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1.
ACS Appl Nano Mater ; 6(9): 7668-7678, 2023 May 12.
Article in English | MEDLINE | ID: mdl-37304254

ABSTRACT

The enzymatic production of hydrogen sulfide (H2S) from cysteine in various metabolic processes has been exploited as an intrinsically "green" and sustainable mode for the aqueous biomineralization of functional metal sulfide quantum dots (QDs). Yet, the reliance on proteinaceous enzymes tends to limit the efficacy of the synthesis to physiological temperature and pH, with implications for QD functionality, stability, and tunability (i.e., particle size and composition). Inspired by a secondary non-enzymatic biochemical cycle that is responsible for basal H2S production in mammalian systems, we establish how iron(III)- and vitamin B6 (pyridoxal phosphate, PLP)-catalyzed decomposition of cysteine can be harnessed for the aqueous synthesis of size-tunable QDs, demonstrated here for CdS, within an expanded temperature, pH, and compositional space. Rates of H2S production by this non-enzymatic biochemical process are sufficient for the nucleation and growth of CdS QDs within buffered solutions of cadmium acetate. Ultimately, the simplicity, demonstrated robustness, and tunability of the previously unexploited H2S-producing biochemical cycle help establish its promise as a versatile platform for the benign, sustainable synthesis of an even wider range of functional metal sulfide nanomaterials for optoelectronic applications.

2.
J Mater Chem B ; 10(24): 4529-4545, 2022 06 22.
Article in English | MEDLINE | ID: mdl-35608268

ABSTRACT

The development of high quality, non-toxic (i.e., heavy-metal-free), and functional quantum dots (QDs) via 'green' and scalable synthesis routes is critical for realizing truly sustainable QD-based solutions to diverse technological challenges. Herein, we demonstrate the low-temperature all-aqueous-phase synthesis of silver indium sulfide/zinc (AIS/Zn) QDs with a process initiated by the biomineralization of highly crystalline indium sulfide nanocrystals, and followed by the sequential staging of Ag+ cation exchange and Zn2+ addition directly within the biomineralization media without any intermediate product purification. Therein, we exploit solution phase cation concentration, the duration of incubation in the presence of In2S3 precursor nanocrystals, and the subsequent addition of Zn2+ as facile handles under biomineralization conditions for controlling QD composition, tuning optical properties, and improving the photoluminescence quantum yield of the AIS/Zn product. We demonstrate how engineering biomineralization for the synthesis of intrinsically hydrophilic and thus readily functionalizable AIS/Zn QDs with a quantum yield of 18% offers a 'green' and non-toxic materials platform for targeted bioimaging in sensitive cellular systems. Ultimately, the decoupling of synthetic steps helps unravel the complexities of ion exchange-based synthesis within the biomineralization platform, enabling its adaptation for the sustainable synthesis of 'green', compositionally diverse QDs.


Subject(s)
Quantum Dots , Biomineralization , Cations , Indium/chemistry , Quantum Dots/chemistry , Sulfides/chemistry , Temperature , Water/chemistry , Zinc/chemistry
3.
Langmuir ; 37(41): 12188-12203, 2021 10 19.
Article in English | MEDLINE | ID: mdl-34633195

ABSTRACT

In this study, NMR and molecular dynamics simulations were employed to study IgG1 FC binding to multimodal surfaces. Gold nanoparticles functionalized with two multimodal cation-exchange ligands (Capto and Nuvia) were synthesized and employed to carry out solution-phase NMR experiments with the FC. Experiments with perdeuterated 15N-labeled FC and the multimodal surfaces revealed micromolar residue-level binding affinities as compared to millimolar binding affinities with these ligands in free solution, likely due to cooperativity and avidity effects. The binding of FC with the Capto ligand nanoparticles was concentrated near an aliphatic cluster in the CH2/CH3 interface, which corresponded to a focused hydrophobic region. In contrast, binding with the Nuvia ligand nanoparticles was more diffuse and corresponded to a large contiguous positive electrostatic potential region on the side face of the FC. Results with lower-ligand-density nanoparticles indicated a decrease in binding affinity for both systems. For the Capto ligand system, several aliphatic residues on the FC that were important for binding to the higher-density surface did not interact with the lower-density nanoparticles. In contrast, no significant difference was observed in the interacting residues on the FC to the high- and low-ligand density Nuvia surfaces. The binding affinities of FC to both multimodal-functionalized nanoparticles decreased in the presence of salt due to the screening of multiple weak interactions of polar and positively charged residues. For the Capto ligand nanoparticle system, this resulted in an even more focused hydrophobic binding region in the interface of the CH2 and CH3 domains. Interestingly, for the Nuvia ligand nanoparticles, the presence of salt resulted in a large transition from a diffuse binding region to the same focused binding region determined for Capto nanoparticles at 150 mM salt. Molecular dynamics simulations corroborated the NMR results and provided important insights into the molecular basis of FC binding to these different multimodal systems containing clustered (observed at high-ligand densities) and nonclustered ligand surfaces. This combined biophysical and simulation approach provided significant insights into the interactions of FC with multimodal surfaces and sets the stage for future analyses with even more complex biotherapeutics.


