TY - GEN A1 - Raafat, Dina A1 - Mrochen, Daniel M. A1 - Al’Sholui, Fawaz A1 - Heuser, Elisa A1 - Ryll, René A1 - Pritchett-Corning, Kathleen R. A1 - Jacob, Jens A1 - Walther, Bernd A1 - Matuschka, Franz-Rainer A1 - Richter, Dania T1 - Molecular epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in wild, captive and laboratory rats BT - Effect of habitat on the nasal S. aureus population T2 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 873 KW - Staphylococcus aureus KW - rat KW - clonal complex KW - host adaptation KW - livestock KW - laboratory KW - coagulation KW - immune evasion cluster KW - habitat KW - epidemiology Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-512379 SN - 1866-8364 IS - 2 ER - TY - JOUR A1 - Raafat, Dina A1 - Mrochen, Daniel M. A1 - Al’Sholui, Fawaz A1 - Heuser, Elisa A1 - Ryll, René A1 - Pritchett-Corning, Kathleen R. A1 - Jacob, Jens A1 - Walther, Bernd A1 - Matuschka, Franz-Rainer A1 - Richter, Dania T1 - Molecular epidemiology of methicillin-susceptible and methicillin-resistant Staphylococcus aureus in wild, captive and laboratory rats BT - Effect of habitat on the nasal S. aureus population JF - Toxins N2 - 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. KW - Staphylococcus aureus KW - rat KW - clonal complex KW - host adaptation KW - livestock KW - laboratory KW - coagulation KW - immune evasion cluster KW - habitat KW - epidemiology Y1 - 2020 U6 - https://doi.org/10.3390/toxins12020080 SN - 2072-6651 VL - 12 IS - 2 SP - 1 EP - 22 PB - MDPI CY - Basel ER - TY - JOUR A1 - Ghods, Mojtaba A1 - Georgiou, Iakovos A1 - Schmidt, Jeremias A1 - Kruppa, Philipp T1 - Disease progression and comorbidities in lipedema patients BT - a 10-year retrospective analysis JF - Dermatologic therapy N2 - 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. KW - comorbidities KW - epidemiology KW - lipedema KW - lipoedema KW - subcutaneous adipose tissue Y1 - 2020 U6 - https://doi.org/10.1111/dth.14534 SN - 1529-8019 VL - 33 IS - 6 PB - Wiley-Blackwell CY - Oxford ER - TY - JOUR A1 - Matthias, Katja A1 - Rissling, Olesja A1 - Pieper, Dawid Aleksander A1 - Morche, Johannes A1 - Nocon, Marc A1 - Jacobs, Anja A1 - Wegewitz, Uta Elke A1 - Schirm, Jaqueline A1 - Lorenz, Robert C. T1 - The methodological quality of systematic reviews on the treatment of adult major depression needs improvement according to AMSTAR 2 BT - a cross-sectional study JF - Heliyon N2 - 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. KW - public health KW - epidemiology KW - psychiatry KW - depression KW - evidence-based KW - medicine KW - AMSTAR 2 KW - methodological quality KW - risk of bias KW - systematic KW - review KW - major depression Y1 - 2020 U6 - https://doi.org/10.1016/j.heliyon.2020.e04776 SN - 2405-8440 VL - 6 IS - 9 PB - Elsevier CY - London [u.a.] ER - TY - JOUR A1 - Gisder, Sebastian A1 - Schüler, Vivian A1 - Horchler, Lennart L. A1 - Groth, Detlef A1 - Genersch, Elke T1 - Long-Term Temporal Trends of Nosema spp. Infection Prevalence in Northeast Germany BT - Continuous Spread of Nosema ceranae, an Emerging Pathogen of Honey Bees (Apis mellifera), but No General Replacement of Nosema apis JF - Frontiers in cellular and infection microbiology N2 - 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. KW - honey bee KW - Apis mellifera KW - Nosema spp. KW - epidemiology KW - replacement Y1 - 2017 U6 - https://doi.org/10.3389/fcimb.2017.00301 