Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 65
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
ACS Chem Neurosci ; 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32579336

RESUMO

Ion channels are polymorphic membrane proteins whose high-resolution structures offer images of individual conformations, giving us starting points for identifying the complex and transient allosteric changes that give rise to channel physiology. Here, we report live-cell imaging of voltage-dependent structural changes of voltage-gated Kv2.1 channels using peptidyl tarantula toxins labeled with an environment-sensitive fluorophore, whose spectral shifts enable identification of voltage-dependent conformation changes in the resting voltage sensing domain (VSD) of the channel. We synthesize a new environment-sensitive, far-red fluorophore, julolidine phenoxazone (JP) azide, and conjugate it to tarantula toxin GxTX to characterize Kv2.1 VSD allostery during membrane depolarization. JP has an inherent response to the polarity of its immediate surroundings, offering site-specific structural insight into each channel conformation. Using voltage-clamp spectroscopy to collect emission spectra as a function of membrane potential, we find that they vary with toxin labeling site, the presence of Kv2 channels, and changes in membrane potential. With a high-affinity conjugate in which the fluorophore itself interacts closely with the channel, the emission shift midpoint is 50 mV more negative than the Kv2.1 gating current midpoint. This suggests that substantial conformational changes at the toxin-channel interface are associated with early gating charge transitions and these are not concerted with VSD motions at more depolarized potentials. These fluorescent probes enable study of conformational changes that can be correlated with electrophysiology, putting channel structures and models into a context of live-cell membranes and physiological states.

2.
Sci Rep ; 10(1): 8038, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32415171

RESUMO

Chili peppers produce capsaicin (a vanilloid) that activates the transient receptor potential cation channel subfamily V member 1 (TRPV1) on sensory neurons to alter their membrane potential and induce pain. To identify residues responsible for differential TRPV1 capsaicin sensitivity among species, we used intracellular Ca2+ imaging to characterize chimeras composed of capsaicin-sensitive rat TRPV1 (rTRPV1) and capsaicin-insensitive chicken TRPV1 (cTRPV1) exposed to a series of capsaicinoids. We found that chimeras containing rat E570-V686 swapped into chicken receptors displayed capsaicin sensitivity, and that simply changing the alanine at position 578 in the S4-S5 helix of the chicken receptor to a glutamic acid was sufficient to endow it with capsaicin sensitivity in the micromolar range. Moreover, introduction of lysine, glutamine or proline at residue A578 also elicited capsaicin sensitivity in cTRPV1. Similarly, replacing corresponding rTRPV1 residue E570 with lysine or glutamine retained capsaicin sensitivity. The hydrophilic capsaicin analog Cap-EA activated a cTRPV1-A578E mutant, suggesting that A578 may participate in vanilloid binding. The hydrophilic vanilloid agonist zingerone did not activate any A578 mutants with capsaicin sensitivity, suggesting that the vanilloid group alone is not sufficient for receptor activation. Our study demonstrates that a subtle modification of TRPV1 in different species globally alters capsaicin responses.

3.
J Am Acad Orthop Surg ; 28(11): 464-470, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32287086

RESUMO

On March 14, 2020, the Surgeon General of the United States urged a widespread cessation of all elective surgery across the country. The suddenness of this mandate and the concomitant spread of the COVID-19 virus left many hospital systems, orthopaedic practices, and patients with notable anxiety and confusion as to the near, intermediate, and long-term future of our healthcare system. As with most businesses in the United States during this time, many orthopaedic practices have been emotionally and fiscally devastated because of this crisis. Furthermore, this pandemic is occurring at a time where small and midsized orthopaedic groups are already struggling to cover practice overhead and to maintain autonomy from larger health systems. It is anticipated that many groups will experience financial demise, leading to substantial global consolidation. Because the authors represent some of the larger musculoskeletal multispecialty groups in the country, we are uniquely positioned to provide a framework with recommendations to best weather the ensuing months. We think these recommendations will allow providers and their staff to return to an infrastructure that can adjust immediately to the pent-up healthcare demand that may occur after the COVID-19 pandemic. In this editorial, we address practice finances, staffing, telehealth, operational plans after the crisis, and ethical considerations.


