@article{BirukovPolemitiJaegeretal.2022, author = {Birukov, Anna and Polemiti, Elli and Jaeger, Susanne and Stefan, Norbert and Schulze, Matthias B.}, title = {Fetuin-A and risk of diabetes-related vascular complications}, series = {Cardiovascular diabetology}, volume = {21}, journal = {Cardiovascular diabetology}, number = {1}, publisher = {BMC}, address = {London}, issn = {1475-2840}, doi = {10.1186/s12933-021-01439-8}, pages = {11}, year = {2022}, abstract = {Background Fetuin-A is a hepatokine which has the capacity to prevent vascular calcification. Moreover, it is linked to the induction of metabolic dysfunction, insulin resistance and associated with increased risk of diabetes. It has not been clarified whether fetuin-A associates with risk of vascular, specifically microvascular, complications in patients with diabetes. We aimed to investigate whether pre-diagnostic plasma fetuin-A is associated with risk of complications once diabetes develops. Methods Participants with incident type 2 diabetes and free of micro- and macrovascular disease from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam cohort (n = 587) were followed for microvascular and macrovascular complications (n = 203 and n = 60, respectively, median follow-up: 13 years). Plasma fetuin-A was measured approximately 4 years prior to diabetes diagnosis. Prospective associations between baseline fetuin-A and risk of complications were assessed with Cox regression. Results In multivariable models, fetuin-A was linearly inversely associated with incident total and microvascular complications, hazard ratio (HR, 95\% CI) per standard deviation (SD) increase: 0.86 (0.74; 0.99) for total, 0.84 (0.71; 0.98) for microvascular and 0.92 (0.68; 1.24) for macrovascular complications. After additional adjustment for cardiometabolic plasma biomarkers, including triglycerides and high-density lipoprotein, the associations were slightly attenuated: 0.88 (0.75; 1.02) for total, 0.85 (0.72; 1.01) for microvascular and 0.95 (0.67; 1.34) for macrovascular complications. No interaction by sex could be observed (p > 0.10 for all endpoints). Conclusions Our data show that lower plasma fetuin-A levels measured prior to the diagnosis of diabetes may be etiologically implicated in the development of diabetes-associated microvascular disease.}, language = {en} } @article{EichelmannSellemWittenbecheretal.2022, author = {Eichelmann, Fabian and Sellem, Laury and Wittenbecher, Clemens and J{\"a}ger, Susanne and Kuxhaus, Olga and Prada, Marcela and Cuadrat, Rafael and Jackson, Kim G. and Lovegrove, Julie A. and Schulze, Matthias Bernd}, title = {Deep lipidomics in human plasma: cardiometabolic disease risk and effect of dietary fat modulation}, series = {Circulation}, volume = {146}, journal = {Circulation}, number = {1}, publisher = {Lippincott Williams \& Wilkins}, address = {Philadelphia}, issn = {0009-7322}, doi = {10.1161/CIRCULATIONAHA.121.056805}, pages = {21 -- 35}, year = {2022}, abstract = {Background: In blood and tissues, dietary and endogenously generated fatty acids (FAs) occur in free form or as part of complex lipid molecules that collectively represent the lipidome of the respective tissue. We assessed associations of plasma lipids derived from high-resolution lipidomics with incident cardiometabolic diseases and subsequently tested if the identified risk-associated lipids were sensitive to dietary fat modification. Methods: The EPIC Potsdam cohort study (European Prospective Investigation into Cancer and Nutrition) comprises 27 548 participants recruited within an age range of 35 to 65 years from the general population around Potsdam, Germany. We generated 2 disease-specific case cohorts on the basis of a fixed random subsample (n=1262) and all respective cohort-wide identified incident primary cardiovascular disease (composite of fatal and nonfatal myocardial infarction and stroke; n=551) and type 2 diabetes (n=775) cases. We estimated the associations of baseline plasma concentrations of 282 class-specific FA abundances (calculated from 940 distinct molecular species across 15 lipid classes) with the outcomes in multivariable-adjusted Cox models. We tested the effect of an isoenergetic dietary fat modification on risk-associated lipids in the DIVAS randomized controlled