SN - 2235-2988 VL - 7 PB - Frontiers Research Foundation CY - Lausanne ER - TY - JOUR A1 - Cassel, Michael A1 - Risch, Lucie A1 - Intziegianni, Konstantina A1 - Mueller, Juliane A1 - Stoll, Josefine A1 - Brecht, Pia A1 - Mayer, Frank T1 - Incidence of achilles and patellar tendinopathy in adolescent elite athletes JF - International journal of sports medicine N2 - 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. KW - epidemiology KW - young athletes KW - sonography KW - vascularization KW - hypoechogenicities Y1 - 2018 U6 - https://doi.org/10.1055/a-0633-9098 SN - 0172-4622 SN - 1439-3964 VL - 39 IS - 9 SP - 726 EP - 732 PB - Thieme CY - Stuttgart ER - TY - GEN A1 - Cassel, Michael A1 - Müller, Juliane A1 - Moser, Othmar A1 - Strempler, Mares Elaine A1 - Reso, Judith A1 - Mayer, Frank T1 - Orthopedic Injury Profiles in Adolescent Elite Athletes BT - A Retrospective Analysis From a Sports Medicine Department T2 - Postprints der Universität Potsdam Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 559 KW - overuse injuries KW - epidemiology KW - complaints KW - symptoms KW - risk factors KW - sports Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-434953 SN - 1866-8364 IS - 559 ER - TY - JOUR A1 - Cassel, Michael A1 - Müller, Juliane A1 - Moser, Othmar A1 - Strempler, Mares Elaine A1 - Reso, Judith A1 - Mayer, Frank T1 - Orthopedic Injury Profiles in Adolescent Elite Athletes BT - A Retrospective Analysis From a Sports Medicine Department JF - Frontiers in Physiology N2 - 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. KW - overuse injuries KW - epidemiology KW - complaints KW - symptoms KW - risk factors KW - sports Y1 - 2019 U6 - https://doi.org/10.3389/fphys.2019.00544 SN - 1664-042X VL - 10 PB - Frontiers Research Foundation CY - Lausanne ER - TY - GEN A1 - Schatz, Juliane A1 - Ohlendorf, Bernd A1 - Busse, Peter A1 - Pelz, Gerrit A1 - Dolch, Dietrich A1 - Teubner, Jens A1 - Encarnacao, Jorge A. A1 - Mühle, Ralf-Udo A1 - Fischer, M. A1 - Hoffmann, Bernd A1 - Kwasnitschka, Linda A1 - Balkema-Buschmann, Anne A1 - Mettenleiter, Thomas Christoph A1 - Müller, T. A1 - Freuling, Conrad M. T1 - Twenty years of active bat rabies surveillance in Germany BT - a detailed analysis and future perspectives T2 - Postprints der Universität Potsdam Humanwissenschaftliche Reihe N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Humanwissenschaftliche Reihe - 533 KW - Bat rabies KW - epidemiology KW - lyssavirus KW - surveillance Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-415140 SN - 1866-8364 IS - 533 ER - TY - GEN A1 - Kühn, Tilman A1 - Floegel, Anna A1 - Sookthai, Disorn A1 - Johnson, Theron A1 - Rolle-Kampczyk, Ulrike A1 - Otto, Wolfgang A1 - von Bergen, Martin A1 - Boeing, Heiner A1 - Kaaks, Rudolf T1 - Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study T2 - BMC medicine N2 - 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 437 KW - metabolomics KW - epidemiology KW - breast cancer KW - prostate cancer KW - colorectal cancer Y1 - 2018 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-407258 ER - TY - THES A1 - Wittenbecher, Clemens T1 - Linking whole-grain bread, coffee, and red meat to the risk of type 2 diabetes T1 - Der Einfluss von Vollkornbrot, Kaffee, und rotem Fleisch auf das Typ 2 Diabetesrisiko BT - using metabolomics networks to infer potential biological mechanisms BT - Verwendung von Metabolomics-Netzwerken, um