The OVAREX study: Establishment of ex vivo ovarian cancer models to validate innovative therapies and to identify predictive biomarkers.

BACKGROUND: Ovarian cancer is the first cause of death from gynecological malignancies mainly due to development of chemoresistance. Despite the emergence of PARP inhibitors, which have revolutionized the therapeutic management of some of these ovarian cancers, the 5-year overall survival rate remains around 45%. Therefore, it is crucial to develop new therapeutic strategies, to identify predictive biomarkers and to predict the response to treatments. In this context, functional assays based on patient-derived tumor models could constitute helpful and relevant tools for identifying efficient therapies or to guide clinical decision making. METHOD: The OVAREX study is a single-center non-interventional study which aims at investigating the feasibility of establishing in vivo and ex vivo models and testing ex vivo models to predict clinical response of ovarian cancer patients. Patient-Derived Xenografts (PDX) will be established from tumor fragments engrafted subcutaneously into immunocompromised mice. Explants will be generated by slicing tumor tissues and Ascites-Derived Spheroids (ADS) will be isolated following filtration of ascites. Patient-derived tumor organoids (PDTO) will be established after dissociation of tumor tissues or ADS, cell embedding into extracellular matrix and culture in specific medium. Molecular and histological characterizations will be performed to compare tumor of origin and paired models. Response of ex vivo tumor-derived models to conventional chemotherapy and PARP inhibitors will be assessed and compared to results of companion diagnostic test and/or to the patient's response to evaluate their predictive value. DISCUSSION: This clinical study aims at generating PDX and ex vivo models (PDTO, ADS, and explants) from tumors or ascites of ovarian cancer patients who will undergo surgical procedure or paracentesis. We aim at demonstrating the predictive value of ex vivo models for their potential use in routine clinical practice as part of precision medicine, as well as establishing a collection of relevant ovarian cancer models that will be useful for the evaluation of future innovative therapies. TRIAL REGISTRATION: The clinical trial has been validated by local research ethic committee on January 25th 2019 and registered at ClinicalTrials.gov with the identifier NCT03831230 on January 28th 2019, last amendment v4 accepted on July 18, 2023.

Correlation between unproven therapies and delayed return-to-work for COVID-19-infected healthcare workers.

The objective of this study is to investigate factors influencing the time to return to work (RTW) of HealthCare Workers (HCW) infected with COVID-19 during the initial wave of the pandemic in a southern French university hospital. Data collection of 170 HCW (between March 16 to June 1, 2020) included demographic and professional information, clinical profiles, comorbidities, medical management, therapies and RT-PCR results. The mean time to RTW was 15.6 days. Multivariate analyses revealed that the time to RTW was shorter among laboratory and emergency workers, while it was longer for HCW aged 40 to 49 years, at higher risk of severe illness, with a delayed negative SARS-CoV-2 PCR or those treated with azithromycin and/or hydroxychloroquine. This study highlights diverse factors affecting HCW RTW post-COVID-19 infection, underscoring the importance of exercising caution in administering unproven therapies to HCW during the early stages of a novel infectious pandemic.

Different protein intake in the first year and its effects on adiposity rebound and obesity throughout childhood: 11 years follow-up of a randomized controlled trial.

BACKGROUND AND OBJECTIVES: Infant feeding affects child growth and later obesity risk. We examined whether protein supply in infancy affects the adiposity rebound, body mass index (BMI) and overweight and obesity up to 11 years of age. METHODS: We enrolled healthy term infants from five European countries in a double blind randomized trial, with anticipated 16 examinations within 11 years follow-up. Formula-fed infants (n = 1090) were randomized to isoenergetic formula with higher or lower protein content within the range stipulated by EU legislation in 2001. A breastfed reference group (n = 588) was included. Adiposity rebound and BMI trajectories were estimated by generalized additive mixed models in 917 children, with 712 participating in the 11 year follow-up. RESULTS: BMI trajectories were elevated in the higher compared to the lower protein group, with significantly different BMI at adiposity rebound (0.24 kg/m2, 0.01-0.47, p = 0.040), and an increased risk for overweight at 11 years (adjusted Odds Ratio 1.70; 1.06-2.73; p = 0.027) but no significant difference for obesity (adjusted Odds Ratio 1.47; 0.66-3.27). The two formula groups did not differ in the timing of adiposity rebound, but all children with obesity at 11 years had an early adiposity rebound before four years. CONCLUSIONS: Compared to conventional high protein formula, feeding lower protein formula in infancy lowers BMI trajectories up to 11 years and achieves similar BMI values at adiposity rebound as observed in breastfed infants.

