Quantitative analysis of hypertrophic myocardium using diffusion tensor magnetic resonance imaging

Systemic hypertension is a causative factor in left ventricular hypertrophy (LVH). This study is motivated by the potential to reverse or manage the dysfunction associated with structural remodeling of the myocardium in this pathology. Using diffusion tensor magnetic resonance imaging, we present an analysis of myocardial fiber and laminar sheet orientation in ex vivo hypertrophic (6 SHR) and normal (5 WKY) rat hearts using the covariance of the diffusion tensor. First, an atlas of normal cardiac microstructure was formed using the WKY b0 images. Then, the SHR and WKY b0 hearts were registered to the atlas. The acquired deformation fields were applied to the SHR and WKY heart tensor fields followed by the preservation of principal direction (PPD) reorientation strategy. A mean tensor field was then formed from the registered WKY tensor images. Calculating the covariance of the registered tensor images about this mean for each heart, the hypertrophic myocardium exhibited significantly increased myocardial fiber derangement (p ¼ 0.017) with a mean dispersion of 38.7 deg, and an increased dispersion of the laminar sheet normal (p = 0.030) of 54.8 deg compared with 34.8 deg and 51.8 deg, respectively, in the normal hearts. Results demonstrate significantly altered myocardial fiber and laminar sheet structure in rats with hypertensive LVH

A level set approach to segmenting a deforming myocardium from dynamically acquired SPECT projection data

Dynamic cardiac single photon emission computed tomography (SPECT) offers an effective way for observing fundamental physiological functions of organs and could aid in the early diagnosis of cardiovascular disease, in particular, for those patients with minimal disease. This would improve the chances of recovery by initiating appropriate therapy and an altered life style. To make dynamic cardiac SPECT viable with present clinical scanners methods need to be developed that reconstruct time activity curves from dynamically moving organs representing the change of tracer concentration as a function of time from projection data acquired from slowly rotating gamma cameras. This type of data analysis faces the challenge of modeling both rigid and non-rigid body deformation as well as modeling of a time varying tracer concentration. In the work presented here, we develop methods for segmenting the beating heart using an approach based upon level sets, which can deal naturally with topological changes. A variational formulation of the level set method was implemented. This allowed the inclusion of a priori information and was computationally efficient. The algorithm was first evaluated with simulated dynamic cardiac image data. The MCAT phantom was used to generate data containing 32 time frames over one cardiac cycle. Each frame had a matrix size of 64×64×32 voxels with a resolution of 6.25 mm. Starting with an initial estimate of the boundary, the algorithm then converged to an accurate segmentation of the deforming heart. The initial estimate was not important and we could segment simultaneously both interior and exterior boundaries. This algorithm forms the foundation for the segmentation of the boundary of the deforming myocardium directly from projection data

Diffusion tensor magnetic resonance imaging-derived myocardial fiber disarray in hypertensive left ventricular hypertrophy: visualization, quantification and the effect on mechanical function

Left ventricular hypertrophy induced by systemic hypertension is generally regarded a morphological precursor of unfortunate cardiovascular events. Myocardial fiber disarray has been long recognized as a prevalent hallmark of this pathology. In this chapter, ex vivo diffusion tensor magnetic resonance imaging is employed to delineate the regional loss of myocardial organization that is present in the excised heart of a spontaneously hypertensive rat, as opposed to a control. Fiber tracking results are provided that illustrate in great detail the alterations in the integrity of cardiac muscle microstructure due to the disease. A quantitative analysis is also performed. Another contribution of this chapter is the model-based assessment of the role of the myofiber disarray in modulating the mechanical properties of the myocardium. The results of this study improve our understanding of the structural remodeling mechanisms that are associated with hypetensive left ventricular hypertrophy and their role

Cytolytic replication of echoviruses in colon cancer cell lines

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer is one of the most common cancers in the world, killing nearly 50% of patients afflicted. Though progress is being made within surgery and other complementary treatments, there is still need for new and more effective treatments. Oncolytic virotherapy, meaning that a cancer is cured by viral infection, is a promising field for finding new and improved treatments. We have investigated the oncolytic potential of several low-pathogenic echoviruses with rare clinical occurrence. Echoviruses are members of the enterovirus genus within the family <it>Picornaviridae</it>.</p> <p>Methods</p> <p>Six colon cancer cell lines (CaCo-2, HT29, LoVo, SW480, SW620 and T84) were infected by the human enterovirus B species echovirus 12, 15, 17, 26 and 29, and cytopathic effects as well as viral replication efficacy were investigated. Infectivity was also tested in spheroids grown from HT29 cells.</p> <p>Results</p> <p>Echovirus 12, 17, 26 and 29 replicated efficiently in almost all cell lines and were considered highly cytolytic. The infectivity of these four viruses was further evaluated in artificial tumors (spheroids), where it was found that echovirus 12, 17 and 26 easily infected the spheroids.</p> <p>Conclusions</p> <p>We have found that echovirus 12, 17 and 26 have potential as oncolytic agents against colon cancer, by comparing the cytolytic capacity of five low-pathogenic echoviruses in six colon cancer cell lines and in artificial tumors.</p

