Predictors of postoperative delirium among patients undergoing total knee arthroplasty: a literature review

Delirium is a neurocognitive disorder characterized by the presence of disturbance in attention that develops over a short period of time, which is not explained by another preexisting neurocognitive disorder and it is the physiological consequence of another medical condition. Although there are no known causes of delirium, multiple factors are thought to play a role in the development of the disorder. Postoperative delirium is common in hospitalized patients undergoing surgery. Studies have indicated that postoperative delirium incidence varies depending on the type of surgery performed, the criteria used to diagnose delirium, and the population that is being studied. Consequences of postoperative delirium include prolonged hospitalization, decline in cognitive function, and an increase in mortality rate. The purpose of the study was to review the literature on the risk factors of delirium incidence postoperatively among patients undergoing total knee arthroplasty. A literature review on postoperative delirium in total knee arthroplasty patients and its risk factors was conducted using the PubMed database from January 2011 to March 2018, yielding 15 articles that met inclusion criteria. Articles were reviewed for patient demographic characteristics, postoperative delirium diagnosis methods, findings, strengths, and limitations. There was little consistency on the diagnostic measures of postoperative delirium, where nine of the studies used the same standardized tool, but there was still variation in the frequency of the use of the tool. Among patients undergoing total knee arthroplasty (age range: 60 to >80 years), postoperative delirium incidence ranged from 0.6% to 62.5%. Incidence of postoperative delirium was determined by the following risk factors: older age and/or history of psychiatric disorders and/or ethnicity, electrolyte disorders, preoperative cerebrospinal fluid β-amyloid/tau ratio, preexisting obstructive sleep apnea, use of preventative screening measures, vigorous physiotherapy, and type of pain medication prescribed. In conclusion, accurate prediction of risk factors associated with postoperative delirium incidence may help patients, providers, payers, and health systems with decision-making and opportunities for intervention(s) early in the disease course, therefore prioritizing the public health implications associated with postoperative delirium

Enhanced Uptake of Luminescent Quantum Dots by Live Cells Mediated by a Membrane-Active Peptide

The steady progress made over the past three decades in growing a variety of inorganic nanomaterials, with discreet control over their size and photophysical properties, has been exploited to develop several imaging and sensing applications. However, full integration of these materials into biology has been hampered by the complexity of delivering them into cells. In this report, we demonstrate the effectiveness of a chemically synthesized anticancer peptide to facilitate the rapid delivery of luminescent quantum dots (QDs) into live cells. We combine fluorescence imaging microscopy, flow cytometry, and specific endocytosis inhibition experiments to probe QD–peptide conjugate uptake by different cell lines. We consistently find that a sizable fraction of the internalized conjugates does not co-localize with endosomes or the nuclei. These findings are extremely promising for the potential integration of various nanomaterials into biological systems

A Multifunctional Polymer Combining the Imidazole and Zwitterion Motifs as a Biocompatible Compact Coating for Quantum Dots

We introduce a set of multicoordinating imidazole- and zwitterion-based ligands suited for surface functionalization of quantum dots (QDs). The polymeric ligands are built using a one-step nucleophilic addition reaction between poly­(isobutylene-<i>alt</i>-maleic anhydride) and distinct amine-containing functionalities. This has allowed us to introduce several imidazole anchoring groups along the polymer chain for tight coordination to the QD surface and a controllable number of zwitterion moieties for water solubilization. It has also permitted the introduction of reactive and biomolecular groups for further conjugation and targeting. The QDs capped with these new ligands exhibit excellent long-term colloidal stability over a broad range of pH, toward excess electrolyte, in cell-growth media, and in the presence of natural reducing agents such as glutathione. These QDs are also resistant to the oxidizing agent H₂O₂. More importantly, by the use of zwitterion moieties as the hydrophilic block, this polymer design provides QDs with a thin coating and compact overall dimensions. These QDs are easily self-assembled with full size proteins expressed with a polyhistidine tag via metal–histidine coordination. Additionally, the incorporation of amine groups allows covalent coupling of the QDs to the neurotransmitter dopamine. This yields redox-active QD platforms that can be used to track pH changes and detect Fe ions and cysteine through charge-transfer interactions. Finally, we found that QDs cap-exchanged with folic acid-functionalized ligands could effectively target cancer cells, where folate-receptor-mediated endocytosis of QDs into living cells was time- and concentration-dependent

