Copolymer functional groups modulate extracellular trap accumulation and inflammatory markers in HL60 and murine neutrophils.

Undesirable host responses to implants commonly lead to impaired device function. As the first immune cell to respond to inflammation, activated neutrophils release antimicrobials and neutrophil extracellular traps (NETs) that prime microenvironments for macrophages and other infiltrating cells. This research aims to understand how functional groups in copolymers of isodecyl acrylate (IDA) that are known to modulate healingin vivo, modulate neutrophil cells. Phorbol myristate acetate-activated HL60 cells and bone marrow-derived murine neutrophils (BMDN) were incubated with coatings of IDA copolymerized with, methacrylic acid (MAA films), methyl methacrylate (MM films), or MM functionalized with hexamethylenediamine (HMD films). Cells incubated on HMD films resulted in increased accumulation of NETs at the film's surface in comparison to other copolymers because of increased adhesion of HL60 onto HMD films or increased rates of NETosis from BMDN. Overall, lower inflammation was observed with cells on MAA films. HL60 cells had no increase in classical inflammatory markers such as tumor necrosis factor alpha and intracellular adhesion molecule-1, whereas HL60 on HMD films had increases in these same markers. Taken together, these studies give important insights into how neutrophils interact differently with functionalized copolymers and the proteins that adsorb to them, with MAA (carboxyl groups) leading to behavior associated with lower inflammation and HMD (amine groups) with higher inflammation and accumulation of NETs.

Medical Devices, Invisible Women, Harmful Consequences.

In this commentary, we explore the disproportionate risk women experience with the insertion of various medical devices. Although pre-market device testing and complication tracking could be improved for all, a failure to consider sex differences in hormones, anatomy, inflammatory responses, and physical function puts women at particular risk. This invisibility of women is an example of gender bias in medical science and practice, a bias that could be corrected in the ways we suggest.

Patient and Provider Perspectives on Emergency Department Care Experiences among People with Mental Health Concerns.

Emergency departments (EDs) are an important source of care for people with mental health (MH) concerns. It can be challenging to treat MH in EDs, and there is little research capturing both patient and provider perspectives of these experiences. We sought to summarize the evidence on ED care experiences for people with MH concerns in North America, from both patient and provider perspectives. Medline and EMBASE were searched using PRISMA guidelines to identify primary studies. Two reviewers conducted a qualitative assessment of included papers and inductive thematic analysis to identify common emerging themes from patient and provider perspectives. Seventeen papers were included. Thematic analysis revealed barriers and facilitators to optimal ED care, which were organized into three themes each with sub-themes: (1) interpersonal factors, including communication, patient-staff interactions, and attitudes and behaviours; (2) environmental factors, including accommodations, wait times, and restraint use; and (3) system-level factors, including discharge planning, resources and policies, and knowledge and expertise. People with MH concerns and ED healthcare providers (HCPs) share converging perspectives on improving ED connections with community resources and diverging perspectives on the interplay between system-level and interpersonal factors. Examining both perspectives simultaneously can inform improvements in ED care for people with MH concerns.

Modeling the Effects of Disease, Drug Properties, and Material on Drug Transport From Intraocular Lenses.

Purpose: Surgically implanted intraocular lenses (IOLs) may be used as drug-delivery devices, but their effectiveness is not well defined. Computational fluid dynamics models were developed to investigate the capability of IOLs to release drugs at therapeutic concentrations. Methods: Models were generated using COMSOL Multiphysics. Primary open-angle glaucoma (POAG) and wet age-related macular degeneration (AMD) were simulated by reducing aqueous vein and choroidal blood flow, respectively. Release of dexamethasone, ganciclovir, or dextran was studied using common IOL materials, polydimethylsiloxane (PDMS) and poly(2-hydroxyethyl methacrylate) (PHEMA). Results: Drug clearance proceeds mainly through choroidal blood flow. When fully constricted, maximum concentration at the choroid (Cmax) values increased by 32.4% to 39,800%. Compared to dexamethasone, Cmax in different tissues decreased by 6.07% to 96.0% for ganciclovir and dextran, and clearance rates decreased by 16% to 69% for ganciclovir and by 92% to 100% for dextran. Using PDMS as the IOL reduced clearance rates by 91.3% to 94.6% compared to PHEMA. Conclusions: In diseased eyes, drugs accumulate mainly in posterior tissue; thus, choroidal drug toxicity must be assessed prior to IOL implantation in POAG and AMD patients. Moreover, drug properties modulated concentration profiles in all ocular segments. The hydrophobic small-molecule dexamethasone attained the highest concentrations and cleared the fastest, whereas hydrophilic macromolecular dextran attained the lowest concentrations and cleared the slowest. Furthermore, high concentrations were achieved quickly following release from PHEMA, whereas PDMS allowed for sustained release. Translational Relevance: In silico results can guide scientists and clinicians regarding important physiological and chemical factors that modulate tissue drug concentrations from drug-eluting IOLs.

