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Ein professioneller Orchestermusiker verbringt die meiste Zeit in körperlich ungünstiger Sitzhaltung beim Spielen. Die Folge ist ein Anstieg des Risikos für die Entwicklung von muskuloskelettalen Beschwerden [44, 127, 128]. Eine Verbesserung der Arbeitsbedingungen lässt sich u.a. durch den Einsatz von ergonomischen Stühlen erzielen, da sie einen Einfluss auf die Körperhaltung des Orchestermusikers besitzen. Im Mittelpunkt der vorliegenden Arbeit standen daher sechs unterschiedliche von der Firma Mey für Orchestermusiker konzipierte Stühle. Die Studie beinhaltete eine Untersuchung des Einflusses der Stühle auf die Oberkörperstatik und die Sitzdruckverteilung von Orchestermusikern und den Einfluss auf ihr Instrumentalspiel im Vergleich zur habituellen Sitzhaltung. Das Probandenkollektiv umfasste 24 Berufsmusiker des Polizeiorchesters Mainz (Rheinland-Pfalz, Deutschland) und bestand zum größten Teil aus Blasinstrumentalisten (3 Frauen, 21 Männer). Das Durchschnittsalter betrug 45 Jahre. Die Überprüfung der Oberkörperstatik erfolgte durch einen 3D-Rückenscanner (ABW GmbH, Frickenhausen, Deutschland), eine Evaluation der Druckverhältnisse im Gesäß durch eine Druckmessmatte (GeBioM GmbH, Münster, Deutschland), womit sich bei jedem Stuhl ein bestimmtes Druckmuster kennzeichnen ließ. Die Messung erfolgte pro Stuhl und Messgerät stets im Wechsel zwischen der statischen Position ohne Instrument (oI) und der statischen Position mit Instrument (mI). Bei der statistischen Auswertung kam es zur Verwendung nicht parametrischer Tests (Friedman-, Wilcoxon Matched- Pairs-Test), wobei das Signifikanzniveau bei ≤0,05 lag. Es erfolgte eine Unterteilung in einen Inter- und einen Intrastuhlvergleich.
Die Ergebnisse des Interstuhlvergleichs zeigten bezüglich der Schulterregion keine signifikanten Veränderungen, wohingegen im Hinblick auf die WS-Parameter Signifikanzen zwischen Stuhl 2 und 5 verzeichnet wurden: in der habituellen Position offenbarte die Rumpflänge D die größte Abweichung mit einem Längenunterschied von 14mm (p≤0,001), so auch die Rumpflänge S (16 mm; p≤0,001). Bezüglich dieser Stühle wiesen die restlichen WS-Parameter Abweichungen von max. 4° bzw. 3mm auf. Zwischen Stuhl 2 und 3 ergaben sich m.I. im Hinblick auf den thorakalen (p≤0,01) und lumbalen Biegungswinkel (p≤0,001) max. Diskrepanzen von 2,5°. Die größten Unterschiede in der Beckenregion zeigten sich beim Beckenabstand zwischen Stuhl 3 und 5 o.I. (7mm) und m.I. (4mm), (beide Bedingungen p≤0,001). Im Hinblick auf die Druckparameter fand sich eine Abhängigkeit zwischen belasteter Fläche und Sitzbeinhöckerdruck (SBH): eine kleine Fläche bedeutete eine schlechte Druckverteilung und umgekehrt. Stühle 1 und 4 besaßen den geringsten SBH (p≤0,001). Im Intrastuhlvergleich zeigten die Bereiche der WS, Schultern und Becken jeweils mindestens einen signifikanten Parameter auf, wie z.B. Schulterblattabstand, sagittale Rumpfneigung und Beckenabstand. Korrelationen zwischen den Parametern waren nicht zu erkennen. M.I. kommt es hinsichtlich des SBH auf der linken Hälfte im Schnitt auf allen Stühlen zu einer Druckerhöhung von 8,46%, auf der rechten zu einer von 11,11%. Im Hinblick auf den Oberschenkeldruck (OS) vollzieht sich die größte Veränderung (7,4bar) der rechten Gesäßhälfte auf Stuhl 2 mit p≤0,001. Der Interstuhlvergleich zeigt also, dass die Wahl eines Stuhls keine Auswirkung auf die Körperhaltung hat. Ursache für Diskrepanzen hinsichtlich des SBH ist die unterschiedliche Polsterung und Größe der Sitzfläche, welche eine hohe Relevanz in Bezug auf die Umverteilung des Drucks und den subjektiven Komfort besitzt. Eine gepolsterte und große Oberfläche ist gleichzusetzen mit einer günstigen Druckverteilung und einem angenehmen individuellen Sitzgefühl. Der Intrastuhlvergleich offenbart ebenfalls keine klinisch relevanten Veränderungen im Oberkörper. Ausschließlich in der Druckverteilung ist eine signifikante Variabilität hinsichtlich des OS rechts bei Stuhl 2 vorhanden (p≤0,001). Die Sitzposition der Probanden ist symmetrisch. Die Symmetrie bezieht sich sowohl auf den Schulter-, WS- und Beckenbereich, als auch auf die Druckverhältnisse im Gesäßbereich.
