The relationship between atherosclerosis and gut microbiome in patients with obstructive sleep apnoea

Background: Obstructive sleep apnoea (OSA) and gut dysbiosis are known risk factors for atherosclerosis. However, only very few studies have been focused on the relationship between OSA, atherosclerosis, and the intestinal microbiome, all in animal models. Methods: Twenty-two patients with OSA, 16 with and 6 without carotid atherosclerosis were involved in the study. After a diagnostic sleep examination, the intima media thickness (IMT) was measured and plaques were found using carotid ultrasound. Blood was also drawn for metabolic profile, and a stool sample was provided for 16S ribosomal RNA microbiome investigation. Results: An increased maximal common carotid artery (CCA) IMT was significantly associated with decreased phylum-level diversity. The level of Peptostreptococcaceae was significantly lower in atherosclerotic subjects. Some other candidate microbes appeared in the two groups at the genus level as well: Bilophila, Romboutsia, Slackia, and Veillonella in the non-atherosclerotic group; and Escherichia-Shigella, Prevotella, and Ruminococcaceae in the atherosclerotic group. Conclusions: This is the first pilot research to analyze the association between the gut microbiome and atherosclerosis in adult patients with OSA with and without carotid atherosclerosis. Dysbiosis and individual bacteria may contribute to the development of carotid atherosclerosis in patients with OSA. Further investigations are necessary to reveal a more precise background in a larger sample

Identification of six new susceptibility loci for invasive epithelial ovarian cancer.

Genome-wide association studies (GWAS) have identified 12 epithelial ovarian cancer (EOC) susceptibility alleles. The pattern of association at these loci is consistent in BRCA1 and BRCA2 mutation carriers who are at high risk of EOC. After imputation to 1000 Genomes Project data, we assessed associations of 11 million genetic variants with EOC risk from 15,437 cases unselected for family history and 30,845 controls and from 15,252 BRCA1 mutation carriers and 8,211 BRCA2 mutation carriers (3,096 with ovarian cancer), and we combined the results in a meta-analysis. This new study design yielded increased statistical power, leading to the discovery of six new EOC susceptibility loci. Variants at 1p36 (nearest gene, WNT4), 4q26 (SYNPO2), 9q34.2 (ABO) and 17q11.2 (ATAD5) were associated with EOC risk, and at 1p34.3 (RSPO1) and 6p22.1 (GPX6) variants were specifically associated with the serous EOC subtype, all with P < 5 × 10(-8). Incorporating these variants into risk assessment tools will improve clinical risk predictions for BRCA1 and BRCA2 mutation carriers.COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 ] HEALTH ]F2 ]2009 ]223175). The CIMBA data management and data analysis were supported by Cancer Research.UK grants 12292/A11174 and C1287/A10118. The Ovarian Cancer Association Consortium is supported by a grant from the Ovarian Cancer Research Fund thanks to donations by the family and friends of Kathryn Sladek Smith (PPD/RPCI.07). The scientific development and funding for this project were in part supported by the US National Cancer Institute GAME ]ON Post ]GWAS Initiative (U19 ]CA148112). This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancer Institute and National Human Genome Research Institute (dbGap accession number phs000178.v8.p7). The cBio portal is developed and maintained by the Computational Biology Center at Memorial Sloan ] Kettering Cancer Center. SH is supported by an NHMRC Program Grant to GCT. Details of the funding of individual investigators and studies are provided in the Supplementary Note. This study made use of data generated by the Wellcome Trust Case Control consortium, funding for which was provided by the Wellcome Trust under award 076113. The results published here are, in part, based upon data generated by The Cancer Genome Atlas Pilot Project established by the National Cancerhttp://dx.doi.org/10.1038/ng.3185This is the Author Accepted Manuscript of 'Identification of six new susceptibility loci for invasive epithelial ovarian cancer' which was published in Nature Genetics 47, 164–171 (2015) © Nature Publishing Group - content may only be used for academic research

Identification of 12 new susceptibility loci for different histotypes of epithelial ovarian cancer.

