BiorheologyPub Date : 2019-11-06DOI: 10.3233/BIR-190225
H. Lipowsky
{"title":"Relative shedding of glycosaminoglycans from the endothelial glycocalyx during inflammation and their contribution to stiffness of the glycocalyx.","authors":"H. Lipowsky","doi":"10.3233/BIR-190225","DOIUrl":"https://doi.org/10.3233/BIR-190225","url":null,"abstract":"BACKGROUND\u0000The endothelial (EC) surface layer (glycocalyx) has been shown to act as a barrier to transvascular exchange of solutes, and adhesion of leukocytes (WBCs) during the inflammatory process. It is a labile structure whose components are readily shed by the action of proteases and endoglycosidases. Details of shedding of specific constituents of the glycocalyx remain to be determined.\u0000\u0000\u0000OBJECTIVES\u0000To review the contributions of the primary glycosaminoglycans that comprise the glycocalyx, heparan sulfate (HS), chondroitin sulfate (CS) and hyaluronan (HA), as barrier to WBC-EC adhesion, and elucidate the rates of shedding of each component in response to an inflammatory stimulus. Assess the potential role that stiffness of the glycocalyx plays in resisting infiltration by WBCs during the adhesion process.\u0000\u0000\u0000METHODS\u0000Quantitate shedding of the glycocalyx in post-capillary venules of rat mesentery in response to superfusion of the tissue with 10-6 M fMLP. The presence and loss of HS, CS and HA was assessed by labeling all components with fluorescently labelled lectin (BS-1) or HS antibodies, and HA with fluorescently labelled hyaluronan binding protein (HBP).\u0000\u0000\u0000RESULTS\u0000Following a 30 min exposure of the mesentery to fMLP about 50% of HBP was lost in contrast to a previously shown loss of 20% of lectin labelled GAGs, and 25% loss of Mab labelled HS. The time constant for HBP shedding (5.8 min) was one-third that for BS-1 labelled GAGs (14.3 min). An attempt was made to assess stiffness of the glycocalyx by observing the motion of adhered lectin coated fluorescently labelled microspheres (FLM) under oscillatory flow conditions. Estimates of the elastic modulus of the glycocalyx revealed a value of 26 mPa, which was orders of magnitude below published data obtained by atomic force microscopy.\u0000\u0000\u0000CONCLUSIONS\u0000The relatively rapid shedding of HA compared to HS was consistent with the hypothesis that HA may form the dominant barrier to WBC-EC adhesion. Prior observations that HA lies closer to and parallel to the endothelial membrane, compared to HS suggests that the compact layer of HA near the EC membrane surrounds WBC adhesion receptors that are much shorter in length than the total thickness of the glycocalyx. The relatively low elastic modulus of the glycocalyx under shear is consistent with the hypothesis that the FLMs adhered to strands of HS normal to the EC surface that extended above the relatively more compact and stiffer HA layer below. Gradients of stiffness within the glycocalyx may not be detected by compressive indentation tests published to date.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"1 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2019-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-190225","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"47139577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/BIR-180196
Peter Kilbride, Marina Vazquez Rull, Adam Townsend, Helen Wilson, John Morris
{"title":"Shear-thickening fluids in biologically relevant agents.","authors":"Peter Kilbride, Marina Vazquez Rull, Adam Townsend, Helen Wilson, John Morris","doi":"10.3233/BIR-180196","DOIUrl":"https://doi.org/10.3233/BIR-180196","url":null,"abstract":"<p><strong>Background: </strong>The rheology of shear thickening fluids is well characterized for many physical applications, however the literature surrounding biologically or cryobiologically compatible shear thickening fluids is less well understood.</p><p><strong>Objective: </strong>This study examined fluids consisting of corn-derived hydroxyethyl starch with a variety of sugars and cryoprotectants to characterize their shear-rate viscosity relationship. The objective was to establish if cryobiologically relevant materials could be used to afford biologics protection through shear-thickening.</p><p><strong>Results: </strong>Fluids consisting of 50% hydroxyethyl starch by weight exhibited shear thickening with a variety of cryoprotectants. Lowering the temperature of the fluid both reduced critical shear rates and enhanced thickening magnitude. Starch derived from corn, wheat, and rice all exhibited non-Newtonian shear-dependent viscosity behaviour at 50% by weight in water. Between the starch sources however, the shear-rate viscosity relationship varied widely, with wheat-derived starch shear thinning, and the remaining starches forming shear thickening fluids. Different starch sources had different baseline viscosities, critical shear rates, and rates of viscosity increase.</p><p><strong>Conclusions: </strong>This study established that shear thickening is compatible with cryobiologically relevant agents, particularly so at lower temperatures. This forms the basis for harnessing these phenomena in biological processes such as cryopreservation.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"56 1","pages":"39-50"},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-180196","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37006302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/BIR-190207