Assuntos
Betacoronavirus , Infecções por Coronavirus , Assistência à Saúde/organização & administração , Procedimentos Ortopédicos/economia , Pandemias/prevenção & controle , Pneumonia Viral , Administração da Prática Médica/organização & administração , Análise Custo-Benefício , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , Procedimentos Ortopédicos/métodos , Avaliação de Resultados em Cuidados de Saúde , Estados Unidos
4.
ACS Nano ; 14(2): 1508-1519, 2020 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-32053350

RESUMO

Micron-sized lasers fabricated from upconverting nanoparticles (UCNP) coupled to whispering gallery mode (WGM) microresonators can exhibit continuous-wave anti-Stokes lasing useful for tracking cells, environmental sensing, and coherent stimulation of biological activity. The integration of these microlasers into organisms and microelectronics requires even smaller diameters, however, which raises threshold pump powers beyond practical limits for biological applications. To meet the need for low lasing thresholds and high fidelity fabrication methods, we use correlative optical and electron microscopy to uncover the nanoparticle assembly process and structural factors that determine efficient upconverted lasing. We show that 5 µm microspheres with controlled submonolayer UCNP coatings exhibit, on average, 25-fold lower laser thresholds (1.7 ± 0.7 kW/cm2) compared to the mean values of the lowest threshold UCNP lasers, and variability is reduced 30-fold. WGMs are observed in the upconversion spectra for TiO2-coated microspheres as small as 3 µm, a size at which optical losses had previously prevented such observations. Finally, we demonstrate that the WGM signatures of these upconverting microlasers can be imaged and distinguished through tissue-mimicking phantoms. These advances will enable the fabrication of more efficient upconverting lasers for imaging, sensing, and actuation in optically complex environments.

5.
Biomater Sci ; 8(3): 837-845, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31790090

RESUMO

Semiconductor quantum dots (QDs) have demonstrated utility in long-term single particle tracking of membrane proteins in live cells in culture. To extend the superior optical properties of QDs to more physiologically relevant cell platforms, such as acute brain slices, we examine the photophysics of compact ligand-conjugated CdSe/CdS QDs using both ensemble and single particle analysis in brain tissue media. We find that symmetric core passivation is critical for both photostability in oxygenated media and for prolonged single particle imaging in brain slices. We then demonstrate the utility of these QDs by imaging single dopamine transporters in acute brain slices, achieving 20 nm localization precision at 10 Hz frame rates. These findings detail design requirements needed for new QD probes in complex living environments, and open the door to physiologically relevant studies that capture the utility of QD probes in acute brain slices.

6.
Theranostics ; 9(26): 8239-8252, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754393

RESUMO

Rationale: Intraoperative visualization in small surgical cavities and hard-to-access areas are essential requirements for modern, minimally invasive surgeries and demand significant miniaturization. However, current optical imagers require multiple hard-to-miniaturize components including lenses, filters and optical fibers. These components restrict both the form-factor and maneuverability of these imagers, and imagers largely remain stand-alone devices with centimeter-scale dimensions. Methods: We have engineered INSITE (Immunotargeted Nanoparticle Single-Chip Imaging Technology), which integrates the unique optical properties of lanthanide-based alloyed upconverting nanoparticles (aUCNPs) with the time-resolved imaging of a 25-micron thin CMOS-based (complementary metal oxide semiconductor) imager. We have synthesized core/shell aUCNPs of different compositions and imaged their visible emission with INSITE under either NIR-I and NIR-II photoexcitation. We characterized aUCNP imaging with INSITE across both varying aUCNP composition and 980 nm and 1550 nm excitation wavelengths. To demonstrate clinical experimental validity, we also conducted an intratumoral injection into LNCaP prostate tumors in a male nude mouse that was subsequently excised and imaged with INSITE. Results: Under the low illumination fluences compatible with live animal imaging, we measure aUCNP radiative lifetimes of 600 µs - 1.3 ms, which provides strong signal for time-resolved INSITE imaging. Core/shell NaEr0.6Yb0.4F4 aUCNPs show the highest INSITE signal when illuminated at either 980 nm or 1550 nm, with signal from NIR-I excitation about an order of magnitude brighter than from NIR-II excitation. The 55 µm spatial resolution achievable with this approach is demonstrated through imaging of aUCNPs in PDMS (polydimethylsiloxane) micro-wells, showing resolution of micrometer-scale targets with single-pixel precision. INSITE imaging of intratumoral NaEr0.8Yb0.2F4 aUCNPs shows a signal-to-background ratio of 9, limited only by photodiode dark current and electronic noise. Conclusion: This work demonstrates INSITE imaging of aUCNPs in tumors, achieving an imaging platform that is thinned to just a 25 µm-thin, planar form-factor, with both NIR-I and NIR-II excitation. Based on a highly paralleled array structure INSITE is scalable, enabling direct coupling with a wide array of surgical and robotic tools for seamless integration with tissue actuation, resection or ablation.

