Toward the Standardization of Mycological Examination of Sputum Samples in Cystic Fibrosis: Results from a French Multicenter Prospective Study.

Fungal respiratory colonization of cystic fibrosis (CF) patients emerges as a new concern; however, the heterogeneity of mycological protocols limits investigations. We first aimed at setting up an efficient standardized protocol for mycological analysis of CF sputa that was assessed during a prospective, multicenter study: "MucoFong" program (PHRC-06/1902). Sputa from 243 CF patients from seven centers in France were collected over a 15-month period and submitted to a standardized protocol based on 6 semi-selective media. After mucolytic pretreatment, sputa were plated in parallel on cycloheximide-enriched (ACT37), erythritol-enriched (ERY37), benomyl dichloran-rose bengal (BENO37) and chromogenic (CAN37) media incubated at 37 °C and on Sabouraud-chloramphenicol (SAB27) and erythritol-enriched (ERY27) media incubated at 20-27 °C. Each plate was checked twice a week during 3 weeks. Fungi were conventionally identified; time for detection of fungal growth was noted for each species. Fungal prevalences and media performances were assessed; an optimal combination of media was determined using the Chi-squared automatic interaction detector method. At least one fungal species was isolated from 81% of sputa. Candida albicans was the most prevalent species (58.8%), followed by Aspergillus fumigatus (35.4%). Cultivation on CAN37, SAB27, ACT37 and ERY27 during 16 days provided an optimal combination, detecting C. albicans, A. fumigatus, Scedosporium apiospermum complex and Exophiala spp. with sensitivities of 96.5, 98.8, 100 and 100%. Combination of these four culture media is recommended to ensure the growth of key fungal pathogens in CF respiratory specimens. The use of such consensual protocol is of major interest for merging results from future epidemiological studies.

Association of environmental markers with childhood type 1 diabetes mellitus revealed by a long questionnaire on early life exposures and lifestyle in a case-control study.

BACKGROUND: The incidence of childhood type 1 diabetes (T1D) incidence is rising in many countries, supposedly because of changing environmental factors, which are yet largely unknown. The purpose of the study was to unravel environmental markers associated with T1D. METHODS: Cases were children with T1D from the French Isis-Diab cohort. Controls were schoolmates or friends of the patients. Parents were asked to fill a 845-item questionnaire investigating the child's environment before diagnosis. The analysis took into account the matching between cases and controls. A second analysis used propensity score methods. RESULTS: We found a negative association of several lifestyle variables, gastroenteritis episodes, dental hygiene, hazelnut cocoa spread consumption, wasp and bee stings with T1D, consumption of vegetables from a farm and death of a pet by old age. CONCLUSIONS: The found statistical association of new environmental markers with T1D calls for replication in other cohorts and investigation of new environmental areas. TRIAL REGISTRATION: Clinical-Trial.gov NCT02212522 . Registered August 6, 2014.

11p15 imprinting center region 1 loss of methylation is a common and specific cause of typical Russell-Silver syndrome: clinical scoring system and epigenetic-phenotypic correlations.

CONTEXT: Russell-Silver syndrome (RSS), characterized by intrauterine and postnatal growth retardation, dysmorphic features, and frequent body asymmetry, spares cranial growth. Maternal uniparental disomy for chromosome 7 (mUPD7) is found in 5-10% of cases. We identified loss of methylation (LOM) of 11p15 Imprinting Center Region 1 (ICR1) domain (including IGF-II) as a mechanism leading to RSS. OBJECTIVE: The aim was to screen for 11p15 epimutation and mUPD7 in RSS and non-RSS small-for-gestational-age (SGA) patients and identify epigenetic-phenotypic correlations. STUDIED POPULATION AND METHODS: A total of 127 SGA patients were analyzed. Clinical diagnosis of RSS was established when the criterion of being SGA was associated with at least three of five criteria: postnatal growth retardation, relative macrocephaly, prominent forehead, body asymmetry, and feeding difficulties. Serum IGF-II was evaluated for 82 patients. RESULTS: Of the 127 SGA patients, 58 were diagnosed with RSS; 37 of these (63.8%) displayed partial LOM of the 11p15 ICR1 domain, and three (5.2%) had mUPD7. No molecular abnormalities were found in the non-RSS SGA group (n = 69). Birth weight, birth length, and postnatal body mass index (BMI) were lower in the abnormal 11p15 RSS group (ab-ICR1-RSS) than in the normal 11p15 RSS group [-3.4 vs.-2.6 SD score (SDS), -4.4 vs.-3.4 SDS, and -2.5 vs.-1.6 SDS, respectively; P < 0.05]. Among RSS patients, prominent forehead, relative macrocephaly, body asymmetry, and low BMI were significantly associated with ICR1 LOM. All ab-ICR1-RSS patients had at least four of five criteria of the scoring system. Postnatal IGF-II levels were within normal values. CONCLUSION: The 11p15 ICR1 epimutation is a major, specific cause of RSS exhibiting failure to thrive. We propose a clinical scoring system (including a BMI < -2 SDS), highly predictive of 11p15 ICR1 LOM, for the diagnosis of RSS.

An ancient protein-DNA interaction underlying metazoan sex determination.