Axel R Pries
{"title":"Microvascular hemodynamics: System properties1.","authors":"Axel R Pries","doi":"10.3233/BIR-190207","DOIUrl":"10.3233/BIR-190207","url":null,"abstract":"<p><p>The hemodynamics of the microcirculation reflect system properties of the involved components. The blood itself is a complex suspension of water, small and large molecules and different cell types. Under most conditions, its rheologic properties are dominated by the different behaviour of fluid and cellular compartments. When perfused through small-bore tubes or vessels, the suspension exhibits specific emergent properties. The Fahraeus-effect and the Fahreaeus-Lindqvist-effect result from the interaction of cellular particles with each other and with the vessel wall. Additional phenomena occur in vascular networks due to the uneven distribution of blood cells and blood plasma at divergent microvascular bifurcations. In order to understand microvascular hemodynamics in vivo but also in artificial microfluidic geometries it is thus necessary to recognize the pertinent system properties on the level of the blood, the microvessels and the microvascular networks or perfused structures.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"56 1","pages":"1-13"},"PeriodicalIF":1.0,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37006303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/bir-190212
P. Butler, A. Bhatnagar
{"title":"Mechanobiology of the abluminal glycocalyx.","authors":"P. Butler, A. Bhatnagar","doi":"10.3233/bir-190212","DOIUrl":"https://doi.org/10.3233/bir-190212","url":null,"abstract":"BACKGROUND Endothelial cells (ECs) sense the forces from blood flow through the glycocalyx, a carbohydrate rich luminal surface layer decorating most cells, and through forces transmitted through focal adhesions (FAs) on the abluminal side of the cell. OBJECTIVES This perspective paper explores a complementary hypothesis, that glycocalyx molecules on the abluminal side of the EC between the basement membrane and the EC membrane, occupying the space outside of FAs, work in concert with FAs to sense blood flow-induced shear stress applied to the luminal surface. RESULTS First, we summarize recent studies suggesting that the glycocalyx repels the plasma membrane away from the basement membrane, while integrin molecules attach to extracellular matrix (ECM) ligands. This coordinated attraction and repulsion results in the focal nature of integrin-mediated adhesion making the abluminal glycocalyx a participant in mechanotransduction. Further, the glycocalyx mechanically links the plasma membrane to the basement membrane providing a mechanism of force transduction when the cell deforms in the peri-FA space. To determine if the membrane might deform against a restoring force of an elastic abluminal glycocalyx in the peri-FA space we present some analysis from a multicomponent elastic finite element model of a sheared and focally adhered endothelial cell whose abluminal topography was assessed using quantitative total internal reflection fluorescence microscopy with an assumption that glycocalyx fills the space between the membrane and extracellular matrix. CONCLUSIONS While requiring experimental verification, this analysis supports the hypothesis that shear on the luminal surface can be transmitted to the abluminal surface and deform the cell in the vicinity of the focal adhesions, with the magnitude of deformation depending on the abluminal glycocalyx modulus.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"1 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/bir-190212","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69793266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/BIR-190208
Won Ho Yoon, Keyong Ho Lee
{"title":"Rheological properties and efficacy of the formulation of hyaluronic acid with tamarind seed polysaccharide for arthritis.","authors":"Won Ho Yoon, Keyong Ho Lee","doi":"10.3233/BIR-190208","DOIUrl":"https://doi.org/10.3233/BIR-190208","url":null,"abstract":"<p><strong>Background: </strong>Tamarind seed polysaccharide (TSP) is used as a texturizing agent and a thickener in food and pharmaceutical products. There are no publications describing the addition of TSP to intra-articular injection formulations for arthritis.</p><p><strong>Objective: </strong>The purpose of this study was to investigate the rheology and efficacy of the formulation of TSP with hyaluronic acid (HA) as a new material for injection for arthritis.</p><p><strong>Methods: </strong>We investigated the viscoelastic properties of formulations of HA and TSP as potential lubricants for arthritis, and tested the improvement of right/left paw weight distribution in monosodium iodoacetate-induced arthritis in the rat.</p><p><strong>Results: </strong>HA formulations with 3% and 4% TSP showed improved rheological characteristics and were protected against changes induced by heat sterilization. Addition of TSP also reduced pain in the arthritis model, as evidenced by normalization of the distribution of paw weight.</p><p><strong>Conclusions: </strong>TSP is a potential material as a substitute for HA or in combination with HA for intra-articular injection for arthritis.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"56 1","pages":"31-38"},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-190208","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37088540","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/BIR-190215
