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Background The differential diagnosis between follicular thyroid adenoma and minimal invasive follicular thyroid carcinoma is often difficult for several reasons. One major aspect is the lack of typical cytological criteria in well differentiated specimens. New marker molecules, shown by poly- or monoclonal antibodies proved helpful. Methods We performed global gene expression analysis of 12 follicular thyroid tumours (4 follicular adenomas, 4 minimal invasive follicular carcinomas and 4 widely invasive follicular carcinomas), followed by immunohistochemical staining of 149 cases. The specificity of the antibody was validated by western blot analysis Results In gene expression analysis QPRT was detected as differently expressed between follicular thyroid adenoma and follicular thyroid carcinoma. QPRT protein could be detected by immunohistochemistry in 65% of follicular thyroid carcinomas including minimal invasive variant and only 22% of follicular adenomas. Conclusion Consequently, QPRT is a potential new marker for the immunohistochemical screening of follicular thyroid nodules.
Global betrachtet, bestehen große Unterschiede in der menschlichen Entwicklungsfähigkeit sowohl zwischen verschiedenen Gruppierungen innerhalb einer Gesellschaft als auch zwischen unterschiedlichen Gesellschaften. Diese Differenzen bedürfen einer Begründung. Armut mit ihren Begleiterscheinungen Hunger, Unter- und Mangelernährung (Ernährungsunsicherheit) ist ein menschlich und individuell nicht wünschenswerter Zustand. Angemessene Ernährung ist der Grundstein für jegliche Form von Entwicklung. Armut ist ein absoluter Zustand, der die Betroffenen der Erfüllung grundlegender menschlicher Bedürfnisse und der vollwertigen Teilhabe an der Menschengemeinschaft beraubt. Um Armut als ungerecht verstehen zu können, muss sie von einer bestimmten Art (z.B. strukurell) oder Gründen sein. Biodiversität ist ein grundlegender Baustein, um den Fortbestand der Erde und der Menschheit zu sichern. Ohne biologische Vielfalt ist kurzfristig kein qualitativ hochwertiges und langfristig überhaupt kein Leben möglich. Diverse Regionen und gesellschaftliche Gruppierungen sind unterschiedlich stark von ihrer Nutzung für das alltägliche Überleben abhängig und von einem Verlust der (Agro-)Biodiversität betroffen. Biodiverse Ernährungsstrategien werden selten zur Verringerung der Unterernährung eingesetzt. Die Themen Recht auf Nahrung und landwirtschaftliche Vielfalt sind in dieser Form noch nirgends behandelt worden. Es gibt bislang keine normative Debatte bzw. Literatur, die eine moralphilosophische Begründung des Rechts auf Nahrung versucht und sie in Bezug zu relevanten Abkommen und Rechtskommentaren daraufhin untersucht, welche Gerechtigkeits-konzeptionen implizit und explizit vorhanden sind und inwiefern sie die strukturelle Dimension von Armut und Unterernährung thematisieren. Dies ist ein Versuch der partiellen Aufarbeitung, der sowohl normative als auch empirische Elemente enthält. Nach der umfassenden Analyse landwirtschaftlicher Strukturen sowie der strukturellen Bedingtheiten von Armut untersuche ich die Plausibilität der Begründungsoptionen eines sozialen Menschenrechts und prüfe im Anschluss ob sich Elemente einer moralischen Argumentation innerhalb des UN Sozialpakts, der Allgemeinen Anmerkung 12 des UN Wirtschafts- und Sozialrats sowie der Freiwilligen Leitlinien der FAO rechtfertigen lassen. Abschließend plädiere ich für eine vielfältige Landwirtschaft und die Hinwendung von Ernährungssicherungs-strategien zu biodiverser Ernährung.
Biventricular pacing has been suggested in end-stage heart failure. We present a 59-year-old patient undergoing second re-do CABG (coronary artery bypass graft) and carotid artery endarterectomy. Ejection fraction was 15%, QRS-width 175 ms. Following the carotid and CABG procedure, an implanted single-chamber ICD (implantable cardioverter defibrillator) was upgraded to permanent biventricular DDD pacing by implantation of one epicardial left ventricular and one epicardial atrial electrode. At follow-up two months postoperatively ejection fraction had significantly improved to 45%, the patient underwent stress test with adequate load and reported a good quality of life.
