Lebenswissenschaften und Ethik
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Epigenetic modifiers of the histone deacetylase (HDAC) family contribute to autoimmunity, cancer, HIV infection, inflammation, and neurodegeneration. Hence, histone deacetylase inhibitors (HDACi), which alter protein acetylation, gene expression patterns, and cell fate decisions, represent promising new drugs for the therapy of these diseases. Whereas pan-HDACi inhibit all 11 Zn2+-dependent histone deacetylases (HDACs) and cause a broad spectrum of side effects, specific inhibitors of histone deacetylase 6 (HDAC6i) are supposed to have less side effects. We present the synthesis and biological evaluation of Marbostats, novel HDAC6i that contain the hydroxamic acid moiety linked to tetrahydro-β-carboline derivatives. Our lead compound Marbostat-100 is a more potent and more selective HDAC6i than previously established well-characterized compounds in vitro as well as in cells. Moreover, Marbostat-100 is well tolerated by mice and effective against collagen type II induced arthritis. Thus, Marbostat-100 represents a most selective known HDAC6i and the possibility for clinical evaluation of a HDAC isoform-specific drug.
Over the past decade, veno-venous extracorporeal membrane oxygenation (vvECMO) has been increasingly utilized in respiratory failure in patients. This study presents our institution´s experience focusing on the life span of ECMO systems reflecting the performance of a particular system. A retrospective review of our ECMO database identified 461 adult patients undergoing vvECMO (2010-2017). Patients that required more than one system and survived the first exchange >24 hours (n = 139) were included. Life span until the first exchange and exchange criteria were analyzed for all systems (PLS, Cardiohelp HLS-set, both Maquet Cardiopulmonary, Rastatt, Germany; Deltastream/Hilite7000LT, iLA-activve, Xenios/NovaLung, Heilbronn, Germany; ECC.O5, LivaNova, Mirandola, Italy). At our ECMO center, the frequency of a system exchange was 30%. The median (IQR) life span was 9 (6-12) days. There was no difference regarding the different systems (p = 0.145 and p = 0.108, respectively). However, the Deltastream systems were exchanged more frequently due to elective technical complications (e. g. worsened gas transfer, development of coagulation disorder, increased bleedings complications) compared to the other exchanged systems (p = 0.013). In summary, the used ECMO systems are safe and effective for acute respiratory failure. There is no evidence for the usage of a specific system. Only the increased predictability of an imminent exchange preferred the usage of a Deltastream system. However, the decision to use a particular system should not depend solely on the possible criteria for an exchange.
Degradation and release of tannic acid from an injectable tissue regeneration bead matrix in vivo
(2021)
The development of multifunctional biomaterials as both tissue regeneration and drug delivery devices is currently a major focus in biomedical research. Tannic Acid (TA), a naturally occurring plant polyphenol, displays unique medicinal abilities as an antioxidant, an antibiotic, and as an anticancer agent. TA has applications in biomaterials acting as a crosslinker in polymer hydrogels improving thermal stability and mechanical properties. We have developed injectable cell seeded collagen beads crosslinked with TA for breast reconstruction and anticancer activity following lumpectomy. This study determined the longevity of the bead implants by establishing a degradation time line and TA release profile in vivo. Beads crosslinked with 0.1% TA and 1% TA were compared to observe the differences in TA concentration on degradation and release. We found collagen/TA beads degrade at similar rates in vivo, yet are resistant to complete degradation after 16 weeks. TA is released over time in vivo through diffusion and cellular activity. Changes in mechanical properties in collagen/TA beads before implantation to after 8 weeks in vivo also indicate loss of TA over a longer period of time. Elastic moduli decreased uniformly in both 0.1% and 1% TA beads. This study establishes that collagen/TA materials can act as a drug delivery system, rapidly releasing TA within the first week following implantation. However, the beads retain TA long term allowing them to resist degradation and remain in situ acting as a cell scaffold and tissue filler. This confirms its potential use as an anticancer and minimally invasive breast reconstructive device following lumpectomy.
Ein interdisziplinäres Forschungsprojekt der Ostbayerischen Hochschule Regensburg untersucht, inwiefern Telemedizin und digitale Anwendungen die Therapie und Pflege von Menschen mit Schlaganfall in ihrem häuslichen Umfeld unterstützen, ihre Lebensqualität beeinflussen und die intersektorale Versorgung verbessern kann.
Blood flow in channels of varying diameters <500μm exhibits strong non-linear effects. Multiphase finite volume approaches are feasible, but still computationally costly. Here, the feasibility of applying convolutional neural networks for blood flow prediction in artificial lungs is investigated. Training targets are precomputed using an Eulerian two-phase approach. To match with experimental data, the interphase drag and lift, as well as intraphase shear-thinning are adapted. A recursively branching regression network and convolution/deconvolution networks with plain skip connections and densely connected skips are investigated. A priori knowledge is incorporated in the loss functional to prevent the network from learning non-physical solutions. Inference from neural networks is approximately six orders of magnitude faster than the classical finite volume approach. Even if resulting in comparably coarse flow fields, the neural network predictions can be used as close to convergence initial solutions greatly accelerating classical flow computations.
