Publications

959 Publications visible to you, out of a total of 959

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OBJECTIVE: There is evidence that sexual hormone concentrations and anthropometric factors influence the human voice. The goal of this study was to investigate to what extent body mass index (BMI), body height, body weight, breast-to-abdomen-ratio, testosterone, estradiol, dehydroepiandrosterone-sulfate (DHEA-S), follicle-stimulating hormone, and luteinizing hormone are associated with the sound pressure level and the fundamental frequency of the speaking voice in a cross-sectional approach among adults in the general population. METHODS: Speaking voice profiles with four different intensity levels, hormone concentrations, and anthropometric parameters were assessed for 2,381 individuals aged 40-79 years, who were randomly sampled from the population of a large city in Germany. Multivariate analysis was performed, adjusting for age and stratified by sex. RESULTS: Taller body height was associated with lower frequencies. Higher body weight was associated with lower frequencies and higher sound pressure levels. The ratio of chest to abdominal circumference was associated with the sound pressure levels in males and females: participants with larger breast-to-abdomen-ratio were found to have higher sound pressure levels. Among the sexual hormones, higher concentrations of DHEA-S were associated with lower fundamental frequencies of the voice while using the normal speaking voice. In addition, bioavailable testosterone was associated with the sound pressure level of the normal speaking voice in men and the softest speaking voice in women. CONCLUSION: Our findings suggest that BMI, body height, body weight, breast-to-abdomen-ratio, bioavailable testosterone, and DHEA-S are associated with the speaking voice in adults. No associations between testosterone and the frequency of the speaking voice were found.

Authors: L. Jost, M. Fuchs, M. Loeffler, J. Thiery, J. Kratzsch, T. Berger, C. Engel

Date Published: 26th Jul 2017

Publication Type: Journal article

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OBJECTIVE: The current study investigates potential pathways from socio-economic status (SES) to BMI in the adult population, considering psychological domains of eating behaviour (restrained eating, uncontrolled eating, emotional eating) as potential mediators stratified for sex. DESIGN: Data were derived from the population-based cross-sectional LIFE-Adult-Study. Parallel-mediation models were conducted to obtain the total, direct and indirect effects of psychological eating behaviour domains on the association between SES and BMI for men and for women. SETTING: Leipzig, Germany. SUBJECTS: We studied 5935 participants aged 18 to 79 years. RESULTS: Uncontrolled eating mediated the association between SES and BMI in men only and restrained eating in both men and women. Emotional eating did not act as mediator in this relationship. The total effect of eating behaviour domains on the association between SES and BMI was estimated as beta=-0.03 (se 0.02; 95 % CI -0.062, -0.003) in men and beta=-0.18 (se 0.02; 95 % CI -0.217, -0.138) in women. CONCLUSIONS: Our findings do not indicate a strong overall mediation effect of the eating behaviour domains restrained eating, uncontrolled eating and emotional eating on the association between SES and BMI. Further research on other pathways of this association is strongly recommended. Importantly, our findings indicate that, independent from one's social position, focusing on psychological aspects in weight reduction might be a promising approach.

Authors: A. Loffler, T. Luck, F. S. Then, C. Luck-Sikorski, A. Pabst, P. Kovacs, Y. Bottcher, J. Breitfeld, A. Tonjes, A. Horstmann, M. Loffler, C. Engel, J. Thiery, A. Villringer, M. Stumvoll, S. G. Riedel-Heller

Date Published: 25th Jul 2017

Publication Type: Journal article

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

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Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated-for the first time to our knowledge-associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 \times 10-6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 \times 10-9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

