134 results on '"Bailey JK"'
Search Results
2. Identification of cutaneous functional units related to burn scar contracture development.
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Richard RL, Lester ME, Miller SF, Bailey JK, Hedman TL, Dewey WS, Greer M, Renz EM, Wolf SE, Blackbourne LH, Richard, Reginald L, Lester, Mark E, Miller, Sidney F, Bailey, J Kevin, Hedman, Travis L, Dewey, William S, Greer, Michelle, Renz, Evan M, Wolf, Steven E, and Blackbourne, Lorne H
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- 2009
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3. Methicillin-resistant Staphylococcus aureus furunculitis in the outpatient burn setting.
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Warner P, Neely A, Bailey JK, Yakuboff KP, Kagan RJ, Warner, Petra, Neely, Alice, Bailey, J Kevin, Yakuboff, Kevin P, and Kagan, Richard J
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- 2009
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4. The extended phenotype of Eucalyptus globulus
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Potts, BM, Vaillancourt, RE, Barbour, RC, O'Reilly-Wapstra, J, Baker, SC, Schweitzer, JA, Bailey, JK, Whitham, TG, Humphreys, JR, Freeman, JS, Potts, BM, Vaillancourt, RE, Barbour, RC, O'Reilly-Wapstra, J, Baker, SC, Schweitzer, JA, Bailey, JK, Whitham, TG, Humphreys, JR, and Freeman, JS
5. Selection by mammalian herbivores on key eucalypt defenses and implications of plant heteroblasty
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O'Reilly-Wapstra, J, Bailey, JK, Humphreys, JR, McArthur, C, Potts, BM, O'Reilly-Wapstra, J, Bailey, JK, Humphreys, JR, McArthur, C, and Potts, BM
6. The extended phenotype of Eucalyptus globulus
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Potts, BM, Vaillancourt, RE, Barbour, RC, O'Reilly-Wapstra, J, Baker, SC, Schweitzer, JA, Bailey, JK, Whitham, TG, Humphreys, JR, Freeman, JS, Potts, BM, Vaillancourt, RE, Barbour, RC, O'Reilly-Wapstra, J, Baker, SC, Schweitzer, JA, Bailey, JK, Whitham, TG, Humphreys, JR, and Freeman, JS
7. Selection by mammalian herbivores on key eucalypt defenses and implications of plant heteroblasty
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O'Reilly-Wapstra, J, Bailey, JK, Humphreys, JR, McArthur, C, Potts, BM, O'Reilly-Wapstra, J, Bailey, JK, Humphreys, JR, McArthur, C, and Potts, BM
8. The extended phenotype of Eucalyptus globulus
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Potts, BM, Vaillancourt, RE, Barbour, RC, O'Reilly-Wapstra, J, Baker, SC, Schweitzer, JA, Bailey, JK, Whitham, TG, Humphreys, JR, Freeman, JS, Potts, BM, Vaillancourt, RE, Barbour, RC, O'Reilly-Wapstra, J, Baker, SC, Schweitzer, JA, Bailey, JK, Whitham, TG, Humphreys, JR, and Freeman, JS
9. Selection by mammalian herbivores on key eucalypt defenses and implications of plant heteroblasty
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O'Reilly-Wapstra, J, Bailey, JK, Humphreys, JR, McArthur, C, Potts, BM, O'Reilly-Wapstra, J, Bailey, JK, Humphreys, JR, McArthur, C, and Potts, BM
10. Respiratory arrest from Ascaris lumbricoides.
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Bailey JK and Warner P
- Abstract
We report here the successful treatment of a 9-year-old boy who suffered a high-voltage electrical injury and a hospital course complicated by unexpected airway obstruction from Ascaris lumbricoides. Review of the literature revealed 4 previous reports of this complication. We also discuss options for prevention and treatment of this rare complication of a common infestation. [ABSTRACT FROM AUTHOR]
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- 2010
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11. Review of practice: feeding tube placement in pediatric burn patients.
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Bailey JK, Gottschlich MM, Allgeier CC, and Kagan RJ
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- 2007
12. Dynamics of microRNA secreted via extracellular vesicles during the maturation of embryonic stem cell-derived retinal pigment epithelium.
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Pollalis D, Nair GKG, Leung J, Bloemhof CM, Bailey JK, Pennington BO, Kelly KR, Khan AI, Yeh AK, Sundaram KS, Clegg DO, Peng CC, Xu L, Georgescu C, Wren JD, and Lee SY
- Abstract
Retinal pigment epithelial (RPE) cells are exclusive to the retina, critically multifunctional in maintaining the visual functions and health of photoreceptors and the retina. Despite their vital functions throughout lifetime, RPE cells lack regenerative capacity, rendering them vulnerable which can lead to degenerative retinal diseases. With advancements in stem cell technology enabling the differentiation of functional cells from pluripotent stem cells and leveraging the robust autocrine and paracrine functions of RPE cells, extracellular vesicles (EVs) secreted by RPE cells hold significant therapeutic potential in supplementing RPE cell activity. While previous research has primarily focused on the trophic factors secreted by RPE cells, there is a lack of studies investigating miRNA, which serves as a master regulator of gene expression. Profiling and defining the functional role of miRNA contained within RPE-secreted EVs is critical as it constitutes a necessary step in identifying the optimal phenotype of the EV-secreting cell and understanding the biological cargo of EVs to develop EV-based therapeutics. In this study, we present a comprehensive profile of miRNA in small extracellular vesicles (sEVs) secreted during RPE maturation following differentiation from human embryonic stem cells (hESCs); early - stage hESC-RPE (20-21 days in culture), mid - stage hESC-RPE (30-31 days in culture) and late - stage hESC-RPE (60-61 days in culture). This exploration is essential for ongoing efforts to develop and optimize EV-based intraocular therapeutics utilizing RPE-secreted EVs, which may significantly impact the function of dysfunctional RPE cells in retinal diseases., Competing Interests: The authors declare no conflicts of interest., (© 2024 The Author(s). Journal of Extracellular Biology published by Wiley Periodicals LLC on behalf of International Society for Extracellular Vesicles.)
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- 2024
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13. Initial Characterization of WDR5B Reveals a Role in the Proliferation of Retinal Pigment Epithelial Cells.
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Bailey JK, Ma D, and Clegg DO
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- Animals, Humans, Cell Differentiation, Cell Line, CRISPR-Cas Systems genetics, Epithelial Cells metabolism, Gene Editing, Intracellular Signaling Peptides and Proteins metabolism, Intracellular Signaling Peptides and Proteins genetics, Cell Proliferation, Retinal Pigment Epithelium metabolism, Retinal Pigment Epithelium cytology
- Abstract
The chromatin-associated protein WDR5 has been widely studied due to its role in histone modification and its potential as a pharmacological target for the treatment of cancer. In humans, the protein with highest sequence homology to WDR5 is encoded by the retrogene WDR5B, which remains unexplored. Here, we used CRISPR-Cas9 genome editing to generate WDR5B knockout and WDR5B-FLAG knock-in cell lines for further characterization. In contrast to WDR5, WDR5B exhibits low expression in pluripotent cells and is upregulated upon neural differentiation. Loss or shRNA depletion of WDR5B impairs cell growth and increases the fraction of non-viable cells in proliferating retinal pigment epithelial (RPE) cultures. CUT&RUN chromatin profiling in RPE and neural progenitors indicates minimal WDR5B enrichment at established WDR5 binding sites. These results suggest that WDR5 and WDR5B exhibit several divergent biological properties despite sharing a high degree of sequence homology.
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- 2024
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14. An evolutionary case for plant rarity: Eucalyptus as a model system.
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Nytko AG, Senior JK, Wooliver RC, O'Reilly-Wapstra J, Schweitzer JA, and Bailey JK
- Abstract
Species rarity is a common phenomenon across global ecosystems that is becoming increasingly more common under climate change. Although species rarity is often considered to be a stochastic response to environmental and ecological constraints, we examined the hypothesis that plant rarity is a consequence of natural selection acting on performance traits that affect a species range size, habitat specificity, and population aggregation; three primary descriptors of rarity. Using a common garden of 25 species of Tasmanian Eucalyptus , we find that the rarest species have 70% lower biomass than common species. Although rare species demonstrate lower biomass, rare species allocated proportionally more biomass aboveground than common species. There is also a negative phylogenetic autocorrelation underlying the biomass of rare and common species, indicating that traits associated with rarity have diverged within subgenera as a result of environmental factors to reach different associated optima. In support of our hypothesis, we found significant positive relationships between species biomass, range size and habitat specificity, but not population aggregation. These results demonstrate repeated convergent evolution of the trait-based determinants of rarity across the phylogeny in Tasmanian eucalypts. Furthermore, the phylogenetically driven patterns in biomass and biomass allocation seen in rare species may be representative of a larger plant strategy, not yet considered, but offering a mechanism as to how rare species continue to persist despite inherent constraints of small, specialized ranges and populations. These results suggest that if rarity can evolve and is related to plant traits such as biomass, rather than a random outcome of environmental constraints, we may need to revise conservation efforts in these and other rare species to reconsider the abiotic and biotic factors that underlie the distributions of rare plant species., Competing Interests: The authors declare that there are no conflicts of interest., (© 2024 The Author(s). Ecology and Evolution published by John Wiley & Sons Ltd.)
