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Article ; Online: Establishing an effective clinical data collecting tool for optimal evaluation of native and allograft renal biopsies

Shifaa’ Al Qa'qa’ / Rehab Al-Fatani / Sonia Rodriguez-Ramirez / Prakash Gudsoorkar / Laurette Geldenhuys / Carmen Avila-Casado

Heliyon, Vol 9, Iss 3, Pp e14264- (2023)

2023

Abstract: Introduction: Percutaneous kidney biopsy is the gold standard method to reach a precise diagnosis in most medical kidney diseases, which positively impacts patient care by personalizing the treatment. Accurate diagnosis in the pathology report for ... ...

Abstract	Introduction: Percutaneous kidney biopsy is the gold standard method to reach a precise diagnosis in most medical kidney diseases, which positively impacts patient care by personalizing the treatment. Accurate diagnosis in the pathology report for medical kidney diseases requires clinicopathological correlation, and clinical data is not always reachable to the nephropathologist. This study aimed to create a standardized, paperless requisition form compatible with medical renal biopsies. Methods: An initial form was prepared for native and allograft renal biopsies according to the current classification of medical kidney diseases. We invited 33 nephropathologists working in Canadian healthcare institutions to answer survey questions about the need to include a particular aspect of clinical information. According to the responses, we modified the experimental form. Eighty nephrologists were asked to complete a clinical data-collecting form given out as PDF files. The time for completing the form and clinicians’ satisfaction were assessed. Results: The experimental form survey was answered by 20 out of 33 nephropathologists (61%) from 14 Canadian healthcare centers. The agreement rate on the questions was from 38.89% to 100.00% (average 83.33% and 77.14% for the native and the allograft section, respectively). Seventeen out of 80 nephrologists and their assistants (21%) responded by completing 22 PDF forms. The time required to finish a PDF form was 10.4 min on average. Nephrologists considered the form time-consuming and suggested making it more clinically relevant. Only seven nephrologists responded to the satisfaction survey; four (57%) were satisfied. Conclusions: Medical information is critical in renal pathology diagnoses. A uniform paperless clinical data requisition form was evolved through an agreement by Canadian nephropathologists.
Keywords	Clinical data ; Effective ; Electronic ; Quality improvement ; Collecting form ; Renal biopsy ; Science (General) ; Q1-390 ; Social sciences (General) ; H1-99
Subject code	616
Language	English
Publishing date	2023-03-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Alteration of the Fatty Acid Metabolism in the Rat Kidney Caused by the Injection of Serum from Patients with Collapsing Glomerulopathy.

Soria-Castro, Elizabeth / Guarner-Lans, Verónica / Soto, María Elena / Carmen Avila-Casado, María Del / Manzano Pech, Linaloe / Pérez-Torres, Israel

Biomedicines

2020 Volume 8, Issue 10

Abstract: Patients with collapsing glomerulopathy (CG) have marked proteinuria that rapidly progresses to chronic renal failure. In this study, we investigated if the nephropathy produced in a rat model by the injection of serum from CG patients induced ... ...

Abstract	Patients with collapsing glomerulopathy (CG) have marked proteinuria that rapidly progresses to chronic renal failure. In this study, we investigated if the nephropathy produced in a rat model by the injection of serum from CG patients induced alterations in fatty acid (FA) metabolism. Twenty-four female Sprague-Dawley rats were divided into four groups of six rats each: Group I, control rats (C); Group II, rats that received injections of 1 mL of 0.9% NaCl saline solution (SS); Group III, rats injected with 25 mg/mL of serum from healthy subjects (HS); and Group IV, rats injected with 25 mg/mL of serum from CG patients. In all groups, the systolic blood pressure (SBP), proteinuria, creatinine clearance (CC), cholesterol and total FA composition in the kidney and serum were evaluated. The administration of serum from CG patients to rats induced glomerular collapse, proteinuria, reduced CC and elevated SBP (
Language	English
Publishing date	2020-09-29
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2720867-9
ISSN	2227-9059
ISSN	2227-9059
DOI	10.3390/biomedicines8100388
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Article ; Online: Cytokine storm–based mechanisms for extrapulmonary manifestations of SARS-CoV-2 infection

Maria Del Nogal Avila / Ranjan Das / Joubert Kharlyngdoh / Eduardo Molina-Jijon / Hector Donoro Blazquez / Stéphanie Gambut / Michael Crowley / David K. Crossman / Rasheed A. Gbadegesin / Sunveer S. Chugh / Sunjeet S. Chugh / Carmen Avila-Casado / Camille Macé / Lionel C. Clement / Sumant S. Chugh

JCI Insight, Vol 8, Iss

2023 Volume 10

Abstract: Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2/COVID-19 or rhinovirus ... ...

