bluuebunny/crossref_metadata_2025 huggingface dataset:
Efeitos da Fisioterapia Aquática em um indivíduo com Síndrome Pós-Pólio
Authors: Albarello Priscilla Maia , Spalvieri Daiane Fiorina , Spalvieri Daiane Fiorina
Published: July 2012

Introdução. A Síndrome Pós-Pólio (SPP) é uma desordem do sistema nervoso, que se manifesta em indivíduos que tiveram poliomielite, após 15 anos ou mais, com um novo quadro sintomatológico: fraque­za muscular progressiva, fadiga e dor, resultando numa diminuição da capacidade funcional e/ou no surgimento de novas incapacidades. As vantagens do ambiente aquático na reabilitação da doença neurológica têm sido observadas por muitos séculos, os exercícios na água são faci­litados pelo alívio do peso corporal que proporciona a movimentação voluntária com menor fadiga. Objetivo. O Objetivo deste trabalho foi verificar a eficácia do tratamento da síndrome pós-pólio em um indivíduo portador, através da terapia aquática. Método. Realizado protocolo de exercícios para tronco, membros inferiores, membros superiores, para relaxamento, fortalecimento, alongamento e mobi­lização articular de ombros. Resultados e Discussão. Foi constatado através deste estudo por meio de escala de fadiga (FSS), escala visual analógica para dor (EVA), e SF36 para qualidade de vida, a redução da dor, a melhora importante da qualidade de vida, e a redução signi­ficativa da fadiga para este indivíduo. Conclusão. A terapia aquática atingiu os objetivos esperados para esta pesquisa, sendo útil na confec­ção de trabalhos futuros.
Ossification with Extensive Calcification of Uterine Leiomyoma in a Postmenopausal Woman
Authors: Suranagi Vijayalaxmi , Bannur Hema B , Davanagere Reshma , Dafale Sujata
Published: July 2012

Ossification in uterine leiomyomas is extremely rare. Very few cases of ossification and such extensive calcification in leiomyoma have been reported earlier in the literature. Most of the leiomyomas in uterus are known to regress after menopause. Ossification as a secondary change is generally present in the long standing leiomyomas with other degenerative changes like hyalinization and calcification. Most of these changes result from inadequate blood supply. We report a case of an incidental large leiomyoma showing extensive calcification and ossification, which is very rare, occurring in a postmenopausal woman, who died due to organophosphorus poisoning, found at autopsy. This could be an incidental finding probably because of lack of any relevant symptoms and patient's ignorance about the presence of the lesion when alive. This case is reported in view of its rarity. The pathogenesis is also discussed.

How to cite this article

Suranagi VV, Bannur HB, Davanagere R, Dafale S. Ossification with Extensive Calcification of Uterine Leiomyoma in a Postmenopausal Woman. J South Asian Feder Obst Gynae 2012;4(1):54-55.
Total Uterine Necrosis: A Complication of B-Lynch Suture
Authors: Jain Sheela , Somalwar Savita A , Joshi Sulbha A , Kawthalkar Anjali S , Mahore Sadhana
Published: July 2012

Uterine atony is the most common cause of postpartum hemorrhage (PPH) which leads to maternal mortality and morbidity. Herewith reporting a case of 35-year-old woman who underwent cesarean section for transverse lie with hand prolapse. She had atonic PPH for which uterine artery ligation was done along with B-lynch suture. She had subinvolution of uterus secondary to multiple abscesses in uterine wall. She underwent subtotal hystrectomy. Hispathology showed uterine necrosis.

How to cite this article

Somalwar SA, Joshi SA, Bhalerao AV, Kawthalkar AS, Jain S, Mahore S. Total Uterine Necrosis: A Complication of B-Lynch Suture. J South Asian Feder Obst Gynae 2012;4(1):61-63.
Anemia in Pregnancy—Consequences and Challenges: A Review of Literature
Authors: Noronha Judith Angelitta , Khasawneh Esra Al , Seshan Vidya , Ramasubramaniam Shanthi , Raman Savithri
Published: July 2012

Anemia during pregnancy is a global public health challenge facing the world today, especially in the developing countries. Anemia in pregnancy is an important contributor to maternal mortality/morbidity as well as to the low birth weight which in turn might contribute to increased percentage for infant mortality. Many epidemiological studies in the past have reported the problem in high magnitude. This review was conducted to identify the persistence of the problem in the South Asian countries during the last 5 years irrespective of iron supplementation as a measure to tackle this problem.

Materials and methods

A review of all published literature related to prevalence of anemia for a period of 5 years (2007- 2011) in South Asian countries was carried out. The online databases MEDLINE, CINAHL, Science Direct, Scopus, and Cochrane were used to identify relevant studies. Data from studies meeting inclusion/exclusion criteria were abstracted into a standardized form.

Results

Eleven studies with a total of 1,93,131 pregnant women were included in the review. The maximum and minimum reported prevalence rates of anemia during pregnancy were 80 and 18% respectively. The maximum and minimum prevalence of severe anemia affecting pregnant women is 20 and 2.7%. The risk factors that are involved are young age, educational status and socioeconomic status, poor birth spacing and lack of compliance to iron and folic acid supplementation.

