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1.
Integr Environ Assess Manag ; 20(3): 725-748, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37417421

RESUMEN

Despite advances in toxicity testing and the development of new approach methodologies (NAMs) for hazard assessment, the ecological risk assessment (ERA) framework for terrestrial wildlife (i.e., air-breathing amphibians, reptiles, birds, and mammals) has remained unchanged for decades. While survival, growth, and reproductive endpoints derived from whole-animal toxicity tests are central to hazard assessment, nonstandard measures of biological effects at multiple levels of biological organization (e.g., molecular, cellular, tissue, organ, organism, population, community, ecosystem) have the potential to enhance the relevance of prospective and retrospective wildlife ERAs. Other factors (e.g., indirect effects of contaminants on food supplies and infectious disease processes) are influenced by toxicants at individual, population, and community levels, and need to be factored into chemically based risk assessments to enhance the "eco" component of ERAs. Regulatory and logistical challenges often relegate such nonstandard endpoints and indirect effects to postregistration evaluations of pesticides and industrial chemicals and contaminated site evaluations. While NAMs are being developed, to date, their applications in ERAs focused on wildlife have been limited. No single magic tool or model will address all uncertainties in hazard assessment. Modernizing wildlife ERAs will likely entail combinations of laboratory- and field-derived data at multiple levels of biological organization, knowledge collection solutions (e.g., systematic review, adverse outcome pathway frameworks), and inferential methods that facilitate integrations and risk estimations focused on species, populations, interspecific extrapolations, and ecosystem services modeling, with less dependence on whole-animal data and simple hazard ratios. Integr Environ Assess Manag 2024;20:725-748. © 2023 His Majesty the King in Right of Canada and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

2.
Integr Environ Assess Manag ; 20(3): 699-724, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-37259706

RESUMEN

Model species (e.g., granivorous gamebirds, waterfowl, passerines, domesticated rodents) have been used for decades in guideline laboratory tests to generate survival, growth, and reproductive data for prospective ecological risk assessments (ERAs) for birds and mammals, while officially adopted risk assessment schemes for amphibians and reptiles do not exist. There are recognized shortcomings of current in vivo methods as well as uncertainty around the extent to which species with different life histories (e.g., terrestrial amphibians, reptiles, bats) than these commonly used models are protected by existing ERA frameworks. Approaches other than validating additional animal models for testing are being developed, but the incorporation of such new approach methodologies (NAMs) into risk assessment frameworks will require robust validations against in vivo responses. This takes time, and the ability to extrapolate findings from nonanimal studies to organism- and population-level effects in terrestrial wildlife remains weak. Failure to adequately anticipate and predict hazards could have economic and potentially even legal consequences for regulators and product registrants. In order to be able to use fewer animals or replace them altogether in the long term, vertebrate use and whole organism data will be needed to provide data for NAM validation in the short term. Therefore, it is worth investing resources for potential updates to existing standard test guidelines used in the laboratory as well as addressing the need for clear guidance on the conduct of field studies. Herein, we review the potential for improving standard in vivo test methods and for advancing the use of field studies in wildlife risk assessment, as these tools will be needed in the foreseeable future. Integr Environ Assess Manag 2024;20:699-724. © 2023 His Majesty the King in Right of Canada and The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC). Reproduced with the permission of the Minister of Environment and Climate Change Canada. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

3.
Conserv Biol ; 37(5): e14091, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37021393

RESUMEN

Understanding how habitat fragmentation affects individual species is complicated by challenges associated with quantifying species-specific habitat and spatial variability in fragmentation effects within a species' range. We aggregated a 29-year breeding survey data set for the endangered marbled murrelet (Brachyramphus marmoratus) from >42,000 forest sites throughout the Pacific Northwest (Oregon, Washington, and northern California) of the United States. We built a species distribution model (SDM) in which occupied sites were linked with Landsat imagery to quantify murrelet-specific habitat and then used occupancy models to test the hypotheses that fragmentation negatively affects murrelet breeding distribution and that these effects are amplified with distance from the marine foraging habitat toward the edge of the species' nesting range. Murrelet habitat declined in the Pacific Northwest by 20% since 1988, whereas the proportion of habitat comprising edges increased by 17%, indicating increased fragmentation. Furthermore, fragmentation of murrelet habitat at landscape scales (within 2 km of survey stations) negatively affected occupancy of potential breeding sites, and these effects were amplified near the range edge. On the coast, the odds of occupancy decreased by 37% (95% confidence interval [CI] -54 to 12) for each 10% increase in edge habitat (i.e., fragmentation), but at the range edge (88 km inland) these odds decreased by 99% (95% CI 98 to 99). Conversely, odds of murrelet occupancy increased by 31% (95% CI 14 to 52) for each 10% increase in local edge habitat (within 100 m of survey stations). Avoidance of fragmentation at broad scales but use of locally fragmented habitat with reduced quality may help explain the lack of murrelet population recovery. Further, our results emphasize that fragmentation effects can be nuanced, scale dependent, and geographically variable. Awareness of these nuances is critical for developing landscape-level conservation strategies for species experiencing broad-scale habitat loss and fragmentation.