How do educational disparities in smoking develop during early life? A Swedish longitudinal study.

Smoking contributes to health inequalities, but how social inequalities in smoking develop in early life remains unclear. This study examines how measures of education attained over the early life course (representing socioeconomic position of origin, socioeconomic position of destination, and in-between) contribute to smoking behavior in a Swedish longitudinal sample. We used data obtained from the Swedish Level-of-Living Surveys in addition to national register data. Young adults (aged 20-28, n = 749) self-reported their educational attainment and smoking behavior (initiation and cessation) in 2010. Ten years earlier, their parents self-reported their own education and smoking behavior. We used linked register data on school performance in adolescence (in grade 9). Logistic regression models showed that lower parental education, lower adolescent school performance, and low young adult educational attainment were respectively associated with young adult smoking initiation. The association between parental education and young adult smoking initiation was explained by adolescent school performance and not parental smoking. Young adult smoking cessation was associated with high parental education and high adolescent school performance (marks in the top quartile), but only school performance remained significant in the final model, which included all measures of education and parental smoking. Results suggest that school performance in adolescence (which connects adolescents' socioeconomic position of origin with their destination) may play an important role in how educational disparities in smoking form over the life course.

Hyaluronic Acid and Poly-l-Lysine Layers on Calcium Alginate Microspheres to Modulate the Release of Encapsulated FITC-Dextran.

Alginate solutions crosslink into microspheres in calcium alginate, enabling the encapsulation and subsequent release of biological macromolecules and drugs. However, release from calcium alginate into PBS is relatively fast because it will decrosslink the gel relatively quickly. In this research, FITC-dextran (MW 10 kDa) was encapsulated in 2% (w/v) calcium alginate microspheres by electrospraying. The resulting microspheres (diameter = 247 ± 13 µm) were then layered with thin polyelectrolyte films of hyaluronic acid (HA) and poly-l-lysine (PLL) to attempt to slow the diffusion of FITC-dextran out of the microspheres and the coating parameters were modified to modulate diffusion and release. Increasing the concentration of FITC-dextran encapsulated in the microspheres resulted in an increase in its release over time into PBS. Crosslinking PLL/HA layers on the microspheres did not decrease the in vitro release rates of encapsulated FITC-dextran into PBS. Increasing the number of layers on the microspheres from 3 to 5 layers significantly decreased the amount of encapsulated FITC-dextran released. However, increasing the number of layers to 7 did not further sustain the release of FITC-dextran, likely because these microspheres collapsed to a smaller size during the coating procedure, resulting in release controlled by both diffusion and swelling. Multiple layers of PLL and HA provided a robust mechanism to sustain and control release of large molecules from calcium alginate.

DNA-crosslinked alginate and layered microspheres to modulate the release of encapsulated FITC-dextran.

