Objective: To investigate whether delivery mode (vaginal versus by caesarean section), maternal pre-pregnancy body mass index (BMI) and early exposure to antibiotics (o6 months of age) influence child's risk of overweight at age 7 years, hence supporting the hypotheses that environmental factors influencing the establishment and diversity of the gut microbiota are associated with later risk of overweight. Design: Longitudinal, prospective study with measure of exposures in infancy and follow-up at age 7 years. Methods: A total of 28 354 mother-child dyads from the Danish National Birth Cohort, with information on maternal prepregnancy BMI, delivery mode and antibiotic administration in infancy, were assessed. Logistic regression analyses were performed with childhood height and weight at the 7-year follow-up as outcome measures. Results: Delivery mode was not significantly associated with childhood overweight (odds ratio (OR):1.18, 95% confidence interval (CI): 0.95-1.47). Antibiotics during the first 6 months of life led to increased risk of overweight among children of normal weight mothers (OR: 1.54, 95% CI: 1.09-2.17) and a decreased risk of overweight among children of overweight mothers (OR: 0.54, 95% CI: 0.30-0.98). The same tendency was observed among children of obese mothers (OR: 0.85, 95% CI: 0.41-1.76). Conclusion: The present cohort study revealed that a combination of early exposures, including delivery mode, maternal pre-pregnancy BMI and antibiotics in infancy, influences the risk of overweight in later childhood. This effect may potentially be explained by an impact on establishment and diversity of the microbiota.

No abstract

Progressive myoclonus epilepsy type 1 (EPM1, also known as Unverricht-Lundborg disease) is an autosomal recessive disorder characterized by progressively worsening myoclonic jerks, frequent generalized tonic-clonic seizures, and a slowly progressive decline in cognition. Recently, two mutations in the cystatin B gene (also known as stefin B, STFB) mapping to 21q22.3 have been implicated in the EPM1 phenotype: a G-->C substitution in the last nucleotide of intron 1 that was predicted to cause a splicing defect in one family, and a C-->T substitution that would change an Arg codon (CGA) to a stop codon (TGA) at amino acid position 68, resulting in a truncated cystatin B protein in two other families. A fourth family showed undetectable amounts of STFB mRNA by northern blot analysis in an affected individual. We present haplotype and mutational analyses of our collection of 20 unrelated EPM1 patients and families from different ethnic groups. We identify four different mutations, the most common of which consists of an unstable approximately 600-900 bp insertion which is resistant to PCR amplification. This insertion maps to a 12-bp polymorphic tandem repeat located in the 5' flanking region of the STFB gene, in the region of the promoter. The size of the insertion varies between different EPM1 chromosomes sharing a common haplotype and a common origin, suggesting some level of meiotic instability over the course of many generations. This dynamic mutation, which appears distinct from conventional trinucleotide repeat expansions, may arise via a novel mechanism related to the instability of tandemly repeated sequences.

ABSTRACT

Objective: To investigate whether a hypo-energetic low-fat diet is superior to a hypo-energetic high-fat diet for the treatment of obesity. Design: Open-label, 10-week dietary intervention comparing two hypo-energetic (À600 kcal/day) diets with a fat energy percent of 20-25 or 40-45. Subjects: Obese (BMI X30 kg/m 2 ) adult subjects (n ¼ 771), from eight European centers. Measurements: Body weight loss, dropout rates, proportion of subjects who lost more than 10% of initial body weight, blood lipid profile, insulin and glucose. Results: The dietary fat energy percent was 25% in the low-fat group and 40% in the high-fat group (mean difference: 16 (95% confidence interval (CI) 15-17)%). Average weight loss was 6.9 kg in the low-fat group and 6.6 kg in the high-fat group (mean difference: 0.3 (95% CI À0.2 to 0.8) kg). Dropout was 13.6% (n ¼ 53) in the low-fat group and 18.3% (n ¼ 70) in the high-fat group (P ¼ 0.001). Among completers, more subjects lost 410% in the low-fat group than in the high-fat group ((20.8%, n ¼ 70) versus (14.7%, n ¼ 46), P ¼ 0.02). Fasting plasma total, low-density lipoprotein-and high-density lipoprotein-cholesterol decreased in both groups, but more so in the low-fat group than in the high-fat group. Fasting plasma insulin and glucose were lowered equally by both diets. Conclusions: The low-fat diet produced similar mean weight loss as the high-fat diet, but resulted in more subjects losing 410% of initial body weight and fewer dropouts. Both diets produced favorable changes in fasting blood lipids, insulin and glucose.