Strukturelle und funktionelle Analyse des Signalmoleküls Sema3A

Die Semaphorine repräsentieren die größte Proteinfamilie von Signalmolekülen, die an der axonalen Wegfindung im embryonalen Nervensystem beteiligt sind. Für eine spätere Kristallstrukturanalyse wurde die kollabierende Aktivität eines 65 kDa Fragmentes von Sema3A, welches die vollständige Semaphorin-Domäne enthält, bestimmt. Eine auf der Struktur basierende Analyse konservierter Aminosäurereste gab Aufschluss über potentielle Interaktionsstellen, und durch gezielte Mutagenese des Proteins wurden die Bindungsstellen für die Rezeptoruntereinheiten Nrp-1 und Plexin-A1 identifiziert. Weiterhin wurde die Funktion der GTPase RhoD im von Sema3A aktivierten Signalweg untersucht. Es konnte gezeigt werden, dass die Interaktion von RhoD mit PlexinA1 für die inhibierende Wirkung von RhoD nicht essentiell ist. Vielmehr scheint die Interaktion von RhoD mit dem Protein Diaphanous2C eine wichtige Rolle zu spielen. Zusätzlich wurde eine potentielle GAP-Aktivität von Plexin-A1 für Ras GTPasen untersucht

A biomechanical intervention study

The demographic change clearly shows that the population is aging and, as one consequence, the risk of falls in the later stages of life becomes more and more a critical problem. In this context, Feder et al. (2000) showed that half of all persons older than 80 and one third of all persons older than 65 years old fall on average at least once per year. Therefore, more research is needed to be able to reduce the risk of falls in the elderly population. One approach to prevent falls during ageing may be the use of unstable shoes for everyday life activities, but so far only few studies have investigated whether unstable shoes can improve balance and prevent falls in an elderly population. As a consequence, the aim of this study was to determine the influence of a new unstable shoe construction on the balance performance in elderly women with respect to the risk of falls. METHODS 70 healthy elderly women aged between 52 and 81 years (66.1 ± 6.6 years) participated in this study. The subjects were measured three times: First measurements were taken before the intervention started (PRE) and repeated after four (INTER) respectively twelve weeks (POST) of intervention. Two different shoe designs were used for this study, a conventional sport shoe (KS) was chosen as control condition (CG). The experimental group (EG) wore a shoe which was unstable in medio-lateral direction (ES) as it was built with a harder midsole material along the gait line. The gait line area was elevated and the midsole thickness gradually decreased from this central area to the border of the shoe. This combination of harder material and geometrical shape of the sole created instability around the gait line during walking. On each of the three testing days, the subjects were analyzed with the help of clinical as well as biomechanical tests. The participants executed movements of everyday life, including standing balance or rising from a chair for the Tinetti-Test (TT) (Tinetti (1986)) and the Berg Balance Scale (BBS) (Berg (1989)). Moreover, they had to fill a questionnaire including their history of falls and their experience with unstable footwear as well as the SF-36 Health Survey (Bullinger & Kirchberger (1998)). Additionally, handgrip force (MAP 80 K1, Germany) and vibration perception on the medial malleolus and the dorsal side of the hallux were measured (modified Horwell Neurothesiometer, UK) on both sides of the body (left and right). Moreover, the participants had to perform three different balance tasks (bipedal standing with open eyes, bipedal standing with closed eyes and a tandem stand with open eyes) on a force platform (Kistler Inc., Switzerland). These balancing tasks were performed in different conditions (own shoes (EIS), ES, KS) as well as barefoot (BAR) and measurements were executed three times for each condition with duration of 10 s. Additionally, the path of the center of gravity (COG) was also measured during the balancing tasks. As the time requirements of the measurements were substantial, only a small randomized chosen subgroup of 28 women out of the 70 subjects performed additional measurements. For the measurements of the vibration perception thresholds, the medial