Alginate can be gently crosslinked by calcium into hydrogels and microspheres for the encapsulation and release of proteins and drugs. However, the release is often over short periods unless alginate is also covalently modified or crosslinked. This research aims to sustain the release of encapsulated model drug FITC-dextran by covalently crosslinking alginate with short oligomers DNA because evidence suggests that DNA may also interact with alginate to further increase effective crosslinking. Furthermore, modulating the release of drugs from alginate in response to specific proteins could tailor release profiles to improve patient treatment. This research develops a DNA-crosslinked alginate hydrogel and layered alginate microspheres to encapsulate and then sustain the release FITC-dextran (model drug). An aptamer sequence to hen egg-white lysozyme is included in one DNA strand to allow for the disruption of the crosslinks by interactions with human lysozyme. Alginate was covalently modified with complementary strands of DNA to crosslink the alginate into hydrogels, which had increased crosslinking density when re-swollen (in comparison to controls crosslinked with PEG) and could sustained the release of encapsulated FITC-dextran. When an aptamer sequence for hen lysozyme was included in the DNA crosslinks, the hydrogels decrosslinked when incubated in human lysozyme for 60 days. In addition, calcium alginate microspheres were coated with 3 alternating layers of poly-Lysine, DNA-crosslinked alginate, and poly-L-lysine. FITC-dextran loaded into the microspheres released in a sustained manner past 30 days (into PBS at 37 °C) and would likely continue to release for far longer had the studies continued. When incubated with 3 µM of human lysozyme, a burst release of FITC-dextran occurred from both the hydrogels and microspheres, with no changes in the controls. The increased release was in bursts followed by similar sustained release rates suggesting that the human lysozyme temporarily disrupted the DNA crosslinks which were then re-established or were influenced by interactions between DNA and alginate. Importantly, covalently bound complementary strands of DNA could crosslink the alginate and additional interactions appeared to further sustain the release of encapsulated therapeutics.

Aerosol-jet printing facilitates the rapid prototyping of microfluidic devices with versatile geometries and precise channel functionalization.

Microfluidics has emerged as a powerful analytical tool for biology and biomedical research, with uses ranging from single-cell phenotyping to drug discovery and medical diagnostics, and only small sample volumes required for testing. The ability to rapidly prototype new designs is hugely beneficial in a research environment, but the high cost, slow turnaround, and wasteful nature of commonly used fabrication techniques, particularly for complex multi-layer geometries, severely impede the development process. In addition, microfluidic channels in most devices currently play a passive role and are typically used to direct flows. The ability to "functionalize" the channels with different materials in precise spatial locations would be a major advantage for a range of applications. This would involve incorporating functional materials directly within the channels that can partake in, guide or facilitate reactions in precisely controlled microenvironments. Here we demonstrate the use of Aerosol Jet Printing (AJP) to rapidly produce bespoke molds for microfluidic devices with a range of different geometries and precise "in-channel" functionalization. We show that such an advanced microscale additive manufacturing method can be used to rapidly design cost-efficient and customized microfluidic devices, with the ability to add functional coatings at specific locations within the microfluidic channels. We demonstrate the functionalization capabilities of our technique by specifically coating a section of a microfluidic channel with polyvinyl alcohol to render it hydrophilic. This versatile microfluidic device prototyping technique will be a powerful aid for biological and bio-medical research in both academic and industrial contexts.

Parental education differentially predicts young adults' frequency and quantity of alcohol use in a longitudinal Swedish sample.

BACKGROUND: Alcohol consumption contributes to health inequalities, but few studies have examined how socially differentiated alcohol use develops across the life course. In this study, we examine how one aspect of childhood socioeconomic position (parental education) relates to two often-conflated young adult drinking patterns: drinking frequency and quantity per occasion. Using a life course perspective, we also explore whether parental drinking patterns or young adults' own educational attainment might account for such associations. METHODS: This study used longitudinal data from the nationally representative Swedish Level of Living Surveys (LNU). Young adults' (aged 20-28, n = 803) drinking patterns and educational attainment were determined through the LNU 2010 and official registers. A decade earlier, parents self-reported their education and drinking patterns in the LNU 2000 and Partner-LNU 2000. RESULTS: Logistic regression models showed that high parental education predicted young adult frequent drinking, while low parental education predicted young adult high quantity drinking. Drinking patterns were associated inter-generationally, but parental alcohol use did not account for differences in young adult drinking patterns by parental education. Young adults' own education similarly predicted their drinking patterns but did not account for differences in drinking frequency by parental education. Differences in drinking quantity by parental education were no longer significant when young adults' own education was included in the final model. CONCLUSIONS: Findings suggest that parental education constitutes an early-life structural position that confers differential risk for young adult drinking patterns. Young adults whose parents had low education were less likely to drink frequently but were more likely to drink heavily per occasion, a drinking pattern that may place more disadvantaged young adults at a greater health risk.