Efectos de la fragmentación sobre las especies en peligro a lo largo de un gradiente desde el interior hasta el borde de su distribución Resumen Es complicado entender el efecto de la fragmentación del hábitat sobre las especies individuales debido a los retos asociados con la cuantificación de hábitats específicos por especie y la variabilidad espacial de los efectos de la fragmentación dentro de la distribución de la especie. Combinamos los datos de un censo reproductivo realizado durante 29 años para el mérgulo jaspeado (Brachyramphus marmoratus) de >42,000 sitios boscosos a lo largo del noroeste del Pacífico (Oregón, Washington, y el norte de California, EE. UU.). Construimos un modelo de distribución de especie (MDE) en el cual los sitios ocupados estuvieron vinculados con imágenes de Landsat para cuantificar el hábitat específico del mérgulo y después usamos los modelos de ocupación para comprobar la hipótesis de que la fragmentación afecta negativamente la distribución reproductiva de la especie y que estos efectos se amplifican con la distancia entre el hábitat de forrajeo marino y el borde de la distribución de anidación de la especie. El hábitat del mérgulo declinó en la zona en un 20% a partir de 1988, mientras que la proporción de hábitat que comprende bordes incrementó en un 17%, lo que indica un aumento en la fragmentación. Además, la fragmentación del hábitat del mérgulo a escala de paisaje (a de 2 km de las estaciones de censo) afectó negativamente a la ocupación de sitios potenciales de reproducción y estos efectos se amplificaron cerca del borde de la distribución. La probabilidad de ocupación disminuyó en un 37% (95% IC -54 a 12) por cada 10% de incremento en el hábitat de borde (es decir, fragmentación) en la costa, pero en el borde de la distribución (88 km tierra adentro), esta probabilidad disminuyó en un 99% (95% IC 98 a 99). De forma contraria, la probabilidad de ocupación incrementó en un 31% (95% IC 14 a 52) por cada 10% de incremento en el hábitat de borde local (a 100 m de las estaciones de censo). La evasión de la fragmentación a gran escala y el uso de hábitats con calidad reducida y fragmentados a nivel local podría explicar la falta de recuperación poblacional del mérgulo. Más allá, nuestros resultados resaltan que los efectos de la fragmentación pueden estar matizados, depender de la escala y tener variación geográfica. Es importante tener conciencia de estos matices para desarrollar estrategias de conservación a nivel paisaje para las especies que experimentan fragmentación y pérdida del hábitat a gran escala.


Asunto(s)
Conservación de los Recursos Naturales , Especies en Peligro de Extinción , Animales , Ecosistema , Bosques , Washingtón
4.
Med Sci Educ ; 33(2): 409-421, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36820280

RESUMEN

The arrival of COVID-19 restrictions and the increasing demand of online instruction options posed challenges to education communities worldwide, especially in human anatomy. In response, Colorado State University developed and deployed an 8-week-long large-scale virtual reality (VR) course to supplement online human anatomy instruction. Students (n = 75) received a VR-capable laptop and head-mounted display and participated in weekly synchronous group laboratory sessions with instructors. The software enabled students to remotely collaborate in a common virtual space to work with human anatomy using an artist-rendered cadaver. Qualitative data were collected on student engagement, confidence, and reactions to the new technology. Quantitative data assessed student knowledge acquisition and retention of anatomical spatial relationships. Results indicated that students performed better in the online course (mean = 82.27%) when compared to previous in-person laboratories (mean = 80.08%). The utilization of VR promoted student engagement and increased opportunities for student interaction with teaching assistants, peers, and course content. Notably, students reported benefits that focused on unique aspects of their virtual learning environment, including the ability to infinitely scale the cadaver and walk inside and around anatomical structures. Results suggested that using VR was equivalent to 2D methods in student learning and retention of anatomical relationships. Overall, the virtual classroom maintained the rigor of traditional gross anatomy laboratories without negatively impacting student examination scores and provided a high level of accessibility, without compromising learner engagement. Supplementary Information: The online version contains supplementary material available at 10.1007/s40670-023-01751-w.

