Comparative analysis of antibodies to four major periodontal bacteria in respiratory diseases: a cohort study.

OBJECTIVES: To make a descriptive comparison of antibodies to four major periodontal bacteria and their relation to the respiratory diseases asthma and bronchitis/emphysema, and to cancer incidence. METHODS: The serum of a random sample of men with no history of cancer incidence (n=621) was analysed by the ELISA method for antibody levels of four periodontal bacteria; the anaerobes of the so-called red complex Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD), and the facultative anaerobe Aggregatibacter actinomycetemcomitans (AA). The antibody readings were divided into quartiles and the distribution of cases of the relevant diseases as compared with the non-cases. Comparisons of the quartile distributions were by the Pearson χ2 test. Data and serum from the Oslo II study of Norwegian men from 2000 were used. The ELISA analyses were performed on thawed frozen serum. Cancer data from 17.5 years of follow-up were provided by the Norwegian Cancer Registry. RESULTS: In all, 52 men had reported asthma and 23 men had bronchitis/emphysema at the health screening. Results on cancer incidence are given for all respiratory cancers, n=23, and bronchi and lung cancers separately, n=18. Stratified analyses were performed for the four endpoints showing significant association with low levels of TD antibodies for bronchitis; p=0.035. Both TF and TD were significant for low levels of antibodies among daily smokers; p=0.030 for TF and p<0.001 for TD in the analysis of the full study sample. For PG and AA, no such associations were observed. An association with respiratory cancers was not observed. CONCLUSION: A low level of TD was associated with bronchitis/emphysema compared with the rest of the cohort. In the total study sample, low levels of antibodies to both TF and TD were associated with daily smoking.

Low level of antibodies to the oral bacterium Tannerella forsythia predicts bladder cancers and Treponema denticola predicts colon and bladder cancers: A prospective cohort study.

This study explores the risk for cancer by level of antibodies to the anaerobe oral bacteria of periodontitis Tannerella forsythia (TF), Porphyromonas gingivalis (PG), and Treponema denticola (TD) all three collectively termed the red complex, and the facultative anaerobe bacterium Aggregatibacter actinomycetemcomitans (AA). The prospective cohort, the Oslo II-study from 2000, the second screening of the Oslo study of 1972/73, has been followed for 17 ½ years with regard to cancer incidence and mortality. A random sample of 697 elderly men comprised the study cohort. The antibody results measured by enzyme linked immunosorbent assay (ELISA) were used in the Cox proportional hazards analyses, and quartile risk on cancer incidence in a 17 ½ years follow-up. Among the 621 participants with no prior cancer diagnoses, 221 men developed cancer. The incidence trend was inverse, and the results are shown as 1st quartile of highest value and 4th as lowest of antibody levels. The results of the Cox proportional regression analyses showed that TF inversely predicts bladder cancer (n = 22) by Hazard Ratio (HR) = 1.71 (95% CI: 1.12, 2.61). TD inversely predicts colon cancer (n = 26) by HR = 1.52 (95% CI: 1.06, 2.19) and bladder cancer (n = 22) by HR = 1.60 (95% CI: 1.05, 2.43). Antibodies to two oral bacteria, TF and TD, showed an inverse risk relationship with incidence of specific cancers: TF bladder cancer, TD bladder and colon cancer. Lowered immunological response to the oral infection, periodontitis, is shown to be a risk factor in terms of cancer aetiology.

Parechovirus Infection in Early Childhood and Association With Subsequent Celiac Disease.