Parental Perception of Body Weight Status of Their 8-year-old Children: Findings from the European CHOP Study.

BACKGROUND: Maternal perception of child weight status in children with overweight or obesity has received a lot of attention but data on paternal perception of children from presumably healthy cohorts are lacking. OBJECTIVE: We aimed to investigate paternal and maternal perception of child weight status at the age of 8 years in a cohort of 591 children from 5 European countries. MATERIAL AND METHODS: Included were 8-year-old children and their parents participating in the European Childhood Obesity Project (EU CHOP). Weight and height of children and parents were measured and Body Mass Index (BMI, kg/m2) was calculated. Both parents were asked to assess their perception of child weight status using Eckstein scales and their concern about child overweight. The agreement between mother and father perceptions was assessed by Cohen kappa coefficient and their relationship was analyzed by linear mixed effects models based on ordinal logistic regression, accounting for country, child gender and BMI, parental BMI, level of education, concern and type of feeding during first year of life. RESULTS: Data from children and both parents were available for 432 girls and boys. Mean BMI was comparable in boys and girls (16.7 ± 2.31 vs. 16.9 ± 2.87 kg/m2, P = 0.55). In total, 172 children (29.3%) were overweight or obese. There was a high degree of agreement between mother and father perceptions of their child's weight status (Cohen kappa 0.77). Multivariate modelling showed that perception levels significantly increased with child BMI but were globally lower than assessed. They differed between countries, gender and types of feeding during first year of life, were influenced by education level of the father but were not related to parental BMI and concern about childhood overweight. CONCLUSIONS: The study showed no overall differences between mothers and fathers in rating their child's weight status but both parents had a propensity to underestimate their child's actual weight, particularly in boys. The EU CHOP trial registered at clinicaltrials.gov as NCT00338689.

Sleep duration and problem behaviour in 8-year-old children in the Childhood Obesity Project.

There is growing evidence that insufficient sleep has negative effects on the mental health of children. The aim of this study is to examine the associations between device-measured sleep duration and internalizing and externalizing problems in 8-year-old children. The study is a secondary analysis of data from the Childhood Obesity Project conducted in five European countries. Nocturnal sleep duration was measured with the SenseWear™ Armband 2. Parents rated their child's internalizing and externalizing problems on the Child Behaviour Checklist. Behaviour scores were dichotomized at the 90th percentile based on sex- and country-specific z-scores. Logistic regression models were applied to test the associations between sleep duration and behaviour. Data were available for 406 8-year-old children. The average sleep duration was 9.25 h per night (SD: 0.67) with 1464 nights measured in total. The sleep duration recommendation of the American Academy of Sleep Medicine for school-aged children (9-12 h) was met by 66.7% of children. One hour of additional sleep per night significantly reduced the risk of having internalizing problems (adjusted OR = 0.51; 95% CI 0.29-0.91). Children who adhered to the sleep duration recommendation had a lower risk for internalizing problems (adjusted OR = 0.45; 95% CI 0.21-0.99). Sleep duration and externalizing problems showed no significant association. Longer sleep duration was associated with a reduced risk of having internalizing problems but not externalizing problems. Results highlight that it is important to ensure adequate sleep duration throughout primary-school years for the optimal emotional health of children. Trial registration number: NCT00338689. Registered: June 19, 2006.

Screening of health workers exposed to SARS-CoV-2 in a university hospital in the south of France.

