The Bioactive Core and Corona Synergism of Quantized Gold Enables Slowed Inflammation and Increased Tissue Regeneration in Wound Hypoxia.

The progress of wound regeneration relies on inflammation management, while neovascular angiogenesis is a critical aspect of wound healing. In this study, the bioactive core and corona synergism of quantized gold (QG) were developed to simultaneously address these complicated issues, combining the abilities to eliminate endotoxins and provide oxygen. The QG was constructed from ultrasmall nanogold and a loosely packed amine-based corona via a simple process, but it could nonetheless eliminate endotoxins (a vital factor in inflammation also called lipopolysaccharides) and provide oxygen in situ for the remodeling of wound sites. Even while capturing endotoxins through electrostatic interactions, the catalytic active sites inside the nanogold could maintain its surface accessibility to automatically transform the overexpressed hydrogen peroxide in hypoxic wound regions into oxygen. Since the inflammatory stage is an essential stage of wound healing, the provision of endotoxin clearance by the outer organic corona of the QG could slow inflammation in a way that subsequently promoted two other important stages of wound bed healing, namely proliferation and remodeling. Relatedly, the efficacy of two forms of the QG, a liquid form and a dressing form, was demonstrated at wound sites in this study, with both forms promoting the development of granulation, including angiogenesis and collagen deposition. Thus, the simply fabricated dual function nanocomposite presented herein not only offers reduced batch-to-batch variation but also increased options for homecare treatments.

Spatially Specific Attention Mechanisms Are Sensitive to Competition during Visual Search.

Extensive studies have focused on selection mechanisms during visual search. One important influence on these mechanisms is the perceptual characteristics of the stimuli. We investigated the impact of perceptual similarity between targets and nontargets (T-N similarity) in a visual search task using EEG. Participants searched for a predefined target letter among five nontargets. The T-N similarity was manipulated with three levels: high, middle, and low. We tested for the influences of T-N similarity on an ERP (e.g., N2pc) and alpha oscillations. We observed a significant N2pc effect across all levels of similarity. The N2pc amplitude was reduced and occurred later for high similarity relative to low and middle similarities. We also showed that the N2pc amplitude was inversely correlated with the RTs across all similarities. Importantly, we found a significant alpha phase adjustment about the same time as the N2pc for high similarity; by contrast, no such effect was observed for middle and low similarities. Finally, we showed a positive correlation between the phase-locking value and the N2pc-the stronger the alpha phase-locking value, the larger the N2pc, when the T-N similarity was high. In conclusion, our results provide novel evidence for multiple competitive mechanisms during visual search.

Summative Objective Structured Clinical Examination Assessment at the End of Anesthesia Residency for Perioperative Ultrasound.

While standardized examinations and data from simulators and phantom models can assess knowledge and manual skills for ultrasound, an Objective Structured Clinical Examination (OSCE) could assess workflow understanding. We recruited 8 experts to develop an OSCE to assess workflow understanding in perioperative ultrasound. The experts used a binary grading system to score 19 graduating anesthesia residents at 6 stations. Overall average performance was 86.2%, and 3 stations had an acceptable internal reliability (Kuder-Richardson formula 20 coefficient >0.5). After refinement, this OSCE can be combined with standardized examinations and data from simulators and phantom models to assess proficiency in ultrasound.

Epoxylated Zwitterionic Triblock Copolymers Grafted onto Metallic Surfaces for General Biofouling Mitigation.

Titanium and stainless steel materials are widely used in numerous devices or in custom parts for their excellent mechanical properties. However, their lack of biocompatibility seriously limits their usage in the biomedical field. This study focuses on the grafting of triblock copolymers on titanium and stainless steel metal susbtrates for improving their general biofouling resistance. The series of copolymers that we designed is composed of two blocks of zwitterionic sulfobetaine (SBMA) monomers and one block of glycidyl methacrylate (GMA). The number of repeat units forming each block, n, was finely tuned and controlled to 25, 50, 75, or 100, permitting regulation of the grafting thickness, the morphology, and the dependent properties such as the surface hydrophilicity and biofouling resistance. It was shown that the copolymer possessing n = 50 repeat units in each block, corresponding to a molecular weight of about 15.2 kDa, led to the best nonfouling properties, assessed using plasma proteins, blood cells, fibroblasts cells, and various bacteria. This was explained by an optimized grafting degree and chain organization of the copolymer. Lower value (n = 25) and higher values (n = 75, 100) led to low surface coverage and the formation of aggregates, respectively. The best copolymer was grafted onto scalpels (steel) and dental roots (titanium), and antifouling properties demonstrated using Escherichia coli and HT1080 cells. Results of this work show that this unique triblock copolymer holds promise as a potential material for surface modification of biomedical metallic devices, provided a fine-tuning of the blocks organization and length.