5.
PLoS One ; 17(8): e0273572, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36037158

RESUMEN

Current estimates of terrestrial bird losses across Europe from ingestion of lead ammunition are based on uncertain or generic assumptions. A method is needed to develop defensible European-specific estimates compatible with available data that does not require long-term field studies. We propose a 2-step method using carcass data and population models. The method estimates percentage of deaths diagnosed as directly caused by lead poisoning as a lower bound and, as an upper bound, the percentage of possible deaths from sublethal lead poisoning that weakens birds, making them susceptible to death by other causes. We use these estimates to modify known population-level annual mortality. Our method also allows for potential reductions in reproduction from lead shot ingestion because reductions in survival and reproduction are entered into population models of species with life histories representative of the most groups of susceptible species. The models estimate the sustainability and potential population decreases from lead poisoning in Europe. Using the best available data, we demonstrate the method on two taxonomic groups of birds: gallinaceous birds and diurnal raptors. The direction of the population trends affects the estimate, and we incorporated such trends into the method. Our midpoint estimates of the reduction in population size of the European gallinaceous bird (< 2%) group and raptor group (2.9-7.7%) depend on the species life history, maximum growth rate, population trend, and if reproduction is assumed to be reduced. Our estimates can be refined as more information becomes available in countries with data gaps. We advocate use of this method to improve upon or supplement approaches currently being used. As we demonstrate, the method also can be applied to individual species of concern if enough data across countries are available.


Asunto(s)
Intoxicación por Plomo , Rapaces , Animales , Aves , Ingestión de Alimentos , Plomo/toxicidad , Intoxicación por Plomo/epidemiología , Intoxicación por Plomo/veterinaria , Dinámica Poblacional
6.
Front Bioeng Biotechnol ; 9: 727869, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34485262

RESUMEN

Tissue engineering using decellularized whole lungs as matrix scaffolds began as a promise for creating autologous transplantable lungs for patients with end-stage lung disease and can also be used to study strategies for lung regeneration. Vascularization remains a critical component for all solid organ bioengineering, yet there has been limited success in generating functional re-endothelialization of most pulmonary vascular segments. We evaluated recellularization of the blood vessel conduits of acellular mouse scaffolds with highly proliferating, rat pulmonary microvascular endothelial progenitor cells (RMEPCs), pulmonary arterial endothelial cells (PAECs) or microvascular endothelial cells (MVECs). After 8 days of pulsatile perfusion, histological analysis showed that PAECs and MVECs possessed selective tropism for larger vessels or microvasculature, respectively. In contrast, RMEPCs lacked site preference and repopulated all vascular segments. RMEPC-derived endothelium exhibited thrombomodulin activity, expression of junctional genes, ability to synthesize endothelial signaling molecules, and formation of a restrictive barrier. The RMEPC phenotype described here could be useful for identifying endothelial progenitors suitable for efficient vascular organ and tissue engineering, regeneration and repair.

7.
J Med Educ Curric Dev ; 7: 2382120520941822, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32775692

RESUMEN

Using cadaveric instruction in a graduate-level anatomy course is an expensive and time-consuming undertaking. While this is a worthwhile endeavor, most first-year medical students and students in the health fields struggle with the independent, self-directed learning approach in the cadaveric laboratory, and going beyond rote memorization of the material. As such, effective assessment tools that maximize student learning in the cadaveric laboratory are critical, especially if no lecture component is present. Dissection quality often reflects student attention to detail and therefore may be tied to overall performance in the course. The aim of this study was to investigate the relationship between weekly table quizzes and the overall student outcomes in a graduate biomedical human dissection class as well as examining the benefits and implications of this approach. In this course, a uniquely structured weekly quiz assessed dissection quality and probed student understanding in human anatomy. Student data compiled from 5 years of dissection courses were analyzed to evaluate the relationship between performance in the weekly assessment and on the unit examinations. The results showed a statistically significant relationship between the weekly quizzes and the student examinations at the end of each dissection block in 2013, 2015, 2016, and 2017. The data suggest a potential correlation between performance on weekly quizzes and on unit examinations. The unique nature of the table quizzes provides the students with the opportunity to practice the retrieval of their knowledge, feel more guided throughout their dissection, and receive immediate feedback on their performance. This assessment tool also provides a way to predict student outcomes and an opportunity for early intervention to help at-risk students. The analysis of this research study contributes to the need for more data on the usage of assessment tools in a graduate human dissection class.