Conclusion

Anemia is the most frequent maternal complication of pregnancy. All the 11 studies reviewed focused on assessing the prevalence of anemia during various stages of pregnancy. It shows anemia is prevalent from mild to severe degree with substantial variations across trimesters. The outcomes of these suggest prevalence of anemia is due to associated factors and lack of deficiency of vitamin B12, low BMI, infection with ascariasis, deficient dietary consumption of foods fortified with iron, low socioeconomic conditions and high parity.

How to cite this article

Noronha JA, Al Khasawneh E, Seshan V, Ramasubramaniam S, Raman S. Anemia in Pregnancy— Consequences and Challenges: A Review of Literature. J South Asian Feder Obst Gynae 2012;4(1):64-70.
The Effect of Tourism on Crime in Italy: A Dynamic Panel Approach
Authors: Biagi Bianca , Brandano Maria Giovanna , Detotto Claudio
Published: July 2012

The purpose of this paper is to demonstrate that, for the case of Italy, ceteris paribus, tourist areas tend to have a greater amount of crime than non-tourist ones in the short and long run. Following the literature of the economics of crime à la Becker (Crime and Punishment: An Economic Approach, 1968) and Enrlich (Participation in Illegitimate Activities: A Theoretical and Empirical Investigation, 1973) and using a System GMM approach for the time span 1985–2003, the authors empirically test whether total crime in Italy is affected by the presence of tourists. Findings confirm the initial intuition of a positive relationship between tourism and crime in destinations. When using the level rather than the rate of total crime and controlling for the equivalent tourists (i.e. the number of tourists per day in a given destination) the effect of the tourist variable is confirmed. Overall results indicate however that the resident population has a greater effect on crime than the tourist population. Therefore, the main explanation for the impact of tourism on crime seems to be agglomeration effects.
Halogenation processes of secondary organic aerosol and implications on halogen release mechanisms
Authors: Ofner J. , Balzer N. , Buxmann J. , Grothe H. , Schmitt-Kopplin Ph. , Platt U. , Zetzsch C.
Published: July 2012

Abstract. Reactive halogen species (RHS), such as X·, X2 and HOX containing X = chlorine and/or bromine, are released by various sources like photo-activated sea-salt aerosol or from salt pans, and salt lakes. Despite many studies of RHS reactions, the potential of RHS reacting with secondary organic aerosol (SOA) and organic aerosol derived from biomass-burning (BBOA) has been neglected. Such reactions can constitute sources of gaseous organohalogen compounds or halogenated organic matter in the tropospheric boundary layer and can influence physicochemical properties of atmospheric aerosols. Model SOA from α-pinene, catechol, and guaiacol was used to study heterogeneous interactions with RHS. Particles were exposed to molecular chlorine and bromine in an aerosol smog-chamber in the presence of UV/VIS irradiation and to RHS, released from simulated natural halogen sources like salt pans. Subsequently, the aerosol was characterized in detail using a variety of physicochemical and spectroscopic methods. Fundamental features were correlated with heterogeneous halogenation, which results in new functional groups (FTIR spectroscopy), changes UV/VIS absorption, chemical composition (ultrahigh resolution mass spectroscopy (ICR-FT/MS)), or aerosol size distribution. However, the halogen release mechanisms were also found to be affected by the presence of organic aerosol. Those interaction processes, changing chemical and physical properties of the aerosol are likely to influence e.g. the ability of the aerosol to act as cloud condensation nuclei, its potential to adsorb other gases with low-volatility, or its contribution to radiative forcing and ultimately the Earth's radiation balance.
How have both cultivation and warming influenced annual global isoprene and monoterpene emissions since the preindustrial era?
Authors: Tanaka K. , Kim H.-J. , Saito K. , Takahashi H. G. , Watanabe M. , Yokohata T. , Kimoto M. , Takata K. , Yasunari T.
Published: July 2012

Abstract. To examine the influence of both crop cultivation and surface air temperature (SAT) on annual global isoprene and monoterpene emissions, which can lead to the formation of secondary organic aerosols (SOAs), we simulated the annual emissions of volatile organic compounds (VOCs) during the period 1854–2000. The model estimates were based on historical climate data such as SATs, and downward solar radiation (DSR) reproduced with an atmospheric-ocean circulation model, as well as a time series of the global distribution of cropland (to test the hypothesis that conversion of forests into croplands lowers emissions). The simulations demonstrated that global SAT, DSR, the combination of SAT and DSR, and the expansion of cropland all affected emissions. The effect of cropland expansion (i.e., forest conversion) on annual emissions during this period was larger for isoprene (~7% reduction on a global scale) than for monoterpenes (~2% reduction), mainly because of the reduction in broadleaf evergreen forests (BEFs) in Southeast Asia, which have the highest and most constant emissions of isoprene and where both temperature and radiation are high all year round. The reduction in the Amazon region and in parts of Africa, which are other primary sources of annual global isoprene emissions, but where the conversion of BEF to cropland has been much smaller than in Southeast Asia, was less remarkable, probably because the broadleaf deciduous forests and C4 grasslands in these areas have lower and seasonal emissions; hence, their conversion has less effect. On the other hand, the difference in the emission factors (ε) between cropland and the other vegetation types was much lower for monoterpenes than for isoprene, although the ε for cropland was generally the lowest for both emissions. Thus, the expansion of cropland also contributed to the reduction in monoterpene emissions to some degree, but had less effect. A ~5% increase in emissions due to rising SAT was more than offset by the decrease in isoprene emissions and a concurrent ~2% reduction caused by a decrease in DSR. Overall, annual global isoprene emissions in 2000 were lower than in 1854, whereas annual global monoterpene emissions were higher.
Occurrence and distribution of ladderane oxidation products in different oceanic regimes
Authors: Rush D. , Hopmans E. C. , Wakeham S. G. , Schouten S. , Sinninghe Damsté J. S.
Published: July 2012

