29 research outputs found
1029-175 Anti-ErbB2 modulation of Bcl-xL/Bcl-xScauses mitochondrial dysfunction and apoptosis
Performance characteristics of a novel blood bag in-line closure device and subsequent product quality assessment
The T-pod is as stable as supraacetabular fixation using 1 or 2 Schanz screws in partially unstable pelvic fractures: a biomechanical study
Introduction: Unstable fractures of the pelvis remain the predominant cause of severe hemorrhage, shock and early death in severely injured patients. The use of pelvic binders has become increasingly popular, particularly in the preclinical setting. There is currently insufficient evidence available about the stability of the pelvic binder versus supraacetabular fixation using 1 or 2 Schanz screws. We aimed to analyze the stability of the pelvic binder and supraacetabular fixateurs using either 1 or 2 Schanz screws in a cadaver model of an induced pelvic B-type fracture.
Materials and methods: The study was undertaken in 7 human fresh-frozen cadaveric pelvises with induced AO-type B fractures. Three stabilization techniques were compared: T-POD (pelvic bandage), supraacetabular external fixator with 1 pin on each side and external fixator with 2 pins on each side. Stability and stiffness were analyzed in a biomechanical testing machine using a 5-step protocol with static and dynamic loading, dislocation data were retrieved by ultrasound sensors at the fracture sites.
Results: No significant differences in fracture fragment displacement were detected when using either the T-POD, a 1-pin external fixator or a 2-pin external fixator (P > 0.05). The average difference in displacement between the three methods was < 1 mm.
Conclusions: Pelvic binders are suitable for reduction of pelvic B-type fractures. They provide stability comparable to that of supraacetabular fixators, independently of whether 1 or 2 Schanz screws per side are used. Pelvic binders provide sufficient biomechanical stability for transferring patients without the need to first replace them with surgically applied external fixators. However, soft tissue irritation has to be taken into consideration and prolonged wear should be avoided.
Level of evidence: Level III
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2018 Proceedings of the International Conference on Trauma Surgery Technology in Giessen
The overarching goal of the gathering was to define a concept for technology design research in Giessen to improve patient outcomes through the design of assistive technology that assists both patients and surgeons. The emerging field of regenerative rehabilitation where trauma patients are treated by methods of regenerative medicine promises great improvements for our field, but clinical success is yet to be realised. The symposium was specifically organised to acknowledge and address these issues
Inter- versus intramodal integration in sensorimotor synchronization: a combined behavioral and magnetoencephalographic study
Although the temporal occurrence of the pacing signal is predictable in sensorimotor synchronization tasks, normal subjects perform on-the-beat-tapping to an isochronous auditory metronome with an anticipatory error. This error originates from an intermodal task, that is, subjects have to bring information from the auditory and tactile modality to coincide. The aim of the present study was to illuminate whether the synchronization error is a finding specific to an intermodal timing task and whether the underlying cortical mechanisms are modality-specific or supramodal. We collected behavioral data and cortical evoked responses by magneto-encephalography (MEG) during performance of cross- and unimodal tapping-tasks. As expected, subjects showed negative asynchrony in performing an auditorily paced tapping task. However, no asynchrony emerged during tactile pacing, neither during pacing at the opposite finger nor at the toe. Analysis of cortical signals resulted in a three dipole model best explaining tap-contingent activity in all three conditions. The temporal behavior of the sources was similar between the conditions and, thus, modality independent. The localization of the two earlier activated sources was modality-independent as well whereas location of the third source varied with modality. In the auditory pacing condition it was localized in contralateral primary somatosensory cortex, during tactile pacing it was localized in contralateral posterior parietal cortex. In previous studies with auditory pacing the functional role of this third source was contradictory: A special temporal coupling pattern argued for involvement of the source in evaluating the temporal distance between tap and click whereas subsequent data gave no evidence for such an interpretation. Present data shed new light on this question by demonstrating differences between modalities in the localization of the third source with similar temporal behavior
Multiancestry analysis of the HLA locus in Alzheimerâs and Parkinsonâs diseases uncovers a shared adaptive immune response mediated by HLA-DRB1*04 subtypes
Across multiancestry groups, we analyzed Human Leukocyte Antigen (HLA) associations in over 176,000 individuals with Parkinsonâs disease (PD) and Alzheimerâs disease (AD) versus controls. We demonstrate that the two diseases share the same protective association at the HLA locus. HLA-specific fine-mapping showed that hierarchical protective effects of HLA-DRB1*04 subtypes best accounted for the association, strongest with HLA-DRB1*04:04 and HLA-DRB1*04:07, and intermediary with HLA-DRB1*04:01 and HLA-DRB1*04:03. The same signal was associated with decreased neurofibrillary tangles in postmortem brains and was associated with reduced tau levels in cerebrospinal fluid and to a lower extent with increased AÎČ42. Protective HLA-DRB1*04 subtypes strongly bound the aggregation-prone tau PHF6 sequence, however only when acetylated at a lysine (K311), a common posttranslational modification central to tau aggregation. An HLA-DRB1*04-mediated adaptive immune response decreases PD and AD risks, potentially by acting against tau, offering the possibility of therapeutic avenues
Tape suture for stabilization of incomplete posterior pelvic ring fractures - biomechanical analysis of a new minimally invasive treatment for incomplete lateral compression pelvic ring fractures
Background: Incomplete lateral compression fractures (including AO Type B2.1) are among the most common pelvic ring injuries. Although the treatment of choice remains controversial, sacroiliac (SI) screws are commonly used for the operative treatment of incomplete lateral compression fractures of the pelvic ring. However, the disadvantages of SI screws include the risk of nerve root or blood vessel injury. Recently, tape sutures have been found useful as stabilizing material for the treatment of injuries of the syndesmosis, the rotator cuff and knee ligaments. In this current study, we aimed to test the biomechanical feasibility of tape sutures to stabilize the pelvis in the setting of AO Type B2.1 injury.
