Einfluss eines schweren Traumas auf die Frakturheilung

Es gibt klinische Hinweise, dass die Frakturheilung bei polytraumatisierten Patienten gestört ist. Eine der Ursachen könnte die posttraumatische systemische Inflammation darstellen. Das Thoraxtrauma ist eines der häufigsten und zugleich kritischsten Begleitverletzungen, da es verglichen mit anderen Verletzungen zu einer stärkeren systemischen Inflammation führt. Diese systemische Inflammation ist gekennzeichnet durch die Freisetzung von pro inflammatorischen Zytokinen, einer starken Aktivierung der Komplementkaskade und einer dadurch hervorgerufenen Überaktivierung von Immunzellen, was zu einer Schädigung von Organen führt, die initial nicht vom Trauma betroffen waren. Daher stellte sich in dieser Arbeit die Frage, ob die posttraumatische systemische Inflammation der Grund für die klinisch beobachtete Frakturheilungsverzögerung bei polytraumatisierten Patienten darstellt. Des Weiteren wurde der therapeutische Ansatz verfolgt, die Frakturheilungsstörung nach schwerem Trauma durch die Immunmodulation der systemischen Inflammation mittels eines spezifischen C5aR Antagonisten aufzuheben. In Ratten wurde eine Femurosteotomie erzeugt und mittels eines Fixateurs externe stabilisiert. Die Hälfte der Tiere erhielt ein stumpfes Thoraxtrauma. Den Tieren wurde postoperativ Blut entnommen, um die systemische Inflammation nachzuweisen. Um die Frakturheilung nach Thoraxtrauma zu untersuchen, wurden die Kalli nach einer Heilungszeit von 35 Tagen biomechanisch sowie strukturell durch mikrocomputertomographische Messungen und Histomorphometrie analysiert. Um die C5a-vermittelte systemische Inflammation zu inhibieren und somit die Frakturheilung zu verbessern, erhielt eine weitere Tiergruppe unmittelbar und 12 h nach dem Thoraxtrauma einen spezifischen C5aR Antagonisten. Diese Arbeit konnte zeigen, dass das stumpfe Thoraxtrauma und die resultierende systemische Inflammation zu einer drastischen Frakturheilungsverzögerung führte, was durch eine signifikant verminderte Biegesteifigkeit in Verbindung mit einem signifikant kleineren Kallus mit schlechterer Knochenstruktur und weniger neugebildetem Knochen im Frakturspalt gezeigt werden konnte. Die Immunmodulation mittels eines C5aR-Antagonisten konnte den negativen Effekt des stumpfen Thoraxtraumas auf die Frakturheilung vollständig aufheben, möglicherweise durch die Normalisierung der Anzahl und/oder Funktion von Immun- und Knochenzellen lokal im Frakturheilungsgebiet. C5a stellt daher ein therapeutisches Ziel zur Vermeidung von Frakturheilungsstörungen polytraumatisierter Patienten dar.There is clinical evidence, that fracture healing is impaired in polytraumatic patients. One reason might be the complex posttraumatic systemic inflammatory response. In this context the blunt chest trauma represents one oft the most common and most critical injuries because it leads to a stronger systemic inflammation compared to other injury patterns. This systemic inflammation is characterized by the release of pro-inflammatory cytokines, a massive activation of the complement system and the resulting over-activation of inflammatory cells, together frequently leading to secondary tissue and organ damage after severe trauma. Therefore, the question arose, whether the posttraumatic systemic inflammation might be the reason for the delayed fracture healing observed clinically in polytraumatic patients. Furthermore it was investigated whether the impairment of fracture healing after a severe trauma could be abolished by the immunomodulation of the systemic inflammation with a specific C5aR-antagonist. Rats received a femur osteotomy, which was stabilized with an external fixator. Half of the animals underwent an additional blunt chest trauma. Blood was taken from the animals postoperatively in order to evaluate the early systemic inflammatory response. For evaluating the fracture healing outcome, the fracture calli were tested mechanically as well as structurally by micro-computed tomography measurements and by histomorphometry after a healing period of 35 days. To inhibit the C5a-dependent posttraumatic systemic inflammation and therefore to enhance the fracture healing outcome, a further group received a C5aR-antagonist intravenously immediately and 12 h after the blunt chest trauma. This study showed that the blunt chest trauma and the resulting systemic inflammation led to considerably delayed fracture healing, as shown by a significantly reduced flexural rigidity in combination with a significantly diminished callus volume, moment of inertia and relative bone surface as well as decreased amounts of newly formed bone in fracture calli of animals subjected to a blunt chest trauma. Furthermore the immunomodulation by a C5aR-antagonist completely abolished the deleterious effects of a blunt chest trauma on fracture healing, possibly by normalizing the amount and/or function of inflammatory and bone cells locally at the fracture site. C5a therefore represents a potential therapeutic target to prevent delayed bone healing in patients with severe trauma

