Three dimensional three component whole heart cardiovascular magnetic resonance velocity mapping: comparison of flow measurements from 3D and 2D acquisitions

<p>Abstract</p> <p>Background</p> <p>Two-dimensional, unidirectionally encoded, cardiovascular magnetic resonance (CMR) velocity mapping is an established technique for the quantification of blood flow in large vessels. However, it requires an operator to correctly align the planes of acquisition. If all three directional components of velocity are measured for each voxel of a 3D volume through the phases of the cardiac cycle, blood flow through any chosen plane can potentially be calculated retrospectively. The initial acquisition is then more time consuming but relatively operator independent.</p> <p>Aims</p> <p>To compare the curves and volumes of flow derived from conventional 2D and comprehensive 3D flow acquisitions in a steady state flow model, and in vivo through planes transecting the ascending aorta and pulmonary trunk in 10 healthy volunteers.</p> <p>Methods</p> <p>Using a 1.5 T Phillips Intera CMR system, 3D acquisitions used an anisotropic 3D segmented k-space phase contrast gradient echo sequence with a short EPI readout, with prospective ECG and diaphragm navigator gating. The 2D acquisitions used segmented k-space phase contrast with prospective ECG and diaphragm navigator gating. Quantitative flow analyses were performed retrospectively with dedicated software for both the in vivo and in vitro acquisitions.</p> <p>Results</p> <p>Analysis of in vitro data found the 3D technique to have overestimated the continuous flow rate by approximately 5% across the entire applied flow range. In vivo, the 2D and the 3D techniques yielded similar volumetric flow curves and measurements. Aortic flow: (mean ± SD), 2D = 89.5 ± 13.5 ml & 3D = 92.7 ± 17.5 ml. Pulmonary flow: 2D = 98.8 ± 18.4 ml & 3D = 94.9 ± 19.0 ml). Each in vivo 3D acquisition took about 8 minutes or more.</p> <p>Conclusion</p> <p>Flow measurements derived from the 3D and 2D acquisitions were comparable. Although time consuming, comprehensive 3D velocity acquisition could be relatively operator independent, and could potentially yield information on flow through several retrospectively chosen planes, for example in patients with congenital or valvular heart disease.</p

Finite element analysis of the effect of cementing concepts on implant stability and cement fatigue failure

Background and purpose Two contradictory cementing techniques (using an undersized stem versus a canal-filling stem) can both lead to excellent survival rates, a phenomenon known as the “French paradox”. Furthermore, previous studies have indicated that the type of bone supporting the cement mantle may affect implant survival. To further evaluate the mechanical consequences of variations in cementing technique, we studied the effect of implant size and type of bone supporting the cement mantle on the mechanical performance of cemented total hip arthroplasty, using finite element analysis

Heterozygous Yeast Deletion Collection Screens Reveal Essential Targets of Hsp90

Hsp90 is an essential eukaryotic chaperone with a role in folding specific “client” proteins such as kinases and hormone receptors. Previously performed homozygous diploid yeast deletion collection screens uncovered broad requirements for Hsp90 in cellular transport and cell cycle progression. These screens also revealed that the requisite cellular functions of Hsp90 change with growth temperature. We present here for the first time the results of heterozygous deletion collection screens conducted at the hypothermic stress temperature of 15°C. Extensive bioinformatic analyses were performed on the resulting data in combination with data from homozygous and heterozygous screens previously conducted at normal (30°C) and hyperthermic stress (37°C) growth temperatures. Our resulting meta-analysis uncovered extensive connections between Hsp90 and (1) general transcription, (2) ribosome biogenesis and (3) GTP binding proteins. Predictions from bioinformatic analyses were tested experimentally, supporting a role for Hsp90 in ribosome stability. Importantly, the integrated analysis of the 15°C heterozygous deletion pool screen with previously conducted 30°C and 37°C screens allows for essential genetic targets of Hsp90 to emerge. Altogether, these novel contributions enable a more complete picture of essential Hsp90 functions

Macrophage signaling in HIV-1 infection

The human immunodeficiency virus-1 (HIV-1) is a member of the lentivirus genus. The virus does not rely exclusively on the host cell machinery, but also on viral proteins that act as molecular switches during the viral life cycle which play significant functions in viral pathogenesis, notably by modulating cell signaling. The role of HIV-1 proteins (Nef, Tat, Vpr, and gp120) in modulating macrophage signaling has been recently unveiled. Accessory, regulatory, and structural HIV-1 proteins interact with signaling pathways in infected macrophages. In addition, exogenous Nef, Tat, Vpr, and gp120 proteins have been detected in the serum of HIV-1 infected patients. Possibly, these proteins are released by infected/apoptotic cells. Exogenous accessory regulatory HIV-1 proteins are able to enter macrophages and modulate cellular machineries including those that affect viral transcription. Furthermore HIV-1 proteins, e.g., gp120, may exert their effects by interacting with cell surface membrane receptors, especially chemokine co-receptors. By activating the signaling pathways such as NF-kappaB, MAP kinase (MAPK) and JAK/STAT, HIV-1 proteins promote viral replication by stimulating transcription from the long terminal repeat (LTR) in infected macrophages; they are also involved in macrophage-mediated bystander T cell apoptosis. The role of HIV-1 proteins in the modulation of macrophage signaling will be discussed in regard to the formation of viral reservoirs and macrophage-mediated T cell apoptosis during HIV-1 infection

Inflammatory response of disc cells against Propionibacterium acnes depends on the presence of lumbar Modic changes

PurposeIntervertebral disc with Propionibacterium acnes (P. acnes) is suggested to be an etiology of Modic type I changes in the adjacent bone marrow. However it is unknown if disc cells can respond to P. acnes and if bone marrow cells respond to bacterial and disc metabolites draining from infected discs.MethodsHuman disc cells (n&nbsp;=&nbsp;10) were co-cultured with 10- and 100-fold excess of P. acnes over disc cells for 3&nbsp;h and 24&nbsp;h. Lipopolysaccharide was used as positive control. Expression of IL1, IL6, IL8, and CCL2 by disc cells was quantified by quantitative PCR. Lipase activity was measured in culture supernatants (n&nbsp;=&nbsp;6). Human vertebral bone marrow mononuclear cells (BMNCs) (n&nbsp;=&nbsp;2) were cultured in conditioned media from disc cell/P. acnes co-cultures and expression of IL1, IL6, IL8, and CCL2 was measured after 24&nbsp;h.ResultsAll disc cells responded to lipopolysaccharide but only 6/10 responded to P. acnes with increased cytokine expression. Cytokine increase was time- but not P. acnes concentration-dependent. Disc cell responsiveness was associated with the presence of lumbar Modic changes in the donor. Lipase activity was increased independent of disc cell responsiveness. BMNCs responded with inflammatory activity only when cultured in supernatants from responsive disc cell lines.ConclusionDisc cell responsiveness to P. acnes associates with the presence of lumbar Modic changes. Furthermore, bone marrow cells had an inflammatory response to the cocktail of disc cytokines and P. acnes metabolites. These data indicate that low virulent P. acnes infection of the disc is a potential exacerbating factor to Modic changes