INTRODUCTION: To test whether parechovirus and anellovirus, frequent enteric viruses, were associated with subsequent celiac disease (CD). We hypothesized that children who later developed CD would have increased frequency of parechovirus infections before transglutaminase 2 (TG2) antibody development. Anellovirus testing was exploratory, as a potential marker of immune status. METHODS: Matched case-control design nested within a longitudinal birth cohort (the MIDIA study) of children at genetic risk of CD (carrying the human leukocyte antigen genotype DR4-DQ8/DR3-DQ2, recruited throughout Norway during 2001-2007). We retrospectively tested blood samples taken at age 3, 6, 9, and 12 months, and then annually, to determine when TG2 antibodies developed. Of 220 genetically at-risk children tested, 25 were diagnosed with CD (cases; ESPGHAN 2012 criteria) and matched for follow-up time, birthdate, and county of residence with 2 randomly selected children free from CD (controls) from the cohort. Viruses were quantified in monthly stool samples (collected from 3 through 35 months of age) using real-time polymerase chain reaction methods. RESULTS: Parechovirus was detected in 222 of 2,005 stool samples (11.1%) and was more frequent in samples from cases before developing TG2 antibodies (adjusted odds ratio 1.67, 95% confidence interval 1.14-2.45, P = 0.01). The odds ratio was higher when a sample was positive for both parechovirus and enterovirus (adjusted odds ratio 4.73, 95% confidence interval 1.26-17.67, P = 0.02). Anellovirus was detected in 1,540 of 1,829 samples (84.2%), but did not differ significantly between case and control subjects. DISCUSSION: Early-life parechovirus infections were associated with development of CD in genetically at-risk children.

Oral health and cardiovascular disease risk factors and mortality of cerebral haemorrhage, cerebral infarction and unspecified stroke in elderly men: A prospective cohort study.

Background: Stroke mortality comprises different specific diagnoses as cerebral infarction, different haemorrhagic conditions and unspecified stroke. This study seeks to explore the prediction of oral health indicators versus known cardiovascular disease risk factors for stroke mortality. Methods: Altogether, 12,764 men aged 58 to 77 years were invited to the health screening Oslo II in the year 2000. It included general medical measurements and questionnaire information. Mortality data were supplied by Statistics Norway for the 6530 attending men. Cox proportional hazards regression analyses were used to establish prediction models for mortality. Results: Oral health by number of tooth extractions >10 was found to be an independent predictor for cerebral infarction hazard ratio = 2.92, 95% confidence interval (1.24-6.89). This was independent of HDL-Cholesterol (inversely) hazard ratio = 0.21, 95% confidence interval (0.06-0.76), frequent alcohol consumption (drinking 4-7 times per week) hazard ratio = 3.58, 95% confidence interval (1.40-9.13) and diabetes hazard ratio = 4.28, 95% confidence interval (1.68-10.89). Predictors for cerebral haemorrhage were age, hs-C-reactive protein and body mass index (inversely). Age and total cholesterol (inversely) were predictors for unspecified stroke. Conclusions: Oral health measured by number of tooth extractions >10 was an independent predictor for cerebral infarction in addition to age, HDL-C, hs-C-reactive protein and diabetes. The pattern of risk factors varied between the specific stroke diagnoses.

Enterovirus as trigger of coeliac disease: nested case-control study within prospective birth cohort.

OBJECTIVE: To determine whether infection with human enterovirus or adenovirus, both common intestinal viruses, predicts development of coeliac disease. DESIGN: Case-control study nested within Norwegian birth cohort recruited between 2001 and 2007 and followed to September 2016. SETTING: Norwegian population. PARTICIPANTS: Children carrying the HLA genotype DR4-DQ8/DR3-DQ2 conferring increased risk of coeliac disease. EXPOSURES: Enterovirus and adenovirus detected using real time polymerase chain reaction in monthly stool samples from age 3 to 36 months. MAIN OUTCOME MEASURE: Coeliac disease diagnosed according to standard criteria. Coeliac disease antibodies were tested in blood samples taken at age 3, 6, 9, and 12 months and then annually. Adjusted odds ratios from mixed effects logistic regression model were used to assess the relation between viral infections before development of coeliac disease antibodies and coeliac disease. RESULTS: Among 220 children, and after a mean of 9.9 (SD 1.6) years, 25 children were diagnosed as having coeliac disease after screening and were matched to two controls each. Enterovirus was found in 370 (17%) of 2135 samples and was significantly more frequent in samples collected before development of coeliac disease antibodies in cases than in controls (adjusted odds ratio 1.49, 95% confidence interval 1.07 to 2.06; P=0.02). The association was restricted to infections after introduction of gluten. High quantity samples (>100 000 copies/µL) (adjusted odds ratio 2.11, 1.24 to 3.60; P=0.01) and long lasting infections (>2 months) (2.16, 1.16 to 4.04; P=0.02) gave higher risk estimates. Both the commonly detected enterovirus species Enterovirus A and Enterovirus B were significantly associated with coeliac disease. The association was not found for infections during or after development of coeliac disease antibodies. Adenovirus was not associated with coeliac disease. CONCLUSIONS: In this longitudinal study, a higher frequency of enterovirus, but not adenovirus, during early childhood was associated with later coeliac disease. The finding adds new information on the role of viral infections in the aetiology of coeliac disease.