DMRT transcription factors are deeply conserved regulators of metazoan sexual development. They share the DM DNA-binding domain, a unique intertwined double zinc-binding module followed by a C-terminal recognition helix, which binds a pseudopalindromic target DNA. Here we show that DMRT proteins use a unique binding interaction, inserting two adjacent antiparallel recognition helices into a widened DNA major groove to make base-specific contacts. Versatility in how specific base contacts are made allows human DMRT1 to use multiple DNA binding modes (tetramer, trimer and dimer). Chromatin immunoprecipitation with exonuclease treatment (ChIP-exo) indicates that multiple DNA binding modes also are used in vivo. We show that mutations affecting residues crucial for DNA recognition are associated with an intersex phenotype in flies and with male-to-female sex reversal in humans. Our results illuminate an ancient molecular interaction underlying much of metazoan sexual development.

The CEMHaVi program: control, evaluation, and modification of lifestyles in obese youth.

PURPOSE: Obesity in children has increased in recent years. Many studies with differing methodologies have been undertaken to treat obesity. The Control, Evaluation, and Modification of Lifestyles in Obese Youth (CEMHaVi) program is a unique 2-year health-wellness program of physical activity and health education for obese youth. Findings of this study represent results at 1-year follow-up. The purpose of this study was to evaluate the effects of the CEMHaVi program. METHODS: Physician-referred subjects (N = 26) participated in the study, 14 girls (13.4 +/- 2.9 years) and 12 boys (12.3 +/- 2.8 years). Measurements included height, weight, body mass index (BMI), academic performance, sleep habits, and health knowledge. The intervention consisted of a unique program of physical activity, including a variety of games specifically selected to be enjoyable, maintain interest, and motivate subjects to adhere. Activity sessions were offered once per week, 2 hours each session, for 12 months. A health education program was offered once every 3 months for 2 hours per session. Health knowledge, academic performance, self-esteem, and sleep were assessed before and after the intervention. Means were calculated at baseline and following intervention and were compared by paired t tests. RESULTS: Findings suggest significant improvements in academic performance (P < .001), quality and quantity of sleep (P < .05), and obesity (P < .05). CONCLUSIONS: The program reduced BMI and improved health knowledge, sleep, and academic performance in obese children. The feasibility of a beneficial lifestyle intervention program is encouraging in addressing obesity and related issues in young boys and girls.

Changes in lung function in young cystic fibrosis patients between two courses of intravenous antibiotics against Pseudomonas aeruginosa.

BACKGROUND AND AIMS: Repeated intravenous antibiotic therapy (IVAT) against chronic pulmonary infection with Pseudomonas aeruginosa is often necessary in cystic fibrosis patients (CF). The aim of this study was to monitor kinetics of degradation of pulmonary and nutritional status after IVAT in CF patients. METHODS: Lung function, nutritional status and physical activity (PA) were measured for 21 CF patients (mean +/- SD age, 16 +/- 1.9 years; 9 boys) who were chronically colonized by P. aeruginosa. Each parameter was measured every 15 days during 3-6 months. RESULTS: Nutritional status as well as PA did not change in the interval of 2 IVAT. In contrary, lung function worsened with a decrease of -14.6% of the FEV(1) (P < 0.05). CONCLUSION: In CF, there is a progressive decrease in lung function without any evident deterioration of nutritional status and PA between two IVAT.

Impact of intravenous antibiotic therapy on total daily energy expenditure and physical activity in cystic fibrosis children with Pseudomonas aeruginosa pulmonary exacerbation.

Resting energy expenditure (REE) increases during pulmonary exacerbation by Pseudomonas aeruginosa in cystic fibrosis (CF) patients, and decreases after i.v. anti-Pseudomonas aeruginosa antibiotic therapy (IVAT). However, the impact of IVAT on total energy expenditure (TEE) is unknown. The aim of this study was to assess the changes in TEE and its main components after IVAT administered at home. Body composition measured by skinfold thickness and bio-impedance analysis, energy intake (EI) assessed by a weekly diary, REE measured by indirect calorimetry (IC), TEE assessed by a technique using 24-h heart-rate monitoring method and physical activity (PA) monitored using an activity diary (AD) were assessed in 16 patients (9 boys and 7 girls) aged 12.1 +/- 2.3 y (range, 7.1-14.6 y), before and after 28 +/- 4 d including a 14-d IVAT course. After IVAT, weight increased significantly by 1.9% (32.1 +/- 7.5 versus 32.7 +/- 7.6 kg; p < 0.05), while fat mass and fat free mass increased non significantly. EI increased by 4.6% (10,797 +/- 3039 versus 11320 +/- 3074 kJ/d; p < 0.05). TEE was not affected by IVAT (7014 +/- 1929 versus 7081 +/- 1478 kJ/d) whereas REE decreased by 4.1% (5295 +/- 909 versus 5093 +/- 837 kJ/d; p < 0.05), resulting in 9.3% increase in PA assessed by AD converted to metabolic equivalent tasks (MET) (37.0 +/- 3.1 versus 40.7 +/- 4.5 MET; p < 0.05). The improvement in nutritional status after IVAT is not related to a decrease in TEE, but probably to an increase in EI and a decrease of REE after IVAT. After IVAT, the reduction in REE is probably compensated by an increase in PA in CF patients.