Intermittent hypoxia in a mouse model of apnea of prematurity leads to a retardation of cerebellar development and long-term functional deficits.

BACKGROUND: Apnea of prematurity (AOP) is caused by respiratory control immaturity and affects nearly 50% of premature newborns. This pathology induces perinatal intermittent hypoxia (IH), which leads to neurodevelopmental disorders. The impact on the brain has been well investigated. However, despite its functional importance and immaturity at birth, the involvement of the cerebellum remains poorly understood. Therefore, this study aims to identify the effects of IH on cerebellar development using a mouse model of AOP consisting of repeated 2-min cycles of hypoxia and reoxygenation over 6 h and for 10 days starting on postnatal day 2 (P2). RESULTS: At P12, IH-mice cerebella present higher oxidative stress associated with delayed maturation of the cerebellar cortex and decreased dendritic arborization of Purkinje cells. Moreover, mice present with growth retardation and motor disorders. In response to hypoxia, the developing cerebellum triggers compensatory mechanisms resulting in the unaltered organization of the cortical layers from P21 onwards. Nevertheless, some abnormalities remain in adult Purkinje cells, such as the dendritic densification, the increase in afferent innervation, and axon hypomyelination. Moreover, this compensation seems insufficient to allow locomotor recovery because adult mice still show motor impairment and significant disorders in spatial learning. CONCLUSIONS: All these findings indicate that the cerebellum is a target of intermittent hypoxia through alterations of developmental mechanisms leading to long-term functional deficits. Thus, the cerebellum could contribute, like others brain structures, to explaining the pathophysiology of AOP.

Short communication: Effects of in-ovo injection of endocrine disruptors and methyltransferase inhibitor on quail growth and egg-laying performances.

Early experiences, including prenatal environment, are known to influence a wide variety of mechanisms involved in the phenotype elaboration. We investigated the effect of the addition of endocrine disruptors or of a methyltransferase inhibitor during the embryonic development of quails from different genetic backgrounds (four different quail lines) on their growth and egg-laying performances. Fifty-four pairs of parents per line were used and fertilised eggs from each pair were randomly divided into five groups: a control group without any injection, an injected control group treated by injection into the egg of sesame oil, and three groups treated by injection of Genistein, Bisphenol A or 5-Aza-2'-deoxycytidine. All quails were individually weighed at 8, 21, 36 and 78 days. The age at first egg laid and the number of eggs laid were recorded. These analyses revealed a significant impact of the treatment on growth but no influence on the egg-laying traits. All three molecules significantly affected at least one of the analysed growth traits. In conclusion, we showed that the injection of endocrine disruptors or DNA methyltransferase inhibitor into the egg had significant effects on quail development; these effects were specific to each treatment, but no interaction between line and treatment was observed.

Population pharmacokinetics of ceftazidime in critically ill children: impact of cystic fibrosis.

BACKGROUND: Pharmacokinetics data on ceftazidime are sparse for the paediatric population, particularly for children with cystic fibrosis (CF) or severe infections. OBJECTIVES: To characterize the population pharmacokinetics of ceftazidime in critically ill children, identify covariates that affect drug disposition and evaluate the current dosing regimens. METHODS: The study was registered with Clinicaltrials.gov (NCT01344512). Children receiving ceftazidime were selected in 13 French hospitals. Plasma concentrations were determined by UPLC-MS/MS. Population pharmacokinetic analyses were performed using NONMEN software. RESULTS: One hundred and eight patients, aged 28 days to 12 years, with CF (n = 32), haematology and/or oncology disorders (n = 47) or severe infection (n = 29) were included. Ceftazidime was administered by continuous or intermittent infusions; 271 samples were available for analysis. A two-compartment model with first-order elimination and allometric scaling was developed and covariate analysis showed that ceftazidime pharmacokinetics were also significantly affected by CLCR and CF. Ceftazidime clearance was 82% higher in CF than in non-CF patients. Monte Carlo simulations showed that the percentage of target attainment (PTA) for the target of T>MIC = 65% was (i) lower in CF than in non-CF children with intermittent infusions and (ii) higher with continuous than intermittent infusion in all children. CONCLUSIONS: The population pharmacokinetics model for ceftazidime in children was influenced by body weight, CLCR and CF. A higher PTA was obtained with continuous versus intermittent infusions. Further studies should explore the benefits of continuous versus intermittent infusion of ceftazidime, including current versus increased doses in CF children.