Physical Inactivity From Adolescence to Young Adulthood: The Relevance of Various Dimensions of Inequality in a Swedish Longitudinal Sample.

As physical inactivity may track from adolescence to adulthood, it is important to identify social determinants of physical inactivity in early life. However, most studies have measured socioeconomic position as one dimension. We examine whether multiple dimensions of socioeconomic position, in addition to other dimensions of inequality (i.e., gender, immigrant background), associate with physical inactivity at two time points in youth. Longitudinal data were drawn from the Swedish Level of Living Survey ( N = 765) and analysed by gender-stratified logistic regression. Among girls, low parental social class (odds ratio [OR] = 2.63, 95% confidence interval [CI; 1.28, 5.42]) and income (OR = 2.28, 95% [CI 1.12, 4.65]) were associated with physical inactivity, while immigrant background (OR = 2.33, 95% CI [1.03, 5.23]) and a low level of parental education (OR = 3.38, 95% CI [1.15, 9.95]) predicted physical inactivity among women. Among boys, low parental income (OR = 3.27, 95% CI [1.39, 7.69]) was associated with physical inactivity, whereas immigrant background (OR = 2.29, 95% CI [1.04, 5.03]) predicted physical inactivity among men. Our results suggest that physical inactivity is socially patterned, but different dimensions of social stratification should not be considered interchangeable as they may operate independently, through intersection with gender, and at different time points in youth in increasing the risk of physical inactivity.

The profile of adsorbed plasma and serum proteins on methacrylic acid copolymer beads: Effect on complement activation.

Polymer beads made of 45% methacrylic acid co methyl methacrylate (MAA beads) promote vascular regenerative responses in contrast to control materials without methacrylic acid (here polymethyl methacrylate beads, PMMA). In vitro and in vivo studies suggest that MAA copolymers induce differences in macrophage phenotype and polarization and inflammatory responses, presumably due to protein adsorption differences between the beads. To explore differences in protein adsorption in an unbiased manner, we used high resolution shotgun mass spectrometry to identify and compare proteins that adsorb from human plasma or serum onto MAA and PMMA beads. From plasma, MAA beads adsorbed many complement proteins, such as C1q, C4-related proteins and the complement inhibitor factor H, while PMMA adsorbed proteins, such as albumin, C3 and apolipoproteins. Because of the differences in complement protein adsorption, follow-up studies focused on using ELISA to assess complement activation. When incubated in serum, MAA beads generated significantly lower levels of soluble C5b9 and C3a/C3adesarg in comparison to PMMA beads, indicating a decrease in complement activation with MAA beads. The differences in adsorbed protein on the two materials likely alter subsequent cell-material interactions that ultimately result in different host responses and local vascularization.

Identification of Emotional Facial Expressions: Effects of Expression, Intensity, and Sex on Eye Gaze.

The identification of emotional expressions is vital for social interaction, and can be affected by various factors, including the expressed emotion, the intensity of the expression, the sex of the face, and the gender of the observer. This study investigates how these factors affect the speed and accuracy of expression recognition, as well as dwell time on the two most significant areas of the face: the eyes and the mouth. Participants were asked to identify expressions from female and male faces displaying six expressions (anger, disgust, fear, happiness, sadness, and surprise), each with three levels of intensity (low, moderate, and normal). Overall, responses were fastest and most accurate for happy expressions, but slowest and least accurate for fearful expressions. More intense expressions were also classified most accurately. Reaction time showed a different pattern, with slowest response times recorded for expressions of moderate intensity. Overall, responses were slowest, but also most accurate, for female faces. Relative to male observers, women showed greater accuracy and speed when recognizing female expressions. Dwell time analyses revealed that attention to the eyes was about three times greater than on the mouth, with fearful eyes in particular attracting longer dwell times. The mouth region was attended to the most for fearful, angry, and disgusted expressions and least for surprise. These results extend upon previous findings to show important effects of expression, emotion intensity, and sex on expression recognition and gaze behaviour, and may have implications for understanding the ways in which emotion recognition abilities break down.

