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Ziele: Das Ziel dieser offiziellen Leitlinie, die von der Deutschen Gesellschaft für Gynäkologie und Geburtshilfe (DGGG) und der Deutschen Krebsgesellschaft (DKG) publiziert und koordiniert wurde, ist es, die Früherkennung, Diagnostik, Therapie und Nachsorge des Mammakarzinoms zu optimieren.
Methoden: Der Aktualisierungsprozess der S3-Leitlinie aus 2012 basierte zum einen auf der Adaptation identifizierter Quellleitlinien und zum anderen auf Evidenzübersichten, die nach Entwicklung von PICO-(Patients/Interventions/Control/Outcome-)Fragen, systematischer Recherche in Literaturdatenbanken sowie Selektion und Bewertung der gefundenen Literatur angefertigt wurden. In den interdisziplinären Arbeitsgruppen wurden auf dieser Grundlage Vorschläge für Empfehlungen und Statements erarbeitet, die im Rahmen von strukturierten Konsensusverfahren modifiziert und graduiert wurden.
Empfehlungen: Der Teil 1 dieser Kurzversion der Leitlinie zeigt Empfehlungen zur Früherkennung, Diagnostik und Nachsorge des Mammakarzinoms: Der Stellenwert des Mammografie-Screenings wird in der aktualisierten Leitlinienversion bestätigt und bildet damit die Grundlage der Früherkennung. Neben den konventionellen Methoden der Karzinomdiagnostik wird die Computertomografie (CT) zum Staging bei höherem Rückfallrisiko empfohlen. Die Nachsorgekonzepte beinhalten Untersuchungsintervalle für die körperliche Untersuchung, Ultraschall und Mammografie, während weiterführende Gerätediagnostik und Tumormarkerbestimmungen bei der metastasierten Erkrankung Anwendung finden.
Purpose: The aim of this official guideline coordinated and published by the German Society for Gynecology and Obstetrics (DGGG) and the German Cancer Society (DKG) was to optimize the screening, diagnosis, therapy and follow-up care of breast cancer.
Methods: The process of updating the S3 guideline dating from 2012 was based on the adaptation of identified source guidelines which were combined with reviews of evidence compiled using PICO (Patients/Interventions/Control/Outcome) questions and the results of a systematic search of literature databases and the selection and evaluation of the identified literature. The interdisciplinary working groups took the identified materials as their starting point to develop recommendations and statements which were modified and graded in a structured consensus procedure.
Recommendations: Part 1 of this short version of the guideline presents recommendations for the screening, diagnosis and follow-up care of breast cancer. The importance of mammography for screening is confirmed in this updated version of the guideline and forms the basis for all screening. In addition to the conventional methods used to diagnose breast cancer, computed tomography (CT) is recommended for staging in women with a higher risk of recurrence. The follow-up concept includes suggested intervals between physical, ultrasound and mammography examinations, additional high-tech diagnostic procedures, and the determination of tumor markers for the evaluation of metastatic disease.
Aims: We investigated N471D WASH complex subunit strumpellin (Washc5) knock-in and Washc5 knock-out mice as models for hereditary spastic paraplegia type 8 (SPG8). Methods: We generated heterozygous and homozygous N471D Washc5 knock-in mice and subjected them to a comprehensive clinical, morphological and laboratory parameter screen, and gait analyses. Brain tissue was used for proteomic analysis. Furthermore, we generated heterozygous Washc5 knock-out mice. WASH complex subunit strumpellin expression was determined by qPCR and immunoblotting. Results: Homozygous N471D Washc5 knock-in mice showed mild dilated cardiomyopathy, decreased acoustic startle reactivity, thinner eye lenses, increased alkaline phosphatase and potassium levels and increased white blood cell counts. Gait analyses revealed multiple aberrations indicative of locomotor instability. Similarly, the clinical chemistry, haematology and gait parameters of heterozygous mice also deviated from the values expected for healthy animals, albeit to a lesser extent. Proteomic analysis of brain tissue depicted consistent upregulation of BPTF and downregulation of KLHL11 in heterozygous and homozygous knock-in mice. WASHC5-related protein interaction partners and complexes showed no change in abundancies. Heterozygous Washc5 knock-out mice showing normal WASHC5 levels could not be bred to homozygosity. Conclusions: While biallelic ablation of Washc5 was prenatally lethal, expression of N471D mutated WASHC5 led to several mild clinical and laboratory parameter abnormalities, but not to a typical SPG8 phenotype. The consistent upregulation of BPTF and downregulation of KLHL11 suggest mechanistic links between the expression of N471D mutated WASHC5 and the roles of both proteins in neurodegeneration and protein quality control, respectively.
Knowledge about the biogeographic affinities of the world’s tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world’s tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.
The nucleosynthesis of elements beyond iron is dominated by neutron captures in the s and r processes. However, 32 stable, proton-rich isotopes cannot be formed during those processes, because they are shielded from the s-process flow and r-process β-decay chains. These nuclei are attributed to the p and rp process.
