No Contribution of GAD-65 and IA-2 Autoantibodies around Time of Diagnosis to the Increasing Incidence of Juvenile Type 1 Diabetes:A 9-Year Nationwide Danish Study

Aims. A new perspective on autoantibodies as pivotal players in the pathogenesis of type 1 diabetes (T1D) has recently emerged. Our key objective was to examine whether increased levels of autoantibodies against the β-cell autoantigens glutamic acid decarboxylase (isoform 65) (GADA) and insulinoma associated antigen-2A (IA-2A) mirrored the 3.4% annual increase in incidence of T1D. Methods. From the Danish Childhood Diabetes Register, we randomly selected 500 patients and 500 siblings for GADA and IA-2A analysis (1997 through 2005). Blood samples were taken within three months after onset. A robust log-normal regression model was used. Nine hundred children and adolescents had complete records and were included in the analysis. Cochran-Armitage test for trend was used to evaluate changes in prevalence of autoantibody positivity by period. Results. No significant changes in levels of GADA and IA-2A were found over our 9-year study period. No trends in autoantibody positivity—in either patients or siblings—were found. Levels of GADA and IA-2A were significantly associated with HLA risk groups and GADA with age. Conclusion. The prevalence of positivity and the levels of GADA and IA-2A have not changed between 1997 and 2005 in newly diagnosed patients with T1D and their siblings without T1D

Investigation of the human nasal microbiome in persons with long- And short-term exposure to methicillin-resistant <i>Staphylococcus aureus</i> and other bacteria from the pig farm environment

Since its emergence in the early 2000s, livestock-associated methicillin-resistant Staphylococcus aureus clonal complex 398 (LA-MRSA CC398) has led to an increasing number of human infections in Denmark and other European countries with industrial pig production. LA-MRSA CC398 is primarily associated with skin infections among pig farm workers but is also increasingly recognized as a cause of life-threatening disease among elderly and immunocompromised people. Pig farm workers may serve as vehicles for the spread of LA-MRSA CC398 and other farm-origin bacteria between farms and into the general population. Yet, little is known about the bacterial community dynamics in pig farm workers and other persons with long- and short-term exposure to the pig farm environment. To gain insight into this, we investigated the nasal microbiomes in pig farm workers during a workweek on four LA-MRSA CC398-positive pig farms, as well as in short-term visitors two hours before, immediately after, and 48 hours after a 1-hour visit to another LA-MRSA CC398-positive pig farm. S. aureus and LA-MRSA CC398 carriage was quantified by means of culture, and the composition of the bacterial communities was investigated through sequencing of the 16S rRNA gene. Pig farm workers often carried LA-MRSA CC398 and other bacteria from the pig farm environment, both at work and at home, although at lower levels at home. In contrast, short-term visitors were subject to a less dramatic and rapidly reversible change in the nasal bacterial community composition. These results suggest that pig farm workers may be an important source of LA-MRSA CC398 and perhaps other pathogens of human and veterinary relevance

Parental Smoking and Risk of Childhood-onset Type 1 Diabetes

Background: A few prospective studies suggest an association between maternal smoking during pregnancy and lower risk of type 1 diabetes. However, the role of unmeasured confounding and misclassification remains unclear. Methods: We comprehensively evaluated whether maternal smoking in pregnancy predicts lower risk of childhood-onset type 1 diabetes in two Scandinavian pregnancy cohorts (185,076 children; 689 cases) and a Norwegian register-based cohort (434,627 children; 692 cases). We measured cord blood cotinine as an objective marker of nicotine exposure during late pregnancy in 154 cases and 476 controls. We also examined paternal smoking during pregnancy, in addition to environmental tobacco smoke exposure the first 6 months of life, to clarify the role of characteristics of smokers in general. Results: In the pregnancy cohorts, maternal smoking beyond gestational week 12 was inversely associated with type 1 diabetes, pooled adjusted hazard ratio (aHR) 0.66 (95% CI = 0.51, 0.85). Similarly, in the Norwegian register-based cohort, children of mothers who still smoked at the end of pregnancy had lower risk of type 1 diabetes, aHR 0.65 (95% CI = 0.47, 0.89). Cord blood cotinine >=30 nmol/L was also associated with reduced risk of type 1 diabetes, adjusted odds ratio 0.42 (95% CI = 0.17, 1.0). We observed no associations of paternal smoking during pregnancy, or environmental tobacco smoke exposure, with childhood-onset type 1 diabetes. Conclusion: Maternal sustained smoking during pregnancy is associated with lower risk of type 1 diabetes in children. This sheds new light on the potential intrauterine environmental origins of the disease

Moderate Multiple Parentage and Low Genetic Variation Reduces the Potential for Genetic Incompatibility Avoidance Despite High Risk of Inbreeding

Background: Polyandry is widespread throughout the animal kingdom. In the absence of direct benefits of mating with different males, the underlying basis for polyandry is enigmatic because it can carry considerable costs such as elevated exposure to sexual diseases, physical injury or other direct fitness costs. Such costs may be balanced by indirect genetic benefits to the offspring of polyandrous females. We investigated polyandry and patterns of parentage in the spider Stegodyphus lineatus. This species experiences relatively high levels of inbreeding as a result of its spatial population structure, philopatry and limited male mating dispersal. Polyandry may provide an opportunity for post mating inbreeding avoidance that reduces the risk of genetic incompatibilities arising from incestuous matings. However, multiple mating carries direct fitness costs to females suggesting that genetic benefits must be substantial to counter direct costs. Methodology/Principal Findings: Genetic parentage analyses in two populations from Israel and a Greek island, showed mixed-brood parentage in approximately 50 % of the broods. The number of fathers ranged from 1–2 indicating low levels of multiple parentage and there was no evidence for paternity bias in mixed-broods from both populations. Microsatellite loci variation suggested limited genetic variation within populations, especially in the Greek island population. Relatedness estimates among females in the maternal generation and potentially interacting individuals were substantial indicating fullsib and half-sib relationships