U1-snRNA is an integral part of the U1 ribonucleoprotein pivotal for pre-mRNA splicing. Toll-like receptor (TLR) signaling has recently been associated with immunoregulatory capacities of U1-snRNA. Using lung A549 epithelial/carcinoma cells, we report for the first time on interferon regulatory factor (IRF)-3 activation initiated by endosomally delivered U1-snRNA. This was associated with expression of the IRF3-inducible genes interferon-b (IFN-b), CXCL10/IP-10 and indoleamine 2,3-dioxygenase. Mutational analysis of the U1-snRNA-activated IFN-b promoter confirmed the crucial role of the PRDIII element, previously proven pivotal for promoter activation by IRF3. Notably, expression of these parameters was suppressed by bafilomycin A1, an inhibitor of endosomal acidification, implicating endosomal TLR activation. Since resiquimod, an agonist of TLR7/8, failed to stimulate A549 cells, data suggest TLR3 to be of prime relevance for cellular activation. To assess the overall regulatory potential of U1-snRNA-activated epithelial cells on cytokine production, co-cultivation with peripheral blood mononuclear cells (PBMC) was performed. Interestingly, A549 cells activated by U1-snRNA reinforced phytohemagglutinin-induced interleukin-10 release by PBMC but suppressed that of tumor necrosis factor-a, indicating an antiinflammatory potential of U1-snRNA. Since U1-snRNA is enriched in apoptotic bodies and epithelial cells are capable of performing efferocytosis, the present data in particular connect to immunobiological aspects of apoptosis at host/environment interfaces.
Nach Ende der napoleonischen Kriege und nach Aufhebung der Kontinentalsperre drängten die Briten auf das Festland. Sie nutzten dabei den Rhein als einen Wegabschnitt von besonderem Reiz, bevor sie nach Italien weiter reisten, indem sie an die Tradition der grand tour des 18. Jahrhunderts anknüpften. Durch die auf der britischen Insel weit vorangeschrittene industrielle Revolution zu Reichtum gekommen, konnte sich eine breitere Bevölkerungsschicht erlauben den Kontinent zu erkunden. Binnen weniger Jahre entwickelte sich der Tourismus zu einer gesellschaftlichen Konvention für die stetig wachsende Bürgerschicht. [...] So viele reisende Engländer fielen unter Einheimischen und Mitreisenden unter anderem wegen des von ihnen betriebenen enormen Reiseaufwands auf und schienen einer Kommentierung wert. [...] Briefe, Reiseberichte, Erzählungen und Novellen erwähnen das bemerkenswerte Verhalten der Briten. Aus den zahlreichen Quellen hat Barbara Wagner eine Auswahl getroffen, die einerseits den Zeitraum des Vormärz abdeckt und andererseits die verschiedenen Textarten berücksichtigt. Das besondere Augenmerk galt solchen Äußerungen, die sich auf die von den Briten in der ersten Hälfte des 19. Jahrhunderts bevorzugten Reisegebiete Rhein und Italien konzentrieren. Auch der selbstreflexive Blick von Engländern auf ihre Landsleute wird in die Auseinandersetzung mit den Konventionen des Reisens einbezogen. Oft münden solche Schilderungen in Satiren und Karikaturen.
In der vorliegenden Arbeit wurde in einer Fall-Kontroll-Studie mit 295 Fällen und 327 Kontrollen das Gonarthroserisiko beim Heben und Tragen schwerer Lasten im Beruf untersucht. Dabei ergab sich eine statistisch signifikante Risikoerhöhung durch das kumulative Heben und Tragen schwerer Lasten. Ebenso ergab sich eine statistisch signifikante Risikoerhöhung durch die kumulative Dauer von Tätigkeiten im Knien/Hocken oder Fersensitz in Kombination mit dem kumulativen Heben und Tragen schwerer Lasten. Eine Dosis-Wirkungs-Beziehung war nachzuweisen, was für eine kausale Verknüpfung der Ereignisse spricht. Die Ergebnisse dieser Arbeit verweisen darauf, dass erhöhte BMI-Werte mit einem erhöhten Gonarthroserisiko assoziiert sind. Die Daten wurden deshalb für den BMI adjustiert. Bestimmte sportliche Tätigkeiten gehen mit einem erhöhten Verschleiss der Kniegelenke einher. Die Ergebnisse gaben diskrete Hinweise darauf, dass das Joggen oder die Leichtathletik den Kniegelenksverschleiss begünstigen. Deshalb wurden die Daten hinsichtlich dieser Ergebnisse adjustiert, und diese sportlichen Belastungen wurden als Störvariablen, confounder, behandelt. In der vorliegenden Arbeit konnte jedoch ein doppeltes Gonarthroserisiko bereits ab einem kumulativen Heben und Tragen von schweren Lasten im gesamten Berufsleben von über 5120kg*h aufgezeigt werden. Bei der Kombination von der kumulativen Dauer von Tätigkeiten im Knien/Hocken oder Fersensitz zwischen 4757 - <10800 Stunden oder dem kumulativen Heben und Tragen von schweren Lasten zwischen 5120 - <37000 kg*h konnte ein mehr als doppeltes Gonarthroserisiko dargestellt werden. Die vorliegende Arbeit liefert die Evidenz für die Annahme eines erhöhten Gonarthroserisikos beim Heben und Tragen schwerer Lasten.
