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Article ; Online: Critical Care Utilization and Outcomes of Interhospital Medical Transfers at Lower Risk of Death.

Baig, Saqib H / Gorth, Deborah J / Yoo, Erika J

2021 Volume 37, Issue 5, Page(s) 679–685

Abstract: Purpose: To evaluate utilization and mortality outcomes of interhospital transferred critically-ill medical patients with lower predicted risk of hospital mortality.: Materials & methods: Multisite retrospective cohort analysis of patients with Acute ...

Abstract	Purpose: To evaluate utilization and mortality outcomes of interhospital transferred critically-ill medical patients with lower predicted risk of hospital mortality. Materials & methods: Multisite retrospective cohort analysis of patients with Acute Physiology and Chronic Health Evaluation (APACHE) IV-a predicted mortality of ≤20% from 335 ICUs in 208 hospitals in the Philips eICU database between 2014-2015. Differences in length-of-stay (LOS) and mortality between transferred and local patients were evaluated using negative binomial logistic regression and logistic regression, respectively. Stratified analyses were conducted for subgroups of predicted mortality: 0%-5%, 6%-10%, 11%-15%, and 16%-20%. Results: Transfers had a higher risk of longer ICU and hospital LOS across all risk strata (IRR 1.12; 95% CI 1.09-1.16, Conclusions: Interhospital transfer of critically-ill medical patients with lower illness severity is associated with higher ICU and hospital utilization and increased mortality. Better understanding of factors driving patient selection for and characteristics of interhospital transfer for this population will have an impact on ICU resource utilization, care efficiency, and hospital quality.
MeSH term(s)	APACHE ; Critical Care ; Critical Illness/therapy ; Hospital Mortality ; Humans ; Intensive Care Units ; Length of Stay ; Patient Transfer ; Retrospective Studies
Language	English
Publishing date	2021-06-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	632828-3
ISSN	1525-1489 ; 0885-0666
ISSN (online)	1525-1489
ISSN	0885-0666
DOI	10.1177/08850666211022613
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Article ; Online: Gender Disparity in Evaluation of Internal Medicine Clerkship Performance.

Gorth, Deborah J / Magee, Rogan G / Rosenberg, Sarah E / Mingioni, Nina

JAMA network open

2021 Volume 4, Issue 7, Page(s) e2115661

Abstract: Importance: Women studying medicine currently equal men in number, but evidence suggests that men and women might not be evaluated equally throughout their education.: Objective: To examine whether there are differences associated with gender in ... ...

