IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes.

GWAS have identified >200 risk loci for Inflammatory Bowel Disease (IBD). The majority of disease associations are known to be driven by regulatory variants. To identify the putative causative genes that are perturbed by these variants, we generate a large transcriptome data set (nine disease-relevant cell types) and identify 23,650 cis-eQTL. We show that these are determined by ∼9720 regulatory modules, of which ∼3000 operate in multiple tissues and ∼970 on multiple genes. We identify regulatory modules that drive the disease association for 63 of the 200 risk loci, and show that these are enriched in multigenic modules. Based on these analyses, we resequence 45 of the corresponding 100 candidate genes in 6600 Crohn disease (CD) cases and 5500 controls, and show with burden tests that they include likely causative genes. Our analyses indicate that ≥10-fold larger sample sizes will be required to demonstrate the causality of individual genes using this approach

Long-term reliable change of pain scores in individual myogenous TMD patients.

A within-patient change in pain score after treatment is statistically 'reliable' when it exceeds the smallest detectable difference (SDD). The aims of the present study were to: (i) determine SDDs for VAS-scores of pain intensity, for sufficiently long test-retest intervals to include most biological fluctuations, (ii) examine whether SDD is invariant to baseline score, and (iii) discuss the value of reliable change (RC) for detecting clinically important difference (CID) or as a possible indicator of successful treatment. SDDs were determined using duplicate data from 118 patients with myogenous Temporomandibular disorders: (1) VAS-scores of pain intensity from the masticatory system in a pre-treatment diary, and (2) VAS-scores of pain intensity from the hand (cold-pressor test). RC was determined in VAS-scores from a pre- and post-treatment questionnaire. The long-term SDD was 49mm. A regression analysis on duplicate VAS-scores showed that SDD was largely invariant to the baseline level. Because RC (change>SDD) exceeded CID, it might serve as an indicator of successful treatment. However, only 17% of the patients showed RC after treatment, mainly because the baseline was smaller than SDD in 67% of the patients thus making detection of any treatment effect impossible. For patients with possible detection (33%), the frequency of RC was 51%. If the detection threshold would be avoided by provoking pain in patients with a low baseline, a long-term RC in VAS-scores might occur in about half of all myogenous TMD patients and might then serve as an indicator of cases of treatment success

Tongue function in patients treated for malignancies in tongue and/or floor of mouth; a one year prospective study.

Contains fulltext : 98481.pdf (publisher's version ) (Closed access)Progress in (reconstructive) surgery and radiotherapy tends to improve survival and reduce oral functional deficits. Despite the growing sophistication of cancer treatment, patients still report deterioration in tongue function. Sensory function, mobility, and force of the tongue were determined in 45 patients with a carcinoma of tongue and/or floor of mouth. Measurements were performed before surgery, shortly after surgery, shortly after radiotherapy, 6, and 12 months after surgery. Surgery had a negative impact on tongue sensory function and mobility. Post-surgery radiotherapy did not further deteriorate sensory function, mobility, or force of the tongue. Patients in the surgery-radiotherapy group (SRG) had significantly worse tongue sensory function and mobility than patients in the surgery group (SG), probably caused by more advanced tumour stage and more extensive reconstructions and related scar tissue. The tongue force in patients in both groups significantly increased in the first 6 months after surgery, but this increase disappeared in the next 6 months. The authors conclude that surgery had a significant negative influence on tongue function, especially in the group of patients treated with radiotherapy. No further deterioration of tongue function was observed after post-surgical radiotherapy within the first year after surgery.1 december 201