Subject(s)
Metal Nanoparticles , Molecular Dynamics Simulation , Gold , Immunoglobulin G , Ligands , Magnetic Resonance Spectroscopy
4.
Arthroplast Today ; 10: 180-189.e7, 2021 Aug.
Article in English | MEDLINE | ID: mdl-34527801

ABSTRACT

BACKGROUND: Wound closure is a key, and often underrecognized, component of hip and knee arthroplasty. Methods for wound closure are an important consideration to better avoid wound-related adverse events; however, there is a lack of consensus on optimal methods. The objective of the following review was twofold: to characterize the wound closure methods used by layer in the total knee arthroplasty and total hip arthroplasty literature and summarize optimal wound-healing strategies to address the risk of adverse events. METHODS: A systematic literature review was performed to identify total knee arthroplasty and total hip arthroplasty randomized controlled trials and nonrandomized studies reporting wound closure methods by layer and wound-healing adverse events (including superficial, deep, or periprosthetic joint infections, wound dehiscence, or prolonged wound drainage). Studies on revision procedures were excluded. Wound closure methods and adverse events were summarized qualitatively as meta-analyses were not possible because of study heterogeneity. RESULTS: Forty studies met the inclusion criteria: 22 randomized controlled trials and 18 observational studies. Across studies, 6 categories and 22 unique techniques for closure were identified. Conventional closure methods exhibited large ranges of adverse event rates. Studies of multilayer barbed sutures with topical skin adhesives and polyester mesh or multilayer antimicrobial sutures reported narrow ranges of adverse events rates. CONCLUSIONS: Considerable variability exists for wound closure methods, with a wide range reported in adverse events. Recent technologies and methods for standardized watertight, multilayer closure show promise for avoiding adverse events and unnecessary health-care costs; however, higher quality, comparative studies are required to enable future meta-analyses. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

5.
J Chromatogr A ; 1653: 462398, 2021 Sep 13.
Article in English | MEDLINE | ID: mdl-34280791

ABSTRACT

In this paper, we examined the chromatographic behavior of a new class of guanidine-based multimodal anion exchange resins. The selectivities and protein recoveries on these resins were first evaluated using linear gradient chromatography with a model acidic protein library at pH 5, 6 and 7. While a single-guanidine based resin exhibited significant recovery issues at high ligand density, a bis-guanidine based resin showed high recoveries of all but two of the proteins evaluated in the study. In addition, the bis-guanidine resin showed a more pH dependent selectivity pattern as compared to the low density single-guanidine resin. The salt elution range for the low density single-guanidine and bis-guanidine resins was also observed to vary from 0.250 to 0.621 M and 0.162 to 0.828 M NaCl, respectively. A QSAR model was then developed to predict the elution behavior of these proteins on the guanidine prototypes at multiple pH with overall training and test scores of 0.88 and 0.85, respectively. In addition, molecular dynamics simulations were performed with these ligands immobilized on a self-assembled monolayer (SAM) to characterize their conformational preferences and to gain insight into the molecular basis of their chromatographic behavior. Finally, a recently developed framework was employed to evaluate the separability of the bis-guanidine resin as well as its orthogonality to the multimodal cation exchanger, Nuvia cPrime. This evaluation was carried out using a second model protein library which included both acidic and basic proteins. The results of this analysis indicated that the bis-guanidine prototype exhibited both higher pair separability (0.73) and pair enhancement (0.42) as compared to the less hydrophobic commercial Nuvia aPrime 4A with pair separability and enhancement factors of 0.57 and 0.22, respectively. The enhanced selectivity and orthogonality of this new multimodal anion exchange ligand may offer potential opportunities for bioprocessing applications.