Abstract	Viral illnesses like SARS-CoV-2 have pathologic effects on nonrespiratory organs in the absence of direct viral infection. We injected mice with cocktails of rodent equivalents of human cytokine storms resulting from SARS-CoV-2/COVID-19 or rhinovirus common cold infection. At low doses, COVID-19 cocktails induced glomerular injury and albuminuria in zinc fingers and homeoboxes 2 (Zhx2) hypomorph and Zhx2+/+ mice to mimic COVID-19–related proteinuria. Common Cold cocktail induced albuminuria selectively in Zhx2 hypomorph mice to model relapse of minimal change disease, which improved after depletion of TNF-α, soluble IL-4Rα, or IL-6. The Zhx2 hypomorph state increased cell membrane to nuclear migration of podocyte ZHX proteins in vivo (both cocktails) and lowered phosphorylated STAT6 activation (COVID-19 cocktail) in vitro. At higher doses, COVID-19 cocktails induced acute heart injury, myocarditis, pericarditis, acute liver injury, acute kidney injury, and high mortality in Zhx2+/+ mice, whereas Zhx2 hypomorph mice were relatively protected, due in part to early, asynchronous activation of STAT5 and STAT6 pathways in these organs. Dual depletion of cytokine combinations of TNF-α with IL-2, IL-13, or IL-4 in Zhx2+/+ mice reduced multiorgan injury and eliminated mortality. Using genome sequencing and CRISPR/Cas9, an insertion upstream of ZHX2 was identified as a cause of the human ZHX2 hypomorph state.
Keywords	Nephrology ; Medicine ; R
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Alteration of the Fatty Acid Metabolism in the Rat Kidney Caused by the Injection of Serum from Patients with Collapsing Glomerulopathy

Elizabeth Soria-Castro / Verónica Guarner-Lans / María Elena Soto / María del Carmen Avila-Casado / Linaloe Manzano Pech / Israel Pérez-Torres

Biomedicines, Vol 8, Iss 388, p

2020 Volume 388

Abstract	Patients with collapsing glomerulopathy (CG) have marked proteinuria that rapidly progresses to chronic renal failure. In this study, we investigated if the nephropathy produced in a rat model by the injection of serum from CG patients induced alterations in fatty acid (FA) metabolism. Twenty-four female Sprague-Dawley rats were divided into four groups of six rats each: Group I, control rats (C); Group II, rats that received injections of 1 mL of 0.9% NaCl saline solution (SS); Group III, rats injected with 25 mg/mL of serum from healthy subjects (HS); and Group IV, rats injected with 25 mg/mL of serum from CG patients. In all groups, the systolic blood pressure (SBP), proteinuria, creatinine clearance (CC), cholesterol and total FA composition in the kidney and serum were evaluated. The administration of serum from CG patients to rats induced glomerular collapse, proteinuria, reduced CC and elevated SBP ( p ≤ 0.01) in comparison with the C, SS and HS rats. The FA composition of the serum of rats that received the CG serum showed an increase in palmitic acid (PA) and a decrease in arachidonic acid (AA) when compared to serum from HS ( p ≤ 0.02). In rats receiving the CG serum, there was also a decrease in the AA in the kidney but there was an increase in the PA in the serum and kidney ( p ≤ 0.01). These results suggest that the administration of serum from CG patients to rats induces alterations in FA metabolism including changes in PA and in AA, which are precursors for the biosynthesis of the prostaglandins that are involved in the elevation of SBP and in renal injury. These changes may contribute to collapsing glomerulopathy disease.
Keywords	collapsing glomerulopathy ; systolic blood pressure ; fatty acids ; proteinuria ; Biology (General) ; QH301-705.5
Subject code	630
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Vascular Hyperactivity in the Rat Renal Aorta Participates in the Association between Immune Complex-Mediated Glomerulonephritis and Systemic Hypertension

Israel Pérez-Torres / Bernardo Moguel-González / Elizabeth Soria-Castro / Verónica Guarner-Lans / María del Carmen Avila-Casado / Teresa Imelda Fortoul Vander Goes

International Journal of Environmental Research and Public Health, Vol 15, Iss 6, p

2018 Volume 1164

Abstract: Introduction: systemic hypertension (SH) involving endothelial dysfunction contributes to immune complex-mediated glomerulonephritis (ICGN). Objective, we demonstrate a relationship between ICGN and SH by analyzing vascular reactivity in renal aortic ... ...