Chicken adaptive response to low energy diet: main role of the hypothalamic lipid metabolism revealed by a phenotypic and multi-tissue transcriptomic approach.

BACKGROUND: Production conditions of layer chicken can vary in terms of temperature or diet energy content compared to the controlled environment where pure-bred selection is undertaken. The aim of this study was to better understand the long-term effects of a 15%-energy depleted diet on egg-production, energy homeostasis and metabolism via a multi-tissue transcriptomic analysis. Study was designed to compare effects of the nutritional intervention in two layer chicken lines divergently selected for residual feed intake. RESULTS: Chicken adapted to the diet in terms of production by significantly increasing their feed intake and decreasing their body weight and body fat composition, while their egg production was unchanged. No significant interaction was observed between diet and line for the production traits. The low energy diet had no effect on adipose tissue and liver transcriptomes. By contrast, the nutritional challenge affected the blood transcriptome and, more severely, the hypothalamus transcriptome which displayed 2700 differentially expressed genes. In this tissue, the low-energy diet lead to an over-expression of genes related to endocannabinoid signaling (CN1R, NAPE-PLD) and to the complement system, a part of the immune system, both known to regulate feed intake. Both mechanisms are associated to genes related polyunsaturated fatty acids synthesis (FADS1, ELOVL5 and FADS2), like the arachidonic acid, a precursor of anandamide, a key endocannabinoid, and of prostaglandins, that mediate the regulatory effects of the complement system. A possible regulatory role of NR1H3 (alias LXRα) has been associated to these transcriptional changes. The low-energy diet further affected brain plasticity-related genes involved in the cholesterol synthesis and in the synaptic activity, revealing a link between nutrition and brain plasticity. It upregulated genes related to protein synthesis, mitochondrial oxidative phosphorylation and fatty acid oxidation in the hypothalamus, suggesting reorganization in nutrient utilization and biological synthesis in this brain area. CONCLUSIONS: We observed a complex transcriptome modulation in the hypothalamus of chicken in response to low-energy diet suggesting numerous changes in synaptic plasticity, endocannabinoid regulation, neurotransmission, lipid metabolism, mitochondrial activity and protein synthesis. This global transcriptomic reprogramming could explain the adaptive behavioral response (i.e. increase of feed intake) of the animals to the low-energy content of the diet.

Variability of ciprofloxacin pharmacokinetics in children: impact on dose range in sickle cell patients.

Objectives: To determine the ciprofloxacin population pharmacokinetics in paediatric patients and the impact of underlying disease and evaluate the appropriateness of current dosage regimens. Patients and methods: Plasma concentrations of ciprofloxacin from children treated with ciprofloxacin were measured by HPLC. The pharmacokinetic population analysis was performed using NONMEM v7.2 (Icon Development Solutions, USA). Results: Two datasets were combined and 128 plasma concentrations in 60 patients aged 5.6 years (range 0.3-18.9), treated with a median daily dose of 30.0 mg/kg (range 6.5-52.0) presenting with sickle cell disease (SCD; n = 20, 33%), haemopathy (n = 15, 25%), cystic fibrosis (CF; n = 3, 5%) and other diseases (n  =  22, 37%) were analysed. Data were best described by a two-compartment model with first-order elimination. Ciprofloxacin clearance (mean ±â€Šâ€ŠSD) was 0.81 ±â€Š0.30 L/h/kg, increased allometrically with weight, decreased with increasing creatinine concentration, was 89% higher in SCD compared with non-SCD patients and increased by 0.95 L/h/kg per year of age. The volume of distribution was 6.9 L/kg and depended only on the weight. Monte Carlo simulations were performed separately in SCD and non-SCD patients to target an AUC/MIC ratio >125 at steady-state, required for antibacterial efficacy, and recommendations of dosing regimens were proposed. Conclusions: In addition to known covariates, ciprofloxacin clearance is greater in SCD children compared with non-SCD patients. The dosing of this agent needs to be adapted to this subgroup of patients.