auf biologische Mechanismen zu schließen N2 - 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. N2 - Hintergrund: Evidenz aus prospektiven Kohortenstudien belegt, dass der gewohnheitsmäßige Verzehr von Vollkorn, Kaffee und rotem Fleisch mit dem Risiko an Typ 2 Diabetes zu erkranken assoziiert ist. Dieser Risikobeziehung eventuell zugrunde liegende Mechanismen sind allerdings noch weitgehend unklar. Des Weiteren wurde gezeigt, dass Metabolitenprofile im Blut durch die oben genannten Ernährungs-expositionen beeinflusst werden und außerdem in Zusammenhang mit dem Typ 2 Diabetesrisiko stehen. Zusätzlich wurde beschrieben, dass grafische Netzwerkmodelle von Metabolitenprofilen die zugrunde liegenden Stoffwechselprozesse gut abbilden. Zielstellung: Das Ziel dieser Arbeit war es, Hypothesen bezüglich biologischer Mechanismen zu generieren, die die Assoziationen des Vollkornverzehrs, des Kaffeekonsums und des Fleischverzehrs mit dem Typ 2 Diabetesrisiko erklären könnten. Im speziellen sollten Aminosäure- und Lipidprofile als mögliche Mediatoren des Risikozusammenhangs untersucht werden. Studienpopulation: Analysen wurden auf Grundlage von Daten aus der prospektiven EPIC-Potsdam Kohortenstudie (n=27,548) durchgeführt, wobei ein Fall-Kohorten-Design verwendet wurde (n=2317, darunter 692 inzidente Typ 2 Diabetesfälle). Ernährungsgewohnheiten wurden mit einem validierten, semiquantitativen Verzehrshäufigkeitsfragebogen erfasst. Die Konzentrationen von 126 Metaboliten (Aminosäuren, Acylcarnitine, Sphingomyeline und Phosphatidylcholine) wurden zur Basiserhebung genommen Blutproben gemessen. Inzidente Typ 2 Diabetesfälle wurden im Rahmen einer aktiven Folgeerhebung detektiert und verifiziert. Die mediane Dauer des berücksichtigten prospektiven Erhebungszeitraums lag für diese Studie bei 6,6 Jahren. Aufbau der Analysen: Die theoretische Grundlage für den methodischen Ansatz dieser Arbeit bildete die kontrafaktische Theorie der Kausalinferenz. Die in Netzwerken kodierte konditionale Unabhängigkeitsstruktur wurde genutzt, um den Raum möglicher Modelle zu begrenzen, die die beobachteten Zusammenhänge zwischen den Metaboliten erklären könnten. Unter Annahme weniger grundlegender Effektrichtungen (von der Ernährung auf die Netzwerke gerichtete Effekte; von den Netzwerken auf das Diabetesrisiko gerichtete Effekte) genügt die Adjustierung für eine Teilmenge der direkten Nachbarn im Netzwerk, um netzwerkunabhängige direkte Effekte konsistent zu schätzen. Eine weitere Spezifizierung der Modelle war allerdings aufgrund fehlender Richtungsinformationen zu den Metaboliten-abhängigkeiten nicht möglich. Deshalb wurde ein Multi-Modellierungsansatz gewählt, um die Grenzen möglicher Effekte zu schlussfolgern. Alle möglichen Ernährungs-Metaboliten-Beziehungen und Metaboliten-Typ 2 Diabetesrisiko-Beziehungen wurden dadurch in eine der folgenden drei Kategorien klassifiziert: Direkter Effekt, Unklar, Kein Effekt. Querschnittsbeziehungen wurden in multivariabel adjustierten linearen Regressionsmodellen untersucht. Longitudinale Zusammenhänge wurden mit Cox-Regressionsmodellen geschätzt. Alle Modelle wurden für Alter, Geschlecht, Body-Mass-Index, prävalente Hypertonie, Ernährungs- und Lebensstilfaktoren und die Einnahme von Medikamenten adjustiert. Ergebnisse: Der Verzehr von Vollkornbrot stand im Zusammenhang mit niedrigeren Konzentrationen gesättigter und einfach ungesättigter