Colon wall motility: comparison of novel quantitative semi-automatic measurements using cine MRI

Background Recently, cine magnetic resonance imaging (MRI) has shown promise for visualizing movement of the colonic wall, although assessment of data has been subjective and observer dependent. This study aimed to develop an objective and semi-automatic imaging metric of ascending colonic wall movement, using image registration techniques. Methods Cine balanced turbo field echo MRI images of ascending colonic motility were acquired over 2 min from 23 healthy volunteers (HVs) at baseline and following two different macrogol stimulus drinks (11 HVs drank 1 L and 12 HVs drank 2 L). Motility metrics derived from large scale geometric and small scale pixel movement parameters following image registration were developed using the post ingestion data and compared to observer grading of wall motion. Inter and intra-observer variability in the highest correlating metric was assessed using Bland–Altman analysis calculated from two separate observations on a subset of data. Key Results All the metrics tested showed significant correlation with the observer rating scores. Line analysis (LA) produced the highest correlation coefficient of 0.74 (95% CI: 0.55–0.86), p < 0.001 (Spearman Rho). Bland–Altman analysis of the inter- and intra-observer variability for the LA metric, showed almost zero bias and small limits of agreement between observations (−0.039 to 0.052 intra-observer and −0.051 to 0.054 inter-observer, range of measurement 0–0.353). Conclusions & Inferences The LA index of colonic motility derived from cine MRI registered data provides a quick, accurate and non-invasive method to detect wall motion within the ascending colon following a colonic stimulus in the form of a macrogol drink

Genome-wide DNA methylation analysis of transient neonatal diabetes type 1 patients with mutations in ZFP57

BackgroundTransient neonatal diabetes mellitus 1 (TNDM1) is a rare imprinting disorder characterized by intrautering growth retardation and diabetes mellitus usually presenting within the first six weeks of life and resolves by the age of 18 months. However, patients have an increased risk of developing diabetes mellitus type 2 later in life. Transient neonatal diabetes mellitus 1 is caused by overexpression of the maternally imprinted genes PLAGL1 and HYMAI on chromosome 6q24. One of the mechanisms leading to overexpression of the locus is hypomethylation of the maternal allele of PLAGL1 and HYMAI. A subset of patients with maternal hypomethylation at PLAGL1 have hypomethylation at additional imprinted loci throughout the genome, including GRB10, ZIM2 (PEG3), MEST (PEG1), KCNQ1OT1 and NESPAS (GNAS-AS1). About half of the TNDM1 patients carry mutations in ZFP57, a transcription factor involved in establishment and maintenance of methylation of imprinted loci. Our objective was to investigate whether additional regions are aberrantly methylated in ZFP57 mutation carriers.MethodsGenome-wide DNA methylation analysis was performed on four individuals with homozygous or compound heterozygous ZFP57 mutations, three relatives with heterozygous ZFP57 mutations and five controls. Methylation status of selected regions showing aberrant methylation in the patients was verified using bisulfite-sequencing.ResultsWe found large variability among the patients concerning the number and identity of the differentially methylated regions, but more than 60 regions were aberrantly methylated in two or more patients and a novel region within PPP1R13L was found to be hypomethylated in all the patients. The hypomethylated regions in common between the patients are enriched for the ZFP57 DNA binding motif.ConclusionsWe have expanded the epimutational spectrum of TNDM1 associated with ZFP57 mutations and found one novel region within PPP1R13L which is hypomethylated in all TNDM1 patients included in this study. Functional studies of the locus might provide further insight into the etiology of the disease.<br/

Interview with Carolyn Hahnemann

Carolyn Hahnemann talks about what it\u27s like to live in a house on stilts.https://digital.kenyon.edu/lak_interviews/1019/thumbnail.jp

Assessment of motion of colonic contents in the human colon using MRI tagging

Background We have previously reported a non-invasive, semi-automated technique to assess motility of the wall of the ascending colon (AC) using Magnetic Resonance Imaging. This study investigated the feasibility of using a tagged MRI technique to visualise and assess the degree of flow within the human ascending colon in healthy subjects and those suffering from constipation. Methods An open-labelled study of 11 subjects with constipation and 11 subjects without bowel disorders was performed. MRI scans were acquired fasted, then 60 and 120 mins after ingestion of a 500ml macrogol preparation. The amount of free fluid in the small and large bowel was assessed using a heavily T2-weighted MRI sequence. The internal movement of the contents of the AC were visualised using a cine tagged MRI sequence and assessed by a novel analysis technique. Comparisons were made between fasting and postprandial scans within individuals, and between the constipation and control groups. Key results. Macrogol significantly increased the mobile, MR visible water content of the ascending colon at 60 mins post ingestion compared to fasted data (controls p=0.001, constipated group p=0.0039). The contents of the AC showed increased motion in healthy subjects but not in the constipated group with significant differences between groups at 60 minutes (p<0.002) and 120 minutes (p<0.003). Conclusions and inferences. This study successfully demonstrated the use of a novel MRI tagging technique to visualise and assess the motion of ascending colon contents following a 500ml macrogol challenge. Significant differences were demonstrated between healthy and constipated subjects

Effect of Intense Sound Waves on a Stationary Gas Flame

Intense sound waves with a resonant frequency of 5000 cycles per second were imposed on a stationary propane-air flame issuing from a nozzle. In addition to a slight increase of the flame velocity, a fundamental change both in the shape of the burning zone and in the flow pattern could be observed. An attempt is made to explain the origin of the variations in the flame configuration on the basis of transition at the nozzle from jet flow to potential flow

Non-disjunction of chromosome 13

We performed a molecular study with 21 microsatellites on a sample of 82 trisomy 13 conceptuses, the largest number of cases studied to date. The parental origin was determined in every case and in 89% the extra chromosome 13 was of maternal origin with an almost equal number of maternal MI and MII errors. The latter finding is unique among human autosomal trisomies, where maternal MI (trisomies 15, 16, 21, 22) or MII (trisomy 18) errors dominate. Of the nine paternally derived cases five were of MII origin but none arose from MI errors. There was some evidence for elevated maternal age in cases with maternal meiotic origin for liveborn infants. Maternal and paternal ages were elevated in cases with paternal meiotic origin. This is in contrast to results from a similar study of non-disjunction of trisomy 21 where paternal but not maternal age was elevated. We find clear evidence for reduced recombination in both maternal MI and MII errors and the former is associated with a significant number of tetrads (33%) that are nullichiasmate, which do not appear to be a feature of normal chromosome 13 meiosis. This study supports the evidence for subtle chromosome-specific influences on the mechanisms that determine non-disjunction of human chromosomes, consistent with the diversity of findings for other trisomie

Jordfordelingen på Samsø og Endelave i det 16. og 17. århundrede set i lyset af den middelalderlige engelske jordhandel

Hahnemann har i sin artikel påvist bolets dynamiske rolle i jordfordelingen på de to øer, hvor man længere har holdt fast i systemer, der peger bagud mod middelalderens jordfordelinger. Artiklen drager en spændende sammenligning med forholdene i middelalderens England