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Article ; Online: Fibrin Nanoparticles Coupled with Keratinocyte Growth Factor Enhance the Dermal Wound-Healing Rate.

Muhamed, Ismaeel / Sproul, Erin P / Ligler, Frances S / Brown, Ashley C

ACS applied materials & interfaces

2019 Volume 11, Issue 4, Page(s) 3771–3780

Abstract: Expediting the wound-healing process is critical for patients chronically ill from nonhealing wounds and diseases such as hemophilia or diabetes or who have suffered trauma including easily infected open wounds. FDA-approved external tissue sealants ... ...

Abstract	Expediting the wound-healing process is critical for patients chronically ill from nonhealing wounds and diseases such as hemophilia or diabetes or who have suffered trauma including easily infected open wounds. FDA-approved external tissue sealants include the topical application of fibrin gels, which can be 500 times denser than natural fibrin clots. With lower clot porosity and higher polymerization rates than physiologically formed fibrin clots, the commercial gels quickly stop blood loss but impede the later clot degradation kinetics and thus retard tissue-healing rates. The fibrin nanoparticles (FBNs) described here are constructed from physiologically relevant fibrin concentrations that support new tissue and dermal wound scaffold formation when coupled with growth factors. The FBNs, synthesized in a microfluidic droplet generator, support cell adhesion and traction generation, and when coupled to keratinocyte growth factor (KGF), support cell migration and in vivo wound healing. The FBN-KGF particles enhance cell migration in vitro greater than FBN alone or free KGF and also improve healing outcomes in a murine full thickness injury model compared to saline, bulk fibrin sealant, free KGF, or bulk fibrin mixed with KGF treatments. Furthermore, FBN can be potentially administered with other tissue-healing factors and inflammatory mediators to improve wound-healing outcomes.
MeSH term(s)	Animals ; Biocompatible Materials/chemistry ; Cell Movement/drug effects ; Fibrin/chemistry ; Fibroblast Growth Factor 7/chemistry ; Fibroblast Growth Factor 7/therapeutic use ; Mice ; Microfluidics ; Nanoparticles/chemistry ; Wound Healing/drug effects
Chemical Substances	Biocompatible Materials ; Fibroblast Growth Factor 7 (126469-10-1) ; Fibrin (9001-31-4)
Language	English
Publishing date	2019-01-15
Publishing country	United States
Document type	Journal Article
ISSN	1944-8252
ISSN (online)	1944-8252
DOI	10.1021/acsami.8b21056
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Biophysical Tools to Study Cellular Mechanotransduction.

Muhamed, Ismaeel / Chowdhury, Farhan / Maruthamuthu, Venkat

Bioengineering (Basel, Switzerland)

2017 Volume 4, Issue 1

Abstract: The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane ... ...

Abstract	The cell membrane is the interface that volumetrically isolates cellular components from the cell's environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane's bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na⁺, Ca
Language	English
Publishing date	2017-02-07
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2746191-9
ISSN	2306-5354
ISSN	2306-5354
DOI	10.3390/bioengineering4010012
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Article ; Online: Synthesis of sonicated fibrin nanoparticles that modulate fibrin clot polymerization and enhance angiogenic responses.

Roosa, Colleen A / Muhamed, Ismaeel / Young, Ashlyn T / Nellenbach, Kimberly / Daniele, Michael A / Ligler, Frances S / Brown, Ashley C

Colloids and surfaces. B, Biointerfaces

2021 Volume 204, Page(s) 111805

Abstract: Chronic wounds can occur when the healing process is disrupted and the wound remains in a prolonged inflammatory stage that leads to severe tissue damage and poor healing outcomes. Clinically used treatments, such as high density, FDA-approved fibrin ... ...