Alternative methods for the treatment of post-menopausal troubles

[english] Menopause is described as the transition from the reproductive phase of a women to the non reproductive. Changes in hormone levels might lead to complaints and health consequences especially during peri- and postmenopause. Hormone therapy has a potential damaging health risk profile and is recommended for temporal limited therapy for acute vasomotor symptoms only.The present HTA-report aims to assess the effectiveness and the cost-effectiveness of alternative treatment methods for women with postmenopausal symptoms in Germany regarding patient relevant endpoints (reduction of symptoms and frequency of adverse events and improvement of quality of life).A systematic literature search was carried out in 33 relevant databases in September 2010. Citations were selected according to pre-defined criteria and were extracted and evaluated.In the systematic research 22 studies are identified for the effectiveness evaluation, 22 primary studies and one review.High doses of isolated genistein reduce the frequency/intensity of hot flashes while low doses of genistein show no significant effect. Intake of isoflavone extract such as genistein, daidzein, glycitein in various combinations does not have an effect on improvement of cognitive function or vaginal dryness. The effect of black cohosh and hop extract for menopausal complaints cannot be determined since results are heterogenous. The combination of isoflavone, black cohosh, monk’s pepper, valerian and vitamin E has a positive effect on menopause symptoms. Ginkgo biloba shows no significant effect on menopause symptoms and cognitive improvement beside mental flexibility. Acupuncture has a significant influence on hot flashes especially in severe cases.No final statement can be drawn regarding the effectiveness of alter­ne treatment methods due to qualitative shortcomings of included studies and a general limited availability of studies in this field. Furthermore, the generalization of the present HTA is limited due to the inclusion of only postmenopausal women.<br><br>[german] Als Wechseljahre wird der Übergang von der reproduktiven Phase der Frau zur nicht-reproduktiven beschrieben. Insbesondere in der Peri- und Postmenopause können Beschwerden aufgrund des sich veränderten Hormonspiegels auftreten. Aktuell wird die Hormontherapie wegen der mit dieser verbundenen Risiken nur noch zur kurzfristigen Behandlung akuter vasomotorischer Symptome empfohlen. Von den betroffenen Frauen werden alternative und komplementäre Heilmethoden eingesetzt.Im vorliegenden Health Technology Assessment (HTA) sollen die Effektivität und Kosteneffektivität alternativer Behandlungsmethoden von postmenopausalen Wechseljahresbeschwerden in Deutschland hinsichtlich der patientenrelevanten Endpunkte Verringerung der Symptomatik, Häufigkeit unerwünschter Ereignisse sowie Verbesserung der Lebensqualität bewertet werden. In 33 relevanten Datenbanken wird im September 2010 eine systematische Literatursuche durchgeführt. Gefundene und relevante Literaturstellen werden gemäß vorab definierter Kriterien selektiert. Die Daten der Literaturstellen werden gezielt herausgesucht, bewertet und zusammenfassend beurteilt.Aus der systematischen Recherche werden 22 Studien, davon 15 Primärstudien und ein Review zur Bewertung der Effektivität identifiziert.Hochdosiertes isoliertes Genistein reduziert die Anzahl/Schwere von Hitzewallungen, während niedrig dosiertes Genistein keinen signifikanten Effekt zeigt. Die Gabe von Isoflavonextrakten, die Genistein, Daidzein, Glycitein in unterschiedlicher Zusammensetzung enthalten, hat keinen signifikanten Einfluss auf die Verbesserung kognitiver Fähigkeiten oder vaginale Trockenheit. Traubensilberkerzen- und Hopfenextrakt führen zu unterschiedlichen Ergebnissen bezüglich der Wirksamkeit bei postmenopausalen Beschwerden, sodass keine abschließende Aussage zur Effektivität getroffen werden kann. Die Kombination von Isoflavonen, Traubensilberkerze, Mönchspfeffer, Baldrian und Vitamin E hat eine positive Wirkung auf postmenopausale Symptome. Ginkgo biloba zeigt keinen signifikanten Effekt auf postmenopausale Symptome und eine kognitive Verbesserung mit Ausnahme der mentalen Flexibilität. Akupunktur hat einen signifikanten Einfluss auf Hitzewallungen, insbesondere auf deren Schweregrad.Aufgrund der qualitativen Mängel (Concealment, Randomisierung, Fallzahlplanung) der eingeschlossenen Studien und der begrenzten Anzahl an Studien kann keine abschließende zusammenfassende Bewertung zur Wirksamkeit alternativer Heilmethoden gegeben werden. Die Verallgemeinerbarkeit des vorliegenden HTA wird durch die Beschränkung auf postmenopausale Frauen reduziert

