Publications

26 Publications matching the given criteria: (Clear all filters)

Abstract (Expand)

3D-body scanning anthropometry is a suitable method for characterization of physiological development of children and adolescents, and for understanding onset and progression of disorders like overweight and obesity. Here we present a novel body typing approach to describe and to interpret longitudinal 3D-body scanning data of more than 800 children and adolescents measured in up to four follow-ups in intervals of 1 year, referring to an age range between 6 and 18 years. We analyzed transitions between body types assigned to lower-, normal- and overweight participants upon development of children and adolescents. We found a virtually parallel development of the body types with only a few transitions between them. Body types of children and adolescents tend to conserve their weight category. 3D body scanning anthropometry in combination with body typing constitutes a novel option to investigate onset and progression of obesity in children.

Authors: H. Loeffler-Wirth, M. Vogel, T. Kirsten, F. Glock, T. Poulain, A. Korner, M. Loeffler, W. Kiess, H. Binder

Date Published: 14th Sep 2018

Publication Type: Not specified

Human Diseases: obesity

Abstract (Expand)

Colorectal cancer (CRC) arising in Lynch syndrome (LS) comprises tumours with constitutional mutations in DNA mismatch repair genes. There is still a lack of whole-genome and transcriptome studies of LS-CRC to address questions about similarities and differences in mutation and gene expression characteristics between LS-CRC and sporadic CRC, about the molecular heterogeneity of LS-CRC, and about specific mechanisms of LS-CRC genesis linked to dysfunctional mismatch repair in LS colonic mucosa and the possible role of immune editing. Here, we provide a first molecular characterization of LS tumours and of matched tumour-distant reference colonic mucosa based on whole-genome DNA-sequencing and RNA-sequencing analyses. Our data support two subgroups of LS-CRCs, G1 and G2, whereby G1 tumours show a higher number of somatic mutations, a higher amount of microsatellite slippage, and a different mutation spectrum. The gene expression phenotypes support this difference. Reference mucosa of G1 shows a strong immune response associated with the expression of HLA and immune checkpoint genes and the invasion of CD4+ T cells. Such an immune response is not observed in LS tumours, G2 reference and normal (non-Lynch) mucosa, and sporadic CRC. We hypothesize that G1 tumours are edited for escape from a highly immunogenic microenvironment via loss of HLA presentation and T-cell exhaustion. In contrast, G2 tumours seem to develop in a less immunogenic microenvironment where tumour-promoting inflammation parallels tumourigenesis. Larger studies on non-neoplastic mucosa tissue of mutation carriers are required to better understand the early phases of emerging tumours. Copyright (c) 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Authors: H. Binder, L. Hopp, M. R. Schweiger, S. Hoffmann, F. Juhling, M. Kerick, B. Timmermann, S. Siebert, C. Grimm, L. Nersisyan, A. Arakelyan, M. Herberg, P. Buske, H. Loeffler-Wirth, M. Rosolowski, C. Engel, J. Przybilla, M. Peifer, N. Friedrichs, G. Moeslein, M. Odenthal, M. Hussong, S. Peters, S. Holzapfel, J. Nattermann, R. Hueneburg, W. Schmiegel, B. Royer-Pokora, S. Aretz, M. Kloth, M. Kloor, R. Buettner, J. Galle, M. Loeffler

Date Published: 21st Jul 2017

Publication Type: Not specified

Human Diseases: Lynch syndrome, colorectal cancer

Abstract (Expand)