The Predictive Role of Tooth Extractions, Oral Infections, and hs-C-Reactive Protein for Mortality in Individuals with and without Diabetes: A Prospective Cohort Study of a 12 1/2-Year Follow-Up.

The predictive role of high-sensitivity C-reactive protein (hs-CRP), number of tooth extractions, and oral infections for mortality in people with and without diabetes is unclear. This prospective cohort study is a 12 1/2-year follow-up of the Oslo II study, a health survey in 2000. In all, 12,764 men were invited. Health information was retrieved from 6434 elderly men through questionnaire information, serum measurements, and anthropometric and blood pressure measurements. Diabetes was reported by 425 men. Distinct differences were observed in baseline characteristics in individuals with and without diabetes. In the diabetes group, age and hs-CRP were statistically significant whereas in the nondiabetes group, age, hs-CRP, number of tooth extractions, tooth extractions for infections and oral infections combined, nonfasting glucose, systolic blood pressure, total cholesterol, regular alcohol drinking, daily smoking, and level of education were independent risk factors. The number of tooth extractions <5 was inversely related whereas more extractions increased the risk. Multivariate analyses showed that hs-CRP was a significant predictor in persons with diabetes and tooth extractions and oral infections combined; the number of teeth extracted and hs-CRP were for persons without diabetes. Infection and inflammation were associated with mortality in individuals both with and without diabetes.

Infant Feeding and Risk of Type 1 Diabetes in Two Large Scandinavian Birth Cohorts.

OBJECTIVE: Our aim was to study the relation between the duration of full and any breastfeeding and risk of type 1 diabetes. RESEARCH DESIGN AND METHODS: We included two population-based cohorts of children followed from birth (1996-2009) to 2014 (Denmark) or 2015 (Norway). We analyzed data from a total of 155,392 children participating in the Norwegian Mother and Child Cohort Study (MoBa) and the Danish National Birth Cohort (DNBC). Parents reported infant dietary practices when their child was 6 and 18 months old. The outcome was clinical type 1 diabetes, ascertained from nationwide childhood diabetes registries. Hazard ratios (HRs) were estimated using Cox regression. RESULTS: Type 1 diabetes was identified in 504 children during follow-up, and the incidence of type 1 diabetes per 100,000 person-years was 30.5 in the Norwegian cohort and 23.5 in the Danish cohort. Children who were never breastfed had a twofold increased risk of type 1 diabetes compared with those who were breastfed (HR 2.29 [95% CI 1.14-4.61] for no breastfeeding vs. any breastfeeding for ≥12 months). Among those who were breastfed, however, the incidence of type 1 diabetes was independent of duration of both full breastfeeding (HR per month 0.99 [95% CI 0.97-1.01]) and any breastfeeding (0.97 [0.92-1.03]). CONCLUSIONS: Suggestive evidence supports the contention that breastfeeding reduces the risk of type 1 diabetes. Among those who were breastfed, however, no evidence indicated that prolonging full or any breastfeeding was associated with a reduced risk of type 1 diabetes.