"Topographic Shift": a new digital approach to evaluating topographic changes of the female breast
(2021)
Purpose
To assess precise topographic changes of the breast, objective documentation and evaluation of pre- and postoperative results are crucial. New technologies for mapping the body using digital, three-dimensional surface measurements have offered novel ways to numerically assess the female breast. Due to the lack of clear demarcation points of the breast contour, the selection of landmarks on the breast is highly dependent on the examiner, and, therefore, is prone to error when conducting before-after comparisons of the same breast. This study describes an alternative to volumetric measurements, focusing on topographic changes of the female breast, based on three-dimensional scans.
Method
The study was designed as an interventional prospective study of 10 female volunteers who had planned on having aesthetic breast augmentation with anatomical, textured implants. Three dimensional scans of the breasts were performed intraoperatively, first without and then with breast implants. The topographic change was determined as the mean distance between two three-dimensional layers before and after augmentation. This mean distance is defined as the Topographic Shift. Results The mean implant volume was 283 cc (SD = 68.6 cc, range = 210-395 cc). The mean Topographic Shift was 7.4 mm (SD = 1.9 mm, range = 4.8-10.7 mm). The mean Topographic Shifts per quadrant were: I: 8.0 mm (SD = 3.3 mm); II: 9.2 mm (SD = 3.1 mm); III: 6.9 mm (SD = 3.5 mm); IV: 1.9 mm (SD = 4.3 mm).
Conclusion
The Topographic Shift, describing the mean distance between two three-dimensional layers (for example before and after a volume changing therapy), is a new approach that can be used for assessing topographic changes of a body area. It was found that anatomical, textured breast implants cause a topographic change, particularly on the upper breast, in quadrant II, the decollete.
One of the fundamental challenges in L-PBF of filigree geometries, such as aortic stents used in biomedical applications, is the requirement for a robust yet easily removable support structure that allows each component to be successfully fabricated without distortion. To solve this challenge, an integrative experimental approach was attempted in the present study by identifying an optimal support structure design and an optimized support removal strategy for this design. The specimens were manufactured using four different support structure designs based on the geometry exposed to the laser beam during the L-PBF. Support removal procedures included sand blasting (SB), glass bead blasting (GB), and electrochemical polishing (ECP). The two best-performing designs (line and cross) were chosen due to shorter lead times and lower material consumption. As an additional factor that indicates a stable design, the breaking load requirement to remove the support structures was determined. A modified line support with a 145° included angle was shown to be the best support structure design in terms of breaking load, material consumption, and manufacturing time. All three procedures were used to ensure residue-free support removal for this modified line support design, with ECP proving to be the most effective.
Vitamin C is an essential nutrient for humans and is involved in a plethora of health-related functions. Several studies have shown a connection between vitamin C intake and an improved resistance to infections that involves the immune system. However, the body cannot store vitamin C and both the elevated oral intake, and the intravenous application have certain disadvantages. In this study, we wanted to show a new formulation for the liposomal packaging of vitamin C. Using freeze etching electron microscopy, we show the formed liposomes. With a novel approach of post-processing procedures of real-time sonography that combines enhancement effects by contrast-like ultrasound with a transducer, we wanted to demonstrate the elevated intestinal vitamin C resorption on four participants. With the method presented in this study, it is possible to make use of the liposomal packaging of vitamin C with simple household materials and equipment for intake elevation. For the first time, we show the enhanced resorption of ingested liposomes using microbubble enhanced ultrasound imaging.
Resting motor threshold and magnetic field output of the figure-of-8 and the double-cone coil
(2020)
The use of the double-cone (DC) coil in transcranial magnetic stimulation (TMS) is promoted with the notion that the DC coil enables stimulation of deeper brain areas in contrast to conventional figure-of-8 (Fo8) coils. However, systematic comparisons of these two coil types with respect to the spatial distribution of the magnetic field output and also to the induced activity in superficial and deeper brain areas are limited. Resting motor thresholds of the left and right first dorsal interosseous (FDI) and tibialis anterior (TA) were determined with the DC and the Fo8 coil in 17 healthy subjects. Coils were orientated over the corresponding motor area in an angle of 45 degrees for the hand area with the handle pointing in posterior direction and in medio-lateral direction for the leg area. Physical measurements were done with an automatic gantry table using a Gaussmeter. Resting motor threshold was higher for the leg area in contrast to the hand area and for the Fo8 in contrast to the DC coil. Muscle by coil interaction was also significant providing higher differences between leg and hand area for the Fo8 (about 27%) in contrast to the DC coil (about 15%). Magnetic field strength was higher for the DC coil in contrast to the Fo8 coil. The DC coil produces a higher magnetic field with higher depth of penetration than the figure of eight coil.