To identify common alleles associated with different histotypes of epithelial ovarian cancer (EOC), we pooled data from multiple genome-wide genotyping projects totaling 25,509 EOC cases and 40,941 controls. We identified nine new susceptibility loci for different EOC histotypes: six for serous EOC histotypes (3q28, 4q32.3, 8q21.11, 10q24.33, 18q11.2 and 22q12.1), two for mucinous EOC (3q22.3 and 9q31.1) and one for endometrioid EOC (5q12.3). We then performed meta-analysis on the results for high-grade serous ovarian cancer with the results from analysis of 31,448 BRCA1 and BRCA2 mutation carriers, including 3,887 mutation carriers with EOC. This identified three additional susceptibility loci at 2q13, 8q24.1 and 12q24.31. Integrated analyses of genes and regulatory biofeatures at each locus predicted candidate susceptibility genes, including OBFC1, a new candidate susceptibility gene for low-grade and borderline serous EOC

Welche Macht darf es denn Sein? Tracing ‘Power’ in German Foreign Policy Discourse

The relationship between ‘Germany’ and ‘power’ remains a sensitive issue. While observers tend to agree that Germany has regained the status of the most powerful country in Europe, there is debate whether that is to be welcomed or whether that is a problem. Underpinning this debate are views, both within Germany and amongst its neighbours, regarding the kind of power Germany has, or should (not) have. Against this backdrop, the article reviews the dominant role conceptions used in the expert discourse on German foreign policy since the Cold War that depict Germany as a particular type of ‘power’. Specifically, we sketch the evolution of three prominent conceptions (constrained power, civilian power, hegemonic power) and the recent emergence of a new one (shaping power). The article discusses how these labels have emerged to give meaning to Germany’s position in international relations, points to their normative and political function, and to the limited ability of such role images to tell us much about how Germany actually exercises power

Developing older adults' learner autonomy through one-to-one counselling: Results of an exploratory investigation

Developing autonomous learning to maintain independent learning practice in an effective way is a crucial ability in adult education (Confessore & Park, 2004). Therefore, this study investigates the potential of one-to-one learning counselling to promote older learners' learner autonomy (aged 50 and older). Twenty-five older learners participated in the exploratory study. Reflective learning diaries and qualitatively oriented questionnaires were used as research tools to track participants' autonomous learning behaviour. We applied grounded theory and network analysis to see the complex interrelations of underlying constructs. Results show that comprehension and speaking development are significant incentives for older adults' language learning. Further, self-awareness in learning and metacognitive knowledge were identified as important constructs for self-study practice. Cognitive stimulation, sustained learner motivation and certain self-relating constructs continuously affected older adults' learning behaviour. Application of cognitive-and memory-enhancing learning strategies, as well as technology-supported learning materials, played an important role in independent learning practice. General perceived self-efficacy and self-management were areas developed beyond language learning

Parlamentswahlen in Ungarn 1998 Parteien, Eliten und Gesellschaft im Spiegel der Wahlergebnisse

'The elections of 1998 - the third to be held in the post-communist era - demonstrate the viability of Hungarian democracy an d of the country's electoral system. The party system that came into being in 1989/90 is stable. While there is some debate about whether Hungary's parties can be divided into two or three political camps, the foundations have been laid for a parliamentary system in which power alternates among different parties. The Hungarian party system is less fragmented than those of other Central and East European countries, as shown by the fact that in each of the three parliamentary elections six parties won seats in parliament.' (extract)'Die 1998 nun schon zum dritten Mal durchgefuehrten Wahlen stellen die Lebensfaehigkeit der jungen ungarischen Demokratie und die Funktionsfaehigkeit des Wahlsystems unter Beweis, Das 1989/90 entstandene ungarische Parteiensystem ist stabil. Es wird zwar darueber diskutiert, ob das ungarische System zwei- oder dreigeteilt ist, aber es entstehen die Grundbedingungen fuer eine parlamentarische Wechselwirtschaft. Im Gegensatz zu den Parteiensystemen anderer mittel- und osteuropaeischer Laender ist das ungarische weniger zersplittert, was darin zum Ausdruck kommt, dass bei allen drei Wahlen sechs Parteien in das Parlament gelangten.' (Textauszug)SIGLEAvailable from UuStB Koeln(38)-980106379 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekDEGerman

Association between Gut Microbial Diversity and Carotid Intima-Media Thickness.

