is mediated by small sequence motifs, the silencer elements (SEs), that are present in multiple copies in the regulatory region of brk. In this work, we manipulated the SEs in the brk locus. We precisely quantified the effects of the individual SEs on the Brk gradient in the wing disc by employing a 1D data extraction method, followed by the quantification of the data with reference to an internal control. We found that mutating the SEs results in an expansion of the brk expression domain. However, even after mutating all predicted SEs, repression could still be observed in regions of maximal Dpp levels. Thus, our data point to the presence of additional, low affinity binding sites in the brk locus.

Exercise dose and insulin sensitivity: relevance for diabetes prevention.

PURPOSE: Exercise improves insulin resistance and is a first line for the prevention and treatment of type 2 diabetes. The extent, however, to which these responses are dose dependent is not known. The purpose of this study was to examine whether exercise dose was associated with improvements in insulin sensitivity after 4 months of exercise training in previously sedentary adults. METHODS: Fifty-five healthy volunteers participated in a 16-wk supervised endurance exercise intervention with a pre/postintervention design. Insulin sensitivity was assessed by euglycemic hyperinsulinemic clamp, peak oxygen uptake by a graded exercise test, and body composition by dual-energy x-ray absorptiometry. The exercise intervention consisted of three to five sessions per week with a minimum of three sessions supervised. A ramped exercise prescription protocol was used to achieve 75% of peak HR for 45 min per session. Exercise dose, expressed as average kilocalories expended per week, was computed as the product of exercise intensity, duration and frequency. RESULTS: Improved insulin sensitivity was significantly related to exercise dose in a graded dose-response relationship. No evidence of threshold or maximal dose-response effect was observed. Age and gender did not influence this dose-response relationship. Exercise intensity was also significantly related to improvements in insulin sensitivity, whereas frequency was not. CONCLUSIONS: This study identifies a graded dose-response relationship between exercise dose and improvements in insulin sensitivity. The implication of this observation is of importance for the adaptation of exercise prescription in clinical situations.

Effects of fructose and glucose overfeeding on hepatic insulin sensitivity and intrahepatic lipids in healthy humans.

OBJECTIVE: To assess how intrahepatic fat and insulin resistance relate to daily fructose and energy intake during short-term overfeeding in healthy subjects. DESIGN AND METHODS: The analysis of the data collected in several studies in which fasting hepatic glucose production (HGP), hepatic insulin sensitivity index (HISI), and intrahepatocellular lipids (IHCL) had been measured after both 6-7 days on a weight-maintenance diet (control, C; n = 55) and 6-7 days of overfeeding with 1.5 (F1.5, n = 7), 3 (F3, n = 17), or 4 g fructose/kg/day (F4, n = 10), with 3 g glucose/kg/day (G3, n = 11), or with 30% excess energy as saturated fat (fat30%, n = 10). RESULTS: F3, F4, G3, and fat30% all significantly increased IHCL, respectively by 113 ± 86, 102 ± 115, 59 ± 92, and 90 ± 74% as compared to C (all P < 0.05). F4 and G3 increased HGP by 16 ± 10 and 8 ± 11% (both P < 0.05), and F3 and F4 significantly decreased HISI by 20 ± 22 and 19 ± 14% (both P < 0.01). In contrast, there was no significant effect of fat30% on HGP or HISI. CONCLUSIONS: Short-term overfeeding with fructose or glucose decreases hepatic insulin sensitivity and increases hepatic fat content. This indicates short-term regulation of hepatic glucose metabolism by simple carbohydrates.

Development of Elispot and CFSE flow cytometric assays for detecting beryllium sensitivity

Background: Beryllium sensitization (BeS) is caused by exposure to beryllium in the workplace and may progress to chronic beryllium disease (CBD). This granulomatous lung disorder mimicks sarcoidosis clinically, but is characterized by beryllium specific CD4+ T-cells immune response. BeS is classically detected by beryllium lymphocyte proliferation test (BeLPT), but this assay requires radioactivity and is not very sensitive. In the context of a study aiming to evaluate if CBD patients are misdiagnosed as sarcoidosis patients in Switzerland, we developed EliSpot and CFSE beryllium flow cytometric test. Methods: 23 patients considered as having sarcoidosis (n = 21), CBD (n = 1) and possible CBD (n = 1) were enrolled. Elispot was performed using plate covered with gamma-IFN mAb. Cells were added to wells and incubated overnight at 37 °C with medium (neg ctrl), SEB (pos ctrl) or BeSO4 at 1, 10 and 100 microM. Anti-IFN-gamma biotinylated mAb were added and spots were visualized using streptavidinhorseradish peroxidase and AEC substrate reagent. Results were reported as spot forming unit (SFU). For Beryllium specific CFSE flow cytometry analysis, CFSE labelled cells were cultured in the presence of SEB and 1, 10 or 100 microM BeSO4. Unstimulated CFSE labeled cells were defined as controls. The cells were incubated for 6 days at 37 °C and 5% CO2. Surface labelling of T-lymphocytes and vivid as control of cells viability was performed at the time of harvest. Results: Using EliSpot technology, we were able to detect a BeS in 1/23 enrolled patients with a mean of 780 SFU (cut off value at 50 SFU). This positive result was confirmed using different concentration of BeSO4. Among the 23 patients tested, 22 showed negative results with EliSpot. Using CFSE flow cytometry, 1/7 tested patients showed a positive result with a beryllium specific CD4+ count around 30% versus 45% for SEB stimulation as positif control and 0.6 % for negative control. This patient was the one with a positive EliSpot assay. Conclusions: The preliminary data demonstrated the feasibility of Elispot and CFSE flow cytometry to detect BeS. The patient with a beryllium specific positive EliSpot and CFSE flow cytometry result had been exposed to beryllium at her workplace 20 years ago and is still regularly controlled for her pulmonary status. A positive BeLPT had already been described in 2001 in France for this patient. Further validation of these techniques are in progress.