Background The to date evidence for a dose-response relationship between physical workload and the development of lumbar disc diseases is limited. We therefore investigated the possible etiologic relevance of cumulative occupational lumbar load to lumbar disc diseases in a multi-center case-control study. Methods In four study regions in Germany (Frankfurt/Main, Freiburg, Halle/Saale, Regensburg), patients seeking medical care for pain associated with clinically and radiologically verified lumbar disc herniation (286 males, 278 females) or symptomatic lumbar disc narrowing (145 males, 206 females) were prospectively recruited. Population control subjects (453 males and 448 females) were drawn from the regional population registers. Cases and control subjects were between 25 and 70 years of age. In a structured personal interview, a complete occupational history was elicited to identify subjects with certain minimum workloads. On the basis of job task-specific supplementary surveys performed by technical experts, the situational lumbar load represented by the compressive force at the lumbosacral disc was determined via biomechanical model calculations for any working situation with object handling and load-intensive postures during the total working life. For this analysis, all manual handling of objects of about 5 kilograms or more and postures with trunk inclination of 20 degrees or more are included in the calculation of cumulative lumbar load. Confounder selection was based on biologic plausibility and on the change-in-estimate criterion. Odds ratios (OR) and 95% confidence intervals (CI) were calculated separately for men and women using unconditional logistic regression analysis, adjusted for age, region, and unemployment as major life event (in males) or psychosocial strain at work (in females), respectively. To further elucidate the contribution of past physical workload to the development of lumbar disc diseases, we performed lag-time analyses. Results We found a positive dose-response relationship between cumulative occupational lumbar load and lumbar disc herniation as well as lumbar disc narrowing among men and women. Even past lumbar load seems to contribute to the risk of lumbar disc disease. Conclusions According to our study, cumulative physical workload is related to lumbar disc diseases among men and women.
The archaeal ATP synthase is a multisubunit complex that consists of a catalytic A(1) part and a transmembrane, ion translocation domain A(0). The A(1)A(0) complex from the hyperthermophile Pyrococcus furiosus was isolated. Mass analysis of the complex by laser-induced liquid bead ion desorption (LILBID) indicated a size of 730 +/- 10 kDa. A three-dimensional map was generated by electron microscopy from negatively stained images. The map at a resolution of 2.3 nm shows the A(1) and A(0) domain, connected by a central stalk and two peripheral stalks, one of which is connected to A(0), and both connected to A(1) via prominent knobs. X-ray structures of subunits from related proteins were fitted to the map. On the basis of the fitting and the LILBID analysis, a structural model is presented with the stoichiometry A(3)B(3)CDE(2)FH(2)ac(10).