Authors: Julie Lecarpentier, Valentina Silvestri, Karoline B. Kuchenbaecker, Daniel Barrowdale, Joe Dennis, Lesley McGuffog, Penny Soucy, Goska Leslie, Piera Rizzolo, Anna Sara Navazio, Virginia Valentini, Veronica Zelli, Andrew Lee, Ali Amin Al Olama, Jonathan P. Tyrer, Melissa Southey, Esther M. John, Thomas A. Conner, David E. Goldgar, Saundra S. Buys, Ramunas Janavicius, Linda Steele, Yuan Chun Ding, Susan L. Neuhausen, Thomas v. O. Hansen, Ana Osorio, Jeffrey N. Weitzel, Angela Toss, Veronica Medici, Laura Cortesi, Ines Zanna, Domenico Palli, Paolo Radice, Siranoush Manoukian, Bernard Peissel, Jacopo Azzollini, Alessandra Viel, Giulia Cini, Giuseppe Damante, Stefania Tommasi, Paolo Peterlongo, Florentia Fostira, Ute Hamann, D. Gareth Evans, Alex Henderson, Carole Brewer, Diana Eccles, Jackie Cook, Kai-Ren Ong, Lisa Walker, Lucy E. Side, Mary E. Porteous, Rosemarie Davidson, Shirley Hodgson, Debra Frost, Julian Adlard, Louise Izatt, Ros Eeles, Steve Ellis, Marc Tischkowitz, Andrew K. Godwin, Alfons Meindl, Andrea Gehrig, Bernd Dworniczak, Christian Sutter, Christoph Engel, Dieter Niederacher, Doris Steinemann, Eric Hahnen, Jan Hauke, Kerstin Rhiem, Karin Kast, Norbert Arnold, Nina Ditsch, Shan Wang-Gohrke, Barbara Wappenschmidt, Dorothea Wand, Christine Lasset, Dominique Stoppa-Lyonnet, Muriel Belotti, Francesca Damiola, Laure Barjhoux, Sylvie Mazoyer, Mattias van Heetvelde, Bruce Poppe, Kim de Leeneer, Kathleen B. M. Claes, Miguel de La Hoya, Vanesa Garcia-Barberan, Trinidad Caldes, Pedro Perez Segura, Johanna I. Kiiski, Kristiina Aittomäki, Sofia Khan, Heli Nevanlinna, Christi J. van Asperen, Tibor Vaszko, Miklos Kasler, Edith Olah, Judith Balmaña, Sara Gutiérrez-Enríquez, Orland Diez, Alex Teulé, Angel Izquierdo, Esther Darder, Joan Brunet, Jesús Del Valle, Lidia Feliubadalo, Miquel Angel Pujana, Conxi Lazaro, Adalgeir Arason, Bjarni A. Agnarsson, Oskar Th Johannsson, Rosa B. Barkardottir, Elisa Alducci, Silvia Tognazzo, Marco Montagna, Manuel R. Teixeira, Pedro Pinto, Amanda B. Spurdle, Helene Holland, Jong Won Lee, Min Hyuk Lee, Jihyoun Lee, Sung-Won Kim, Eunyoung Kang, Zisun Kim, Priyanka Sharma, Timothy R. Rebbeck, Joseph Vijai, Mark Robson, Anne Lincoln, Jacob Musinsky, Pragna Gaddam, Yen Y. Tan, Andreas Berger, Christian F. Singer, Jennifer T. Loud, Mark H. Greene, Anna Marie Mulligan, Gord Glendon, Irene L. Andrulis, Amanda Ewart Toland, Leigha Senter, Anders Bojesen, Henriette Roed Nielsen, Anne-Bine Skytte, Lone Sunde, Uffe Birk Jensen, Inge Sokilde Pedersen, Lotte Krogh, Torben A. Kruse, Maria A. Caligo, Sook-Yee Yoon, Soo-Hwang Teo, Anna von Wachenfeldt, Dezheng Huo, Sarah M. Nielsen, Olufunmilayo I. Olopade, Katherine L. Nathanson, Susan M. Domchek, Christa Lorenchick, Rachel C. Jankowitz, Ian Campbell, Paul James, Gillian Mitchell, Nick Orr, Sue Kyung Park, Mads Thomassen, Kenneth Offit, Fergus J. Couch, Jacques Simard, Douglas F. Easton, Georgia Chenevix-Trench, Rita K. Schmutzler, Antonis C. Antoniou, Laura Ottini

Date Published: 10th Jul 2017

Publication Type: Journal article

Human Diseases: hereditary breast ovarian cancer syndrome

Abstract (Expand)

Age-related white matter hyperintensities (WMH) are a manifestation of white matter damage seen on magnetic resonance imaging (MRI). They are related to vascular risk factors and cognitive impairment. This study investigated the cognitive profile at different stages of WMH in a large community-dwelling sample; 849 subjects aged 21 to 79 years were classified on the 4-stage Fazekas scale according to hyperintense lesions seen on individual T2-weighted fluid-attenuated inversion recovery MRI scans. The evaluation of cognitive functioning included seven domains of cognitive performance and five domains of subjective impairment, as proposed by the DSM-5. For the first time, the impact of age-related WMH on Theory of Mind was investigated. Differences between Fazekas groups were analyzed non-parametrically and effect sizes were computed. Effect sizes revealed a slight overall cognitive decline in Fazekas groups 1 and 2 relative to healthy subjects. Fazekas group 3 presented substantial decline in social cognition, attention and memory, although characterized by a high inter-individual variability. WMH groups reported subjective cognitive decline. We demonstrate that extensive WMH are associated with specific impairment in attention, memory, social cognition, and subjective cognitive performance. The detailed neuropsychological characterization of WMH offers new therapeutic possibilities for those affected by vascular cognitive decline.