Subject(s)
Anion Exchange Resins , Proteins , Chromatography, Ion Exchange , Guanidine/chemistry , Ligands , Proteins/analysis , Proteins/isolation & purification
6.
J Phys Chem B ; 125(23): 6112-6120, 2021 06 17.
Article in English | MEDLINE | ID: mdl-34097423

ABSTRACT

Multimodal chromatography is a powerful approach for purifying proteins that uses ligands containing multiple modes of interaction. Recent studies have shown that selectivity in multimodal chromatographic separations is a function of the ligand structure and geometry. Here, we performed molecular dynamics simulations to explore how the ligand structure and geometry affect ligand-water interactions and how these differences in solution affect the nature of protein-ligand interactions. Our investigation focused on three chromatography ligands: Capto MMC, Nuvia cPrime, and Prototype 4, a structural variant of Nuvia cPrime. First, the solvation characteristics of each ligand were quantified via three metrics: average water density, fluctuations, and residence time. We then explored how solvation was perturbed when the ligand was bound to the protein surface and found that the probability of the phenyl ring dewetting followed the order: Capto MMC > Prototype 4 > Nuvia cPrime. To explore how these differences in dewetting affect protein-ligand interactions, we calculated the probability of each ligand binding to different types of residues on the protein surface and found that the probability of binding to a hydrophobic residue followed the same order as the dewetting behavior. This study illustrates the role that wetting and dewetting play in modulating protein-ligand interactions.


Subject(s)
Chromatography , Water , Hydrophobic and Hydrophilic Interactions , Ligands , Molecular Dynamics Simulation , Protein Binding , Proteins
7.
Biotechnol Bioeng ; 118(2): 809-822, 2021 02.
Article in English | MEDLINE | ID: mdl-33107976

ABSTRACT

In this study, the binding of multimodal chromatographic ligands to the IgG1 FC domain were studied using nuclear magnetic resonance and molecular dynamics simulations. Nuclear magnetic resonance experiments carried out with chromatographic ligands and a perdeuterated 15 N-labeled FC domain indicated that while single-mode ion exchange ligands interacted very weakly throughout the FC surface, multimodal ligands containing negatively charged and aromatic moieties interacted with specific clusters of residues with relatively high affinity, forming distinct binding regions on the FC . The multimodal ligand-binding sites on the FC were concentrated in the hinge region and near the interface of the CH 2 and CH 3 domains. Furthermore, the multimodal binding sites were primarily composed of positively charged, polar, and aliphatic residues in these regions, with histidine residues exhibiting some of the strongest binding affinities with the multimodal ligand. Interestingly, comparison of protein surface property data with ligand interaction sites indicated that the patch analysis on FC corroborated molecular-level binding information obtained from the nuclear magnetic resonance experiments. Finally, molecular dynamics simulation results were shown to be qualitatively consistent with the nuclear magnetic resonance results and to provide further insights into the binding mechanisms. An important contribution to multimodal ligand-FC binding in these preferred regions was shown to be electrostatic interactions and π-π stacking of surface-exposed histidines with the ligands. This combined biophysical and simulation approach has provided a deeper molecular-level understanding of multimodal ligand-FC interactions and sets the stage for future analyses of even more complex biotherapeutics.


Subject(s)
Binding Sites, Antibody , Immunoglobulin Fc Fragments/chemistry , Immunoglobulin G/chemistry , Molecular Dynamics Simulation , Nuclear Magnetic Resonance, Biomolecular , Humans
8.
ACS Appl Mater Interfaces ; 12(38): 42773-42780, 2020 Sep 23.
Article in English | MEDLINE | ID: mdl-32865390

