Ready for Discharge, but Are They Ready to Go Home? Examining Neighborhood-Level Disadvantage as a Marker of the Social Exposome and the Swallowing Care Process in a Retrospective Cohort of Inpatients With Dementia.

PURPOSE: Socioeconomically disadvantaged areas are more resource poor, impacting adherence to swallowing care recommendations. Neighborhood-level disadvantage metrics, such as the Area Deprivation Index (ADI), allow for examination of social determinants of health (SDOH) in a precise region. We examined ADI in a cohort of persons living with dementia (PLWD) to determine representation of those residing in areas of socioeconomic disadvantage (high ADI), distribution of swallowing care provided, and frequency of SDOH-related counseling or resource linking prior to discharge. METHOD: A retrospective chart abstraction was performed for all inpatients with a diagnosis of dementia (N = 204) seen by the Swallow Service at a large academic hospital in 2014. State ADI Deciles 1 (least) to 10 (most socioeconomic disadvantage) and decile groups (1-3, 4-7, and 8-10) were compared with the surrounding county. Frequency of videofluoroscopic swallowing evaluations (VFSEs) based on ADI deciles was recorded. To determine whether SDOH-related counseling or resource linking occurred for those in high ADI (8-10) neighborhoods, speech-language pathology notes, and discharge summaries were reviewed. Descriptive statistics, independent samples t tests, and one-way analysis of variance were calculated. RESULTS: ADI was significantly higher in this cohort (M = 3.84, SD = 2.58) than in the surrounding county (M = 2.79, SD = 1.88, p = .000). There was no significant difference in utilization of swallowing services across decile groups (p = .88). Although the majority (85%) in high ADI areas was recommended diet modifications or alternative nutrition likely requiring extra resources, there was no documentation indicating that additional SDOH resource linking or counseling was provided. CONCLUSIONS: These findings raise important questions about the role and responsibility of speech-language pathologists in tailoring swallowing services to challenges posed by the lived environment, particularly in socioeconomically disadvantaged areas. This underscores the need for further research to understand and address gaps in postdischarge support for PLWD in high-ADI regions and advocate for more equitable provision of swallowing care.

Recent advances in shape memory polymeric nanocomposites for biomedical applications and beyond.

Shape memory polymers (SMPs), which initiate shape transformation in response to environmental stimuli, have attracted significant attention in both academic research and technological innovation. The combination of functional nanomaterials and SMPs has led to the emergence of a variety of shape memory polymeric nanocomposites (SMPNs) with multifunctional properties. This has injected new vitality and vigor into fields such as tissue engineering, biomedicine, optical sensing, aerospace and mechanical engineering. In this review article, we present a brief introduction to the fundamentals of SMPs and SMPNs, followed by a discussion of the recent advances in their multifunctional applications in biomedical manufacturing, drug delivery devices, mechanical sensing, micro-engines, etc. The opportunities and challenges in the future development of SMPs are also discussed.

Using silver nanoparticle-decorated whey protein isolate amyloid fibrils to modify the electrode surface used for electrochemical detection of para-nitrophenol.

Due to their organized structures, remarkable stiffness, and nice biocompatibility and biodegradability, amyloid fibrils serve as building blocks for versatile sustainable materials. Silver nanoparticles (AgNPs) are commonly used as the nano-catalysts for various electrochemical reactions. Given their large specific surface area and high surface energy, AgNPs exhibit high aggregation propensity, which hampers their electrocatalytic performance. Food protein wastes have been identified to be associated with climate change and environmental impacts, and a surplus of whey proteins in dairy industries causes high biological and chemical demands, and greenhouse gas emissions. This study is aimed at constructing sustainable electrode surface modifiers using AgNP-deposited whey protein amyloid fibrils (AgNP/WPI-AFs). AgNP/WPI-AFs were synthesized and characterized via spectroscopic techniques, electron microscopy, and X-ray diffraction. Next, the electrocatalytic performance of AgNP/WPI-AF modified electrode was assessed via para-nitrophenol (p-NP) reduction combined with various electrochemical analyses. Moreover, the reaction mechanism of p-NP electrocatalysis on the surface of AgNP/WPI-AF modified electrode was investigated. The detection range, limit of detection, sensitivity, and selectivity of the AgNP/WPI-AF modified electrode were evaluated accordingly. This work not only demonstrates an alternative for whey valorization but also highlights the feasibility of using amyloid-based hybrid materials as the electrode surface modifier for electrochemical sensing purposes.