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- 2024
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15. Long-term Follow-up of a Phase 1/2a Clinical Trial of a Stem Cell-Derived Bioengineered Retinal Pigment Epithelium Implant for Geographic Atrophy.
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Humayun MS, Clegg DO, Dayan MS, Kashani AH, Rahhal FM, Avery RL, Salehi-Had H, Chen S, Chan C, Palejwala N, Ingram A, Mitra D, Pennington BO, Hinman C, Faynus MA, Bailey JK, Johnson LV, and Lebkowski JS
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- Humans, Aged, Female, Aged, 80 and over, Male, Follow-Up Studies, Tomography, Optical Coherence, Human Embryonic Stem Cells transplantation, Human Embryonic Stem Cells cytology, Stem Cell Transplantation, Treatment Outcome, Geographic Atrophy surgery, Geographic Atrophy physiopathology, Retinal Pigment Epithelium transplantation, Retinal Pigment Epithelium pathology, Visual Acuity physiology
- Abstract
Purpose: To report long-term results from a phase 1/2a clinical trial assessment of a scaffold-based human embryonic stem cell-derived retinal pigmented epithelium (RPE) implant in patients with advanced geographic atrophy (GA)., Design: A single-arm, open-label phase 1/2a clinical trial approved by the United States Food and Drug Administration., Participants: Patients were 69-85 years of age at the time of enrollment and were legally blind in the treated eye (best-corrected visual acuity [BCVA], ≤ 20/200) as a result of GA involving the fovea., Methods: The clinical trial enrolled 16 patients, 15 of whom underwent implantation successfully. The implant was administered to the worse-seeing eye with the use of a custom subretinal insertion device. The companion nonimplanted eye served as the control. The primary endpoint was at 1 year; thereafter, patients were followed up at least yearly., Main Outcome Measures: Safety was the primary endpoint of the study. The occurrence and frequency of adverse events (AEs) were determined by scheduled eye examinations, including measurement of BCVA and intraocular pressure and multimodal imaging. Serum antibody titers were collected to monitor systemic humoral immune responses to the implanted cells., Results: At a median follow-up of 3 years, fundus photography revealed no migration of the implant. No unanticipated, severe, implant-related AEs occurred, and the most common anticipated severe AE (severe retinal hemorrhage) was eliminated in the second cohort (9 patients) through improved intraoperative hemostasis. Nonsevere, transient retinal hemorrhages were noted either during or after surgery in all patients as anticipated for a subretinal surgical procedure. Throughout the median 3-year follow-up, results show that implanted eyes were more likely to improve by > 5 letters of BCVA and were less likely to worsen by > 5 letters compared with nonimplanted eyes., Conclusions: This report details the long-term follow-up of patients with GA to receive a scaffold-based stem cell-derived bioengineered RPE implant. Results show that the implant, at a median 3-year follow-up, is safe and well tolerated in patients with advanced dry age-related macular degeneration. The safety profile, along with the early indication of efficacy, warrants further clinical evaluation of this novel approach for the treatment of GA., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
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- 2024
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16. Evolution of rarity and phylogeny determine above- and belowground biomass in plant-plant interactions.
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Nytko AG, Hord AM, Senior JK, O'Reilly-Wapstra J, Schweitzer JA, and Bailey JK
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- Ecosystem, Biological Evolution, Species Specificity, Plants classification, Biomass, Phylogeny, Eucalyptus growth & development, Eucalyptus genetics
- Abstract
Rare species are often considered inferior competitors due to occupancy of small ranges, specific habitats, and small local populations. However, the phylogenetic relatedness and rarity level (level 1-7 and common) of interacting species in plant-plant interactions are not often considered when predicting the response of rare plants in a biotic context. We used a common garden of 25 species of Tasmanian Eucalyptus, to differentiate non-additive patterns in the biomass of rare versus common species when grown in mixtures varying in phylogenetic relatedness and rarity. We demonstrate that rare species maintain progressively positive non-additive responses in biomass when interacting with phylogenetically intermediate, less rare and common species. This trend is not reflected in common species that out-performed in monocultures compared to mixtures. These results offer predictability as to how rare species' productivity will respond within various plant-plant interactions. However, species-specific interactions, such as those involving E. globulus, yielded a 97% increase in biomass compared to other species-specific interaction outcomes. These results are important because they suggest that plant rarity may also be shaped by biotic interactions, in addition to the known environmental and population factors normally used to describe rarity. Rare species may utilize potentially facilitative interactions with phylogenetically intermediate and common species to escape the effects of limiting similarity. Biotically mediated increases in rare plant biomass may have subsequent effects on the competitive ability and geographic occurrence of rare species, allowing rare species to persist at low abundance across plant communities. Through the consideration of species rarity and evolutionary history, we can more accurately predict plant-plant interaction dynamics to preserve unique ecosystem functions and fundamentally challenge what it means to be "rare"., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Nytko et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
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- 2024
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17. Rescuing Photoreceptors in RPE Dysfunction-Driven Retinal Degeneration: The Role of Small Extracellular Vesicles Secreted from Retinal Pigment Epithelium.
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Pollalis D, Georgescu C, Wren JD, Tombulyan G, Leung JM, Lo PA, Bloemhof CM, Lee RH, Bae E, Bailey JK, Pennington BO, Khan AI, Kelly KR, Yeh AK, Sundaram KS, Humayun M, Louie S, Clegg DO, and Lee SY
- Abstract
Dysfunction of the retinal pigment epithelium (RPE) is a common shared pathology in major degenerative retinal diseases despite variations in the primary etiologies of each disease. Due to their demanding and indispensable functional roles throughout the lifetime, RPE cells are vulnerable to genetic predisposition, external stress, and aging processes. Building upon recent advancements in stem cell technology for differentiating healthy RPE cells and recognizing the significant roles of small extracellular vesicles (sEV) in cellular paracrine and autocrine actions, we investigated the hypothesis that the RPE-secreted sEV alone can restore essential RPE functions and rescue photoreceptors in RPE dysfunction-driven retinal degeneration. Our findings support the rationale for developing intravitreal treatment of sEV. We demonstrate that intravitreally delivered sEV effectively penetrate the full thickness of the retina. Xenogenic intraocular administration of human-derived EVs did not induce acute immune reactions in rodents. sEV derived from human embryonic stem cell (hESC)-derived fully differentiated RPE cells, but not sEV-depleted conditioned cell culture media (CCM minus sEV), rescued photoreceptors and their function in a Royal College of Surgeons (RCS) rat model. This model is characterized by photoreceptor death and retinal degeneration resulting from a mutation in the MerTK gene in RPE cells. From the bulk RNA sequencing study, we identified 447 differently expressed genes in the retina after hESC-RPE-sEV treatment compared with the untreated control. Furthermore, 394 out of 447 genes (88%) showed a reversal in expression toward the healthy state in Long-Evans (LE) rats after treatment compared to the diseased state. Particularly, detrimental alterations in gene expression in RCS rats, including essential RPE functions such as phototransduction, vitamin A metabolism, and lipid metabolism were partially reversed. Defective photoreceptor outer segment engulfment due to intrinsic MerTK mutation was partially ameliorated. These findings suggest that RPE-secreted sEV may play a functional role similar to that of RPE cells. Our study justifies further exploration to fully unlock future therapeutic interventions with sEV in a broad array of degenerative retinal diseases.
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- 2024
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18. Isolation and Characterization of Extracellular Vesicles Through Orthogonal Approaches for the Development of Intraocular EV Therapy.
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Leung J, Pollalis D, Nair GKG, Bailey JK, Pennington BO, Khan AI, Kelly KR, Yeh AK, Sundaram KS, Clegg DO, Peng CC, Xu L, and Lee SY
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- Humans, Culture Media, Conditioned, Filtration, Retinal Pigment Epithelium, Extracellular Vesicles, Human Embryonic Stem Cells
- Abstract
Purpose: Isolating extracellular vesicles (EVs) with high yield, replicable purity, and characterization remains a bottleneck in the development of EV therapeutics. To address these challenges, the current study aims to establish the necessary framework for preclinical and clinical studies in the development of stem cell-derived intraocular EV therapeutics., Methods: Small EVs (sEVs) were separated from the conditioned cell culture medium (CCM) of the human embryogenic stem cell-derived fully polarized retinal pigment epithelium (hESC-RPE-sEV) by a commercially available microfluidic tangential flow filtration (TFF) device ExoDisc (ED) or differential ultracentrifugation (dUC). The scaling and concentration capabilities and purity of recovered sEVs were assessed. Size, number, and surface markers of sEVs were determined by orthogonal approaches using multiple devices., Results: ED yielded higher numbers of sEVs, ranging from three to eight times higher depending on the measurement device, compared to dUC using the same 5 mL of CCM input. Within the same setting, the purity of ED-recovered hESC-RPE-sEVs was higher than that for dUC-recovered sEVs. ED yielded a higher concentration of particles, which is strongly correlated with the input volume, up to 10 mL (r = 0.98, P = 0.016). Meanwhile, comprehensive characterization profiles of EV surface markers between ED- and dUC-recovered hESC-RPE-sEVs were compatible., Conclusions: Our study supports TFF as a valuable strategy for separating sEVs for the development of intraocular EV therapeutics. However, there is a growing need for diverse devices to optimize TFF for use in EV preparation. Using orthogonal approaches in EV characterization remains ideal for reliably characterizing heterogeneous EV.