Authors: J. Kynast, L. Lampe, T. Luck, S. Frisch, K. Arelin, K. T. Hoffmann, M. Loeffler, S. G. Riedel-Heller, A. Villringer, M. L. Schroeter

Date Published: 8th Jul 2017

Publication Type: Journal article

Human Diseases: COL4A1-related familial vascular leukoencephalopathy

Abstract (Expand)

OBJECTIVES: The study investigated whether high mental demands at work, which have shown to promote a good cognitive functioning in old age, could offset the adverse association between social isolation and cognitive functioning. METHODS: Based on data from the population-based LIFE-Adult-Study, the association between cognitive functioning (Verbal Fluency Test, Trail Making Test B) and social isolation (Lubben Social Network Scale) as well as mental demands at work (O*NET database) was analyzed via linear regression analyses adjusted for age, sex, education, and sampling weights. RESULTS: Cognitive functioning was significantly lower in socially isolated individuals and in individuals working in low mental demands jobs-even in old age after retirement and even after taking into account the educational level. An interaction effect suggested stronger effects of mental demands at work in socially isolated than nonisolated individuals. CONCLUSIONS: The findings suggest that working in high mental-demand jobs could offset the adverse association between social isolation and cognitive functioning. Further research should evaluate how interventions that target social isolation and enhance mentally demanding activities promote a good cognitive functioning in old age.

Authors: F. S. Rodriguez, M. L. Schroeter, A. V. Witte, C. Engel, M. Loffler, J. Thiery, A. Villringer, T. Luck, S. G. Riedel-Heller

Date Published: 4th Jul 2017

Publication Type: Journal article

Abstract (Expand)

Background: There is an on-going debate whether 2- or 3-weekly administration of R-CHOP is the preferred first-line treatment for elderly patients with diffuse large B-cell lymphoma (DLBCL). The UK NCRI R-CHOP14v21 randomized phase 3 trial did not demonstrate a difference in outcomes between R-CHOP-14 and R-CHOP-21 in newly diagnosed DLBCL patients aged 19-88 years, but data on elderly patients have not been reported in detail so far. Here, we provide a subgroup analysis of patients >/=60 years treated on the R-CHOP14v21 trial with extended follow-up. Patients and methods: Six hundred and four R-CHOP14v21 patients >/=60 years were included in this subgroup analysis, with a median follow-up of 77.7 months. To assess the impact of MYC rearrangements (MYC-R) and double-hit-lymphoma (DHL) on outcome in elderly patients, we performed a joint analysis of cases with available molecular data from the R-CHOP14v21 (N = 217) and RICOVER-60 (N = 204) trials. Results: Elderly DLBCL patients received high dose intensities with median total doses of >/=98% for all agents. Toxicities were similar in both arms with the exception of more grade >/=3 neutropenia (P < 0.0001) and fewer grade >/=3 thrombocytopenia (P = 0.05) in R-CHOP-21 versus R-CHOP-14. The elderly patient population had a favorable 5-year overall survival (OS) of 69% (95% CI: 65-73). We did not identify any subgroup of patients that showed differential response to either regimen. In multivariable analysis including individual factors of the IPI, gender, bulk, B2M and albumin levels, only age and B2M were of independent prognostic significance for OS. Molecular analyses demonstrated a significant impact of MYC-R (HR = 1.96; 95% CI: 1.22-3.16; P = 0.01) and DHL (HR = 2.21; 95% CI: 1.18-4.11; P = 0.01) on OS in the combined trial cohorts, independent of other prognostic factors. Conclusions: Our data support equivalence of both R-CHOP application forms in elderly DLBCL patients. Elderly MYC-R and DHL patients have inferior prognosis and should be considered for alternative treatment approaches. Trial numbers: ISCRTN 16017947 (R-CHOP14v21); NCT00052936 (RICOVER-60).

Authors: A. Kuhnl, D. Cunningham, N. Counsell, E. A. Hawkes, W. Qian, P. Smith, N. Chadwick, A. Lawrie, P. Mouncey, A. Jack, C. Pocock, K. M. Ardeshna, J. Radford, A. McMillan, J. Davies, D. Turner, A. Kruger, P. W. Johnson, J. Gambell, A. Rosenwald, G. Ott, H. Horn, M. Ziepert, M. Pfreundschuh, D. Linch

Date Published: 1st Jul 2017

Publication Type: Not specified

Human Diseases: diffuse large B-cell lymphoma

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