malleolus, the dorsal side of the hallux as well as the perception of the finger pad of the middle finger was measured. These participants also performed the balance tasks in two additional shoe conditions (MBT and Reebok Easytone (RET)). While performing the three different balance tasks in 6 different conditions (BAR, EIS, RET, MBT, KS, ES), the muscle activity of the m. tibialis anterior (TA), the m. vastus lateralis (VL), the m. biceps femoris (BF), and the lateral side of the m. gastrocnemius (GL) was measured additionally. After the PRE measurements each subject received one pair of shoes to take home. Subjects were randomly chosen to receive either shoe KS (Control Group) or shoe ES (Experimental Group). The subjects were instructed to wear the assigned shoes for at least one hour per day and to document the duration of wearing in a diary. Beyond that, 20 out of the 70 subjects participated in an additional testing to elucidate the biomechanical characteristics of the two intervention shoes. For these measurements, each subject walked across a force platform in four different shoes (MBT, RET, KS, ES) at a given speed of 1,4 ± 0,05 m/s. During this task, ground reaction forces, rear foot range of motion, pronation velocity and tibial acceleration were measured. RESULTS & DISCUSSION The results showed that both subject groups were comparable regarding their anthropometrical data as well as in their daily duration of wearing the intervention shoes. Handgrip force measurements as well as the detection of the vibration perception thresholds did not deliver any statistically significant differences between the two groups. The additional biomechanical testing showed that both interventional shoes (KS, ES) displayed similar biomechanical characteristics and were comparable to the other two shoes (MBT, RET). Moreover, a difference between the KS and the ES regarding the rear foot motion was discovered: compared to the KS, the ES causes a greater range of rear foot motion combined with a lower pronation velocity. In relation to the aim of the study, these results demonstrated that both intervention shoes were very similar in their biomechanical properties beside the influence of the slight instability of the ES, which is clearly shown by the results of the rear foot parameters. The clinical tests (Tinetti-Test, Berg Balance Scale) showed slightly improved results during the intervention period of 3 months in both groups. The results of the path length of the COG revealed no statistically significant differences between the two intervention groups CG and EG. In general, a decrease in COG sway was detected during the intervention period of 3 months. During the measurements with 6 different conditions in tandem stance, the subjects generated comparably higher values for the ES and the MBT than in the other conditions. These results indicate that the special sole construction of the ES challenges the subjects balance performance. Moreover, muscle activity was statistically significantly higher in the ES than in the EIS and the KS and showed altogether higher activity values compared to the MBT. These results suggest that the ES provokes a higher amount of sway together with an increase of muscle activity in spite of its only slight extent of instability. CONCLUSION The findings of this study show that all subjects were in good physical shape, which resulted in similar or even better results in all measurements during the intervention period of 3 months. All in all only slight changes were detected in balance performance, which may have been caused by the slight extent of instability in the ES. Regarding the KS, the results showed that both kinds of intervention had a small effect on balance performance in elderly women. This indicates positive effects on all subjects concerning the risk of falls. To sum up, this study showed that the new unstable shoe construction with a slight extent of instability could cause positive effects on the balance performance in the elderly without increasing the risk of falls. Moreover, these findings confirm that wearing unstable shoes can be an approach to prevent falls and increase balance performance during ageing

Prognostische Auswirkung von Arzneimittelinteraktionen bei Patienten mit fortgeschrittenen Tumorleiden