trial (Dietary Intervention and Vascular Function; n=113). Participants consumed either a diet rich in saturated FAs (control), monounsaturated FAs, or a mixture of monounsaturated and n-6 polyunsaturated FAs for 16 weeks. Results: Sixty-nine lipids associated (false discovery rate<0.05) with at least 1 outcome (both, 8; only cardiovascular disease, 49; only type 2 diabetes, 12). In brief, several monoacylglycerols and FA16:0 and FA18:0 in diacylglycerols were associated with both outcomes; cholesteryl esters, free fatty acids, and sphingolipids were largely cardiovascular disease specific; and several (glycero)phospholipids were type 2 diabetes specific. In addition, 19 risk-associated lipids were affected (false discovery rate<0.05) by the diets rich in unsaturated dietary FAs compared with the saturated fat diet (17 in a direction consistent with a potential beneficial effect on long-term cardiometabolic risk). For example, the monounsaturated FA-rich diet decreased diacylglycerol(FA16:0) by 0.4 (95\% CI, 0.5-0.3) SD units and increased triacylglycerol(FA22:1) by 0.5 (95\% CI, 0.4-0.7) SD units. Conclusions: We identified several lipids associated with cardiometabolic disease risk. A subset was beneficially altered by a dietary fat intervention that supports the substitution of dietary saturated FAs with unsaturated FAs as a potential tool for primary disease prevention.}, language = {en} } @misc{RaafatMrochenAl’Sholuietal.2020, author = {Raafat, Dina and Mrochen, Daniel M. and Al'Sholui, Fawaz and Heuser, Elisa and Ryll, Ren{\´e} and Pritchett-Corning, Kathleen R. and Jacob, Jens and Walther, Bernd and Matuschka, Franz-Rainer and Richter, Dania}, title = {Molecular epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in wild, captive and laboratory rats}, series = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, journal = {Zweitver{\"o}ffentlichungen der Universit{\"a}t Potsdam : Humanwissenschaftliche Reihe}, number = {2}, issn = {1866-8364}, doi = {10.25932/publishup-51237}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-512379}, pages = {24}, year = {2020}, abstract = {Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4\%) than laboratory rats (12.3\%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages—many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus, respectively.}, language = {en} } @article{RaafatMrochenAl’Sholuietal.2020, author = {Raafat, Dina and Mrochen, Daniel M. and Al'Sholui, Fawaz and Heuser, Elisa and Ryll, Ren{\´e} and Pritchett-Corning, Kathleen R. and Jacob, Jens and Walther, Bernd and Matuschka, Franz-Rainer and Richter, Dania}, title = {Molecular epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in wild, captive and laboratory rats}, series = {Toxins}, volume = {12}, journal = {Toxins}, number = {2}, publisher = {MDPI}, address = {Basel}, issn = {2072-6651}, doi = {10.3390/toxins12020080}, pages = {1 -- 22}, year = {2020}, abstract = {Rats are a reservoir of human- and livestock-associated methicillin-resistant Staphylococcus aureus (MRSA). However, the composition of the natural S. aureus population in wild and laboratory rats is largely unknown. Here, 144 nasal S. aureus isolates from free-living wild rats, captive wild rats and laboratory rats were genotyped and profiled for antibiotic resistances and human-specific virulence genes. The nasal S. aureus carriage rate was higher among wild rats (23.4\%) than laboratory rats (12.3\%). Free-living wild rats were primarily colonized with isolates of clonal complex (CC) 49 and CC130 and maintained these strains even in husbandry. Moreover, upon livestock contact, CC398 isolates were acquired. In contrast, laboratory rats were colonized with many different S. aureus lineages—many of which are commonly found in humans. Five captive wild rats were colonized with CC398-MRSA. Moreover, a single CC30-MRSA and two CC130-MRSA were detected in free-living or captive wild rats. Rat-derived S. aureus isolates rarely harbored the phage-carried immune evasion gene cluster or superantigen genes, suggesting long-term adaptation to their host. Taken together, our study revealed a natural S. aureus population in wild rats, as well as a colonization pressure on wild and laboratory rats by exposure to livestock- and human-associated S. aureus, respectively.