Biodegradable scaffold with built-in vasculature for organ-on-a-chip engineering and direct surgical anastomosis.

We report the fabrication of a scaffold (hereafter referred to as AngioChip) that supports the assembly of parenchymal cells on a mechanically tunable matrix surrounding a perfusable, branched, three-dimensional microchannel network coated with endothelial cells. The design of AngioChip decouples the material choices for the engineered vessel network and for cell seeding in the parenchyma, enabling extensive remodelling while maintaining an open-vessel lumen. The incorporation of nanopores and micro-holes in the vessel walls enhances permeability, and permits intercellular crosstalk and extravasation of monocytes and endothelial cells on biomolecular stimulation. We also show that vascularized hepatic tissues and cardiac tissues engineered by using AngioChips process clinically relevant drugs delivered through the vasculature, and that millimetre-thick cardiac tissues can be engineered in a scalable manner. Moreover, we demonstrate that AngioChip cardiac tissues implanted with direct surgical anastomosis to the femoral vessels of rat hindlimbs establish immediate blood perfusion.

Psychopathic traits are associated with reduced attention to the eyes of emotional faces among adult male non-offenders.

Psychopathic traits are linked with impairments in emotional facial expression recognition. These impairments may, in part, reflect reduced attention to the eyes of emotional faces. Although reduced attention to the eyes has been noted among children with conduct problems and callous-unemotional traits, similar findings are yet to be found in relation to psychopathic traits among adult male participants. Here we investigated the relationship of primary (selfish, uncaring) and secondary (impulsive, antisocial) psychopathic traits with attention to the eyes among adult male non-offenders during an emotion recognition task. We measured the number of fixations, and overall dwell time, on the eyes, and the mouth of male and female faces showing the six basic emotions at varying levels of intensity. We found no relationship of primary or secondary psychopathic traits with recognition accuracy. However, primary psychopathic traits were associated with a reduced number of fixations, and lower overall dwell time, on the eyes relative to the mouth across expressions, intensity, and sex. Furthermore, the relationship of primary psychopathic traits with attention to the eyes of angry and fearful faces was influenced by the sex and intensity of the expression. We also showed that a greater number of fixations on the eyes, relative to the mouth, were associated with increased accuracy for angry and fearful expression recognition. These results are the first to show effects of psychopathic traits on attention to the eyes of emotional faces in an adult male sample, and may support amygdala based accounts of psychopathy. These findings may also have methodological implications for clinical studies of emotion recognition.

Unbiased phosphoproteomic method identifies the initial effects of a methacrylic acid copolymer on macrophages.

An unbiased phosphoproteomic method was used to identify biomaterial-associated changes in the phosphorylation patterns of macrophage-like cells. The phosphorylation differences between differentiated THP1 (dTHP1) cells treated for 10, 20, or 30 min with a vascular regenerative methacrylic acid (MAA) copolymer or a control methyl methacrylate (MM) copolymer were determined by MS. There were 1,470 peptides (corresponding to 729 proteins) that were differentially phosphorylated in dTHP1 cells treated with the two materials with a greater cellular response to MAA treatment. In addition to identifying pathways (such as integrin signaling and cytoskeletal arrangement) that are well known to change with cell-material interaction, previously unidentified pathways, such as apoptosis and mRNA splicing, were also discovered.

Cell Interactions with Vascular Regenerative MAA-Based Materials in the Context of Wound Healing.