In der vorliegenden Studie konnte belegt werden, dass gepolsterte und breite Sitzoberflächen mit gleichmäßiger Druckverteilung und gleichzeitig hohem Komfort einhergehen. Im Hinblick auf das Musizieren über einen längeren Zeitraum ist das Vorhandensein eines hohen Komforts für den Orchestermusiker von Bedeutung. Diese Erkenntnisse sind bei der Weiterentwicklung von ergonomischen Stühlen zu berücksichtigen. Eine Analyse der Schulter- und Rumpfmuskulatur und Messung des Beckenwinkels ist in weiteren Studien zusätzlich erforderlich, um zu erforschen, inwieweit die Stühle die Fehlfunktionen des Bewegungsapparates beeinflussen.
Die Therapie langstreckiger Knochendefekte stellt auch weiterhin eine große Herausforderung dar. Dies beruht unter anderem darauf, dass der therapeutische Goldstandard - die Verwendung von autogener Knochensubstanz aus dem Beckenkamm - neben der begrenzten Verfügbarkeit vor allem Komplikationen im Bereich der Entnahmestelle mit sich bringen kann. Es wurde bisher aber noch kein durchschlagendes Ergebnis in der Entwicklung neuer Scaffolds zum Einsatz bei langstreckigen Knochendefekten erreicht. Dies kann eine Vielzahl an Ursachen haben, die sich von der verwendeten Ausgangssubstanz, bis hin zum verwendeten Design erstrecken können. Neben dem Ausgangsmaterial spielen vor
allem die Formgebung und physikalische Eigenschaften, wie Porosität und Mikroarchitektur, eine wichtige Rolle.
Ein aktueller Ansatz zur Nutzung als alternatives Knochenersatzmaterial ist das Knochen-Tissue-Engineering. Hierbei werden körpereigene, knochen-regenerative Zellen mit einem dreidimensionalen Gerüststoff (Knochenersatzmaterial oder -scaffold) kombiniert und in den Knochendefekt implantiert. In dieser Arbeit wurde der Fokus auf die Designentwicklung eines neuen Kochenersatz-Scaffolds gelegt. Nach Vorbild schon vorgestellter Knochenersatzdesigns und unter Berücksichtigung einer Grundstruktur, die auch Phasen der Knochenheilung wie die Frakturhämatomausbreitung und initiale Nährstoffversorgung einbeziehen sollte, wurden mehrere Designs (Raster, Tempel, Zwiebel) entwickelt. Mithilfe des additiv extrusionsbasierten Schmelzschichtverfahrens (Fused Filament Fabrication) wurden die in Computer-Aided Design entworfenen Scaffolds realisiert.
Dieser Ansatz beinhaltet, unter Verwendung des resorbierbaren und biokompatiblen Trägerpolymers Polylaktat, mehrstufige Designs, die kleine biologisch funktionelle Einheiten in eine tragende, kompressionsfeste Rahmenstruktur einbetten. Hierdurch entsteht einerseits die nötige mechanische Belastbarkeit und andererseits eine offene Architektur mit Poren, die Diffusion von Sauerstoff und
Nährstoffen in die inneren Bereiche des Implantats ermöglicht. Es wurden verschiedene Designs entwickelt, gedruckt und mechanisch sowie in vitro in den Kernbereichen Zelladhäsion, Zellaktivität und osteogene Differenzierung nach Besiedelung mit Saos-2-Zellen charakterisiert.