Manifestly Supersymmetric RG Flows

Renormalisation group (RG) equations in two-dimensional N=1 supersymmetric field theories with boundary are studied. It is explained how a manifestly N=1 supersymmetric scheme can be chosen, and within this scheme the RG equations are determined to next-to-leading order. We also use these results to revisit the question of how brane obstructions and lines of marginal stability appear from a world-sheet perspective.Comment: 22 pages; references added, minor change

DBI analysis of generalised permutation branes

We investigate D-branes on the product GxG of two group manifolds described as Wess-Zumino-Novikov-Witten models. When the levels of the two groups coincide, it is well known that there exist permutation D-branes which are twisted by the automorphism exchanging the two factors. When the levels are different, the D-brane charge group demands that there should be generalisations of these permutation D-branes, and a geometric construction for them was proposed in hep-th/0509153. We give further evidence for this proposal by showing that the generalised permutation D-branes satisfy the Dirac-Born-Infeld equations of motion for arbitrary compact, simply connected and simple Lie groups G.Comment: 19 pages, computation in section 3.5.1 corrected, conclusions unchange

Symmetries of perturbed conformal field theories

The symmetries of perturbed conformal field theories are analysed. We explain which generators of the chiral algebras of a bulk theory survive a perturbation by an exactly marginal bulk field. We also study the behaviour of D-branes under current-current bulk deformations. We find that the branes always continue to preserve as much symmetry as they possibly can, i.e. as much as is preserved in the bulk. We illustrate these findings with several examples, including permutation branes in WZW models and B-type D-branes in Gepner models.Comment: 30 pages, 3 figures. V2: Small error in eq. (2.14) correcte

Generalised permutation branes

We propose a new class of non-factorising D-branes in the product group GxG where the fluxes and metrics on the two factors do not necessarily coincide. They generalise the maximally symmetric permutation branes which are known to exist when the fluxes agree, but break the symmetry down to the diagonal current algebra in the generic case. Evidence for the existence of these branes comes from a Lagrangian description for the open string world-sheet and from effective Dirac-Born-Infeld theory. We state the geometry, gauge fields and, in the case of SU(2)xSU(2), tensions and partial results on the open string spectrum. In the latter case the generalised permutation branes provide a natural and complete explanation for the charges predicted by K-theory including their torsion.Comment: 33 pages, 6 figures, v2: Extended discussion of K-theory interpretation of our branes for products of higher rank groups in the conclusions; v3: Correction of formula (35) and adjustment of the discussion below equation (45) (no change of result). Footnote 9 points out a previously unnoticed subtlety and provides a reference to a more detailed discussio

Boundary Liouville theory at c=1

The c=1 Liouville theory has received some attention recently as the Euclidean version of an exact rolling tachyon background. In an earlier paper it was shown that the bulk theory can be identified with the interacting c=1 limit of unitary minimal models. Here we extend the analysis of the c=1-limit to the boundary problem. Most importantly, we show that the FZZT branes of Liouville theory give rise to a new 1-parameter family of boundary theories at c=1. These models share many features with the boundary Sine-Gordon theory, in particular they possess an open string spectrum with band-gaps of finite width. We propose explicit formulas for the boundary 2-point function and for the bulk-boundary operator product expansion in the c=1 boundary Liouville model. As a by-product of our analysis we also provide a nice geometric interpretation for ZZ branes and their relation with FZZT branes in the c=1 theory.Comment: 37 pages, 1 figure. Minor error corrected, slight change in result (1.6

Obstructions and lines of marginal stability from the world-sheet

The behaviour of supersymmetric D-branes under deformations of the closed string background is studied using world-sheet methods. We explain how lines of marginal stability and obstructions arise from this point of view. We also show why N=2 B-type branes may be obstructed against (cc) perturbations, but why such obstructions do not occur for N=4 superconformal branes at c=6, i.e. for half-supersymmetric D-branes on K3. Our analysis is based on a field theory approach in superspace, as well as on techniques from perturbed conformal field theory.Comment: 32 page

Boundary conditions in Toda theories and minimal models

We show that the disc bulk one-point functions in a sl(n) Toda conformal field theory have a well-defined limit for the central charge c=n-1, and that their limiting values can be obtained from a limit of bulk one-point functions in the W_n minimal models. This comparison leads to a proposal for one-point functions for twisted boundary conditions in Toda theory.Comment: 33 pages, 1 figure; v2: Minor corrections; v3: version accepted at JHE

Production of soybean seeds (Legumes Translated video)

In this video, the experts explain what to look for in soybean seed production, including seeding, location, and variety selection, threshing, the quick soaking test to determine seed quality, the importance of crop management, Diaporthe Phomopsis Complex, preparation of the seed, and legal aspects