Abstract. Ladderane fatty acids are commonly used as biomarkers for bacteria involved in anaerobic ammonium oxidation (anammox). These lipids have been experimentally shown to undergo aerobic microbial degradation to form short chain ladderane fatty acids. However, nothing is known of the production or the distribution of these oxic biodegradation products in the natural environment. In this study, we analysed marine water column particulate matter and sediment from three different oceanic regimes for the presence of ladderane oxidation products (C14 ladderane fatty acids) and of original ladderane fatty acids (C18 and C20 ladderane fatty acids). We found that ladderane oxidation products, i.e. C14 ladderane fatty acids, are already produced within the water column of the Arabian Sea oxygen minimum zone (OMZ) and thus only low amounts of oxygen (< 3 μM) are needed for the β-oxidation of original ladderane fatty acids to proceed. However, no short chain ladderane fatty acids were detected in the Cariaco Basin water column, where oxygen concentrations were below detection limit, suggesting that the β-oxidation pathway is inhibited by the absence of molecular oxygen, or that the microbes performing the degradation are not proliferating under these conditions. Comparison of distributions of ladderane fatty acids indicates that short chain ladderane fatty acids are mostly produced in the water column and at the sediment surface, before being preserved deeper in the sediments. Short chain ladderane fatty acids were abundant in Arabian Sea and Peru Margin sediments (ODP Leg 201), often in higher concentrations than the original ladderane fatty acids. In a sediment core taken from within the Arabian Sea OMZ, short chain ladderanes made up more than 90% of the total ladderanes at depths greater than 5 cm below sea floor. We also found short chain ladderanes in higher concentrations in hydrolysed sediment residues compared to those freely occurring in lipid extracts, suggesting that they had become bound to the sediment matrix. Furthermore, these matrix-bound short chain ladderanes were found at greater sediment depths than short chain ladderanes in the lipid extract, suggesting that binding to the sediment matrix aids the preservation of these lipids. Though sedimentary degradation of short chain ladderane fatty acids did occur, it appeared to be at a slower rate than that of the original ladderane fatty acids, and short chain ladderane fatty acids were found in sediments from the Late Pleistocene (~ 100 kyr). Together these results suggest that the oxic degradation products of ladderane fatty acids may be suitable biomarkers for past anammox activity in OMZs.
Assessing variable speed pump efficiency in water distribution systems
Authors: Marchi A. , Simpson A. R. , Ertugrul N.
Published: July 2012

Abstract. Energy savings and greenhouse gas emission reductions are increasingly becoming important design targets in many industrial systems where fossil fuel based electrical energy is heavily utilised. In water distribution systems (WDSs) a significant portion of operational cost is related to pumping. Recent studies have considered variable speed pumps (VSPs) which aim to vary the operating point of the pump to match demand to pumping rate. Depending on the system characteristics, this approach can lead to considerable savings in operational costs. In particular, cost reductions can take advantage of the demand variability and can decrease energy consumption significantly. One of the issues in using variable speed pumping systems, however, is the total efficiency of the electric motor/pump arrangement under a given operating condition. This paper aims to provide a comprehensive discussion about the components of WDS that incorporate variable speed pumps (including electric motors, variable frequency drives and the pumps themselves) to provide an insight of ways of increasing the system efficiency and hence to reduce energy consumption. In addition, specific attention is given to selection of motor types, sizing, duty cycle of pump (ratio of on-time and time period), losses due to installation and motor faults. All these factors affect the efficiency of motor drive/pump system.
Predictability of Western Himalayan River flow: melt seasonal inflow into Bhakra Reservoir in Northern India
Authors: Pal I. , Lall U. , Robertson A. W. , Cane M. A. , Bansal R.
Published: July 2012

Abstract. Snowmelt dominated streamflow of the Western Himalayan Rivers is an important water resource during the dry pre-monsoon spring months to meet the irrigation and hydropower needs in Northern India. Here we study the seasonal prediction of melt-dominated total inflow into the Bhakra Dam in Northern India based on statistical relationships with meteorological variables during the preceding winter. Total inflow into the Bhakra dam includes the Satluj River flow together with a flow diversion from its tributary, the Beas River. Both are tributaries of the Indus River that originate from the Western Himalayas, which is an under-studied region. Average measured winter snow volume at the upper elevation stations and corresponding lower elevation rainfall and temperature of the Satluj River basin were considered as empirical predictors. Akaike Information Criteria (AIC) and Bayesian Information Criteria (BIC) were used to select the best subset of inputs from all the possible combinations of predictors for a multiple linear regression framework. To test for potential issues arising due to multi-collinearity of the predictor variables, cross-validated prediction skills of best subset were also compared with the prediction skills of Principal Component Regression (PCR) and Partial Least Squares Regression (PLSR) techniques, which yielded broadly similar results. As a whole, the forecasts of the melt season at the end of winter and as the melt season commences were shown to have potential skill for guiding the development of stochastic optimization models to manage the trade-off between irrigation and hydropower releases versus flood control during the annual fill cycle of the Bhakra reservoir, a major energy and irrigation source in the region.
Print Without Borders:
Authors: Allen Jung Nathan
Published: July 2012