Development of subunit selective proteasome substrates for Schistosoma species.

Schistosomiasis, or bilharzia, is a neglected tropical disease caused by Schistosoma spp. blood flukes that infects over 200 million people worldwide. Just one partially effective drug is available, and new drugs and drug targets would be welcome. The 20S proteasome is a validated drug target for many parasitic infections, including those caused by Plasmodium and Leishmania. We previously showed that anticancer proteasome inhibitors that act through the Schistosoma mansoni 20S proteasome (Sm20S) kill the parasite in vitro. To advance these initial findings, we employed Multiplex Substrate Profiling by Mass Spectrometry (MSP-MS) to define the substrate cleavage specificities of the three catalytic ß subunits of purified Sm20S. The profiles in turn were used to design and synthesize subunit-specific optimized substrates that performed two to eight fold better than the equivalent substrates used to measure the activity of the constitutive human proteasome (c20S). These specific substrates also eliminated the need to purify Sm20S from parasite extracts - a single step enrichment was sufficient to accurately measure substrate hydrolysis and its inhibition with proteasome inhibitors. Finally, we show that the substrate and inhibition profiles for the 20S proteasome from the three medically important schistosome species are similar, suggesting that data arising from an inhibitor development campaign that focuses on Sm20S can be extrapolated to the other two targets with consequent time and cost savings.

Forced capillary wetting of viscoelastic fluids.

HYPOTHESIS: Achieving rapid capillary wetting is highly desirable in nature and industries. Previous endeavors have primarily concentrated on passive wetting strategies through surface engineering. However, these approaches are inadequate for high-viscosity fluids due to the significant viscous resistance, especially for non-Newtonian fluids. In contrast, forced wetting emerges as a promising method to address the challenges associated with achieving rapid wetting of non-Newtonian fluids in capillaries. EXPERIMENTS: To investigate the forced wetting behavior of viscoelastic fluids in capillaries, we employ Xanthan Gum (XG) aqueous solutions as target fluids with the storage modulus significantly exceeding the loss modulus. We utilize smooth glass capillaries connected to a syringe pump to achieve high moving speeds of up to 1 m/s. FINDINGS: Our experiments reveal a significant distinction in the power-law exponent that governs the scaling relationship between the dynamic contact angle and velocity for viscoelastic fluids compared to Newtonian fluids. This exponent is considerably smaller and varies based on the concentration of viscoelastic fluids and the diameter of the capillaries. We suggest that the viscosity dominates the wetting dynamics of viscoelastic fluids, manifested by the contact line morphology-dependent behavior. This insight has significant implications for microfluidics and drug injectability.

Laser-Induced Electron Synchronization Excitation for Photochemical Synthesis and Patterning Graphene-Based Electrode.

Micro-supercapacitors (MSCs) represent a pressing requirement for powering the forthcoming generation of micro-electronic devices. The simultaneous realization of high-efficiency synthesis of electrode materials and precision patterning for MSCs in a single step presents an ardent need, yet it poses a formidable challenge. Herein, a unique shaped laser-induced patterned electron synchronization excitation strategy has been put forward to photochemical synthesis RuO2 /reduced graphene oxide (rGO) electrode and simultaneously manufacture the micron-scale high-performance MSCs with ultra-high resolution. Significantly, the technique represents a noteworthy advancement over traditional laser direct writing (LDW) patterning and photoinduced synthetic electrode methods. It not only improves the processing efficiency for MSCs and the controllability of laser-induced electrode material but also enhances electric fields and potentials at the interface for better electrochemical performance. The resultant MSCs exhibit excellent area and volumetric capacitance (516 mF cm-2 and 1720 F cm-3 ), and ultrahigh energy density (0.41 Wh cm-3 ) and well-cycle stability (retaining 95% capacitance after 12000 cycles). This investigation establishes a novel avenue for electrode design and underscores substantial potential in the fabrication of diverse microelectronic devices.

Recent advances in the biological depolymerization and upcycling of polyethylene terephthalate.