Ein weiterer Entwicklungsschritt stellte das Einführen eines neuartigen, innerhalb der Designs kompatiblen Baukastensystems dar. Hierdurch wird nicht nur die Anpassbarkeit an den Knochendefekt verbessert, es sind auch weitere Funktionen ergänzbar und die unterschiedlichen Designs untereinander kombinierbar.
Die Ergebnisse dieser Dissertationsarbeit dienen als Basis für einen völlig neuen Ansatz von Knochenersatzmaterialien mit positiven biologischen sowie biophysikalischen Eigenschaften.
The intestinal epithelium acts as a selective barrier for the absorption of water, nutrients and orally administered drugs. To evaluate the gastrointestinal permeability of a candidate molecule, scientists and drug developers have a multitude of cell culture models at their disposal. Static transwell cultures constitute the most extensively characterized intestinal in vitro system and can accurately categorize molecules into low, intermediate and high permeability compounds. However, they lack key aspects of intestinal physiology, including the cellular complexity of the intestinal epithelium, flow, mechanical strain, or interactions with intestinal mucus and microbes. To emulate these features, a variety of different culture paradigms, including microfluidic chips, organoids and intestinal slice cultures have been developed. Here, we provide an updated overview of intestinal in vitro cell culture systems and critically review their suitability for drug absorption studies. The available data show that these advanced culture models offer impressive possibilities for emulating intestinal complexity. However, there is a paucity of systematic absorption studies and benchmarking data and it remains unclear whether the increase in model complexity and costs translates into improved drug permeability predictions. In the absence of such data, conventional static transwell cultures remain the current gold-standard paradigm for drug absorption studies.
Verletzungen der Fingerkuppen stellen einen häufigen Grund für die Vorstellung in der Notaufnahme dar. Während viele Verletzungen konservativ behandelt werden können, benötigen einige Patienten eine operative Versorgung. Dabei kommen verschiedene operative Verfahren zur Anwendung, darunter eine Fingerkuppenrekonstruktion mit einer neurovaskulären Insel-Lappenplastik.
Ziel der neurovaskulären Insel-Lappenplastik ist die Wiederherstellung einer taktil sensiblen und wieder belastungsfähigen Fingerkuppe ohne ein Längendefizit des Fingers.
In der vorliegenden Studie wurden Langzeit-Behandlungsergebnisse mit einer mittleren Nachuntersuchungsdauer von 105 Monaten bei 28 Patienten mit 29 durch neurovaskuläre Insel-Lappenplastiken rekonstruierten Fingerkuppen in der Berufsgenossenschaftlichen Unfallklinik Frankfurt am Main erfasst. Die untersuchten Patienten hatten zum Zeitpunkt der Verletzung ein Durchschnittsalter von 38,4 Jahren. Es handelte sich überwiegend um männliche und berufstätige Patienten.
Es wurden nur Fingerkuppenverletzungen mit freiliegenden Knochen (Allen-Klassifikation Zone III und IV) operativ versorgt. In unserer Studie traten am häufigsten die Verletzungen am Mittelfinger, Zeigefinger und Ringfinger auf. Die Mehrheit der Fingerkuppenverletzungen geschah in Folge eines Arbeitsunfalls, die Arbeitsunfähigkeitsdauer betrug ca. 6,1 Wochen. Die maximale Größe eines neurovaskulären Insel-Lappen lag bei 6 x 3,5 cm.
Alle Patienten waren mit den Behandlungsergebnissen anhand der numerischen Rating-Skala und des DASH Fragebogens bezüglich Funktionalität sowie dem ästhetischen Outcome zufrieden und würden sich wieder operieren lassen.
Die Sensibilität konnte anhand der Zwei-Punkte-Diskrimination sowie Semmes-Weinstein Monofilament-Testes als gut bewertet werden und normale physiologische Werte erreichen. Die Narbe war überwiegend weich und in der Mehrheit der Fälle entsprach sie anhand der Vancouver Scar Scale Werte annähend der normalen Haut. Zwei Drittel der Patienten gaben keine Schmerzen in Ruhe an. Die Hälfte der Patienten gaben Schmerzen unter Belastung anhand der numerischen Rating-Scala an.
Trotz der hohen Anzahl von Krallennagelbildungen in 56,5 % und einer Differenz der Nagellänge bzw. Form waren alle Patienten mit dem Erhalt des Nagels zufrieden und haben dies subjektiv nicht als störend empfunden.
