A Novel Method for Detecting Association Between DNA Methylation and Diseases Using Spatial Information

DNA methylation may represent an important contributor to the missing heritability described in complex trait genetics. However, technology to measure DNA methylation has outpaced statistical methods for analysis. Taking advantage of the recent finding that methylated sites cluster together, we propose a Spatial Clustering Method (SCM) to detect differentially methylated regions (DMRs) in the genome in case and control studies using spatial location information. This new method compares the distribution of distances in cases and controls between DNA methylation marks in the genomic region of interest. A statistic is computed based on these distances. Proper type I error rate is maintained and statistical significance is evaluated using permutation test. The effectiveness of the SCM we propose is evaluated by a simulation study. By simulating a simple disease model, we demonstrate that SCM has good power to detect DMRs associated with the disease. Finally, we applied the SCM to an exploratory analysis of chromosome 14 from a colorectal cancer data set and identified statistically significant genomic regions. Identification of these regions should lead to a better understanding of methylated sites and their contribution to disease. The SCM can be used as a reliable statistical method for the identification of DMRs associated with disease states in exploratory epigenetic analyses.     

Aortico-right ventricular tunnel: prenatal diagnosis leading to neonatal survival

In the 36th week of gestation a large aortico-right ventricular tunnel with an otherwise structurally normal heart was diagnosed by fetal echocardiography. This report describes for the first time the impact of the timely prenatal diagnosis of an aortico-right ventricular tunnel followed by successful management in early infancy.     

Prediction of progression of radiologic damage in newly diagnosed rheumatoid arthritis

Objective. To investigate the extent to which early radiologic damage is predicted by joint inflammation in patients with newly diagnosed rheumatoid arthritis (RA). Methods. Regression analysis was performed on 1-year progression of total radiologic damage for baseline characteristics and cumulative disease activity measures, and the effects of continued joint inflammation on the progression of damage in separate joint groups were investigated. Results. Odds ratios for progression of total damage were 12 for the presence of rheumatoid factor, 5 for the presence of damage at baseline, and 2 for cumulative joint inflammation. A positive association between continued joint inflammation and progression of damage was found to be statistically significant for most joint groups. Conclusion. Progression of radiologic damage in patients with newly diagnosed RA is independently associated with the presence of rheumatoid factor and damage at baseline and with cumulative joint inflammation.     

Narcolepsy and pregnancy: a retrospective European evaluation of 249 pregnancies

In a retrospective cohort study undertaken in 12 European countries, 249 female narcoleptic patients with cataplexy (n = 216) and without cataplexy (n = 33) completed a self‐administrated questionnaire regarding pregnancy and childbirth. The cohort was divided further into patients whose symptoms of narcolepsy started before or during pregnancy (308 pregnancies) and those in whom the first symptoms of narcolepsy appeared after delivery (106 pregnancies). Patients with narcolepsy during pregnancy were older during their first pregnancy (P < 0.001) and had a higher body mass index (BMI) prior to pregnancy (P < 0.01). Weight gain during pregnancy was higher in narcoleptic patients with cataplexy (P < 0.01). More patients with narcolepsy–cataplexy during pregnancy had impaired glucose metabolism and anaemia. Three patients experienced cataplexy during delivery. The rate of caesarean sections was higher in the narcolepsy–cataplexy group compared to the narcolepsy group (P < 0.05). The mean birth weight and gestational age of neonates were within the normal range and did not differ across groups. Neonatal care was affected adversely by symptoms of narcolepsy in 60.1% of those with narcolepsy during pregnancy. This study reports more obstetric complications in patients with narcolepsy–cataplexy during pregnancy; however, these were not severe. This group also had a higher BMI and higher incidence of impaired glucose metabolism during pregnancy. Caesarian section was conducted more frequently in narcolepsy–cataplexy patients, despite cataplexy being a rare event during delivery. Furthermore, symptoms of narcolepsy may render care of the infant more difficult.     

Über die Galletreibende Wirkung von Cichorium Intybus L.

Ohne Zusammenfassung     

Decision-making after ultrasound diagnosis of fetal abnormality

During the last few decades, the use of ultrasonography for the detection of fetal abnormalities has become widespread in many industrialised countries. This resulted in a shift in timing of the diagnosis of congenital abnormalities in infants from the neonatal period to the prenatal period. This has major implications for both clinicians and the couples involved. In case of ultrasound diagnosis of fetal anomaly, there are several options for the obstetric management, ranging from standard care to non-aggressive care and termination of pregnancy. This essay explores the context of both clinical and parental decision making after ultrasound diagnosis of fetal abnormality, with emphasis on the Dutch situation. While normal findings at ultrasound examination have strong beneficial psychological effects on the pregnant woman and her partner, the couple is often ill prepared for bad news about the health of their unborn child in the case of abnormal findings. This is, in particular, true in settings where ultrasonography for the detection of fetal abnormalities is offered as an integral part of antenatal care without appropriate counselling. An important question is to what extent the couple should be supported in decision making when a fetal abnormality is diagnosed. In this context, the parental perception of having a choice varies markedly. When parents consider end-of-life decisions, they experience both ambivalent and emotional feelings. On the one hand, they are committed to their pregnancy, while on the other hand, they want to protect their child, themselves and the family from the burden of severe disability. These complex parental reactions have implications for the counselling strategy.