Polyethylene terephthalate (PET) is favored for its exceptional properties and widespread daily use. This review highlights recent advancements that enable the development of biological tools for PET decomposition, transforming PET into valuable platform chemicals and materials in upcycling processes. Enhancing PET hydrolases' catalytic activity and efficiency through protein engineering strategies is a priority, facilitating more effective PET waste management. Efforts to create novel PET hydrolases for large-scale PET depolymerization continue, but cost-effectiveness remains challenging. Hydrolyzed monomers must add additional value to make PET recycling economically attractive. Valorization of hydrolysis products through the upcycling process is expected to produce new compounds with different values and qualities from the initial polymer, making the decomposed monomers more appealing. Advances in synthetic biology and enzyme engineering hold promise for PET upcycling. While biological depolymerization offers environmental benefits, further research is needed to make PET upcycling sustainable and economically feasible.

One-dimensionally oriented self-assembly of ordered mesoporous nanofibers featuring tailorable mesophases via kinetic control.

One-dimensional (1D) nanomaterials have sparked widespread research interest owing to their fascinating physicochemical properties, however, the direct self-assembly of 1D porous nanomaterials and control over their porosity still presents a grand challenge. Herein, we report a monomicelle oriented self-assembly approach to fabricate 1D mesoporous nanostructures with uniform diameter, high aspect ratio and ordered mesostructure. This strategy features the introduction of hexamethylenetetramine as a curing agent, which can subtly control the monomicelle self-assembly kinetics, thus enabling formation of high-quality 1D ordered mesostructures. Meanwhile, the micellar structure can be precisely manipulated by changing the reactant stoichiometric ratio, resulting in tailorable mesophases from 3D cubic (Im-3m) to 2D hexagonal (p6mm) symmetries. More interestingly, the resultant mesoporous nanofibers can be assembled into 3D hierarchical cryogels on a large scale. The 1D nanoscale of the mesoporous nanofibers, in combination with small diameter (~65 nm), high aspect ratio (~154), large surface area (~452 m2 g-1), and 3D open mesopores (~6 nm), endows them with excellent performances for sodium ion storage and water purification. Our methodology opens up an exciting way to develop next-generation ordered mesoporous materials for various applications.

Soft ferroelectret ultrasound receiver for targeted peripheral neuromodulation.

Bioelectronic medicine is a rapidly growing field where targeted electrical signals can act as an adjunct or alternative to drugs to treat neurological disorders and diseases via stimulating the peripheral nervous system on demand. However, current existing strategies are limited by external battery requirements, and the injury and inflammation caused by the mechanical mismatch between rigid electrodes and soft nerves. Here we report a wireless, leadless, and battery-free ferroelectret implant, termed NeuroRing, that wraps around the target peripheral nerve and demonstrates high mechanical conformability to dynamic motion nerve tissue. As-fabricated NeuroRing can act as an ultrasound receiver that converts ultrasound vibrations into electrostimulation pulses, thus stimulating the targeted peripheral nerve on demand. This capability is demonstrated by the precise modulation of the sacral splanchnic nerve to treat colitis, providing a framework for future bioelectronic medicines that offer an alternative to non-specific pharmacological approaches.

Increased Purinergic Signaling in Human Dental Pulps With Inflammatory Pain is Sex-Dependent.

An enhanced understanding of neurotransmitter systems contributing to pain transmission aids in drug development, while the identification of biological variables like age and sex helps in the development of personalized pain management and effective clinical trial design. This study identified enhanced expression of purinergic signaling components specifically in painful inflammation, with levels increased more in women as compared to men. Inflammatory dental pain is common and potentially debilitating; as inflammation of the dental pulp can occur with or without pain, it provides a powerful model to examine distinct pain pathways in humans. In control tissues, P2X3 and P2X2 receptors colocalized with PGP9.5-positive nerves. Expression of the ecto-nucleotidase NTPDase1 (CD39) increased with exposure to extracellular adenosine triphosphate (ATP), implying CD39 acted as a marker for sustained elevation of extracellular ATP. Both immunohistochemistry and immunoblots showed P2X2, P2X3, and CD39 increased in symptomatic pulpitis, suggesting receptors and the ATP agonist were elevated in patients with increased pain. The increased expression of P2X3 and CD39 was more frequently observed in women than men. In summary, this study identifies CD39 as a marker for chronic elevation of extracellular ATP in fixed human tissue. It supports a role for increased purinergic signaling in humans with inflammatory dental pain and suggests the contribution of purines shows sexual dimorphism. This highlights the potential for P2X antagonists to treat pain in humans and stresses the need to consider sex in clinical trials that target pain and purinergic pathways. PERSPECTIVE: This article demonstrates an elevation of ATP-marker CD39 and of ATP receptors P2X2 and P2X3 with inflammatory pain and suggests the rise is greater in women. This highlights the potential for P2X antagonists to treat pain and stresses the consideration of sexual dimorphism in studies of purines and pain.

