In-vivo heterogeneous functional and residual strains in human aortic valve leaflets

Residual and physiological functional strains in soft tissues are known to play an important role in modulating organ stress distributions. Yet, no known comprehensive information on residual strains exist, or non-invasive techniques to quantify in-vivo deformations for the aortic valve (AV) leaflets. Herein we present a completely non-invasive approach for determining heterogeneous strains – both functional and residual – in semilunar valves and apply it to normal human AV leaflets. Transesophageal 3D echocardiographic (3DE) images of the AV were acquired from open-heart transplant patients, with each AV leaflet excised after heart explant and then imaged in a flattened configuration ex-vivo. Using an established spline parameterization of both 3DE segmentations and digitized ex-vivo images (Aggarwal et al., 2014), surface strains were calculated for deformation between the ex-vivo and three in-vivo configurations: fully open, just-coapted, and fully-loaded. Results indicated that leaflet area increased by an average of 20% from the ex-vivo to in-vivo open states, with a highly heterogeneous strain field. The increase in area from open to just-coapted state was the highest at an average of 25%, while that from just-coapted to fully-loaded remained almost unaltered. Going from the ex-vivo to in-vivo mid-systole configurations, the leaflet area near the basal attachment shrank slightly, whereas the free edge expanded by ~10%. This was accompanied by a 10° −20° shear along the circumferential-radial direction. Moreover, the principal stretches aligned approximately with the circumferential and radial directions for all cases, with the highest stretch being along the radial direction. Collectively, these results indicated that even though the AV did not support any measurable pressure gradient in the just-coapted state, the leaflets were significantly pre-strained with respect to the excised state. Furthermore, the collagen fibers of the leaflet were almost fully recruited in the just-coapted state, making the leaflet very stiff with marginal deformation under full pressure. Lastly, the deformation was always higher in the radial direction and lower along the circumferential one, the latter direction made stiffer by the preferential alignment of collagen fibers. These results provide significant insight into the distribution of residual strains and the in-vivo strains encountered during valve opening and closing in AV leaflets, and will form an important component of the tool that can evaluate valve׳s functional properties in a non-invasive manner

Dimerization of the transmembrane domain of amyloid precursor proteins and familial Alzheimer's disease mutants

<p>Abstract</p> <p>Background</p> <p>Amyloid precursor protein (APP) is enzymatically cleaved by γ-secretase to form two peptide products, either Aβ40 or the more neurotoxic Aβ42. The Aβ42/40 ratio is increased in many cases of familial Alzheimer's disease (FAD). The transmembrane domain (TM) of APP contains the known dimerization motif GXXXA. We have investigated the dimerization of both wild type and FAD mutant APP transmembrane domains.</p> <p>Results</p> <p>Using synthetic peptides derived from the APP-TM domain, we show that this segment is capable of forming stable transmembrane dimers. A model of a dimeric APP-TM domain reveals a putative dimerization interface, and interestingly, majority of FAD mutations in APP are localized to this interface region. We find that FAD-APP mutations destabilize the APP-TM dimer and increase the population of APP peptide monomers.</p> <p>Conclusion</p> <p>The dissociation constants are correlated to both the Aβ42/Aβ40 ratio and the mean age of disease onset in AD patients. We also show that these TM-peptides reduce Aβ production and Aβ42/Aβ40 ratios when added to HEK293 cells overexpressing the Swedish FAD mutation and γ-secretase components, potentially revealing a new class of γ-secretase inhibitors.</p

Multimodal image analysis and subvalvular dynamics in ischemic mitral regurgitation

Background: The exact geometric pathogenesis of leaflet tethering in ischemic mitral regurgitation (IMR) and the relative contribution of each component of the mitral valve complex (MVC) remain largely unknown. In this study, we sought to further elucidate mitral valve (MV) leaflet remodeling and papillary muscle dynamics in an ovine model of IMR with magnetic resonance imaging (MRI) and 3-dimensional echocardiography (3DE). Methods: Multimodal imaging combining 3DE and MRI was used to analyze the MVC at baseline, 30 minutes post–myocardial infarction (MI), and 12 weeks post-MI in ovine IMR models. Advanced 3D imaging software was used to trace the MVC from each modality, and the tracings were verified against resected specimens. Results: 3DE MV remodeling was regionally heterogenous and observed primarily in the anterior leaflet, with significant increases in surface area, especially in A2 and A3. The posterior leaflet was significantly shortened in P2 and P3. Mean posteromedial papillary muscle (PMPM) volume was decreased from 1.9 ± 0.2 cm3 at baseline to 0.9 ± 0.3 cm3 at 12 weeks post-MI (P <.05). At 12 weeks post-MI, the PMPM was predominately displaced horizontally and outward along the intercommissural axis with minor apical displacement. The subvalvular contribution to tethering is a combination of unilateral movement, outward displacement, and degeneration of the PMPM. These findings have led to a proposed new framework for characterizing PMPM dynamics in IMR. Conclusions: This study provides new insights into the complex interrelated and regionally heterogenous valvular and subvalvular mechanisms involved in the geometric pathogenesis of IMR tethering