}, language = {en} } @article{GhodsGeorgiouSchmidtetal.2020, author = {Ghods, Mojtaba and Georgiou, Iakovos and Schmidt, Jeremias and Kruppa, Philipp}, title = {Disease progression and comorbidities in lipedema patients}, series = {Dermatologic therapy}, volume = {33}, journal = {Dermatologic therapy}, number = {6}, publisher = {Wiley-Blackwell}, address = {Oxford}, issn = {1529-8019}, doi = {10.1111/dth.14534}, pages = {8}, year = {2020}, abstract = {Multiple associated comorbidities have been described for lipedema patients. Disease diagnosis still remains challenging in many cases and is frequently delayed. The purpose of this study was to determine the most common comorbidities in lipedema patients and the impact of surgical treatment onto disease progression. A retrospective assessment of disease-related epidemiologic data was performed for patients who underwent liposuction between July 2009 and July 2019 in a specialized clinic for lipedema surgery. All patients received a standardized questionnaire regarding the clinical history and changes of lipedema-associated symptoms and comorbidities after surgery. 106 patients who underwent a total of 298 liposuction procedures were included in this study after returning the questionnaire fully filled-in. Multiple comorbidities were observed in the assessed collective. The prevalence for obesity, hypothyroidism, migraine, and depression were markedly increased in relation to comparable nonlipedema populations. Despite a median body mass index (BMI) of 31.6 kg/m(2) (IQR 26.4-38.8), unexpected low prevalence of diabetes (5\%) and dyslipidemia (7\%) was found. Diagnosis and initiation of guideline-appropriate treatment were delayed by years in many patients. After surgical treatment (medium follow-up 20 months, IQR 11-42), a significant reduction of lipedema-associated symptoms was demonstrated. Lipedema occurs with a diversity of associated comorbidities. Therefore, on the basis of available data, the authors suggest the necessity of a multimodal therapy concept for a comprehensive and holistic treatment. Despite a commonly increased BMI, lipedema patients appear to have an advantageous metabolic risk profile.}, language = {en} } @article{MatthiasRisslingPieperetal.2020, author = {Matthias, Katja and Rissling, Olesja and Pieper, Dawid Aleksander and Morche, Johannes and Nocon, Marc and Jacobs, Anja and Wegewitz, Uta Elke and Schirm, Jaqueline and Lorenz, Robert C.}, title = {The methodological quality of systematic reviews on the treatment of adult major depression needs improvement according to AMSTAR 2}, series = {Heliyon}, volume = {6}, journal = {Heliyon}, number = {9}, publisher = {Elsevier}, address = {London [u.a.]}, issn = {2405-8440}, doi = {10.1016/j.heliyon.2020.e04776}, pages = {7}, year = {2020}, abstract = {Background: Several standards have been developed to assess methodological quality of systematic reviews (SR). One widely used tool is the AMSTAR. A recent update -AMSTAR 2 -is a 16 item evaluation tool that enables a detailed assessment of SR that include randomised (RCT) or non-randomised studies (NRS) of healthcare interventions. Methods: A cross-sectional study of SR on pharmacological or psychological interventions in major depression in adults was conducted. SR published during 2012-2017 were sampled from MEDLINE, EMBASE and the Cochrane Database of SR. Methodological quality was assessed using AMSTAR 2. Potential predictive factors associated with quality were examined. Results: In rating overall confidence in the results of 60 SR four reviews were rated "high", two were "moderate", one was "low" and 53 were "critically low". The mean AMSTAR 2 percentage score was 45.3\% (standard deviation 22.6\%) in a wide range from 7.1\% to 93.8\%. Predictors of higher quality were: type of review (higher quality in Cochrane Reviews), SR including only randomized trials and higher journal impact factor. Limitations: AMSTAR 2 is not intended to be used for the generation of a percentage score. Conclusions: According to AMSTAR 2 the overall methodological quality of SR on the treatment of adult major depression needs improvement. Although there is a high need for summarized information in the field of mental health, this work demonstrates the need to critically assess SR before using their findings. Better adherence to established reporting guidelines for SR is needed.