Finite Element Analysis Model for Assessing Expansion Patterns from Surgically Assisted Rapid Palatal Expansion.

Surgically assisted rapid palatal expansion (SARPE) was introduced to release bony resistance to facilitate skeletal expansion in skeletally mature patients. However, asymmetric expansion between the left and right sides has been reported in 7.52% of all SARPE patients, of which 12.90% had to undergo a second surgery for correction. The etiologies leading to asymmetric expansion remain unclear. Finite element analysis has been used to evaluate the stress associated with SARPE in the maxillofacial structures. However, as a collision of the bone at the LeFort I osteotomy sites occurs only after a certain amount of expansion, most of the existing models do not truly represent the force distribution, given that the expansion amount of these existing models rarely exceeds 1 mm. Therefore, there is a need to create a novel finite element model of SARPE that could perform a clinically required amount of expander activation for further analysis of the expansion patterns of the hemimaxillae in all three dimensions. A three-dimensional (3D) skull model from cone beam computed tomography (CBCT) was imported into Mimics and converted into mathematical entities to segment the maxillary complex, maxillary first premolars, and maxillary first molars. These structures were transferred into Geomagic for surface smoothing and cancellous bone and periodontal ligament creation. The right half of the maxillary complex was then retained and mirrored to create a perfectly symmetrical model in SolidWorks. A Haas expander was constructed and banded to the maxillary first premolars and first molars. Finite element analysis of various combinations of buccal osteotomies at different angles with 1 mm clearance was performed in Ansys. A convergence test was conducted until the desired amount of expansion on both sides (at least 6 mm in total) was achieved. This study lays the foundation for evaluating how buccal osteotomy angulation influences the expansion patterns of SARPE.

Identification of tyrosine sulfation in the variable region of a bispecific antibody and its effect on stability and biological activity.

Despite tyrosine sulfation being a relatively common post-translational modification (PTM) on the secreted proteins of higher eukaryotic organisms, there have been surprisingly few reports of this modification occurring in recombinant monoclonal antibodies (mAbs) expressed by mammalian cell lines and even less information regarding its potential impact on mAb efficacy and stability. This discrepancy is likely due to the extreme lability of this modification using many of the mass spectrometry methods typically used within the biopharmaceutical industry for PTM identification, as well as the possible misidentification as phosphorylation. Here, we identified sulfation on a single tyrosine residue located within the identical variable region sequence of a 2 + 1 bispecific mAbs heavy and heavy-heavy chains using a multi-enzymatic approach in combination with mass spectrometry analysis and examined its impact on binding, efficacy, and physical stability. Unlike previous reports, we found that tyrosine sulfation modestly decreased the mAb cell binding and T cell-mediated killing, primarily by increasing the rate of antigen disassociation as determined from surface plasmon resonance-binding experiments. We also found that, while this acidic modification had no significant impact on the mAb thermal stability, sulfation did modestly increase its rate of aggregation, presumably by lowering the mAb's colloidal stability as indicated by polyethylene glycol induced liquid-liquid phase separation experiments.

Breakthrough Curve Modeling and Analysis for Lysozyme Adsorption by Tris(hydroxymethyl)aminomethane Affinity Nanofiber Membrane.