Abstract	Chronic wounds can occur when the healing process is disrupted and the wound remains in a prolonged inflammatory stage that leads to severe tissue damage and poor healing outcomes. Clinically used treatments, such as high density, FDA-approved fibrin sealants, do not provide an optimal environment for native cell proliferation and subsequent tissue regeneration. Therefore, new treatments outside the confines of these conventional fibrin bulk gel therapies are required. We have previously developed flowable, low-density fibrin nanoparticles that, when coupled to keratinocyte growth factor, promote cell migration and epithelial wound closure in vivo. Here, we report a new high throughput method for generating the fibrin nanoparticles using probe sonication, which is less time intensive than the previously reported microfluidic method, and investigate the ability of the sonicated fibrin nanoparticles (SFBN) to promote clot formation and cell migration in vitro. The SFBNs can form a fibrin gel when combined with fibrinogen in the absence of exogenous thrombin, and the polymerization rate and fiber density in these fibrin clots is tunable based on SFBN concentration. Furthermore, fibrin gels made with SFBNs support cell migration in an in vitro angiogenic sprouting assay, which is relevant for wound healing. In this report, we show that SFBNs may be a promising wound healing therapy that can be easily produced and delivered in a flowable formulation.
MeSH term(s)	Fibrin ; Fibrin Tissue Adhesive ; Nanoparticles ; Polymerization ; Wound Healing
Chemical Substances	Fibrin Tissue Adhesive ; Fibrin (9001-31-4)
Language	English
Publishing date	2021-04-29
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1500523-9
ISSN	1873-4367 ; 0927-7765
ISSN (online)	1873-4367
ISSN	0927-7765
DOI	10.1016/j.colsurfb.2021.111805
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Article ; Online: Biophysical Tools to Study Cellular Mechanotransduction

Ismaeel Muhamed / Farhan Chowdhury / Venkat Maruthamuthu

Bioengineering, Vol 4, Iss 1, p

2017 Volume 12

Abstract: The cell membrane is the interface that volumetrically isolates cellular components from the cell’s environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane ... ...

Abstract	The cell membrane is the interface that volumetrically isolates cellular components from the cell’s environment. Proteins embedded within and on the membrane have varied biological functions: reception of external biochemical signals, as membrane channels, amplification and regulation of chemical signals through secondary messenger molecules, controlled exocytosis, endocytosis, phagocytosis, organized recruitment and sequestration of cytosolic complex proteins, cell division processes, organization of the cytoskeleton and more. The membrane’s bioelectrical role is enabled by the physiologically controlled release and accumulation of electrochemical potential modulating molecules across the membrane through specialized ion channels (e.g., Na+, Ca2+, K+ channels). The membrane’s biomechanical functions include sensing external forces and/or the rigidity of the external environment through force transmission, specific conformational changes and/or signaling through mechanoreceptors (e.g., platelet endothelial cell adhesion molecule (PECAM), vascular endothelial (VE)-cadherin, epithelial (E)-cadherin, integrin) embedded in the membrane. Certain mechanical stimulations through specific receptor complexes induce electrical and/or chemical impulses in cells and propagate across cells and tissues. These biomechanical sensory and biochemical responses have profound implications in normal physiology and disease. Here, we discuss the tools that facilitate the understanding of mechanosensitive adhesion receptors. This article is structured to provide a broad biochemical and mechanobiology background to introduce a freshman mechano-biologist to the field of mechanotransduction, with deeper study enabled by many of the references cited herein.
Keywords	mechanotransduction ; traction force microscopy ; magnetic twisting cytometry ; shear flow microfluidic device ; integrins ; focal adhesions ; cadherins ; adherens junction ; Technology ; T ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2017-02-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Fibrin Nanoparticles Coupled with Keratinocyte Growth Factor Enhance the Dermal Wound-Healing Rate