Background: Hippocampal volume, assessed via high-resolution MRI, is associated with memory and visuospatial performance in humans (Squire, 2004) and specifically prone to develop atrophy with age (Apostolova,2015). This process has been linked to neurodegenerative diseases, such as Alzheimer’s disease (Apostolova,2015) and a decline of cognitive functions (Bruno,2016). However, due to differences in study-design and characteristics certain heterogeneity in results remains, in particular considering subfieldspecific effects (deFlores,2015). Therefore, we aim to determine the association of volumes of the whole hippocampus and its subfields on cognition in a large population-based cohort. Methods: Subjects: 1956 healthy participants from the Leipzig Research-Center-for-Civilization-Disease, aged 19-82years with MRI and neuropsychological tests (mean-age=57.61,±15.08SD). Exclusion: stroke, major-brain-pathologies, central-nervous-medication. Independent Variables: Volume of hippocampus and its subfields (CornuAmmonis1, 2-3, 4-DentateGyrus,(Pre-)subiculum). Dependent Variables: Verbal word-list learning, verbal-fluency, TrailMakingTask-(TMT)-A&B. Covariates: sex, age, years-of-education, total grey-mattervolume Image Analysis on high-resolution T1-images assessed at 3T. Hippocampal volumes were estimated using automatic segmentation analysis implemented in FreeSurfer (www.freesurfer.net). Statistical Analysis: Independent and dependent variables were first entered into Pearson Correlations. Variables with a correlation coefficient of r>0.1 were entered into multiple linear-regressions and adjusted for potential confounding(forward inclusion-model). Results: According to bivariate correlations, better performance in verbal-learning, verbal-fluency and TMT-A&B correlated moderately with larger whole-hippocampal volume and the volumes of all subfields(all |r|>0.102, all p0.046, all p0.5). Conclusions: Using a large cross-sectional cohort of healthy adults we found that volumes of the whole-hippocampus and subfields covering the CA4/dentate-gyrus region were weakly, yet specifically associated with verbal-learning and spatial processing-speed. Our preliminary results are in line with previous studies presuming a differential involvement of the hippocampus in tasks of verbal-learning and spatial processing (Oosterman,2010). Upcoming analyses implementing parcellation along the anteriorposterior- axis and random-effect-models might help to further disentangle these effects.

Authors: S. Huhn, R. Zhang, Frauke Beyer, L. Lampe, T. Luck, S. G. Riedel-Heller, M. L. Schroeter, Markus Löffler, M. Stumvoll, A. Villringer, A. V. Witte

Date Published: 1st Jul 2017

Publication Type: Not specified

Human Diseases: cognitive disorder, dementia

Abstract (Expand)

BACKGROUND/OBJECTIVES: The brain has a central role in regulating ingestive behavior in obesity. Analogous to addiction behaviors, an imbalance in the processing of rewarding and salient stimuli results in maladaptive eating behaviors that override homeostatic needs. We performed network analysis based on graph theory to examine the association between body mass index (BMI) and network measures of integrity, information flow and global communication (centrality) in reward, salience and sensorimotor regions and to identify sex-related differences in these parameters. SUBJECTS/METHODS: Structural and diffusion tensor imaging were obtained in a sample of 124 individuals (61 males and 63 females). Graph theory was applied to calculate anatomical network properties (centrality) for regions of the reward, salience and sensorimotor networks. General linear models with linear contrasts were performed to test for BMI and sex-related differences in measures of centrality, while controlling for age. RESULTS: In both males and females, individuals with high BMI (obese and overweight) had greater anatomical centrality (greater connectivity) of reward (putamen) and salience (anterior insula) network regions. Sex differences were observed both in individuals with normal and elevated BMI. In individuals with high BMI, females compared to males showed greater centrality in reward (amygdala, hippocampus and nucleus accumbens) and salience (anterior mid-cingulate cortex) regions, while males compared to females had greater centrality in reward (putamen) and sensorimotor (posterior insula) regions. CONCLUSIONS: In individuals with increased BMI, reward, salience and sensorimotor network regions are susceptible to topological restructuring in a sex-related manner. These findings highlight the influence of these regions on integrative processing of food-related stimuli and increased ingestive behavior in obesity, or in the influence of hedonic ingestion on brain topological restructuring. The observed sex differences emphasize the importance of considering sex differences in obesity pathophysiology.