7.
Nat Mater ; 18(11): 1172-1176, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31548631

RESUMO

Miniaturized lasers are an emerging platform for generating coherent light for quantum photonics, in vivo cellular imaging, solid-state lighting and fast three-dimensional sensing in smartphones1-3. Continuous-wave lasing at room temperature is critical for integration with opto-electronic devices and optimal modulation of optical interactions4,5. Plasmonic nanocavities integrated with gain can generate coherent light at subwavelength scales6-9, beyond the diffraction limit that constrains mode volumes in dielectric cavities such as semiconducting nanowires10,11. However, insufficient gain with respect to losses and thermal instabilities in nanocavities has limited all nanoscale lasers to pulsed pump sources and/or low-temperature operation6-9,12-15. Here, we show continuous-wave upconverting lasing at room temperature with record-low thresholds and high photostability from subwavelength plasmons. We achieve selective, single-mode lasing from Yb3+/Er3+-co-doped upconverting nanoparticles conformally coated on Ag nanopillar arrays that support a single, sharp lattice plasmon cavity mode and greater than wavelength λ/20 field confinement in the vertical dimension. The intense electromagnetic near-fields localized in the vicinity of the nanopillars result in a threshold of 70 W cm-2, orders of magnitude lower than other small lasers. Our plasmon-nanoarray upconverting lasers provide directional, ultra-stable output at visible frequencies under near-infrared pumping, even after six hours of constant operation, which offers prospects in previously unrealizable applications of coherent nanoscale light.


Assuntos
Lasers , Nanotecnologia , Fenômenos Ópticos , Fótons , Temperatura
8.
Foot Ankle Int ; 40(12): 1375-1381, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31434509

RESUMO

BACKGROUND: The purpose of this study was to evaluate patients for intermediate-term pain relief, functional outcome, and changes in hallux alignment following isolated, complete fibular sesamoidectomy via a plantar approach for sesamoid-related pain recalcitrant to conservative treatment. METHODS: A retrospective query of a tertiary referral center administrative database was performed using the Current Procedural Terminology code 28135 for sesamoidectomy between 2005 and 2016. Patients who underwent an isolated fibular sesamoidectomy were identified and contacted to return for an office visit. The primary outcome measure was change in visual analog pain score at final follow-up. Secondary measures included satisfaction, hallux flexion strength, hallux alignment, pedobarographic assessment, and postoperative functional outcome scores. Patients who met the 2-year clinical or radiographic follow-up minimum were included. Ninety fibular sesamoidectomies were identified. Thirty-six sesamoidectomies met inclusion criteria (median 60-month follow-up). The average patient was 36 years old and underwent sesamoidectomy 1.1 years after initial diagnosis. RESULTS: Median visual analog scale scores improved 5 (6 to 1) points at final follow-up (P < .001). Final postoperative mean hallux valgus angle did not differ from preoperative values (10.5 degrees/8.5 degrees, P = .12); similarly, the intermetatarsal angle did not differ (8.0 degrees/7.9 degrees, P = .53). Eighty-eight percent of patients would have surgery again and 70% were "very satisfied" with their result. Hallux flexion strength (mean 14.7 pounds) did not differ relative to the contralateral foot (mean 16.1 pounds) (P = .23). Among the full 92 case cohort, 3 patients underwent 4 known reoperations. CONCLUSION: Fibular sesamoidectomy effectively provided pain relief (median 5-year follow-up) for patients with sesamoid pathology without affecting hallux alignment. LEVEL OF EVIDENCE: Level IV, retrospective case series.