Muhamed, Ismaeel / Sproul, Erin P / Ligler, Frances S / Brown, Ashley C

ACS applied materials & interfaces. 2019 Jan. 03, v. 11, no. 4

2019

Abstract	Expediting the wound-healing process is critical for patients chronically ill from nonhealing wounds and diseases such as hemophilia or diabetes or who have suffered trauma including easily infected open wounds. FDA-approved external tissue sealants include the topical application of fibrin gels, which can be 500 times denser than natural fibrin clots. With lower clot porosity and higher polymerization rates than physiologically formed fibrin clots, the commercial gels quickly stop blood loss but impede the later clot degradation kinetics and thus retard tissue-healing rates. The fibrin nanoparticles (FBNs) described here are constructed from physiologically relevant fibrin concentrations that support new tissue and dermal wound scaffold formation when coupled with growth factors. The FBNs, synthesized in a microfluidic droplet generator, support cell adhesion and traction generation, and when coupled to keratinocyte growth factor (KGF), support cell migration and in vivo wound healing. The FBN–KGF particles enhance cell migration in vitro greater than FBN alone or free KGF and also improve healing outcomes in a murine full thickness injury model compared to saline, bulk fibrin sealant, free KGF, or bulk fibrin mixed with KGF treatments. Furthermore, FBN can be potentially administered with other tissue-healing factors and inflammatory mediators to improve wound-healing outcomes.
Keywords	blood ; cell adhesion ; cell movement ; diabetes ; fibrin ; gels ; generators (equipment) ; growth factors ; hemophilia ; keratinocytes ; mice ; models ; nanoparticles ; patients ; polymerization ; porosity ; sealants ; topical application
Language	English
Dates of publication	2019-0103
Size	p. 3771-3780.
Publishing place	American Chemical Society
Document type	Article
ISSN	1944-8252
DOI	10.1021/acsami.8b21056
Database	NAL-Catalogue (AGRICOLA)

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Article: Typical leiomyoma of the scrotum: A rare case report.

Fakhralddin, Saman Salih / Bapir, Rawa / Babarasul, Muhamed Hussen / Ibrahim, Zheen Bahaddin / Aghaways, Ismaeel

International journal of surgery case reports

2020 Volume 67, Page(s) 142–145

Abstract: Introduction: Scrotal leiomyomas are benign tumors arising from the dartos layer of the scrotal wall. The exact cause of this tumor is not yet clear. Malignant transformation to leiomyosarcomas has been reported.: Case presentation: A 52-year-old ... ...

Abstract	Introduction: Scrotal leiomyomas are benign tumors arising from the dartos layer of the scrotal wall. The exact cause of this tumor is not yet clear. Malignant transformation to leiomyosarcomas has been reported. Case presentation: A 52-year-old male who complained of a painless lump on the right side of the scrotum that lasted 12 years. Physical examination revealed a single, firm, and non-tender, mobile lump on the anterior aspect of the right scrotum. Both testes were normal and no inguinal lymph nodes could be palpated. Ultrasound scan of the scrotum showed a 40 mm × 20 mm hypoechoic, poorly vascular lesion in the scrotum. Under spinal anesthesia, the mass has been excised. Histopathological and immunohistochemical findings were consistent with the diagnosis of scrotal leiomyoma. Discussion: Leiomyomas may originate from any location in the genitourinary system where there is smooth muscle. Scrotal smooth muscle tumors can be categorized into Leiomyomas, atypical or symplastic leiomyomas, which are not hypercellular and lack mitotic activity, and leiomyosarcomas. Ultrasound is the first-line imaging investigation in patients with suspected scrotal masses. Typical leiomyomas and atypical ones behave similarly. Therefore, they are managed only with surgical excision, while leiomyosarcomas need a wide 3-5 cm margin resection. Both recurrence and malignancy have been described. Close follow-up is required to detect recurrence. Conclusion: Scrotal leiomyoma is a rare benign mesenchymal tumor of the middle-aged men. The current report describes the clinical and histopathological characteristics to help reduce erroneous diagnoses of this rare tumor.
Language	English
Publishing date	2020-02-06
Publishing country	Netherlands
Document type	Case Reports
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2020.01.057
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Article: Structural change and economic growth in selected emerging economies

Majid, Muhamed Zulkhibri Abdul / Ghazal, Reza / Naiya, Ismaeel

International journal of development issues : IJDI Vol. 14, No. 2 , p. 98-116

2015 Volume 14, Issue 2, Page(s) 98–116

Author's details	Muhamed Zulkhibri (Islamic Research and Training Institute, Islamic Development Bank, Jeddah, Saudi Arabia), Ismaeel Naiya (Economic Research and Policy Deptartment, Islamic Development Bank, Jeddah, Saudi Arabia), and Reza Ghazal (Business and Management Sciences Deptartment, University of Kurdistan-Hawler (UKH), Kurdistan, Iraq)
Keywords	Economic growth ; Panel cointegration ; Structural change
Language	Undetermined
Publisher	Emerald
Publishing place	Bingley
Document type	Article
ZDB-ID	2529514-7 ; 2423663-9
ISSN	1446-8956
ISSN	1446-8956
Database	ECONomics Information System

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Article ; Online: E-cadherin-mediated force transduction signals regulate global cell mechanics.