Authors: A. Gupta, E. A. Mayer, K. Hamadani, R. Bhatt, C. Fling, M. Alaverdyan, C. Torgerson, C. Ashe-McNalley, J. D. Van Horn, B. Naliboff, K. Tillisch, C. P. Sanmiguel, J. S. Labus

Date Published: 1st Apr 2017

Publication Type: Not specified

Human Diseases: eating disorder

Abstract (Expand)

Clinical and epidemiological studies are commonly used in medical sciences. They typically collect data by using different input forms and information systems. Metadata describing input forms, database schemas and input systems are used for data integration but are typically distributed over different software tools; each uses portions of metadata, such as for loading (ETL), data presentation and analysis. In this paper, we describe an approach managing metadata centrally and consistently in a dedicated Metadata Repository (MDR). Metadata can be provided to different tools. Moreover, the MDR includes a matching component creating schema mappings as a prerequisite to integrate captured medical data. We describe the approach, the MDR infrastructure and provide algorithms for creating schema mappings. Finally, we show selected evaluation results. The MDR is fully operational and used to integrate data from a multitude of input forms and systems in the epidemiological study LIFE.

Authors: Toralf Kirsten, A. Kiel, M. Rühle, J.Wagner

Date Published: 2nd Mar 2017

Publication Type: Not specified

Abstract (Expand)

Background and objectives: Obesity has been associated with increased risk of dementia. Grey and white matter (WM) of the brain are commonly used as biomarkers for early detection of dementia. However, considering WM, available neuroimaging studies had mainly small sample size and yielded less conclusive results (Kullmann et al., 2015). Recently, a positive correlation between obesity and fractional anisotropy (FA) in a middle age group was reported (Birdsill et al. 2017). Furthermore, obesity is related to many medical problems such as diabetes and hypertension. Diabetes and hypertension were found to be correlated with brain structures independently (de Leeuw et al., 2002; Weinstein et al., 2015). Yet, studies rarely investigated non-lesion WM microstructure and its association with diabetes and blood pressure. Therefore we aim to investigate the relation between abdominal obesity, diabetes, blood pressure and WM microstructural variability in a large cohort of community-dwelling healthy adults. Methods: The sample included dementia-free participants (mean age 55 ± 16 years; 50.7% women) of the LIFE cohort with brain MRI scans (n = 1255). WM microstructure was measured with diffusion tensor imaging (DTI). Mean FA was derived from the individual WM skeleton processed by tract-based-spatial-statistic method. Linear regression models were used to assess the relationships between diabetes, blood pressure, waist to hip ratio (WHR) and DTI parameters. Adjustments were made for age, sex, education and Apoe4. Results: The preliminary result indicated diabetes, systolic blood pressure and WHR were independently associated with lower FA, and diabetes explained the most variance besides age. Subgroup analysis revealed both systolic blood pressure and WHR were negatively associated with mean FA in the non-diabetes group (n=1101). Conclusions: The preliminary result of our study indicates that diabetes accelerated brain aging on directional diffusion of WM. Abdominal fat and blood pressure were associated with WM variabilities independently from age, sex and diabetes. With subsequent analysis of additional DTI measures, blood parameters, WM hyperintensity maps and voxel-based microstructural WM “integrity”, we aim to further characterize the associations between obesity, diabetes, blood pressure and WM microstructure. This will contribute to the existing literature and help to disentangle the underlying mechanism.

Authors: Rui Zhang, Frauke Beyer, L. Lampe, T. Luck, S. G. Riedel-Heller, M. Stumvoll, Markus Löffler, M. L. Schroeter, A. Villringer, A. V. Witte

Date Published: 2017

Publication Type: Not specified

Human Diseases: diabetes mellitus, obesity, hypertension

Abstract (Expand)

Epidemiological studies analyze and monitor the health state of a population. They typically use different methods and techniques to capture and to integrate data of interest before they can be analyzed. As new technologies and, thus, devices are available for data capturing, such as wearables, new requirements arise for current data integration approaches. In this paper, we review current techniques and approaches as well as new trends in data capturing and the resulting requirement for its integration.

Authors: T. Kirsten, J. Bumberger, G. Ivanova, P. Dietrich, C. Engel, M. Loeffler, W. Kiess

Date Published: 2017

Publication Type: InBook

Powered by
(v.1.13.0-master)
Copyright © 2008 - 2021 The University of Manchester and HITS gGmbH
Institute for Medical Informatics, Statistics and Epidemiology, University of Leipzig

By continuing to use this site you agree to the use of cookies