Pharmacokinetics and safety of fluconazole and micafungin in neonates with systemic candidiasis: a randomized, open-label clinical trial.

AIMS: The pharmacokinetics (PK) of fluconazole and micafungin differ in neonates compared with children and adults. Dosing instructions in product labels appear to be inconsistent with the emerging scientific evidence. Limited information is available on the safety profile of these agents in neonates. Our objective was to study the population PK and safety of both drugs, randomly administered in neonates with suspected or confirmed systemic candidiasis. METHODS: Neonates were randomized 1:1 to fluconazole (loading dose 25 mg kg-1 ; maintenance dose 12 mg kg-1 day-1 or 20 mg kg-1 day-1 , respectively, for infants <30 weeks or ≥30 weeks' corrected gestational age) or micafungin (loading dose 15 mg kg-1 day-1 ; maintenance dose 10 mg kg-1 day-1 ). PK samples were taken on treatment days 1 and 5. Population parameters were determined using NONMEM and Monte Carlo simulations performed to reach predefined targets. Clinical and laboratory data, and adverse events were collected up to 36 weeks' corrected gestational age or hospital discharge. RESULTS: Thirty-six neonates were enrolled. The median (range) gestational age was 28.2 (24.1-40.1) and 26.8 (23.5-40.0) weeks for fluconazole and micafungin, respectively. Based on 163 PK samples, the median population clearance (l h-1 kg-1 ) and volume of distribution (l kg-1 ) for fluconazole were: 0.015 [95% confidence interval (CI) 0.008, 0.039] and 0.913, and for micafungin were: 0.020 (95% CI 0.010, 0.023) and 0.354 (95% CI 0.225, 0.482), respectively. The loading dose was well tolerated. No adverse events associated with micafungin or fluconazole were reported. CONCLUSION: Based on Monte Carlo simulations, a loading dose for fluconazole and dosing higher than recommended for both drugs are required to increase the area under the plasma drug concentration-time curve target attainment rate in neonates.

[Infants living with their mothers in the Rennes, France, prison for women between 1998 and 2013. Facts and perspectives]. / Les nourrissons vivant auprès de leur mère incarcérée au centre pénitentiaire des femmes de Rennes entre 1998 et 2013. Constats et perspectives.

Every year in France, nearly 50 infants live in a prison nursery with their mother. According to French law, infants can live with their mother in the prison nursery until they reach 18 months of age. The international community is concerned about the lack of validated social, medical and legal data on these infants living in prison. This was a retrospective and descriptive study. Medical and paramedical files of the General Council of Île-et-Vilaine, France, were studied. Every infant born between 1998 and 2013 while their mother was in prison were included. Fifty-four files were collected. The average length of stay was 6.2 months (n=54). The type of the mother's prison sentence was property damage in 40 % of cases, personal injury in 51.1 % of cases and both in 8.9 % of cases (n=45). The length of the mother's imprisonment was on average 45 months, ranging from 3 to 216 months (n=34). After prison, 42.9 % of the infants were placed in foster care and 57.1 % resided with their family (n=42). This child-mother incarceration could be an opportunity for positive intergenerational paramedical, medical and social services. The lack of data and problems collecting data restrict our knowledge of these families. This should motivate a national follow-up for these children.

[Maternal deaths related to social vulnerabilities. Results from the French confidential enquiry into maternal deaths, 2010-2012]. / Mortalité maternelle chez les femmes en situation de précarité. Résultats de l'ENCMM, France 2010­2012.