}, language = {en} } @article{GisderSchuelerHorchleretal.2017, author = {Gisder, Sebastian and Sch{\"u}ler, Vivian and Horchler, Lennart L. and Groth, Detlef and Genersch, Elke}, title = {Long-Term Temporal Trends of Nosema spp. Infection Prevalence in Northeast Germany}, series = {Frontiers in cellular and infection microbiology}, volume = {7}, journal = {Frontiers in cellular and infection microbiology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {2235-2988}, doi = {10.3389/fcimb.2017.00301}, pages = {14}, year = {2017}, abstract = {The Western honey bee (Apis mellifera) is widely used as commercial pollinator in worldwide agriculture and, therefore, plays an important role in global food security. Among the parasites and pathogens threatening health and survival of honey bees are two species of microsporidia, Nosema apis and Nosema ceranae. Nosema ceranae is considered an emerging pathogen of the Western honey bee. Reports on the spread of N. ceranae suggested that this presumably highly virulent species is replacing its more benign congener N. apis in the global A. mellifera population. We here present a 12 year longitudinal cohort study on the prevalence of N. apis and N. ceranae in Northeast Germany. Between 2005 and 2016, a cohort of about 230 honey bee colonies originating from 23 apiaries was sampled twice a year (spring and autumn) resulting in a total of 5,600 bee samples which were subjected to microscopic and molecular analysis for determining the presence of infections with N. apis or/and N. ceranae. Throughout the entire study period, both N. apis- and N. ceranae-infections could be diagnosed within the cohort. Logistic regression analysis of the prevalence data demonstrated a significant increase of N. ceranae-infections over the last 12 years, both in autumn (reflecting the development during the summer) and in spring (reflecting the development over winter) samples. Cell culture experiments confirmed that N. ceranae has a higher proliferative potential than N. apis at 27. and 33 degrees C potentially explaining the increase in N. ceranae prevalence during summer. In autumn, characterized by generally low infection prevalence, this increase was accompanied by a significant decrease in N. apis- infection prevalence. In contrast, in spring, the season with a higher prevalence of infection, no significant decrease of N. apis infections despite a significant increase in N. ceranae infections could be observed. Therefore, our data do not support a general advantage of N. ceranae over N. apis and an overall replacement of N. apis by N. ceranae in the studied honey bee population.}, language = {en} } @article{CasselRischIntziegiannietal.2018, author = {Cassel, Michael and Risch, Lucie and Intziegianni, Konstantina and Mueller, Juliane and Stoll, Josefine and Brecht, Pia and Mayer, Frank}, title = {Incidence of achilles and patellar tendinopathy in adolescent elite athletes}, series = {International journal of sports medicine}, volume = {39}, journal = {International journal of sports medicine}, number = {9}, publisher = {Thieme}, address = {Stuttgart}, issn = {0172-4622}, doi = {10.1055/a-0633-9098}, pages = {726 -- 732}, year = {2018}, abstract = {The study investigated the incidence of Achilles and patellar tendinopathy in adolescent elite athletes and non-athletic controls. Furthermore, predictive and associated factors for tendinopathy development were analyzed. The prospective study consisted of two measurement days (M1/M2) with an interval of 3.2 +/- 0.9 years. 157 athletes (12.1 +/- 0.7 years) and 25 controls (13.3 +/- 0.6 years) without Achilles/patellar tendinopathy were included at Ml. Clinical and ultrasound examinations of both Achilles (AT) and patellar tendons (PT) were performed. Main outcome measures were incidence tendinopathy and structural intratendinous alterations (hypo-/hyperechogenicity, vascularization) at M2 [\%]. Incidence of Achilles tendinopathy was 1\% in athletes and 0\% in controls. Patellar tendinopathy was more frequent in athletes (13 \%)than in controls (4\%). Incidence of intratendinous alterations in ATs was 1-2\% in athletes and 0 \% in controls, whereas in PTs it was 4-6 \% in both groups (p >0.05). Intratendinous alterations at M2 were associated with patellar tendinopathy in athletes (p <= 0.01). Intratendinous alterations at M1, anthropometric data, training amount, sports or sex did not predict tendinopathy development (p>0.05). Incidence often dinopathy and intratendinous alterations in adolescent athletes is low in ATs and more common in PTs. Development of intratendinous alterations in PT is associated with tend in opathy. However, predictive factors could not be identified.