The University of Delaware recently hosted an interdisciplinary “Mediamorphosis” symposium on modernist print cultures. Organized by Ann Ardis and Patrick Collier, the conference assembled a diverse group of researchers from several fields, whose breadth of scholarship proved essential to encompassing the sprawling, overlapping, and transnational nature of modernist periodical networks. The symposium continued work begun by its 2007 predecessor “Transatlantic Print Culture, 1880–1940: Emerging Media, Emerging Modernisms,” while also offering a welcome forum for new scholarship. Speakers were organized into nine panels over two days, and the weekend concluded with an open-forum discussion held over dinner and drinks. The conference was accompanied by a print exhibit Mediamorphosis: Periodical across the Pond curated by Mark Samuels Lasner and Timothy D. Murray, which featured rare periodicals drawn from the University of Delaware's special collections. The organizers scheduled no concurrent panels, and as a result participants developed a shared context for discussing current and future concerns in periodical research. These discussions pursued the roles of digital humanities in print culture research; relationships between mass culture and marginal publics; the politics of bridging global and local concerns in periodical circulation, layout, and content; and finally, questions of attribution and ownership. This review offers an overview of the conference and some key papers, situating the scholarship on display within broader discussions about institutional responses to more expansive approaches to print culture and emerging research methodologies.
Editing Modernism, Editing Theology:
Authors: Domestico Anthony
Published: July 2012

In this essay, I trace the presence of Protestant neo-Orthodox theology within the pages of the Criterion. In particular, I show that Karl Barth, whose radical Protestantism would appear to be at odds with Eliot's orthodox Anglo-Catholicism, was in fact one of the Criterion's major theological interlocutors from 1934 onward. Recovering Barth's presence helps us to see two facts: first, that the Criterion was not as close-minded in theological matters as we tend to imagine; and second, that interwar theology, and in particular Barth's dialectical theology, bears interesting resemblances to the literature of the same period.
Bio-inspired Anisotropic Nanofibrillar Matrices for Heart Valve Engineering
Authors: Sohier Jerome , Carubelli Ivan , Latif Najma , Sarathchandra Padmini , Chester Adrian H. , Yacoub Magdi
Published: July 2012

Our strategy for heart valve tissue engineering is the use of autologous cells to populate appropriate template matrices. In this context, an important goal is to devise a suitable biomimetic scaffold that supports proper cell growth and cell-matrix interactions by reproducing the specific anisotropic fibrillar structure of valves extracellular matrix (ECM). A novel type of highly porous anisotropic nanobrillar matrices was developed and evaluated with regards to structure, mechanical properties and ability to support human adipose derived stem cell (hADSC) colonization, growth and ECM production in vitro. Nanofibrillar structures were obtained by jet-spraying poly (ε-caprolactone) dissolved in chloroform on a variably rotating drum. Morphological evaluations of the structures were performed using scanning electron microscopy while porosity was calculated from polymer density, weight and volume. Elastic modulus of dry scaffolds (10x6x1 mm, n=5) was measured with a planar biaxial test bench with displacement rate of 0.05 mm/s. Human adipose derived stem cells (500,000) were top and rotary seeded on nanofibrillar discs (diameter 1 cm and thickness 0.8 mm) and cultured in 10 ml of complete medium under rotation (10 rpm) for 18 days. Histology (DAPI staining), DNA quantification and immunohistochemistry were used to characterize the resulting cellularized structures.
The speed of drum rotation was adjusted up to 3000 rpm to produce highly aligned fibres (600 nm of average diameter) from the sprayed polymer. In conjunction with fibres anisotropy, the scaffolds Young's modulus was simultaneously increased (from 0.3 to 0.7 Mpa) and decreased (from 0.3 to 0.01 Mpa) longitudinally and orthogonally to fibre alignment, respectively. In addition, fibre alignment further increased scaffolds porosity from 97 % (isotropic) to 99%. Anisotropic matrices allowed a more extensive cellular invasion than isotropic scaffolds, possibly linked to their higher porosity and therefore open structure. hADSC proliferated significantly (up to 6-fold DNA increase), bridged the entire scaffolds thicknesses after 10 days and produced their own ECM as evidenced by collagen I production. This study highlights the potential of a newly developed highly porous anisotropic nanofibrillar matrices as substrate for tissue engineering, and in particular for heart valve engineering.
PCL Scaffolds and Reduced In-Vitro Cell Expansion to Improve Engineered Valvular Tissue Formation
Authors: Brugmans Marieke C.P. , Driessen-Mol Anita , Cox Martijn A.J. , Rubbens Mirjam.P. , Baaijens Frank P.T.
Published: July 2012