Quantitative three-dimensional echocardiographic analysis of the bicuspid aortic valve and aortic root:A single modality approach

Background Patients with bicuspid aortic valves (BAV) are heterogeneous with regard to patterns of root remodeling and valvular dysfunction. Two-dimensional echocardiography is the standard surveillance modality for patients with aortic valve dysfunction. However, ancillary computed tomography or magnetic resonance imaging is often necessary to characterize associated patterns of aortic root pathology. Conversely, the pairing of three-dimensional (3D) echocardiography with novel quantitative modeling techniques allows for a single modality description of the entire root complex. We sought to determine 3D aortic valve and root geometry with this quantitative approach. Methods Transesophageal real-time 3D echocardiography was performed in five patients with tricuspid aortic valves (TAV) and in five patients with BAV. No patient had evidence of valvular dysfunction or aortic root pathology. A customized image analysis protocol was used to assess 3D aortic annular, valvular, and root geometry. Results Annular, sinus and sinotubular junction diameters and areas were similar in both groups. Coaptation length and area were higher in the TAV group (7.25 +/- 0.98 mm and 298 +/- 118 mm(2), respectively) compared to the BAV group (5.67 +/- 1.33 mm and 177 +/- 43 mm(2); P = .07 and P = .01). Cusp surface area to annular area, coaptation height, and the sub- and supravalvular tenting indices did not differ significantly between groups. Conclusions Single modality 3D echocardiography-based modeling allows for a quantitative description of the aortic valve and root geometry. This technique together with novel indices will improve our understanding of normal and pathologic geometry in the BAV population and may help to identify geometric predictors of adverse remodeling and guide tailored surgical therapy

Convective Fingering of an Autocatalytic Reaction Front

We report experimental observations of the convection-driven fingering instability of an iodate-arsenous acid chemical reaction front. The front propagated upward in a vertical slab; the thickness of the slab was varied to control the degree of instability. We observed the onset and subsequent nonlinear evolution of the fingers, which were made visible by a {\it p}H indicator. We measured the spacing of the fingers during their initial stages and compared this to the wavelength of the fastest growing linear mode predicted by the stability analysis of Huang {\it et. al.} [{\it Phys. Rev. E}, {\bf 48}, 4378 (1993), and unpublished]. We find agreement with the thickness dependence predicted by the theory.Comment: 11 pages, RevTex with 3 eps figures. To be published in Phys Rev E, [email protected], [email protected], [email protected]

The Otterbein Miscellany - June 1984

https://digitalcommons.otterbein.edu/miscellany/1007/thumbnail.jp

A Prospective Controlled Study of Magnetic Resonance Imaging of the Brain in Gay Men and Parenteral Drug Users with Human Immunodeficiency Virus Infection

To detect the earliest structural changes in the brain in human immunodeficiency virus (HIV) infection, 118 gay men and 115 parenteral drug users enrolled in a study of the natural history of HIV infection underwent magnetic resonance imaging evaluations. Routine T2-weighted and heavily T2-weighted scans for quantification of brain water were obtained, blinded to HIV serostatus. Atrophy and foci of increased signal did not correlate with any medical, immunologic, neurologic, or neuropsychologic parameters in the group as a whole, or in the gay men or parenteral drug user subgroups. Three subjects had progressive multifocal leukoencephalopathy and one had central nervous system lymphoma. In a subgroup in whom intracranial water percent was calculated, correlations were found with CD4 counts and CD4/CD8 ratios. We conclude that standard magnetic resonance imaging of the brain does not differentiate asymptomatic and mildly symptomatic HIV-positive individuals from HIV-negative individuals, regardless of risk group. However, intracranial water percent may distinguish HIV-positive from HIV-negative individuals because it correlates with raw CD4 counts and CD4/CD8 ratios

A Comparison of Cerebral Spect Abnormalities in Hiv-Positive Homosexual Men with and without Cognitive Impairment