Abstract	Importance: Women studying medicine currently equal men in number, but evidence suggests that men and women might not be evaluated equally throughout their education. Objective: To examine whether there are differences associated with gender in either objective or subjective evaluations of medical students in an internal medicine clerkship. Design, setting, and participants: This single-center retrospective cohort study evaluated data from 277 third-year medical students completing internal medicine clerkships in the 2017 to 2018 academic year at an academic hospital and its affiliates in Pennsylvania. Data were analyzed from September to November 2020. Exposure: Gender, presumed based on pronouns used in evaluations. Main outcomes and measures: Likert scale evaluations of clinical skills, standardized examination scores, and written evaluations were analyzed. Univariate and multivariate linear regression were used to observe trends in measures. Word embeddings were analyzed for narrative evaluations. Results: Analyses of 277 third-year medical students completing an internal medicine clerkship (140 women [51%] with a mean [SD] age of 25.5 [2.3] years and 137 [49%] presumed men with a mean [SD] age of 25.9 [2.7] years) detected no difference in final grade distribution. However, women outperformed men in 5 of 8 domains of clinical performance, including patient interaction (difference, 0.07 [95% CI, 0.04-0.13]), growth mindset (difference, 0.08 [95% CI, 0.01-0.11]), communication (difference, 0.05 [95% CI, 0-0.12]), compassion (difference, 0.125 [95% CI, 0.03-0.11]), and professionalism (difference, 0.07 [95% CI, 0-0.11]). With no difference in examination scores or subjective knowledge evaluation, there was a positive correlation between these variables for both genders (women: r = 0.35; men: r = 0.26) but different elevations for the line of best fit (P < .001). Multivariate regression analyses revealed associations between final grade and patient interaction (women: coefficient, 6.64 [95% CI, 2.16-11.12]; P = .004; men: coefficient, 7.11 [95% CI, 2.94-11.28]; P < .001), subjective knowledge evaluation (women: coefficient, 6.66 [95% CI, 3.87-9.45]; P < .001; men: coefficient, 5.45 [95% CI, 2.43-8.43]; P < .001), reported time spent with the student (women: coefficient, 5.35 [95% CI, 2.62-8.08]; P < .001; men: coefficient, 3.65 [95% CI, 0.83-6.47]; P = .01), and communication (women: coefficient, 6.32 [95% CI, 3.12-9.51]; P < .001; men: coefficient, 4.21 [95% CI, 0.92-7.49]; P = .01). The model based on the men's data also included growth mindset as a significant variable (coefficient, 4.09 [95% CI, 0.67-7.50]; P = .02). For narrative evaluations, words in context with "he or him" and "she or her" differed, with agentic terms used in descriptions of men and personality descriptors used more often for women. Conclusions and relevance: Despite no difference in final grade, women scored higher than men on various domains of clinical performance, and performance in these domains was associated with evaluators' suggested final grade. The content of narrative evaluations significantly differed by student gender. This work supports the hypothesis that how students are evaluated in clinical clerkships is associated with gender.
MeSH term(s)	Adult ; Clinical Clerkship/statistics & numerical data ; Clinical Clerkship/trends ; Cross-Sectional Studies ; Educational Measurement/standards ; Educational Measurement/statistics & numerical data ; Female ; Gender Equity/psychology ; Gender Equity/statistics & numerical data ; Humans ; Internal Medicine/education ; Internal Medicine/statistics & numerical data ; Male ; Middle Aged
Language	English
Publishing date	2021-07-01
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2574-3805
ISSN (online)	2574-3805
DOI	10.1001/jamanetworkopen.2021.15661
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A New Understanding of the Role of IL-1 in Age-Related Intervertebral Disc Degeneration in a Murine Model.

Gorth, Deborah J / Shapiro, Irving M / Risbud, Makarand V

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2019 Volume 34, Issue 8, Page(s) 1531–1542

Abstract: Increased cytokine expression, in particular interleukin-1β (IL-1β), is considered a hallmark of intervertebral disc degeneration. However, the causative relationship between IL-1 and age-dependent degeneration has not been established. To investigate ... ...

Abstract	Increased cytokine expression, in particular interleukin-1β (IL-1β), is considered a hallmark of intervertebral disc degeneration. However, the causative relationship between IL-1 and age-dependent degeneration has not been established. To investigate the role of IL-1 in driving age-related disc degeneration, we studied the spine phenotype of global IL-1α/β double knockout (IL-1KO) mice at 12 and 20 months. Multiplex ELISA analysis of blood revealed significant reductions in the concentrations of IFN-γ, IL-5, IL-15, TNF-α, IP-10, and a trend of reduced concentrations of IL-10, macrophage inflammatory protein 1α (MIP-1α), keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO), and IL-6. However, the circulating level of MIP-2, a neutrophil chemoattractant, was increased in the IL-1KO. The alterations in systemic cytokine levels coincided with altered bone morphology-IL-1KO mice exhibited significantly thicker caudal cortical bone at 12 and 20 months. Despite these systemic inflammatory and bony changes, IL-1 deletion only minimally affected disc health. Both wild-type (WT) and IL-1KO mice showed age-dependent disc degeneration. Unexpectedly, rather than protecting the animals from degeneration, the aging phenotype was more pronounced in IL-1KO animals: knockout mice evidenced significantly more degenerative changes in the annulus fibrosis (AF) together with alterations in collagen type and maturity. At 20 months, there were no changes in nucleus pulposus (NP) extracellular matrix composition or cellular marker expression; however, the IL-1KO NP cells occupied a smaller proportion of the NP compartment that those of WT controls. Taken together, these results show that IL-1 deletion altered the systemic inflammatory environment and vertebral bone morphology. However, instead of protecting discs from age-related disc degeneration, global IL-1 deletion amplified the degenerative phenotype. © 2019 American Society for Bone and Mineral Research.
MeSH term(s)	Aging/genetics ; Aging/metabolism ; Aging/pathology ; Animals ; Disease Models, Animal ; Interleukin-1/deficiency ; Interleukin-1/metabolism ; Intervertebral Disc/metabolism ; Intervertebral Disc/pathology ; Intervertebral Disc Degeneration/genetics ; Intervertebral Disc Degeneration/metabolism ; Intervertebral Disc Degeneration/pathology ; Mice ; Mice, Knockout
Chemical Substances	Interleukin-1
Language	English
Publishing date	2019-05-29
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.3714
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Article ; Online: Differential Effect of Long-Term Systemic Exposure of TNFα on Health of the Annulus Fibrosus and Nucleus Pulposus of the Intervertebral Disc.