Sen Lu, Shusheng Zhang
{"title":"Effect of arterial curvature on hemodynamics and mass transport.","authors":"Sen Lu, Shusheng Zhang","doi":"10.3233/BIR-190215","DOIUrl":"https://doi.org/10.3233/BIR-190215","url":null,"abstract":"<p><strong>Background: </strong>Atherosclerotic lesions develop preferentially at certain sites in the human arterial system, such as the inner wall of curved segments and the outer wall of bifurcations. Local wall shear stress (WSS) and concentration of low density lipoprotein (LDL) have been identified as two important factors contributing to these lesions.</p><p><strong>Objective: </strong>To determine if a connection exists between arterial curvature and the formation of atherosclerosis.</p><p><strong>Methods: </strong>A set of 3-D vessel models with different bend angles was constructed. By comparing blood flow, WSS, and LDL aggregation, the influence of bend curvature on atherosclerotic lesions was assessed.</p><p><strong>Results: </strong>Upon increasing arterial bending, low WSS regions were formed at the outer wall of the junction between straight and curved segments, as well as the inner wall of curved segments. However, high LDL concentrations only appeared at the inner wall of the bend region. A connection between secondary flow and LDL concentration was observed; high LDL concentration regions had stronger secondary flow. Higher water infiltration velocity could enhance LDL aggregation, while blood non-Newtonian properties, by easing secondary flow, diminished its aggregation.</p><p><strong>Conclusions: </strong>Under the same flow rate, a larger bend angle increased flow resistance, lowered WSS, and increased LDL surface concentrations, thus indicating an increased risk of atherosclerosis.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"56 4","pages":"253-263"},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-190215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37125896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/bir-190213
S. Cırrık, E. Ugurel, A. C. Aksu, B. Oronsky, P. Cabrales, O. Yalcin
{"title":"Nitrite may serve as a combination partner and a biomarker for the anti-cancer activity of RRx-001.","authors":"S. Cırrık, E. Ugurel, A. C. Aksu, B. Oronsky, P. Cabrales, O. Yalcin","doi":"10.3233/bir-190213","DOIUrl":"https://doi.org/10.3233/bir-190213","url":null,"abstract":"BACKGROUND RRx-001 is an anti-cancer immunotherapeutic that increases the sensitivity of drug resistant tumors via multiple mechanisms which involve binding to hemoglobin and enhancing nitrite reductase activity of deoxyhemoglobin. OBJECTIVE In the present study, the effect of clinically used doses of RRx-001 on erythrocyte deformability was examined. METHODS A dose dependent effect of RRx-001 (1-1000 micro molar) on erythrocyte deformability was measured by ektacytometer under hypoxia (n = 8). Low dose RRx-001 (20 micro molar) in the presence of ODQ (1H-[1,2,4]Oxadiazolo[4,3-a]quinoxalin-1-one), L-NAME (L-NG-Nitroarginine methyl ester) or nitrite were examined both in normoxia and hypoxia. Intracellular nitric oxide (NO) levels were measured fluorometrically with DAF-FM-DA. RESULTS Higher doses of RRx-001 (100, 1000 micro molar) significantly decreased erythrocyte deformability under hypoxia (p < 0.01; p < 0.05, respectively). RRx-001 (20 micro molar), alone or in combination with ODQ or L-NAME, did not change deformability. However, RRx-001 and nitrite caused an increase in deformability (p < 0.01) under hypoxia. RRx-001 induced NO production was more pronounced in the presence of nitrite (p < 0.05). CONCLUSIONS Co-administration of RRx-001 and nitrite under hypoxic conditions results in a significant increase in erythrocyte deformability that is related to increased NO production. We suggest that measurement of serum nitrite level in RRx-001 treated cancer patients should be routinely undertaken and supplemented if levels are low for maximal activity.","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"1 1","pages":""},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/bir-190213","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"69793460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/BIR-180200
Norman R Harris, Wendy Leskova, Gaganpreet Kaur, Randa S Eshaq, Patsy R Carter