Methods: Six human cadaveric pelvises underwent cyclic loading to compare the biomechanical stability of different osteosynthesis methods in a B2.1 fracture model. The methods tested in this experiment were a FiberTapeÂź suture and the currently established SI screw. A 3D ultrasound tracking system was used to measure fracture fragment motion. Linear regression was used to model displacement and stiffness at the posterior and anterior pelvic ring.
Results: At the posterior fracture site, the FiberTapeŸ demonstrated similar displacement (2.2 ± 0.8 mm) and stiffness (52.2 ± 18.0 N/mm) compared to the sacroiliac screw (displacement 2.1 ± 0.6 mm, P > 0.999; stiffness 50.8 ± 13.0 N/mm, P > 0.999). Considering the anterior fracture site, the FiberTapeŸ again demonstrated similar displacement (3.8 ± 1.3 mm) and stiffness (29.5 ± 9.0 N/mm) compared to the sacroiliac screw (displacement 2.9 ± 0.8 mm, P = 0.2196; stiffness 37.5 ± 11.5 N/mm, P = 0.0711).
Conclusion: The newly presented osteosynthesis, the FiberTapeÂź, shows promising results for the stabilization of the posterior pelvic ring in AO Type B2.1 lateral compression fractures compared to a sacroiliac screw osteosynthesis based on its minimal-invasiveness and the statistically similar biomechanical properties
Novel technique of aortic banding followed by gene transfer during hypertrophy and heart failure
Inhibition of ErbB2 causes mitochondrial dysfunction in cardiomyocytes. Implications for herceptin-induced cardiomyopathy
ObjectivesWe investigated the effects of erbB2 inhibition by anti-erbB2 antibody on cardiomyocyte survival and mitochondrial function.BackgroundErbB2 is an important signal integrator for the epidermal growth factor family of receptor tyrosine kinases. Herceptin, an inhibitory antibody to the erbB2 receptor, is a potent chemotherapeutic but causes cardiac toxicity.MethodsPrimary cultures of neonatal rat ventricular myocytes were exposed to anti-erbB2 antibody (Ab) (7.5 ÎŒg/ml) for up to 24 h. Cell viability, mitochondrial function, and apoptosis were measured using multiple complementary techniques.ResultsErbB2 inhibition was associated with a dramatic increase in expression of the pro-apoptotic Bcl-2 family protein Bcl-xS and decreased levels of anti-apoptotic Bcl-xL. There was a time-dependent increase in mitochondrial translocation and oligomerization of bcl-associated protein (BAX), as indicated by 1,6-bismaleimidohexane crosslinking. The BAX oligomerization was associated with cytochrome c release and caspase activation. These alterations induced mitochondrial dysfunction, a loss of mitochondrial membrane potential (Ï) (76.9 ± 2.4 vs. 51.7 ± 0.1; p < 0.05; n = 4), a 35% decline in adenosine triphosphate levels (p < 0.05), and a loss of redox capacity (0.72 ± 0.04 vs. 0.64 ± 0.02; p< 0.01). Restoration of Bcl-xL levels through transactivating regulatory protein-mediated protein transduction prevented the decline in Ï mitochondrial reductase activity and cytosolic adenosine triphosphate.ConclusionsAnti-erbB2 activates the mitochondrial apoptosis pathway through a previously undescribed modulation of Bcl-xL and -xS, causing impairment of mitochondrial function and integrity and disruption of cellular energetics