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- 2024
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19. Above- and belowground fungal biodiversity of Populus trees on a continental scale.
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Van Nuland ME, Daws SC, Bailey JK, Schweitzer JA, Busby PE, and Peay KG
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- Trees microbiology, Ecosystem, Biodiversity, Populus microbiology, Mycorrhizae
- Abstract
Understanding drivers of terrestrial fungal communities over large scales is an important challenge for predicting the fate of ecosystems under climate change and providing critical ecological context for bioengineering plant-microbe interactions in model systems. We conducted an extensive molecular and microscopy field study across the contiguous United States measuring natural variation in the Populus fungal microbiome among tree species, plant niche compartments and key symbionts. Our results show clear biodiversity hotspots and regional endemism of Populus-associated fungal communities explained by a combination of climate, soil and geographic factors. Modelling climate change impacts showed a deterioration of Populus mycorrhizal associations and an increase in potentially pathogenic foliar endophyte diversity and prevalence. Geographic differences among these symbiont groups in their sensitivity to environmental change are likely to influence broader forest health and ecosystem function. This dataset provides an above- and belowground atlas of Populus fungal biodiversity at a continental scale., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2023
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20. American Burn Association Strategic Quality Summit 2022: Setting the Direction for the Future.
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Parry I, Mandell SP, Hoarle KA, Bailey JK, Dissanaike S, Harrington DT, Holmes JH, and Cartotto R
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- United States, Humans, Quality of Health Care, Illinois, Forecasting, Burns therapy
- Abstract
The American Burn Association (ABA) hosted a Burn Care Strategic Quality Summit (SQS) in an ongoing effort to advance the quality of burn care. The goals of the SQS were to discuss and describe characteristics of quality burn care, identify goals for advancing burn care, and develop a roadmap to guide future endeavors while integrating current ABA quality programs. Forty multidisciplinary members attended the two-day event. Prior to the event, they participated in a pre-meeting webinar, reviewed relevant literature, and contemplated statements regarding their vision for improving burn care. At the in-person, professionally facilitated Summit in Chicago, Illinois, in June 2022, participants discussed various elements of quality burn care and shared ideas on future initiatives to advance burn care through small and large group interactive activities. Key outcomes of the SQS included burn-related definitions of quality care, avenues for integration of current ABA quality programs, goals for advancing quality efforts in burn care, and work streams with tasks for a roadmap to guide future burn care quality-related endeavors. Work streams included roadmap development, data strategy, quality program integration, and partners and stakeholders. This paper summarizes the goals and outcomes of the SQS and describes the status of established ABA quality programs as a launching point for futurework., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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21. Scar Management and Dyschromia: A Summary Report from the 2021 American Burn Association State of the Science Meeting.
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Carney BC, Bailey JK, Powell HM, Supp DM, and Travis TE
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- Humans, Research Report, Quality of Life, Silicone Gels, Burns complications, Burns therapy, Cicatrix, Hypertrophic etiology, Cicatrix, Hypertrophic prevention & control
- Abstract
Burn scars, and in particular, hypertrophic scars, are a challenging yet common outcome for survivors of burn injuries. In 2021, the American Burn Association brought together experts in burn care and research to discuss critical topics related to burns, including burn scars, at its State of the Science conference. Clinicians and researchers with burn scar expertise, as well as burn patients, industry representatives, and other interested stakeholders met to discuss issues related to burn scars and discuss priorities for future burn scar research. The various preventative strategies and treatment modalities currently utilized for burn scars were discussed, including relatively noninvasive therapies such as massage, compression, and silicone sheeting, as well as medical interventions such as corticosteroid injection and laser therapies. A common theme that emerged is that the efficacy of current therapies for specific patient populations is not clear, and further research is needed to improve upon these treatments and develop more effective strategies to suppress scar formation. This will necessitate quantitative analyses of outcomes and would benefit from creation of scar biobanks and shared data resources. In addition, outcomes of importance to patients, such as scar dyschromia, must be given greater attention by clinicians and researchers to improve overall quality of life in burn survivors. Herein we summarize the main topics of discussion from this meeting and offer recommendations for areas where further research and development are needed., (© The Author(s) 2023. Published by Oxford University Press on behalf of the American Burn Association. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2023
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22. Climate-driven convergent evolution in riparian ecosystems on sky islands.
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Love SJ, Schweitzer JA, and Bailey JK
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- Islands, Biomass, Phenotype, Ecosystem, Genetic Drift
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Climate-induced evolution will determine population persistence in a changing world. However, finding natural systems in which to study these responses has been a barrier to estimating the impact of global change on a broad scale. We propose that isolated sky islands (SI) and adjacent mountain chains (MC) are natural laboratories for studying long-term and contemporary climatic pressures on natural populations. We used greenhouse common garden trees to test whether populations on SI exposed to hot and dry climates since the end of the Pleistocene have phenotypically diverged from populations on MC, and if SI populations have converged in these traits. We show: (1) populations of Populus angustifolia from SI have diverged from MC, and converged across SI, in reproductive and productivity traits, (2) these traits (cloning and aboveground biomass, respectively) are significantly correlated, suggesting a genetic linkage between them, and (3) the trait variation is driven by both natural selection and genetic drift. These shifts represent potentially beneficial phenotypes for population persistence in a changing world. These results suggest that the SI-MC comparison is a natural laboratory, as well as a predictive framework, for studying long-term responses to climate change across the globe., (© 2023. The Author(s).)
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- 2023
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23. Stacked distribution models predict climate-driven loss of variation in leaf phenology at continental scales.
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Bayliss SLJ, Mueller LO, Ware IM, Schweitzer JA, and Bailey JK
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- Plant Leaves genetics, Seasons, Phenotype, Climate Change, Populus genetics
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Climate change is having profound effects on species distributions and is likely altering the distribution of genetic variation across landscapes. Maintaining population genetic diversity is essential for the survival of species facing rapid environmental change, and variation loss will further ecological and evolutionary change. We used trait values of spring foliar leaf-out phenology of 400 genotypes from three geographically isolated populations of Populus angustifolia grown under common conditions, in concert with stacked species distribution modeling, to ask: (a) How will climate change alter phenological variation across the P. angustifolia species-range, and within populations; and (b) will the distribution of phenological variation among and within populations converge (become more similar) in future climatic conditions? Models predicted a net loss of phenological variation in future climate scenarios on 20-25% of the landscape across the species' range, with the trailing edge population losing variation on as much as 47% of the landscape. Our models also predicted that population's phenological trait distributions will become more similar over time. This stacked distribution model approach allows for the identification of areas expected to experience the greatest loss of genetically based functional trait variation and areas that may be priorities to conserve as future genetic climate refugia., (© 2022. The Author(s).)
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- 2022
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24. Aggregate population-level models informed by genetics predict more suitable habitat than traditional species-level model across the range of a widespread riparian tree.
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Bayliss SLJ, Papeş M, Schweitzer JA, and Bailey JK
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- Acclimatization, Adaptation, Physiological, Climate Change, Ecosystem, Trees
- Abstract
Identifying and predicting how species ranges will shift in response to climate change is paramount for conservation and restoration. Ecological niche models are the most common method used to estimate potential distributions of species; however, they traditionally omit knowledge of intraspecific variation that can allow populations to respond uniquely to change. Here, we aim to test how population X environment relationships influence predicted suitable geographic distributions by comparing aggregated population-level models with species-level model predictions of suitable habitat within population ranges and across the species' range. We also test the effect of two variable selection methods on these predictions-both addressing the possibility of local adaptation: Models were built with (a) a common set, and number, of predictors and, (b) a unique combination and number of predictors specific to each group's training extent. Our study addresses the overarching hypothesis that populations have unique environmental niches, and specifically that (1) species-level models predict more suitable habitat within the ranges of genetic populations than individual models built from those groups, particularly when compared models are built with the same set of environmental predictors; and (2) aggregated genetic population models predict more suitable habitat across the species' range than the species-level model, an = d this difference will increase when models are trained with individualized predictors. We found the species models predicted more habitat within population ranges for two of three genetic groups regardless of variable selection, and that aggregated population models predicted more habitat than species' models, but that individualized predictors increased this difference. Our study emphasizes the extent to which changes to model predictions depend on the inclusion of genetic information and on the type and selection of predictors. Results from these modeling decisions can have broad implications for predicting population-level ecological and evolutionary responses to climate change., Competing Interests: The authors have declared that no competing interests exist.
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- 2022
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25. Microcarrier-Based Culture of Human Pluripotent Stem-Cell-Derived Retinal Pigmented Epithelium.