Different types of synthetic scaffolds are used for tissue engineering of heart valves. Tissue-engineered heart valves (TEHV), based on a rapid degrading polyglycolic acid (PGA) scaffold coated with poly-4-hydroxybutyrate (P4HB) and seeded with vascular derived cells, have shown promising in-vivo results. However, a major drawback of these TEHV is compaction and retraction of the leaflets causing regurgitation. It is hypothesized that this is a result of traction forces exerted by the cells, combined with an imbalance of the formed tissue and loss of mechanical integrity of the scaffold due to degradation. The aim of this study is to evaluate alternative approaches to overcome the compaction and retraction of TEHV without compromising on tissue composition and properties. The alternative approaches that are studied here are 1) the use of the slow degrading poly-ε-caprolactone (PCL) scaffold for prolonged mechanical integrity and 2) the use of lower passage vascular cells for enhanced tissue formation. Compaction, tissue formation, cell phenotype and mechanical properties of tissues based on passage 3, 5 and 7 vascular cells in PCL and PGA-P4HB scaffolds are compared. TEHV aim to be designed for humans, but since the ovine model is used to show proof of principle both human and ovine cells were used. Passage 3, 5 and 7 (p3, p5 and p7) human and ovine vascular-derived cells were seeded onto both PGA-P4HB and PCL scaffold strips (n=6 per passage and scaffold material), using fibrin as a cell carrier. After 4 weeks of culture under constrained static conditions, one strip was used for histology. The remaining strips were used for mechanical testing and biochemical assays as indicators for tissue strength and tissue formation, respectively. After 4 weeks, the tissues based on PGA-P4HB showed 50-60% compaction, while PCL-based tissues showed compaction of 0-10%. Cell passage number and species did not influence compaction. Tissue formation was comparable between passage numbers and scaffold materials in ovine while human p5 showed decreased tissue formation in both scaffold materials. Collagen content was increased with decreasing passage numbers in both species and scaffold materials. No differences in cell phenotype between the scaffold materials or cell passage numbers were observed. The Young’s modulus and the ultimate tensile strength of tissues of both species were higher in the lower passage groups of both scaffold groups. This study shows that PCL scaffolds may serve as alternative scaffold material for tissue engineering heart valves with minimal compaction and without compromising on tissue composition and properties. Cells from lower passages showed to improve tissue formation. Reducing cell expansion time will result in faster generation of TEHV, providing a more rapid treatment to patients.
New Biomaterials in Heart Valve Tissue Engineering
Authors: Talacua Hanna , Vink Aryan , Bosman Anton W. , Janssen Henk M. , Söntjens Serge H.M. , van Herwerden Lex A. , Kluin Jolanda
Published: July 2012

In situ tissue engineering may lead to a clinically and economically attractive new generation of heart valve replacement therapies, overcoming the limitations of currently used prostheses. Development of novel scaffolds is required for the proposed in situ tissue engineering. These scaffolds must be able to carry a full mechanical load immediately after implantation, and should subsequently provide all biological cues for the recruitment and attachment of specific circulating cells, and should also induce the growth of new tissue. The properties of the scaffold materials should be optimized with respect to mechanical properties and biodegradability characteristics. Synthetic biomaterials are tunable, which enables the creation of tailor made scaffolds suitable for in situ tissue engineering of heart valves. Two different approaches towards scaffold materials have been investigated, based on a biodegradable polyester (PCL or PLLCL), and either a quadruple hydrogen-bonding ureidopyrimidinone (UPy) unit or a bis-urea (BU) moiety. Both were investigated in vivo regarding biocompatibility and degradation kinetics. Thirty rats received the UPy and BU polyester based, disk-shaped implants subcutaneously. To investigate the effects of the implants over time, samples were explanted on day 2, 5, 10, 21 and 84. Disks with surrounding tissue were fixed in 10% neutral buffered formalin. After fixation, explants were dehydrated in graded alcohols and longitudinal sections were embedded in paraffin and stained. From each explant the foreign body response was quantified per high power field. Both the UPy and the BU-based materials proved biocompatible. In the acute phase all investigated biomaterials showed an infiltration of neutrophil granulocytes and mononuclear cells. In the chronic phase encapsulation by fibroblasts took place in all cases. Degradation rates were investigated by gel permeation chromatography (GPC) after 21 and 84 days. Little degradation was observed for the PCL-based polymers over the course of the experiment. The PLLCL-based polymers with a BU moiety, however, showed little at 21 days, but marked degradation at 84 days. Which of the explored materials is best suitable for in situ tissue engineering of heart valves will depend on further experiments, investigating how much time is needed for cell recruitment, adhesion, differentiation and tissue growth.