Muhamed, Ismaeel / Wu, Jun / Sehgal, Poonam / Kong, Xinyu / Tajik, Arash / Wang, Ning / Leckband, Deborah E

Journal of cell science

2016 Volume 129, Issue 9, Page(s) 1843–1854

Abstract: This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new ... ...

Abstract	This report elucidates an E-cadherin-based force-transduction pathway that triggers changes in cell mechanics through a mechanism requiring epidermal growth factor receptor (EGFR), phosphoinositide 3-kinase (PI3K), and the downstream formation of new integrin adhesions. This mechanism operates in addition to local cytoskeletal remodeling triggered by conformational changes in the E-cadherin-associated protein α-catenin, at sites of mechanical perturbation. Studies using magnetic twisting cytometry (MTC), together with traction force microscopy (TFM) and confocal imaging identified force-activated E-cadherin-specific signals that integrate cadherin force transduction, integrin activation and cell contractility. EGFR is required for the downstream activation of PI3K and myosin-II-dependent cell stiffening. Our findings also demonstrated that α-catenin-dependent cytoskeletal remodeling at perturbed E-cadherin adhesions does not require cell stiffening. These results broaden the repertoire of E-cadherin-based force transduction mechanisms, and define the force-sensitive signaling network underlying the mechano-chemical integration of spatially segregated adhesion receptors.
MeSH term(s)	Animals ; Cadherins/genetics ; Cadherins/metabolism ; Cytoskeleton/genetics ; Cytoskeleton/metabolism ; Dogs ; Humans ; MCF-7 Cells ; Madin Darby Canine Kidney Cells ; Mechanotransduction, Cellular/physiology ; Receptor, Epidermal Growth Factor/genetics ; Receptor, Epidermal Growth Factor/metabolism ; alpha Catenin/genetics ; alpha Catenin/metabolism
Chemical Substances	Cadherins ; alpha Catenin ; EGFR protein, human (EC 2.7.10.1) ; Receptor, Epidermal Growth Factor (EC 2.7.10.1)
Language	English
Publishing date	2016--01
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2993-2
ISSN	1477-9137 ; 0021-9533
ISSN (online)	1477-9137
ISSN	0021-9533
DOI	10.1242/jcs.185447
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Article ; Online: Dynamic visualization of α-catenin reveals rapid, reversible conformation switching between tension states.

Kim, Tae-Jin / Zheng, Shuai / Sun, Jie / Muhamed, Ismaeel / Wu, Jun / Lei, Lei / Kong, Xinyu / Leckband, Deborah E / Wang, Yingxiao

Current biology : CB

2014 Volume 25, Issue 2, Page(s) 218–224

Abstract: The cytosolic protein α-catenin is a postulated force transducer at cadherin complexes. The demonstration of force activation, identification of consequent downstream events in live cells, and development of tools to study these dynamic processes in ... ...