INTRODUCTION: SARS-CoV-2, which causes COVID-19, is a virus that has caused a global pandemic. Health workers (HWs) are major players in the fight against this infection and are occupationally exposed to the virus in the course of their work. In this context, this study presents surveillance data on 1714 workers in a hospital center in the south of France for the period from March 17 to April 20, 2020. MATERIALS AND METHODS: Symptomatic HWs, contact cases and those with high anxiety were tested. Diagnosis of COVID-19 was performed by RT-PCR after nasopharyngeal sampling. RESULTS: During this period, 30.4% of hospital staff received 3028 nasal swabs. Of these, 8.0% were infected with SARS-CoV-2. Among the SARS-CoV-2 positive HWs, 24.3% were asymptomatic. Among COVID unit and non COVID unit, the positive HWs for SARS-CoV-2 were, respectively, 5.8% and 8.2% (p = 0.2). HWs over 50 years of age were less likely to be positive for SARS-CoV-2 (3.8%) than other younger HWs (9.1%) (p < 0.001). No serious cases of COVID-19 were reported in our population during this period. DISCUSSION: Our study suggests that HWs who tested positive for COVID-19 are often asymptomatic. Therefore, PPE is pivotal to prevent HWs to patients and HWs to HWs transmission during workshifts. Contact tracing and screening is essential to limit the spread of the virus within the hospital. On the other hand, HWs working in COVID-19 units are not more often infected probably because they have a higher risk awareness than other HWs.

Influence of total sugar intake on metabolic blood markers at 8 years of age in the Childhood Obesity Project.

PURPOSE: We aimed to characterize the association of dietary sugar intake with blood lipids and glucose-related markers in childhood. METHODS: Data from the multicentric European Childhood Obesity Project Trial were used. Three-day weighed dietary records were obtained at 8 years of age along with serum concentrations of triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), glucose, and insulin. Total sugar intake comprised all mono- and disaccharides; different sugar sources were defined. Linear regression models were applied to investigate the cross-sectional association of total sugar intake with blood lipids and glucose-related markers with adjustment for total energy intake using the residual method. RESULTS: Data were available for 325 children. Children consumed on average 332 kcal (SD 110) and 21% (SD 6) of energy from total sugar. In an energy-adjusted model, an increase of 100 kcal from total sugar per day was significantly associated with a z score HDL-C decrease (- 0.14; 95% CI - 0.01, - 0.27; p value = 0.031). Concerning different food groups of total sugar intake, 100 kcal total sugar from sweetened beverages was negatively associated with z score HDL-C (- 1.67; 95% CI - 0.42, - 2.91; p value = 0.009), while total sugar from milk products was positively related to z score HDL-C (1.38, 95% CI 0.03, 2.72; p value = 0.045). None of the other blood lipids or glucose-related markers showed a significant relationship with total sugar intake. CONCLUSION: Increasing dietary total sugar intake in children, especially from sweetened beverages, was associated with unfavorable effects on HDL-C, which might increase the long-term risk for dyslipidemia and cardiovascular disease. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov Identifier: NCT00338689; Registered: June 19, 2006. URL: https://clinicaltrials.gov/ct2/show/NCT00338689?term=NCT00338689&rank=1 .

Nutritional Quality and Degree of Processing of Children's Foods Assessment on the French Market.

Food packaging marketing techniques which appeal to children (such as cartoon characters and brand mascots) affect children's choices, preferences, and eating habits. Several studies have assessed the nutritional quality of food intended to children in various countries and concluded that most were high in fat, salt, and sugar (HFSS) and ultra-processed foods. The aim of this study is to analyse products intended for children over the age of 3 (foods and beverages with relevant marketing elements on the packaging) available on the French market as regards: (1) nutritional quality, based on the Nutri-Score labelling system, (2) compliance with expected nutritional profile suitable for children, according to the criteria of the WHO Europe Nutrient Profile Model, and (3) degree of processing, as defined by the NOVA classification, from packaging collected in 20 stores (hyper/supermarkets, hard-discount retail chains, and organic food stores). The marketing strategies most often used on children's products are cartoons (97.22%; n = 1120) and mascots (77.78%; n = 896). A total of 1155 products were included in the study, most of which were sugary foods: almost a quarter of the products in the sample (23.81%; n = 275) list a sweetener as the first ingredient, and most of them (89.52%; n = 1034) contain free sugars according to the WHO definition. All the products included in our study feature marketing elements targeting on the packaging, yet 94.88% do not meet the criteria of the WHO Europe Nutrient Profile Model. Most (58.68%; n = 676) belong to Nutri-Score groups D and E, with the highest proportion in group D (39.32%; n = 453) and are ultra-processed (87.97%; n = 1016), especially through the use of flavourings and ultra-processed sugars. Using the Nutri-Score, the WHO Europe Nutrient Profile Model, and the NOVA classification, this study suggests that a significant share of pre-packaged foods marketed to children do not have an adequate nutritional profile. As such, measures are needed to regulate what marketing elements aimed at children can be included on packaging, based on these criteria.