The theme of deprivation is new for the ENCMM. In view of the perceived increase in the number of maternal deaths that may be related to a deprivation situation, we sought to understand the main dimensions that could contribute to maternal death in this context, in order to propose a definition. The selection of cases made a posteriori is mainly based on a qualitative judgment. Between 2010 and 2012, among the deaths evaluated by the CNEMM, one or more elements related to social vulnerability were identified in 8.6% of the cases (18 deaths). The direct criteria used were the concepts of "deprivation" or "social difficulties", difficulties of housing, language barriers and isolation. The absence of prenatal care was retained as an indirect marker. We excluded cases where psychiatric pathology and/or addiction were predominant. Of the 18 cases identified with deprivation factors, death was considered "unavoidable" in 2 cases (11%), "certainly avoidable" or "possibly avoidable" in 13 cases (72%). In 3 cases (17%), avoidability could not be determined. Avoidability was related to the content and adequacy of care in 11 cases out of 13 (85%) and the patient's interaction with the health care system in 10 of 18 cases (56%). The analysis of maternal deaths among women in precarious situations points out that the link between socio-economic deprivation and poor maternal health outcomes potentially includes a specific risk of maternal death.

Medical table: A major tool for antimicrobial stewardship policy.

Infectious diseases are unpredictable, with heterogeneous clinical presentations, diverse pathogens, and various susceptibility rates to anti-infective agents. These features lead to a wide variety of clinical practices, which in turn strongly limits their evaluation. We have been using a medical table since 2005 to monitor the medical activity in our department. The observation of heterogeneous therapeutic practices led to drafting up our own antibiotic guidelines and to implementing a continuous evaluation of their observance and impact on morbidity and mortality associated with infectious diseases, including adverse effects of antibiotics, duration of hospital stay, use of intensive care, and deaths. The 10-year analysis of medical practices using the medical table is based on more than 10,000 hospitalizations. It shows simplified antibiotic therapies and a reduction in infection-related morbidity and mortality. The medical table is a major tool for antimicrobial stewardship, leading to constant benefits for patients.

Whole body-element composition of Atlantic salmon Salmo salar influenced by migration direction and life stage in three distinct populations.

Body-element content was measured for three life stages of wild Atlantic salmon Salmo salar from three distinct Newfoundland populations as individuals crossed between freshwater and marine ecosystems. Life stage explained most of the variation in observed body-element concentration whereas river of capture explained very little variation. Element composition of downstream migrating post-spawn adults (i.e. kelts) and juvenile smolts were similar and the composition of these two life stages strongly differed from adults migrating upstream to spawn. Low variation within life stages and across populations suggests that S. salar may exert rheostatic control of their body-element composition. Additionally, observed differences in trace element concentration between adults and other life stages were probably driven by the high carbon concentration in adults because abundant elements, such as carbon, can strongly influence the observed concentrations of less abundant elements. Thus, understanding variation among individuals in trace elements composition requires the measurement of more abundant elements. Changes in element concentration with ontogeny have important consequences the role of fishes in ecosystem nutrient cycling and should receive further attention.

[Dosing regimens of antibiotics in neonates: Variations in clinical practice and what should be done?]. / Posologie des antibiotiques chez le nouveau-né : variations des pratiques et comment y remédier ?

There is wide variation in neonatal dosages of antibiotics in clinical practice, both nationally and internationally. This reflects the lack of evaluation of drugs in this therapeutic class, although widely prescribed. Given this situation, optimization of antibiotic prescription is required to ensure efficacy and safety of neonatal treatment and reduce microbial resistance. Rational prescription should be based on the knowledge of developmental pharmacokinetics and pharmacodynamics. Rigorous studies, conducted in collaboration between neonatologists and pharmacologists, are essential to develop and validate evidence-based neonatal dosage regimens.

[Single procedure treatment of complex nephrolithiasis: about a modern series of anatrophic nephrolithotomy]. / Traitement en un temps de la lithiase rénale complexe : à propos d'une série moderne de néphrotomies bivalves.