Das Ziel dieser Studie ist die Bewertung des prognostischen Einflusses von Polypharmazie und potentiellen Arzneimittelinteraktionen (PDI, DDI) bei Patienten mit fortgeschrittenen Tumorerkrankungen mit Hilfe von Kaplan Meier Statistiken. Hierzu wurde ein Power von 84% bei einem Siginifikanzniveau von 5% für einen 25% Rückgang des Gesamtüberlebens (OS) bei Patienten mit einer „Major-Risk“ Arzneimittelinteraktion berechnet. Eigeschlossen wurden 105 Patienten mit nicht-kleinzelligen Lungenkarzinom (NSCLC), 100 Patienten mit Mammakarzinom (BC) und 100 Patienten der Palliativstation (PCU). Alle Patienten hatten ein fortgeschrittenes Tumorleiden und erhielten eine palliative Systemtherapie im Zeitraum von 2010 bis 2015 am Kantonsspital St. Gallen in der Schweiz. Die Detektion der Arzneimittelinteraktionen erfolgte auf Basis des HospIndex in Kombination mit der spezialisierten Arzneimittelinteraktionssoftware Documedis CDS der Firma HCI Solution AG. Die Mediane Anzahl der Komedikamente beträgt 5 (Range 0-15). In 74 Patienten (24.3 %) wurde eine „Major-Risk“ PDI ermittelt. Die Gesamtanzahl der verabreichten Arzneimittel ist in allen drei Kohorten mit der PDI signifikant assoziiert (p < 0.0001). Es zeigte sich ein Anstieg für „Major-Risk“ bei gleichzeitiger Verabreichung von <4 Arzneimitteln auf 17.1% mit Zunahme auf 26.2% bei 4-7 Arzneimitteln, 40% bei 8-11 Arzneimitteln und 83.3% bei >11 Arzneimitteln. Die OS in der NSCLC Kohorte beträgt im Median 8.6 Monate, in der BC Kohorte 33 Monate und in der PCU Kohorte 1.2 Monate. Major-Risk PDI sind in der Kohorte der BC Patienten signifikant mit einer niedrigeren OS (HR = 1.32, 95 % KI 1.01-1.74, p = 0.049) assoziiert. Diese Assoziation kann sowohl in der NSCLC Kohorte (HR = 1.11, 95 % KI 0.84-1.47, p = 0.45) als auch in der PCU Kohorte (HR = 1.12, 95 % KI 0.86-1.45, p = 0.41) nicht gezeigt werden. Eine Assoziation zwischen Arzneimittelinteraktionen und dem Gesamtüberleben in der BC Kohorte (HR = 1.32, p = 0.049) bleiben auch im adjustierten Model signifikant bestehen. Zusammenfassend sind Arzneimittelinteraktion und Polypharmazie ein wichtiges Thema in der Behandlung von Patienten mit fortgeschrittenen Tumorerkrankungen. Der Schweregrad einer PDI scheint einen signifikanten und möglicherweise klinisch relevanten prognostischen Faktor für einzelne Patientengruppen darzustellen. In unserer Studie spiegelt sich dies in der Kohorte der Mammakarzinom Patienten. 68 % der Gesamtpopulation erhielten mehr als 7 konkurrierende Arzneimittel (BC 81 %, PCU 67 %, NSCLC 56 %). Das Patientenrisiko für PDI lag vergleichbar mit anderen Studien bei 55,4 %

Nitrogen and carbon allocation in Hieracium pilosella in response to different fertilizer levels

Hömme R, Beyschlag W, Steinlein T. Nitrogen and carbon allocation in Hieracium pilosella in response to different fertilizer levels. In: Zotz G, ed. Funktionelle Bedeutung von Biodiversität. Verhandlungen der Gesellschaft für Ökologie. Vol 31. Berlin: Parey; 2001: 349-349

Investigation of Orthopedic Prosthesis Socket Management after Transfemoral Amputation by Expert Survey

Prosthesis treatment requires the close interaction of different actors. In fitting prostheses to patients, special attention is given to the manufacturing of the socket. The continuous development of the technologies involved in the fitting and optimization of prostheses is shown in the literature. The assessment of orthopedic technicians and their influence in the process is thus far largely unexplored. Ten orthopedic technicians were interviewed about the socket fitting process after transfemoral amputation. The research goal was to clarify the socket treatment process with regards to the German context. The results showed that the orthopedic technicians focussing on the patient during the fitting process. This study underlines the importance of interaction and empathy. Volume fluctuations are decisive within the treatment process and are interactively influenced by various factors. Furthermore, the research emphasizes the need for appropriate assistive technologies and the potential for the further development of existing systems