9.
Adv Mater ; 31(10): e1806899, 2019 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-30663123

RESUMEN

The development of 3D in vitro models capable of recapitulating native tumor microenvironments could improve the translatability of potential anticancer drugs and treatments. Here, 3D bioprinting techniques are used to build tumor constructs via precise placement of living cells, functional biomaterials, and programmable release capsules. This enables the spatiotemporal control of signaling molecular gradients, thereby dynamically modulating cellular behaviors at a local level. Vascularized tumor models are created to mimic key steps of cancer dissemination (invasion, intravasation, and angiogenesis), based on guided migration of tumor cells and endothelial cells in the context of stromal cells and growth factors. The utility of the metastatic models for drug screening is demonstrated by evaluating the anticancer efficacy of immunotoxins. These 3D vascularized tumor tissues provide a proof-of-concept platform to i) fundamentally explore the molecular mechanisms of tumor progression and metastasis, and ii) preclinically identify therapeutic agents and screen anticancer drugs.


Asunto(s)
Biomimética , Neoplasias , Impresión Tridimensional , Ingeniería de Tejidos , Microambiente Tumoral , Ensayos de Selección de Medicamentos Antitumorales/métodos , Humanos , Neoplasias/patología , Andamios del Tejido/química
10.
J Cardiovasc Transl Res ; 12(4): 271-279, 2019 08.
Artículo en Inglés | MEDLINE | ID: mdl-30680546

RESUMEN

Dyspnea is a major symptom of heart failure (HF). Here, we have studied the lung remodeling and airway resistance in HF mice. We demonstrated that aortic banding-induced HF caused a dramatic decrease of lung compliance and an increase of lung airway resistance. The decrease of lung compliance was correlated with the increased lung weight in a linear fashion (γ2 = 0.824). An HF-induced increase of lung airway resistance and a decrease of lung compliance were almost identical in anesthetized mice and in the isolated lungs from these mice. HF caused profound lung fibrosis in mice with increased lung weight. Moreover, HF patients of NYHA class III-IV showed increased lung density as revealed by high-resolution CT scanning. These data indicate that lung compliance and lung airway resistance may be useful in determining lung remodeling after HF, and lung structure changes may contribute to dyspnea in HF.


Asunto(s)
Remodelación de las Vías Aéreas (Respiratorias) , Resistencia de las Vías Respiratorias , Disnea/etiología , Insuficiencia Cardíaca/complicaciones , Pulmón/fisiopatología , Fibrosis Pulmonar/etiología , Animales , Modelos Animales de Enfermedad , Disnea/diagnóstico por imagen , Disnea/patología , Disnea/fisiopatología , Insuficiencia Cardíaca/patología , Insuficiencia Cardíaca/fisiopatología , Humanos , Pulmón/diagnóstico por imagen , Pulmón/patología , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Fibrosis Pulmonar/diagnóstico por imagen , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/fisiopatología , Volumen Sistólico , Tomografía Computarizada por Rayos X , Función Ventricular Izquierda
11.
Mod Pathol ; 32(4): 560-567, 2019 04.
Artículo en Inglés | MEDLINE | ID: mdl-30425334

RESUMEN

Amphiregulin, a weak epidermal growth factor receptor agonist, is elevated, while epidermal growth factor, a strong epidermal growth factor receptor agonist, is low in the blood of patients with severe acute graft-versus-host disease. However, the tissue expression and function of these epidermal growth factor receptor ligands in acute graft-versus-host disease target organs is unknown. We compared by immunohistochemistry expression of amphiregulin and epidermal growth factor in archived, formalin-fixed, paraffin-embedded intestinal tissues of 48 patients with biopsy-proven gastrointestinal acute graft-versus-host disease to 3 groups: (1) 10 non-hematopoietic cell transplant normal controls, (2) 11 patients with newly diagnosed ulcerative colitis (ulcerative colitis), (3) 8 patients with a clinical diagnosis of acute graft-versus-host disease despite pathologically non-diagnostic biopsies, (4) and 10 cases of cytomegalovirus colitis. We used a semi-quantitative score of 0 (absent) through 3 (strong) to describe the intensity of immunohistochemical staining. We correlated serum and tissue amphiregulin and epidermal growth factor in patients with acute graft-versus-host disease. Gastrointestinal amphiregulin was significantly lower in acute graft-versus-host disease biopsies (median score 1), ulcerative colitis (median score 1.5), and cytomegalovirus colitis (median score 1) than in normal colon (median score 2, p = 0.004, p = 0.03, p = 0.009 respectively). Amphiregulin expression in was low in 74% of acute graft-versus-host disease cases with or without significant apoptosis. Patients with acute graft-versus-host disease exhibiting the pattern of high gastrointestinal amphiregulin but low serum amphiregulin (n = 14) had the best 1-year survival at 71%, but patients with high serum amphiregulin had poorer survival (<30%) regardless of gastrointestinal amphiregulin expression. Overall, our results lead to the hypothesis that amphiregulin is released into the circulation from damaged intestinal epithelium and stroma, although contributions from other cellular sources are likely. Low gastrointestinal amphiregulin expression by immunohistochemistry may be further studied for its utility in the pathologic acute graft-versus-host disease diagnosis without classic apoptotic changes.