A rapid and efficient method for studies of virus interaction at the host cell surface using enteroviruses and real-time PCR

<p>Abstract</p> <p>Background</p> <p>Measuring virus attachment to host cells is of great importance when trying to identify novel receptors. The presence of a usable receptor is a major determinant of viral host range and cell tropism. Furthermore, identification of appropriate receptors is central for the understanding of viral pathogenesis and gives possibilities to develop antiviral drugs. Attachment is presently measured using radiolabeled and subsequently gradient purified viruses. Traditional methods are expensive and time-consuming and not all viruses are stable during a purification procedure; hence there is room for improvement. Real-time PCR (RT-PCR) has become the standard method to detect and quantify virus infections, including enteroviruses, in clinical samples. For instance, primers directed to the highly conserved 5' untranslated region (5'UTR) of the enterovirus genome enable detection of a wide spectrum of enteroviruses. Here, we evaluate the capacity of the RT-PCR technology to study enterovirus host cell interactions at the cell surface and compare this novel implementation with an established assay using radiolabeled viruses.</p> <p>Results</p> <p>Both purified and crude viral extracts of CVB5 generated comparable results in attachment studies when analyzed with RT-PCR. In addition, receptor binding studies regarding viruses with coxsackie- and adenovirus receptor (CAR) and/or decay accelerating factor (DAF) affinity, further demonstrated the possibility to use RT-PCR to measure virus attachment to host cells. Furthermore, the RT-PCR technology and crude viral extracts was used to study attachment with low multiplicity of infection (0.05 × 10^-4TCID₅₀/cell) and low cell numbers (250), which implies the range of potential implementations of the presented technique.</p> <p>Conclusion</p> <p>We have implemented the well-established RT-PCR technique to measure viral attachment to host cells with high accuracy and reproducibility, at low cost and with less effort than traditional methods. Furthermore, replacing traditional methods with RT-PCR offers the opportunity to use crude virus containing extracts to investigate attachment, which could be considered as a step towards viral attachment studies in a more natural state.</p

Pregnancy and childbirth in English prisons : institutional ignominy and the pains of imprisonment

© 2020 The Authors. Sociology of Health & Illness published by John Wiley & Sons Ltd on behalf of Foundation for SHIL.With a prison population of approximately 9000 women in England, it is estimated that approximately 600 pregnancies and 100 births occur annually. Despite an extensive literature on the sociology of reproduction, pregnancy and childbirth among women prisoners is under‐researched. This article reports an ethnographic study in three English prisons undertaken in 2015‐2016, including interviews with 22 prisoners, six women released from prison and 10 staff members. Pregnant prisoners experience numerous additional difficulties in prison including the ambiguous status of a pregnant prisoner, physical aspects of pregnancy and the degradation of the handcuffed or chained prisoner during visits to the more public setting of hospital. This article draws on Erving Goffman's concepts of closed institutions, dramaturgy and mortification of self, Crewe et al.'s work on the gendered pains of imprisonment and Crawley's notion of ‘institutional thoughtlessness’, and proposes a new concept of institutional ignominy to understand the embodied situation of the pregnant prisoner.Peer reviewe

Highly sensitive and specific protein detection via combined capillary isoelectric focusing and proximity ligation

Detection and quantification of proteins and their post-translational modifications are crucial to decipher functions of complex protein networks in cell biology and medicine. Capillary isoelectric focusing together with antibody-based detection can resolve and identify proteins and their isoforms with modest sample input. However, insufficient sensitivity prevents detection of proteins present at low concentrations and antibody cross-reactivity results in unspecific detection that cannot be distinguished from bona fide protein isoforms. By using DNA-conjugated antibodies enhanced signals can be obtained via rolling circle amplification (RCA). Both sensitivity and specificity can be greatly improved in assays dependent on target recognition by pairs of antibodies using in situ proximity ligation assays (PLA). Here we applied these DNA-assisted RCA techniques in capillary isoelectric focusing to resolve endogenous signaling transducers and isoforms along vascular endothelial growth factor (VEGF) signaling pathways at concentrations too low to be detected in standard assays. We also demonstrate background rejection and enhanced specificity when protein detection depended on binding by pairs of antibodies using in situ PLA, compared to assays where each antibody preparation was used on its own.</p