Zementaugmentation bei Wirbelmetastasen (Vertebro- und Kyphoplastie)

Zusammenfassung: Pathologische Wirbelfrakturen bei Metastasen oder im Rahmen eines multiplen Myeloms können mittels einer Zementaugmentation (Vertebro- oder Kyphoplastie) effizient stabilisiert werden. Die Indikationsstellung beschränkt sich auf Läsionen im Wirbelkörper, sobald die posterioren Elemente involviert sind genügt eine Zementierung nicht mehr, ebenso wenn eine Spinalkanaleinengung/Neurokompression vorhanden ist. Technisch wird gleich verfahren wie bei der osteoporotischen Fraktur - das Extravasationsrisiko ist aber erheblich größer und die klinischen Ergebnisse sind nicht so uniform positiv wie bei Osteoporosefrakturen. Die Zementaugmentation per se ist keine Tumorbehandlung sondern eine Stabilisierung des Wirbels. Osteolysen ohne mechanische Kompromittierung brauchen keine Augmentation. Die Patientenbetreuung sollte interdisziplinär vernetzt erfolge

Differences in endplate deformation of the adjacent and augmented vertebra following cement augmentation

Vertebral cement augmentation can restore the stiffness and strength of a fractured vertebra and relieve chronic pain. Previous finite element analysis, biomechanical tests and clinical studies have indirectly associated new adjacent vertebral fractures following augmentation to altered loading. The aim of this repeated measures in situ biomechanical study was to determine the changes in the adjacent and augmented endplate deformation following cement augmentation of human cadaveric functional spine units (FSU) using micro-computed tomography (micro-CT). The surrounding soft tissue and posterior elements of 22 cadaveric human FSU were removed. FSU were assigned to two groups, control (n=8) (loaded on day 1 and day 2) and augmented (n=14) (loaded on day 1, augmented 20% cement fill, and loaded on day 2). The augmented group was further subdivided into a prophylactic augmentation group (n=9), and vertebrae which spontaneously fractured during loading on day 1 (n=5). The FSU were axially loaded (200, 1,000, 1,500-2,000N) within a custom made radiolucent, saline filled loading device. At each loading step, FSUs were scanned using the micro-CT. Endplate heights were determined using custom software. No significant increase in endplate deformation following cement augmentation was noted for the adjacent endplate (P>0.05). The deformation of the augmented endplate was significantly reduced following cement augmentation for both the prophylactic and fracture group (P<0.05, P<0.01, respectively). Endplate deformation of the controls showed no statistically significant differences between loading on day 1 and day 2. A linear relationship was noted between the applied compressive load and endplate deflection (R 2=0.58). Evidence of significant endplate deformation differences between unaugmented and augmented FSU, while evident for the augmented endplate, was not present for the adjacent endplate. This non-invasive micro-CT method may also be useful to investigate endplate failure, and parameters that predict vertebral failur

Current mode monolithic active pixel sensor with correlated double sampling for charged particle detection

A monolithic active pixel sensor operating in current mode for charged particle detection is described. The sensing element in each pixel is an n-well/p-sub diode with a PMOS transistor integrated in an n-well. The drop of the n-well potential from the collection of charge modulates the transistor channel current. Each pixel features two current mode memory cells. The subtraction of distant-in-time samples frees the signal of fixed pattern noise (FPN) and of the correlated low-frequency temporal noise components, resulting in extraction of the particle footprint. The subtraction circuits are placed at each column end. A transimpedance amplifier, integrating in sequence two current samples and subtracting the results in an arithmetic operation, was adopted. The integrated version of the transimpedance amplifier, designed with a maximized conversion gain, is burdened by a risk of an early saturation, imperiling its operation, if the dispersions of the dc current component are too big. The degree of dispersions could not be estimated during the design. Some number of columns is available as a backup with the direct current readout. An external realization of the subtracting circuit, based on the same principle, is used to process direct output columns. The concept of the data acquisition setup developed, the tested performance of an array of cells, and the processing circuitry are described

Role of the carboxyl terminal di-leucine in phosphorylation and internalization of C5a receptor

AbstractThe carboxyl tail of G protein-coupled receptors contains motifs that regulate receptor interactions with intracellular partners. Activation of the human neutrophil complement fragment C5a receptor (C5aR) is terminated by phosphorylation of the carboxyl tail followed by receptor internalization. In this study, we demonstrated that bulky hydrophobic residues in the membrane-proximal region of the C5aR carboxyl tail play an important role in proper structure and function of the receptor: Substitution of leucine 319 with alanine (L319A) resulted in receptor retention in the endoplasmic reticulum, whereas a L318A substitution allowed receptor transport to the cell surface, but showed slow internalization upon activation, presumably due to a defect in phosphorylation by both PKC and GRK. Normal agonist-induced activation of ERK1/2 and intracellular calcium release suggested that the L318A mutation did not affect receptor signaling. Binding of GRK2 and PKCβII to intracellular loop 3 of C5aR in vitro indicated that mutagenesis of L318 did not affect kinase binding. Limited proteolysis with trypsin revealed a conformational difference between wild type and mutant receptor. Our studies support a model in which the L318/L319 stabilizes an amphipathic helix (Q305–R320) in the membrane-proximal region of C5aR