Abstract	The cytosolic protein α-catenin is a postulated force transducer at cadherin complexes. The demonstration of force activation, identification of consequent downstream events in live cells, and development of tools to study these dynamic processes in living cells are central to elucidating the role of α-catenin in cellular mechanics and tissue function. Here we demonstrate that α-catenin is a force-activatable mechanotransducer at cell-cell junctions by using an engineered α-catenin conformation sensor based on fluorescence resonance energy transfer (FRET). This sensor reconstitutes α-catenin-dependent functions in α-catenin-depleted cells and recapitulates the behavior of the endogenous protein. Dynamic imaging of cells expressing the sensor demonstrated that α-catenin undergoes immediate, reversible conformation switching in direct response to different mechanical perturbations of cadherin adhesions. Combined magnetic twisting cytometry with dynamic FRET imaging revealed rapid, local conformation switching upon the mechanical stimulation of specific cadherin bonds. At acutely stretched cell-cell junctions, the immediate, reversible conformation change further reveals that α-catenin behaves like an elastic spring in series with cadherin and actin. The force-dependent recruitment of vinculin—a principal α-catenin effector—to junctions requires the vinculin binding site of the α-catenin sensor. In cells, the relative rates of force-dependent α-catenin conformation switching and vinculin recruitment reveal that α-catenin activation and vinculin recruitment occur sequentially, rather than in a concerted process, with vinculin accumulation being significantly slower. This engineered α-catenin sensor revealed that α-catenin is a reversible, stretch-activatable sensor that mechanically links cadherin complexes and actin and is an indispensable player in cadherin-specific mechanotransduction at intercellular junctions.
MeSH term(s)	Actins/metabolism ; Cadherins/metabolism ; Fluorescence Resonance Energy Transfer ; Gene Expression Regulation ; Humans ; Intercellular Junctions ; Mechanotransduction, Cellular ; Protein Binding ; alpha Catenin/genetics ; alpha Catenin/metabolism
Chemical Substances	Actins ; CTNNA1 protein, human ; Cadherins ; alpha Catenin
Language	English
Publishing date	2014-12-24
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2014.11.017
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Article ; Online: Endothelial Microparticles and Systemic Complement Activation in Patients With Chronic Kidney Disease.

Jalal, Diana / Renner, Brandon / Laskowski, Jennifer / Stites, Erik / Cooper, James / Valente, Karissa / You, Zhiying / Perrenoud, Loni / Le Quintrec, Moglie / Muhamed, Ismaeel / Christians, Uwe / Klawitter, Jelena / Lindorfer, Margaret A / Taylor, Ronald P / Holers, V Michael / Thurman, Joshua M

Journal of the American Heart Association

2018 Volume 7, Issue 14

Abstract: Background: Endothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement ... ...

Abstract	Background: Endothelial microparticles are associated with chronic kidney disease (CKD) and complement activation. We hypothesized that the complement pathway is activated in patients with CKD via endothelial microparticles and that complement activation correlates with endothelial dysfunction in CKD. Methods and results: We analyzed complement data of 30 healthy subjects, 30 patients with stage III/IV CKD, and 30 renal transplant recipients with stage III/IV CKD, evaluating the potential correlation of complement fragments with brachial artery flow-mediated dilation, Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and urinary albumin/creatinine ratio. Endothelial microparticles were characterized via proteomic analysis and compared between study groups. Complement fragment Ba was significantly increased in CKD and post-kidney transplant CKD. Plasma Ba levels correlated significantly with lower brachial artery flow-mediated dilation, lower Chronic Kidney Disease Epidemiology Collaboration glomerular filtration rate, and higher urinary albumin/creatinine ratio. Factor D levels were significantly higher in the plasma microparticles of patients with CKD versus healthy controls. Plasma microparticles isolated from patients with CKD and containing factor D activated the alternative pathway in vitro. Conclusion: The alternative complement pathway is activated in CKD and correlates with endothelial dysfunction and markers of CKD. Future studies are needed to evaluate whether endothelial microparticles with increased factor D play a pathologic role in CKD-associated vascular disease. Clinical trial registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02230202.
MeSH term(s)	Adult ; Aged ; Brachial Artery/diagnostic imaging ; Brachial Artery/physiopathology ; Case-Control Studies ; Cell-Derived Microparticles/metabolism ; Complement Activation ; Complement C4a/metabolism ; Complement C5a/metabolism ; Complement Factor B/metabolism ; Complement Factor D/metabolism ; Complement Membrane Attack Complex/metabolism ; Complement Pathway, Alternative ; Complement System Proteins/metabolism ; Endothelial Cells ; Endothelium, Vascular/physiopathology ; Female ; Glomerular Filtration Rate ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Pilot Projects ; Proteomics ; Renal Insufficiency, Chronic/metabolism ; Renal Insufficiency, Chronic/physiopathology ; Renal Insufficiency, Chronic/surgery ; Severity of Illness Index ; Vasodilation
Chemical Substances	Complement Membrane Attack Complex ; Complement C4a (80295-49-4) ; Complement C5a (80295-54-1) ; Complement System Proteins (9007-36-7) ; Complement Factor D (EC 3.4.21.46) ; Complement Factor B (EC 3.4.21.47)
Language	English
Publishing date	2018-07-13
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.117.007818
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