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Objective The environmental trigger behind the increasing prevalence of coeliac disease is not known. One suggested cause is iron deficiency, which is common in coeliac disease. We aimed to evaluate this possible association with Mendelian randomisation (MR), which under certain assumptions can suggest a causal relationship.Design We conducted a two-sample MR study examining the relationship between single nucleotide polymorphisms (SNPs) associated with iron status and the presence of coeliac disease. The SNPs were drawn from a meta-analysis of three genome-wide association studies (GWAS). The association between these SNPs and coeliac disease was assessed using GWAS summary statistics from the UK Biobank. This consists of 336 638 white British individuals, 1855 with coeliac disease. We performed an MR Egger test for pleiotropy and assessed the plausibility of the assumptions of MR to evaluate for possible causality.Results There were four SNPs strongly associated with systemic iron status. These were not associated with known risk factors for coeliac disease. All four SNPs were available in the UK Biobank coeliac disease summary statistics. Harmonising exposure and outcome associations, we found that higher iron status was negatively associated with risk of coeliac disease (OR per 1 SD increase in serum iron: 0.65, 95% CI 0.47 to 0.91). Leave-one-out analyses had consistent results, and no single SNP drove the association. All three assumptions of MR appeared plausible.Conclusion We found that genetically lower iron levels were associated with an increased risk of coeliac disease. Our findings highlight a potential opportunity for coeliac disease prevention.

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Abstract Background The thyroid is among the more radiosensitive organs in the body. The goal of this study was twofold: (1) to evaluate age-related changes in what is exposed to ionizing radiation in the neck area, and (2) to assess thyroid shield presence in cephalometric radiographs Methods Cephalometric radiographs at one academic setting were sampled and neck exposure was related to calendar year and patient's gender and age. Results In the absence of shields, children have more vertebrae exposed than adults (p < 0.0001) and females have more neck tissue exposed inferior to the hyoid bone than males (p < 0.0001). The hyoid bone-porion distance increased with age (p Conclusion In the absence of a thyroid shield, children have more neck structure exposed to radiation than adults. In agreement with other reports, thyroid shield utilization in this study was low, particularly in children.

Transposable elements (TE) comprise roughly half of the human genome. Though initially derided as junk DNA, they have been widely hypothesized to contribute to the evolution of gene regulation. However, the contribution of TE to the genetic architecture of diseases remains unknown. Here, we analyze data from 41 independent diseases and complex traits to draw three conclusions. First, TE are uniquely informative for disease heritability. Despite overall depletion for heritability (54% of SNPs, 39 ± 2% of heritability), TE explain substantially more heritability than expected based on their depletion for known functional annotations. This implies that TE acquire function in ways that differ from known functional annotations. Second, older TE contribute more to disease heritability, consistent with acquiring biological function. Third, Short Interspersed Nuclear Elements (SINE) are far more enriched for blood traits than for other traits. Our results can help elucidate the biological roles that TE play in the genetic architecture of diseases.

Background and Aim Irritable bowel syndrome (IBS) affects 12% of the population, and the evidence supporting current medical interventions is poor. There is increasing focus on the therapeutic benefit of diet and supplementation. We aim to compare dietary composition and hematologic and biochemical markers in those with and without IBS to determine potential targets for therapeutic supplementation. Methods All 17 national surveys between 1959 and 2019 were screened, and only 1, the Second National Health and Nutrition Examination Survey (NHANES II) (1976–1980), provided comprehensive data on IBS. We performed a cross‐sectional analysis of hematologic and biochemical markers and dietary composition of 12 295 individuals, aged 18–74, in NHANES II. Results Individuals with IBS had significantly higher copper–zinc ratios (1.70 vs 1.55, P = 0.048) and were more likely to have ratios above 1.8 (odds ratio 1.79, 95% confidence interval 1.02–3.13), indicative of underlying copper–zinc imbalance. While more likely to report dietary avoidances, they had no other evidence of nutritional deficiencies. In addition, dietary recall showed that those with IBS consumed more calories (P = 0.02), were more likely to take vitamin supplements (P = 0.003), and that their macro and micronutrient intake was not significantly different. Conclusions The findings suggest that individuals with IBS should be screened for copper–zinc imbalance. Given zinc's role in the immune system, the “brain–gut” axis, and the gastrointestinal barrier, the identified copper–zinc imbalance may play a role in perpetuating the underlying pathophysiology of IBS. Further studies are needed to investigate this hypothesis and the potential role of therapeutic zinc supplementation.