For all those processes, current research in nuclear astrophysics addresses the need for more precise reaction data involving radioactive isotopes. Depending on the particular reaction, direct or inverse kinematics, forward or time-reversed direction are investigated to determine or at least to constrain the desired reaction cross sections.
The Facility for Antiproton and Ion Research (FAIR) will offer unique, unprecedented opportunities to investigate many of the important reactions. The high yield of radioactive isotopes, even far away from the valley of stability, allows the investigation of isotopes involved in processes as exotic as the r or rp processes.
A floristic description is presented of the study sites of the Research Training Group “The role of biodi-versity for biogeochemical cycles and biotic interactions in temperate deciduous forests”. To investi-gate different aspects of plant biodiversity in Hainich National Park (Thuringia), deciduous forest stands with low, medium and high canopy tree species diversity were compared. The results of species richness and forest communities show that the research sites are characterised by a typical central European forest flora. Greater vascular plant species richness occurs with higher diversity of tree species. Six of altogether twelve research sites are assigned to the beech forest alliance (Galioodorati-Fagion), the second half belongs to the oak-hornbeam forest alliance (Carpinionbetuli). Suballiances within the Galioodorati-Fagion in the study area include the Galio-Fagetum and the Hordelymo-Fagetum. All Carpinionbetuli relevées are assigned to the suballiance Stellario-Carpinetum.
Meeting Abstract : Deutscher Kongress für Orthopädie und Unfallchirurgie ; 73. Jahrestagung der Deutschen Gesellschaft für Unfallchirurgie ; 95. Tagung der Deutschen Gesellschaft für Orthopädie und Orthopädische Chirurgie ; 50. Tagung des Berufsverbandes der Fachärzte für Orthopädie und Unfallchirurgie ; 21. - 24.10.2009, Berlin Fragestellung: Ziel war die Evaluierung der funktionellen und radiologischen Ergebnisse nach osteosynthestischer Versorgung von Olecranonfrakturen mit einer zur Hakenplatte modifizierten Drittelrohrplatte. Methodik: In einem Zeitraum von 12 Monaten wurden 29 Patienten mit Olecranonfrakturen prospektiv erfasst und eine Osteosynthese mit einer zur Hakenplatte modifizierten Kleinfragment-Drittelrohrplatte durchgeführt. Eine additive Verschraubung von zusätzlichen Fragmenten erfolgte bei 6 Patienten (20%). Das mittlere Patientenalter zum Unfallzeitpunkt betrug 50 Jahre (Min 29/ Max 83). Unter Verwendung der Frakturklassifikation nach Schatzker stellte sich in 8 Fällen (28%) eine Querfraktur vom Typ A, in 6 Fällen (20%) eine Querfraktur mit Impaktion vom Typ B und in 15 Fällen (52%) eine Mehrfragmentfraktur vom Typ D dar. Bei 4 Patienten (14%) lag eine offene Fraktursituation vor. Nach im Mittel 7,2 Monaten (Min 6/ Max 8) wurde das funktionelle Outcome anhand des Mayo Elbow Performence Scores (MEPS), der visuellen Analogskala (VAS) und des Disabilities of the Arm, Shoulder and Hand Scores (DASH) bewertet sowie die radiologischen Befunde erhoben. Ergebnisse und Schlussfolgerungen: Das Ziel einer primär übungsstabilen Osteosynthese konnte bei allen Patienten erreicht werden. Unter Verwendung des MEPS wurden annähernd ausschließlich sehr gute (12 Fälle/41%) und gute (16 Fälle/55%) Ergebnisse erzielt. Lediglich bei einem Patienten ergab sich ein nur befriedigendes Ergebnis. Der mittlere Punktwert für den MEPS betrug 91,4 (Min 65/Max 100). In der VAS konnte ein Mittelwert von 8,2 Punkten (Min 7/Max 10) erzielt werden (0=keine Zufriedenheit, 10=volle Zufriedenheit). Der mittlere DASH-Wert betrug 16,2 Punkte (Min 0/Max 39). Der mittlere Bewegungsumfang betrug für Extension/Flexion bei einem durchschnittlichen Streckdefizit von 8° (Min 0°/Max 25°) und einer Beugung von 135° (Min 105°/Max 155°) 125° (Min 90°/Max 155°). Die Unterarmumwendbewegungen waren mit 175° (Min 165°/Max 180°) kaum eingeschränkt. Bei keinem Patienten gab es postoperative Komplikationen. Eine zur Hakenplatte modifizierte Drittelrohrplatte stellt im Gegensatz zu präformierten, winkelstabilen Implantaten eine kostengünstige Alternative zur Osteosynthese bei Olecranonfrakturen dar. Auch bei komplexen mehrfragmentären Frakturtypen und osteoporotischer Knochenqualität konnte so im nachuntersuchten Kollektiv eine sichere Frakturretention erzielt werden. Hinsichtlich des funktionellen Ergebnisses profitieren die Patienten von einer dadurch unmittelbar postoperativ möglichen, physiotherapeutischen Nachbehandlung. Das für die Hakenplatte benötigte Osteosynthesematerial (Kleinfragment-Drittelrohrplatte) ist nahezu überall verfügbar und lässt sich in kurzer Zeit der individuellen Anatomie und Frakturmorphologie anpassen. Eine Drahtmigration, wie bei der weit verbreiteten Zuggurtungsosteosynthese häufig beobachtet, ist ausgeschlossen.