[Robotic surgery in endometrial cancer: Feasibility in obese patients]. / Chirurgie robotique du cancer de l'endomètre chez la patiente obèse.

OBJECTIVE: Minimally invasive surgery is a technique frequently used in gynecologic surgery. The robot-assisted surgery is a recent approach, and the benefits are not yet proven. The objective of this study was to evaluate the feasibility to use robot-assisted surgery for obese patient with endometrial cancer. METHODS: All patients undergoing a robotic surgery for uterus malignant indication between March 2013 and May 2016 in our center were retrospectively included. Patients were divided in two groups, according to their body mass index (BMI). The group with BMI<30kg/m2 was the reference for this comparative study. The main criteria was the robot operative time. The other criteria were total operating time, hospital stay and intraoperative and postoperative complications. RESULTS: Seventy-seven patients met inclusion criteria for analysis. The median robot operative time was 110minutes for all patients [21-341], without difference between the five groups (P=0.60). There was no difference for the total operative time (P=0.50). The median hospital stay was 3 days (P=0.92). There were ten intraoperative complications. One patient had a conversion (1.3%). There was no statistical difference for postoperative complications (P=1). CONCLUSION: Our study found few differences in the surgical management by laparoscopic robot-assisted between obese and non obese women. Robot-assisted surgery seems to be feasible for uterine cancer treatment of obese patients. Prospective and randomized studies are needed to assess the benefit of the robotic surgery.

Comparison of four methods to assess high-on platelet reactivity under P2Y12 receptor inhibitor.

P2Y12 receptor inhibitors are antiplatelet agents commonly prescribed in the treatment of coronary artery disease. Their efficacy can be limited by high on-treatment platelet reactivity (HPR), which can be evaluated by different biological assays. Most commonly, HPR is evaluated by flow cytometric vasodilator-stimulated phosphoprotein-phosphorylation (VASP-P) assay, which can be time consuming. To evaluate the potential interest of novel technologies, we compared four different assays. Ninety patients receiving P2Y12 inhibitors were included. Four technologies were evaluated: the current standard test measuring VASP-P by flow cytometry, the historical reference test based on light transmittance aggregation (LTA), and two relatively novel techniques: whole blood multiple electrode aggregometry (MEA) and platelet function analyzer (PFA), which are less time consuming. The three latter tests were compared with the VASP-P assay as a reference using receiver operating characteristics (ROC) analysis: LTA has an excellent comparability with the VASP test (ROC AUC > 0.9); the other two tests (multiplate and PFA) have only satisfactory comparability (ROC AUC around 0.7) and therefore may not replace the VASP "gold standard" test, if importance is attached to a quantitative assessment of the substitution parameter of VASP. Nevertheless, if a binary approach of the anti-aggregation result is sought, then one can conclude that the three tests are equivalent since Cohen's kappa coefficients are very close for the three tests (k = 0.548 for LTA; k = 0.554 for MEA; k = 0.570 for PFA/P2Y), and a similar proportion of patients are misclassified (15% for LTA, 14% for MEA, and 13.6% for PFA). Discriminant factor analysis using all the parameters provided by each test did not improve the diagnostic performance of MEA or PFA. In conclusion, only LTA shows a good comparability to the VASP assay using ROC curve analysis, probably because misclassified patients have results close to the cutoff values. All three tests have moderate agreement regarding the classification of patients as responders to P2Y12 inhibition.

Risperidone-induced metabolic dysfunction is attenuated by Curcuma longa extract administration in mice.