}, language = {en} } @misc{CasselMuellerMoseretal.2019, author = {Cassel, Michael and M{\"u}ller, Juliane and Moser, Othmar and Strempler, Mares Elaine and Reso, Judith and Mayer, Frank}, title = {Orthopedic Injury Profiles in Adolescent Elite Athletes}, series = {Postprints der Universit{\"a}t Potsdam Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam Humanwissenschaftliche Reihe}, number = {559}, issn = {1866-8364}, doi = {10.25932/publishup-43495}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-434953}, pages = {10}, year = {2019}, abstract = {Aim: The aim of the study was to identify common orthopedic sports injury profiles in adolescent elite athletes with respect to age, sex, and anthropometrics. Methods: A retrospective data analysis of 718 orthopedic presentations among 381 adolescent elite athletes from 16 different sports to a sports medical department was performed. Recorded data of history and clinical examination included area, cause and structure of acute and overuse injuries. Injury-events were analyzed in the whole cohort and stratified by age (11-14/15-17 years) and sex. Group differences were tested by chi-squared-tests. Logistic regression analysis was applied examining the influence of factors age, sex, and body mass index (BMI) on the outcome variables area and structure (a = 0.05). Results: Higher proportions of injury-events were reported for females (60\%) and athletes of the older age group (66\%) than males and younger athletes. The most frequently injured area was the lower extremity (47\%) followed by the spine (30.5\%) and the upper extremity (12.5\%). Acute injuries were mainly located at the lower extremity (74.5\%), while overuse injuries were predominantly observed at the lower extremity (41\%) as well as the spine (36.5\%). Joints (34\%), muscles (22\%), and tendons (21.5\%) were found to be the most often affected structures. The injured structures were different between the age groups (p = 0.022), with the older age group presenting three times more frequent with ligament pathology events (5.5\%/2\%) and less frequent with bony problems (11\%/20.5\%) than athletes of the younger age group. The injured area differed between the sexes (p = 0.005), with males having fewer spine injury-events (25.5\%/34\%) but more upper extremity injuries (18\%/9\%) than females. Regression analysis showed statistically significant influence for BMI (p = 0.002) and age (p = 0.015) on structure, whereas the area was significantly influenced by sex (p = 0.005). Conclusion: Events of soft-tissue overuse injuries are the most common reasons resulting in orthopedic presentations of adolescent elite athletes. Mostly, the lower extremity and the spine are affected, while sex and age characteristics on affected area and structure must be considered. Therefore, prevention strategies addressing the injury-event profiles should already be implemented in early adolescence taking age, sex as well as injury entity into account.}, language = {en} } @article{CasselMuellerMoseretal.2019, author = {Cassel, Michael and M{\"u}ller, Juliane and Moser, Othmar and Strempler, Mares Elaine and Reso, Judith and Mayer, Frank}, title = {Orthopedic Injury Profiles in Adolescent Elite Athletes}, series = {Frontiers in Physiology}, volume = {10}, journal = {Frontiers in Physiology}, publisher = {Frontiers Research Foundation}, address = {Lausanne}, issn = {1664-042X}, doi = {10.3389/fphys.2019.00544}, pages = {10}, year = {2019}, abstract = {Aim: The aim of the study was to identify common orthopedic sports injury profiles in adolescent elite athletes with respect to age, sex, and anthropometrics. Methods: A retrospective data analysis of 718 orthopedic presentations among 381 adolescent elite athletes from 16 different