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The geometric, intensity, and chromatic distortions that are a result of the limitations of the material and processes used to fabricate micro-optical lens arrays (MLAs) degrade the performance of light-field systems. To address these limitations, inkjet print additive manufacturing is used to fabricate planar gradient index (GRIN) lenslet arrays, in which volumetric refractive index profiles are used to embed optical functions that would otherwise require multiple homogeneous index MLA surfaces. By tailoring the optical ink feedstock refractive index spectra, independent control over dispersion is achieved, and achromatic performance is made possible. Digital manufacturing is shown to be beneficial for optimizing individual micro-optical channels in arrays wherein the shape, size, aspect ratio, focal length, and optical axis orientation of the lenslets vary as a function of the position within the optical field. Print fabrication also allows opaque inter-lens baffling and aperture stops that reduce inter-channel cross talk, improve resolution, and enhance contrast. These benefits are demonstrated in a light-field display testbed.
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Gradient-index Alvarez lenses (GALs), a new, to the best of our knowledge, type of freeform optical component, are surveyed in this work for their unique properties in generating variable optical power. GALs display similar behavior to conventional surface Alvarez lenses (SALs) by means of a freeform refractive index distribution that has only recently been achievable in fabrication. A first-order framework is described for GALs including analytical expressions for their refractive index distribution and power variation. A useful feature of Alvarez lenses for introducing bias power is also detailed and is helpful for both GALs and SALs. The performance of GALs is studied, and the value of three-dimensional higher-order refractive index terms is demonstrated in an optimized design. Last, a fabricated GAL is demonstrated along with power measurements agreeing closely with the developed first-order theory.
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This publisher's note contains a correction to Appl. Opt.62, 3485 (2023)APOPAI0003-693510.1364/AO.487089.
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INTRODUCTION: Acute liver failure (ALF) affects 2000 Americans each year with no treatment options other than liver transplantation. We showed previously that mobilization of endogenous stem cells is protective against ALF in rodents. The objective of this study was to assess whether stem cell mobilizing drugs are lifesaving in a large animal preclinical model of ALF, to assess readiness for a clinical trial. METHODS: Male Yorkshire pigs (14-18âkg) were divided into 2 groups, control (n = 6) and treatment (n = 6). All pigs received an intravenous bolus of the hepatotoxin D-galactosamine (0.5âg/kg) via central line and were followed up until death or day 28. Treated animals received simultaneous intramuscular injection of plerixafor (1âmg/kg) and G-CSF (2âµg/kg) at baseline, 24 and 48 hours after toxin infusion to mobilize endogenous stem cells, as previously described. Control animals received saline. RESULTS: All control animals (6/6) succumbed to liver failure within 91 hours, confirmed by clinical, biochemical, and histopathological evidence of ALF. In the treatment group (5/6) animals survived indefinitely despite comparable biochemical changes during the first 48 hours (P = 0.003). White blood cell count increased by a mean of 4× in the treated group at the peak of mobilization (P = 0.0004). CONCLUSIONS: Stem cell mobilizing drugs were lifesaving in a preclinical large animal model of ALF. Since no therapeutic options other than liver transplantation are currently available for critically ill patients with ALF, a multicenter clinical trial is warranted.
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Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/farmacologia , Falência Hepática Aguda/tratamento farmacológico , Animais , Benzilaminas , Ciclamos , Modelos Animais de Doenças , Citometria de Fluxo , Galactosamina , Imuno-Histoquímica , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Masculino , SuínosRESUMO
OBJECTIVE: No therapy except liver transplantation currently exists for patients with acute liver failure (ALF). The aim of this study was to determine whether pharmacologic mobilization of endogenous hematopoietic stem cells (HSCs) can aid in liver repair and improve survival in an animal model of ALF. METHODS: Rodents were treated with a single near-lethal intraperitoneal injection of carbon tetrachloride (CCl4). After 12 hours, animals were randomized to receive plerixafor and granulocyte colony-stimulating factor (G-CSF), agents known to mobilize marrow-derived stem cells, or saline vehicle injection. Mice were observed for survival, and serial assessment of liver injury by serum transaminase measurements, and histologic analysis was performed. RESULTS: In our ALF model, 7-day survival after injection of CCl4 was 25%. Administration of plerixafor and G-CSF following CCl4 resulted in 87% survival (n = 8, P < 0.05). On serial histopathologic analysis, animals treated with plerixafor and G-CSF demonstrated less hepatic injury compared with control animals. Evaluation of peripheral blood demonstrated an increase in circulating HSCs in response to plerixafor and G-CSF, and immunostaining suggested the infiltration of HSCs into the hepatic parenchyma after stem cell mobilization. CONCLUSIONS: Our results suggest a possible new treatment strategy for patients with ALF, a group for whom either liver transplantation or death is frequently the outcome. Pharmacologic agents that mobilize HSCs may lead to an infiltration of the injured liver with cells that may participate in or expedite liver regeneration. This therapy has the potential to avert liver transplantation in some patients with ALF and may be of benefit in a wide variety of medical and surgical patients with liver injury.