Gorth, Deborah J / Ottone, Olivia K / Shapiro, Irving M / Risbud, Makarand V

Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research

2020 Volume 35, Issue 4, Page(s) 725–737

Abstract: The inflammatory cytokine tumor necrosis factor alpha (TNFα) is considered to play a key role in the pathogenesis of intervertebral disc disease. To evaluate the importance of this cytokine we examined the inflammatory environment and spinal phenotype of ...

Abstract	The inflammatory cytokine tumor necrosis factor alpha (TNFα) is considered to play a key role in the pathogenesis of intervertebral disc disease. To evaluate the importance of this cytokine we examined the inflammatory environment and spinal phenotype of 9-month-old human TNFα overexpressing transgenic (hTNFα-TG) mice. The mice evidenced increased circulating levels of interleukin-1β (IL-1β), IL-2, keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO), and monocyte chemoattractant protein-1 (MCP-1) along with thinning of the cortical and trabecular vertebral bone. Surprisingly, although the nucleus pulposus (NP) of these mice was intact and healthy, the caudal annulus fibrosus (AF) evidenced robust cell death and immune cell infiltration. Despite these differences, there were no obvious alterations in the collagen or aggrecan content in the NP and AF. However, there was a reduction in cartilage oligomeric matrix protein (COMP), suggesting destabilization of the AF matrix. Microarray analysis of the NP from hTNFα-TG mice cells revealed minimal changes in global gene expression. These findings lend support to the notion that NP tissue is isolated from systemic inflammation. In contrast, the severe AF phenotype suggests that systemic inflammation interferes with AF health, predisposing discs to herniation as opposed to directly causing NP degeneration. © 2020 American Society for Bone and Mineral Research.
MeSH term(s)	Animals ; Annulus Fibrosus ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Intervertebral Disc Displacement ; Mice ; Nucleus Pulposus
Language	English
Publishing date	2020-01-06
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	632783-7
ISSN	1523-4681 ; 0884-0431
ISSN (online)	1523-4681
ISSN	0884-0431
DOI	10.1002/jbmr.3931
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Article ; Online: Transgenic mice overexpressing human TNF-α experience early onset spontaneous intervertebral disc herniation in the absence of overt degeneration.

Gorth, Deborah J / Shapiro, Irving M / Risbud, Makarand V

Cell death & disease

2018 Volume 10, Issue 1, Page(s) 7

Abstract: There is a well-established link between cytokine expression and the progression of intervertebral disc degeneration. Among these cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are the most commonly studied. To investigate whether ... ...