Assessment of Perioperative Ultrasound Workflow Understanding: A Consensus.

OBJECTIVES: Understanding of the workflow of perioperative ultrasound (US) examination is an integral component of proficiency. Workflow consists of the practical steps prior to executing an US examination (eg, equipment operation). Whereas other proficiency components (ie, cognitive knowledge and manual dexterity) can be tested, workflow understanding is difficult to define and assess due to its contextual and institution-specific nature. The objective was to define the workflow components of specific perioperative US applications using an iterative process to reach a consensus opinion. DESIGN: Expert consensus, survey study. SETTING: Tertiary university hospital. PARTICIPANTS: This study sought expert consensus among a focus group of 9 members of an anesthesia department with experience in perioperative US. Afterward, 257 anesthesia faculty members from 133 academic centers across the United States were surveyed. INTERVENTIONS: A preliminary list of tasks was designed to establish the expectations of workflow understanding by an anesthesiology resident prior to clinical exposure to perioperative US. This list was modified by a focus group through an iterative process. Afterwards, a survey was sent to faculty members nationwide, and Likert scale ratings for each task were obtained and reviewed during a second round. MEASUREMENTS AND MAIN RESULTS: Consensus among members of the focus group was reached after 2 iterations. 72 participants responded to the nationwide survey (28%), and consensus was reached after the second round (Cronbach's α = 0.99, ICC = 0.99) on a final list of 46 workflow-related tasks. CONCLUSIONS: Specific components of perioperative US workflow were identified. Evaluation of workflow understanding may be combined with cognitive knowledge and manual dexterity testing for assessing proficiency in perioperative US.

Computer-guided normal-low versus normal-high potassium control after cardiac surgery: No impact on atrial fibrillation or atrial flutter.

INTRODUCTION: This study was designed to determine the effect of 2 different potassium regulation strategies with different targets (within the reference range) on atrial fibrillation (AF) or atrial flutter (AFL) in a cohort of intensive care unit patients after cardiac surgery. METHODS: The GRIP-COMPASS study was a prospective double-blinded interventional study in 910 patients after cardiac surgery (coronary artery bypass grafting and/or valvular surgery). Patients were assigned to either the normal-low potassium target (nLP group, 4.0 mmol/L) or the normal-high potassium target (nHP group, 4.5 mmol/L) in alternating blocks of 50 patients. Potassium levels were regulated using a validated computer-assisted potassium replacement protocol (GRIP-II). The primary end point was the incidence of AF/AFL on a 12-lead electrocardiogram during the first postoperative week. RESULTS: Of the 910 patients, 447 were assigned to the nLP group; and 463, to the nHP group, with no baseline differences between the 2 groups. The mean daily administered dose of potassium was 30 ± 23 mmol (nLP) versus 52 ± 27 mmol (nHP) (P < .001), which resulted in mean intensive care unit potassium concentration of 4.22 ± 0.36 mmol/L and 4.33 ± 0.34 mmol/L, respectively (P < .001). The incidence of AF/AFL after cardiac surgery did not differ: 38% in the nLP group and 41% in the nHP group. Also in several subgroups (eg, patients not known with prior AF/AFL or with valve surgery), there were no differences. CONCLUSIONS: There were no differences in incidence of AF/AFL with 2 potassium regulation strategies with different potassium targets and different amounts of potassium administered in patients after cardiac surgery.

Hemodynamic Testing of Patient-Specific Mitral Valves Using a Pulse Duplicator: A Clinical Application of Three-Dimensional Printing.