ABSTRACT

Nanocomposite photocatalysts offer a promising route to efficient and clean hydrogen production. However, the multistep, high-temperature, solvent-based syntheses typically utilized to prepare these photocatalysts can limit their scalability and sustainability. Biosynthetic routes to produce functional nanomaterials occur at room temperature and in aqueous conditions, but typically do not produce high-performance materials. We have developed a method to produce a highly efficient hydrogen evolution photocatalyst consisting of CdS quantum dots (QDs) supported on reduced graphene oxide (rGO) via enzyme-based syntheses combined with tuned ligand exchange-mediated self-assembly. All preparation steps are carried out in an aqueous environment at ambient temperature. Size-controlled CdS QDs and rGO are prepared through enzyme-mediated turnover of l-cysteine to HS- in aqueous solutions of Cd-acetate and graphene oxide, respectively. Exchange of cysteamine for the native l-cysteine ligand capping the CdS QDs drives self-assembly of the now positively charged cysteamine-capped CdS (CdS/CA) onto negatively charged rGO. The use of this short linker molecule additionally enables efficient charge transfer from CdS to rGO, increasing exciton lifetime and, subsequently, photocatalytic activity. The visible-light hydrogen evolution rate of the resulting CdS/CA/rGO photocatalyst is 3300 µmol h-1 g-1. This represents, to our knowledge, one of the highest reported rates for a CdS/rGO nanocomposite photocatalyst, irrespective of the synthesis method.

9.
J Orthop ; 18: 191-196, 2020.
Article in English | MEDLINE | ID: mdl-32042225

ABSTRACT

The number of primary total hip and knee replacement surgeries is increasing primarily due to an aging population. There is also a concomitant increase in the number of complications which could be attributed to high variation in arthroplasty techniques, peri-operative methods and the absence of integrated clinical pathways (ICP) to mitigate risks such as surgical site infections (SSIs). The implementation of ICPs incorporating watertight, multi-layer closure could increase the preventative effectiveness against joint prosthetic adverse events. The objective of this review is to describe the ICPs implemented by one US facility to help address ten adverse events synergistically.

10.
ACS Appl Mater Interfaces ; 11(49): 45656-45664, 2019 Dec 11.
Article in English | MEDLINE | ID: mdl-31730749

ABSTRACT

CuZnSnS (CZTS) quantum dots (QDs) have potential application in quantum dot sensitized solar cells (QDSSCs); however, traditional synthesis approaches typically require elevated temperatures, expensive precursors, and organic solvents that can hinder large-scale application. Herein we develop and utilize an enzymatic, aqueous-phase, ambient temperature route to prepare CZTS nanocrystals with good compositional control. Nanoparticle synthesis occurs in a minimal buffered solution containing only the enzyme, metal chloride and acetate salts, and l-cysteine as a capping agent and sulfur source. Beyond isolated nanocrystal synthesis, we further demonstrate biomineralization of these particles within a preformed mesoporous TiO2 anode template where the formed nanocrystals bind to the TiO2 surface. This in situ biomineralization approach facilitates enhanced distribution of the nanocrystals in the anode and, through this, enhanced QDSSC performance.

11.
ACS Appl Mater Interfaces ; 11(46): 43509-43519, 2019 Nov 20.
Article in English | MEDLINE | ID: mdl-31648516

ABSTRACT

The development of facile strategies for simultaneously tailoring robust pore hierarchy and integrated microstructures in carbonaceous materials is critical for the efficient multiscale control of fluid, molecular/ionic, and charge transport in applications spanning separations, catalysis, and energy storage. Here, we synthesize three-dimensionally ordered hierarchically porous carbon powders by the assembly of glucose with silica nanoparticle building blocks of sacrificial NP-crystalline templates. Such template-replica coassembly offers an attractive alternative to conventional nanocasting by circumventing the need for sequential template preformation and infiltration-based replication. In addition, interfacial templating leads to hierarchically structured carbons with tunable mesopore volumes (as high as 5.8 cm3/g). Beyond mesostructuring, we identify the template-replica interface as a potentially versatile but generally unexploited handle for tailoring the sp2 hybridized carbon content in the porous replicas under mild carbonization conditions and without specific chemical activation or catalytic graphitization. This multiscale (meso-micro) templating offered by a single template expands the potential versatility of nanocasting for the hierarchical structuring of replica materials. Application of the resulting carbons as electrochemical double layer capacitors demonstrates the combined benefit of simultaneously tailored pore hierarchy and tuned microstructures upon ion and charge transport, respectively, yielding supercapacitors achieving specific capacitance as high as 275 F/g in the aqueous electrolyte (H2SO4) and retention of 90% up to a current density of 10 A/g.