Abstract	Introduction: systemic hypertension (SH) involving endothelial dysfunction contributes to immune complex-mediated glomerulonephritis (ICGN). Objective, we demonstrate a relationship between ICGN and SH by analyzing vascular reactivity in renal aortic rings. Methods: 48 male Wistar rats were divided into four groups: (a) control (C); (b) injected with bovine serum albumin (BSA); (c) receiving 200 mg/L NAME (an analog of arginine that inhibits NO production) in drinking water; and (d) receiving BSA and 200 mg/L NAME. Rats were pre-immunized subcutaneously with BSA and Freund’s adjuvant. After 10 days, groups (b) and (c) received 1 mg/mL of BSA in saline intravenous (IV) daily for 35 days. The urine of 24 h was measured at days 0, 15, 30 and 45. Results: vascular reactivity to norepinephrine (NE), acetylcholine (Ach) and NAME were tested. Creatinine clearance, vasodilatation, eNOS and elastic fibers were diminished (p ≤ 0.001). Blood pressure, vasoconstriction, iNOS were increased, and glomerular alterations were observed in groups (b), (c) and (d) when compared to group (a) (p ≤ 0.001). Conclusions: SH contributes to the development of progressive renal disease in ICGN. Alterations of the vascular reactivity are mediated by the endothelium in the renal aorta. Thus, the endothelium plays a determinant role in the production of vasoactive substances such as NO during this process.
Keywords	glomerulonephritis ; hypertension ; reactivity vascular ; eNOS ; iNOS ; immune complex ; Medicine ; R
Subject code	630
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Rethinking Lupus Nephritis Classification on a Molecular Level

Salem Almaani / Stephenie D. Prokopec / Jianying Zhang / Lianbo Yu / Carmen Avila-Casado / Joan Wither / James W. Scholey / Valeria Alberton / Ana Malvar / Samir V. Parikh / Paul C. Boutros / Brad H. Rovin / Heather N. Reich

Journal of Clinical Medicine, Vol 8, Iss 10, p

2019 Volume 1524

Abstract: The International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus nephritis (LN) classification is under reconsideration, given challenges with inter-rater reliability and resultant inconsistent relationship with treatment response. ... ...

Abstract	The International Society of Nephrology/Renal Pathology Society (ISN/RPS) lupus nephritis (LN) classification is under reconsideration, given challenges with inter-rater reliability and resultant inconsistent relationship with treatment response. Integration of molecular classifiers into histologic evaluation can improve diagnostic precision and identify therapeutic targets. This study described the relationship between histological and molecular phenotypes and clinical responses in LN. Renal compartmental mRNA abundance was measured in 54 biopsy specimens from LN patients and correlated to ISN/RPS classification and individual histologic lesions. A subset of transcripts was also evaluated in sequential biopsies of a separate longitudinal cohort of 36 patients with paired samples obtained at the time of flare and at follow up. Unsupervised clustering based on mRNA abundance did not demonstrate a relationship with the (ISN/RPS) classification, nor did univariate statistical analysis. Exploratory analyses suggested a correlation with individual histologic lesions. Glomerular FN1 (fibronectin), SPP1 (secreted phosphoprotein 1), and LGALS3 (galectin 3) abundance correlated with disease activity and changed following treatment. Exploratory analyses suggested relationships between specific transcripts and individual histologic lesions, with the important representation of interferon-regulated genes. Our findings suggested that the current LN classification could be refined by the inclusion of molecular descriptors. Combining molecular and pathologic kidney biopsy phenotypes may hold promise to better classify disease and identify actionable treatment targets and merits further exploration in larger cohorts.
Keywords	lupus nephritis ; ISN/RPS classification ; mRNA ; Medicine ; R
Subject code	610
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Detection of IS6110 and HupB gene sequences of Mycobacterium tuberculosis and bovis in the aortic tissue of patients with Takayasu's arteritis.

Soto, María Elena / Del Carmen Ávila-Casado, Ma / Huesca-Gómez, Claudia / Alarcon, Gilberto Vargas / Castrejon, Vicente / Soto, Virgilia / Hernandez, Sergio / Espinola-Zavaleta, Nilda / Vallejo, Maite / Reyes, Pedro A / Gamboa, Ricardo

BMC infectious diseases

2012 Volume 12, Page(s) 194

Abstract: Background: Takayasu's arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, ... ...