Radiation Tolerance of CMOS Monolithic Active Pixel Sensors with Self-Biased Pixels

CMOS Monolithic Active Pixel Sensors (MAPS) are proposed as a technology for various vertex detectors in nuclear and particle physics. We discuss the mechanisms of ionizing radiation damage on MAPS hosting the the dead time free, so-called self bias pixel. Moreover, we discuss radiation hardened sensor designs which allow operating detectors after exposing them to irradiation doses above 1 Mra

The dichotomous structure of the warm conveyor belt

The warm conveyor belt (WCB) of an extratropical cyclone generally splits into two branches. One branch (WCB1) turns anticyclonically into the downstream upper-level tropospheric ridge, while the second branch (WCB2) wraps cyclonically around the cyclone centre. Here, the WCB split in a typical North Atlantic cold-season cyclone is analysed using two numerical models: the Met Office Unified Model and the COSMO model. The WCB flow is defined using off-line trajectory analysis. The two models represent the WCB split consistently. The split occurs early in the evolution of the WCB with WCB1 experiencing maximum ascent at lower latitudes and with higher moisture content than WCB2. WCB1 ascends abruptly along the cold front where the resolved ascent rates are greatest and there is also line convection. In contrast, WCB2 remains at lower levels for longer before undergoing saturated large-scale ascent over the system's warm front. The greater moisture in WCB1 inflow results in greater net potential temperature change from latent heat release, which determines the final isentropic level of each branch. WCB1 also exhibits lower outflow potential vorticity values than WCB2. Complementary diagnostics in the two models are utilised to study the influence of individual diabatic processes on the WCB. Total diabatic heating rates along the WCB branches are comparable in the two models with microphysical processes in the large-scale cloud schemes being the major contributor to this heating. However, the different convective parameterisation schemes used by the models cause significantly different contributions to the total heating. These results have implications for studies on the influence of the WCB outflow in Rossby wave evolution and breaking. Key aspects are the net potential temperature change and the isentropic level of the outflow which together will influence the relative mass going into each WCB branch and the associated negative PV anomalies at the tropopause-level flow

Loss of muscleblind splicing factor shortens Caenorhabditis elegans lifespan by reducing the activity of p38 MAPK/PMK-1 and transcription factors ATF-7 and Nrf/SKN-1

Muscleblind-like splicing regulators (MBNLs) are RNA-binding factors that have an important role in developmental processes. Dysfunction of these factors is a key contributor of different neuromuscular degenerative disorders, including Myotonic Dystrophy type 1 (DM1). Since DM1 is a multisystemic disease characterized by symptoms resembling accelerated aging, we asked which cellular processes do MBNLs regulate that make them necessary for normal lifespan. By utilizing the model organism Caenorhabditis elegans, we found that loss of MBL-1 (the sole ortholog of mammalian MBNLs), which is known to be required for normal lifespan, shortens lifespan by decreasing the activity of p38 MAPK/PM K-1 as well as the function of transcription factors ATF-7 and SKN-1. Furthermore, we show that mitochondrial stress caused by the knockdown of mitochondrial electron transport chain components promotes the longevity of mbl-1 mutants in a partially PMK-1-dependent manner. Together, the data establish a mechanism of how DM1-associated loss of muscleblind affects lifespan. Furthermore, this study suggests that mitochondrial stress could alleviate symptoms caused by the dysfunction of muscleblind splicing factor, creating a potential approach to investigate for therapy.Peer reviewe

Vertebral body stenting: a new method for vertebral augmentation versus kyphoplasty

Vertebroplasty and kyphoplasty are well-established minimally invasive treatment options for compression fractures of osteoporotic vertebral bodies. Possible procedural disadvantages, however, include incomplete fracture reduction or a significant loss of reduction after balloon tamp deflation, prior to cement injection. A new procedure called “vertebral body stenting” (VBS) was tested in vitro and compared to kyphoplasty. VBS uses a specially designed catheter-mounted stent which can be implanted and expanded inside the vertebral body. As much as 24 fresh frozen human cadaveric vertebral bodies (T11-L5) were utilized. After creating typical compression fractures, the vertebral bodies were reduced by kyphoplasty (n = 12) or by VBS (n = 12) and then stabilized with PMMA bone cement. Each step of the procedure was performed under fluoroscopic control and analysed quantitatively. Finally, static and dynamic biomechanical tests were performed. A complete initial reduction of the fractured vertebral body height was achieved by both systems. There was a significant loss of reduction after balloon deflation in kyphoplasty compared to VBS, and a significant total height gain by VBS (mean ± SD in %, p < 0.05, demonstrated by: anterior height loss after deflation in relation to preoperative height [kyphoplasty: 11.7 ± 6.2; VBS: 3.7 ± 3.8], and total anterior height gain [kyphoplasty: 8.0 ± 9.4; VBS: 13.3 ± 7.6]). Biomechanical tests showed no significant stiffness and failure load differences between systems. VBS is an innovative technique which allows for the possibly complete reduction of vertebral compression fractures and helps maintain the restored height by means of a stent. The height loss after balloon deflation is significantly decreased by using VBS compared to kyphoplasty, thus offering a new promising option for vertebral augmentation