OBJECTIVE: To evaluate the feasibility of obtaining hemodynamic metrics of echocardiographically derived 3-dimensional printed mitral valve models deployed in a pulse-duplicator chamber. DESIGN: Exploratory study. SETTING: Tertiary-care university hospital. PARTICIPANTS: Percutaneous MitraClip procedure patient. INTERVENTIONS: Three-dimensional R-wave gated, full-volume transesophageal echocardiography images were obtained after deployment of the MitraClip device. A high-quality diastolic frame of the mitral valve was segmented using Mimics Innovation Suite and merged with a flange. The data were exported as a stereolithography (.stl) file, and a rigid 3-dimensional model was printed using a MakerBot Replicator 2 printer. A flexible silicone cast then was created and deployed in the pulse-duplicator chamber filled with a blood-mimicking fluid. MEASUREMENTS AND MAIN RESULTS: The authors were able to obtain continuous-wave Doppler tracings of the valve inflow with a transesophageal echocardiography transducer. They also were able to generate diastolic ventricular and atrial pressure tracings. Pressure half-time and mitral valve area were computed from these measurements. CONCLUSION: This pulse duplicator shows promising applications in hemodynamic testing of patient-specific anatomy. Future modifications to the system may allow for visualization and data collection of gradients across the aortic valve.

Category-based attention facilitates memory search.

We often need to decide whether the object we look at is also the object we look for. When we look for one specific object, this process can be facilitated by feature-based attention. However, when we look for many objects at the same time (e.g., the products on our shopping list) such a strategy may no longer be possible, as research has shown that we can actively prepare to detect only one or two objects at a time. Therefore, looking for multiple objects additionally requires long-term memory search, slowing down decision making. Interestingly, however, previous research has shown that distractor objects can be efficiently rejected during memory search when they are from a different category than the items in the memory set. Here, using EEG, we show that this efficiency is supported by top-down attention at the category level. In Experiment 1, human participants (both sexes) performed a memory search task on individually presented objects from different categories, most of which were distractors. We observed category-level attentional modulation of distractor processing from ∼150 ms after stimulus onset, expressed both as an evoked response modulation and as an increase in decoding accuracy of same-category distractors. In Experiment 2, memory search was performed on two concurrently presented objects. When both objects were distractors, spatial attention (indexed by the N2pc component) was directed to the object that was of the same category as the objects in the memory set. Together, these results demonstrate how top-down attention can facilitate memory search.Significance statement When we are in the supermarket, we repeatedly decide whether a product we look at (e.g., a banana) is on our memorized shopping list (e.g., apples, oranges, kiwis). This requires searching our memory, which takes time. However, when the product is of an entirely different category (e.g., dairy instead of fruit), the decision can be made quickly. Here, we used EEG to show that this between-category advantage in memory search tasks is supported by top-down attentional modulation of visual processing: The visual response evoked by distractor objects was modulated by category membership, and spatial attention was quickly directed to the location of within-category (vs. between-category) distractors. These results demonstrate a close link between attention and memory.

Temporal profiles of cortical oscillations in novice performers for goal-directed aiming in a shooting task.

Goal-directed aiming relies on the ability to control attention and visuomotor movements while preparing for motor execution. Research in precision sports has investigated cortical oscillations for supporting expert performance. However, the results may be influenced by adaptive and strategic behaviors after intensive training. Whether and at what time points distinctive oscillations support goal-directed aiming without such training remains elusive. In this electroencephalographic (EEG) study, we investigated how the theta, alpha and beta oscillations change to support accurate aiming before novices took an action. We first conducted a model-based analysis to examine the correlation of cortical oscillations with accurate shooting on a trial-by-trial basis in a within-individual manner. The results showed that alpha and beta oscillations at different time points during the aiming period were better predictors of aiming accuracy. We then compared the oscillatory power for good versus poor performance. The results showed decreases in the alpha and beta power across distributed cortical areas and an increase in the frontal theta power successively before shot release. Moreover, greater intertrial phase coherence was observed for good performance than for poor performance in posterior alpha activity and anterior beta activity during the aiming period. In conclusion, these results advance our understanding of the temporal dynamics of theta, alpha and beta oscillations in orchestrating goal setting, motor preparation and focused attention to monitoring both external and internal states for accurate aiming. Among the three, alpha and beta oscillations are critical for predicting aiming performance and theta oscillations reflect effortful cognitive control.

Determinants of renal potassium excretion in critically ill patients: the role of insulin therapy.