Abstract	Background: Takayasu's arteritis (TA) is a chronic inflammatory disease affecting the large arteries and their branches; its etiology is still unknown. In individuals suffering from TA, arterial inflammation progresses to stenosis and/or occlusion, leading to organ damage and affecting survival. Relation of TA with Mycobacterium tuberculosis has been known, but there have been only a few systematic studies focusing on this association. The IS6110 sequence identifies the Mycobacterium tuberculosis complex and the HupB establishes the differences between M. tuberculosis and M. bovis. Our objective was to search the presence of IS6110 and HupB genes in aorta of patients with TA. Methods: We analyzed aorta tissues embedded in paraffin from 5760 autopsies obtained from our institution, we divided the selected samples as cases and controls; Cases: aortic tissues of individuals with Takayasu's arteritis. Control positive: aortic tissues (with tuberculosis disease confirmed) and control negative with other disease aortic (atherosclerosis). Results: Of 181 selected aorta tissues, 119 fulfilled the corresponding criteria for TA, TB or atherosclerosis. Thus 33 corresponded to TA, 33 to tuberculosis (TB) and 53 to atherosclerosis. The mean age was 22 ± 13, 41 ± 19, and 57 ± 10, respectively. IS6110 and HupB sequences were detected in 70% of TA tissues, 82% in tuberculosis, and in 32% with atherosclerosis. Important statistical differences between groups with TA, tuberculosis versus atherosclerosis (p = 0.004 and 0.0001, respectively) were found. Conclusion: We identified a higher frequency of IS6110 and HupB genes in aortic tissues of TA patients. This data suggests that arterial damage could occur due to previous infection with M. tuberculosis.
MeSH term(s)	Adolescent ; Adult ; Aged ; Aorta/metabolism ; Aorta/microbiology ; Bacterial Proteins/metabolism ; Child ; Female ; Histones/metabolism ; Humans ; In Vitro Techniques ; Male ; Middle Aged ; Mycobacterium bovis/metabolism ; Mycobacterium tuberculosis/metabolism ; Takayasu Arteritis/metabolism ; Takayasu Arteritis/microbiology ; Young Adult
Chemical Substances	Bacterial Proteins ; Histones ; HupB protein, Mycobacterium tuberculosis
Language	English
Publishing date	2012-08-20
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1471-2334
ISSN (online)	1471-2334
DOI	10.1186/1471-2334-12-194
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Article: Chronic exposure to high levels of particulate air pollution and small airway remodeling.

Churg, Andrew / Brauer, Michael / del Carmen Avila-Casado, Maria / Fortoul, Teresa I / Wright, Joanne L

Environmental health perspectives

2003 Volume 111, Issue 5, Page(s) 714–718

Abstract: Recent evidence suggests that chronic exposure to high levels of ambient particulate matter (PM) is associated with decreased pulmonary function and the development of chronic airflow obstruction. To investigate the possible role of PM-induced ... ...

Abstract	Recent evidence suggests that chronic exposure to high levels of ambient particulate matter (PM) is associated with decreased pulmonary function and the development of chronic airflow obstruction. To investigate the possible role of PM-induced abnormalities in the small airways in these functional changes, we examined histologic sections from the lungs of 20 women from Mexico City, a high PM locale. All subjects were lifelong residents of Mexico City, were never-smokers, never had occupational dust exposure, and never used biomass fuel for cooking. Twenty never-smoking, non-dust-exposed subjects from Vancouver, British Columbia, Canada, a low PM region, were used as a control. By light microscopy, abnormal small airways with fibrotic walls and excess muscle, many containing visible dust, were present in the Mexico City lungs. Formal grading analysis confirmed the presence of significantly greater amounts of fibrous tissue and muscle in the walls of the airways in the Mexico City compared with the Vancouver lungs. Electron microscopic particle burden measurements on four cases from Mexico City showed that carbonaceous aggregates of ultrafine particles, aggregates likely to be combustion products, were present in the airway mucosa. We conclude that PM penetrates into and is retained in the walls of small airways, and that, even in nonsmokers, long-term exposure to high levels of ambient particulate pollutants is associated with small airway remodeling. This process may produce chronic airflow obstruction.
MeSH term(s)	Aged ; Air Pollutants/adverse effects ; Airway Obstruction/etiology ; Airway Obstruction/pathology ; Autopsy ; British Columbia ; Cities ; Environmental Exposure ; Female ; Humans ; Mexico ; Middle Aged ; Particle Size ; Pulmonary Alveoli/pathology ; Pulmonary Disease, Chronic Obstructive/etiology ; Smoking ; Urban Population
Chemical Substances	Air Pollutants
Language	English
Publishing date	2003-05
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/ehp.6042
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Article ; Online: The Application of Digital Pathology to Improve Accuracy in Glomerular Enumeration in Renal Biopsies.

Avi Z Rosenberg / Matthew Palmer / Lino Merlino / Jonathan P Troost / Adil Gasim / Serena Bagnasco / Carmen Avila-Casado / Duncan Johnstone / Jeffrey B Hodgin / Catherine Conway / Brenda W Gillespie / Cynthia C Nast / Laura Barisoni / Stephen M Hewitt

PLoS ONE, Vol 11, Iss 6, p e

2016 Volume 0156441

Abstract: In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent ... ...

Abstract	In renal biopsy reporting, quantitative measurements, such as glomerular number and percentage of globally sclerotic glomeruli, is central to diagnostic accuracy and prognosis. The aim of this study is to determine the number of glomeruli and percent globally sclerotic in renal biopsies by means of registration of serial tissue sections and manual enumeration, compared to the numbers in pathology reports from routine light microscopic assessment.We reviewed 277 biopsies from the Nephrotic Syndrome Study Network (NEPTUNE) digital pathology repository, enumerating 9,379 glomeruli by means of whole slide imaging. Glomerular number and the percentage of globally sclerotic glomeruli are values routinely recorded in the official renal biopsy pathology report from the 25 participating centers. Two general trends in reporting were noted: total number per biopsy or average number per level/section. Both of these approaches were assessed for their accuracy in comparison to the analogous numbers of annotated glomeruli on WSI.The number of glomeruli annotated was consistently higher than those reported (p<0.001); this difference was proportional to the number of glomeruli. In contrast, percent globally sclerotic were similar when calculated on total glomeruli, but greater in FSGS when calculated on average number of glomeruli (p<0.01). The difference in percent globally sclerotic between annotated and those recorded in pathology reports was significant when global sclerosis is greater than 40%.Although glass slides were not available for direct comparison to whole slide image annotation, this study indicates that routine manual light microscopy assessment of number of glomeruli is inaccurate, and the magnitude of this error is proportional to the total number of glomeruli.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2016-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Aldosterone synthase gene polymorphism and renal histopathologic changes in kidney transplant patients receiving a calcineurin inhibitor

Patricia C Ruiz-Palacios / Francisco E Rodríguez-Castellanos / Eduardo Mancilla-Urrea / María Del Carmen Ávila-Casado / Mónica X Inofuentes-Rivero / Francisco Rodriguez-Illana / José M Fragoso / Gilberto Vargas-Alarcón

Journal of the Renin-Angiotensin-Aldosterone System, Vol

2014 Volume 15

Abstract: Introduction: Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. The objective of this study was to assess aldosterone ... ...

Abstract	Introduction: Aldosterone participates in the pathogenesis of calcineurin inhibitor nephrotoxicity (CIN), producing renal vasoconstriction and transforming growth factor beta (TGFß) expression. The objective of this study was to assess aldosterone polymorphisms and relationships to plasma aldosterone levels and the development of renal histological lesions in kidney transplant patients. Material and methods: Patients with kidney graft biopsy were divided according to the presence or absence of CIN. We determined aldosterone synthase (AS) -344 T/C and int 2 W/C gene polymorphisms and plasma aldosterone levels. Histological, biochemical and clinical variables were measured. Results: Calcineurin inhibitor (CI) levels were significantly higher in patients with the int 2 WW genotype than in patients with WC or CC genotypes. There was a greater degree of interstitial fibrosis in patients with int 2 CC genotype. No relationship was found between the different polymorphisms and a higher degree and/or frequency of CIN. There was also no relationship with plasma aldosterone levels. Conclusion: The frequency of the different polymorphisms studied was not related to plasma aldosterone levels or the development of CIN; however, the int 2 CC genotype was related to a greater degree of interstitial fibrosis, whereas the WW genotype was related to higher CI serum levels.
Keywords	Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2014-09-01T00:00:00Z
Publisher	Hindawi - SAGE Publishing
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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