Longitudinal plasma metabolic profiles, infant feeding, and islet autoimmunity in the MIDIA study.

AIMS: The aim of this study was to investigate the longitudinal plasma metabolic profiles in healthy infants and the potential association with breastfeeding duration and islet autoantibodies predictive of type 1 diabetes. METHOD: Up to four longitudinal plasma samples from age 3 months from case children who developed islet autoimmunity (n = 29) and autoantibody-negative control children (n = 29) with the HLA DR4-DQ8/DR3-DQ2 genotype were analyzed using two-dimensional gas chromatography coupled to a time-of-flight mass spectrometer for detection of small polar metabolites. RESULTS: Plasma metabolite levels were found to depend strongly on age, with fold changes varying up to 50% from age 3 to 24 months (p < 0.001 after correction for multiple testing). Tyrosine levels tended to be lower in case children, but this was not significant after correction for multiple testing. Ornithine levels were lower in case children compared with the controls at the time of seroconversion, but the difference was not statistically significant after correcting for multiple testing. Breastfeeding for at least 3 months as compared with shorter duration was associated with higher plasma levels of isoleucine, and lower levels of methionine and 3,4-dihydroxybutyric acid at 3 months of age. CONCLUSIONS: Plasma levels of several small, polar metabolites changed with age during early childhood, independent of later islet autoimmunity status and sex. Breastfeeding was associated with higher levels of branched-chain amino acids, and lower levels of methionine and 3,4-dihydroxybutyric acid.

Plasma phospholipid pentadecanoic acid, EPA, and DHA, and the frequency of dairy and fish product intake in young children.

BACKGROUND: There is a lack of studies comparing dietary assessment methods with the biomarkers of fatty acids in children. OBJECTIVE: The objective was to evaluate the suitability of a food frequency questionnaire (FFQ) to rank young children according to their intake of dairy and fish products by comparing food frequency estimates to the plasma phospholipid fatty acids pentadecanoic acid, eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). DESIGN: Cross-sectional data for the present study were derived from the prospective cohort 'Environmental Triggers of Type 1 Diabetes Study'. Infants were recruited from the Norwegian general population during 2001-2007. One hundred and ten (age 3-10 years) children had sufficient volumes of plasma and FFQ filled in within 2 months from blood sampling and were included in this evaluation study. The quantitative determination of plasma phospholipid fatty acids was done by fatty acid methyl ester analysis. The association between the frequency of dairy and fish product intake and the plasma phospholipid fatty acids was assessed by a Spearman correlation analysis and by investigating whether participants were classified into the same quartiles of distribution. RESULTS: Significant correlations were found between pentadecanoic acid and the intake frequency of total dairy products (r=0.29), total fat dairy products (r=0.39), and cheese products (r=0.36). EPA and DHA were significantly correlated with the intake frequency of oily fish (r=0.26 and 0.37, respectively) and cod liver/fish oil supplements (r=0.47 for EPA and r=0.50 DHA). To a large extent, the FFQ was able to classify individuals into the same quartile as the relevant fatty acid biomarker. CONCLUSIONS: The present study suggests that, when using the plasma phospholipid fatty acids pentadecanoic acid, EPA, and DHA as biomarkers, the FFQ used in young children showed a moderate capability to rank the intake frequency of dairy products with a high-fat content and cod liver/fish oil supplements.

Genetic Determinants of Enterovirus Infections: Polymorphisms in Type 1 Diabetes and Innate Immune Genes in the MIDIA Study.