Antipsychotics, such as risperidone, increase food intake and induce alteration in glucose and lipid metabolism concomitantly with overweight and body fat increase, these biological abnormalities belong to the metabolic syndrome definition (high visceral adiposity, hypertriglyceridemia, hyperglycemia, low HDL-cholesterol and high blood pressure). Curcumin is a major component of traditional turmeric (Curcuma longa) which has been reported to improve lipid and glucose metabolism and to decrease weight in obese mice. We questioned the potential capacity of curcumin, contained in Curcuma longa extract (Biocurcuma™), to attenuate the risperidone-induced metabolic dysfunction. Two groups of mice were treated once a week, for 22 weeks, with intraperitoneal injection of risperidone (Risperdal) at a dose 12.5 mpk. Two other groups received intraperitoneal injection of the vehicle of Risperdal following the same schedule. Mice of one risperidone-treated groups and of one of vehicle-treated groups were fed a diet with 0.05% Biocurcuma™ (curcumin), while mice of the two other groups received the standard diet. Curcumin limited the capacity of risperidone to reduce spontaneous motricity, but failed to impede risperidone-induced increase in food intake. Curcumin did not reduce the capacity of risperidone to induce weight gain, but decreased visceral adiposity and decreased the risperidone-induced hepatomegaly, but not steatosis. Furthermore, curcumin repressed the capacity of risperidone to induce the hepatic over expression of enzymes involved in lipid metabolism (LXRα, FAS, ACC1, LPL, PPARγ, ACO, SREBP2) and decreased risperidone-induced glucose intolerance and hypertriglyceridemia. Curcumin decreased risperidone-induced increases in serum markers of hepatotoxicity (ALAT, ASAT), as well as of one major hepatic pro-inflammatory transcription factor (NFκB: p105 mRNA and p65 protein). These findings support that nutritional doses of curcumin contained in Curcuma longa extract are able to partially counteract the risperidone-induced metabolic dysfunction in mice, suggesting that curcumin ought to be tested to reduce the capacity of risperidone to induce the metabolic syndrome in human.

Efficacy and safety of bevacizumab-containing neoadjuvant therapy followed by interval debulking surgery in advanced ovarian cancer: Results from the ANTHALYA trial.

AIM: To investigate whether adding bevacizumab to neoadjuvant carboplatin-paclitaxel (CP) helps achieve optimal debulking, measured by complete resection rate (CRR) at interval debulking surgery (IDS), in patients with initially unresectable International Federation of Gynecology and Obstetrics stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma. METHODS: Multicentre, open-label, non-comparative phase II study. Ninety-five patients randomised (2:1) to receive four cycles of neoadjuvant CP ±3 concomitant cycles of bevacizumab 15 mg/kg (BCP) followed by IDS. Primary objective is to evaluate the CRR at IDS in the BCP group (reference CRR rate defined as 45% CRR). A stopping rule based on bevacizumab-related adverse events (AEs) of special interest was implemented. RESULTS: In the BCP group (N = 58), IDS was performed in 40 (69%) patients, of whom 85% had a complete resection. The CRR of this group was therefore 58.6% (34 patients), statistically over pre-defined 45%. The CRR in the CP group was 51.4%: 22 (60%) patients underwent IDS (85% had a complete resection). Grade ≥3 adverse events occurred in 62% of the BCP-treated patients and 63% of the CP-treated patients: mainly blood and lymphatic, gastrointestinal and vascular disorders, without more toxicity with BCP. Postoperative complications (mainly wound, infectious and gastrointestinal complications) occurred in 28% and 36% of the patients, respectively. The pre-specified safety stopping rule was not reached. CONCLUSION: The primary objective was met as the CRR with BCP was significantly higher than the reference rate. Bevacizumab may be safely added to a preoperative program in patients deemed non-optimally resectable, whatever the final surgical decision. Bevacizumab's role in this setting should be further investigated.

Associations of IGF-1 gene variants and milk protein intake with IGF-I concentrations in infants at age 6 months - results from a randomized clinical trial.

OBJECTIVE: The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied. DESIGN: European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow's milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6 g/100 mL) or higher (HP: 2.05 and 3.2 g/100 mL) protein contents for the first 12 months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6 months were regressed on determined SNPs and feeding groups in 501 infants. RESULTS: IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3 ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3 ng/mL and ~1.3 and decreased in BF infants by ~0.6 ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450 ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing. CONCLUSIONS: Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth.