Fluoride has no tangible health benefits other than preventing dental caries and there is a small difference between its minimum effective dose and its minimum toxic dose. Leading global organizations currently recommend fluoride supplementation because they recommend high-carbohydrate diets which can cause dental caries. Low-carbohydrate diets prevent dental caries making such fluoride recommendations largely unnecessary. A dental organization was among the first to initiate the public health recommendations which started fluoride-supplemented high-carbohydrate nutritional guidelines. This start required expert panels at this dental organization to reverse on three key scientific points between 1942 and 1949: (1) that topical fluoride had potential harms, (2) that dental caries was a marker for micronutrient deficiencies, and (3) that low-carbohydrate diets are to be recommended for dental caries prevention. Internal documents show that private interests motivated the events which led these expert panels to engage in pivotal scientific reversals. These private interests biased scientific processes and these reversals occurred largely in an absence of supporting evidence. It is concluded that private interests played a significant role in the start of public health endorsements of fluoride-supplemented high-carbohydrate nutritional guidelines.

The latitudinal gradient effect is described for several autoimmune diseases including celiac disease in the United States. However, the association between latitude and global celiac disease prevalence is unknown. We aimed to explore the association between latitude and serology-based celiac disease prevalence through meta-analysis. We searched MEDLINE, Embase, Cochrane, and Scopus databases from their beginning through June 29, 2018, to identify screening studies that targeted a general population sample, used serology-based screening tests, and provided a clear location from which we could assign a latitude. Studies were excluded if sampling was based on symptoms, risk factors, or referral. Study selection and data extraction were performed by independent reviewers. The association measures between latitude and prevalence of serology-based celiac disease were evaluated with random-effects meta-analyses and meta-regression. Of the identified 4667 unique citations, 128 studies were included, with 155 prevalence estimates representing 40 countries. Celiac disease was more prevalent at the higher latitudes of 51° to 60° (relative risk [RR], 1.62; 95% CI, 1.09–2.38) and 61° to 70° (RR, 2.30; 95% CI, 1.36–3.89) compared with the 41° to 50° reference level. No statistically significant difference was observed at lower latitudes. When latitude was treated as continuous, we found a statistically significant association between CD prevalence and latitude overall in the world (RR, 1.03, 95% CI, 1.01–1.05) and a subregional analysis of Europe (RR, 1.05; 95% CI, 1.02–1.07) and North America (RR, 1.1; 95% CI, 1.0–1.2). In this comprehensive review of screening studies, we found that a higher latitude was associated with greater serology-based celiac disease prevalence. [ABSTRACT FROM AUTHOR]

Gluten ingestion in patients with celiac disease can lead to gastrointestinal symptoms and small intestinal mucosal injury. This gluten challenge phase 2 trial was double blind and placebo controlled, and it assessed the efficacy and safety of a 1200-mg dose of IMGX003 in patients with celiac disease exposed to 2 g of gluten per day for 6 weeks. The change in the ratio of villus height to crypt depth was the primary endpoint. Secondary endpoints included density of intraepithelial lymphocytes and symptom severity. These endpoints were evaluated by analysis of covariance. Additional endpoints included serology and gluten-immunogenic peptides in urine. Fifty patients were randomized, and 43 patients completed the study (IMGX003, n = 21; placebo, n = 22). The mean change in the ratio of villus height to crypt depth (primary endpoint) for IMGX003 vs placebo was –0.04 vs –0.35 (P =.057). The mean change in the density of intraepithelial lymphocytes (secondary endpoint) for IMGX003 vs placebo was 9.8 vs 24.8 cells/mm epithelium (P =.018). The mean change (worsening) in symptom severity in relative units (secondary endpoint) for IMGX003 vs placebo was 0.22 vs 1.63 (abdominal pain, P =.231), 0.96 vs 3.29 (bloating, P =.204), and 0.02 vs 3.20 (tiredness, P =.113). The 3 × 2-week trend line significance values for these symptoms, respectively, were P =.014,.030, and.002. IMGX003 reduced gluten-induced intestinal mucosal damage and symptom severity. (ClinicalTrials.gov , Number: NCT03585478) [Display omitted] [ABSTRACT FROM AUTHOR]

Oral-health-related quality of life (OHRQoL) is expected to have multiple dimensions. It was the aim of this study to investigate the dimensional structure of OHRQoL measured by the Oral Health Impact Profile (German version) (OHIP-G) and to derive a summary score for the instrument. Subjects (N = 2050; age, 16-79 yrs) came from a national survey. We used rotated principal-components analysis to derive a summary score and to explore the dimensional structure of OHIP-G. The first principal component explained 50% of the variance in the data. The sum of OHIP-G item responses was highly associated with the first principal component (r = 0.99). This simple but informative OHIP-G summary score may indicate that simple sums are also potentially useful scores for other OHRQoL instruments. Four dimensions (psychosocial impact, orofacial pain, oral functions, appearance) were found. These OHIP-G dimensions may serve as a parsimonious set of OHRQoL dimensions in general. [ABSTRACT FROM AUTHOR]