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Faynus MA, Bailey JK, Pennington BO, Katsura M, Proctor DA, Yeh AK, Menon S, Choi DG, Lebkowski JS, Johnson LV, and Clegg DO
- Abstract
Dry age-related macular degeneration (AMD) is estimated to impact nearly 300 million individuals globally by 2040. While no treatment options are currently available, multiple clinical trials investigating retinal pigmented epithelial cells derived from human pluripotent stem cells (hPSC-RPE) as a cellular replacement therapeutic are currently underway. It has been estimated that a production capacity of >109 RPE cells annually would be required to treat the afflicted population, but current manufacturing protocols are limited, being labor-intensive and time-consuming. Microcarrier technology has enabled high-density propagation of many adherent mammalian cell types via monolayer culture on surfaces of uM-diameter matrix spheres; however, few studies have explored microcarrier-based culture of RPE cells. Here, we provide an approach to the growth, maturation, and differentiation of hPSC-RPE cells on Cytodex 1 (C1) and Cytodex 3 (C3) microcarriers. We demonstrate that hPSC-RPE cells adhere to microcarriers coated with Matrigel, vitronectin or collagen, and mature in vitro to exhibit characteristic epithelial cell morphology and pigmentation. Microcarrier-grown hPSC-RPE cells (mcRPE) are viable; metabolically active; express RPE signature genes including BEST1, RPE65, TYRP1, and PMEL17; secrete the trophic factors PEDF and VEGF; and demonstrate phagocytosis of photoreceptor outer segments. Furthermore, we show that undifferentiated hESCs also adhere to Matrigel-coated microcarriers and are amenable to directed RPE differentiation. The capacity to support hPSC-RPE cell cultures using microcarriers enables efficient large-scale production of therapeutic RPE cells sufficient to meet the treatment demands of a large AMD patient population.
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- 2022
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26. Natural soil microbiome variation affects spring foliar phenology with consequences for plant productivity and climate-driven range shifts.
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Van Nuland ME, Ware IM, Schadt CW, Yang Z, Bailey JK, and Schweitzer JA
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- Climate Change, Ecosystem, Seasons, Soil, Microbiota, Populus
- Abstract
Identifying the potential for natural soil microbial communities to predictably affect complex plant traits is an important frontier in climate change research. Plant phenology varies with environmental and genetic factors, but few studies have examined whether the soil microbiome interacts with plant population differentiation to affect phenology and ecosystem function. We compared soil microbial variation in a widespread tree species (Populus angustifolia) with different soil inoculum treatments in a common garden environment to test how the soil microbiome affects spring foliar phenology and subsequent biomass growth. We hypothesized and show that soil bacterial and fungal communities vary with tree conditioning from different populations and elevations, that this soil community variation influences patterns of foliar phenology and plant growth across populations and elevation gradients, and that transferring lower elevation plant genotypes to higher elevation soil communities delayed foliar phenology, thereby shortening the growing season and reducing annual biomass production. Our findings show the importance of plant-soil interactions that help shape the timing of tree foliar phenology and productivity. These geographic patterns in plant population × microbiome interactions also broaden our understanding of how soil communities impact plant phenotypic variation across key climate change gradients, with consequences for ecosystem functioning., (© 2021 No claim to US Government works New Phytologist © 2021 New Phytologist Foundation.)
- Published
- 2021
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27. One-Year Follow-Up in a Phase 1/2a Clinical Trial of an Allogeneic RPE Cell Bioengineered Implant for Advanced Dry Age-Related Macular Degeneration.
- Author
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Kashani AH, Lebkowski JS, Rahhal FM, Avery RL, Salehi-Had H, Chen S, Chan C, Palejwala N, Ingram A, Dang W, Lin CM, Mitra D, Pennington BO, Hinman C, Faynus MA, Bailey JK, Mohan S, Rao N, Johnson LV, Clegg DO, Hinton DR, and Humayun MS
- Subjects
- Follow-Up Studies, Humans, Visual Acuity, Geographic Atrophy therapy, Hematopoietic Stem Cell Transplantation, Macular Degeneration therapy
- Abstract
Purpose: To report 1-year follow-up of a phase 1/2a clinical trial testing a composite subretinal implant having polarized human embryonic stem cell (hESC)-derived retinal pigment epithelium (RPE) cells on an ultrathin parylene substrate in subjects with advanced non-neovascular age-related macular degeneration (NNAMD)., Methods: The phase 1/2a clinical trial included 16 subjects in two cohorts. The main endpoint was safety assessed at 365 days using ophthalmic and systemic exams. Pseudophakic subjects with geographic atrophy (GA) and severe vision loss were eligible. Low-dose tacrolimus immunosuppression was utilized for 68 days in the peri-implantation period. The implant was delivered to the worst seeing eye with a custom subretinal insertion device in an outpatient setting. A data safety monitoring committee reviewed all results., Results: The treated eyes of all subjects were legally blind with a baseline best-corrected visual acuity (BCVA) of ≤ 20/200. There were no unexpected serious adverse events. Four subjects in cohort 1 had serious ocular adverse events, including retinal hemorrhage, edema, focal retinal detachment, or RPE detachment, which was mitigated in cohort 2 using improved hemostasis during surgery. Although this study was not powered to assess efficacy, treated eyes from four subjects showed an increased BCVA of >5 letters (6-13 letters). A larger proportion of treated eyes experienced a >5-letter gain when compared with the untreated eye (27% vs. 7%; P = not significant) and a larger proportion of nonimplanted eyes demonstrated a >5-letter loss (47% vs. 33%; P = not significant)., Conclusions: Outpatient delivery of the implant can be performed routinely. At 1 year, the implant is safe and well tolerated in subjects with advanced dry AMD., Translational Relevance: This work describes the first clinical trial, to our knowledge, of a novel implant for advanced dry AMD.
- Published
- 2021
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28. Climate-driven divergence in plant-microbiome interactions generates range-wide variation in bud break phenology.
- Author
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Ware IM, Van Nuland ME, Yang ZK, Schadt CW, Schweitzer JA, and Bailey JK
- Subjects
- Genetic Variation, Microbiota, Rhizosphere, Trees microbiology, United States, Climate Change, Ecosystem, Populus microbiology, Soil chemistry, Soil Microbiology
- Abstract
Soil microbiomes are rapidly becoming known as an important driver of plant phenotypic variation and may mediate plant responses to environmental factors. However, integrating spatial scales relevant to climate change with plant intraspecific genetic variation and soil microbial ecology is difficult, making studies of broad inference rare. Here we hypothesize and show: 1) the degree to which tree genotypes condition their soil microbiomes varies by population across the geographic distribution of a widespread riparian tree, Populus angustifolia; 2) geographic dissimilarity in soil microbiomes among populations is influenced by both abiotic and biotic environmental variation; and 3) soil microbiomes that vary in response to abiotic and biotic factors can change plant foliar phenology. We show soil microbiomes respond to intraspecific variation at the tree genotype and population level, and geographic variation in soil characteristics and climate. Using a fully reciprocal plant population by soil location feedback experiment, we identified a climate-based soil microbiome effect that advanced and delayed bud break phenology by approximately 10 days. These results demonstrate a landscape-level feedback between tree populations and associated soil microbial communities and suggest soil microbes may play important roles in mediating and buffering bud break phenology with climate warming, with whole ecosystem implications.
- Published
- 2021
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29. Xeno-free cryopreservation of adherent retinal pigmented epithelium yields viable and functional cells in vitro and in vivo.
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Pennington BO, Bailey JK, Faynus MA, Hinman C, Hee MN, Ritts R, Nadar V, Zhu D, Mitra D, Martinez-Camarillo JC, Lin TC, Thomas BB, Hinton DR, Humayun MS, Lebkowski J, Johnson LV, and Clegg DO
- Subjects
- Animals, Cell Differentiation, Cell Line, Cell Survival, Disease Models, Animal, Epithelial Cells cytology, Epithelial Cells metabolism, Eye Proteins metabolism, Human Embryonic Stem Cells cytology, Humans, Nerve Growth Factors metabolism, Polymers, Rats, Rats, Nude, Regenerative Medicine methods, Retinal Pigment Epithelium cytology, Retinal Pigment Epithelium metabolism, Serpins metabolism, Tissue Scaffolds, Treatment Outcome, Xylenes, Cryopreservation methods, Epithelial Cells transplantation, Macular Degeneration therapy, Retinal Pigment Epithelium transplantation, Specimen Handling methods, Stem Cell Transplantation methods
- Abstract
Age-related macular degeneration (AMD) is the primary cause of blindness in adults over 60 years of age, and clinical trials are currently assessing the therapeutic potential of retinal pigmented epithelial (RPE) cell monolayers on implantable scaffolds to treat this disease. However, challenges related to the culture, long-term storage, and long-distance transport of such implants currently limit the widespread use of adherent RPE cells as therapeutics. Here we report a xeno-free protocol to cryopreserve a confluent monolayer of clinical-grade, human embryonic stem cell-derived RPE cells on a parylene scaffold (REPS) that yields viable, polarized, and functional RPE cells post-thaw. Thawed cells exhibit ≥ 95% viability, have morphology, pigmentation, and gene expression characteristic of mature RPE cells, and secrete the neuroprotective protein, pigment epithelium-derived factor (PEDF). Stability under liquid nitrogen (LN
2 ) storage has been confirmed through one year. REPS were administered immediately post-thaw into the subretinal space of a mammalian model, the Royal College of Surgeons (RCS)/nude rat. Implanted REPS were assessed at 30, 60, and 90 days post-implantation, and thawed cells demonstrate survival as an intact monolayer on the parylene scaffold. Furthermore, immunoreactivity for the maturation marker, RPE65, significantly increased over the post-implantation period in vivo, and cells demonstrated functional attributes similar to non-cryopreserved controls. The capacity to cryopreserve adherent cellular therapeutics permits extended storage and stable transport to surgical sites, enabling broad distribution for the treatment of prevalent diseases such as AMD.- Published
- 2021
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30. Response to the Letter to the Editor: Fractional CO 2 laser ablation of porcine burn scars after grafting: Is deeper better?
