Population-specific material properties of the implantation site for transcatheter aortic valve replacement finite element simulations

Patient-specific computational models are an established tool to support device development and test under clinically relevant boundary conditions. Potentially, such models could be used to aid the clinical decision-making process for percutaneous valve selection; however, their adoption in clinical practice is still limited to individual cases. To be fully informative, they should include patient-specific data on both anatomy and mechanics of the implantation site. In this work, fourteen patient-specific computational models for transcatheter aortic valve replacement (TAVR) with balloon-expandable Sapien XT devices were retrospectively developed to tune the material parameters of the implantation site mechanical model for the average TAVR population.Pre-procedural computed tomography (CT) images were post-processed to create the 3D patient-specific anatomy of the implantation site. Balloon valvuloplasty and device deployment were simulated with finite element (FE) analysis. Valve leaflets and aortic root were modelled as linear elastic materials, while calcification as elastoplastic. Material properties were initially selected from literature; then, a statistical analysis was designed to investigate the effect of each implantation site material parameter on the implanted stent diameter and thus identify the combination of material parameters for TAVR patients.These numerical models were validated against clinical data. The comparison between stent diameters measured from post-procedural fluoroscopy images and final computational results showed a mean difference of 2.5 ± 3.9%. Moreover, the numerical model detected the presence of paravalvular leakage (PVL) in 79% of cases, as assessed by post-TAVR echocardiographic examination.The final aim was to increase accuracy and reliability of such computational tools for prospective clinical applications.     

Structural modeling reveals microstructure-strength relationship for human ascending thoracic aorta

High lethality of aortic dissection necessitates accurate predictive metrics for dissection risk assessment. The not infrequent incidence of dissection at aortic diameters <5.5 cm, the current threshold guideline for surgical intervention (Nishimura et al., 2014), indicates an unmet need for improved evidence-based risk stratification metrics. Meeting this need requires a fundamental understanding of the structural mechanisms responsible for dissection evolution within the vessel wall. We present a structural model of the repeating lamellar structure of the aortic media comprised of elastic lamellae and collagen fiber networks, the primary load-bearing components of the vessel wall. This model was used to assess the role of these structural features in determining in-plane tissue strength, which governs dissection initiation from an intimal tear. Ascending aortic tissue specimens from three clinically-relevant patient populations were considered: non-aneurysmal aorta from patients with morphologically normal tricuspid aortic valve (CTRL), aneurysmal aorta from patients with tricuspid aortic valve (TAV), and aneurysmal aorta from patients with bicuspid aortic valve (BAV). Multiphoton imaging derived collagen fiber organization for each patient cohort was explicitly incorporated in our model. Model parameters were calibrated using experimentally-measured uniaxial tensile strength data in the circumferential direction for each cohort, while the model was validated by contrasting simulated tissue strength against experimentally-measured strength in the longitudinal direction. Orientation distribution, controlling the fraction of loaded collagen fibers at a given stretch, was identified as a key feature governing anisotropic tissue strength for all patient cohorts.     

Therapy refractory hypertension in adults: aortic coarctation has to be ruled out

In patients with unexplained hypertension, especially in combination with a cardiac murmur, the presence of an aortic coarctation should always be ruled out given the high morbidity and mortality. However, particularly patients with an isolated coarctation often remain asymptomatic for years and the defect may be unnoticed even until the fifth or sixth decade of life. In the present article, we describe two patients with late detected coarctation to illustrate the clinical consequences, diagnostic clues for earlier detection and current therapeutic options to achieve optimal treatment. The key sign of an aortic coarctation, a difference in arterial blood pressure measured between the upper and lower extremities, should always be examined, followed by echocardiography. We conclude that even in case of a late detected severe coarctation, surgical or percutaneous repair has proven to be feasible and substantially effective, improving quality of life and lowering the risk of further hypertension-associated problems.     

Chroococcopsis epiphytica n. sp., eine neue Cyanophycee aus dem Gebiet des Neusiedler Sees

The morphology and life history ofChroococcopsis epiphytica nova spec. is described, a German and Latin diagnosis is added. Cultivated plants display some differences in comparison with plants in their natural habitat: calcification occurs only in the natural medium, endosporangia are developed only by cultivated plants. At the basis, where single cells and thalli are attached, a special sort of jelly is produced; it is discernible only by elective staining with methylene blue. The systematic position of the new species is discussed.

     

Variability,function and phylogenetic significance of periostracal microprojections in unionoid bivalves (Mollusca)

Microprojections of unionoid shells are virtually unstudied but could be important characters for resolving questions on the phylogeny and ecology of these bivalves. By investigating 26 unionoid and three species of their closest living relatives, the Trigonioida, using scanning electron microscopy, we identified three types of periostracal microprojections. (1) Microridges were present only in one species from each of the two unionoid families Mycetopodidae (Anodontites trapesialis) and Iridinidae (Chambardia bourguignati) and may represent a synapomorphy for the mycetopodid‐iridinid clade. In A. trapesialis, microridges were additionally equipped with (2)ensp;flag‐like projections (microfringes), possibly a synapomorphic character for the Mycetopodidae. Examination of partially bleached specimens indicated that both microridges and microfringes are predominantly or purely organic. In contrast, previously undescribed (3) spicule‐like spikes represent calcifications within the periostracum. These were found in 20 of the 29 species and four of the six unionoid families. Spikes were particularly large and abundant in umbonal (juvenile) shell regions and species characteristic of fast‐flowing habitats. These structures may thus serve in protecting the periostracum and shell underneath, and/or stabilizing life position by increasing shell friction. Microfringes and microridges, on the other hand, possibly aid in the orientation of the mussel within the sediment.     