Epithelial-Mesenchymal Transition in Cancer: Parallels Between Normal Development and Tumor Progression

From the earliest stages of embryonic development, cells of epithelial and mesenchymal origin contribute to the structure and function of developing organs. However, these phenotypes are not always permanent, and instead, under the appropriate conditions, epithelial and mesenchymal cells convert between these two phenotypes. These processes, termed Epithelial-Mesenchymal Transition (EMT), or the reverse Mesenchymal-Epithelial Transition (MET), are required for complex body patterning and morphogenesis. In addition, epithelial plasticity and the acquisition of invasive properties without the full commitment to a mesenchymal phenotype are critical in development, particularly during branching morphogenesis in the mammary gland. Recent work in cancer has identified an analogous plasticity of cellular phenotypes whereby epithelial cancer cells acquire mesenchymal features that permit escape from the primary tumor. Because local invasion is thought to be a necessary first step in metastatic dissemination, EMT and epithelial plasticity are hypothesized to contribute to tumor progression. Similarities between developmental and oncogenic EMT have led to the identification of common contributing pathways, suggesting that the reactivation of developmental pathways in breast and other cancers contributes to tumor progression. For example, developmental EMT regulators including Snail/Slug, Twist, Six1, and Cripto, along with developmental signaling pathways including TGF-β and Wnt/β-catenin, are misexpressed in breast cancer and correlate with poor clinical outcomes. This review focuses on the parallels between epithelial plasticity/EMT in the mammary gland and other organs during development, and on a selection of developmental EMT regulators that are misexpressed specifically during breast cancer.     

Personalized augmented reality for anatomy education

Anatomy education is a challenging but vital element in forming future medical professionals. In this work, a personalized and interactive augmented reality system is developed to facilitate education. This system behaves as a “magic mirror” which allows personalized in‐situ visualization of anatomy on the user's body. Real‐time volume visualization of a CT dataset creates the illusion that the user can look inside their body. The system comprises a RGB‐D sensor as a real‐time tracking device to detect the user moving in front of a display. In addition, the magic mirror system shows text information, medical images, and 3D models of organs that the user can interact with. Through the participation of 7 clinicians and 72 students, two user studies were designed to respectively assess the precision and acceptability of the magic mirror system for education. The results of the first study demonstrated that the average precision of the augmented reality overlay on the user body was 0.96 cm, while the results of the second study indicate 86.1% approval for the educational value of the magic mirror, and 91.7% approval for the augmented reality capability of displaying organs in three dimensions. The usefulness of this unique type of personalized augmented reality technology has been demonstrated in this paper. Clin. Anat. 29:446–453, 2016. © 2015 Wiley Periodicals, Inc.     

MRI/linac integration.

PURPOSE/OBJECTIVES: In radiotherapy the healthy tissue involvement still poses serious dose limitations. This results in sub-optimal tumour dose and complications. Daily image guided radiotherapy (IGRT) is the key development in radiation oncology to solve this problem. MRI yields superb soft-tissue visualization and provides several imaging modalities for identification of movements, function and physiology. Integrating MRI functionality with an accelerator can make these capacities available for high precision, real time IGRT. DESIGN AND RESULTS: The system being built at the University Medical Center Utrecht is a 1.5T MRI scanner, with diagnostic imaging functionality and quality, integrated with a 6MV radiotherapy accelerator. The realization of a prototype of this hybrid system is a joint effort between the Radiotherapy Department of the University of Utrecht, the Netherlands, Elekta, Crawley, U.K., and Philips Research, Hamburg, Germany. Basically, the design is a 1.5 T Philips Achieva MRI scanner with a Magnex closed bore magnet surrounded by a single energy (6 MV) Elekta accelerator. Monte Carlo simulations are used to investigate the radiation beam properties of the hybrid system, dosimetry equipment and for the construction of patient specific dose deposition kernels in the presence of a magnetic field. The latter are used to evaluate the IMRT capability of the integrated MRI linac. CONCLUSIONS: A prototype hybrid MRI/linac for on-line MRI guidance of radiotherapy (MRIgRT) is under construction. The aim of the system is to deliver the radiation dose with mm precision based on diagnostic quality MR images.