Enteroviruses have been suggested as triggers of type 1 diabetes (T1D). We aimed to assess whether established T1D susceptibility single nucleotide polymorphisms (SNPs) and candidate SNPs in innate immune genes were associated with the frequency of enterovirus infection in otherwise healthy children. Fifty-six established T1D SNPs and 97 other candidate immunity SNPs were typed in 419 children carrying the T1D high-risk genotype, HLA-DR4-DQ8/DR3-DQ2 genotype, and 373 children without this genotype. Enteroviral RNA was detected using real-time polymerase chain reaction, with primers detecting essentially all enterovirus serotypes, in 7,393 longitudinal stool samples collected monthly (age range 3-36 months). The most significant association was with two T1D SNPs, rs12150079 (ZPBP2/ORMDL3/GSDMB region) (enterovirus frequency: AA 7.3%, AG 8.7%, GG 9.7%, RR = 0.86, overall p = 1.87E-02) and rs229541 (C1QTNF6/SSTR3/RAC2) (enterovirus frequency: CC 7.8%, CT 9.7%, TT 9.4%, RR = 1.13, overall p = 3.6E-02), followed by TLR8 (rs2407992) (p = 3.8E-02), TLR3 (1914926) (p = 4.9E-02), and two other T1D SNPs (IFIH1 rs3747517, p = 4.9E-02 and PTPN22, rs2476601, p = 5.3E-02). However, the quantile-quantile plot of p-values with confidence intervals for all 153 SNPs did not reveal clear evidence for rejection of the complete null hypothesis. Among a number of SNPs in candidate genes, we found no evidence for strong associations with enterovirus presence in stool samples from Norwegian children.

Saffold Virus, a Human Cardiovirus, and Risk of Persistent Islet Autoantibodies in the Longitudinal Birth Cohort Study MIDIA.

The aim of this study was to describe the frequency and distribution of Saffold virus in longitudinal stool samples from children, and test for association with development of persistent autoantibodies predictive of type 1 diabetes. A cohort of Norwegian children carrying the HLA genotype associated with highest risk of type 1 diabetes ("DR4-DQ8/DR3-DQ2") was followed with monthly stool samples from 3 to 35 months of age. Blood samples were tested for autoantibodies to insulin, glutamic acid decarboxylase65 and Islet Antigen-2. 2077 stool samples from 27 children with ≥ 2 repeatedly positive islet autoantibodies (cases), and 53 matched controls were analysed for Saffold virus genomic RNA by semi-quantitative real-time reverse transcriptase PCR. Saffold virus was found in 53 of 2077 (2.6%) samples, with similar proportions between cases (2.5%) and controls (2.6%). The probability of being infected by 3 years of age was 28% (95% CI 0.18-0.40). Viral quantities ranged from <1 to almost 105 copies/µl. Estimated odds ratio between islet autoimmunity and infection episodes prior to seroconversion was 1.98 (95% CI: 0.57-6.91, p = 0.29). Saffold virus had no statistically significant association with islet autoimmunity.

The influence of sample collection methodology and sample preprocessing on the blood metabolic profile.

AIM: Blood serum and plasma have intrinsic differences in their composition and the preprocessing, such as clotting temperature in serum, and storage at room temperature may have further effect on metabolite concentrations. METHODS: The influence of sampling preprocessing on the metabolic profiles in serum and different types of plasma was investigated using liquid chromatography and comprehensive 2D gas chromatography coupled to a mass spectrometer. RESULTS: The profiles of polar metabolites were significantly dependent on the type of the sample, while lipid profiles were similar in serum and different types of plasma. Extended storage of plasma at room temperature resulted in degradation of lipids already after 1 day. Serum clotting at room temperature generally resulted in higher metabolite concentration compared with serum clotting on ice.

Environmental trigger(s) of type 1 diabetes: why so difficult to identify?

Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease has increased two- to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself so that, in a very specific and targeted way, it destroys the pancreatic ß-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will focus on factors which have to be evaluated and decision to take before starting a new prospective cohort study. Considering all the large ongoing prospective studies, new and more conclusive data than that obtained so far should instead come from international collaboration on the ongoing cohort studies.

Infant feeding in relation to islet autoimmunity and type 1 diabetes in genetically susceptible children: the MIDIA Study.