Abstract	There is a well-established link between cytokine expression and the progression of intervertebral disc degeneration. Among these cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are the most commonly studied. To investigate whether systemic hTNF-α overexpression affects intervertebral disc health, we studied the spine phenotype of Tg197 mice, a widely used hTNF-α transgenic line. These mice were studied at 12-16 weeks of age using comprehensive histochemical and immunohistological analysis of the spinal motion segment. Micro-CT analysis was performed to quantify vertebral trabecular bone architecture. The Tg197 mice evidenced spontaneous annular tears and herniation with increased vascularity in subchondral bone and significant immune cell infiltration. The full-thickness annular tear without nucleus pulposus (NP) extrusion resulted in neutrophil, macrophage, and mast cell infiltration into the disc, whereas the disc with full-thickness tear and pronounced NP herniation showed additional presence of CD4+ and CD8+ T cells. While the observed defects involved failure of the annular, endplate, and vertebral junction, there were no obvious alterations in the collagen or aggrecan content in the NP and annulus fibrosus or the maturity of collagen fibers in Tg197 mice. Despite elevated systemic inflammation and pronounced loss of trabecular bone in the vertebrae, intact Tg197 discs were healthy and showed an increase in NP cell number. The NP cells in intact discs preserved expression of phenotypic markers: CAIII, Glut1, and Krt19. In conclusion, elevated systemic TNF-α increases the susceptibility of mice to spontaneous disc herniation and possibly radiculopathy, without adversely affecting intact intervertebral disc health.
MeSH term(s)	Animals ; CD4-Positive T-Lymphocytes/metabolism ; CD8-Positive T-Lymphocytes/metabolism ; Humans ; Interleukin-1beta/biosynthesis ; Interleukin-1beta/genetics ; Intervertebral Disc Displacement/diagnostic imaging ; Intervertebral Disc Displacement/genetics ; Intervertebral Disc Displacement/metabolism ; Macrophages/metabolism ; Mast Cells/metabolism ; Mice ; Mice, Transgenic ; Neutrophils/metabolism ; Nucleus Pulposus/diagnostic imaging ; Nucleus Pulposus/metabolism ; Tumor Necrosis Factor-alpha/biosynthesis ; Tumor Necrosis Factor-alpha/genetics ; X-Ray Microtomography
Chemical Substances	IL1B protein, mouse ; Interleukin-1beta ; Tumor Necrosis Factor-alpha
Language	English
Publishing date	2018-12-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2541626-1
ISSN	2041-4889 ; 2041-4889
ISSN (online)	2041-4889
ISSN	2041-4889
DOI	10.1038/s41419-018-1246-x
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Article ; Online: Discovery of the drivers of inflammation induced chronic low back pain: from bacteria to diabetes.

Gorth, Deborah J / Shapiro, Irving M / Risbud, Makarand V

Discovery medicine

2015 Volume 20, Issue 110, Page(s) 177–184

Abstract: The intervertebral disc is a unique avascular organ that supports axial skeleton flexion and rotation. The high proteoglycan content of the nucleus pulposus tissue, present at the center of the disc, is pivotal for its mechanical function, distribution ... ...

Abstract	The intervertebral disc is a unique avascular organ that supports axial skeleton flexion and rotation. The high proteoglycan content of the nucleus pulposus tissue, present at the center of the disc, is pivotal for its mechanical function, distribution of compressive loads. Chronic low back pain, a prevalent and costly condition, is strongly associated with disc degeneration. Degenerated discs exhibit high levels of inflammatory cytokines, matrix catabolizing enzymes, and an overall reduction in proteoglycan content. Although the cytokine profile of diseased discs has been widely studied, little is known of what initiates and drives inflammation and subsequent low back pain. Recent studies have shown that anaerobic bacteria are present in a high percentage of painful, herniated discs and long-term treatment with antibiotics resolves symptoms associated with chronic low back pain. It is thought that these anaerobic bacteria in the disc may stimulate inflammation through toll-like receptors to further exacerbate disc degeneration. Despite the promise and novelty of this theory, there are other possible inflammatory mediators that need careful consideration. The metabolic environment associated with diabetes and atypical matrix degradation products also have the ability to activate many of the same inflammatory pathways as seen during microbial infection. It is therefore imperative that the research community must investigate the contribution of all possible drivers of inflammation to address the wide spread problem of discogenic chronic low back pain.
MeSH term(s)	Bacterial Infections/complications ; Diabetes Mellitus/pathology ; Humans ; Inflammation/complications ; Intervertebral Disc Degeneration/pathology ; Low Back Pain/etiology ; Low Back Pain/microbiology ; Metabolic Syndrome/complications ; Toll-Like Receptors/metabolism
Chemical Substances	Toll-Like Receptors
Language	English
Publishing date	2015-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ISSN	1944-7930
ISSN (online)	1944-7930
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Silver nanoparticle toxicity in Drosophila: size does matter.