Objective: To determine whether technetium Tc 99m exametazime (HMPAO) single-photon emission computed tomography (SPECT) can distinguish between human immunodeficiency virus (HIV)-positive homosexual men with normal neuropsychologic test results and HIV-positive homosexual men with abnormal neuropsychologic test results. Design: Neurologic, neuropsychologic, magnetic resonance imaging, and Tc 99m HMPAO SPECT examinations were performed on 10 HIV-positive homosexual men without cognitive impairment and five HIV-positive homosexual men with cognitive impairment. Patients: Human immunodeficiency virus—positive homosexual men from New York City were recruited for the study. Main Outcome Measures: Findings on SPECT scans were evaluated qualitatively for focal defects, heterogeneity of the cortical margin, white matter hypoperfusion, and decreased global cortical uptake. All SPECT focal defects were coregistered with magnetic resonance images; SPECT heterogeneity and global cortical uptake were also measured quantitatively. Results: Coregistration with magnetic resonance imaging revealed that 63% of the focal SPECT defects corresponded to brain gyri and 37% corresponded to sulci. There was no significant difference in the frequency of qualitative or quantitative SPECT abnormalities between HIV-positive homosexual men with and without cognitive impairment. However, after examining individual neuropsychologic test factors, impaired motor speed performance was associated with decreased quantitative global cerebral uptake. Conclusions: Qualitative SPECT abnormalities are not increased in frequency in HIV-positive homosexual men with global cognitive impairment compared with those in HIV-positive homosexual men without cognitive impairment. Impaired motor speed performance may be associated with decreased quantitative global cerebral uptake

Are Thiel-embalmed Cadavers Effective Tools in Educating Medical Students to Perform Knee Arthrocentesis?

INTRODUCTION: The purposes of this study are to determine whether Thiel-embalmed cadavers are an effective educational tool in teaching medical students to perform knee arthrocentesis, to compare the use of Thiel-embalmed cadavers to formalin-embalmed cadavers in arthrocentesis education, and to determine whether the use of Thiel-embalmed cadavers is potentially generalizable to the instruction of other orthopedic procedures. METHODS: Sixty-eight third-year medical students participated in the study. The participants first completed a pre-survey to assess their prior experience with arthrocentesis procedures and Thiel-embalmed cadavers. Participants then attended an instructional session where the knee arthrocentesis procedure was demonstrated on a Thiel-embalmed cadaver. Participants then individually performed the simulated knee arthrocentesis procedure twice: once on a Thiel-embalmed cadaver and once on a formalin-embalmed cadaver. Success of each attempt was determined through the visualization of aspirated joint fluid. Following the laboratory session, each participant completed a post-survey to determine whether the session improved their perceived confidence in performing knee arthrocentesis, if they preferred the use of Thiel-embalmed cadavers or formalin-embalmed cadavers as a teaching tool, and if they believed simulated practice using Thiel-embalmed cadavers would be effective for learning other orthopedic procedural skills. RESULTS: Sixty-eight students participated in the laboratory session and successfully completed both pre- and post-course surveys. 96% of participants reported that they felt confident performing knee arthrocentesis under physician supervision following their participation in the laboratory session (versus 15% of participants in the pre-survey). 96% of participants reported that the Thiel-embalmed cadavers provided a more realistic teaching model than formalin-embalmed cadavers for learning knee arthrocentesis. 100% of participants believed the incorporation of simulated practice using Thiel-embalmed cadavers is an effective method in teaching students to perform knee arthrocentesis. 100% of participants reported that they would participate in future sessions using Thiel-embalmed cadavers to learn and practice other orthopedic procedural techniques. DISCUSSION: This study used a moderate sample size of third-year medical students to provide data regarding the suitability of using Thiel cadavers in arthrocentesis education. Results indicate that Thiel cadavers are effective tools in teaching medical students to perform knee arthrocentesis, that students preferred the Thiel cadavers to the formalin cadavers, and that the use of Thiel cadavers is a safe, engaging, and high-quality teaching modality for demonstrating proper arthrocentesis procedural technique to medical students. Since this study looked specifically at teaching knee arthrocentesis to medical students, it is uncertain whether the benefits of Thiel cadavers are generalizable to the education of other orthopedic procedures and subject groups such as residents, fellows, and practicing physicians. Further studies should be performed to assess whether Thiel cadavers are beneficial in teaching other orthopaedic procedures and if these benefits extend to other subject groups