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Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/uso terapêutico , Falência Hepática Aguda/tratamento farmacológico , Animais , Antígenos CD34/imunologia , Benzilaminas , Tetracloreto de Carbono , Ciclamos , Feminino , Citometria de Fluxo , Imuno-Histoquímica , Fígado/imunologia , Fígado/patologia , Falência Hepática Aguda/induzido quimicamente , Falência Hepática Aguda/patologia , Camundongos , Ratos , Ratos Endogâmicos Lew , Transaminases/sangueRESUMO
INTRODUCTION: Severe burns are often associated with high morbidity and unsatisfactory functional and esthetic outcomes. Over the last two decades, stem cells have generated great hopes for the treatment of numerous conditions including burns. The aim of this systematic review is to evaluate the role of stem cell therapy as a means to promote burn wound healing. METHODS: Comprehensive searches in major databases were carried out in March 2017 for articles on stem cell therapy in burn wound healing. In total 2103 articles were identified and screened on the basis of pre-determined inclusion and exclusion criteria. RESULTS: Fifteen experimental and two clinical studies were included in the review. The majority of studies reported significant improvement in macroscopic burn wound appearance as well as a trend toward improved microscopic appearance, after stem cell therapy. Other parameters evaluated, such as re-vascularization, collagen formation, level of pro- and anti-inflammatory mediators, apoptosis and cellular infiltrates, yielded heterogeneous results across studies. CONCLUSION: Stem cell therapy appears to exert a positive effect in burn wound healing. There is, therefore, justification for continued efforts to evaluate the use of stem cells as an adjunct to first-line therapies in burns.
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Queimaduras/terapia , Transplante de Células-Tronco , Cicatrização , Tecido Adiposo/citologia , Animais , Transplante de Medula Óssea , Humanos , Transplante de Células-Tronco Mesenquimais , RegeneraçãoRESUMO
Stem cell therapy has shown promise in treating a variety of pathologies including skin wounds, but practical applications remain elusive. Here, we demonstrate that endogenous stem cell mobilization produced by AMD3100 and low-dose tacrolimus is able to reduce by 25% the time of complete healing of full-thickness wounds created by surgical excision. Equally important, healing was accompanied by reduced scar formation and regeneration of hair follicles. Searching for mechanisms, we found that AMD3100 combined with low-dose tacrolimus mobilized increased number of lineage-negative c-Kit+, CD34+, and CD133+ stem cells. Low-dose tacrolimus also increased the number of SDF-1-bearing macrophages in the wound sites amplifying the "pull" of mobilized stem cells into the wound. Lineage tracing demonstrated the critical role of CD133 stem cells in enhanced capillary and hair follicle neogenesis, contributing to more rapid and perfect healing. Our findings offer a significant therapeutic approach to wound healing and tissue regeneration.
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Mobilização de Células-Tronco Hematopoéticas/métodos , Compostos Heterocíclicos/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Pele/citologia , Tacrolimo/farmacologia , Animais , Benzilaminas , Linhagem da Célula/efeitos dos fármacos , Cicatriz/patologia , Ciclamos , Modelos Animais de Doenças , Sinergismo Farmacológico , Folículo Piloso/citologia , Folículo Piloso/efeitos dos fármacos , Imunossupressores/farmacologia , Células-Tronco Mesenquimais/citologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Ratos Endogâmicos , Receptores CXCR4/antagonistas & inibidores , Medicina Regenerativa/métodos , Cicatrização/efeitos dos fármacosRESUMO
OBJECTIVE: There is increasing evidence that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) reduce cardiovascular and cerebrovascular events through anti-inflammatory, plaque stabilization, and neuroprotective effects independent of lipid lowering. This study was designed to investigate whether statin use reduces the incidence of perioperative stroke and mortality among patients undergoing carotid endarterectomy (CEA). METHODS: All patients undergoing CEA from 1994 to 2004 at a large academic medical center were retrospectively reviewed. The independent association of statin use and perioperative morbidity was assessed via multivariate logistic regression analysis. RESULTS: CEA was performed by 13 surgeons on 1566 patients (987 men and 579 women; mean age, 72 +/- 10 years), including 1440 (92%) isolated and 126 (8%) combined CEA/coronary artery bypass grafting procedures. The indication for CEA was symptomatic disease in 660 (42%) cases. Six hundred fifty-seven (42%) patients received a statin medication for at least 1 week before surgery. Statin use was associated with a reduction in perioperative strokes (1.2% vs 4.5%; P < .01), transient ischemic attacks (1.5% vs 3.6%; P < .01), all-cause mortality (0.3% vs 2.1%; P < .01), and median (interquartile range) length of hospitalization (2 days [2-5 days] vs 3 days [2-7 days]; P < .05). Adjusting for all demographics and comorbidities in multivariate analysis, statin use independently reduced the odds of stroke threefold (odds ratio [95% confidence interval], 0.35 [0.15-0.85]; P < .05) and death fivefold (odds ratio [95% confidence interval], 0.20 [0.04-0.99]; P < .05). CONCLUSIONS: These data suggest that perioperative statin use may reduce the incidence of cerebrovascular events and mortality among patients undergoing CEA.