12.
Philos Trans A Math Phys Eng Sci ; 376(2130)2018 Oct 13.
Article in English | MEDLINE | ID: mdl-30177566

ABSTRACT

The Palaeocene-Eocene Thermal Maximum (PETM) was a significant global warming event in Earth's deep past (56 Mya). The warming across the PETM boundary was driven by a rapid rise in greenhouse gases. The event also coincided with a time of maximum insolation in Northern Hemisphere summer. There is increased evidence that the mean warming was accompanied by enhanced seasonality and/or extremes in precipitation (and flooding) and drought. A high horizontal resolution (50 km) global climate model is used to explore changes in the seasonal cycle of surface temperature, precipitation, evaporation minus precipitation and river run-off for regions where proxy data are available. Comparison for the regions indicates the model accurately simulates the observed changes in these climatic characteristics with North American interior warming and drying, and warming and increased river run-off at other regions. The addition of maximum insolation in Northern Hemisphere summer leads to a drier North America, but wetter conditions at most other locations. Long-range transport of atmospheric moisture plays a critical role in explaining regional changes in the water cycle. Such high-frequency variations in precipitation might also help explain discrepancies or misinterpretation of some climate proxies from the same locations, especially where sampling is coarse, i.e. at or greater than the frequency of precession.This article is part of a discussion meeting issue 'Hyperthermals: rapid and extreme global warming in our geological past'.

13.
J Chromatogr A ; 1569: 101-109, 2018 Sep 28.
Article in English | MEDLINE | ID: mdl-30041873

ABSTRACT

The increasing prevalence of low pI non-mAb therapeutics as well as current challenges in mAb-aggregate separations and low recoveries motivate further development in the multimodal anion exchange (MM AEX) space. In this work, linear salt gradient experiments at pH 7 were used to evaluate the retention of model proteins (with pI from 3.4 to 6.8) in 17 novel MM AEX prototype systems. The ligands were organized into three series. Series 1 extended previous work in multimodal ligand design and included a hydroxyl variant and linker length variants. Series 2 and 3 investigated the nature of hydrophobicity in MM AEX systems by adding hydrophobic (series 2) or fluorine (series 3) substituents to a solvent exposed phenyl ring. Compared to the commercial resin Capto Adhere, the series 1 and 3 ligands exhibited weaker binding, while some of the series 2 aliphatic prototypes showed dramatically increased retention and unique selectivities. Within series 1, the model proteins eluted earlier in the gradient as the charge-hydrophobic group distance on the ligand was increased from 4.9 Å to 8.5 Å. For the aliphatic variants in series 2, proteins that eluted early in the salt gradient were not affected by the increase in ligand hydrophobicity, while the later eluting proteins bound stronger as the length of the aliphatic substituent increased. The series 3 variants indicated that phenyl ring fluorination created subtle changes in protein elution in these MM AEX systems. Retention data from the three series was used to generate a partial least squares QSAR model based on both protein and ligand descriptors which accurately predicted protein retention with a training R2 of 0.81 and a test R2 of 0.76. The retention characteristics of some prototypes such as the earlier elution and unique selectivities compared to Capto Adhere suggest that they could potentially provide unique selectivities and increased recovery for the downstream processing of both mAb and non-mAb biotherapeutics.


Subject(s)
Chromatography, Ion Exchange/methods , Hydrocarbons, Aromatic/chemistry , Proteins/chemistry , Amines/chemistry , Anions , Halogenation , Hydrophobic and Hydrophilic Interactions , Ligands , Quantitative Structure-Activity Relationship
14.
Langmuir ; 34(3): 991-998, 2018 01 23.
Article in English | MEDLINE | ID: mdl-29111738

ABSTRACT

Most binary superlattices created using DNA functionalization rely on particle size differences to achieve compositional order and structural diversity. Here we study two-dimensional (2D) assembly of DNA-functionalized micron-sized particles (DFPs), and employ a strategy that leverages the tunable disparity in interparticle interactions, and thus enthalpic driving forces, to open new avenues for design of binary superlattices that do not rely on the ability to tune particle size (i.e., entropic driving forces). Our strategy employs tailored blends of complementary strands of ssDNA to control interparticle interactions between micron-sized silica particles in a binary mixture to create compositionally diverse 2D lattices. We show that the particle arrangement can be further controlled by changing the stoichiometry of the binary mixture in certain cases. With this approach, we demonstrate the ability to program the particle assembly into square, pentagonal, and hexagonal lattices. In addition, different particle types can be compositionally ordered in square checkerboard and hexagonal-alternating string, honeycomb, and Kagome arrangements.