Methodological approaches for dietary intake assessment in formula-fed infants.

BACKGROUND AND OBJECTIVE: The estimation of dietary intake remains a challenge in human nutritional studies. In infants, the use of food diaries (FDs) is a suitable method already validated; however, this method is not exempt from error. In formula-fed infants, dilution of powdered formulas may produce errors. Our aim was to develop and validate standard operating procedures (SOPs) for the assessment of dietary intake in formula-fed infants, attending potential sources of error. METHODS: We analysed sources of error in a random subsample of 3-day FDs from 100 infants enrolled in the European Childhood Obesity Project. Calculations to estimate intakes were standardised and included in a software tool (SOPsystem). An evaluation of a simulated FD was performed by 9 trained nutritionists and 23 nutrition students (n=225 and n=575 bottle evaluations, respectively) to compare the results obtained when using or not the SOPsystem. Correct answers (%), coefficients of variation, and the time spent (minutes) to assess the simulated FD were analysed. RESULTS: Overall, 60% of the FDs contained reports of incorrect volumes, and 37% reported incorrect formula dilutions. When the SOPsystem was used, correct answers in the simulated FD were more frequent (P<0.001) and the mean coefficient of variation and the time spent were lower (P<0.005 and P<0.01, respectively). CONCLUSIONS: The development and implementation of SOPs with a software tool that identifies specific sources of error in record-keeping achieved a harmonised and improved process for assessing dietary intakes in formula-fed infants, minimising errors in calculations and reducing the work time invested.

Introduction of potentially allergenic foods in the infant's diet during the first year of life in five European countries.

BACKGROUND: Little information is available on infants' age at first introduction of potentially allergenic foods as part of complementary feeding. We aimed to analyze age at the introduction of potentially allergenic foods in healthy term infants relative to recommendations in 5 European countries. METHOD: Recruitment was conducted from October 2002 to June 2004. A total of 1,678 infants [588 breastfed (BF) and 1,090 formula-fed (FF) infants] were studied. In 1,368 infants, at least one 3-day weighed food diary at the age of 1-9 and 12 completed months was available. RESULTS: Six percent of BF infants and 13% of FF infants consumed some potentially allergenic food already prior to the recommended minimum age of 4 months, and 4% of BF infants and 11% of FF infants had already received gluten. There were significant differences in the timing of the introduction of potentially allergenic foods between the countries at the age of 4-6 months (p < 0.001). CONCLUSION: The time of first introduction of potentially allergenic foods in infants differed significantly between countries, and they were introduced much earlier than recommended in some countries. FF infants received potentially allergenic foods earlier than BF infants. Better information and counseling of parents is desirable.

Overweight induced by chronic risperidone exposure is correlated with overexpression of the SREBP-1c and FAS genes in mouse liver.

Weight gain and metabolic disturbances, such as dyslipidemia and hyperglycaemia, are common side effects of most antipsychotic drugs, including risperidone. The aim of this study was to investigate the effects of chronic treatment with risperidone on body weight, fat accumulation, liver weight, and hepatic expression of key genes involved in lipid metabolism in female mice. We also addressed the mechanism of risperidone induction of metabolic side effects by exploring its effect on lipid and cholesterol metabolism in primary cultures of rat hepatocytes. Eleven weeks of treatment with long-acting risperidone (12.5 mpk/week) resulted in a significant weight gain associated with an increase of liver and adipose tissue weight. These effects were positively correlated with hepatic mRNA induction of two key genes involved in lipogenesis: sterol regulatory element binding protein-1c (SREBP-1c) and fatty acid synthase (FAS). Furthermore, in line with these in vivo results, risperidone elicited significant inductions of SREBP-1 maturation and FAS mRNA expression in primary cultures of rat hepatocytes associated with an increase of free fatty acid, triacylglycerol, and phospholipid synthesis as assessed by acetate incorporation. The current investigations underscore the usefulness of a mouse model to study the weight gain observed with risperidone treatment in humans. This study shows that risperidone induces similar effects in the liver (in vivo) and in hepatocyte cell cultures (in vitro) on the expression of key genes and/or proteins that control lipid metabolism. This suggests that risperidone could alter lipid metabolism in the liver and induce weight gain in a way that is partly independent of its action on the central nervous system.

