Acoustic monitoring (RFM) of total hip arthroplasty results of a cadaver study

<p>Abstract</p> <p>Introduction</p> <p>At present there are no reliable non-traumatic and non-invasive methods to analyse the healing process and loosening status after total hip replacement. Therefore early as well as late loosening of prosthesis and interface component problems are difficult to be found or diagnosed at any time.</p> <p>Methods</p> <p>In a cadaver study the potential application of Resonance Frequency Monitoring (RFM) will be evaluated as a non-invasive and non-traumatic method to monitor loosening and interface problems in hip replacement. In a 65 year old female cadaver different stability scenarios for a total hip replacement (shaft, head/modular head and cup, ESKA, Luebeck, Germany) are simulated in cemented and cement less prosthesis and then analysed with RFM. The types of stability vary from secure/press-fit to interface-shaft disruption.</p> <p>Results</p> <p>The RFM shows in cemented as well as cement less prosthesis significant intra-individual differences in the spectral measurements with a high dynamic (20 dB difference corresponding to the factor 100 (10000%)), regarding the simulated status of stability in the prosthesis system.</p> <p>Conclusion</p> <p>The results of the study demonstrate RFM as a highly sensitive non-invasive and non-traumatic method to support the application of RFM as a hip prosthesis monitoring procedure. The data obtained shows the possibility to use RFM for osteointegration surveillance and early detection of interface problems, but will require further evaluation in clinical and experimental studies.</p

Structural basis for delta cell paracrine regulation in pancreatic islets

International audienceLittle is known about the role of islet delta cells in regulating blood glucose homeostasis in vivo. Delta cells are important paracrine regulators of beta cell and alpha cell secretory activity, however the structural basis underlying this regulation has yet to be determined. Most delta cells are elongated and have a well-defined cell soma and a filopodia-like structure. Using in vivo optogenetics and high-speed Ca2+ imaging, we show that these filopodia are dynamic structures that contain a secretory machinery, enabling the delta cell to reach a large number of beta cells within the islet. This provides for efficient regulation of beta cell activity and is modulated by endogenous IGF-1/VEGF-A signaling. In pre-diabetes, delta cells undergo morphological changes that may be a compensation to maintain paracrine regulation of the beta cell. Our data provides an integrated picture of how delta cells can modulate beta cell activity under physiological conditions

CD69 is a TGF-β/1α,25-dihydroxyvitamin D3 target gene in monocytes

CD69 is a transmembrane lectin that can be expressed on most hematopoietic cells. In monocytes, it has been functionally linked to the 5-lipoxygenase pathway in which the leukotrienes, a class of highly potent inflammatory mediators, are produced. However, regarding CD69 gene expression and its regulatory mechanisms in monocytes, only scarce data are available. Here, we report that CD69 mRNA expression, analogous to that of 5-lipoxygenase, is induced by the physiologic stimuli transforming growth factor-β (TGF-β) and 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3) in monocytic cells. Comparison with T- and B-cell lines showed that the effect was specific for monocytes. CD69 expression levels were increased in a concentration-dependent manner, and kinetic analysis revealed a rapid onset of mRNA expression, indicating that CD69 is a primary TGF-β/1α,25(OH)2D3 target gene. PCR analysis of different regions of the CD69 mRNA revealed that de novo transcription was initiated and proximal and distal parts were induced concomitantly. In common with 5-lipoxygenase, no activation of 0.7 kb or ~2.3 kb promoter fragments by TGF-β and 1α,25(OH)2D3 could be observed in transient reporter assays for CD69. Analysis of mRNA stability using a transcription inhibitor and a 3′UTR reporter construct showed that TGF-β and 1α,25(OH)2D3 do not influence CD69 mRNA stability. Functional knockdown of Smad3 clearly demonstrated that upregulation of CD69 mRNA, in contrast to 5-LO, depends on Smad3. Comparative studies with different inhibitors for mitogen activated protein kinases (MAPKs) revealed that MAPK signalling is involved in CD69 gene regulation, whereas 5-lipoxygenase gene expression was only partly affected. Mechanistically, we found evidence that CD69 gene upregulation depends on TAK1-mediated p38 activation. In summary, our data indicate that CD69 gene expression, conforming with 5-lipoxygenase, is regulated monocyte-specifically by the physiologic stimuli TGF-β and 1α,25(OH)2D3 on mRNA level, although different mechanisms account for the upregulation of each gene