Subject(s)
DNA/metabolism , DNA/chemistry , Molecular Structure , Particle Size , Silicon Dioxide/chemistry , Thermodynamics
15.
Langmuir ; 33(26): 6601-6610, 2017 07 05.
Article in English | MEDLINE | ID: mdl-28605902

ABSTRACT

Convectively assembled colloidal crystal templates, composed of size-tunable (ca. 15-50 nm) silica (SiO2) nanoparticles, enable versatile sacrificial templating of three-dimensionally ordered mesoporous (3DOm) metal oxides (MOx) at both mesoscopic and microscopic size scales. Specifically, we show for titania (TiO2) and zirconia (ZrO2) how this approach not only enables the engineering of the mesopore size, pore volume, and surface area but can also be leveraged to tune the crystallite polymorphism of the resulting 3DOm metal oxides. Template-mediated volumetric (i.e., interstitial) effects and interfacial factors are shown to preserve the metastable crystalline polymorphs of each corresponding 3DOm oxide (i.e., anatase TiO2 (A-TiO2) and tetragonal ZrO2 (t-ZrO2)) during high-temperature calcination. Mechanistic investigations suggest that this polymorph stabilization is derived from the combined effects of the template-replica (MOx/SiO2) interface and simultaneous interstitial confinement that limit the degree of coarsening during high-temperature calcination of the template-replica composite. The result is the identification of a facile yet versatile templating strategy for realizing 3DOm oxides with (i) surface areas that are more than an order of magnitude larger than untemplated control samples, (ii) pore diameters and volumes that can be tuned across a continuum of size scales, and (iii) selectable polymorphism.

17.
Annu Rev Chem Biomol Eng ; 8: 115-137, 2017 06 07.
Article in English | MEDLINE | ID: mdl-28301730

ABSTRACT

With technological advancement of thermocatalytic processes for valorizing renewable biomass carbon, development of effective separation technologies for selective recovery of bioproducts from complex reaction media and their purification becomes essential. The high thermal sensitivity of biomass intermediates and their low volatility and high reactivity, along with the use of dilute solutions, make the bioproducts separations energy intensive and expensive. Novel separation techniques, including solvent extraction in biphasic systems and reactive adsorption using zeolite and carbon sorbents, membranes, and chromatography, have been developed. In parallel with experimental efforts, multiscale simulations have been reported for predicting solvent selection and adsorption separation. We discuss various separations that are potentially valuable to future biorefineries and the factors controlling separation performance. Particular emphasis is given to current gaps and opportunities for future development.


Subject(s)
Biofuels/analysis , Biomass , Chemical Fractionation/methods , Adsorption , Carbon/chemistry , Chemical Fractionation/instrumentation , Chromatography/instrumentation , Chromatography/methods , Equipment Design , Membranes, Artificial , Temperature
18.
J Arthroplasty ; 32(5): 1478-1482, 2017 05.
Article in English | MEDLINE | ID: mdl-28159420

ABSTRACT

BACKGROUND: Aspirin at 325 mg twice daily is now included as a nationally approved venous thromboembolism (VTE) prophylaxis protocol for low-risk total knee arthroplasty (TKA) patients. The purpose of this study is to examine whether there is a difference in deep vein thrombosis (DVT) occurrence after a limited tourniquet TKA using aspirin-based prophylaxis with or without extended use of mechanical compression device (MCD) therapy. METHODS: One hundred limited tourniquet TKA patients, whose DVT risk was managed with aspirin 325 mg twice daily for 3 weeks, were randomized to either using an MCD during hospitalization only or extended use at home up to 6 weeks postoperatively. Lower extremity duplex venous ultrasonography (LEDVU) was completed on the second postoperative day, 14 days postoperatively, and at 3 months postoperatively to confirm the absence of DVT after treatment. RESULTS: The DVT rate for the postdischarge MCD therapy group was 0% and 23.1% for the inpatient MCD group (P < .001). All DVTs resolved by 3 months postoperatively. Patient satisfaction was 9.56 (±0.82) for postdischarge MCD patients vs 8.50 (±1.46) for inpatient MCD patients (P < .001). CONCLUSION: Limited tourniquet TKA patients who were mobilized early, managed with aspirin for 3 weeks postoperatively, and on MCD therapy for up to 6 weeks postoperatively experienced superior DVT prophylaxis than patients receiving MCD therapy only as an inpatient (P < .05). The 0% incidence of nonsymptomatic DVTs prevented by aspirin and extended-use MCD further validates this type of prophylaxis in low DVT risk TKA patients.