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Powell HM, Supp DM, Bailey JK, and Baumann ME
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- Animals, Carbon Dioxide, Cicatrix etiology, Cicatrix pathology, Cicatrix surgery, Swine, Burns surgery, Cicatrix, Hypertrophic surgery, Laser Therapy, Lasers, Gas therapeutic use
- Published
- 2021
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31. Direct comparison of reproducibility and reliability in quantitative assessments of burn scar properties.
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Baumann ME, DeBruler DM, Blackstone BN, Coffey RA, Boyce ST, Supp DM, Bailey JK, and Powell HM
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- Humans, Photography, Pigmentation, Reproducibility of Results, Burns complications, Cicatrix etiology, Cicatrix pathology
- Abstract
Introduction: Determining the efficacy of anti-scar technologies can be difficult as qualitative, subjective assessments are often utilized instead of systematic, objective measures. Perceptions regarding the reliability of instruments for quantitative measurements along with their high cost and increased data collection time may discourage their use, leading to use of scar scales which are relatively quick and low-cost. To directly evaluate the reliability of instruments for quantitative measurements of scar properties, instruments and two qualitative scales were compared by assessing a variety of cutaneous scars., Methods: Scar height and surface texture were evaluated using a 3D scanner and a mold/cast technique. Scar color was evaluated by using a spectroscopy-based tool, the Mexameter®, and digital photography with image analysis. Scar biomechanics were evaluated using the BTC-2000™, Dermal Torque Meter (DTM®), and ballistometer®. The Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS) were used to qualitatively evaluate the same scar properties. Intraclass correlation coefficients (ICC) were used to determine inter- and intra-user reliability (poor, moderate, good, excellent) with all instruments and the kappa reliability statistic was used to asses inter-user reliability (poor, fair, moderate, good, very good) for VSS and POSAS. Time for measurement collection and after collection analysis was also recorded., Results: The Mexameter® was the most reliable method for evaluating erythema and pigmentation compared to digital photography and image processing, POSAS and VSS. Digital photography and analysis was more reliable than POSAS and VSS. Assessment of scar height was significantly more reliable when using a 3D scanner versus VSS and POSAS. The 3D scanner and mold-cast techniques also offered an additional benefit of providing an absolute value of scar height relative to the surrounding tissue. Intra-user reliability for all mechanical tests was moderate to good. Inter-user reliability was greater when using the BTC-2000™ and ballistometer® versus the DTM®. All quantitative measurements took less than 90 s for collection, with the exception of the mold/cast technique., Conclusion: Non-invasive instruments allow scar properties to be quantitatively assessed with high sensitivity and as a function of time and/or treatment without the need for biopsy collection. Overall, the reliability of scar assessments was significantly improved when quantitative instruments were utilized versus scar scales. Quantitative assessment of color and biomechanics were swift, requiring less than 90 s per measurement while assessments of texture and height required additional analysis time after collection. With proper training of clinical staff and well-defined protocols for measurement collection, reliable, quantitative assessments of scar properties can be collected with little disruption to the clinical workflow., (Published by Elsevier Ltd.)
- Published
- 2021
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32. Cultured Epithelial Autograft Combined with Micropatterned Dermal Template Forms Rete Ridges In Vivo .
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Malara MM, Blackstone BN, Baumann ME, Bailey JK, Supp DM, and Powell HM
- Subjects
- Animals, Autografts, Cells, Cultured, Collagen, Epidermis, Fibroblasts, Humans, Mice, Burns surgery, Epithelium transplantation, Skin Transplantation, Tissue Scaffolds
- Abstract
For patients with large, full-thickness burn wounds, sufficient donor sites for autografting are not available, and thus, alternate strategies must be used to close these wounds. Cultured epithelial autografts (CEAs) can aid in closing these wounds but are often associated with slow deposition of basement membrane proteins, leading to blistering and graft loss. Rete ridges and dermal papillae present at the dermal-epidermal junction (DEJ) play a key role in epidermal adhesion and skin homeostasis. Promoting the development of an interdigitated DEJ may enhance basement membrane protein deposition and provide enhanced physical interlock of the epidermis and dermis. To develop a dermal template with stable dermal papillae, an electrospun collagen scaffold was seeded with human dermal fibroblasts. Ridged topographies were patterned into the cell-seeded dermal template using laser ablation, creating wide and shallow (ActiveFX) or narrow and deep (DeepFX) wells. Micropatterned or flat (control) dermal templates were combined with CEAs immediately before grafting to full-thickness excisional wounds on immunodeficient mice. CEAs grafted in conjunction with ridged templates showed rete ridge formation at 2 weeks after grafting and led to increased epidermal thickness, proliferation, and stemness compared to templates with a flat DEJ. As this technology is further developed, the dermal papilla-containing dermal templates may be utilized in combination with CEAs to improve adhesion and clinical function. Impact statement Cultured epithelial autografts (CEAs) serve as an adjunct to conventional split-thickness autograft in patients with very large burns, but they are susceptible to blistering that can reduce engraftment. Blistering results, in part, from relatively slow basement membrane deposition after grafting. This study demonstrates that basement membrane deposition and rete ridge formation are enhanced by combination of CEAs with a micropatterned, cell-seeded dermal template. These findings may lead to improved treatment and increased survival in patients with very large burns.
- Published
- 2020
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33. Safety, feasibility, and acceptability of patient-controlled anxiolysis with dexmedetomidine for burn-care dressing changes: an open-label, single-arm, pilot study.
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Murphy CV, Coffey R, Moore K, Abdel-Rasoul M, Chlan L, Bailey JK, and Jones LM
- Abstract
Anxiety is common among patients with burn injury, occurring frequently surrounding wound care. Few pharmacologic interventions targeting anxiety in burn injury have been evaluated. This study aimed to evaluate patient-controlled anxiolysis using dexmedetomidine (PCA-DEX) in patients undergoing burn dressing changes. This was a prospective, open-label, single-arm pilot study to determine the feasibility, safety, and acceptability of PCA-DEX. PCA-DEX included a loading dose, continuous infusion, and patient-administered boluses during dressing changes for up to 5 days. Vital signs were monitored throughout PCA-DEX. Procedural pain and anxiety were evaluated before and after each dressing change. Nursing and patient satisfaction were evaluated after each dressing change. Twenty patients were included; 9 (45%) males and 11 females (55%) with a mean age of 45.1 ± 16.9 years and median total body surface area burn injury of 7 [IQR 4-9.5]%. Median heart rate and systolic blood pressure prior to PCA-DEX on day 1 were 82 [75-97] bpm and 147 [128-170] mmHg. Overall PCA-DEX was tolerated well with a median heart rate of 72 [66-82] bpm and systolic blood pressure 115 [99-141] mmHg after PCA-DEX. One patient was withdrawn due to severe bradycardia (heart rate < 45 bpm) not attributed to PCA-DEX; 4 patients experienced mild hypotension (systolic blood pressure 85-89/diastolic blood pressure 45-49 mmHg), all of which resolved without intervention. The majority of both nurses and patients were either satisfied or highly satisfied with PCA-DEX overall (78.1% for nursing, 86.5% for patients). PCA-DEX is a novel, safe and feasible method of anxiolysis during burn dressing changes with high patient and nurse satisfaction rates. A randomized, controlled trial is warranted to confirm the efficacy of PCA-DEX., Competing Interests: None., (IJBT Copyright © 2020.)
- Published
- 2020
34. Plant genetic variation drives geographic differences in atmosphere-plant-ecosystem feedbacks.
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Bayliss SLJ, Mueller LO, Ware IM, Schweitzer JA, and Bailey JK
- Abstract
The objective of this study was to understand how genetic variation in a riparian species, Populus angustifolia , affects mass and energy exchange between the land and atmosphere across ~1,700 km of latitude of the western United States. To examine the potential for large-scale land-atmosphere feedbacks in hydrologic processes driven by geographic differences in plant population traits, we use a physical hydrology model, paired field, and greenhouse observations of plant traits, and stable isotope compositions of soil, stem, and leaf water of P. angustifolia populations. Populations show patterns of local adaptation in traits related to landscape hydrologic functioning-a 47% difference in stomatal density in greenhouse conditions and a 74% difference in stomatal ratio in the field. Trait and stable isotope differences reveal that populations use water differently which is related to historical landscape hydrologic functioning (evapotranspiration and streamflow). Overall, results suggest that populations from landscapes with different hydrologic histories will differ in their ability to maintain favorable water balance with changing atmospheric demands for water, with ecosystem consequences., Competing Interests: The authors declare no conflict of interest. [Correction added on 11 June 2021, after first online publication: Conflict of Interest statement added to provide full transparency.], (© 2020 The Authors. Journal of Plant‐Environment Interactions Published by John Wiley & Sons Ltd.)
- Published
- 2020
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35. Improved Scar Outcomes with Increased Daily Duration of Pressure Garment Therapy.