Asunto(s)
Anfirregulina/análisis , Anfirregulina/biosíntesis , Biomarcadores/análisis , Enfermedad Injerto contra Huésped/diagnóstico , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Adolescente , Adulto , Anciano , Niño , Preescolar , Receptores ErbB/análisis , Femenino , Humanos , Intestinos/patología , Masculino , Persona de Mediana Edad , Adulto Joven
12.
Artículo en Inglés | MEDLINE | ID: mdl-30377470

RESUMEN

Both research and practical experience in education support the use of case studies in the classroom to engage students and develop critical thinking skills. In particular, working through case studies in scientific disciplines encourages students to incorporate knowledge from a variety of backgrounds and apply a breadth of information. While it is recognized that critical thinking is important for student success in professional school and future careers, a specific strategy to tackle a novel problem is lacking in student training. We have developed a four-step systematic approach to solving case studies that improves student confidence and provides them with a definitive road map that is useful when solving any novel problem, both in and out of the classroom. This approach encourages students to define unfamiliar terms, create a timeline, describe the systems involved, and identify any unique features. This method allows students to solve complex problems by organizing and applying information in a logical progression. We have incorporated case studies in anatomy and neuroanatomy courses and are confident that this systematic approach will translate well to courses in various scientific disciplines.

13.
Transpl Int ; 31(12): 1405-1417, 2018 12.
Artículo en Inglés | MEDLINE | ID: mdl-29981183

RESUMEN

Portable normothermic EVLP has been evaluated in clinical trials using standard and extended-criteria donor lungs. We describe a swine model of lung transplant following donation after circulatory death using prolonged normothermic EVLP to assess the relationship between EVLP data and acute lung allograft function. Adult swine were anesthetized and heparinized. In the control group (n = 4), lungs were procured, flushed, and transplanted. Treatment swine underwent either standard procurement (n = 3) or agonal hypoxia followed by 1 (n = 4) or 2 hours (H) (n = 4) of ventilated warm ischemia. Lungs were preserved for 24H using normothermic blood-based EVLP then transplanted. Recipients were monitored for 4 H. After 24H of preservation, mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR), and dynamic compliance (Cdyn ) were improved in all EVLP groups. After transplant, EVLP groups showed similar allograft oxygenation. EVLP PVR, mPAP, and lung block weights had significant negative correlations with post-transplant allograft oxygenation. EVLP P:F ratio did not correlate with acute post-transplant allograft function until 24H of preservation. Data measured in the first 8H of EVLP were sufficient for predicting acute post-transplant allograft function. This study provides a benchmark and platform for evaluation of therapies for donor-related allograft injury in injured lungs treated with prolonged normothermic EVLP.


Asunto(s)
Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/métodos , Pulmón/patología , Perfusión , Aloinjertos , Animales , Modelos Animales de Enfermedad , Hemodinámica , Hipoxia , Inflamación , Masculino , Preservación de Órganos , Oxígeno/química , Edema Pulmonar , Daño por Reperfusión , Porcinos , Factores de Tiempo , Trasplante Homólogo , Isquemia Tibia
14.
Radiother Oncol ; 124(3): 468-474, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28778346