OBJECTIVES: Insulin administration lowers plasma potassium concentration by augmenting intracellular uptake of potassium. The effect of insulin administration on renal potassium excretion is unclear. Some studies suggest that insulin has an antikaliuretic effect although plasma potassium levels were poorly controlled. Since the introduction of glycemic control in the intensive care unit, insulin use has increased. We examined the relation between administered insulin and renal potassium excretion in critically ill patients under computer-assisted glucose and potassium regulation. DESIGN: Prospective observational study. SETTING: Twelve-bed surgical intensive care unit of a university teaching hospital. PATIENTS: Consecutive intensive care unit patients. INTERVENTIONS: Potassium and glucose levels were regulated by a computer-assisted decision support system. Both potassium and insulin were continuously administered by syringe pump. MEASUREMENTS AND MAIN RESULTS: Renal potassium excretion was measured daily in the 24-hr urine collections. The 24-hr urinary samples of patients with kidney failure or on renal replacement therapy were excluded. Multivariate analysis with potassium excretion as the dependent variable was performed. In 178 consecutive patients, 1,456 24-hr urinary samples, were analyzed. Mean ± SD plasma potassium was 4.2 ± 0.3 mmol/L, with 79 ± 46 mmol/d of potassium administered and a mean insulin dose of 53 ± 38 U/day. Renal potassium excretion was 126 ± 51 mmol/day. After multivariate analysis correcting for relevant variables (including diuretics, pH, potassium levels and renal sodium excretion), insulin administration was independently and positively associated with renal potassium excretion. Other significant variables were potassium levels, potassium administration, renal sodium and chloride excretion, creatinine clearance, diuretic therapy, pH, known diabetes and intensive care unit admission day (R = .52; p <. 001). CONCLUSION: Insulin administration is associated with an increase in the renal potassium excretion in critically ill patients.

The time course of categorical and perceptual similarity effects in visual search.

During visual search for objects (e.g., an apple), the surrounding distractor objects may share perceptual (tennis ball), categorical (banana), or both (peach) properties with the target. Previous studies showed that the perceptual similarity between target and distractor objects influences visual search. Here, we tested whether categorical target-distractor similarity also influences visual search, and how this influence depends on perceptual similarity. By orthogonally manipulating categorical and perceptual target-distractor similarity, we could investigate how and when the two similarities interactively affect search performance and neural correlates of spatial attention (N2pc) using electroencephalography (EEG). Behavioral results showed that categorical target-distractor similarity interacted with perceptual target-distractor similarity, such that the effect of categorical similarity was strongest when target and distractor objects were perceptually similar. EEG results showed that perceptual similarity influenced the early part of the N2pc (200-250 ms after stimulus onset), while categorical similarity influenced the later part (250-300 ms). Mirroring the behavioral results, categorical similarity interacted with perceptual similarity during this later time window, with categorical effects only observed for perceptually similar target-distractor pairs. Together, these results provide evidence for hierarchical processing in visual search: categorical properties influence spatial attention only when perceptual properties are insufficient to guide attention to the target. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

A Potent Histone Deacetylase Inhibitor MPT0E028 Mitigates Emphysema Severity via Components of the Hippo Signaling Pathway in an Emphysematous Mouse Model.

Background: Chronic obstructive pulmonary disease (COPD) is a major cause of chronic mortality. The objective of this study was to investigate the therapeutic potential of a novel potent histone deacetylase (HDAC) inhibitor MPT0E028 on emphysema. Materials and Methods: A mouse model of porcine pancreatic elastase (PPE)-induced emphysema was orally administered 0, 25, or 50 mg/kg body weight (BW) of the MPT0E028 five times/week for 3 weeks. Pulmonary function, mean linear intercept (MLI), chest CT, inflammation, yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), surfactant protein C (SPC), T1-α, p53, and sirtuin 1 (SIRT1) levels were examined. Results: 50 mg/kg BW of the MPT0E028 significantly decreased the tidal volume in emphysematous mice (p < 0.05). Emphysema severity was significantly reduced from 26.65% (PPE only) to 13.83% (50 mg/kg BW of the MPT0E028). Total cell counts, neutrophils, lymphocytes, and eosinophils significantly decreased with both 25 and 50 mg/kg BW of the MPT0E028 (p < 0.05). Also, 50 mg/kg BW of the MPT0E028 significantly decreased the levels of KC, TNF-α, and IL-6 in lung tissues and serum (p < 0.05). Expressions of p-TAZ/TAZ in lung tissues significantly decreased with 50 mg/kg BW of the MPT0E028 (p < 0.05). Expressions of p53 significantly decreased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05), and the expression of SPC increased in alveolar regions with 50 mg/kg BW of the MPT0E028 (p < 0.05). Conclusions: Our study showed that the potent HDAC inhibitor MPT0E028 reduced the severity and inflammation of emphysema with improvement in lung function, which could be regulated by Hippo signaling pathway. The MPT0E028 may have therapeutic potential for emphysema.