Subject(s)
Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/methods , Aspirin/therapeutic use , Intermittent Pneumatic Compression Devices , Venous Thromboembolism/prevention & control , Venous Thrombosis/prevention & control , Aged , Aspirin/administration & dosage , Female , Humans , Male , Middle Aged , Postoperative Period , Prospective Studies , Treatment Outcome , Ultrasonography, Doppler , Venous Thromboembolism/etiology , Venous Thrombosis/etiology , Wound Healing
19.
Surg Technol Int ; 30: 261-267, 2016 Nov 11.
Article in English | MEDLINE | ID: mdl-27824434

ABSTRACT

INTRODUCTION: Liposomal bupivacaine, a prolonged-release formulation of bupivacaine hydrochloride, is indicated for infiltration into the surgical site for postsurgical analgesia. Results from previous total knee arthroplasty (TKA) studies suggest that analgesic efficacy associated with liposomal bupivacaine may be impacted by variability in infiltration technique. The PILLAR study is designed to assess liposomal bupivacaine efficacy in TKA using a standardized infiltration protocol. Materials and Methods/Design: This phase 4, multicenter, randomized, double-blind, controlled, parallel-group study will compare the safety and efficacy of infiltration with liposomal bupivacaine versus standard bupivacaine for postsurgical pain control in adults undergoing primary unilateral TKA. All subjects will receive a standardized pre-surgical analgesic regimen, and will be randomized to receive either liposomal bupivacaine 266 mg/20 mL (admixed with standard bupivacaine 0.5% 20 mL and expanded to a total volume of 120 mL) or bupivacaine 0.5% 20 mL (expanded to a total volume of 120 mL). The study drug will be infiltrated using six syringes (prefilled with 20 mL of study drug solution) to deliver 1-1.5 mL infusions into prespecified periarticular tissues. All subjects will receive standardized postsurgical analgesia and access to rescue medication. The co-primary efficacy endpoints are area under the curve of visual analog scale pain intensity scores from 12-48 hours postsurgery and total postsurgical opioid consumption from 0-48 hours. Secondary efficacy endpoints include other pain assessments, time to first use of rescue medication, discharge readiness, use of skilled nursing facilities, and hospital length of stay. Safety will be evaluated based on adverse events. DISCUSSION/CONCLUSION: The use of a standardized protocol comparing infiltration of equal volumes of the study drug, designed by experienced investigators to ensure complete coverage of all areas innervating the surgical site while minimizing leakage of study drug, will help define the role of liposomal bupivacaine in the setting of TKA.


Subject(s)
Anesthetics, Local/administration & dosage , Arthroplasty, Replacement, Knee/adverse effects , Bupivacaine/administration & dosage , Pain, Postoperative/drug therapy , Analgesia , Anesthetics, Local/pharmacokinetics , Bupivacaine/pharmacokinetics , Double-Blind Method , Humans , Liposomes
20.
Langmuir ; 32(39): 10017-10025, 2016 10 04.
Article in English | MEDLINE | ID: mdl-27595803

ABSTRACT

We report the effect of nonionic surfactants (Pluronics F127 and F88) on the melting transition of micron-sized colloids confined in two dimensions, mediated by complementary single-stranded DNA as a function of the surfactant concentration. Micron-sized silica particles were functionalized with single-stranded DNA using cyanuric chloride chemistry. The existence of covalently linked DNA on particles was confirmed by fluorescence spectroscopy. The nonionic surfactant not only plays a significant role in stabilization of particles, with minimization of nonspecific binding, but also impacts the melting temperature, which increases as a function of the nonionic surfactant concentration. These results suggest that the melting transition for DNA-mediated assembly is sensitive to commonly used additives in laboratory buffers, and that these common solution components may be exploited as a facile and independent handle for tuning the melting temperature and, thus, the assembly and possibly crystallization within these systems.


Subject(s)
Colloids/chemistry , DNA, Single-Stranded/chemistry , Poloxamer/chemistry , Silicon Dioxide/chemistry , Surface-Active Agents/chemistry , Base Sequence , Micelles , Nucleic Acid Hybridization , Particle Size , Phase Transition , Transition Temperature
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