This research forms part of the Project P1.01 iValve of the research program of the BioMedical Materials institute, co-funded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation. The financial contribution of the Nederlandse Hartstichting is gratefully acknowledged.
Sufficient Tissue Engineered Heart Valves: A Question of Cell Source?
Authors: Weber Miriam , Frese Julia , Hatam Nima , Sachweh Joerg , Schmitz-Rode Thomas , Jockenhoevel Stefanl , Mela Petra
Published: July 2012

A promising approach to solve the problems of currently used heart valve prostheses, e.g. degeneration, need for anticoagulation and risk of endocarditis, is the tissue engineering of heart valves. By using patient derived cells and fibrin as a scaffold for these valves we aim at completely autologous heart valves which have the potential to grow and hence are especially interesting for valve replacement in paediatric surgery. However, a major obstacle on the way to clinical application of tissue engineered heart valves (TEHV) is the cell-mediated tissue contraction which leads to the shrinkage of the valve’s leaflets and thus to its insufficiency. Several groups tested TEHV in the pulmonary position in the sheep model and reported mild to moderate regurgitation already at a short postimplantation time. Our goal was to analyse the influence of the cell source on the sufficiency of TEHV. Different cell sources, among which ovine carotid artery (OCA) and umbilical artery (OUA), were compared on their contractility and contraction of fibrin gels in which the cells were embedded. Cell phenotype was characterized by immunostaining of α-smooth muscle actin (α-SMA) and myosin light-chain kinase (MLCK) as markers for cell contractile activity. For the gel contraction assay, fibrin gels with a cell concentration of 5 × 10^6/ml were moulded in a 24-well plate (n ≥ 3) and their retraction was evaluated over 15 days by measuring the gels' area in relation to their original area. Hydroxyproline content, cell proliferation and burst strength were also determined.
Ovine carotid artery cells exhibited a highly contractile myofibroblast phenotype (high α-SMA and MLCK expression), while OUA cells were mostly non-contractile fibroblasts with only few cells expressing α-SMA and MLCK. After 15 days, OCA embedded gels were contracted to 30.6 ± 2.0% of the original size while OUA gels maintained a size of 83.2 ± 3.7% of the initial area.
To directly correlate cell contractility and valve sufficiency we moulded fibrin based heart valves using OUA and OCA cells. All valves were conditioned statically for 14 days in the closed-leaflet configuration and successively dynamically in the open-leaflet configuration in bioreactors for 30 days. While the leaflets of TEHV with OCA cells contracted and led to insufficient valves at the end of the conditioning protocol, we were able to produce completely sufficient heart valves after in vitro conditioning using non-contractile OUA cells. In an on-going animal study OUA embedded TEHV, after being seeded with endothelial cells, are implanted in the pulmonary artery in lambs to analyse their growth potential and their hemodynamic performance in vivo. Transesophageal echocardiography showed both in colour Doppler and in cw Doppler mode that after fourteen weeks a first implanted valve was still completely sufficient and showed no sign of cell-mediated tissue contraction.
Subcutaneous Testing of E-spun PCL Patches Suitable for in Situ Heart Valve Tissue Engineering
Authors: Talacua Hanna , Vink Aryan , Cox Martijn A.J. , Simonet Marc , Baaijens Frank P.T. , van Herwerden Lex A. , Kluin Jolanda
Published: July 2012

In situ tissue engineered heart valves yields a new generation of cardiovascular substitutes. The body is used as a bioreactor where it relies on the natural regenerative potential of the body. The shift from the classical way of tissue engineering to in-situ tissue engineering emphasizes the role of the scaffold. The scaffold should be able to capture and preserve cells for tissue formation and it has to maintain valve functionality while tissue is developing. The use of synthetic biomaterials is very attractive. Poly(ε-caprolactone) (PCL) is an important polymer due to its mechanical properties and miscibility with a large range of other polymers. Electrospinning attracted great interest as a production method of biomaterials for in situ tissue engineering. The electrospinning process of PCL offers a nice technique for thin fiber formation to eventually create three dimensional scaffolds with the characteristic three layers, typical for heart valves. The fibers produced with electrospinning provide a similar physical structure as the extra cellular matrix. The space between fibers needs to be large enough for cells to adhere and migrate into the scaffold. Sufficient cellular in growth is needed for tissue formation. In this study cellular in growth was measured in subcutaneously implanted electrospun PCL patches. Furthermore tissue formation and degradation of the polymer is investigated. Thirty healthy male F344 Rats are used. The implants with surrounding tissue were explanted after 2, 5, 10, 21 or 84 days and embedded in paraffin. The explanted tissues were examined using immunohistochemistry (HE,MPO, ED1, α-SMA, and PSR). The electrospun fibers had a diameter of 10 μm. SEM pictures showed controlled void spaces. In the electrospun PCL samples we found a very high cellular infiltration rate after 84 days, mean of 396.819 cells per high power field. First infiltration of mainly neutrophil granulocytes was seen, followed by macrophages. Cells infiltrate throughout the whole sample. After 84 days fibroblast were seen, which were able to produce collagen. Furthermore after 84 days, macrophage giant cells and neo-vessel formation was observed. PCL was degraded in the cytoplasm of the macrophages. Electrospun PCL scaffolds with a fiber diameter of 10 μm, are suitable for cellular in growth and tissue formation. This research forms part of the Project P1.01 iValve of the research program of the BioMedical Materials institute, co-funded by the Dutch Ministry of Economic Affairs, Agriculture and Innovation. The financial contribution of the Nederlandse Hartstichting is gratefully acknowledged.
Mechanical Properties of Bioprostheses Leaflets Compared to Human Aortic Valve
Authors: Kalejs Martins , Stradins Peteris , Lacis Lacis , Ozolanta Iveta , Kasyanov Vladimir
Published: July 2012