OBJECTIVE: We aimed to study the association of breast-feeding duration and age at the introduction of solid foods with the risk of islet autoimmunity and type 1 diabetes in genetically susceptible children. RESEARCH DESIGN AND METHODS: Newborns were recruited from the Norwegian general population during 2001-2007. After genetic screening of nearly 50,000 newborns, 908 children with the high-risk HLA genotype were followed up with blood samples and questionnaires at age 3, 6, 9, and 12 months and then annually. Complete infant diet data were available for 726 children. RESULTS: Any breast-feeding for 12 months or longer predicted a decreased risk of developing type 1 diabetes compared with any breast-feeding for less than 12 months before and after adjusting for having a first-degree relative with type 1 diabetes, vitamin D supplementation, maternal education, sex, and delivery type (hazard ratio 0.37 [95% CI 0.15-0.93]). Any breast-feeding for 12 months or longer was not associated with islet autoimmunity but predicted a lower risk of progression from islet autoimmunity to type 1 diabetes (hazard ratio 0.35 [95% CI 0.13-0.94]). Duration of full breast-feeding was not significantly associated with the risk of islet autoimmunity or type 1 diabetes nor was age at introduction of solid foods or breast-feeding at the time of introduction of any solid foods. CONCLUSIONS: These results suggest that breast-feeding for 12 months or longer predict a lower risk of progression from islet autoimmunity to type 1 diabetes among genetically predisposed children.

HLA associated type 1 diabetes risk in children of Pakistani migrants to Norway.

Type 1 diabetes (T1D) results from poorly defined interaction between susceptibility genes and environmental factors. The objective was to investigate Human Leukocyte Antigens (HLA) associated T1D risk among Pakistani newborns in Norway based on what published globally. DNA samples from 189 newborns, whose parents were first generation migrants from Pakistan, were analyzed. The hypothesis was tested using high resolution HLA genotyping for the -DRB1 and -DQB1 loci and high/intermediate for the -DQA1 locus. We identified 28 different DRB1, 13 DQB1 and 9 DQA1 alleles. Of the 39 different haplotypes identified, only five have been reported to confer T1D susceptibility. Among these the DR3-DQ2 (DRB1*03:01:01-DQA1*05-DQB1*02:01:01) haplotype was found in 18.5% (n=70) of the newborns, and 18.6% (n=13) of these were homozygotes. A diverse range of HLA haplotypes were identified amongst an ethnically homogenous group of newborns, with only a small proportion associated with T1D risk. The incidence of T1D among immigrants form South/East Asia is the lowest in the Norwegian Type 1 Diabetes Registry. The few included so far, are children of first generation immigrants. If incidence of T1D rises in the Norwegian Pakistani childhood population, as observed in the UK, then environmental triggers rather than genetic susceptibility will be the explanation.

Long-term storage of blood RNA collected in RNA stabilizing Tempus tubes in a large biobank--evaluation of RNA quality and stability.

BACKGROUND: Establishing methods for secure long term storage of RNA is critical to realizing the promise of biobanks in biomedical research. Here, we describe the results of yearly analyses of the same set of umbilical cord and adult whole blood RNA collected in Tempus Blood RNA tubes and stored at -80 °C, over a period of up to six years. We systematically investigated the effects of long-term storage of samples (75 Tempus tubes form three adult donors and 30 Tempus tubes from three cord blood donors) on the RNA quality and transcript stability of six selected genes (CDKN1A, FOS, IL1B, IL8, MYC and TP53). This is the first systematic study of both cord and adult blood samples stored for many years. FINDINGS: The RNA purity and integrity, expressed as RIN-values, were stable up to six years of storage, and there were no storage-related deleterious effects on RNA purity. There were limited intra- and inter-individual variations in RNA yields; however, no consistent trend of decreasing RNA yield was observed with the duration of storage. Some long-term storage effects were found on the relative transcript levels of the six genes when compared to the year 0 samples. However, these changes were within ± 2-fold for both types of blood samples, except for two genes. Our results show that storage of these samples for up to six years did not have significant effects on the RNA quality and transcript stability of the six genes. CONCLUSIONS: Blood RNA is stable in Tempus tubes stored at -80 °C over a period of six years. Intact and good-quality RNA suitable for transcript profiling analyses in epidemiological studies was obtained from blood samples stored in Tempus tubes. This suggests that blood samples collected in large biobanks-such as the Mother and Child (MoBa) Cohort at Norwegian Institute of Public Health (NIPH) and frozen in suitable collection tubes for total RNA stabilization, can be used for quantitative studies after at least six years of storage.