sports to a sports medical department was performed. Recorded data of history and clinical examination included area, cause and structure of acute and overuse injuries. Injury-events were analyzed in the whole cohort and stratified by age (11-14/15-17 years) and sex. Group differences were tested by chi-squared-tests. Logistic regression analysis was applied examining the influence of factors age, sex, and body mass index (BMI) on the outcome variables area and structure (a = 0.05). Results: Higher proportions of injury-events were reported for females (60\%) and athletes of the older age group (66\%) than males and younger athletes. The most frequently injured area was the lower extremity (47\%) followed by the spine (30.5\%) and the upper extremity (12.5\%). Acute injuries were mainly located at the lower extremity (74.5\%), while overuse injuries were predominantly observed at the lower extremity (41\%) as well as the spine (36.5\%). Joints (34\%), muscles (22\%), and tendons (21.5\%) were found to be the most often affected structures. The injured structures were different between the age groups (p = 0.022), with the older age group presenting three times more frequent with ligament pathology events (5.5\%/2\%) and less frequent with bony problems (11\%/20.5\%) than athletes of the younger age group. The injured area differed between the sexes (p = 0.005), with males having fewer spine injury-events (25.5\%/34\%) but more upper extremity injuries (18\%/9\%) than females. Regression analysis showed statistically significant influence for BMI (p = 0.002) and age (p = 0.015) on structure, whereas the area was significantly influenced by sex (p = 0.005). Conclusion: Events of soft-tissue overuse injuries are the most common reasons resulting in orthopedic presentations of adolescent elite athletes. Mostly, the lower extremity and the spine are affected, while sex and age characteristics on affected area and structure must be considered. Therefore, prevention strategies addressing the injury-event profiles should already be implemented in early adolescence taking age, sex as well as injury entity into account.}, language = {en} } @misc{SchatzOhlendorfBusseetal.2013, author = {Schatz, Juliane and Ohlendorf, Bernd and Busse, Peter and Pelz, Gerrit and Dolch, Dietrich and Teubner, Jens and Encarnacao, Jorge A. and M{\"u}hle, Ralf-Udo and Fischer, M. and Hoffmann, Bernd and Kwasnitschka, Linda and Balkema-Buschmann, Anne and Mettenleiter, Thomas Christoph and M{\"u}ller, T. and Freuling, Conrad M.}, title = {Twenty years of active bat rabies surveillance in Germany}, series = {Postprints der Universit{\"a}t Potsdam Humanwissenschaftliche Reihe}, journal = {Postprints der Universit{\"a}t Potsdam Humanwissenschaftliche Reihe}, number = {533}, issn = {1866-8364}, doi = {10.25932/publishup-41514}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-415140}, pages = {12}, year = {2013}, abstract = {In Germany, active bat rabies surveillance was conducted between 1993 and 2012. A total of 4546 oropharyngeal swab samples from 18 bat species were screened for the presence of EBLV-1- , EBLV-2- and BBLV-specific RNA. Overall, 0 center dot 15\% of oropharyngeal swab samples tested EBLV-1 positive, with the majority originating from Eptesicus serotinus. Interestingly, out of seven RT-PCR-positive oropharyngeal swabs subjected to virus isolation, viable virus was isolated from a single serotine bat (E. serotinus). Additionally, about 1226 blood samples were tested serologically, and varying virus neutralizing antibody titres were found in at least eight different bat species. The detection of viral RNA and seroconversion in repeatedly sampled serotine bats indicates long-term circulation of the virus in a particular bat colony. The limitations of random-based active bat rabies surveillance over passive bat rabies surveillance and its possible application of targeted approaches for future research activities on bat lyssavirus dynamics and maintenance are discussed.