9.
Nat Nanotechnol ; 14(5): 420-425, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30833691

RESUMO

Electron microscopy has been instrumental in our understanding of complex biological systems. Although electron microscopy reveals cellular morphology with nanoscale resolution, it does not provide information on the location of different types of proteins. An electron-microscopy-based bioimaging technology capable of localizing individual proteins and resolving protein-protein interactions with respect to cellular ultrastructure would provide important insights into the molecular biology of a cell. Here, we synthesize small lanthanide-doped nanoparticles and measure the absolute photon emission rate of individual nanoparticles resulting from a given electron excitation flux (cathodoluminescence). Our results suggest that the optimization of nanoparticle composition, synthesis protocols and electron imaging conditions can lead to sub-20-nm nanolabels that would enable high signal-to-noise localization of individual biomolecules within a cellular context. In ensemble measurements, these labels exhibit narrow spectra of nine distinct colours, so the imaging of biomolecules in a multicolour electron microscopy modality may be possible.


Assuntos
Corantes Fluorescentes/química , Microscopia Eletrônica de Transmissão , Nanopartículas/química
10.
Foot Ankle Int ; 40(1): 18-23, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30284492

RESUMO

BACKGROUND:: The purpose of this study was to examine the clinical outcomes and complications of patients with midfoot Charcot managed with midfoot osteotomy, realignment arthrodesis, and stabilization using intramedullary beams. METHODS:: Consecutive patients with midfoot Charcot treated at a tertiary-care foot and ankle center from January 2013 to July 2016 who underwent corrective osteotomy with internal beam fixation were identified; 25 patients were included in the final analysis. Patients with a minimum 1-year follow-up were evaluated with physical examination, weightbearing radiographs, and patient-reported outcome measures. The primary outcome measure was defined as restoration of a stable, plantigrade, ulcer-free foot. Median age was 58 years, median BMI was 32, and 80% were diabetic (75% insulin-dependent). RESULTS:: An ulcer-free, stable, plantigrade foot was obtained in 84% of patients. The radiographic lateral and anteroposterior Meary angle medians improved 9° and 15°, respectively, from preoperative to final postoperative weightbearing measurements ( P < .001 and P = .02). Overall, 46% of midfoot osteotomies were united on final radiographs at a median 18-month radiographic follow-up. Deep infection developed in 6 (24%) patients. The presence of a preoperative ulcer was found to be predictive of postoperative infection (P = .04); all 6 deep infections occurred in patients with preoperative ulceration. Four (16%) patients progressed to amputation at a mean 15 postoperative months, all for deep infection. CONCLUSION:: Midfoot Charcot reconstruction with intramedullary beaming allowed for restoration of an ulcer-free, plantigrade foot in most patients, but the complication rates were high, especially in patients with preoperative ulceration. LEVEL OF EVIDENCE:: Level IV, retrospective case series.


Assuntos
Artropatia Neurogênica/cirurgia , Pé/cirurgia , Osteotomia , Parafusos Ósseos/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia/efeitos adversos , Osteotomia/instrumentação , Osteotomia/métodos , Medidas de Resultados Relatados pelo Paciente , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Reconstrutivos , Estudos Retrospectivos , Infecção da Ferida Cirúrgica
11.
ACS Synth Biol ; 8(1): 181-190, 2019 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-30577690