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DeBruler DM, Baumann ME, Zbinden JC, Blackstone BN, Bailey JK, Supp DM, and Powell HM
- Subjects
- Animals, Autografts, Biomechanical Phenomena, Disease Models, Animal, Patient Compliance, Swine, Transplantation, Autologous, Treatment Outcome, Burns complications, Burns therapy, Cicatrix, Hypertrophic etiology, Cicatrix, Hypertrophic therapy, Clothing, Compression Bandages
- Abstract
Objective: Despite the development of a number of treatment modalities, scarring remains common postburn injury. To reduce burn scarring, pressure garment therapy has been widely utilized but is complicated by low patient adherence. To improve adherence, reduced hours of daily garment wear has been proposed. Approach: To examine the efficacy of pressure garment therapy at reduced durations of daily wear, a porcine burn-excise-autograft model was utilized. Grafted burns were treated with pressure garments (20 mmHg) for 8, 16, or 24 h of daily wear with untreated burns serving as controls. Scar area, thickness, biomechanical properties, and tissue structure were assessed over time. Results: All treatment groups reduced scar thickness and contraction versus controls and improved scar pliability and elasticity. Pressure garments worn 24 h per day significantly reduced contraction versus the 8- and 16-h groups and prevented alignment of collagen within the dermis. Innovation: Though pressure garment therapy is prescribed for use 23 h per day, the need for almost continuous use has not been previously examined. Adjustable, low-fatigue pressure garments were developed for this porcine study to examine the role of daily duration of wear without confounding factors such as garment fatigue and patient adherence. Conclusion: For maximum efficacy, pressure garments should be worn 23 to 24 h per day; however, garments worn as little as 8 h per day significantly improve scar outcomes versus no treatment.
- Published
- 2020
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36. Reply to Letter to the Editor on "The impact of serum zinc normalization on clinical outcomes in severe burn patients".
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Olson LM, Coffey R, Porter K, Thomas S, Bailey JK, Jones LM, and Murphy CV
- Subjects
- Humans, Zinc, Burns
- Published
- 2020
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- View/download PDF
37. One center's experience developing a burn outpatient registry.
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Coffey R, Penny R, Jones L, and Bailey JK
- Subjects
- Accident Prevention, Burns prevention & control, Cost-Benefit Analysis, Humans, Outcome Assessment, Health Care, Quality Assurance, Health Care, Ambulatory Care, Burns therapy, Registries
- Abstract
Introduction: Recent advances in burn care have resulted in the transition of care from inpatient to outpatient. There is a growing appreciation that with improved survival, meaningful markers of quality need to include recovery of form, function, and reconstruction. Capture of the data describing care delivered in the outpatient setting is being missed., Methods: Development of our outpatient database included providers, registrar, program manager, and outpatient nursing staff. Data points were included if they described the population, and epidemiology of our patients, were useful for programmatic changes and improvements as well as anticipated research focus areas., Results: The database platform chosen was Midas+™ because it was in use by hospital quality and integrated with the electronic medical record. Fields were customized based on changing program needs and are updated for new programs or outcomes measures. Reports can be easily built and both outpatients and inpatients are included. This allows for longitudinal tracking of burn patients. Ongoing additions to original data points include variables to track outcomes related to laser therapy for scar management, time to custom garment donning, and to track functional outcomes. Epidemiologic data collected is used to target high-risk populations for prevention and outreach efforts. Outcome data is used for evaluation of programs and care., Conclusions: High quality databases serve to measure effectiveness of care and offer insight for areas of improvement. There is a clear need for inclusion of outpatient activity in the National Burn Registry (NBR)., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)
- Published
- 2020
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38. Fractional CO 2 laser ablation of porcine burn scars after grafting: Is deeper better?
- Author
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Baumann ME, Blackstone BN, Malara MM, Clairmonte IA, Supp DM, Bailey JK, and Powell HM
- Subjects
- Animals, Biomechanical Phenomena, Cicatrix genetics, Cicatrix pathology, Cicatrix physiopathology, Erythema, Matrix Metalloproteinase 1 genetics, Matrix Metalloproteinase 9 genetics, Pigmentation, RNA, Messenger metabolism, Skin physiopathology, Skin Transplantation, Sus scrofa, Tissue Inhibitor of Metalloproteinase-1 genetics, Tissue Inhibitor of Metalloproteinase-2 genetics, Burns surgery, Cicatrix surgery, Laser Therapy methods, Lasers, Gas therapeutic use, Skin pathology
- Abstract
Introduction: Fractional CO
2 lasers have been used in clinical settings to improve scarring following burn injury. Though used with increasing frequency, the appropriate laser settings are not well defined and overall efficacy of this therapy has not been definitively established. As it has been proposed that for thick hypertrophic scars proportionally greater fluence and thus deeper ablation into the scar tissue would be most effective, the goal of this study was to examine the role of ablation depth on scar outcomes in a highly-controlled porcine model for burn scars-after grafting., Methods: Properties of laser ablated wells were quantified on ex vivo pig skin as a function of laser energy (20, 70 or 150mJ). Full-thickness burn wounds were created on the dorsum of red Duroc pigs with the eschar excised and grafted with a split-thickness autograft meshed and expanded 1.5:1. After four weeks of healing, sites were treated with either 20, 70, or 150mJ pulse energy from a fractional CO2 laser at 5% density or left untreated as a control. Sites were treated every four weeks with three total sessions. Scar area, pigmentation, erythema, roughness, histology, and biomechanics were evaluated prior to each laser treatment at day 28, 56, and 83, as well as four weeks after the final laser treatment, day 112. Additional biopsies were collected at day 112 for gene expression analysis., Results: The depth of the laser ablated wells increased with increasing pulse energy while the width of the wells was smaller in the 20mJ group and not significantly different in the 70 and 150mJ groups. Scar properties (area, color, biomechanics) were not significantly altered by laser therapy at any of the laser energies tested versus controls. Average scar roughness was improved by laser therapy in a dose dependent manner with scars treated with 150mJ of energy having the smoothest surface; however, these changes were not statistically significant. Assessment of matrix metalloproteinase 9 gene expression showed a slight upregulation in scars treated with 70 or 150mJ versus control scars and scars treated with 20mJ pulse energy., Conclusion: The current study demonstrated that the properties of the ablative well (depth and width) are not linearly correlated with laser pulse energy, with only a small increase in well depth at energies between 70 and 150mJ. Overall, the study suggests that there is little difference in outcomes as a function of laser energy. Fractional CO2 laser therapy did not result in any statistically significant benefit to scar properties assessed by quantitative, objective measures, thus highlighting the need for additional clinical investigation of laser therapy efficacy with non-treated controls and objective measures of outcome., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)- Published
- 2020
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39. The impact of serum zinc normalization on clinical outcomes in severe burn patients.
- Author
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Olson LM, Coffey R, Porter K, Thomas S, Bailey JK, Jones LM, and Murphy CV
- Subjects
- Adult, Aged, Body Surface Area, Burns pathology, Burns therapy, Female, Humans, Hyperglycemia epidemiology, Infections epidemiology, Male, Middle Aged, Re-Epithelialization, Retrospective Studies, Skin Transplantation, Time Factors, Trace Elements therapeutic use, Trauma Severity Indices, Treatment Outcome, Zinc deficiency, Zinc therapeutic use, Burns blood, Length of Stay statistics & numerical data, Zinc blood
- Abstract
Introduction: Patients with thermal burns become zinc deficient due to exudative losses, increased urinary excretion, and reduction of carrier proteins which results in impaired immunity, wound healing and glucose control. Previous trials have demonstrated improved wound healing utilizing fixed zinc supplementation, but none have assessed the potential benefits associated with normalizing serum zinc concentrations. The objective of this study was to compare the impact of zinc normalization on clinical outcomes in patients with severe thermal burns., Methods: This retrospective, single-center study of patients with at least 10% total body surface area (TBSA) burn and three serum zinc concentrations compared the ratio of hospital length of stay (LOS) over TBSA burned (LOS/TBSA index) between those with normal (≥60 mcg/mL) and non-normal (<60 mcg/mL) serum zinc concentrations; delineated by the third measurement. Secondary outcomes were time to 90% epithelialization, infection incidence, and percentage of blood glucose values greater than 180 mg/dL. Data are reported as median [25-75% interquartile range] for continuous variables and frequency (percent) for categorical variables., Results: A total of 56 patients were included for evaluation (11 normal and 45 non-normal). Burn size was 20.5% TBSA [11-29] for those with normal zinc and 27.3% [22-36] for non-normal; number of grafts for each group was 1 [0-1] vs 2 [1-3] respectively. LOS/TBSA index did not differ significantly between groups (1.10 normal vs. 1.21 non-normal, unadjusted p = 0.69; p = 0.75 adjusting for number of grafts). Time to 90% epithelialization was reduced in the normal group (27.5 vs. 57 days, p = 0.02), but this did not remain statistically significant after adjustment for %TBSA and number of grafts (p = 0.18). The groups did not differ significantly in incidence of infection or hyperglycemia in either unadjusted or adjusted analyses., Conclusions: This was the first study, to our knowledge, to assess the clinical impact of normalizing serum zinc levels in patients with severe burns. Our results suggest the normalization of serum zinc levels through individualized zinc supplementation is not associated with improvement in clinical outcomes during hospitalization and therefore fixed-dose zinc supplementation without acquisition of serum zinc measurements should be considered., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)
- Published
- 2020
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40. Intraspecific trait variation across elevation predicts a widespread tree species' climate niche and range limits.