PURPOSE: Advances in endourology have significantly reduced indications of open surgery in the treatment of staghorn calculi. However, in our experience, open surgery is still the treatment of choice in some cases. This study presents the results of a series of selected patients and discusses the results in terms of efficacy and morbidity. MATERIALS: A cohort of 26 patients underwent anatrophic nephrolithotomy by lombotomy to treat a complex staghorn calculus. RESULTS: The mean stone size was 68,5mm, 70% were complete staghorn calculi. The operative time was 100minutes. Blood loss was 225mL, with a postoperative transfusion rate of 15.4%. The hospital stay was 8.4 days. The stone free rate following the procedure was 92%. The creatinine clearance (MDRD) at 3 months was improved from 5.9mL/min/m(2) on average over the entire series. CONCLUSION: There are clearly still indications for open surgery in staghorn stones management, with good results in this contemporary series on both stone removal and nephronic preservation. Yet, it appears that this technique is no longer taught. LEVEL OF EVIDENCE: 5.

[Hurler syndrome: early diagnosis and treatment]. / Syndrome de Hurler : diagnostic et prise en charge précoces.

Hurler syndrome, the most severe form of mucopolysaccharidosis type I (MPS I), is a rare lysosomal storage disease. The overall incidence of MPS I is 0.99-1.99/100,000 live births. Accumulation of glycosaminoglycans causes the progressive dysfunction of multiple organs. We report the case of a 3-week-old newborn who was hospitalized in the Neonatal Intensive Care Unit for feeding problems. Coarse facial features and gingival hypertrophy, associated with axial hypotonia, upper airway obstruction, and moderate hepatomegaly, led to the early diagnosis of MPS I at 3 weeks of age and was confirmed by an abnormally elevated amount of dermatan and heparan sulphate in the urine and complete deficiency of alpha-L-iduronidase lysosomal enzyme activity. The child was homozygous for the p.W402X mutation, located on chromosome 4p16.3 of the alpha-L-iduronidase (IDUA) gene. The clinical condition gradually deteriorated until the age of 4 months, with thoracic and lumbar dysostoses, glaucoma, cerebral ventricular dilatation and cervical spinal stenosis, dilated cardiomyopathy, and umbilical hernia. Early diagnosis allowed enzyme replacement therapy (iaronidase, Aldurazyme(®), Genzyme) started at the age of 5 months, which provided stabilization of the heart disease, significant regression of rhinologic symptoms, and regression of hepatomegaly. Cord blood hematopoietic stem cell transplantation was performed at 11 months of age, allowing optimal preservation of cognitive development.

Management and diagnostic guidelines for fungal diseases in infectious diseases and clinical microbiology: critical appraisal.

Invasive fungal infections (IFIs) are life-threatening conditions that require rapid diagnostic and optimal management to mitigate their high morbidity and mortality rate. They are also associated with a high economic burden, owing to prolonged hospitalization, the need for intensive supportive care, and the consumption of costly new antifungal agents. To address these issues, several international organizations have proposed guidelines for the management of IFIs. The consistency and reliability of these guidelines have rarely been assessed. This article is a review of the differences between the recommendations of the Infectious Diseases Society of America, the European Conference on Infection in Leukaemia, and the European Society of Clinical Microbiology and Infectious Diseases, and will focus on targeted treatment and diagnostic procedures. Although the conclusions of the three groups of experts are in many points similar we outlined some important differences in the methodology and conclusions of ESCMID. The use of these guidelines has the potential to enhance the management of fungal infections but is probably currently suboptimal.

A mutation in the promoter of the chicken ß,ß-carotene 15,15'-monooxygenase 1 gene alters xanthophyll metabolism through a selective effect on its mRNA abundance in the breast muscle.