RESUMO

Materials synthesized by organisms, such as bones and wood, combine the ability to self-repair with remarkable mechanical properties. This multifunctionality arises from the presence of living cells within the material and hierarchical assembly of different components across nanometer to micron scales. While creating engineered analogues of these natural materials is of growing interest, our ability to hierarchically order materials using living cells largely relies on engineered 1D protein filaments. Here, we lay the foundation for bottom-up assembly of engineered living material composites in 2D along the cell body using a synthetic biology approach. We engineer the paracrystalline surface-layer (S-layer) of Caulobacter crescentus to display SpyTag peptides that form irreversible isopeptide bonds to SpyCatcher-modified proteins, nanocrystals, and biopolymers on the extracellular surface. Using flow cytometry and confocal microscopy, we show that attachment of these materials to the cell surface is uniform, specific, and covalent, and its density can be controlled on the basis of the insertion location within the S-layer protein, RsaA. Moreover, we leverage the irreversible nature of this attachment to demonstrate via SDS-PAGE that the engineered S-layer can display a high density of materials, reaching 1 attachment site per 288 nm2. Finally, we show that ligation of quantum dots to the cell surface does not impair cell viability, and this composite material remains intact over a period of 2 weeks. Taken together, this work provides a platform for self-organization of soft and hard nanomaterials on a cell surface with precise control over 2D density, composition, and stability of the resulting composite, and is a key step toward building hierarchically ordered engineered living materials with emergent properties.


Assuntos
Caulobacter crescentus/genética , Membrana Celular/genética , DNA Bacteriano/genética , Caulobacter crescentus/metabolismo , Membrana Celular/metabolismo , Cianobactérias/genética , Cianobactérias/metabolismo , Edição de Genes
12.
Conf Proc IEEE Eng Med Biol Soc ; 2018: 1-4, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30440277

RESUMO

Optimal cancer therapy requires targeted and individualized treatment of all tumor cells, including both gross and microscopic disease. Intraoperatively hard to visualize and often left behind, microscopic foci of residual cancer cells significantly increase the risk of cancer recurrence and treatment failure rates. Fluorescently-tagged targeted molecular labels are employed to guide surgery, but conventional fluorescent intraoperative imagers suffer from lack of sensitivity and maneuverability, limiting practicality in small tumor cavities owing to their cumbersome sizes driven by optics. This work does away with conventional lenses and filters and introduces an optics-free molecular imaging "skin" consisting of only a $25\mu \mathrm{m}$ thin CMOS contact imager that synergistically integrates the long emission lifetimes of upconverting nanoparticles (UCNP) combined with upconversion to use a time domain approach to acquire the image coupled with infrared illumination allowing deep tissue penetration and elimination of autofluorescence. Using this strategy, we are able to visualize UCNPs at fluences (W/cm2) compatible with intraoperative use, opening the door to visualize targeted areas with microscopic sensitivity and facilitate residual microscopic disease detection during surgery, and laying the groundwork for precision post-operative radiation.


Assuntos
Nanopartículas , Neoplasia Residual/diagnóstico , Humanos , Raios Infravermelhos , Cuidados Intraoperatórios , Imagem Molecular/métodos , Recidiva Local de Neoplasia , Fatores de Tempo
13.
Nat Commun ; 9(1): 3082, 2018 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-30082844

RESUMO

Multiphoton imaging techniques that convert low-energy excitation to higher energy emission are widely used to improve signal over background, reduce scatter, and limit photodamage. Lanthanide-doped upconverting nanoparticles (UCNPs) are among the most efficient multiphoton probes, but even UCNPs with optimized lanthanide dopant levels require laser intensities that may be problematic. Here, we develop protein-sized, alloyed UCNPs (aUCNPs) that can be imaged individually at laser intensities >300-fold lower than needed for comparably sized doped UCNPs. Using single UCNP characterization and kinetic modeling, we find that addition of inert shells changes optimal lanthanide content from Yb3+, Er3+-doped NaYF4 nanocrystals to fully alloyed compositions. At high levels, emitter Er3+ ions can adopt a second role to enhance aUCNP absorption cross-section by desaturating sensitizer Yb3+ or by absorbing photons directly. Core/shell aUCNPs 12 nm in total diameter can be imaged through deep tissue in live mice using a laser intensity of 0.1 W cm-2.