The 10th Biennial Hatter Cardiovascular Institute workshop: cellular protection—evaluating new directions in the setting of myocardial infarction, ischaemic stroke, and cardio-oncology

Due to its poor capacity for regeneration, the heart is particularly sensitive to the loss of contractile cardiomyocytes. The onslaught of damage caused by ischaemia and reperfusion, occurring during an acute myocardial infarction and the subsequent reperfusion therapy, can wipe out upwards of a billion cardiomyocytes. A similar program of cell death can cause the irreversible loss of neurons in ischaemic stroke. Similar pathways of lethal cell injury can contribute to other pathologies such as left ventricular dysfunction and heart failure caused by cancer therapy. Consequently, strategies designed to protect the heart from lethal cell injury have the potential to be applicable across all three pathologies. The investigators meeting at the 10th Hatter Cardiovascular Institute workshop examined the parallels between ST-segment elevation myocardial infarction (STEMI), ischaemic stroke, and other pathologies that cause the loss of cardiomyocytes including cancer therapeutic cardiotoxicity. They examined the prospects for protection by remote ischaemic conditioning (RIC) in each scenario, and evaluated impasses and novel opportunities for cellular protection, with the future landscape for RIC in the clinical setting to be determined by the outcome of the large ERIC-PPCI/CONDI2 study. It was agreed that the way forward must include measures to improve experimental methodologies, such that they better reflect the clinical scenario and to judiciously select combinations of therapies targeting specific pathways of cellular death and injury

Wheat-barley hybridization – the last forty years

Abstract Several useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat 9 barley hybridization over the last forty years, including the development of wheat 9 barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat 9 barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat 9 barley hybrids is presented, with special regard to the detection of wheat– barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (b-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed

HtrA1 Mediated Intracellular Effects on Tubulin Using a Polarized RPE Disease Model

Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss. The protein HtrA1 is enriched in retinal pigment epithelial (RPE) cells isolated from AMD patients and in drusen deposits. However, it is poorly understood how increased levels of HtrA1 affect the physiological function of the RPE at the intracellular level. Here, we developed hfRPE (human fetal retinal pigment epithelial) cell culture model where cells fully differentiated into a polarized functional monolayer. In this model, we fine-tuned the cellular levels of HtrA1 by targeted overexpression. Our data show that HtrA1 enzymatic activity leads to intracellular degradation of tubulin with a corresponding reduction in the number of microtubules, and consequently to an altered mechanical cell phenotype. HtrA1 overexpression further leads to impaired apical processes and decreased phagocytosis, an essential function for photoreceptor survival. These cellular alterations correlate with the AMD phenotype and thus highlight HtrA1 as an intracellular target for therapeutic interventions towards AMD treatment

The Effect of Axial Length on the Thickness of Intraretinal Layers of the Macula.

PURPOSE: The aim of this study was to evaluate the effect of axial length (AL) on the thickness of intraretinal layers in the macula using optical coherence tomography (OCT) image analysis. METHODS: Fifty three randomly selected eyes of 53 healthy subjects were recruited for this study. The median age of the participants was 29 years (range: 6 to 67 years). AL was measured for each eye using a Lenstar LS 900 device. OCT imaging of the macula was also performed by Stratus OCT. OCTRIMA software was used to process the raw OCT scans and to determine the weighted mean thickness of 6 intraretinal layers and the total retina. Partial correlation test was performed to assess the correlation between the AL and the thickness values. RESULTS: Total retinal thickness showed moderate negative correlation with AL (r = -0.378, p = 0.0007), while no correlation was observed between the thickness of the retinal nerve fiber layer (RNFL), ganglion cell layer (GCC), retinal pigment epithelium (RPE) and AL. Moderate negative correlation was observed also between the thickness of the ganglion cell layer and inner plexiform layer complex (GCL+IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL) and AL which were more pronounced in the peripheral ring (r = -0.402, p = 0.004; r = -0.429, p = 0.002; r = -0.360, p = 0.01; r = -0.448, p = 0.001). CONCLUSIONS: Our results have shown that the thickness of the nuclear layers and the total retina is correlated with AL. The reason underlying this could be the lateral stretching capability of these layers; however, further research is warranted to prove this theory. Our results suggest that the effect of AL on retinal layers should be taken into account in future studies