A polymorphism in the promoter of the ß,ß-carotene 15,15'-monooxygenase 1 (BCMO1) gene recently was identified in an experimental cross between 2 chicken lines divergently selected on growth rate and found to be associated with variations in the yellow color of the breast meat. In this study, the effects of the polymorphism on several aspects of carotenoid metabolism were evaluated in chickens sharing the same genetic background except for their genotype at the BCMO1 locus. We confirmed that BCMO1 mRNA abundance varied (P < 0.001) between the 2 homozygous genotypes (GG << AA) and in the pectoralis major muscle. By contrast, BCMO1 mRNA expression was not affected (P > 0.05) by the polymorphism in the duodenum, liver, or sartorius muscle. The breast meat of GG chickens was more (P < 0.001) yellow and richer in lutein (P < 0.01) and zeaxanthin (P < 0.05) compared to that of AA chickens whereas these variables did not differ (P > 0.05) in the other tissues tested. The GG were also characterized by reduced (P < 0.01) plasma lutein and zeaxanthin concentrations than AA without affecting plasma and tissue content of fat-soluble vitamins A and E. As lutein and zeaxanthin are usually not considered as substrates of the BCMO1 enzyme, the impact of BCMO1 polymorphism on the activity of other genes involved in carotenoid transport (SCARB1 and CD36 encoding the scavenger receptor class B type I and the cluster determinant 36, respectively) and metabolism (BCDO2 encoding ß,ß-carotene 9',10'-dioxygenase 2) was evaluated. The BCMO1 polymorphism did not affect mRNA abundance of BCDO2, SCARB1, or CD36, regardless of tissue considered. Taken together, these results indicated that a genetic variant of BCMO1 specifically changes lutein and zeaxanthin content in the chicken plasma and breast muscle without impairing vitamin A and E metabolism.

[Computerized management of a medical department, disease-related group management, clinical research and evaluations]. / Gestion de services, tarification à l'activité, recherche clinique et évaluation des pratiques professionnelles: un même outil informatique.

The current French hospital reform is based on the disease-related group (DRG) approach and the constitution of bigger units pooling several departments of different specialties. This reform needed an efficient assessment of various medical activities. We report our experience of a medical table of our hospital activities used for 27 months. This medical table was made with a basic software integrating 24 parameters. The original concept was the translation of the specific final diagnosis for DRG defined by the site of infection. To create this medical table, we first simplified the conclusions of the patient's chart using a consensual and systematic plan. The number of patients per DRG and their evolution were therefore specifically determined. The medical table helped us in the daily management of our department, to identify the area of recruitment, the potential for heterogeneous care, allowing the implementation of protocols and their applications. Moreover, the table quantified morbidity and mortality, indicating our need for cooperation with other departments. All this data used medical-lexical terms, allowing other than economic analyses, even if this table identifies hospitalization-related costs, namely duration of hospital-stay, nosocomial infections and iatrogenic events. Finally, our table supports medical research and evaluation of practice. Our future goals are to introduce this table in several infectious-diseases units, and create specific tables for the main RDG, including economic parameters.

Incidence of histomonosis in turkeys in France since the bans of dimetridazole and nifursol.

Between April 2003 and March 2005, 113 outbreaks of histomonosis were recorded in standard turkey farms in France, and 15 cases were recorded in turkey breeding centres. Most of the cases were in north-west France, the principal farming area for turkeys. The majority of the cases occurred during the hottest months, from April to September. Large numbers of cases occurred among birds from four to eight weeks of age, but there were some cases in three-week-old birds and some in birds up to 17 weeks of age. In most of the standard turkey flocks the mortality was less than 10 per cent, but it was above 30 per cent in nearly 20 per cent of the outbreaks. In the breeding flocks, the average mortality was 60.2 per cent. The size of the flocks, the sex of the birds and the age at which the first clinical signs appeared did not seem to influence the mortality.

The chicken RH map: current state of progress and microchromosome mapping.