14.
Nat Nanotechnol ; 13(7): 572-577, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29915271

RESUMO

Reducing the size of lasers to microscale dimensions enables new technologies1 that are specifically tailored for operation in confined spaces ranging from ultra-high-speed microprocessors2 to live brain tissue3. However, reduced cavity sizes increase optical losses and require greater input powers to reach lasing thresholds. Multiphoton-pumped lasers4-7 that have been miniaturized using nanomaterials such as lanthanide-doped upconverting nanoparticles (UCNPs)8 as lasing media require high pump intensities to achieve ultraviolet and visible emission and therefore operate under pulsed excitation schemes. Here, we make use of the recently described energy-looping excitation mechanism in Tm3+-doped UCNPs9 to achieve continuous-wave upconverted lasing action in stand-alone microcavities at excitation fluences as low as 14 kW cm-2. Continuous-wave lasing is uninterrupted, maximizing signal and enabling modulation of optical interactions10. By coupling energy-looping nanoparticles to whispering-gallery modes of polystyrene microspheres, we induce stable lasing for more than 5 h at blue and near-infrared wavelengths simultaneously. These microcavities are excited in the biologically transmissive second near-infrared (NIR-II) window and are small enough to be embedded in organisms, tissues or devices. The ability to produce continuous-wave lasing in microcavities immersed in blood serum highlights practical applications of these microscale lasers for sensing and illumination in complex biological environments.


Assuntos
Lasers , Nanopartículas/química , Nanotecnologia/instrumentação , Túlio/química , Animais , Bovinos , Desenho de Equipamento , Luz , Substâncias Luminescentes/química , Microesferas , Poliestirenos/química , Soro/química
15.
ACS Nano ; 12(5): 4469-4477, 2018 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-29608274

RESUMO

Functionalization of nanocrystals is essential for their practical application, but synthesis on nanocrystal surfaces is limited by incompatibilities with certain key reagents. The copper-catalyzed azide-alkyne cycloaddition is among the most useful methods for ligating molecules to surfaces, but has been largely useless for semiconductor quantum dots (QDs) because Cu+ ions quickly and irreversibly quench QD fluorescence. To discover nonquenching synthetic conditions for Cu-catalyzed click reactions on QD surfaces, we developed a combinatorial fluorescence assay to screen >2000 reaction conditions to maximize cycloaddition efficiency while minimizing QD quenching. We identify conditions for complete coupling without significant quenching, which are compatible with common QD polymer surfaces and various azide/alkyne pairs. Based on insight from the combinatorial screen and mechanistic studies of Cu coordination and quenching, we find that superstoichiometric concentrations of Cu can promote full coupling if accompanied by ligands that selectively compete with the Cu from the QD surface but allow it to remain catalytically active. Applied to the conjugation of a K+ channel-specific peptidyl toxin to CdSe/ZnS QDs, we synthesize unquenched QD conjugates and image their specific and voltage-dependent affinity for K+ channels in live cells.


Assuntos
Alquinos/química , Azidas/química , Cobre/química , Pontos Quânticos/química , Estrutura Molecular , Tamanho da Partícula , Semicondutores , Propriedades de Superfície
16.
Foot Ankle Int ; 39(6): 664-668, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29448827

RESUMO

BACKGROUND: Achilles tendon insertional sleeve avulsions occur when the Achilles distal tendon sleeve ruptures off of its insertion into the calcaneal tuberosity, sometimes with a small bony fragment from calcific tendinosis. Little evidence exists describing the outcomes and rerupture rate after operative management of Achilles tendon sleeve avulsions. METHODS: A retrospective chart review was performed to identify patients who sustained an Achilles sleeve avulsion injury treated with operative repair between October 2005 and July 2014. A cohort of 16 patients from the general population and 12 professional athletes were included in the study. The primary outcome variable was rerupture of the Achilles tendon or need for revision surgery. Secondary outcome variables included the Coughlin Satisfaction Scale, visual VR-12, and Foot and Ankle Ability Measure (FAAM). RESULTS: In the general population cohort, median follow-up was 8.1 years (range, 3.2-11.1 years). The median FAAM Activities of Daily Living score was 100 (range, 42.9-106), and the median FAAM Sports score was 100 (range, 7.1-103.6). The median VR-12 Mental Component Score was 66.9 (range, 45.6-71.8), and the median VR-12 Physical Component Score was 53 (range, 30.8-57.5). In the cohort of professional athletes, preceding insertional Achilles symptoms were present in 91.7% (11/12) of athletes for more than 9 months prior to rupture. All athletes returned to play with an average time of 13.4 months. No patients sustained a rerupture in the follow-up period. CONCLUSION: Operative repair of Achilles tendon sleeve avulsions was safe and effective with high patient satisfaction and good clinical outcomes in patients from the general population. LEVEL OF EVIDENCE: Level IV, retrospective case series.