Als besonders beeinträchtigend wurde eine Kälteempfindlichkeit von 48,3 % Patienten beschrieben.
Der Mittelwert der Fingerkraft im Schlüsselgriff mit Hilfe des Pinch-Gauge zwischen Daumen und den vier Fingerspitzen im Wechsel wurde bei fast allen Messungen an den gesunden Fingern gering größer gemessen ohne eine statistisch signifikante Differenz. Die Messung der Handkraft mittels Jamar-Dynamometer ergab ein Defizit von 8,8 % (Vergleich betroffene zur gesunden Hand).
Bei drei von 24 Patienten hat sich eine Beugekontraktur im Interphalangealgelenk von 5°, 15°, 20° und bei einem von 22 Patienten im distalen Interphalangealgelenk von 10° gebildet. Zum Nachuntersuchungszeitpunkt wurden durch die Untersucherin ein Hoffmann-Tinel- Zeichen in 24,1 % und Druckschmerz in 17,2 % im Bereich der verletzten Fingerkuppe festgestellt. Subjektiv empfand kein Patient diese Symptome als störend und alle berufstätigen Patienten konnten ihre vor dem Unfall ausgeübte Tätigkeit wieder aufnehmen. Diese Studie konnte belegen, dass die Defektdeckung der Fingerkuppenverletzungen mit Hilfe von neurovaskulären Insel-Lappenplastiken ein sehr gutes ästhetisches und funktionelles Ergebnis mit einer fast identischen Hautqualität erzielt. Mit dieser Methode konnte eine Wiederherstellung des Weichteilgewebes der sensiblen Fingerkuppe auch bei großflächigen Defekten der Fingerkuppe erreicht werden. Die subjektive Patientenzufriedenheit mit dieser Rekonstruktionsmethode ist hoch.
Background: Dentists are at a higher risk of suffering from musculoskeletal disorders (MSD) than the general population. However, the latest study investigating MSD in the dental profession in Germany was published about 20 years ago. Therefore, the aim of this study was to reveal the current prevalence of MSD in dentists and dental students in Germany. Methods: The final study size contained 450 (287 f/163 m) subjects of different areas of specialization. The age of the participants ranged from 23 to 75 years. The questionnaire consisted of a modified version of the Nordic Questionnaire, work-related questions from the latest questionnaire of German dentists, typical medical conditions and self-developed questions. Results: The overall prevalence showed that dentists suffered frequently from MSD (seven days: 65.6%, twelve months: 92%, lifetime: 95.8%). The most affected body regions included the neck (42.7%–70.9%–78.4%), shoulders (29.8%–55.6%–66.2%) and lower back (22.9%–45.8%–58.7%). Overall, female participants stated that they suffered from pain significantly more frequently, especially in the neck, shoulders and upper back. Conclusion: The prevalence of MSD among dentists, especially in the neck, shoulder and back area, was significantly higher than in the general population. In addition, women suffered more frequently from MSD than men in almost all body regions.
Large spines are stable and important for memory trace formation. The majority of large spines also contains synaptopodin (SP), an actin-modulating and plasticity-related protein. Since SP stabilizes F-actin, we speculated that the presence of SP within large spines could explain their long lifetime. Indeed, using 2-photon time-lapse imaging of SP-transgenic granule cells in mouse organotypic tissue cultures we found that spines containing SP survived considerably longer than spines of equal size without SP. Of note, SP-positive (SP+) spines that underwent pruning first lost SP before disappearing. Whereas the survival time courses of SP+ spines followed conditional two-stage decay functions, SP-negative (SP-) spines and all spines of SP-deficient animals showed single-phase exponential decays. This was also the case following afferent denervation. These results implicate SP as a major regulator of long-term spine stability: SP clusters stabilize spines, and the presence of SP indicates spines of high stability.