Total stimulation gonadotropin dose per oocyte retrieved and fresh embryo quality affect live birth rate after frozen-thawed embryo transfer

Koeputkihedelmöityshoidoissa (IVF) ja munasolujen mikroinjektiohoidoissa (ICSI) elävän lapsen syntymisen todennäköisyyteen vaikuttavia tekijöitä ovat muun muassa kerättyjen munasolujen lukumäärä, saatu gonadotropiinihormonin (FSH) annos sekä luotujen korkealaatuisten alkioiden määrä. Tämän tutkimuksen tarkoituksena oli selvittää, mitkä ominaisuudet alkion tuoresiirtovaiheessa vaikuttavat syntymän todennäköisyyteen jatkossa, jos naiselle tehdään myöhemmin hedelmöityshoidossa pakastetun alkion siirto. Tutkimusaineistona oli yhteinen Suomen lapsettomuusklinikoista kerätty tietokanta, joka sisälsi tiedot yhteensä 9465 pakastusalkionsiirto-tyyppisestä hedelmöityshoidosta vuosilta 2000-2017. Tuorealkionsiirtoja tutkittiin verraten näitä samojen naisten myöhempiin pakastealkionsiirtoihin. Luteaalisen kierron hormonaalista tukea sai naisista 42.9 %, hormonaalisesti indusoitu kuukautiskierto ja ovulaatio oli 40.7 % naisista, ja 16.1 % naisista kuukautiskierto oli täysin spontaani. FSH-annosta/munasolu käytettiin munasarjojen vasteen arviointiin. Tutkimuksessa selvisi, että vertailussa matalin FSH/munasolu -annossuhde <200 IU/munasolu sai aikaan suurimman todennäköisyyden elävän lapsen syntymälle pakastealkionsiirron jälkeen. Korkeampi annossuhde 300-399 IU/munasolu sen sijaan laski merkittävästi tätä todennäköisyyttä. Potilaan hormonaalisesti indusoitu ovulaatiokierto niin ikään assosioitui matalampaan syntymän todennäköisyyteen kuin kierto, jossa oli annettu hormonaalista tukea vain luteaalivaiheessa. Mikäli ainakin yksi korkealaatuinen alkio oli saatavilla hoitojen alussa, oli syntymän todennäköisyys suurempi läpi koko prosessin. Naisen yli 35 vuoden ikä laski syntymän todennäköisyyttä. Hedelmöityshoidoissa FSH/munasolu-annossuhde kuvastaa mahdollisesti munasarjojen toimintaa ja munasolujen laatua. Annossuhde tulisi pyrkiä pitämään mahdollisimman alhaisena, jotta vältytään korkeampiin annoksiin liittyvältä syntymän todennäköisyyden laskulta

Genome-wide DNA methylation and gene expression patterns reflect genetic ancestry and environmental differences across the Indonesian archipelago.

Indonesia is the world's fourth most populous country, host to striking levels of human diversity, regional patterns of admixture, and varying degrees of introgression from both Neanderthals and Denisovans. However, it has been largely excluded from the human genomics sequencing boom of the last decade. To serve as a benchmark dataset of molecular phenotypes across the region, we generated genome-wide CpG methylation and gene expression measurements in over 100 individuals from three locations that capture the major genomic and geographical axes of diversity across the Indonesian archipelago. Investigating between- and within-island differences, we find up to 10.55% of tested genes are differentially expressed between the islands of Sumba and New Guinea. Variation in gene expression is closely associated with DNA methylation, with expression levels of 9.80% of genes correlating with nearby promoter CpG methylation, and many of these genes being differentially expressed between islands. Genes identified in our differential expression and methylation analyses are enriched in pathways involved in immunity, highlighting Indonesia's tropical role as a source of infectious disease diversity and the strong selective pressures these diseases have exerted on humans. Finally, we identify robust within-island variation in DNA methylation and gene expression, likely driven by fine-scale environmental differences across sampling sites. Together, these results strongly suggest complex relationships between DNA methylation, transcription, archaic hominin introgression and immunity, all jointly shaped by the environment. This has implications for the application of genomic medicine, both in critically understudied Indonesia and globally, and will allow a better understanding of the interacting roles of genomic and environmental factors shaping molecular and complex phenotypes