}, language = {en} } @misc{KuehnFloegelSookthaietal.2016, author = {K{\"u}hn, Tilman and Floegel, Anna and Sookthai, Disorn and Johnson, Theron and Rolle-Kampczyk, Ulrike and Otto, Wolfgang and von Bergen, Martin and Boeing, Heiner and Kaaks, Rudolf}, title = {Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study}, series = {BMC medicine}, journal = {BMC medicine}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-407258}, pages = {9}, year = {2016}, abstract = {Background: First metabolomics studies have indicated that metabolic fingerprints from accessible tissues might be useful to better understand the etiological links between metabolism and cancer. However, there is still a lack of prospective metabolomics studies on pre-diagnostic metabolic alterations and cancer risk. Methods: Associations between pre-diagnostic levels of 120 circulating metabolites (acylcarnitines, amino acids, biogenic amines, phosphatidylcholines, sphingolipids, and hexoses) and the risks of breast, prostate, and colorectal cancer were evaluated by Cox regression analyses using data of a prospective case-cohort study including 835 incident cancer cases. Results: The median follow-up duration was 8.3 years among non-cases and 6.5 years among incident cases of cancer. Higher levels of lysophosphatidylcholines (lysoPCs), and especially lysoPC a C18:0, were consistently related to lower risks of breast, prostate, and colorectal cancer, independent of background factors. In contrast, higher levels of phosphatidylcholine PC ae C30:0 were associated with increased cancer risk. There was no heterogeneity in the observed associations by lag time between blood draw and cancer diagnosis. Conclusion: Changes in blood lipid composition precede the diagnosis of common malignancies by several years. Considering the consistency of the present results across three cancer types the observed alterations point to a global metabolic shift in phosphatidylcholine metabolism that may drive tumorigenesis.}, language = {en} } @phdthesis{Wittenbecher2017, author = {Wittenbecher, Clemens}, title = {Linking whole-grain bread, coffee, and red meat to the risk of type 2 diabetes}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-404592}, school = {Universit{\"a}t Potsdam}, pages = {XII, 194, ii}, year = {2017}, abstract = {Background: Consumption of whole-grain, coffee, and red meat were consistently related to the risk of developing type 2 diabetes in prospective cohort studies, but potentially underlying biological mechanisms are not well understood. Metabolomics profiles were shown to be sensitive to these dietary exposures, and at the same time to be informative with respect to the risk of type 2 diabetes. Moreover, graphical network-models were demonstrated to reflect the biological processes underlying high-dimensional metabolomics profiles. Aim: The aim of this study was to infer hypotheses on the biological mechanisms that link consumption of whole-grain bread, coffee, and red meat, respectively, to the risk of developing type 2 diabetes. More specifically, it was aimed to consider network models of amino acid and lipid profiles as potential mediators of these risk-relations. Study population: Analyses were conducted in the prospective EPIC-Potsdam cohort (n = 27,548), applying a nested case-cohort design (n = 2731, including 692 incident diabetes cases). Habitual diet was assessed with validated semiquantitative food-frequency questionnaires. Concentrations of 126 metabolites (acylcarnitines, phosphatidylcholines, sphingomyelins, amino acids) were determined in baseline-serum samples. Incident type 2 diabetes cases were assed and validated in an active follow-up procedure. The median follow-up time was 6.6 years. Analytical design: The methodological approach was conceptually based on counterfactual causal inference theory. Observations on the network-encoded conditional independence structure restricted the space of possible causal explanations of observed metabolomics-data patterns. Given basic directionality assumptions (diet affects metabolism; metabolism affects future diabetes incidence), adjustment for a subset of direct neighbours was sufficient to consistently estimate network-independent direct effects. Further model-specification, however, was limited due to missing directionality information on the links between metabolites. Therefore, a multi-model approach was applied to infer the bounds of possible direct effects. All metabolite-exposure links and metabolite-outcome links, respectively, were classified into one of three categories: direct