Prostate cancer patients whose tumors develop resistance to conventional treatment often turn to natural, plant-derived products, one of which is sulforaphane (SFN). This study was designed to determine whether anti-tumor properties of SFN, identified in other tumor entities, are also evident in cultivated DU145 and PC3 prostate cancer cells. The cells were incubated with SFN (1–20 µM) and tumor cell growth and proliferative activity were evaluated. Having found a considerable anti-growth, anti-proliferative, and anti-clonogenic influence of SFN on both prostate cancer cell lines, further investigation into possible mechanisms of action were performed by evaluating the cell cycle phases and cell-cycle-regulating proteins. SFN induced a cell cycle arrest at the S- and G2/M-phase in both DU145 and PC3 cells. Elevation of histone H3 and H4 acetylation was also evident in both cell lines following SFN exposure. However, alterations occurring in the Cdk-cyclin axis, modification of the p19 and p27 proteins and changes in CD44v4, v5, and v7 expression because of SFN exposure differed in the two cell lines. SFN, therefore, does exert anti-tumor properties on these two prostate cancer cell lines by histone acetylation and altering the intracellular signaling cascade, but not through the same molecular mechanisms.
Human placentation is a highly invasive process. Deficiency in the invasiveness of trophoblasts is associated with a spectrum of gestational diseases, such as preeclampsia (PE). The oncogene B-cell lymphoma 6 (BCL6) is involved in the migration and invasion of various malignant cells. Intriguingly, its expression is deregulated in preeclamptic placentas. We have reported that BCL6 is required for the proliferation, survival, fusion, and syncytialization of trophoblasts. In the present work, we show that the inhibition of BCL6, either by its gene silencing or by using specific small molecule inhibitors, impairs the migration and invasion of trophoblastic cells, by reducing cell adhesion and compromising the dynamics of the actin cytoskeleton. Moreover, the suppression of BCL6 weakens the signals of the phosphorylated focal adhesion kinase, Akt/protein kinase B, and extracellular regulated kinase 1/2, accompanied by more stationary, but less migratory, cells. Interestingly, transcriptomic analyses reveal that a small interfering RNA-induced reduction of BCL6 decreases the levels of numerous genes, such as p21 activated kinase 1, myosin light chain kinase, and gamma actin related to cell adhesion, actin dynamics, and cell migration. These data suggest BCL6 as a crucial player in the migration and invasion of trophoblasts in the early stages of placental development through the regulation of various genes associated with the migratory machinery.
The formation of oligomers of the amyloid-β peptide plays a key role in the onset of Alzheimer's disease. We describe herein the investigation of disease-relevant small amyloid-β oligomers by mass spectrometry and ion mobility spectrometry, revealing functionally relevant structural attributes. In particular, we can show that amyloid-β oligomers develop in two distinct arrangements leading to either neurotoxic oligomers and fibrils or non-toxic amorphous aggregates. Comprehending the key-attributes responsible for those pathways on a molecular level is a pre-requisite to specifically target the peptide's tertiary structure with the aim to promote the emergence of non-toxic aggregates. Here, we show for two fibril inhibiting ligands, an ionic molecular tweezer and a hydrophobic peptide that despite their different interaction mechanisms, the suppression of the fibril pathway can be deduced from the disappearance of the corresponding structure of the first amyloid-β oligomers.
Background: MitraClip ® (MC) is an established procedure for severe mitral regurgitation (MR) in patients deemed unsuitable for surgery. Right ventricular dysfunction (RVD) is associated with a higher mortality risk. The prognostic accuracy of heart failure risk scores like the Seattle heart failure model (SHFM) and Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score in pts undergoing MC with or without RVD has not been investigated so far. Methods: SHFM and MAGGIC score were calculated retrospectively. RVD was determined as tricuspid annular plane systolic excursion (TAPSE) ≤15 mm. Area under receiver operating curves (AUROC) of SHFM and MAGGIC were performed for one-year all-cause mortality after MC. Results: N = 103 pts with MR III° (73 ± 11 years, LVEF 37 ± 17%) underwent MC with a reduction of at least I° MR. One-year mortality was 28.2%. In Kaplan-Meier analysis, one- year mortality was significantly higher in RVD-pts (34.8% vs 2.8%, p = 0.009). Area under the Receiver Operating Characteristic (AUROC) for SHFM and MAGGIC were comparable for both scores (SHFM: 0.704, MAGGIC: 0.692). In pts without RVD, SHFM displayed a higher AUROC and therefore better diagnostic accuracy (SHFM: 0.776; MAGGIC: 0.551, p < 0.05). In pts with RVD, MAGGIC and SHFM displayed comparable AUROCs. Conclusion: RVD is an important prognostic marker in pts undergoing MC. SHFM and MAGGIC displayed adequate over-all prognostic power in these pts. Accuracy differed in pts with and without RVD, indicating higher predictive power of the SHFM score in pts without RVD.