In this study, a polyacrylonitrile nanofiber membrane was first hydrolyzed and then functionalized with tris(hydroxymethyl)aminomethane (P-Tris), then used as an affinity nanofiber membrane for lysozyme adsorption in membrane chromatography. The dynamic adsorption behavior of lysozyme was investigated in a flow system under various operating parameters, including adsorption pHs, initial feed lysozyme concentration, loading flow rate, and the number of stacked membrane layers. Four different kinetic models, pseudo-first-order, pseudo-second-order, Elovich, and intraparticle diffusion kinetic models, were applied to experimental data from breakthrough curves of lysozyme. The results showed that the dynamic adsorption results were fitted well with the pseudo-second-order kinetic model. The breakthrough curve experimental results show significant differences in the breakthrough time, the dynamic binding capacity, the length of the mass transfer zone, and the utilization rate of the membrane bed under different operating parameters. Four dynamic adsorption models (i.e., Bohart-Adams, Thomas, Yoon-Nelson, and BDST models) were used to analyze the breakthrough curve characteristics of the dynamic adsorption experiments. Among them, the Yoon-Nelson model was the best model to fit the breakthrough curve. However, some of the theoretical results based on the Thomas and Bohart-Adams model analyses of the breakthrough curve fit well with the experimental data, with an error percentage of <5%. The Bohart-Adams model has the largest difference from the experimental results; hence it is not suitable for breakthrough curve analysis. These results significantly impact dynamic kinetics studies and breakthrough curve characteristic analysis in membrane bed chromatography.

Dynamic wetting of Newtonian and viscoelastic fluids on microstructured surfaces.

Hypothesis Although extensive research has been conducted on the dynamic wetting of Newtonian fluids, limited insights have been gained for viscoelastic fluids, particularly on engineered surfaces. We hypothesize that differences in dynamic wetting on microstructured surfaces exist between such fluids, which may be attributed to variations in viscosity and elasticity as well as changes in the microscopic morphology of the moving contact line. Experiments To systematically investigate the wetting differences between Newtonian and viscoelastic fluids on microstructured surfaces, we conducted forced wetting experiments of glycerol-water and carboxymethyl cellulose aqueous solutions on microstructured polytetrafluoroethylene surfaces through a modified Wilhelmy plate method. Findings Results demonstrated an apparent difference in the relationship between the dynamic contact angle and moving velocity with different microstructured surfaces for Newtonian and viscoelastic fluids. The power-law exponent between the capillary number and cubic of the dynamic contact angle increases with the strengthening of shear thinning and elastic effects. In contrast, this exponent is rarely influenced by the scale of microstructured surfaces, particularly in highly viscous regions where viscous force dominates. In addition, viscosity affects the viscous bending and distance that liquid molecules jump at the contact line. These findings have potential applications in coating complex fluids on engineered surfaces.

Developing targeted drug delivery carriers for breast cancer using glutathione-sensitive doxorubicin-coupled glycated bovine serum albumin nanoparticles.

Incorporation of the nano-based carriers into drug delivery provides a promising alternative to overcome the limitations of the conventional chemotherapy. Doxorubicin (DOXO) is an effective chemotherapeutic drug widely used in chemotherapy for breast cancer treatment. A globular protein bovine serum albumin (BSA) holds great potential as carriers in pharmaceutical applications. This work is aimed at developing the DOXO-coupled glycated BSA nanoparticles via desolvation method for improving the capability of targeting the GLUT5 transporters over-expressed on breast cancer cells. Fructosamine assay and Fourier transform infrared spectroscopy were employed to determine the content of fructosamine structure and structural changes on the surfaces of nanoparticles, respectively. Additionally, the synthesized BSA nanoparticles were further characterized by electron microscopy and dynamic light scattering. Results revealed that the DOXO-coupled glycated BSA nanoparticles were spherically shaped with a hydrodynamic diameter of ~60.74 nm and a ζ-potential of ~ - 42.20 mV. Moreover, the DOXO release behavior of as-synthesized DOXO-coupled glycated BSA nanoparticles was examined under different conditions. Finally, the DOXO-coupled glycated BSA nanoparticles were found to exhibit cytotoxicity toward both MCF-7 and MDA-MB-231 cells. Our findings evidently suggested that the drug-coupled glycated BSA nanoparticles serve as the potential candidates for targeted drug delivery platform used in breast cancer therapy.