The ChickRH6 radiation hybrid panel has been used to construct consensus chromosome radiation hybrid (RH) maps of the chicken genome. Markers genotyped were either from throughout the genome or targeted to specific chromosomes and a large proportion (one third) of data was the result of collaborative efforts. Altogether, 2,531 markers were genotyped, allowing the construction of RH reference maps for 20 chromosomes and linkage groups for four other chromosomes. Amongst the markers, 581 belong to the framework maps, while 1,721 are on the comprehensive maps. Around 800 markers still have to be assigned to linkage groups. Our attempt to assign the supercontigs from the chrun (virtual chromosome containing all the genome sequence that could not be attributed to a chromosome) as well as EST (Expressed Sequence Tag) contigs that do not have a BLAST hit in the genome assembly led to the construction of new maps for microchromosomes either absent or for which very little data is present in the genome assembly. RH data is presented through our ChickRH webserver (http://chickrh.toulouse.inra.fr/), which is a mapping tool as well as the official repository RH database for genotypes. It also displays the RH reference maps and comparison charts with the sequence thus highlighting the possible discrepancies. Future improvements of the RH maps include complete coverage of the sequence assigned to chromosomes, further mapping of the chrun and mapping of EST contigs absent from the assembly. This will help finish the mapping of the smallest gene-rich microchromosomes.

Effects of early high-dose levothyroxine treatment on auditory brain event-related potentials at school entry in children with congenital hypothyroidism.

AIMS: We tested whether brain event-related potentials (ERPs) are normal in children with congenital hypothyroidism (CH) after early high-dose levothyroxine treatment. METHODS: Auditory ERPs were recorded in 33 normal controls and in 15 children with CH at 5 years 9/12. Based on bone maturation at diagnosis, the CH group was divided into severe (n = 8) and moderate (n = 7) subgroups. CH patients were treated at a median age of 14 days with a mean initial dose of levothyroxine of 11.6 microg/kgxday. Two ERP components (N100 and N200) were measured and clinical follow-up variables collected. RESULTS: The functional anatomical and cognitive organisation of the auditory system, as revealed by the analyses of ERP measures, did not differ between CH and controls, or between severe and moderate CH subjects. However, N200 latency was globally longer in the CH than in the control group (p = 0.01) and was positively correlated with the over-treatment index (r = 0.61; p < 0.05) and verbal IQ. N200 amplitude was negatively correlated with initial dose (r = -0.74; p < 0.005). CONCLUSION: These data suggest that sensitive tools such as ERPs can reveal differences between CH and controls and relate these differences to the adequacy of treatment of CH.

A genome scan with AFLP markers to detect fearfulness-related QTLs in Japanese quail.

A quantitative trait loci (QTL) study was undertaken to identify genome regions involved in the control of fearfulness in Japanese quail (Coturnix japonica). An F2 cross was made between two quail lines divergently selected over 29 generations on duration of tonic immobility (DTI), a catatonic-like state of reduced responsiveness to a stressful stimulation. A total of 1065 animals were measured for the logarithm of DTI (LOGTI), the number of inductions (NI) necessary to induce the immobility reaction, open-field behaviour including locomotor activity (MOVE), latency before first movement (LAT), number of jumps (JUMP), dejections (DEJ) and shouts (SHOUT), corticosterone level after a contention stress (LOGCORT) and body weight at 2 weeks of age (BW2). A total of 310 animals were included in a genome scan using selective genotyping with 248 AFLP markers. A total of 21 suggestive or genome-wide significant QTL were observed. Two highly significant QTL were identified on linkage group 1 (GL1), one for LOGTI and one for NI. In the vicinity of the QTL for LOGTI, a nearly significant QTL for SHOUT and a suggestive QTL for LAT were also identified. On GL3, genome-wide significant QTL were observed for JUMP and DEJ as well as suggestive QTL for LOGTI, MOVE, SHOUT and LAT. A significant QTL for BW2 was observed on GL2 and a nearly significant one on GL1. These results may be useful in the understanding of fearfulness in quail and related species provided that fearfulness has the same genetic basis.