Heart valve bioprostheses suffer from gradual tissue deterioration, which has a causal link with valve tissue mechanical properties. Limited data on mechanical properties of commercially available bioprostheses comparing them to native human aortic valves (AV) is available. Our objective was to determine the mechanical properties of several contemporary bioprostheses and compare them with native human and porcine aortic valves. Leaflets from 5 unchanged human AV, collected from cadaveric hearts and 5 porcine AV, and from 3 of each kind of bioprostheses - Medtronic Hancock II, Sorin Soprano and Medtronic Freestyle were analysed using uniaxial tensile tests in radial and circumferential directions. Data are presented as means ± standard deviation. In both tested directions there's a shift to the stress axis of stress-strain curve for HancockII prostheses and even more for Soprano prostheses when compared to native human valves. In circumferential direction modulus of elasticity (E) of native human AV is 15.34±3.84MPa, porcine AV - 9.7±1.3MPa, Freestyle - 9.0±3.0MPa, HancockII - 22.5±2.2MPa and Soprano - 29.5±6.0MPa. In radial direction E of native human AV is 1.98±0.15MPa, porcine AV - 1.0±0.2MPa, Freestyle - 0.8±0.3MPa, HancockII - 2.5±0.2MPa and Soprano - 15.8±5.4MPa.
Xeno-aortic bioprostheses have a non-linear and anisotropic response to stress in uniaxial tensile tests similar to native AV leaflets. HancockII has gained mechanical strength but lost tissue elasticity compared to native valve tissue. Leaflets of Soprano prostheses are even more rigid and lack pronounced material anisotropy. These differences in mechanical properties may accelerate deterioration of bioprostheses, causing altered stress distribution within valve leaflets. These data provide important information about what mechanical properties future valve substitutes should conform to.
Polymer Nanofiber Materials Matching the Mechanic Properties of Native Aortic Valve
Authors: Kalejs Martins , Stradins Peteris , Priedite Viktorija , Lacis Romans , Ozolanta Iveta , Kasyanov Vladimir
Published: July 2012

Porous electrospun nanofiber materials are very promising as matrices for heart valve tissue engineering. Not only biocompatibility is important for this material but also the mechanical features – it has to be strong enough to withhold the pressure after implantation as well as deformable enough for better distribution of shear stress along its surface. Deformability is also crucial for stimulation of fibre production by fibroblasts on these matrices. Altogether 8 differing density variants of electrospun nanofiber materials from gelatine, polyurethane (PUR), polylactic acid (PLA) and polycaprolactone (PCL) were analysed using uniaxial tensile tests. Data were compared to mechanical properties of porcine aortic valve (AV) leaflets in radial and circumferential directions. Data are presented as means ± standard deviation. In circumferential direction modulus of elasticity (E) of native porcine AV is 9.7±1.3MPa and - 1.0±0.2MPa in radial. Ultimate stress and strain is 44.8±5.9% and 2.3±0.6 MPa in circumferential and 95.6±31.4% and 0.5±0.2MPa in radial direction for native leaflets. Closest of the materials to match the mechanical properties of porcine AV in circumferential direction was PUR with density 6.2 g/sqm showing E of 3.9±0.5 MPa, ultimate stress and strain - 5.3±1.68MPa and 141.8±43.9MPa respectively. Closest to match radial direction was gelatine with density 5.7 g/sqm showing E of 0.64±0.14 MPa, ultimate stress and strain - 0.38±0.05MPa and 82.53±10.20MPa respectively.
Native AV leaflets have a non-linear and anisotropic response to stress in uniaxial tensile tests. Hence to model as precisely as possible their mechanical properties we suggest to use a combined material made in a sandwich fashion with layers of gelatine on the outside and PUR in the middle with their fibbers predominantly orientated in perpendicular directions. The other tested materials PLA and PCL either lacked strength to mimic leaflets in circumferential direction or deformability required for the radial direction.
Prevalence of Severe Aortic Stenosis With Low Flow in Patients With and Without Left Ventricular Dysfunction. A Consecutive Echocardiographic Population
Authors: Mauro Toniolo , Andrea Rossi , Mariantonietta Cicoira , Corinna Bergamini , Corrado Vassanelli
Published: July 2012

Patients with aortic stenosis (AS) may have a severely reduced aortic valve area (AVA) and a paradoxically low mean gradient (MG). Although this condition is well known in presence of left ventricular (LV) dysfunction, it has recently been observed that it can be associated with normal ejection fraction (EF) as well. Since the prevalence of this condition with respect to LV function is not well defined, we aimed to evaluate the distribution of patients with severely reduced valve area and low MG in a group of patients regardless of EF over a set period of time. We retrospectively identified consecutive patients with severe AS (defined as aortic valve area <0.6 cmq/mq) from our echo data-base. Low MG was defined as < 40 mmHg. Left ventricular systolic dysfunction was considered as EF< 50%. 167 patients with AVA <0.6 cmq/mq formed the study population. 94 (56%) patients were characterized by high MG and 73 (44%) by low MG. Among patients with low MG, 38 were characterized by normal EF and 35 by reduced EF. Differences among groups are shown in Table 1. In this echocardiographic series of consecutive patients, the prevalence of low MG despite severely reduced AVA was high. The distribution of low MG was similar in presence of reduced and preserved EF (21 and 23% of the overall population respectively).
Proteoglycan-Rich Leaflet Thickening in Diet-Induced Early Aortic Valve Disease
Authors: Blaser Mark C. , Sider Krista L. , Kwong Andrea V. , Zhou Yu-Qing , Henkelman R. Mark , Simmons Craig A.
Published: July 2012