The risk of deflation
(2009)
This paper was prepared for the meeting on Financial Regulation and Macroeconomic Stability: Key issues for the G20, organised by the CEPR and the Reinventing Bretton Woods Committee, London, 31 January 2009. Introduction: The onset of financial instability in August 2007, which quickly spread across the world, raises a number of questions for policy makers. First, what are the roots of the crisis? Many factors have been emphasized in the debate, including the opacity of complex financial products; the excessive confidence in ratings; weak risk management by financial institutions; massive reliance on wholesale funding; and the presumption that markets would always be liquid. Furthermore, poorly understood incentive effects – arising from the originate-to-distribute-model, remuneration policies and the period of low interest rates – are also widely seen as having played a role. Second, how can a repetition of the crisis can be avoided? Much attention is being focused on regulation and supervision of financial intermediaries. The G-20, at its summit in November 2008, noted that measures need to be taken in five areas: (i) financial market transparency and disclosure by firms need to be strengthened; (ii) regulation needs to be enhanced to ensure that all financial markets, products and participants are regulated or subject to oversight, as appropriate; (iii) the integrity of financial markets should be improved by bolstering investor and consumer protection, avoiding conflicts of interest, and by promoting information sharing; (iv) international cooperation among regulators must be enhanced; and (v) international financial institutions must be reformed to reflect changing economic weights in the world economy better in order to increase the legitimacy and effectiveness of these institutions. Third, how can the consequences for economic activity be minimized? Many of the adverse developments in financial markets – in particular the collapse of term interbank markets – reflect deeply entrenched perceptions of counterparty risk. Prompt and far-reaching action to support the financial system, in particular the infusion of equity capital in financial institutions to reduce counter-party risk and get credit to flow again, is essential in order to restore market functioning. A particular risk at present is that the rapid decline in inflation in many countries in recent months will turn into deflation with highly adverse real economic developments. This background paper considers how large the risk of deflation may be and discusses what policy can do to reduce it. It is organized as follows. Section 2 defines deflation and discusses downward nominal wage rigidities and the zero lower bound on interest rates. While these factors are frequently seen as two reasons why deflation can be associated with very poor economic outcomes, they should not be overemphasized. Section 3 looks at the current situation. Inflation expectations and forecasts in the subset of economies we look at (the euro area, the UK and the US) are positive, indicating that deflation is not expected. This does not imply that the current concerns of deflation are unwarranted, only that the public expects the central bank to be successful in avoiding deflation. The section also looks at the evolution of headline and “core” inflation, focusing on data from the US and the euro area. Section 4 reviews how monetary and fiscal policy can be conducted to ensure that deflation is avoided. Section 5 briefly discusses special issues arising in emerging market economies. Finally, Section 6 offers some conclusions. An Appendix discusses deflation episodes in the period 1882-1939.
Background: Three genes have been confirmed as major joint susceptibility genes for endocrine autoimmune disease:human leukocyte antigen class II, cytotoxic T-lymphocyte antigen 4 and protein tyrosine phosphatase non-receptor type 22. Recent studies showed that a genetic variation within the interferon induced helicase domain 1 (IFIH1) locus (rs1990760 polymorphism) is an additional risk factor in type 1 diabetes and Graves' disease (GD). Methods: The aim of the present study was to investigate the role of the rs1990760 polymorphism within the IFIH1 gene in German patients with GD (n=258), Hashimoto's thyroiditis (HT,n=106), Addison's disease (AD,n=195) and healthy controls (HC,n=227) as well as in 55 GD families (165 individuals, German) and 100 HT families (300 individuals, Italian). Furthermore, the interaction between rs1990760 polymorphism with human leukocyte antigen (HLA) risk haplotype DQ2(DQA*0501-DQB*0201), the risk haplotypes DQ2/DQ8 (DQA*0301-DQB*0302) and the status of thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and TSH receptor antibody (TRAb) in patients and families were analysed. Results:No significant differences were found between the allele and genotype frequencies for rs1990760 IFIH1 polymorphism in patients with GD, HT, AD and HC. Also no differences were observed when stratifying the IFIH1 rs1990760 polymorphism for gender, presence or absence of thyroid antibodies (GD:TRAb and HT:TPOAb/TgAb) and HLA risk haplotypes (DQ2:for GD and HT, DQ2/DQ8:for AD). Furthermore the transmission analysis in GD and HT families revealed no differences in alleles transmission for rs1990760 IFIH1 from parents with or without HLA risk haplotype DQ2 to the affected offspring. In contrast, by dividing the HT parents according to the presence or absence of thyroid Ab titers, mothers and fathers both positive for TPOAb/TgAb overtransmitted the allele A of IFIH1 rs1990760 to their HT affected offspring (61.8% vs 38.2%;p=0.05;corrected p [pc]=0.1). However, these associations did not remain statistically significant after correction of the p-values. Conclusion: In conclusion, our data suggest, no contribution from IFIH1 rs1990760 polymorphism to the pathogenesis of either Graves' disease, Hashimoto's thyroiditis or Addison's disease in our study populations. However, in order to exclude a possible influence of the studied polymorphism in specified subgroups within patients with autoimmune thyroid disease, further investigations in larger populations are needed.