effect, ambiguous (some models indicated an effect others not), and no-effect. Cross-sectional and longitudinal relations were evaluated in multivariable-adjusted linear regression and Cox proportional hazard regression models, respectively. Models were comprehensively adjusted for age, sex, body mass index, prevalence of hypertension, dietary and lifestyle factors, and medication. Results: Consumption of whole-grain bread was related to lower levels of several lipid metabolites with saturated and monounsaturated fatty acids. Coffee was related to lower aromatic and branched-chain amino acids, and had potential effects on the fatty acid profile within lipid classes. Red meat was linked to lower glycine levels and was related to higher circulating concentrations of branched-chain amino acids. In addition, potential marked effects of red meat consumption on the fatty acid composition within the investigated lipid classes were identified. Moreover, potential beneficial and adverse direct effects of metabolites on type 2 diabetes risk were detected. Aromatic amino acids and lipid metabolites with even-chain saturated (C14-C18) and with specific polyunsaturated fatty acids had adverse effects on type 2 diabetes risk. Glycine, glutamine, and lipid metabolites with monounsaturated fatty acids and with other species of polyunsaturated fatty acids were classified as having direct beneficial effects on type 2 diabetes risk. Potential mediators of the diet-diabetes links were identified by graphically overlaying this information in network models. Mediation analyses revealed that effects on lipid metabolites could potentially explain about one fourth of the whole-grain bread effect on type 2 diabetes risk; and that effects of coffee and red meat consumption on amino acid and lipid profiles could potentially explain about two thirds of the altered type 2 diabetes risk linked to these dietary exposures. Conclusion: An algorithm was developed that is capable to integrate single external variables (continuous exposures, survival time) and high-dimensional metabolomics-data in a joint graphical model. Application to the EPIC-Potsdam cohort study revealed that the observed conditional independence patterns were consistent with the a priori mediation hypothesis: Early effects on lipid and amino acid metabolism had the potential to explain large parts of the link between three of the most widely discussed diabetes-related dietary exposures and the risk of developing type 2 diabetes.}, language = {en} } @article{SchatzOhlendorfBusseetal.2014, author = {Schatz, J. and Ohlendorf, B. and Busse, P. and Pelz, G. and Dolch, D. and Teubner, J. and Encarnacao, Jorge A. and Muehle, Ralf -Udo and Fischer, M. and Hoffmann, B. and Kwasnitschka, L. and Balkema-Buschmann, Anne and Mettenleiter, Thomas Christoph and Mueller, T. and Freuling, C. M.}, title = {Twenty years of active bat rabies surveillance in Germany}, series = {Epidemiology and infection}, volume = {142}, journal = {Epidemiology and infection}, number = {6}, publisher = {Cambridge Univ. Press}, address = {New York}, issn = {0950-2688}, doi = {10.1017/S0950268813002185}, pages = {1155 -- 1166}, year = {2014}, abstract = {In Germany, active bat rabies surveillance was conducted between 1993 and 2012. A total of 4546 oropharyngeal swab samples from 18 bat species were screened for the presence of EBLV-1- , EBLV-2- and BBLV-specific RNA. Overall, 0 center dot 15\% of oropharyngeal swab samples tested EBLV-1 positive, with the majority originating from Eptesicus serotinus. Interestingly, out of seven RT-PCR-positive oropharyngeal swabs subjected to virus isolation, viable virus was isolated from a single serotine bat (E. serotinus). Additionally, about 1226 blood samples were tested serologically, and varying virus neutralizing antibody titres were found in at least eight different bat species. The detection of viral RNA and seroconversion in repeatedly sampled serotine bats indicates long-term circulation of the virus in a particular bat colony. The limitations of random-based active bat rabies surveillance over passive bat rabies surveillance and its possible application of targeted approaches for future research activities on bat lyssavirus dynamics and maintenance are discussed.}, language = {en} }