Fettsäuren. Kaffee stand in Beziehung zu niedrigeren Konzentrationen verzweigtkettiger und aromatischer Aminosäuren und hatte potentielle Effekte auf das Fettsäureprofil in den Lipidmetaboliten. Rotes Fleisch zeigte einen Zusammenhang mit niedrigeren Glyzinspiegeln und mit höheren Konzentrationen verzweigtkettiger Aminosäuren. Außerdem stand das Fettsäureprofil in den verschieden Gruppen von Lipidmetaboliten in Zusammenhang mit dem Fleischverzehr. Des Weiteren wurden potentielle Effekte der Metabolite auf das Typ 2 Diabetesrisiko gefunden. Aromatische Aminosäuren und Lipidmetabolite mit geradzahligen, gesättigten (C14-C16) und mit spezifischen mehrfach ungesättigten Fettsäureseitenketten standen mit einem erhöhten Typ 2 Diabetesrisiko in Beziehung. Glyzin, Glutamin und Lipidmetabolite mit einfach ungesättigten und anderen mehrfach ungesättigten Fettsäureseitenketten zeigten einen günstigen Zusammenhang mit dem Diabetesrisiko. Mögliche Mediatoren der Beziehung der Ernährungsexpositionen wurden identifiziert, indem diese Informationen in gemeinsamen grafischen Modellen integriert wurden. Mediationsanalysen zeigten, dass die möglichen Effekte von Vollkornverzehr auf die Lipidmetabolite ungefähr ein Viertel des günstigen Einflusses von Vollkornverzehr auf das Diabetesrisikos erklären könnten. Die möglichen Effekte von Kaffeekonsum und von Fleischverzehr auf Aminosäuren und Lipidmetabolite könnten jeweils ungefähr zwei Drittel der Zusammenhänge mit dem Diabetesrisiko erklären. Schlussfolgerung: Grundlage für die Ergebnisse dieser Arbeit war die Entwicklung eines Algorithmus, der externe Faktoren (kontinuierlich Expositionsvariablen, Ereigniszeit-Daten) und hochdimensionale Metabolitenprofile in einem gemeinsamen grafischen Modell integriert. Die Anwendung dieses Algorithmus auf Daten aus der EPIC-Potsdam Kohortenstudie hat gezeigt, dass die beobachteten konditionalen Unabhängigkeitsstrukturen mit der a priori Mediationshypothese konsistent waren. Der frühe Einfluss auf den Aminosäure- und Lipidstoffwechsel könnte die beobachteten Zusammenhänge zwischen drei wichtigen Ernährungsfaktoren und dem Risiko an Typ 2 Diabetes zu erkranken zu großen Teilen erklären. KW - type 2 diabetes KW - nutrition KW - lipid metabolism KW - metabolomics KW - epidemiology KW - networks KW - graphical models KW - mediation analysis KW - red meat KW - whole-grain KW - Diabetes mellitus Typ 2 KW - Ernährung KW - Fettstoffwechsel KW - Metabolomics KW - Epidemiologie KW - Netzwerke KW - grafische Modelle KW - Mediationsanalyse KW - rotes Fleisch KW - Vollkorn KW - Kaffee KW - coffee Y1 - 2017 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-404592 ER - TY - JOUR A1 - Schatz, J. A1 - Ohlendorf, B. A1 - Busse, P. A1 - Pelz, G. A1 - Dolch, D. A1 - Teubner, J. A1 - Encarnacao, Jorge A. A1 - Muehle, Ralf -Udo A1 - Fischer, M. A1 - Hoffmann, B. A1 - Kwasnitschka, L. A1 - Balkema-Buschmann, Anne A1 - Mettenleiter, Thomas Christoph A1 - Mueller, T. A1 - Freuling, C. M. T1 - Twenty years of active bat rabies surveillance in Germany BT - a detailed analysis and future perspectives JF - Epidemiology and infection N2 - 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. KW - surveillance KW - epidemiology KW - Bat rabies KW - lyssavirus Y1 - 2014 U6 - https://doi.org/10.1017/S0950268813002185 SN - 0950-2688 SN - 1469-4409 VL - 142 IS - 6 SP - 1155 EP - 1166 PB - Cambridge Univ. Press CY - New York ER -