Gorth, Deborah J / Rand, David M / Webster, Thomas J

International journal of nanomedicine

2011 Volume 6, Page(s) 343–350

Abstract: Background: Consumer nanotechnology is a growing industry. Silver nanoparticles are the most common nanomaterial added to commercially available products, so understanding the influence that size has on toxicity is integral to the safe use of these new ... ...

Abstract	Background: Consumer nanotechnology is a growing industry. Silver nanoparticles are the most common nanomaterial added to commercially available products, so understanding the influence that size has on toxicity is integral to the safe use of these new products. This study examined the influence of silver particle size on Drosophila egg development by comparing the toxicity of both nanoscale and conventional-sized silver particles. Methods: The toxicity assays were conducted by exposing Drosophila eggs to particle concentrations ranging from 10 ppm to 100 ppm of silver. Size, chemistry, and agglomeration of the silver particles were evaluated using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering. Results: This analysis confirmed individual silver particle sizes in the ranges of 20-30 nm, 100 nm, and 500-1200 nm, with similar chemistry. Dynamic light scattering and transmission electron microscope data also indicated agglomeration in water, with the transmission electron microscopic images showing individual particles in the correct size range, but the dynamic light scattering z-average sizes of the silver nanoparticles were 782 ± 379 nm for the 20-30 nm silver nanoparticles, 693 ± 114 nm for the 100 nm silver nanoparticles, and 508 ± 32 nm for the 500-1200 nm silver particles. Most importantly, here we show significantly more Drosophila egg toxicity when exposed to larger, nonnanometer silver particles. Upon exposure to silver nanoparticles sized 20-30 nm, Drosophila eggs did not exhibit a statistically significant (P < 0.05) decrease in their likelihood to pupate, but eggs exposed to larger silver particles (500-1200 nm) were 91% ± 18% less likely to pupate. Exposure to silver nanoparticles reduced the percentage of pupae able to emerge as adults. At 10 ppm of silver particle exposure, only 57% ± 48% of the pupae exposed to 20-30 nm silver particles became adults, whereas 89% ± 25% of the control group became adults, and 94% ± 52% and 91% ± 19% of the 500-1200 nm and 100 nm group, respectively, reached adulthood. Conclusion: This research provides evidence that nanoscale silver particles (<100 nm) are less toxic to Drosophila eggs than silver particles of conventional (>100 nm) size.
MeSH term(s)	Animals ; Dose-Response Relationship, Drug ; Drosophila melanogaster/drug effects ; Life Cycle Stages/drug effects ; Metal Nanoparticles/chemistry ; Metal Nanoparticles/toxicity ; Metal Nanoparticles/ultrastructure ; Microscopy, Electron, Transmission ; Particle Size ; Silver/chemistry ; Silver/toxicity ; Structure-Activity Relationship ; Toxicity Tests
Chemical Substances	Silver (3M4G523W1G)
Language	English
Publishing date	2011-02-11
Publishing country	New Zealand
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2364941-0
ISSN	1178-2013 ; 1176-9114
ISSN (online)	1178-2013
ISSN	1176-9114
DOI	10.2147/IJN.S16881
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Article ; Online: Decreased bacteria activity on Si₃N₄ surfaces compared with PEEK or titanium.