Background and Objectives: There is an increasing focus on the effect of the gut microbiome on developing atherosclerosis, but there is still no unified standpoint. We aimed to find associations between intestinal microbiome diversity and a marker of subclinical atherosclerosis, the carotid intima-media thickness (IMT). Materials and Methods: Recruited from the Hungarian Twin Registry, 108 monozygotic (MZ) twins (mean age 52.4 � 14.1 years, 58% female) underwent a comprehensive carotid ultrasound examination (Samsung RS85). Of the 108 MZ twins, 14 pairs (mean age 65 � 6.4 years, 71% female) discordant for carotid IMT were selected to undergo a stool sample collection. A special stool sampling container was mailed and received from each participant. After DNA extraction, library construction was performed specifically for the V3–V4 hypervariable region of microbial 16S rRNA. Next, the microbiome composition of the samples was determined using Kraken software. Two hypotheses were tested with the exact permutation test: (1) in the group with normal IMT, the Shannon index of the phyla is higher; and (2) the Firmicutes/Bacteroidetes ratio is greater in the group with high IMT values. Furthermore, the abundance of different bacterial strains present at higher and normal IMT was also explored. Statistical analysis was carried out using R software. Results: Increased Firmicutes/Bacteroidetes ratio was associated with increased IMT (mean Firmicutes/Bacteroidetes ratio of IMT > 0.9 and IMT < 0.9 groups: 2.299 and 1.436, respectively; p = 0.031). In the group with normal IMT values, a substantially higher fraction of Prevotellaceae was observed in contrast with subjects having subclinical atherosclerosis. However, there was no significant difference in the alpha diversity between the two groups. Conclusions: The determining role of individual genera and their proportions in the development and progression of atherosclerosis can be assumed. Further studies are needed to clarify if these findings can be used as potential therapeutic targets

Strong Genetic Effects on Bone Mineral Density in Multiple Locations with Two Different Techniques: Results from a Cross-Sectional Twin Study

Background and Objectives: Previous studies have demonstrated that risk of hip fracture is at least partly heritable. The aim of this study was to determine the magnitude of the genetic component of bone mineral density (BMD), using both X-ray and ultrasound assessment at multiple sites. Materials and Methods: 216 adult, healthy Hungarian twins (124 monozygotic, MZ, 92 dizygotic, DZ; mean age 54.2 ± 14.3 years), recruited from the Hungarian Twin Registry with no history of oncologic disease underwent cross-sectional BMD studies. We measured BMD, T- and Z-scores with dual energy X-ray absorptiometry (DEXA) at multiple sites (lumbar spine, femoral neck, total hip and radius). Quantitative bone ultrasound (QUS) was also performed, resulting in a calculated value of estimated bone mineral density (eBMD) in the heel bone. Heritability was calculated using the univariate ACE model. Results: Bone density had a strong genetic component at all sites with estimates of heritability ranging from 0.613 to 0.838 in the total sample. Lumbar BMD and calcaneus eBMD had major genetic components with estimates of 0.828 and 0.838 respectively, and least heritable (0.653) at the total hip. BMD of the radius had also a strong genetic component with an estimate of 0.806. No common environmental effect was found. The remaining variance was influenced by unique environment (0.162 to 0.387). In females only, slightly higher additive genetic estimates were found, especially in the case of the femoral neck and total hip. Conclusion: Bone mineral density is strongly heritable, especially in females at all locations using both DEXA and QUS, which may explain the importance of family history as a risk factor for bone fractures. Unshared environmental effects account for the rest of the variance with slight differences in magnitude across various bone regions, supporting the role of lifestyle in preventing osteoporotic fractures with various efficacy in different bone regions

The Relationship between Atherosclerosis and Gut Microbiome in Patients with Obstructive Sleep Apnoea

Background: Obstructive sleep apnoea (OSA) and gut dysbiosis are known risk factors for atherosclerosis. However, only very few studies have been focused on the relationship between OSA, atherosclerosis, and the intestinal microbiome, all in animal models. Methods: Twenty-two patients with OSA, 16 with and 6 without carotid atherosclerosis were involved in the study. After a diagnostic sleep examination, the intima media thickness (IMT) was measured and plaques were found using carotid ultrasound. Blood was also drawn for metabolic profile, and a stool sample was provided for 16S ribosomal RNA microbiome investigation. Results: An increased maximal common carotid artery (CCA) IMT was significantly associated with decreased phylum-level diversity. The level of Peptostreptococcaceae was significantly lower in atherosclerotic subjects. Some other candidate microbes appeared in the two groups at the genus level as well: Bilophila, Romboutsia, Slackia, and Veillonella in the non-atherosclerotic group; and Escherichia-Shigella, Prevotella, and Ruminococcaceae in the atherosclerotic group. Conclusions: This is the first pilot research to analyze the association between the gut microbiome and atherosclerosis in adult patients with OSA with and without carotid atherosclerosis. Dysbiosis and individual bacteria may contribute to the development of carotid atherosclerosis in patients with OSA. Further investigations are necessary to reveal a more precise background in a larger sample