Assuntos
Tendão do Calcâneo/cirurgia , Ruptura/cirurgia , Traumatismos dos Tendões/cirurgia , Atletas , Humanos , Procedimentos Ortopédicos , Satisfação do Paciente , Reoperação , Estudos Retrospectivos
17.
Small ; 14(8)2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29356374

RESUMO

While nanoparticles are an increasingly popular choice for labeling and tracking stem cells in biomedical applications such as cell therapy, their intracellular fate and subsequent effect on stem cell differentiation remain elusive. To establish an effective stem cell labeling strategy, the intracellular nanocrystal concentration should be minimized to avoid adverse effects, without compromising the intensity and persistence of the signal necessary for long-term tracking. Here, the use of second-harmonic generating barium titanate nanocrystals is reported, whose achievable brightness allows for high contrast stem cell labeling with at least one order of magnitude lower intracellular nanocrystals than previously reported. Their long-term photostability enables to investigate quantitatively at the single cell level their cellular fate in hematopoietic stem cells (HSCs) using both multiphoton and electron microscopy. It is found that the concentration of nanocrystals in proliferative multipotent progenitors is over 2.5-fold greater compared to quiescent stem cells; this difference vanishes when HSCs enter a nonquiescent, proliferative state, while their potency remains unaffected. Understanding the nanoparticle stem cell interaction allows to establish an effective and safe nanoparticle labeling strategy into somatic stem cells that can critically contribute to an understanding of their in vivo therapeutic potential.


Assuntos
Compostos de Bário/química , Células-Tronco Hematopoéticas/citologia , Nanopartículas de Magnetita/química , Nanopartículas/química , Microscopia de Geração do Segundo Harmônico/métodos , Titânio/química , Células-Tronco Adultas/citologia , Animais , Diferenciação Celular/fisiologia , Divisão Celular/fisiologia , Proliferação de Células/fisiologia , Humanos
18.
Biomed Opt Express ; 9(9): 4359-4371, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30615722

RESUMO

Optical methods for imaging and stimulation of biological events based on the use of visible light are limited to the superficial layers of tissue due to the significant absorption and scattering of light. Here, we demonstrate the design and implementation of passive micro-structured lightbulbs (MLBs) containing bright-emitting lanthanide-doped upconverting nanoparticles (UCNPs) for light delivery deep into the tissue. The MLBs are realized as cylindrical pillars made of Parylene C polymer that can be implanted deep into the tissue. The encapsulated UCNPs absorb near-infrared (NIR) light at λ = 980 nm, which undergoes much less absorption than the blue light in the brain tissue, and then locally emit blue light (1G4→3H6 and 1D2→3F4 transitions) that can be used for optogenetic excitation of neurons in the brain. The 3H4→3H6 transition will result in the emission of higher energy NIR photons at λ = 800 nm that can be used for imaging and tracking MLBs through thick tissue.

19.
Bioconjug Chem ; 28(11): 2707-2714, 2017 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-28945361

RESUMO

We report the fabrication of aqueous multimodal imaging nanocomposites based on superparamagnetic nanoparticles (MNPs) and two different sizes of photoluminescent upconverting nanoparticles (UCNPs). The controlled and simultaneous incorporation of both types of nanoparticles (NPs) was obtained by controlling the solvent composition and the addition rate of the destabilizing solvent. The magnetic properties of the MNPs remained unaltered after their encapsulation into the polymeric beads as shown by the T2 relaxivity measurements. The UCNPs maintain photoluminescent properties even when embedded with the MNPs into the polymer bead. Moreover, the light emitted by the magnetic and upconverting nanobeads (MUCNBs) under NIR excitation (λexc = 980 nm) was clearly observed through different thicknesses of agarose gel or through a mouse skin layer. The comparison with magnetic and luminescent nanobeads based on red-emitting quantum dots (QDs) demonstrated that while the QD-based beads show significant autofluorescence background from the skin, the signal obtained by the MUCNBs allows a decrease in this background. In summary, these results indicate that MUCNBs are good magnetic and optical probes for in vivo multimodal imaging sensors.