Methodology for longitudinal assessment of nutrient intake and dietary habits in early childhood in a transnational multicenter study.

OBJECTIVES: The aim of this study was to describe developed methods for repeated longitudinal assessment of feeding habits and nutrient intakes of children in a multicenter trial in different European countries and to assess feasibility. PATIENTS AND METHODS: Nutrient intake and dietary habits of formula-fed and breast-fed infants were assessed in 5 European countries (Belgium, Germany, Italy, Poland, and Spain). Prospective age-adapted 3-day weighed food records were used from birth to 2 years of age (1, 2, 3, 4, 5, 6, 7, 8, 9, 12, 18, and 24 months). Standard operating procedures were developed to check each day's food record for quality. Dietitians were trained by using standardized food records. Data entry and nutrient analyses were performed with a dedicated software developed for this project. RESULTS: Of 1368 study participants, at least one 3-day food record was available; of 25,367 1-day food records, data on quality could be evaluated. Overall, between 81% and 97% (depending on the country) of the food records had been completed with high accuracy. The implementation of solid foods and regular family foods decreased the recording quality significantly during the 2-year time course (P < 0.001). The standardized training shows coefficients of variation up to a maximum of about 41%, indicating differences in data entry. CONCLUSIONS: The experiences gathered indicate that collecting dietary and behavioral data in a large number of infants from different cultures is a challenging but feasible task in which permanent supervision and training is vital. However, we conclude that the established methodology is suitable to obtain valuable results on current infant nutrition practice in Europe.

Intake of energy providing liquids during the first year of life in five European countries.

BACKGROUND: Intake of energy providing liquids (EPL) other than breast milk or formula to infants is discouraged because it may displace milk intake. Data on actual practice is lacking. AIM: To describe the current practice of EPL supply to infants in five European countries. METHOD: Breastfed (BF) infants and infants fed using two formulae (FF) with different protein content were recruited from October 2002 to June 2004. Three-day weighed food protocols of 1368 infants were obtained monthly at the ages of 1 to 9 and again at 12 completed months. RESULTS: At the age of 4 months, 13% of BF and 43% of FF infants received EPL. FF infants started EPL earlier (median 17 weeks) than BF infants (median 30 weeks). EPL intake was associated with a lower intake of formula milk and solids (kcal/d) in the first year of life. Multiple regression analysis showed significant differences in EPL introduction between the individual countries. CONCLUSION: In contrast to recommendations, EPL is frequently given during the first months of life to breastfed and particularly to formula fed infants. Infants given EPL showed lower intakes of infant formula and solids. Caregivers should receive better counselling on appropriate infant feeding.

Introduction of complementary feeding in 5 European countries.

OBJECTIVES: Little is known about the practice of introducing complementary feeding across Europe. We aim at describing times of solid introduction in healthy infants in 5 European countries. MATERIALS AND METHODS: Between October 2002 and June 2004, 1678 healthy term infants were either breast-fed (BF) for at least 4 months (n = 588) or study formula-fed (FF) (n = 1090) with different protein contents. Three-day-weighed food protocols were obtained at ages 1, 2, 3, 4, 5, 6, 7, 8, 9, and 12 completed months. RESULTS: Solids were introduced earlier in FF infants (median 19 weeks, interquartile range 17-21) than BF infants (median 21 weeks, interquartile range 19-24). Some 37.2% of FF infants and 17.2% of BF infants received solid foods at 4 completed months, which is earlier than recommended in Europe. Solids had been introduced at 7 completed months in 99.3% of FF infants and 97.7% of BF infants, respectively. Belgium had the highest percentage of solids feeding in FF infants at 3 (15.8%) and 4 (55.6%) completed months, and in BF infants at 4 (43%) and 5 (84.8%) completed months. Multiple regression showed low maternal age, low education level, and maternal smoking to predictors an early introduction of solids at 3 and 4 completed months. CONCLUSIONS: Complementary feeding is introduced earlier than recommended in a sizeable number of infants, particularly among FF infants. Country- and population-specific approaches to adequately inform parents should be explored.