Aortic valve disease (AVD) is a cell-mediated pathology without effective pharmacotherapy, and the early pathogenesis of AVD is drastically understudied. Examining the early stages of disease development may identify biomarkers and novel treatment strategies for use before an untreatable burden of calcification develops. We investigated the effects of a mildly atherogenic diet on early AVD development in mice, and the involvement of proteoglycans (PG) and Sox9 in this process. Male wild-type (WT) C57Bl/6J mice were fed a control diet or BioServ F3282, a high-fat, high-carbohydrate diet (HF/HC) with 58.7% kcal from fat (cholesterol <0.1% w/w) for four months (n = 4-6 per group). Aortic valve function was examined by high-resolution ultrasound biomicroscopy (UBM). Longitudinal aortic valve sections from formalin-fixed and paraffin-embedded hearts were stained by Movat’s pentachrome (morphological changes and ECM composition) and Osteosense 680 (calcification), then immunostained for α-smooth muscle actin (αSMA) and Sox9. Mice on the HF/HC diet for four months became significantly obese (46.7 ± 4.7 vs. 32.3 ± 0.8 g, p < 0.05) but did not develop cardiac hypertrophy. They developed mild but statistically significant hypercholesterolemia (4.7 ± 1.0 vs. 3.1 ± 0.4 mmol/L total cholesterol, p < 0.05). UBM revealed moderate decreases in aortic valve opening area along with increased left ventricular ejection time in HF/HC mice, while no mice exhibited aortic regurgitation. Significant valve thickening was found in the distal third of HF/HC leaflets (84.4 ± 10.4 vs. 37.3 ± 2.7 µm, p < 0.05), while proximal and medial regions were unaltered. Valve thickening was primarily due to PG deposition in HF/HC leaflets (11435 ± 7681 vs. 5448 ± 2948 µm2, p < 0.01), not an increase in collagen content (1729 ± 815 vs. 1771 ± 663 µm2, p = 0.87). Sox9 expression was increased in thickened HF/HC leaflets, and was most highly expressed in PG-rich lesions. HF/HC leaflets did not stain positive for αSMA, implying that changes in leaflet structure and function were not the result of actively synthetic myofibroblasts. Osteosense 680 staining was negative, denoting that the HF/HC diet did not induce leaflet microcalcification.

These studies reveal that a high-fat Western diet lacking cholesterol can induce changes in the ECM and functional properties of a WT mouse aortic valve. This early AVD is characterized by thickened leaflets with lesions that are PG-rich and have increased Sox9 expression. Although AVD is considered to be driven by pathological myofibroblast differentiation leading to fibrosis and calcification, the early changes observed herein occur independently of myofibroblast activation, and provide new insight into the initiation and pathogenesis of AVD.
Angiotensin Receptor Blocker Has no Effect on Atherosclerotic Factors in AVS
Authors: Armstrong Zachary B. , Boughner Derek R. , Carruthers Colin P. , Drangova Maria , Rogers Kem A.
Published: July 2012

Aortic valve sclerosis (AVS) is a chronic progressive disease affecting 25% of the population over the age of 65. Despite this high prevalence, there are currently no preventative therapies which inhibit the progression of AVS. This study sought to determine the effects of an angiotensin II type 1 receptor blocker (ARB), alone or in combination with a statin, on AVS.
Male New Zealand White rabbits were fed either regular chow (Control, n=5) or an atherogenic diet for a period of 18 months to induce AVS. Recognizing the clinical reality, therapy was introduced after disease onset. After 12 months, rabbits were block randomly assigned to four groups receiving either no treatment (Cholesterol, n=6), olmesartan medoxomil (Olmesartan, n=7), atorvastatin calcium (Atorvastatin, n=7), or a combination of both drugs (Combination, n=7) for the final 6 months. Magnetic resonance imaging (MRI) was used to monitor disease progress throughout the treatment period. After sacrifice, valve lesions were analyzed using histology and immunohistochemistry. In vivo disease monitoring yielded no discernible treatment effect. While Cholesterol cusps were significantly thicker than Control throughout the treatment period (0.465 ± 0.030 vs 0.388 ± 0.023mm for Cholesterol and Control, respectively, at 18 months), the various treatments had no positive effect on cusp thickness, and were all identical to Cholesterol at 18 months. Aortic valve area provided similar results; while significant disease was established (0.379 ± 0.033 vs 0.623 ± 0.074cm2 for Cholesterol and Control, respectively, at 18 months), there were no significant differences between treatment groups. Histological analysis of Cholesterol, Atorvastatin, Olmesartan, and Combination cusps revealed fibrosal thickening, lipid deposition, macrophage infiltration, and minor calcification. However, morphological analysis did not reveal significant differences in lesion composition among the treatment groups. Treatment efficacy was confirmed by analysis of aortic lesion area which revealed a significant reduction of atherosclerosis in Olmesartan-treated animals. Neither olmesartan medoxomil nor atorvastatin calcium, alone or in combination, provide demonstrable benefit in the treatment of established AVS despite success in the treatment of atherosclerosis.