Gorth, Deborah J / Puckett, Sabrina / Ercan, Batur / Webster, Thomas J / Rahaman, Mohamed / Bal, B Sonny

International journal of nanomedicine

2012 Volume 7, Page(s) 4829–4840

Abstract: A significant need exists for orthopedic implants that can intrinsically resist bacterial colonization. In this study, three biomaterials that are used in spinal implants--titanium (Ti), polyether-ether-ketone (PEEK), and silicon nitride (Si₃N₄)--were ... ...

Abstract	A significant need exists for orthopedic implants that can intrinsically resist bacterial colonization. In this study, three biomaterials that are used in spinal implants--titanium (Ti), polyether-ether-ketone (PEEK), and silicon nitride (Si₃N₄)--were tested to understand their respective susceptibility to bacterial infection with Staphylococcus epidermidis, Staphlococcus aureus, Pseudomonas aeruginosa, Escherichia coli and Enterococcus. Specifically, the surface chemistry, wettability, and nanostructured topography of respective biomaterials, and the effects on bacterial biofilm formation, colonization, and growth were investigated. Ti and PEEK were received with as-machined surfaces; both materials are hydrophobic, with net negative surface charges. Two surface finishes of Si₃N₄ were examined: as-fired and polished. In contrast to Ti and PEEK, the surface of Si₃N₄ is hydrophilic, with a net positive charge. A decreased biofilm formation was found, as well as fewer live bacteria on both the as-fired and polished Si₃N₄. These differences may reflect differential surface chemistry and surface nanostructure properties between the biomaterials tested. Because protein adsorption on material surfaces affects bacterial adhesion, the adsorption of fibronectin, vitronectin, and laminin on Ti, PEEK, and Si₃N₄ were also examined. Significantly greater amounts of these proteins adhered to Si₃N₄ than to Ti or PEEK. The findings of this study suggest that surface properties of biomaterials lead to differential adsorption of physiologic proteins, and that this phenomenon could explain the observed in-vitro differences in bacterial affinity for the respective biomaterials. Intrinsic biomaterial properties as they relate to resistance to bacterial colonization may reflect a novel strategy toward designing future orthopedic implants.
MeSH term(s)	Bacterial Adhesion/drug effects ; Bacterial Physiological Phenomena/drug effects ; Cell Survival/drug effects ; Joint Prosthesis/microbiology ; Ketones/chemistry ; Ketones/pharmacology ; Materials Testing ; Polyethylene Glycols/chemistry ; Polyethylene Glycols/pharmacology ; Silicon Compounds/chemistry ; Silicon Compounds/pharmacology ; Surface Properties ; Titanium/chemistry ; Titanium/pharmacology
Chemical Substances	Ketones ; Silicon Compounds ; polyetheretherketone (31694-16-3) ; Polyethylene Glycols (3WJQ0SDW1A) ; Titanium (D1JT611TNE) ; silicon nitride (QHB8T06IDK)
Language	English
Publishing date	2012-09-07
Publishing country	New Zealand
Document type	Comparative Study ; Journal Article
ZDB-ID	2364941-0
ISSN	1178-2013 ; 1176-9114
ISSN (online)	1178-2013
ISSN	1176-9114
DOI	10.2147/IJN.S35190
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Article ; Online: Silver nanoparticle toxicity in Drosophila

Deborah J Gorth / David M Rand / Thomas J Webster

International Journal of Nanomedicine, Vol 2011, Iss default, Pp 343-

size does matter

2011 Volume 350

Abstract: Deborah J Gorth1, David M Rand2, Thomas J Webster11School of Engineering, 2Department of Ecology ...

