Real-world effectiveness of a German school-based intervention for primary prevention of anorexia nervosa in preadolescent girls

Objective

Anorexia nervosa (‘AN’) is notoriously difficult to treat, has high mortality rates, and has a prevalence peak in 15-year-old girls. We developed a German school-based intervention program (‘PriMa’) for the primary prevention of AN in preadolescent girls and assessed the effects in a sample of Thuringian girls.

Method

Intervention involved nine guided lessons with special posters and group discussions. A parallel controlled trial with pre-post measurements and a three-month follow-up was conducted in 92 Thuringian schools (n = 1553 girls) in 2007 and 2008. Primary outcomes were conspicuous eating behavior, body self esteem, and AN-related knowledge.

Results

After adjusting for the girls' ages and the type of school, we observed significant improvements in the areas of knowledge (d = .24) and body self esteem (d = .29), but not for eating behavior.

Conclusion

The PriMa intervention provides an efficient and practical model to increase AN-related protection factors.     

Ex vivo intestinal adhesion of Escherichia coli LF82 in Crohn's disease

Adherent-invasive Escherichia coli (AIEC) are reported to inhabit the gut mucosa in Crohn’s disease (CD), however, little is known about the importance of host factors for the interplay between AIEC and the human gut.To examine if differences in bacterial adhesion patterns are disease associated, the AIEC-prototype strain LF82 was evaluated for its ability to adhere to ileal and colonic biopsies from CD and healthy controls (HC). Moreover, the efficacy of the non-pathogenic E. coli Nissle 1917 (ECN) in averting LF82 adhesion to ileal mucosa was assessed.Similar numbers of LF82 adhered to biopsies from CD and HC. A significantly greater LF82 attachment to ileal versus colonic mucosa was found in HC (P < 0.01), however, not in CD. ECN did not reduce the adhesion of LF82 to ileal specimens in CD or HC.These results show that enhanced bacterial adhesion ability is unlikely to play any significant role in CD, thus implying that other host protective factors may be impaired in CD. Further, exclusion of LF82 attachment by ECN co-incubation does not appear to represent a relevant treatment regimen.     

Low birth weight is not associated with thyroid autoimmunity: a population-based twin study

CONTEXT: Low birth weight has been proposed as a risk factor for the development of antibodies toward thyroid peroxidase (TPOAb) and thyroglobulin (TgAb) in adult life. However, the association could also be due to genetic or environmental factors affecting both birth weight and the development of thyroid autoantibodies. The effect of these confounders can be minimized through investigation of twin pairs. OBJECTIVE AND DESIGN: To examine the impact of low birth weight on the development of thyroid autoimmunity, we studied whether within-twin-cohort and within-twin-pair differences in birth weight are associated with differences in the serum concentration of TPOAb and TgAb in adult life. PARTICIPANTS: We studied 1024 euthyroid twin individuals who were distributed in 512 same-sex twin pairs. METHODS: Original midwife protocols were traced manually through the Provincial Archives of Denmark. TPOAb and TgAb were measured using solid-phase time-resolved fluoroimmunometric assays. RESULTS: There were no statistically significant associations between birth weight and serum concentrations of TPOAb [regression coefficient (beta) = 0.003 (95% confidence interval, -0.010 to 0.015); P = 0.67] or TgAb [beta = 0.002 (-0.010 to 0.014); P = 0.77]. When restricting the analysis to twin pairs with a within-pair difference in birth weight of 500 g or greater or to twin pairs born 4 wk or more before term, the regression coefficients were almost unchanged. Controlling for potential confounders (sex, zygosity, gestational age, TSH, and smoking) did not change the findings of nonsignificant regression coefficients. CONCLUSION: Low birth weight per se has no evident role in the etiology of thyroid autoimmunity.     

Effect of maternal dietary cow's milk on the immune response to beta-lactoglobulin in the offspring: a four-generation study in mice

BACKGROUND: Evaluation of immune responses to food proteins in animal models requires that the animals are not already sensitized or orally tolerized against the proteins in question. Since maternal transfer of specific immune responses has been observed, breeding of animals on an antigen-free diet for several generations may be necessary to obtain immunologically naive animals. METHODS: To determine the most appropriate breeding conditions of mice to be used in immunological studies on food proteins, we examined immune responses towards beta-lactoglobulin (BLG) in mice bred on a milk-containing diet (F0) and then for three generations (F1-F3) on a commercially available milk-free diet. The specific antibody and cell-proliferative response to BLG was compared in non-immunized and immunized BALB/c mice, and in mice orally tolerized to BLG prior to immunization. RESULTS: The immune response to BLG in the F1 generation deviated from the response observed in the F0 and F2/F3 generations. Importantly, trace amounts of BLG detected in the commercial milk-free diet did not induce oral tolerance. CONCLUSIONS: The study showed that breeding mice on an antigen-free diet for at least two generations is required to attain animals appropriate for immunological studies of food proteins. Although the small quantity of BLG in the milk-free diet did not induce detectable oral tolerance in the present study, it is strongly recommended that the potential effect of contaminating dietary antigen is considered in future studies on food proteins.     