In diabetic patients the development of chronic non-healing wounds is a common complication. A methacrylic acid-based biomaterial is a vascular regenerative material that enhances diabetic healing without the use of cells or growth factors. The bioactive nature of this material is thought to be associated with its anionic charge or surface chemistry. Contact between the methacrylic acid-based biomaterial and tissue begins with protein (including complement) adsorption and is followed by interaction of the biomaterial with resident and infiltrating cells in the wound bed (e.g., macrophages and endothelial cells). This results in changes to their surface receptors to activate phosphorylation cascades that lead to differential activation of signalling pathways such as those involving osteopontin and sonic hedgehog. These changes modulate the phenotype of the cells in the wound bed, eventually improving vessel formation and wound healing. Understanding the molecular and cellular mechanisms will have broad implications for biomaterials, not just the methacrylic acid-based material, and will facilitate the advancement of regenerative biomaterials for diverse applications.

Fitness to practice and feedback to students: a literature review.

In the United Kingdom (UK), the Nursing and Midwifery Council (NMC) stipulate that practice experience makes up 50% of the nursing curricula. We argue that mentors play a pivotal role in this experience, being the main practitioner responsible for supporting learning in practice, and the NMC's framework to support learning and assessment in practice establishes the knowledge and skills that mentors must apply in practice with students. This framework acts as a resource guide to mentors on how to successfully facilitate students clinical learning experiences, ensuring that students are "fit to practice" at the point of registration. It is recognised, therefore, that it is the mentor's responsibility, once in practice, to bridge the gap between that which students are taught in the classroom, and their actual application to practice. This paper aims to undertake an analysis of the available literature on how effective feedback from mentors to students can help to ensure this fitness to practice.

The effect of methacrylic acid in smooth coatings on dTHP1 and HUVEC gene expression.

Without any external additives such as growth factors, polymer beads containing methacrylic acid (MAA) promoted functional vascularization in vivo leading to faster cutaneous wound healing in diabetic mice and improved skin graft integration in Wistar rats. The aim of this work is to understand this material-driven vascularization by investigating the effect of polymer MAA-content, in the absence of surface roughness, on the behaviour of macrophage-like and endothelial cells. Smooth polymer films containing 20, 30 or 40% MAA or methyl methacrylate as a control copolymerized with isodecyl acrylate, were synthesized to study the effect of MAA content in smooth films, without roughness. Macrophage-like cells (dTHP1) incubated on 40% MAA films for 96 hours increased the expression of the angiogenic genes HIF1α and SDF1α, and of the inflammatory genes IL1ß, IL6 and TNFα, while decreasing the expression of osteopontin. Endothelial cells (HUVEC) on 40% MAA films for 96 hours increased the expression of the angiogenic genes MMP9 and CXCR4, and of osteopontin. In dTHP1 cells, principal component analysis established a positive correlation between MAA polymer content, HIF1α expression and the expression of IL6, IL1ß and TNFα, suggesting that HIF1α and NF-κB pathway may be involved. It was found that MAA chemistry, without topographical differences, promoted changes in gene expression in macrophage-like and endothelial cells. This effect was more significant above a threshold between 30 to 40% MAA. The amount of MAA in the copolymer likely promoted the cell responses, future work will study the effects of varying MAA content. The 40% MAA coatable material developed in this work may also be of interest as a coating to improve the integration of medical devices.

Generic, anthracene-based hydrogel crosslinkers for photo-controllable drug delivery.

Light-responsive polymers with controllable, reversible crosslink mechanisms have the potential to create unique biomaterials with stimulus-controlled swelling, degradation and diffusion properties useful in tissue engineering and drug delivery applications. Generic photodimerizing polyethylene glycol-anthracene macromolecules that may be grafted to various polymers to effectively control their crosslinking via a photodimerization mechanism have been developed. These generic crosslinkers were shown to effectively introduce photoresponsive properties into hyaluronate and alginate as model hydrophilic polymers. In vitro testing using human corneal epithelial cells was used to demonstrate cytocompatibility of the resulting photogels. The effective crosslinking density of the photogels could be increased resulting in a decrease in the release rate of small and large molecules from the photogels following exposure to 365 nm light. This tuneable crosslinking has the potential to manipulate the delivery rates of therapeutics resulting in control over treatment profiles and may lend itself to various applications, which may benefit from light induced changes in crosslinking.