- Author
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Van Nuland ME, Vincent JB, Ware IM, Mueller LO, Bayliss SLJ, Beals KK, Schweitzer JA, and Bailey JK
- Abstract
Global change is widely altering environmental conditions which makes accurately predicting species range limits across natural landscapes critical for conservation and management decisions. If climate pressures along elevation gradients influence the distribution of phenotypic and genetic variation of plant functional traits, then such trait variation may be informative of the selective mechanisms and adaptations that help define climatic niche limits. Using extensive field surveys along 16 elevation transects and a large common garden experiment, we tested whether functional trait variation could predict the climatic niche of a widespread tree species ( Populus angustifolia ) with a double quantile regression approach. We show that intraspecific variation in plant size, growth, and leaf morphology corresponds with the species' total climate range and certain climatic limits related to temperature and moisture extremes. Moreover, we find evidence of genetic clines and phenotypic plasticity at environmental boundaries, which we use to create geographic predictions of trait variation and maximum values due to climatic constraints across the western US. Overall, our findings show the utility of double quantile regressions for connecting species distributions and climate gradients through trait-based mechanisms. We highlight how new approaches like ours that incorporate genetic variation in functional traits and their response to climate gradients will lead to a better understanding of plant distributions as well as identifying populations anticipated to be maladapted to future environments., Competing Interests: None declared., (© 2020 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.)
- Published
- 2020
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41. The Impact of Sustained Immunization Regimens on the Antibody Response to Oligomannose Glycans.
- Author
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Nguyen DN, Redman RL, Horiya S, Bailey JK, Xu B, Stanfield RL, Temme JS, LaBranche CC, Wang S, Rodal AA, Montefiori DC, Wilson IA, and Krauss IJ
- Subjects
- Animals, Antibodies, Neutralizing, Antibody Formation, Binding Sites, Glycosylation, HIV Envelope Protein gp120 metabolism, HIV Envelope Protein gp120 urine, HIV Infections prevention & control, Humans, Immunization, Mannosidases metabolism, Oligosaccharides urine, Protein Binding, Protein Conformation, Rabbits, Small Molecule Libraries chemistry, Vaccination, AIDS Vaccines metabolism, Glycopeptides chemistry, HIV Antibodies metabolism, HIV Envelope Protein gp120 chemistry, Oligosaccharides chemistry, Vaccines, Conjugate metabolism
- Abstract
The high mannose patch (HMP) of the HIV envelope protein (Env) is the structure most frequently targeted by broadly neutralizing antibodies; therefore, many researchers have attempted to use mimics of this region as a vaccine immunogen. In our previous efforts, vaccinating rabbits with evolved HMP mimic glycopeptides containing Man
9 resulted in an overall antibody response targeting the glycan core and linker rather than the full glycan or Manα1→2Man tips of Man9 glycans. A possible reason could be processing of our immunogen by host serum mannosidases. We sought to test whether more prolonged dosing could increase the antibody response to intact glycans, possibly by increasing the availability of intact Man9 to germinal centers. Here, we describe a study investigating the impact of immunization regimen on antibody response by testing immunogen delivery through bolus, an exponential series of mini doses, or a continuously infusing mini-osmotic pump. Our results indicate that, with our glycopeptide immunogens, standard bolus immunization elicited the strongest HIV Env-binding antibody response, even though higher overall titers to the glycopeptide were elicited by the exponential and pump regimens. Antibody selectivity for intact glycan was, if anything, slightly better in the bolus-immunized animals.- Published
- 2020
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42. Guidelines for Thrombolytic Therapy for Frostbite.
- Author
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Hickey S, Whitson A, Jones L, Wibbenmeyer L, Ryan C, Fey R, Litt J, Fabia R, Cancio L, Mohr W, Twomey J, Wagner A, Cochran A, and Bailey JK
- Subjects
- Cyanosis etiology, Finger Injuries etiology, Frostbite complications, Humans, Practice Guidelines as Topic, Rewarming, Cyanosis therapy, Finger Injuries therapy, Frostbite therapy, Thrombolytic Therapy, Toes injuries
- Abstract
The data are insufficient to support standardized treatment of all patients with frostbite with thrombolytic therapy. The following guidelines, however, should be applied to all patients with cyanosis persisting proximal to the distal phalanx (Grade 3 or 4 frostbite injury) and demonstrated loss of perfusion at or proximal to the middle phalanx immediately after rewarming., (© American Burn Association 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2020
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43. Survey of national and local practice of compression therapy timing for burn patients in the United States.
- Author
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Mehta S, Coffey R, Jones LM, Powell HM, and Bailey JK
- Subjects
- Burns complications, Cicatrix etiology, Cicatrix therapy, Cicatrix, Hypertrophic etiology, Cicatrix, Hypertrophic therapy, Humans, Skin Transplantation, Surveys and Questionnaires, Time-to-Treatment, United States, Burns therapy, Cicatrix prevention & control, Cicatrix, Hypertrophic prevention & control, Clothing, Compression Bandages, Practice Patterns, Physicians' statistics & numerical data
- Abstract
Objective: Compression therapy (CT) has been an important, but debated, treatment for burn scars. To better understand one source of variation in observed outcomes after CT, an evaluation of CT timing of application is needed., Materials and Methods: Following IRB approval, 126 burn centers were contacted to complete a 17-question survey regarding the center's practice pattern for compression garment therapy. Locally, study subjects were identified between March 1, 2014 and December 31, 2015 and medical records examined for timing of garment ordering, delivery and fitting., Results: The majority believed that compression therapy is beneficial. Most centers reported using custom-fit and pre-fabricated garments, and a goal time of application between 2-4 weeks (42%) and 4-6 weeks (36%). After the garments are ordered, 61% of centers estimate that it takes 2-4 weeks for them to arrive. No significant differences in practices were found among centers treating pediatric patients only, adults only or both. Locally, the mean number of weeks between the date of original injury and garment order placement was 9.1 weeks with an additional 8.7 weeks between the date of order and date of delivery., Conclusions: The current study identified that although the national reporting of time to garment application is estimated to be between 2-6 weeks at the majority of burn centers including our own, we found our center to be well in excess of 17 weeks. The findings offer an opportunity for local improvement, and raise the possibility of similar incongruity between goals and practice at other centers., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)
- Published
- 2019
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44. Incidence of oxandrolone induced hepatic transaminitis in patients with burn injury.
- Author
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Kiracofe B, Coffey R, Jones LM, Bailey JK, Thomas S, Porter K, and Murphy CV
- Subjects
- Adult, Alanine Transaminase blood, Alkaline Phosphatase blood, Aspartate Aminotransferases blood, Bilirubin blood, Chemical and Drug Induced Liver Injury blood, Chemical and Drug Induced Liver Injury etiology, Female, Fluid Therapy, Hospital Mortality, Humans, Incidence, International Normalized Ratio, Length of Stay statistics & numerical data, Male, Middle Aged, Resuscitation, Retrospective Studies, Risk Factors, Anabolic Agents adverse effects, Burns therapy, Chemical and Drug Induced Liver Injury epidemiology, Oxandrolone adverse effects
- Abstract
The benefits of oxandrolone in burn patients has led to its accepted use in the burn care community, however details regarding the most common adverse effect, transaminitis, remains unclear. The purpose of this study was to determine the incidence of transaminitis in patients with burn injury and identify risk factors associated with the development of transaminitis. This single-center, retrospective risk factor analysis compared burn patients on oxandrolone with and without the development of transaminitis, defined as any aspartate aminotransferase or alanine aminotransferase value >100mg/dL. Patient demographics, past medical history, lab values, and burn characteristics were recorded. Overall 28 out of 66 (42%) patients developed transaminitis. The transaminitis group had a significantly higher proportion of other concomitant medications with a transaminitis risk (p=0.045). No significant difference in liver dysfunction or length of stay was observed between the two groups. Oxandrolone induced transaminitis is occurring in patients significantly more frequently than previously reported warranting further research to guide monitoring requirements, use of concomitant medications, and to determine if rechallenging after resolution should be considered., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)
- Published
- 2019
- Full Text
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45. Climate-driven reduction of genetic variation in plant phenology alters soil communities and nutrient pools.