RESUMEN

PURPOSE: To develop a murine total marrow irradiation (TMI) model in comparison with the total body irradiation (TBI) model. MATERIALS AND METHODS: Myeloablative TMI and TBI were administered in mice using a custom jig, and the dosimetric differences between TBI and TMI were evaluated. The early effects of TBI/TMI on bone marrow (BM) and organs were evaluated using histology, FDG-PET, and cytokine production. TMI and TBI with and without cyclophosphamide (Cy) were evaluated for donor cell engraftment and tissue damage early after allogeneic hematopoietic cell transplantation (HCT). Stromal derived factor-1 (SDF-1) expression was evaluated. RESULTS: TMI resulted in similar dose exposure to bone and 50% reduction in dose to bystander organs. BM histology was similar between the groups. In the non-HCT model, TMI mice had significantly less acute intestinal and lung injury compared to TBI. In the HCT model, recipients of TMI had significantly less acute intestinal injury and spleen GVHD, but increased early donor cell engraftment and BM:organ SDF-1 ratio compared to TBI recipients. CONCLUSIONS: The expected BM damage was similar in both models, but the damage to other normal tissues was reduced by TMI. However, BM engraftment was improved in the TMI group compared to TBI, which may be due to enhanced production of SDF-1 in BM relative to other organs after TMI.


Asunto(s)
Médula Ósea/efectos de la radiación , Irradiación Corporal Total , Anfirregulina/análisis , Animales , Factor de Crecimiento Epidérmico/análisis , Femenino , Trasplante de Células Madre Hematopoyéticas , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Dosis de Radiación
15.
Transplantation ; 101(10): 2303-2311, 2017 10.
Artículo en Inglés | MEDLINE | ID: mdl-28009782

RESUMEN

BACKGROUND: We report the ability to extend lung preservation up to 24 hours (24H) by using autologous whole donor blood circulating within an ex vivo lung perfusion (EVLP) system. This approach facilitates donor lung reconditioning in a model of extended normothermic EVLP. We analyzed comparative responses to cellular and acellular perfusates to identify these benefits. METHODS: Twelve pairs of swine lungs were retrieved after cardiac arrest and studied for 24H on the Organ Care System (OCS) Lung EVLP platform. Three groups (n = 4 each) were differentiated by perfusate: (1) isolated red blood cells (RBCs) (current clinical standard for OCS); (2) whole blood (WB); and (3) acellular buffered dextran-albumin solution (analogous to STEEN solution). RESULTS: Only the RBC and WB groups met clinical standards for transplantation at 8 hours; our primary analysis at 24H focused on perfusion with WB versus RBC. The WB perfusate was superior (vs RBC) for maintaining stability of all monitored parameters, including the following mean 24H measures: pulmonary artery pressure (6.8 vs 9.0 mm Hg), reservoir volume replacement (85 vs 1607 mL), and PaO2:FiO2 ratio (541 vs 223). Acellular perfusion was limited to 6 hours on the OCS system due to prohibitively high vascular resistance, edema, and worsening compliance. CONCLUSIONS: The use of an autologous whole donor blood perfusate allowed 24H of preservation without functional deterioration and was superior to both RBC and buffered dextran-albumin solution for extended lung preservation in a swine model using OCS Lung. This finding represents a potentially significant advance in donor lung preservation and reconditioning.


Asunto(s)
Eritrocitos , Circulación Extracorporea/métodos , Trasplante de Pulmón/métodos , Pulmón/irrigación sanguínea , Pulmón/efectos de los fármacos , Soluciones Preservantes de Órganos/farmacología , Preservación de Órganos/métodos , Perfusión/métodos , Animales , Eritrocitos/metabolismo , Paro Cardíaco , Hemodinámica , Pulmón/patología , Pulmón/cirugía , Lesión Pulmonar/etiología , Trasplante de Pulmón/efectos adversos , Masculino , Modelos Animales , Preservación de Órganos/efectos adversos , Oxígeno/sangre , Perfusión/efectos adversos , Neumonía/etiología , Circulación Pulmonar , Edema Pulmonar/etiología , Daño por Reperfusión/etiología , Sus scrofa , Factores de Tiempo , Supervivencia Tisular/efectos de los fármacos
16.
PLoS One ; 11(3): e0150966, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26954258

RESUMEN

The lung changes functionally and structurally with aging. However, age-related effects on the extracellular matrix (ECM) and corresponding effects on lung cell behavior are not well understood. We hypothesized that ECM from aged animals would induce aging-related phenotypic changes in healthy inoculated cells. Decellularized whole organ scaffolds provide a powerful model for examining how ECM cues affect cell phenotype. The effects of age on ECM composition in both native and decellularized mouse lungs were assessed as was the effect of young vs old acellular ECM on human bronchial epithelial cells (hBECs) and lung fibroblasts (hLFs). Native aged (1 year) lungs demonstrated decreased expression of laminins α3 and α4, elastin and fibronectin, and elevated collagen, compared to young (3 week) lungs. Proteomic analyses of decellularized ECM demonstrated similar findings, and decellularized aged lung ECM contained less diversity in structural proteins compared to young ECM. When seeded in old ECM, hBECs and hLFs demonstrated lower gene expression of laminins α3 and α4, respectively, as compared to young ECM, paralleling the laminin deficiency of aged ECM. ECM changes appear to be important factors in potentiating aging-related phenotypes and may provide clues to mechanisms that allow for aging-related lung diseases.