Location and functional characterization of the right atrioventricular pacemaker ring in the adult avian heart

Previous histological studies showed that in addition to a sinus node, an atrioventricular (AV) node, an AV bundle, left and right bundle branches, birds also possess a right AV‐Purkinje ring that is located in the atrial sheet of the right muscular AV‐valve along all its base length. The functionality of the AV‐Purkinje ring is unknown. In this work, we studied the topology of pacemaker myocytes in the atrial side of the isolated chicken spontaneously contracting right muscular AV‐valve using the method of microelectrode mapping of action potentials. We show that AV‐cells having the ability to show pacemaking reside in the right muscular AV‐valve. Pacemaker action potentials were exclusively recorded close to the base of the valve along its whole length from dorsal to the ventral attachment to the interventricular septum. These action potentials have much slower rate of depolarization, lower amplitude, and higher diastolic depolarization than action potentials of Purkinje (conducting) cells. We conclude the right AV‐valve has a ring bundle of pacemaker cells (but not Purkinje cells) in the adult chicken heart. J. Morphol. 277:363–369, 2016. © 2015 Wiley Periodicals, Inc.     

Linking genotype to phenotype in a changing ocean: inferring the genomic architecture of a blue mussel stress response with genome‐wide association

A key component to understanding the evolutionary response to a changing climate is linking underlying genetic variation to phenotypic variation in stress response. Here, we use a genome‐wide association approach (GWAS) to understand the genetic architecture of calcification rates under simulated climate stress. We take advantage of the genomic gradient across the blue mussel hybrid zone (Mytilus edulis and Mytilus trossulus) in the Gulf of Maine (GOM) to link genetic variation with variance in calcification rates in response to simulated climate change. Falling calcium carbonate saturation states are predicted to negatively impact many marine organisms that build calcium carbonate shells – like blue mussels. We sampled wild mussels and measured net calcification phenotypes after exposing mussels to a ‘climate change’ common garden, where we raised temperature by 3°C, decreased pH by 0.2 units and limited food supply by filtering out planktonic particles >5 μm, compared to ambient GOM conditions in the summer. This climate change exposure greatly increased phenotypic variation in net calcification rates compared to ambient conditions. We then used regression models to link the phenotypic variation with over 170 000 single nucleotide polymorphism loci (SNPs) generated by genotype by sequencing to identify genomic locations associated with calcification phenotype, and estimate heritability and architecture of the trait. We identified at least one of potentially 2–10 genomic regions responsible for 30% of the phenotypic variation in calcification rates that are potential targets of natural selection by climate change. Our simulations suggest a power of 13.7% with our study's average effective sample size of 118 individuals and rare alleles, but a power of >90% when effective sample size is 900.     

Generality in multispecies responses to ocean acidification revealed through multiple hypothesis testing

Decades of research have demonstrated that many calcifying species are negatively affected by ocean acidification, a major anthropogenic threat in marine ecosystems. However, even closely related species may exhibit different responses to ocean acidification and less is known about the drivers that shape such variation in different species. Here, we examine the drivers of physiological performance under ocean acidification in a group of five species of turf‐forming coralline algae. Specifically, quantitating the relative weight of evidence for each of ten hypotheses, we show that variation in coralline calcification and photosynthesis was best explained by allometric traits. Across ocean acidification conditions, larger individuals (measured as noncalcified mass) had higher net calcification and photosynthesis rates. Importantly, our approach was able to not only identify the aspect of size that drove the performance of coralline algae, but also determined that responses to ocean acidification were not dependent on species identity, evolutionary relatedness, habitat, shape, or structural composition. In fact, we found that failure to test multiple, alternative hypotheses would underestimate the generality of physiological performances, leading to the conclusion that each species had different baseline performance under ocean acidification. Testing among alternative hypotheses is an essential step toward determining the generalizability of experiments across taxa and identifying common drivers of species responses to global change.     

MicroRNAs as possible biomarkers for screening of aortic aneurysms: a systematic review and validation study

Context: There is an urgent need to identify non-invasive biomarkers for the early detection of aortic aneurysms, preceding a fatal event. The potential role for MicroRNAs (miRNAs) as diagnostic markers for aortic aneurysms was investigated through the present systematic review.

Objective: To perform a comprehensive review on published studies examining the association of miRNAs with aortic aneurysms and further validate these results with plasma samples collected from thoracic aortic aneurysm (TAA) patients.

Methods: The literature search was performed via numerous databases and articles were only included if they fulfilled the predefined eligibility criteria. The miRNAs reported three times or more with expression consistency were validated using plasma samples from TAA patients collected before and following surgery.

Results: Twenty-four articles were selected from the literature search and 11 miRNAs were chosen for validation using our samples. The miRNAs which were further validated were found to follow the trend in the regulation pattern as with the majority of the published data. MiRNA hsa-miR-193a-5p was found to be significantly down-regulated in the plasma samples collected before the aneurysmal removal when compared with postsurgical serum samples.

Conclusions: Numerous miRNAs have been associated with aortic aneurysms, and specifically hsa-miR-193a-5p and hsa-miR-30b-5p; therefore they warrant further investigation as potential biomarkers.

Registration: The protocol of the review was registered in Prospero Databases (ID: CRD42016039953)