Heterogenous Slippery Surfaces: Enabling Spontaneous and Rapid Transport of Viscous Liquids with Viscosities Exceeding 10 000 mPa s.

Superhydrophobic and slippery lubricant-infused surfaces have garnered significant attention for their potential to passively transport low-viscosity liquids like water (1 mPa s). Despite exciting progress, these designs have proven ineffective for transporting high-viscosity liquids such as polydimethylsiloxane (5500 mPa s) due to their inherent limitations imposed by the homogenous surface design, resulting in high viscous drags and compromised capillary forces. Here, a heterogenous water-infused divergent surface (WIDS) is proposed that achieves spontaneous, rapid, and long-distance transport of viscous liquids. WIDS reduces viscous drag by spatially isolating the viscous liquids and surface roughness through its heterogenous, slippery topological design, and generates capillary forces through its heterogenous wetting distributions. The essential role of surface heterogeneity in viscous liquid transport is theoretically and experimentally verified. Remarkably, such a heterogenous paradigm enables transporting liquids with viscosities exceeding 12 500 mPa s, which is two orders of magnitude higher than state-of-the-art techniques. Furthermore, this heterogenous design is generic for various viscous liquids and can be made flexible, making it promising for various systems that require viscous liquid management, such as micropatterning.

Comparison of margins and survival between transoral robotic surgery (TORS) and non-robotic endoscopic surgery for oropharyngeal cancer.

OBJECTIVE: To evaluate the impact of transoral robotic surgery (TORS) and non-robotic transoral endoscopic surgery on margin positivity, rates of adjuvant therapy and survival in early stage oropharyngeal squamous cell carcinoma. STUDY DESIGN: Retrospective cohort review. SUBJECTS AND METHODS: The National Cancer Database was queried to form a cohort of patients with T1-T2 N0-N1 MO oropharyngeal squamous cell carcinoma who underwent TORS or Non-robotic endoscopic surgery from 2010 to 2015. Demographics, disease characteristics and rate of positive margin and adjuvant therapy were summarized. A binary logistic regression and a cox-proportional hazard model were performed to evaluate patient demographic, disease, and treatment factors that could predict margin positivity and survival respectively. RESULTS: 1026 patients received TORS treatment while 734 patients received non-robotic endoscopic primary surgery. Non-robotic surgery was more likely to have residual tumor (31.6 % of all cases) compared to TORS procedures (13.6 % of TORS cases); p < .0001. Non-robotic surgery more frequently had non-evaluable margins at 8.1 % compared to only 1.4 % of TORS cases (p < .0001). Non-robotic cases had a significantly higher proportion of patients receiving adjuvant radiotherapy and systemic therapy compared to TORS (66.4 % vs 51.3 % for radiotherapy; p < .0001 and 33.4 % vs 22.2 % for chemotherapy; p < .0001). There was no difference in mortality between the two modalities (non-robotic vs TORS, HR 1.357, 95 % CI 0.937-1.967). CONCLUSION: TORS and non-robotic surgery may have a similar impact on survival in early-stage OPSCC, but non-robotic surgery was found to have a higher likelihood of positive margins and a higher rate of adjuvant chemoradiation therapy.

Therapy-associated remodeling of pancreatic cancer revealed by single-cell spatial transcriptomics and optimal transport analysis.

In combination with cell intrinsic properties, interactions in the tumor microenvironment modulate therapeutic response. We leveraged high-plex single-cell spatial transcriptomics to dissect the remodeling of multicellular neighborhoods and cell-cell interactions in human pancreatic cancer associated with specific malignant subtypes and neoadjuvant chemotherapy/radiotherapy. We developed Spatially Constrained Optimal Transport Interaction Analysis (SCOTIA), an optimal transport model with a cost function that includes both spatial distance and ligand-receptor gene expression. Our results uncovered a marked change in ligand-receptor interactions between cancer-associated fibroblasts and malignant cells in response to treatment, which was supported by orthogonal datasets, including an ex vivo tumoroid co-culture system. Overall, this study demonstrates that characterization of the tumor microenvironment using high-plex single-cell spatial transcriptomics allows for identification of molecular interactions that may play a role in the emergence of chemoresistance and establishes a translational spatial biology paradigm that can be broadly applied to other malignancies, diseases, and treatments.