Abstract	Deborah J Gorth1, David M Rand2, Thomas J Webster11School of Engineering, 2Department of Ecology and Evolutionary Biology, Brown University, Providence, RI, USABackground: Consumer nanotechnology is a growing industry. Silver nanoparticles are the most common nanomaterial added to commercially available products, so understanding the influence that size has on toxicity is integral to the safe use of these new products. This study examined the influence of silver particle size on Drosophila egg development by comparing the toxicity of both nanoscale and conventional-sized silver particles.Methods: The toxicity assays were conducted by exposing Drosophila eggs to particle concentrations ranging from 10 ppm to 100 ppm of silver. Size, chemistry, and agglomeration of the silver particles were evaluated using transmission electron microscopy, X-ray photoelectron spectroscopy, and dynamic light scattering.Results: This analysis confirmed individual silver particle sizes in the ranges of 20–30 nm, 100 nm, and 500–1200 nm, with similar chemistry. Dynamic light scattering and transmission electron microscope data also indicated agglomeration in water, with the transmission electron microscopic images showing individual particles in the correct size range, but the dynamic light scattering z-average sizes of the silver nanoparticles were 782 ± 379 nm for the 20–30 nm silver nanoparticles, 693 ± 114 nm for the 100 nm silver nanoparticles, and 508 ± 32 nm for the 500–1200 nm silver particles. Most importantly, here we show significantly more Drosophila egg toxicity when exposed to larger, nonnanometer silver particles. Upon exposure to silver nanoparticles sized 20–30 nm, Drosophila eggs did not exhibit a statistically significant (P < 0.05) decrease in their likelihood to pupate, but eggs exposed to larger silver particles (500–1200 nm) were 91% ± 18% less likely to pupate. Exposure to silver nanoparticles reduced the percentage of pupae able to emerge as adults. At 10 ppm of silver particle exposure, only 57% ± 48% of ...
Keywords	Medicine (General) ; R5-920
Subject code	550
Language	English
Publishing date	2011-02-01T00:00:00Z
Publisher	Dove Medical Press
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: In vivo retention and bioactivity of IL-1ra microspheres in the rat intervertebral disc: a preliminary investigation.

Gorth, Deborah J / Martin, John T / Dodge, George R / Elliott, Dawn M / Malhotra, Neil R / Mauck, Robert L / Smith, Lachlan J

Journal of experimental orthopaedics

2014 Volume 1, Issue 1, Page(s) 15

Abstract: Background: Inflammatory cytokines such as interleukin-1 beta (IL-1β) contribute to the progression of intervertebral disc degeneration. Previously we demonstrated, in vitro, that by delivering interleukin-1 receptor antagonist (IL-1ra) from poly(lactic ...

Abstract	Background: Inflammatory cytokines such as interleukin-1 beta (IL-1β) contribute to the progression of intervertebral disc degeneration. Previously we demonstrated, in vitro, that by delivering interleukin-1 receptor antagonist (IL-1ra) from poly(lactic co-glycolic acid) (PLGA) microspheres, we could attenuate the degradative effects of IL-1β on the nucleus pulposus (NP) for up to 20 days. The objective of this study was to undertake a preliminary investigation into whether microspheres could be successfully delivered to and retained in the disc in vivo, and whether IL-1ra released from those microspheres remained biologically active. For retention studies, fluorescently-labeled microspheres were delivered to the NPs of rat caudal discs. Rats were sacrificed at time points up to 56 days, and microspheres were localized using fluorescent microscopy. To investigate whether IL-1ra microspheres could effectively inhibit the effects of IL-1β in vivo, four disc levels were allocated to the following treatment groups: intact; saline; IL-1β; or IL-1β + IL-1ra microspheres. Rats were sacrificed after seven days and NP glycosaminoglycan content was measured. Findings: Microspheres were visible in the disc at all time points up to 28 days, and localized to the NP, the annulus fibrosus (AF), or both. Glycosaminoglycan content for discs injected with IL-1β alone was significantly lower than for intact controls. For discs injected with IL-1β along with IL-1ra microspheres, glycosaminoglycan content was not significantly different from intact controls. Conclusions: Microspheres can successfully be delivered to the disc in vivo and retained for a clinically relevant time frame. IL-1ra released from microspheres can effectively prevent IL-1β-induced NP glycosaminoglycan loss in vivo.
Language	English
Publishing date	2014-11-21
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2780021-0
ISSN	2197-1153
ISSN	2197-1153
DOI	10.1186/s40634-014-0015-8
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