Objective. A study supported by the EULAR and the ACR being conducted to establish classification criteria for polymyalgia rheumatica (PMR) will include ultrasound examination of the shoulders and hips. Ultrasound (US) depicts glenohumeral joint effusion, biceps tenosynovitis, subdeltoid bursitis, hip joint synovitis, and trochanteric bursitis in PMR. These findings may aid in distinguishing PMR from other diseases. The purpose of this study was to assess standards and US interreader agreement of participants in the PMR classification criteria study. Methods. Sixteen physicians in four groups examined shoulders and hips of 4 patients and 4 healthy adults with ultrasound. Overall agreement and interobserver agreement were calculated. Results. The overall agreement (OA) between groups was 87%. The OA for healthy shoulders was 88.8%, for healthy hips 100%, for shoulders with pathology 85.2%, and 74.3% for hips with pathology, respectively. Conclusion. There was a high degree of agreement found for the examination of healthy shoulders and pathologic hips. Agreement was moderate for pathologic shoulders and perfect for healthy hips. US of shoulder and hips performed by different examiners is a reliable and feasible tool for assessment of PMR related disease pathology and can be incorporated into a classification criteria study.
Introduction: Immune paralysis with massive T-cell apoptosis is a central pathogenic event during sepsis and correlates with septic patient mortality. Previous observations implied a crucial role of peroxisome proliferator-activated receptor gamma (PPARγ) during T-cell apoptosis.
Methods: To elucidate mechanisms of PPARγ-induced T-cell depletion, we used an endotoxin model as well as the caecal ligation and puncture sepsis model to imitate septic conditions in wild-type versus conditional PPARγ knockout (KO) mice.
Results: PPARγ KO mice showed a marked survival advantage compared with control mice. Their T cells were substantially protected against sepsis-induced death and showed a significantly higher expression of the pro-survival factor IL-2. Since PPARγ is described to repress nuclear factor of activated T cells (NFAT) transactivation and concomitant IL-2 expression, we propose inhibition of NFAT as the underlying mechanism allowing T-cell apoptosis. Corroborating our hypothesis, we observed up-regulation of the pro-apoptotic protein BIM and downregulation of the anti-apoptotic protein Bcl-2 in control mice, which are downstream effector proteins of IL-2 receptor signaling. Application of a neutralizing anti-IL-2 antibody reversed the pro-survival effect of PPARγ-deficient T cells and confirmed IL-2-dependent apoptosis during sepsis.
Conclusion: Apparently antagonizing PPARγ in T cells might improve their survival during sepsis, which concomitantly enhances defence mechanisms and possibly provokes an increased survival of septic patients.
Background: The interferon-inducible immunity-related GTPases (IRG proteins/p47 GTPases) are a distinctive family of GTPases that function as powerful cell-autonomous resistance factors. The IRG protein, Irga6 (IIGP1), participates in the disruption of the vacuolar membrane surrounding the intracellular parasite, Toxoplasma gondii, through which it communicates with its cellular hosts. Some aspects of the protein's behaviour have suggested a dynamin-like molecular mode of action, in that the energy released by GTP hydrolysis is transduced into mechanical work that results in deformation and ultimately rupture of the vacuolar membrane. Results: Irga6 forms GTP-dependent oligomers in vitro and thereby activates hydrolysis of the GTP substrate. In this study we define the catalytic G-domain interface by mutagenesis and present a structural model, of how GTP hydrolysis is activated in Irga6 complexes, based on the substrate-twinning reaction mechanism of the signal recognition particle (SRP) and its receptor (SRalpha). In conformity with this model, we show that the bound nucleotide is part of the catalytic interface and that the 3'hydroxyl of the GTP ribose bound to each subunit is essential for trans-activation of hydrolysis of the GTP bound to the other subunit. We show that both positive and negative regulatory interactions between IRG proteins occur via the catalytic interface. Furthermore, mutations that disrupt the catalytic interface also prevent Irga6 from accumulating on the parasitophorous vacuole membrane of T. gondii, showing that GTP-dependent Irga6 activation is an essential component of the resistance mechanism. Conclusions: The catalytic interface of Irga6 defined in the present experiments can probably be used as a paradigm for the nucleotide-dependent interactions of all members of the large family of IRG GTPases, both activating and regulatory. Understanding the activation mechanism of Irga6 will help to explain the mechanism by which IRG proteins exercise their resistance function. We find no support from sequence or G-domain structure for the idea that IRG proteins and the SRP GTPases have a common phylogenetic origin. It therefore seems probable, if surprising, that the substrate-assisted catalytic mechanism has been independently evolved in the two protein families.