Nanoparticle-assisted, image-guided laser interstitialthermal therapy for cancer treatment

Laser interstitial thermal therapy (LITT) guided by magnetic resonance imaging (MRI) is a new treatment option for patients with brain and non-central nervous system (non-CNS) tumors. MRI guidance allows for precise placement of optical fiber in the tumor, while MR thermometry provides real-time monitoring and assessment of thermal doses during the procedure. Despite promising clinical results, LITT complications relating to brain tumor procedures, such as hemorrhage, edema, seizures, and thermal injury to nearby healthy tissues, remain a significant concern. To address these complications, nanoparticles offer unique prospects for precise interstitial hyperthermia applications that increase heat transport within the tumor while reducing thermal impacts on neighboring healthy tissues. Furthermore, nanoparticles permit the co-delivery of therapeutic compounds that not only synergize with LITT, but can also improve overall effectiveness and safety. In addition, efficient heat-generating nanoparticles with unique optical properties can enhance LITT treatments through improved real-time imaging and thermal sensing. This review will focus on (1) types of inorganic and organic nanoparticles for LITT; (2) in vitro, in silico, and ex vivo studies that investigate nanoparticles' effect on light–tissue interactions; and (3) the role of nanoparticle formulations in advancing clinically relevant image-guided technologies for LITT.https://doi.org/10.1002/wnan.182

Intracellular Delivery of Luminescent Quantum Dots Mediated by a Virus-Derived Lytic Peptide

We describe a new quantum dot (QD)-conjugate prepared with a lytic peptide, derived from a nonenveloped virus capsid protein, capable of bypassing the endocytotic pathways and delivering large amounts of QDs to living cells. The polypeptide, derived from the Nudaurelia capensis Omega virus, was fused onto the C-terminus of maltose binding protein that contained a hexa-HIS tag at its N-terminus, allowing spontaneous self-assembly of controlled numbers of the fusion protein per QD via metal–HIS interactions. We found that the efficacy of uptake by several mammalian cell lines was substantial even for small concentrations (10–100 nM). Upon internalization the QDs were primarily distributed outside the endosomes/lysosomes. Moreover, when cells were incubated with the conjugates at 4 °C, or in the presence of chemical endocytic inhibitors, significant intracellular uptake continued to occur. These findings indicate an entry mechanism that does not involve endocytosis, but rather the perforation of the cell membrane by the lytic peptide on the QD surfaces

Photoligation of an Amphiphilic Polymer with Mixed Coordination Provides Compact and Reactive Quantum Dots

We introduce a new set of multicoordinating polymers as ligands that combine two distinct metal-chelating groups, lipoic acid and imidazole, for the surface functionalization of QDs. These ligands combine the benefits of thiol and imidazole coordination to reduce issues of thiol oxidation and weak binding affinity of imidazole. The ligand design relies on the introduction of controllable numbers of lipoic acid and histamine anchors, along with hydrophilic moieties and reactive functionalities, onto a poly­(isobutylene-<i>alt</i>-maleic anhydride) chain via a one-step nucleophilic addition reaction. We further demonstrate that this design is fully compatible with a novel and mild photoligation strategy to promote the in situ ligand exchange and phase transfer of hydrophobic QDs to aqueous media under borohydride-free conditions. Ligation with these polymers provides highly fluorescent QDs that exhibit great long-term colloidal stability over a wide range of conditions, including a broad pH range (3–13), storage at nanomolar concentration, under ambient conditions, in 100% growth media, and in the presence of competing agents with strong reducing property. We further show that incorporating reactive groups in the ligands permits covalent conjugation of fluorescent dye and redox-active dopamine to the QDs, producing fluorescent platforms where emission is controlled/tuned by Förster Resonance Energy Transfer (FRET) or pH-dependent charge transfer (CT) interactions. Finally, the polymer-coated QDs have been coupled to cell-penetrating peptides to facilitate intracellular uptake, while subsequent cytotoxicity tests show no apparent decrease in cell viability