Enterovirus RNA in longitudinal blood samples and risk of islet autoimmunity in children with a high genetic risk of type 1 diabetes: the MIDIA study.

AIMS/HYPOTHESIS: Only a few longitudinal molecular studies of enterovirus and islet autoimmunity have been reported, and positive results seem to be limited to Finland. We aimed to investigate an association between enterovirus RNA in blood and islet autoimmunity in the MIDIA study from Norway, a country which largely shares environmental and economic features with Finland. METHODS: We analysed serial blood samples collected at ages 3, 6, and 9 months and then annually from 45 children who developed confirmed positivity for at least two autoantibodies (against insulin, GAD65 and IA-2) and 92 matched controls, all from a cohort of children with a single high-risk HLA-DQ-DR genotype. Enterovirus was tested in RNA extracted from frozen blood cell pellets, using real-time RT-PCR with stringent performance control. RESULTS: Out of 807 blood samples, 72 (8.9%) were positive for enterovirus. There was no association between enterovirus RNA and islet autoimmunity in samples obtained strictly before (7.6% cases, 10.0% controls, OR 0.75 [95% CI 0.36, 1.57]), or strictly after the first detection of islet autoantibodies (10.5% case, 5.8% controls, OR 2.00 [95% CI 0.64, 6.27]). However, there was a tendency towards a higher frequency of enterovirus detection in the first islet autoantibody-positive sample (15.8%) compared with the corresponding time point in matched controls (3.2%, OR 8.7 [95% CI 0.97, 77]). Neither of these results was changed by adjusting for potential confounders, restricting to various time intervals or employing various definitions of enterovirus positivity. CONCLUSIONS/INTERPRETATION: Positivity for enterovirus RNA in blood did not predict the later induction of islet autoantibodies, but enterovirus tended to be detected more often at the islet autoantibody seroconversion stage.

Context-dependent competition in a model gut bacterial community.

Understanding the ecological processes that generate complex community structures may provide insight into the establishment and maintenance of a normal microbial community in the human gastrointestinal tract, yet very little is known about how biotic interactions influence community dynamics in this system. Here, we use natural strains of Escherichia coli and a simplified model microbiota to demonstrate that the colonization process on the strain level can be context dependent, in the sense that the outcome of intra-specific competition may be determined by the composition of the background community. These results are consistent with previous models for competition between organisms where one competitor has adapted to low resource environments whereas the other is optimized for rapid reproduction when resources are abundant. The genomic profiles of E. coli strains representing these differing ecological strategies provide clues for deciphering the genetic underpinnings of niche adaptation within a single species. Our findings extend the role of ecological theory in understanding microbial systems and the conceptual toolbox for describing microbial community dynamics. There are few, if any, concrete examples of context-dependent competition on a single trophic level. However, this phenomenon can have potentially dramatic effects on which bacteria will successfully establish and persist in the gastrointestinal system, and the principle should be equally applicable to other microbial ecosystems.

Type 1 diabetes: prospective cohort studies for identification of the environmental trigger.

Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease incidence has increased two to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself, destroying in a very specific and targeted way-the pancreatic ß-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will give an overview of ongoing prospective cohort studies aiming to identify the environmental trigger(s) causing T1D.