Association of the TSHR gene with Graves' disease: the first disease specific locus

The development of autoimmune thyroid disease (AITD) is associated with autoantibodies directed against the thyroid stimulating hormone receptor (TSHR). Previous studies have failed to demonstrate a consistent association between the TSHR and AITD, or any of its sub-phenotypes. In the present study, we analysed the linkage disequilibrium (LD) structure encompassing the TSHR, to identify LD 'blocks' and SNPs, which capture the majority of intra-block haplotype diversity. The haplotype tagging SNPs, plus all common SNPs reported in previous studies were genotyped in 1,059 AITD Caucasian cases and 971 Caucasian controls. A haplotype, across two LD blocks, showed association (P<1 x 10(-6), OR 1.7) with Graves' disease (GD) but not autoimmune hypothyroidism (AIH). We replicated these findings by genotyping the most associated GD SNP, rs2268458, in a separate UK Caucasian cohort of 1,366 AITD cases and 1,061 controls (GD, P=2 x 10(-6), OR 1.3; AIH, P=NS). These results in two independent Caucasian data sets suggest that the TSHR is the first replicated GD-specific locus meriting further fine mapping and functional analysis to identify the aetiological variants.     

Monozygotic twin pairs discordant for Hashimoto's thyroiditis share a high proportion of thyroid peroxidase autoantibodies to the immunodominant region A. Further evidence for genetic transmission of epitopic "fingerprints"

Thyroid peroxidase antibodies (TPOAbs) in patients with Hashimoto's thyroiditis (HT) predominantly react with two immunodominant regions (IDR-A, IDR-B). Theoretically, as shown for the level of TPOAbs, the autoantibody epitopic recognition of the IDRs could be under genetic control. To examine this, we compared the distribution of TPOAb epitopic fingerprints between healthy monozygotic (MZ) co-twins and siblings to patients with clinically overt HT with a control group of euthyroid subjects, matched for sex and age, but without autoimmune thyroid disease (AITD) among their first-degree relatives. Two ELISAs based on competition with rabbit antisera were used to determine the IDR specificities in 23 patients with HT, 6 MZ co-twins, 8 siblings to patients with HT, and 11 healthy euthyroid subjects without predisposition to AITD. The fraction of TPOAbs recognizing IDR-A was 19, 18, and 9% in HT patients, MZ-co-twins, and siblings, respectively, which was higher than the 0% found in the group of healthy subjects without predisposition to AITD (p = 0.007 vs. HT; p = 0.1078 vs. MZ co-twin and p = 0.069 vs. siblings). Moreover, the IDR-A fraction differed between healthy MZ-co-twins and ordinary siblings (18% vs. 9%, p = 0.0127). In conclusion, our data indicate that the propensity to produce autoantibodies directed against the IDR-A epitope of TPO is genetically determined. This finding may have implications with respect to inheritance of autoantibody specificities in other autoimmune diseases.     

European guidance for the molecular diagnosis of pseudohypoparathyroidism not caused by point genetic variants at GNAS: an EQA study

Pseudohypoparathyroidism is a rare endocrine disorder that can be caused by genetic (mainly maternally inherited inactivating point mutations, although intragenic and gross deletions have rarely been reported) or epigenetic alterations at GNAS locus. Clinical and molecular characterization of this disease is not that easy because of phenotypic, biochemical and molecular overlapping features between both subtypes of the disease. The European Consortium for the study of PHP (EuroPHP) designed the present work with the intention of generating the standards of diagnostic clinical molecular (epi)genetic testing in PHP patients. With this aim, DNA samples of eight independent PHP patients carrying GNAS genetic and/or epigenetic defects (three patients with GNAS deletions, two with 20q uniparental disomy and three with a methylation defect of unknown origin) without GNAS point mutations were anonymized and sent to the five participant laboratories for their routine genetic analysis (methylation-specific (MS)-MLPA, pyrosequencing and EpiTYPER) and interpretations. All laboratories were able to detect methylation defects and, after the data analysis, the Consortium compared the results to define technical advantages and disadvantages of different techniques. To conclude, we propose as first-level investigation in PHP patients copy number and methylation analysis by MS-MLPA. Then, in patients with partial methylation defect, the result should be confirmed by single CpG bisulphite-based methods (ie pyrosequencing), whereas in case of a complete methylation defect without detectable deletion, microsatellites or SNP genotyping should be performed to exclude uniparental disomy 20.