- Author
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Ware IM, Van Nuland ME, Schweitzer JA, Yang Z, Schadt CW, Sidak-Loftis LC, Stone NE, Busch JD, Wagner DM, and Bailey JK
- Abstract
We examined the hypothesis that climate-driven evolution of plant traits will influence associated soil microbiomes and ecosystem function across the landscape. Using a foundation tree species, Populus angustifolia, observational and common garden approaches, and a base population genetic collection that spans 17 river systems in the western United States, from AZ to MT, we show that (a) as mean annual temperature (MAT) increases, genetic and phenotypic variation for bud break phenology decline; (b) soil microbiomes, soil nitrogen (N), and soil carbon (C) vary in response to MAT and conditioning by trees; and (c) with losses of genetic variation due to warming, population-level regulation of community and ecosystem functions strengthen. These results demonstrate a relationship between the potential evolutionary response of populations and subsequent shifts in ecosystem function along a large temperature gradient., (© 2019 John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
46. Oligomannose Glycopeptide Conjugates Elicit Antibodies Targeting the Glycan Core Rather than Its Extremities.
- Author
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Nguyen DN, Xu B, Stanfield RL, Bailey JK, Horiya S, Temme JS, Leon DR, LaBranche CC, Montefiori DC, Costello CE, Wilson IA, and Krauss IJ
- Abstract
Up to ∼20% of HIV-infected individuals eventually develop broadly neutralizing antibodies (bnAbs), and many of these antibodies (∼40%) target a region of dense high-mannose glycosylation on gp120 of the HIV envelope protein, known as the "high-mannose patch" (HMP). Thus, there have been numerous attempts to develop glycoconjugate vaccine immunogens that structurally mimic the HMP and might elicit bnAbs targeting this conserved neutralization epitope. Herein, we report on the immunogenicity of glycopeptides, designed by in vitro selection, that bind tightly to anti-HMP antibody 2G12. By analyzing the fine carbohydrate specificity of rabbit antibodies elicited by these immunogens, we found that they differ from some natural human bnAbs, such as 2G12 and PGT128, in that they bind primarily to the core structures within the glycan, rather than to the Manα1 → 2Man termini (2G12) or to the whole glycan (PGT128). Antibody specificity for the glycan core may result from extensive serum mannosidase trimming of the immunogen in the vaccinated animals. This finding has broad implications for vaccine design aiming to target glycan-dependent HIV neutralizing antibodies., Competing Interests: The authors declare no competing financial interest.
- Published
- 2019
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47. Role of Early Application of Pressure Garments following Burn Injury and Autografting.
- Author
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DeBruler DM, Baumann ME, Blackstone BN, Zbinden JC, McFarland KL, Bailey JK, Supp DM, and Powell HM
- Subjects
- Animals, Biomechanical Phenomena, Biopsy, Needle, Burns pathology, Cicatrix pathology, Combined Modality Therapy, Disease Models, Animal, Immunohistochemistry, Injury Severity Score, Postoperative Care methods, Random Allocation, Swine, Time Factors, Transplantation, Autologous methods, Burns therapy, Cicatrix prevention & control, Compression Bandages, Skin Transplantation methods, Wound Healing physiology
- Abstract
Background: Pressure garment therapy, used for reduction of postburn scarring, is commonly initiated after complete healing of the wound or autograft. Although some clinicians have suggested that earlier treatment may improve outcomes, the effect of early initiation of therapy has not been studied in a controlled environment., Methods: Full-thickness burns were created on red Duroc pigs, burn eschar was excised, and the wound bed was grafted with split-thickness autografts. Grafts were treated with pressure garments immediately, 1 week (early), or 5 weeks (delayed) after grafting with nontreated grafts as controls. Scar morphology, biomechanics, and gene expression were measured at multiple time points up to 17 weeks after grafting., Results: Grafts that received pressure within 1 week after grafting exhibited no reduction in engraftment rates. Immediate and early application of pressure resulted in scars with decreased contraction, reduced scar thickness, and improved biomechanics compared with controls. Pressure garment therapy did not alter expression of collagen I, collagen III, or transforming growth factor β1 at the time points investigated; however, expression of matrix metalloproteinase 1 was significantly elevated in the immediate pressure garment therapy group at week 3, whereas the delayed pressure garment therapy and control groups approached baseline levels at this time point., Conclusions: Early application of pressure garments is safe and effective for reducing scar thickness and contraction and improving biomechanics. This preclinical study suggests that garments should be applied as soon as possible after grafting to achieve greatest benefit, although clinical studies are needed to validate the findings in humans.
- Published
- 2019
- Full Text
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48. MRI compatibility of silver based wound dressings.
- Author
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Bailey JK, Sammet S, Overocker J, Craft-Coffman B, Acevedo CM, Cowan ME, and Powell HM
- Subjects
- Animals, Artifacts, Hot Temperature, Pain, Procedural prevention & control, Swine, Bandages, Burns therapy, Magnetic Resonance Imaging methods, Silver Compounds
- Abstract
As silver dressings gain more widespread use, it is more likely that patients with silver-based dressings will also undergo magnetic resonance imaging (MRI). In current practice, these dressings are removed prior to imaging due to concerns over heating and image distortion. As dressing changes can be painful, the need to remove dressings simply for MRI may increase pain and contribute to opioid dependency. To examine the need for dressing removal, American Society for Testing and Materials International standards for assessing device deflection and torque were performed on 5 silver containing and 3 non-silver control dressings. Magnetically induced heating and image distortion were examined in a porcine hind limb wound dressed with control and test dressings. The limb was scanned in a clinical high field 3T MRI scanner using a series of standard MRI sequences (Survey, T
1 -weighted SE, T1 -weighted IR TSE, T2 -weighted TSE, DUAL TSE, and FLAIR). Deflection and torsion were not detected in control or silver-based dressings. For all combinations of dressings and MRI scans, average heating was between 0-0.2°C. Additionally, dressings, in dry and hydrated forms, caused no image distortion in any MRI scan performed. Evaluation of MRI safety and compatibility revealed no concerns for safety or image distortion in any of the silver-containing wound dressings tested thus it would be acceptable to leave these dressings intact during MRI. The ability to leave dressings in place during imaging will provide a significant benefit to patient care by reducing pain associated with dressing removal., (Copyright © 2018 Elsevier Ltd and ISBI. All rights reserved.)- Published
- 2018
- Full Text
- View/download PDF
49. Incidence of Unplanned 30-Day Readmissions in Adult Burn Patients in the United States.
- Author
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Hodosevich Z, Wheeler KK, Shi J, Coffey R, Bailey JK, Jones LM, Thakkar RK, Fabia RB, Groner JI, and Xiang H
- Subjects
- Adult, Aged, Comorbidity, Female, Humans, Incidence, Male, Middle Aged, Risk Factors, United States, Burns therapy, Patient Readmission statistics & numerical data
- Abstract
This study characterizes adult burn readmissions in the United States using a nationally representative hospital inpatient sample. Readmission rates, diagnoses, and risk factors are discussed. We analyzed the 2013 and 2014 Nationwide Readmission Database for adult burn patients. The data were weighted to estimate national 30-day readmission rates. Principal readmission diagnoses were sorted into burn-specific or other readmission categories. We used multivariable logistic regression to assess the effects of patient and hospital stay risk factors on readmissions. An estimated 42,957 U.S. adult burn patients were discharged between January and November of 2013 and 2014. Of these patients, an estimated 3203 had unscheduled readmissions within 30 days (all-cause readmission rate: 7.5%, 95% CI: 6.7-8.2). An estimated 55.4 per cent of unplanned readmissions were for burn-specific principal readmission diagnoses. Burn-specific readmission was associated with burn severity and increased with both patient age and the number of comorbidities. Patients whose length of stay was less than 1 day per % total body surface area (%TBSA) burned had higher readmission risk (Adjusted odds ratio = 2.10, 95% CI = 1.48-2.99). The results of logistic regression models were similar for burn-specific readmissions and all-cause readmissions. In a nationally representative sample of adult burn patients, 4.1 per cent had unplanned 30-day readmissions for burn-specific reasons; 7.5 per cent were readmitted for any reason. Patient comorbidities and discharge before 1 day per %TBSA from the hospital impact readmission risk. Healthcare providers can use this information to identify at-risk patients, modify their treatment plans, and prevent readmissions.
- Published
- 2018
- Full Text
- View/download PDF
50. Structural, Chemical, and Mechanical Properties of Pressure Garments as a Function of Simulated Use and Repeated Laundering.
- Author
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Malara MM, Kim JY, Clark JA, Blackstone BN, Ruegsegger MA, Bailey JK, Supp DM, and Powell HM
- Subjects
- Child, Equipment Design, Humans, Manikins, Materials Testing, Pressure, Textiles, Burns therapy, Cicatrix prevention & control, Clothing, Laundering
- Abstract
Pressure garments are widely employed for management of postburn scarring. Although pressure magnitude has been linked to efficacy, maintenance of uniform pressure delivery is challenging. An understanding of garment fabric properties is needed to optimize pressure delivery for the duration of garment use. To address this issue, compression vests were manufactured using two commonly used fabrics, Powernet or Dri-Tek Tricot, to achieve 10% reduction in circumference for a child-sized mannequin. Applied pressure was tracked on five anatomical sites over 23 hours, before laundering or after one and five laundering cycles. Load relaxation and fatigue of fabrics were tested before laundering or after one and five laundering cycles, and structural analysis via scanning electron microscopy was performed. Prior to laundering, pressure vests fabricated using Powernet or Dri-Tek Tricot generated a maximum pressure on the mannequin of 20 and 23 mm Hg, respectively. With both fabrics, pressure decreased during daily wear. Following five laundering cycles, Dri-Tek Tricot vests delivered a maximum of 7 vs 15 mm Hg pressure for Powernet at the same site. In cyclic tensile and load relaxation tests, exerted force correlated with fabric weave orientation with greatest force measured parallel to a fabric's long axis. The results demonstrate that Powernet exhibited the greatest applied force with the least garment fatigue. Fabric orientation with respect to the primary direction of tension was a critical factor in pressure generation and maintenance. This study suggests that fabrication of garments using Powernet with its long axis parallel to patient's body part circumference may enhance the magnitude and maintenance of pressure delivery.
- Published
- 2018
- Full Text
- View/download PDF
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