{"title":"Blood flow distribution and the endothelial surface layer in the diabetic retina.","authors":"Norman R Harris, Wendy Leskova, Gaganpreet Kaur, Randa S Eshaq, Patsy R Carter","doi":"10.3233/BIR-180200","DOIUrl":"https://doi.org/10.3233/BIR-180200","url":null,"abstract":"<p><p>Diabetic retinopathy is known as a microvascular complication of hyperglycemia, with a breakdown of the blood-retinal barrier, loss of pericytes, formation of microhemorrhages, early decreases in perfusion and areas of ischemia, with the latter speculated to induce the eventual proliferative, angiogenic phase of the disease. Our animal models of diabetic retinopathy demonstrate similar decreases in retinal blood flow as seen in the early stages of diabetes in humans. Our studies also show an alteration in the retinal distribution of red blood cells, with the deep capillary layer receiving a reduced fraction, and with flow being diverted more towards the superficial vascular layer. Normal red blood cell distribution is dependent on the presence of the endothelial surface layer, specifically the glycocalyx, which has been reported to be partially lost in the diabetic retina of both humans and animals. This review addresses these two phenomena in diabetes: altered perfusion patterns and loss of the glycocalyx, with a possible connection between the two.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"56 2-3","pages":"181-189"},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-180200","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9265864","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/BIR-180202
Coşkun Bilgi, Kunt Atalık
{"title":"Numerical investigation of the effects of blood rheology and wall elasticity in abdominal aortic aneurysm under pulsatile flow conditions.","authors":"Coşkun Bilgi, Kunt Atalık","doi":"10.3233/BIR-180202","DOIUrl":"https://doi.org/10.3233/BIR-180202","url":null,"abstract":"<p><strong>Background: </strong>Previous studies on aneurysm modeling have focused on the blood rheology and vessel elasticity separately. The combined effects of blood shear thinning properties and wall elasticity need to be revealed.</p><p><strong>Objective: </strong>To provide insights on how pulsatile hemodynamics vary with blood rheology and vessel elasticity for a developed abdominal aortic aneurysm (AAA).</p><p><strong>Method: </strong>An Arbitrary Lagrangian-Eulerian fluid-solid interaction method is adopted with the Newtonian and the shear thinning Carreau constitutive models for the fluid with the linearly elastic and the hyperelastic Yeoh models for the vessel. Finite element based numerical solver is used to simulate the blood flow in the AAA.</p><p><strong>Results: </strong>Newtonian model overestimates the velocity values compared to the Carreau model and the difference in the velocity field increases as the shear rate decreases at the instances of the cardiac cycle. The rigid walled simulations display higher deviations in the velocity and wall shear stress with the fluid rheology. The risk indicators show that Newtonian assumption combined with the linearly elastic model may overlook degeneration risk of arterial tissue.</p><p><strong>Conclusions: </strong>Newtonian assumption for the blood as well as modelling the arterial wall as linearly elastic lead to significant differences in oscillatory hemodynamic properties with respect to the use of Carreau fluid together with hyperelastic vessel model, even in large vessel aneurysms.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"56 1","pages":"51-71"},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-180202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37366758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
BiorheologyPub Date : 2019-01-01DOI: 10.3233/BIR-180185
Asma Alanazi, Hafsa Munir, Mohammed Alassiri, Lewis S C Ward, Helen M McGettrick, Gerard B Nash
{"title":"Comparative adhesive and migratory properties of mesenchymal stem cells from different tissues.","authors":"Asma Alanazi, Hafsa Munir, Mohammed Alassiri, Lewis S C Ward, Helen M McGettrick, Gerard B Nash","doi":"10.3233/BIR-180185","DOIUrl":"https://doi.org/10.3233/BIR-180185","url":null,"abstract":"<p><strong>Background: </strong>Mesenchymal stem cells (MSC) are used in therapy, often by injection into the blood.</p><p><strong>Objective: </strong>We aimed to compare the adhesive and migratory properties of MSC from umbilical cords (UCMSC), bone marrow (BMMSC) or trabecular bone (TBMSC), which might influence delivery to injured tissue.</p><p><strong>Methods: </strong>MSC were perfused through glass capillaries coated with matrix proteins, collagen or fibronectin, or albumin. Adherent cells were counted microscopically and their spreading analysed over time. MSC migration through 8 μm pore filters coated with the same proteins was analysed.</p><p><strong>Results: </strong>The number of MSC adhering to collagen was greater than fibronectin, decreased as wall shear rate increased from 17 to 70 s-1, and was in the order UCMSC>BMMSC>TBMSC. Conversely, spreading was more effective on fibronectin and was in the order BMMSC>TBMSC≥UCMSC. Migration was promoted by coating the lower surface of filters with either matrix protein, with UCMSC migrating more efficiently than BMMSC.</p><p><strong>Conclusions: </strong>MSC show origin-dependent variations in their efficiency of capture from flow and subsequent spreading or ability to migrate on matrix proteins. UCMSC showed most efficient capture from flow, which was followed by less spreading, but more rapid migration. These responses might be associated with more effective delivery from the circulation into damaged tissue.</p>","PeriodicalId":9167,"journal":{"name":"Biorheology","volume":"56 1","pages":"15-30"},"PeriodicalIF":1.1,"publicationDate":"2019-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3233/BIR-180185","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"36926421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}