Assuntos
Substâncias Luminescentes/química , Nanopartículas de Magnetita/química , Nanopartículas/química , Imagem Óptica/métodos , Animais , Linhagem Celular Tumoral , Células HeLa , Humanos , Camundongos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Imagem Multimodal , Pontos Quânticos/química , Pele/diagnóstico por imagem
20.
Foot Ankle Int ; 38(11): 1188-1191, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28814096

RESUMO

BACKGROUND: Postoperative pain is often difficult to control with oral medications, requiring large doses of opioid analgesia. Regional anesthesia may be used for primary anesthesia, reducing the need for general anesthetic and postoperative pain medication requirements in the immediate postoperative period. The purpose of this study was to compare the analgesic effects of an ankle block (AB) to a single-shot popliteal fossa block (PFB) for patients undergoing orthopedic forefoot procedures. METHODS: All patients having elective outpatient orthopedic forefoot procedures were invited to participate in the study. Patients were prospectively randomized to receive either an ultrasound-guided AB or PFB by a board-certified anesthesiologist prior to their procedure. Intraoperative conversion to general anesthesia and postanesthesia care unit (PACU) opioid requirements were recorded. Postoperative pain was assessed using the visual analog scale (VAS) at regular time intervals until 8 am on postoperative day (POD) 2. Patients rated the effectiveness of the block on a 1 to 5 scale, with 5 being very effective. A total of 167 patients participated in the study with 88 patients (53%) receiving an AB and 79 (47%) receiving a single-shot PFB. RESULTS: There was no significant difference in the rate of conversion to general anesthesia between the 2 groups (13.6% [12/88] AB vs 12.7% [10/79] PFB). PACU morphine requirements and doses were significantly reduced in the PFB group ( P = .004) when compared to the AB group. The VAS was also significantly lower for the PFB patients at 10 pm on POD 0 (4.6 vs 1.6, P < .001), 8 am on POD 1 (5.9 vs 4.2, P = .003), and 12 pm on POD 1 (5.4 vs 4.1, P = .01). Overall complication rates were similar between the groups (AB 9% vs PFB 10.1%, P = .51) and there were no significant differences in residual sensory paresthesias (AB 2.3% [2/88] vs PFB 5.1% [4/79], P = .29), motor loss (0% vs 0%), or block site pain and/or erythema (AB 6.9% [6/88] vs PFB 5.1% [4/79], P = .44). The analgesic effect of the PFB lasted significantly longer when compared to the ankle block (AB 14.5 hours vs PFB 20.9 hours, P < .001). There was no significant difference in patient-perceived effectiveness of the block between the 2 groups, with both blocks being highly effective (AB 4.79/5 vs PFB 4.82/5, P = .68). CONCLUSION: Regional anesthesia was a safe and reliable adjunct to perioperative pain management and highly effective in patients undergoing elective orthopedic forefoot procedures. However, patients who received a PFB had significantly better pain management and decreased opioid requirements in the immediate perioperative period than patients who received an ankle block. LEVEL OF EVIDENCE: Level I, prospective randomized study.


Assuntos
Analgésicos Opioides/administração & dosagem , Pé/cirurgia , Bloqueio Nervoso/métodos , Procedimentos Ortopédicos/métodos , Dor Pós-Operatória/fisiopatologia , Adulto , Idoso , Procedimentos Cirúrgicos Ambulatórios , Anestesia por Condução/métodos , Tornozelo/diagnóstico por imagem , Bupivacaína/administração & dosagem , Distribuição de Qui-Quadrado , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Seguimentos , Pé/diagnóstico por imagem , Humanos , Injeções Intralesionais , Masculino , Pessoa de Meia-Idade , Medição da Dor , Dor Pós-Operatória/prevenção & controle , Seleção de Pacientes , Assistência Perioperatória/métodos , Estudos Prospectivos , Estatísticas não Paramétricas , Resultado do Tratamento , Ultrassonografia de Intervenção/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA