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[PMID]: 25776801
[Au] Autor:Lacroix J; Hébert PC; Fergusson DA; Tinmouth A; Cook DJ; Marshall JC; Clayton L; McIntyre L; Callum J; Turgeon AF; Blajchman MA; Walsh TS; Stanworth SJ; Campbell H; Capellier G; Tiberghien P; Bardiaux L; van de Watering L; van der Meer NJ; Sabri E; Vo D; ABLE Investigators and the Canadian Critical Care Trials Group
[Ad] Address:From Centre Hospitalier Universitaire (CHU) Sainte-Justine, Université de Montréal (J.L., L.C.) and Centre de Recherche du Centre Hospitalier de l'Université de Montréal, Montreal (P.C.H.), Ottawa Hospital Research Institute, University of Ottawa, Ottawa (D.A.F., A.T., L.M., E.S., D.V.), McMaster University, Hamilton, ON (D.J.C., M.A.B.), University of Toronto, Toronto (J.C.M., J.C.), and Centre de Recherche du CHU de Québec, Université Laval, Quebec, QC (A.F.T.) - all in Canada; University of Edinburgh (T.S.W.) and NHS Blood and Transplant-Oxford University Hospitals NHS Trust, University of Oxford, Oxford (S.J.S., H.C.) - both in the United Kingdom; Université de Franche-Comté, Besançon (G.C., P.T.) and Établissement Français du Sang, La Plaine St. Denis (P.T., L.B.) - both in France; and Sanquin Blood Supply, Amsterdam (L.W.), Amphia Hospital, Breda and Oosterhout (N.J.M.), and TIAS School for Business and Society-Tilburg University, Tilburg (N.J.M.) - all in the Netherlands.
[Ti] Title:Age of transfused blood in critically ill adults.
[So] Source:N Engl J Med;372(15):1410-8, 2015 Apr 9.
[Is] ISSN:1533-4406
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:Background Fresh red cells may improve outcomes in critically ill patients by enhancing oxygen delivery while minimizing the risks of toxic effects from cellular changes and the accumulation of bioactive materials in blood components during prolonged storage. Methods In this multicenter, randomized, blinded trial, we assigned critically ill adults to receive either red cells that had been stored for less than 8 days or standard-issue red cells (the oldest compatible units available in the blood bank). The primary outcome measure was 90-day mortality. Results Between March 2009 and May 2014, at 64 centers in Canada and Europe, 1211 patients were assigned to receive fresh red cells (fresh-blood group) and 1219 patients were assigned to receive standard-issue red cells (standard-blood group). Red cells were stored a mean (±SD) of 6.1±4.9 days in the fresh-blood group as compared with 22.0±8.4 days in the standard-blood group (P<0.001). At 90 days, 448 patients (37.0%) in the fresh-blood group and 430 patients (35.3%) in the standard-blood group had died (absolute risk difference, 1.7 percentage points; 95% confidence interval [CI], -2.1 to 5.5). In the survival analysis, the hazard ratio for death in the fresh-blood group, as compared with the standard-blood group, was 1.1 (95% CI, 0.9 to 1.2; P=0.38). There were no significant between-group differences in any of the secondary outcomes (major illnesses; duration of respiratory, hemodynamic, or renal support; length of stay in the hospital; and transfusion reactions) or in the subgroup analyses. Conclusions Transfusion of fresh red cells, as compared with standard-issue red cells, did not decrease the 90-day mortality among critically ill adults. (Funded by the Canadian Institutes of Health Research and others; Current Controlled Trials number, ISRCTN44878718 .).
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:AIM; IM
[St] Status:In-Data-Review
[do] DOI:10.1056/NEJMoa1500704

  2 / 1877178 MEDLINE  
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[PMID]: 24836048
[Au] Autor:Graci V; Salsich GB
[Ad] Address:University of Maryland School of Medicine, Department of Neurology, USA. Electronic address: vgraci@som.umaryland.edu.
[Ti] Title:Trunk and lower extremity segment kinematics and their relationship to pain following movement instruction during a single-leg squat in females with dynamic knee valgus and patellofemoral pain.
[So] Source:J Sci Med Sport;18(3):343-7, 2015 May.
[Is] ISSN:1878-1861
[Cp] Country of publication:Australia
[La] Language:eng
[Ab] Abstract:OBJECTIVES: To understand how instructing females with patellofemoral pain to correct dynamic knee valgus affects pelvis, femur, tibia and trunk segment kinematics. To determine if pain reduction in the corrected condition was associated with improved segment kinematics. DESIGN: Cross-sectional. METHODS: A 3D-motion capture system was used to collect multi-joint kinematics on 20 females with dynamic knee valgus and patellofemoral pain during a single-leg squat in two conditions: usual movement pattern, and corrected dynamic knee valgus. During each condition pain was assessed using a visual analog scale. Pelvis, femur, tibia and trunk kinematics in the frontal and transverse planes were compared between conditions using a paired T-test. Pearson correlation coefficients were generated between visual analog scale score and the kinematic variables in the corrected condition. RESULTS: In the corrected condition subjects had increased lateral flexion of the pelvis toward the weight-bearing limb (p<0.001), decreased femoral adduction (p=0.001) and internal rotation (p=0.01). A trend toward decreased tibial internal rotation (p=0.057) and increased trunk lateral flexion toward the weight-bearing limb (p=0.055) was also found. Lower pain levels were associated with less femoral internal rotation (p=0.04) and greater trunk lateral flexion toward the weight-bearing limb (p=0.055). CONCLUSIONS: Decreased hip adduction after instruction was comprised of motion at both the pelvis and femur. Decreased pain levels were associated with lower extremity segment kinematics moving in the direction opposite to dynamic knee valgus. These results increase our understanding of correction strategies used by females with patellofemoral pain and provide insight for rehabilitation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  3 / 1877178 MEDLINE  
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[PMID]: 25652900
[Au] Autor:Wang K; Pan D; Schmieder AH; Senpan A; Hourcade DE; Pham CT; Mitchell LM; Caruthers SD; Cui G; Wickline SA; Shen B; Lanza GM
[Ad] Address:Department of Radiology, the Fourth Hospital of Harbin Medical University Molecular Imaging Center of Harbin Medical University, Harbin, China; Division of Cardiology, Washington University School of Medicine, St. Louis, MO, USA....
[Ti] Title:Synergy between surface and core entrapped metals in a mixed manganese-gadolinium nanocolloid affords safer MR imaging of sparse biomarkers.
[So] Source:Nanomedicine;11(3):601-9, 2015 Apr.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: High-relaxivity T1-weighted (T1w) MR molecular imaging nanoparticles typically present high surface gadolinium payloads that can elicit significant acute complement activation (CA). The objective of this research was to develop a high T1w contrast nanoparticle with improved safety. We report the development, optimization, and characterization of a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC; 138±10 (Dav)/nm; PDI: 0.06; zeta: -27±2mV). High r1 particulate relaxivity with minute additions of Gd-DOTA-lipid conjugate to the MnOL nanocolloid surface achieved an unexpected paramagnetic synergism. This hybrid MnOL-Gd NC provided optimal MR TSE signal intensity at 5nM/voxel and lower levels consistent with the level expression anticipated for sparse biomarkers, such as neovascular integrins. MnOL NC produced optimal MR TSE signal intensity at 10nM/voxel concentrations and above. Importantly, MnOL-Gd NC avoided acute CA in vitro and in vivo while retaining minimal transmetallation risk. FROM THE CLINICAL EDITOR: The authors developed a gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) in this study. These were used as a high-relaxivity paramagnetic MR molecular imaging agent in experimental models. It was shown that MnOL-Gd NC could provide high T1w MR contrast for targeted imaging. As the level of gadolinium used was reduced, there was also reduced risk of systemic side effects from complement activation.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  4 / 1877178 MEDLINE  
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[PMID]: 25652897
[Au] Autor:Wang K; Pan D; Schmieder AH; Senpan A; Caruthers SD; Cui G; Allen JS; Zhang H; Shen B; Lanza GM
[Ad] Address:Department of Radiology, the Fourth Hospital of Harbin Medical University and Molecular Imaging Center of Harbin Medical University, Harbin, China; Division of Cardiology, Washington University School of Medicine, St. Louis, MO, USA....
[Ti] Title:Atherosclerotic neovasculature MR imaging with mixed manganese-gadolinium nanocolloids in hyperlipidemic rabbits.
[So] Source:Nanomedicine;11(3):569-78, 2015 Apr.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: A high r1 relaxivity manganese-gadolinium nanocolloid (αvß3-MnOL-Gd NC) was developed and effectively detected atherosclerotic angiogenesis in rabbits fed cholesterol-rich diets for 12months using a clinical MRI scanner (3T). 3D mapping of neovasculature signal intensity revealed the spatial coherence and intensity of plaque angiogenic expansion, which may, with other high risk MR bioindicators, help identify high-risk patients with moderate (40% to 60%) vascular stenosis. Microscopy confirmed the predominant media and plaque distribution of fluorescent αvß3-MnOL-Gd NC, mirroring the MR data. An expected close spatial association of αvß3-integrin neovasculature and macrophages was noted, particularly within plaque shoulder regions. Manganese oleate bioelimination occurred via the biliary system into feces. Gd-DOTA was eliminated through the bile-fecal and renal excretion routes. αvß3-MnOL-Gd NC offers an effective vehicle for T1w neovascular imaging in atherosclerosis. FROM THE CLINICAL EDITOR: Cerebrovascular accidents are a leading cause of mortality and morbidity worldwide. The acute formation of thrombus following atherosclerotic plaque rupture has been well recognized as the etiology of stroke. The authors studied microanatomical features of vulnerable atherosclerotic plaque in this article, in an attempt to identify those with high risk of rupture. Gadolinium-manganese hybrid nanocolloid (MnOL-Gd NC) was developed as a novel contrast agent for MRI. They show that this agent is effective in providing neovascular imaging.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  5 / 1877178 MEDLINE  
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[PMID]: 25596079
[Au] Autor:Robbins GR; Roberts RA; Guo H; Reuter K; Shen T; Sempowski GD; McKinnon KP; Su L; DeSimone JM; Ting JP
[Ad] Address:Department of Microbiology and Immunology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA; Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA....
[Ti] Title:Analysis of human innate immune responses to PRINT fabricated nanoparticles with cross validation using a humanized mouse model.
[So] Source:Nanomedicine;11(3):589-99, 2015 Apr.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: Ideal nanoparticle (NP)-based drug and vaccine delivery vectors should be free of inherent cytotoxic or immunostimulatory properties. Therefore, determining baseline immune responses to nanomaterials is of utmost importance when designing human therapeutics. We characterized the response of human immune cells to hydrogel NPs fabricated using Particle Replication in Non-wetting Templates (PRINT) technology. We found preferential NP uptake by primary CD14(+) monocytes, which was significantly reduced upon PEGylation of the NP surface. Multiplex cytokine analysis of NP treated primary human peripheral blood mononuclear cells suggests that PRINT based hydrogel NPs do not evoke significant inflammatory responses nor induce cytotoxicity or complement activation. We furthered these studies using an in vivo humanized mouse model and similarly found preferential NP uptake by human CD14(+) monocytes without systemic inflammatory cytokine responses. These studies suggest that PRINT hydrogel particles form a desirable platform for vaccine and drug delivery as they neither induce inflammation nor toxicity. FROM THE CLINICAL EDITOR: The authors here fabricated hydrogel nanorods using the PRINT (Particle Replication In Nonwetting Templates) fabrication process. They tested the interaction of human immune cells with these particles and found no immunoreactivity. This finding would suggest that monodisperse PRINT particles of identical shape and size could serve a variety of clinical applications.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  6 / 1877178 MEDLINE  
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[PMID]: 25596077
[Au] Autor:Pita-Thomas W; Steketee MB; Moysidis SN; Thakor K; Hampton B; Goldberg JL
[Ad] Address:Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA; Department of Anatomy and Neurobiology, Washington University, St. Louis, MO, USA....
[Ti] Title:Promoting filopodial elongation in neurons by membrane-bound magnetic nanoparticles.
[So] Source:Nanomedicine;11(3):559-67, 2015 Apr.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: Filopodia are 5-10µm long processes that elongate by actin polymerization, and promote axon growth and guidance by exerting mechanical tension and by molecular signaling. Although axons elongate in response to mechanical tension, the structural and functional effects of tension specifically applied to growth cone filopodia are unknown. Here we developed a strategy to apply tension specifically to retinal ganglion cell (RGC) growth cone filopodia through surface-functionalized, membrane-targeted superparamagnetic iron oxide nanoparticles (SPIONs). When magnetic fields were applied to surface-bound SPIONs, RGC filopodia elongated directionally, contained polymerized actin filaments, and generated retrograde forces, behaving as bona fide filopodia. Data presented here support the premise that mechanical tension induces filopodia growth but counter the hypothesis that filopodial tension directly promotes growth cone advance. Future applications of these approaches may be used to induce sustained forces on multiple filopodia or other subcellular microstructures to study axon growth or cell migration. FROM THE CLINICAL EDITOR: Mechanical tension to the tip of filopodia is known to promote axonal growth. In this article, the authors used superparamagnetic iron oxide nanoparticles (SPIONs) targeted specifically to membrane molecules, then applied external magnetic field to elicit filopodial elongation, which provided a tool to study the role of mechanical forces in filopodia dynamics and function.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  7 / 1877178 MEDLINE  
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[PMID]: 25596075
[Au] Autor:Moysidis SN; Alvarez-Delfin K; Peschansky VJ; Salero E; Weisman AD; Bartakova A; Raffa GA; Merkhofer RM; Kador KE; Kunzevitzky NJ; Goldberg JL
[Ad] Address:Bascom Palmer Eye Institute and Interdisciplinary Stem Cell Institute, University of Miami Miller School of Medicine, Miami, FL, USA....
[Ti] Title:Magnetic field-guided cell delivery with nanoparticle-loaded human corneal endothelial cells.
[So] Source:Nanomedicine;11(3):499-509, 2015 Apr.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: To improve the delivery and integration of cell therapy using magnetic cell guidance for replacement of corneal endothelium, here we assess magnetic nanoparticles' (MNPs') effects on human corneal endothelial cells (HCECs) in vitro. Biocompatible, 50nm superparamagnetic nanoparticles endocytosed by cultured HCECs induced no short- or long-term change in viability or identity. Assessment of guidance of the magnetic HCECs in the presence of different magnet shapes and field strengths showed a 2.4-fold increase in delivered cell density compared to gravity alone. After cell delivery, HCECs formed a functional monolayer, with no difference in tight junction formation between MNP-loaded and control HCECs. These data suggest that nanoparticle-mediated magnetic cell delivery may increase the efficiency of cell delivery without compromising HCEC survival, identity or function. Future studies may assess the safety and efficacy of this therapeutic modality in vivo. FROM THE CLINICAL EDITOR: The authors show in this article that magnetic force facilitates the delivery of human corneal endothelial cells loaded by superparamagnetic nanoparticles to cornea, without changing their morphology, identity or functional properties. This novel idea can potentially have vast impact in the treatment of corneal endothelial dystrophies by providing self-endothelial cells after ex-vivo expansion.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  8 / 1877178 MEDLINE  
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[PMID]: 25461281
[Au] Autor:Dam DH; Culver KS; Kandela I; Lee RC; Chandra K; Lee H; Mantis C; Ugolkov A; Mazar AP; Odom TW
[Ad] Address:Department of Chemistry, Northwestern University, Evanston, IL, USA....
[Ti] Title:Biodistribution and in vivo toxicity of aptamer-loaded gold nanostars.
[So] Source:Nanomedicine;11(3):671-9, 2015 Apr.
[Is] ISSN:1549-9642
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:UNLABELLED: This paper reports an in vivo evaluation of toxicology and biodistribution of a highly anisotropic Au nanoconstruct composed of a gold nanostar (AuNS) core and a ligand shell of a G-quadruplex DNA aptamer AS1411 (Apt) supporting both targeting and therapy capabilities. We examined the toxicity of the nanoconstructs (Apt-AuNS) at four different injected concentrations. At the highest dose tested (48 mg/kg), maximal tolerated dose was not reached. Clinical pathology showed no apparent signs of acute toxicity. Interestingly, the nanoconstructs circulated longer in female rats compared to male rats. In two different tumor models, the biodistribution of Apt-AuNS, especially tumor accumulation, was different. Accumulation of Apt-AuNS was 5 times higher in invasive breast cancer tumors compared to fibrosarcoma tumors. These results provide insight on identifying a tumor model and nanoconstruct for in vivo studies, especially when an in vitro therapeutic response is observed in multiple cancer cell lines. FROM THE CLINICAL EDITOR: This study investigated the toxicity and distribution of aptamer loaded gold nanostars in a rodent model of invasive breast cancer and fibrosarcoma. Acute toxicity was not identified even in the highest studied doses. Fivefold accumulation was demonstrated in the breast cancer model compared to the fibrosarcoma model. Studies like this are critically important in further clarifying the potential therapeutic use of these nanoconstructs, especially when ex vivo effects are clearly demonstrated.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review

  9 / 1877178 MEDLINE  
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[PMID]: 25474345
[Au] Autor:Zaneveld J; Siddiqui S; Li H; Wang X; Wang H; Wang K; Li H; Ren H; Lopez I; Dorfman A; Khan A; Wang F; Salvo J; Gelowani V; Li Y; Sui R; Koenekoop R; Chen R
[Ad] Address:1] Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, USA [2] Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas, USA....
[Ti] Title:Comprehensive analysis of patients with Stargardt macular dystrophy reveals new genotype-phenotype correlations and unexpected diagnostic revisions.
[So] Source:Genet Med;17(4):262-70, 2015 Apr.
[Is] ISSN:1530-0366
[Cp] Country of publication:United States
[La] Language:eng
[Ab] Abstract:PURPOSE: Stargardt macular dystrophy (STGD) results in early central vision loss. We sought to explain the genetic cause of STGD in a cohort of 88 patients from three different cultural backgrounds. METHODS: Next-generation sequencing using a novel capture panel was used to search for disease-causing mutations. Patients with undetermined causes were clinically reexamined and tested for copy-number variations as well as intronic mutations. RESULTS: We determined the cause of disease in 67% of our patients. Our analysis identified 35 novel ABCA4 alleles. Eleven patients had mutations in genes not previously reported to cause STGD. Finally, 45% of our patients with unsolved causes had single deleterious mutations in ABCA4, a recessive disease gene. No likely pathogenic copy-number variations were identified. CONCLUSION: This study expands our knowledge of STGD by identifying dozens of novel alleles that cause the disease. The frequency of single mutations in ABCA4 among STGD patients is higher than that among controls, indicating that these mutations contribute to disease. Disease in 11 patients was explained by mutations outside ABCA4, underlining the need to genotype all retinal disease genes to maximize genetic diagnostic rates. Few ABCA4 mutations were observed in our French Canadian patients. This population may contain an unidentified founder mutation. Our results indicate that copy-number variations are unlikely to be a major cause of STGD.Genet Med 17 4, 262-270.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.1038/gim.2014.174

  10 / 1877178 MEDLINE  
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[PMID]: 25750210
[Au] Autor:Whidbey C; Vornhagen J; Gendrin C; Boldenow E; Samson JM; Doering K; Ngo L; Ezekwe EA; Gundlach JH; Elovitz MA; Liggitt D; Duncan JA; Adams Waldorf KM; Rajagopal L
[Ad] Address:Department of Pediatric Infectious Diseases, University of Washington and Seattle Children's Research Institute, Seattle, WA, USA Department of Global Health, University of Washington, Seattle, WA, USA....
[Ti] Title:A streptococcal lipid toxin induces membrane permeabilization and pyroptosis leading to fetal injury.
[So] Source:EMBO Mol Med;7(4):488-505, 2015.
[Is] ISSN:1757-4684
[Cp] Country of publication:England
[La] Language:eng
[Ab] Abstract:Group B streptococci (GBS) are Gram-positive bacteria that cause infections in utero and in newborns. We recently showed that the GBS pigment is hemolytic and increased pigment production promotes bacterial penetration of human placenta. However, mechanisms utilized by the hemolytic pigment to induce host cell lysis and the consequence on fetal injury are not known. Here, we show that the GBS pigment induces membrane permeability in artificial lipid bilayers and host cells. Membrane defects induced by the GBS pigment trigger K(+) efflux leading to osmotic lysis of red blood cells or pyroptosis in human macrophages. Macrophages lacking the NLRP3 inflammasome recovered from pigment-induced cell damage. In a murine model of in utero infection, hyperpigmented GBS strains induced fetal injury in both an NLRP3 inflammasome-dependent and NLRP3 inflammasome-independent manner. These results demonstrate that the dual mechanism of action of the bacterial pigment/lipid toxin leading to hemolysis or pyroptosis exacerbates fetal injury and suggest that preventing both activities of the hemolytic lipid is likely critical to reduce GBS fetal injury and preterm birth.
[Pt] Publication type:JOURNAL ARTICLE
[Em] Entry month:1504
[Cu] Class update date: 150404
[Lr] Last revision date:150404
[Js] Journal subset:IM
[St] Status:In-Data-Review
[do] DOI:10.15252/emmm.201404883


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