Ultra-Small Platinum Nanoparticle-Enabled Catalysis and Corrosion Susceptibility Reverse Tumor Hypoxia for Cancer Chemoimmunotherapy.

A major challenge in the use of chemotherapy and immunotherapy is hypoxia-induced progression of tumor cells. We aim to curb hypoxia using metal-based O2-producing nanomedicine. The key focus is therapeutic targeting of hypoxia-inducible factor 1α (HIF-1α), a major reactive oxygen species (ROS)-activated player that drives hypoxia-dependent tumor progression. Inhibition of tumor growth by blocking both HIF-1α and immune checkpoint molecules via ROS removal is a promising new strategy to avoid ROS-induced hypoxia signaling and boost antitumor immunity. Here, we investigated the synergistic effect of ultra-small platinum nanoparticles (Pt-nano) with dual functions of enzyme-mimicking catalysis and corrosion susceptibility to block hypoxia signaling of tumors. Ultra-small Pt-nano with highly corrosive susceptibility can efficiently catalyze ROS scavenging and promote oxygen accumulation for hypoxia reversal, leading to reduced HIF-1α expression. The unique corrosion susceptibility allows ultra-small Pt-nano to effectively exert platinum cytotoxicity, induce reversal of hypoxia-mediated immune suppression by promoting cytotoxic T-cell infiltration of tumors, and reduce the levels of tumoral immune checkpoint molecules and immunosuppressive cytokines. In combination with immune checkpoint blockade using monoclonal antibodies, nanoparticle-enabled enzyme-mimicking is a promising strategy for the enhancement of chemoimmunotherapeutic efficacy through the reversal of tumor hypoxia.

Evaluation of the quality of transesophageal echocardiography images and verification of proficiency

Various metrics have been used in curriculum-based transesophageal echocardiography (TEE) training programs to evaluate acquisition of proficiency. However, the quality of task completion, that is the final image quality, was subjectively evaluated in these studies. Ideally, the endpoint metric should be an objective comparison of the trainee-acquired image with a reference ideal image. Therefore, we developed a simulator-based methodology of preclinical verification of proficiency (VOP) in trainees by tracking objective evaluation of the final acquired images. We utilized geometric data from the simulator probes to compare image acquisition of anesthesia residents who participated in our structured longitudinal simulator-based TEE educational program vs ideal image planes determined from a panel of experts. Thirty-three participants completed the study (15 experts, 7 postgraduate year (PGY)-1 and 11 PGY-4). The results of our study demonstrated a significant difference in image capture success rates between learners and experts (χ2 = 14.716, df = 2, P < 0.001) with the difference between learners (PGY-1 and PGY-4) not being statistically significant (χ2 = 0, df = 1, P = 1.000). Therefore, our results suggest that novices (i.e. PGY-1 residents) are capable of attaining a level of proficiency comparable to those with modest training (i.e. PGY-4 residents) after completion of a simulation-based training curriculum. However, professionals with years of clinical training (i.e. attending physicians) exhibit a superior mastery of such skills. It is hence feasible to develop a simulator-based VOP program in performance of TEE for junior anesthesia residents.

Low-cost three-dimensional printed phantom for neuraxial anesthesia training: Development and comparison to a commercial model.

METHODS: Anonymized CT DICOM data was segmented to create a 3D model of the lumbar spine. The 3D model was modified, placed inside a digitally designed housing unit and fabricated on a desktop 3D printer using polylactic acid (PLA) filament. The model was filled with an echogenic solution of gelatin with psyllium fiber. Twenty-two staff anesthesiologists performed a spinal and epidural on the 3D printed simulator and a commercially available Simulab phantom. Participants evaluated the tactile and ultrasound imaging fidelity of both phantoms via Likert-scale questionnaire. RESULTS: The 3D printed neuraxial phantom cost $13 to print and required 25 hours of non-supervised printing and 2 hours of assembly time. The 3D printed phantom was found to be less realistic to surface palpation than the Simulab phantom due to fragility of the silicone but had significantly better fidelity for loss of resistance, dural puncture and ultrasound imaging than the Simulab phantom. CONCLUSION: Low-cost neuraxial phantoms with fidelity comparable to commercial models can be produced using CT data and low-cost infrastructure consisting of FLOS software and desktop 3D printers.