Asunto(s)
Células Epiteliales Alveolares/metabolismo , Fibroblastos/metabolismo , Expresión Génica , Laminina/genética , Factores de Edad , Animales , Cadherinas/genética , Cadherinas/metabolismo , Técnicas de Cultivo de Célula , Matriz Extracelular/metabolismo , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Femenino , Perfilación de la Expresión Génica , Laminina/metabolismo , Pulmón/metabolismo , Pulmón/patología , Masculino , Ratones , Fenotipo , Tromboplastina/genética , Tromboplastina/metabolismo
17.
PLoS One ; 11(1): e0147189, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26799815

RESUMEN

Little is known about the magnitude of the effects of lead shot ingestion alone or combined with poisons (e.g., in bait or seeds/granules containing pesticides) on population size, growth, and extinction of non-waterbird avian species that ingest these substances. We used population models to create example scenarios demonstrating how changes in these parameters might affect three susceptible species: grey partridge (Perdix perdix), common buzzard (Buteo buteo), and red kite (Milvus milvus). We added or subtracted estimates of mortality due to lead shot ingestion (4-16% of mortality, depending on species) and poisons (4-46% of mortality) reported in the UK or France to observed mortality of studied populations after models were calibrated to observed population trends. Observed trends were decreasing for partridge (in continental Europe), stable for buzzard (in Germany), and increasing for red kite (in Wales). Although lead shot ingestion and poison at modeled levels did not change the trend direction for the three species, they reduced population size and slowed population growth. Lead shot ingestion at modeled rates reduced population size of partridges by 10%, and when combined with bait and pesticide poisons, by 18%. For buzzards, decrease in mean population size by lead shot and poisons combined was much smaller (≤ 1%). The red kite population has been recovering; however, modeled lead shot ingestion reduced its annual growth rate from 6.5% to 4%, slowing recovery. If mortality from poisoned baits could be removed, the kite population could potentially increase at a rapid annual rate of 12%. The effects are somewhat higher if ingestion of these substances additionally causes sublethal reproductive impairment. These results have uncertainty but suggest that declining or recovering populations are most sensitive to lead shot or poison ingestion, and removal of poisoned baits can have a positive impact on recovering raptor populations that frequently feed on carrion.


Asunto(s)
Aves/crecimiento & desarrollo , Plomo/toxicidad , Animales , Europa (Continente) , Humanos , Crecimiento Demográfico
18.
PLoS One ; 11(1): e0147716, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-26824231

RESUMEN

Selenium is an essential element required for activity of several antioxidant enzymes, including glutathione peroxidase. Because of the critical role of the antioxidant system in responding to traumatic events, we hypothesized that dietary selenium supplementation would enhance neuroprotection in a rodent model of spinal cord injury. Rats were maintained on either a control or selenium-enriched diet prior to, and following, injury. Dietary selenium supplementation, provided as selenized yeast added to normal rat chow, resulted in a doubling of selenium levels in the spinal cord. Dietary selenium reduced the time required for recovery of bladder function following thoracic spinal cord injury. However, this was not accompanied by improvement in locomotor function or tissue sparing.


Asunto(s)
Suplementos Dietéticos , Locomoción/efectos de los fármacos , Compuestos de Organoselenio/uso terapéutico , Traumatismos de la Médula Espinal/tratamiento farmacológico , Médula Espinal/efectos de los fármacos , Vejiga Urinaria/efectos de los fármacos , Animales , Suplementos Dietéticos/análisis , Femenino , Ratas , Ratas Sprague-Dawley , Recuperación de la Función , Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/fisiopatología , Vejiga Urinaria/fisiopatología
19.
High Alt Med Biol ; 16(2): 154-61, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25950723

RESUMEN

Lipman, Grant S., Nicholas C. Kanaan, Caleb Phillips, Dave Pomeranz, Patrick Cain, Kristin Fontes, Becky Higbee, Carolyn Meyer, Michael Shaheen, Sean Wentworth, and Diane Walsh. Study Looking at End Expiratory Pressure for Altitude Illness Decrease (SLEEP-AID). High Alt Med Biol 16:154-161, 2015.--Acute mountain sickness (AMS) affects 25%-70% of the tens of millions of high altitude travelers annually, with hypoxia and nocturnal desaturations as major contributing factors. This is the first double blind randomized placebo controlled trial to assess expiratory positive airway pressure (EPAP) for AMS prevention and nocturnal hypoxic events. Healthy adult participants trekking in the Khumbu region of the Himalayas were randomized to a single-use EPAP nasal strip, or a visually identical sham device (placebo) prior to first night sleeping between 4371-4530 m (14,340-14,800 ft). The primary outcome was AMS incidence, measured by Lake Louise Questionnaire (LLQ), with secondary outcomes of AMS severity (by LLQ) and physiologic sleep indices measured by continuous sleep monitor. Intent-to-treat analysis included 219 participants with comparable demographic characteristics, of which 115 received EPAP and 104 placebo. There was no decrease in AMS with EPAP intervention (14% EPAP vs. 17% placebo; p=0.65; risk difference (-)3.15%, 95% CI (-)12.85%-6.56%). While overall AMS severity was not different between groups, EPAP reported decreased incidence of headache (64% vs. 76%; p<0.05, OR 0.51, 95% CI 0.27-0.95) and dizziness (81% vs. 98%; p<0.03, OR 0.29, 95% CI 0.09-0.78). During sleep, EPAP resulted in significant improvements in average peripheral oxygenation (Spo(2)) (80% versus 78%; p<0.01, mean difference=2, 95% CI 0.58-3.63) and a reduced percentage of time below 80% Spo(2) (31% vs. 46%; p<0.03, median difference=16, 95% CI 2.22-28.18). This lightweight and inexpensive EPAP device did not prevent acute mountain sickness, but did reduce the subgroup incidence of headache and dizziness while improving average nighttime peripheral oxygenation.


Asunto(s)
Mal de Altura/prevención & control , Altitud , Respiración con Presión Positiva , Sueño/fisiología , Enfermedad Aguda , Adulto , Mal de Altura/epidemiología , Método Doble Ciego , Femenino , Humanos , Incidencia , Masculino , Nepal , Oxígeno/metabolismo , Polisomnografía , Intercambio Gaseoso Pulmonar/fisiología , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Factores de Tiempo
20.
Integr Environ Assess Manag ; 11(1): 67-79, 2015 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-25158048

RESUMEN

Current scientific advances in metal and metalloid risk assessment were applied to evaluate risk to aquatic and riparian wildlife species potentially impacted by residual coal fly ash after cleanup of an unprecedented large ash release into an aquatic environment-the first assessment of its kind. Risk was evaluated using multiple lines of evidence (LOE), including 1) tissue-based risk assessment of inorganic concentrations in piscivorous and insectivorous bird eggs and raccoon organs, 2) deterministic and probabilistic diet-based risk estimates for 10 receptors species, 3) raccoon health metrics, and 4) tree swallow nest productivity measures. Innovative approaches included use of tissue-based toxicity reference values (TRVs), adjustment of bioavailability in the dietary uptake models (using sequential metal extractions in sediment), partitioning chemical species into uptake compartments (e.g., prey gut, nongut, sediment), incorporating uncertainty in both modeled dose and dietary TRVs, matching TRVs to chemical forms of constituents, and pairing these LOEs with reproductive success or health status of sensitive receptor species. The weight of evidence revealed that risk to wildlife from residual ash was low and that risk, though low, was most pronounced for insectivorous birds from exposure to Se and As. This information contributes to the debate surrounding coal combustion residue regulations prompted by this ash release. Because of the responsible party's proactive approach of applying state-of-the-art methods to assess risk using several LOEs that produced consistent results, and because of their inclusion of the regulating agencies in decisions at every step of the process, the risk assessment results were accepted, and an effective approach toward cleanup protective of the environment was quickly implemented. This study highlights the value of using multiple LOEs and the latest scientific advances to assist in timely decision making to obtain an effective remedy for an emergency spill.


Asunto(s)
Arsénico/análisis , Liberación de Peligros Químicos , Ceniza del Carbón , Metales/análisis , Contaminantes Químicos del Agua/análisis , Animales , Animales Recién Nacidos , Arsénico/sangre , Arvicolinae , Aves , Química Encefálica , Quirópteros , Sedimentos Geológicos , Gónadas/química , Cabello/química , Riñón/química , Hígado/química , Metales/sangre , Visón , Músculos/química , Óvulo/química , Mapaches , Reproducción , Medición de Riesgo , Ríos , Tennessee , Contaminantes Químicos del Agua/sangre
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